Family members in 14/15 cases detailed in Cleckley’s
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5078",leadTitle:null,fullTitle:"Advances in Molecular Retrovirology",title:"Advances in Molecular Retrovirology",subtitle:null,reviewType:"peer-reviewed",abstract:"This book gives a comprehensive overview of recent advances in Retrovirology, as well as general concepts of molecular biology of retroviral infections, immunopathology, diagnosis, and prevention, to current clinical recommendations in management of retroviruses, including endogenous retroviruses, highlighting the ongoing issues, recent advances, with future directions in diagnostic approaches and therapeutic strategies.",isbn:"978-953-51-2261-6",printIsbn:null,pdfIsbn:"978-953-51-5424-2",doi:"10.5772/60583",price:119,priceEur:129,priceUsd:155,slug:"advances-in-molecular-retrovirology",numberOfPages:202,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"1c523c89d0884b6e909a6d49d8c3a9dd",bookSignature:"Shailendra K. Saxena",publishedDate:"March 16th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5078.jpg",numberOfDownloads:13174,numberOfWosCitations:7,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:7,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:19,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 8th 2015",dateEndSecondStepPublish:"April 29th 2015",dateEndThirdStepPublish:"July 26th 2015",dateEndFourthStepPublish:"August 25th 2015",dateEndFifthStepPublish:"September 24th 2015",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"12",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"427",title:"Virology",slug:"biochemistry-genetics-and-molecular-biology-microbiology-virology"}],chapters:[{id:"50038",title:"Molecular Biology and Pathogenesis of Retroviruses",doi:"10.5772/62885",slug:"molecular-biology-and-pathogenesis-of-retroviruses",totalDownloads:3366,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Retroviruses consist of a varied family of enveloped RNA viruses with positive-sense RNAs that replicate in a host cell through the process of reverse transcription. Retroviruses belong to the Retroviridae family that typically carries their genetic material in the form of ribonucleic acid, while the genetic material of their hosts is in the form of deoxyribonucleic acid. Infections with a number of retroviruses can lead to serious conditions, such as AIDS, a range of malignancies, neurological diseases, and added clinical conditions. In addition, some can even become integrated as DNA in the germ line and passed as endogenous viruses from generation to generation. Surprisingly, retroviruses do not appear to straightforwardly activate host innate defenses. On the other hand, attention in these viruses extends beyond their disease causing capabilities. For example, studies on the retroviruses led to the discovery of oncogenes, understanding of mechanisms that regulate eukaryotic gene expression, and these are proving to be valuable research tools in molecular biology and have been used successfully in gene therapy. The central goals of retrovirology today are the treatment and the prevention of human and non-human diseases and to use this virus in research.",signatures:"Shailendra K. Saxena and Sai V. Chitti",downloadPdfUrl:"/chapter/pdf-download/50038",previewPdfUrl:"/chapter/pdf-preview/50038",authors:[{id:"158026",title:"Prof.",name:"Shailendra K.",surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],corrections:null},{id:"49875",title:"Role of Host Proteins in HIV-1 Early Replication",doi:"10.5772/62108",slug:"role-of-host-proteins-in-hiv-1-early-replication",totalDownloads:1586,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"After 33 years of the identification of HIV-1 infection, very little is known about the role of host cellular proteins. Till now considerable work has been done in the area of host- pathogen interactions facilitated by the viral proteins and host receptors. The role of the main receptor CD4 and co-receptors like CCR5, CXCR4 and their alternative receptors were well studied in disease progression. But the intracellular events during the host- pathogen interactions were poorly understood. Much data is available based on the global analysis of genome-wide RNA interference screens, yeast two-hybrid system and co-immunoprecipitation studies but their exact roles are not yet characterized. There are very few host proteins like APOBEC3G, LEDGF/p75, INI1, HMG I(Y), BAF which are well studied and characterized. Majority of the reported proteins are attributed to multiple functions. It will be useful to study such proteins to develop as future candidates in HIV-1 therapeutics.",signatures:"Lokeswara S. Balakrishna and Anand K. Kondapi",downloadPdfUrl:"/chapter/pdf-download/49875",previewPdfUrl:"/chapter/pdf-preview/49875",authors:[{id:"176706",title:"Prof.",name:"Anand K",surname:"Kondapi",slug:"anand-k-kondapi",fullName:"Anand K Kondapi"},{id:"176713",title:"Dr.",name:"Lokeaswara",surname:"Balakrishna S",slug:"lokeaswara-balakrishna-s",fullName:"Lokeaswara Balakrishna S"}],corrections:null},{id:"49704",title:"Molecular Mechanisms Controlling HIV Transcription and Latency – Implications for Therapeutic Viral Reactivation",doi:"10.5772/61948",slug:"molecular-mechanisms-controlling-hiv-transcription-and-latency-implications-for-therapeutic-viral-re",totalDownloads:2259,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Persistence of transcriptionally silent replication competent HIV-1 is a major barrier to clearance of the virus from patients; current combinatorial antiretroviral therapies are successful in abrogating active viral replication, but are unable to eradicate latent HIV-1. A “shock and kill” strategy has been proposed as a curative approach in which latent virus is activated and infected cells are removed by immune clearance, while new rounds of infection are prevented by antiretroviral therapy. Much effort has been put toward understanding the molecular mechanisms maintaining HIV latency and the nature of reservoirs, to provide novel therapeutic targets. This has led to the development of latency reversal agents (LRAs), some of which are undergoing clinical trials. Targeting multiple mechanisms underlying HIV latency via a combination of LRAs is likely to result in more potent activation of the latent reservoir. Therefore, novel as well as synergistic combinations of therapeutic molecules are required to accomplish more potent latency reversal.",signatures:"Michael D. Röling, Mateusz Stoszko and Tokameh Mahmoudi",downloadPdfUrl:"/chapter/pdf-download/49704",previewPdfUrl:"/chapter/pdf-preview/49704",authors:[{id:"176509",title:"Associate Prof.",name:"Tokameh",surname:"Mahmoudi",slug:"tokameh-mahmoudi",fullName:"Tokameh Mahmoudi"},{id:"176551",title:"M.Sc.",name:"Michael",surname:"Röling",slug:"michael-roling",fullName:"Michael Röling"},{id:"176552",title:"MSc.",name:"Mateusz",surname:"Stoszko",slug:"mateusz-stoszko",fullName:"Mateusz Stoszko"}],corrections:null},{id:"49621",title:"Which Vaccination Strategies and Immune Responses are More Effective Against HIV Infections?",doi:"10.5772/61913",slug:"which-vaccination-strategies-and-immune-responses-are-more-effective-against-hiv-infections-",totalDownloads:1730,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Vaccination is one of the most successful approaches for controlling various viral diseases. Novel approaches will be needed to develop highly effective vaccines to prevent infectious diseases such as HIV. There are many aspects of HIV-1 biology that make the development of an HIV vaccine difficult, including viral diversity, effective type of immune response, and suitable experimental model for preclinical trials. In spite of these challenges, recent published results showed that a vaccine regimen could reduce HIV infection rates by 31% in Thailand. This vaccine named as RV144 is composed of a recombinant canarypox vector expressing three HIV-1 proteins as a prime and two different recombinant HIV-1 gp120 envelope glycoproteins with alum adjuvant as a boost. In addition, a subunit vaccine constructed from the viral envelope protein could be efficiently developed using new techniques available through genetic engineering. The current HIV-1 vaccine development focuses on antibody-based approaches. It was shown that immunization with the viral envelope glycoprotein, gp120, should generate neutralizing antibodies that would prevent infection, thereby yielding protective immunity. However, HIV could develop many pathways to escape from antibodies that bind to the different parts of the viral envelope molecules. Thus, the generation of neutralizing antibodies is very difficult after viral infection or immunization protocols. Indeed, the viral envelope molecules (Env) possess glycosylated residues that cover surface epitopes for binding and neutralizing antibodies, even if the antibodies are produced. Furthermore, the trimeric structures of envelope molecules show rapid conformational changes due to the interaction with viral cell surface receptors, CCR5/CXCR4 and CD4; thus the transition state is very poor to be recognized by the immune system. Currently, studies focus on generating stable trimeric envelope molecules (gp120/gp41) as immunogens that can induce neutralizing antibodies that can compete for binding to the cell surface receptors. Altogether, it is clear that the design of a vaccine to elicit HIV-neutralizing antibodies is not straightforward, and it causes major challenges in structural biology and immunology, several other studies strongly suggest cytotoxic T-lymphocyte (CTL)-based immune responses against HIV infections. Indeed, CD8+ T cells play a major role in controlling viral replication during primary HIV infections and in maintaining a stable viral load during the chronic phase. In this line, live-attenuated vaccines could elicit more potent and durable pathogen-specific immune responses than inactivated or subunit vaccines. Generally, DNA vaccines are poorly immunogenic alone, and viral vector vaccines are ineffective due to vector-specific immune responses if used repeatedly; hence, the two approaches have often been tested in combination as prime-boost vaccination strategies. Indeed, the prime-boost vaccination has been considered as an efficient strategy against HIV infections. In this chapter, we will represent challenges to determine the best vaccine strategies against HIV infections.",signatures:"Azam Bolhassani",downloadPdfUrl:"/chapter/pdf-download/49621",previewPdfUrl:"/chapter/pdf-preview/49621",authors:[{id:"43525",title:"Prof.",name:"Azam",surname:"Bolhassani",slug:"azam-bolhassani",fullName:"Azam Bolhassani"}],corrections:null},{id:"49607",title:"Retroviral Vectors in Gene Therapy",doi:"10.5772/61844",slug:"retroviral-vectors-in-gene-therapy",totalDownloads:2567,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Several decades ago, the first retroviral vectors were constructed. They have been proved as delivery vehicles in basic and translational research; many of them were used in clinical trials in the treatment of genetic and immunologic disorders or malignancies to deliver therapeutic genes into target tissue. Gammaretroviral and lentiviral vectors are popular viral delivery vehicles; their ability to integrate into genome of the host cell enables permanent genetic modification of the target cell and long-term expression of the transgene. Besides classical cancer gene therapy, they are used in cell-mediated cancer gene therapy in combination with mesenchymal stromal cells (MSC) or neural progenitors. Based on the promising preclinical studies, clinical trials with genetically engineered cell vehicles were initiated.",signatures:"Miroslava Matuskova and Erika Durinikova",downloadPdfUrl:"/chapter/pdf-download/49607",previewPdfUrl:"/chapter/pdf-preview/49607",authors:[{id:"176504",title:"Dr.",name:"Miroslava",surname:"Matuskova",slug:"miroslava-matuskova",fullName:"Miroslava Matuskova"},{id:"177393",title:"Dr.",name:"Erika",surname:"Durinikova",slug:"erika-durinikova",fullName:"Erika Durinikova"}],corrections:null},{id:"49403",title:"HERVs in Multiple Sclerosis — From Insertion to Therapy",doi:"10.5772/61726",slug:"hervs-in-multiple-sclerosis-from-insertion-to-therapy",totalDownloads:1666,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Genome-wide association studies (GWAS) have not been able to completely elucidate the genetic background of complex diseases. Part of it could lie in repetitive sequences not studied in the GWAS, as those corresponding to Human Endogenous Retroviruses (HERVs). In the present work, we aim to review the potential role of HERVs in the etiology of autoimmune diseases, especially in multiple sclerosis (MS); their potential pathogenic role and their putative consideration as a good target for new treatments. For this purpose, we carried out an in-depth literature review on HERVs, and we integrated our previous findings about HERV-W, HERV-K18, and HERV-Fc1 and MS susceptibility. The study was carried out by a systematic search from electronic databases using the keywords “HERV,” “Multiple sclerosis,” “HERV-W,” “MSRV,” “HERV-K,” “HERV-Fc1,” and “GNbAC1.”",signatures:"Belén de la Hera and Elena Urcelay",downloadPdfUrl:"/chapter/pdf-download/49403",previewPdfUrl:"/chapter/pdf-preview/49403",authors:[{id:"176421",title:"Dr.",name:"Elena",surname:"Urcelay",slug:"elena-urcelay",fullName:"Elena Urcelay"},{id:"177568",title:"MSc.",name:"Belén",surname:"De La Hera",slug:"belen-de-la-hera",fullName:"Belén De La Hera"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"3311",title:"Current Perspectives in HIV Infection",subtitle:null,isOpenForSubmission:!1,hash:"1bcacf84d50370cac414fea1616244c6",slug:"current-perspectives-in-hiv-infection",bookSignature:"Shailendra K. 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Saxena",coverURL:"https://cdn.intechopen.com/books/images_new/6667.jpg",editedByType:"Edited by",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,isOpenForSubmission:!1,hash:"d92a4085627bab25ddc7942fbf44cf05",slug:"current-perspectives-in-human-papillomavirus",bookSignature:"Shailendra K. Saxena",coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",editedByType:"Edited by",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8959",title:"Innate Immunity in Health and Disease",subtitle:null,isOpenForSubmission:!1,hash:"cea4f56328f9d1ee0c6f1486a12afa23",slug:"innate-immunity-in-health-and-disease",bookSignature:"Shailendra K. Saxena and Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/8959.jpg",editedByType:"Edited by",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],equalEditorOne:{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash",profilePictureURL:"https://mts.intechopen.com/storage/users/287184/images/system/287184.jpg",biography:"Dr. Hridayesh Prakash is a fellow of the Royal Society of Biology, London. Currently, he is an associate professor at the Institute of Virology and Immunology, Amity University, NOIDA. He has expertise in innate immunity with a special interest in macrophage immunobiology, tumor immunology/immunotherapy, cell-based immunotherapies, pulmonary infection biology, and radiation biology. \n\nDr. Prakash conducts research to exploit various immunotherapeutics for managing persistent bacterial and viral Infections and gastric cancer. He is unraveling the therapeutic potential of M1 effector macrophages against solid tumors. He is also studying various mechanisms that certain pathogens like Helicobacter pylori, Chlamydia, and Mycobacteria are exploiting for polarizing M1 effector macrophages towards the M2 phenotype during chronic and persistent infections. 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Although the connection between psychopathy and crime perpetration is well-documented, rate of victimization of friends and relatives is unknown [2, 3]. Intrafamilial physical, sexual, psychological, and financial abuse is the subject of epidemiologic investigations; however, the connection between familial victimization and symptoms of psychopathy in perpetrators is not established. If psychopathy is indeed the
Cleckley mentioned the plight of numerous family members in 15 case studies he presented in
The plight of family members of psychopathic individuals (a predominant theme in 14/15 cases reported in Cleckley’s | |
---|---|
Family relationship | Hardship endured |
Parents | Regarding “Walter’s” father, “His grief and shame seemed almost, but not quite too much for him” |
Regarding “Roberta,” “such conduct of course suggests she might have been deliberately trying to hurt her parents” | |
“Stanley’s” mother is quoted, “…and it’s just killing us, all the things he does” | |
Siblings | “Jack’s” story, “In time he became an all but unbearable burden on the other members of his family (4 siblings)” |
Spouses | Spouses are described in 9 cases, suffering desertion, financial abuse, infidelity and assault (2 cases) |
Children | Children are only mentioned in two cases and no details are given regarding parenting behavior |
Family members in 14/15 cases detailed in Cleckley’s
Although epidemiologic data are lacking, it is possible to estimate the scope of the problem of family psychopathy using data from “Frank” and the United States Census as a model. The prevalence of antisocial personality disorder (ASPD) is about 4% of the adult population [15] and severe psychopathy may be 0.06% [16]; there are 219,726,708 adults between 18 and 65 years in the USA [17]. Hence, there are an estimated 8.8 million individuals with ASPD including 1.3 million with severe psychopathy. If Frank is typical of those with moderate psychopathy and each person with ASPD adversely affects eight close others, then the public health problem of psychopathy may impact 70.4 million Americans or nearly a third of the adult population. Given the familial nature of personality and related disorders, many impacted individuals also have their own psychiatric morbidity, and many families are coping with more than one psychopathic individual [18].
To coerce means to compel or force another to comply. Coercive behavior reflects reactance and a motive to dominate others; it is a tool for obtaining control over resources and other people [19, 20]. Patterson identified “coercive family interactions” that occur in the families of children and teens with the externalizing disorders that are precursors to adult psychopathy. He hypothesized that children learn coercion tactics early in life because such tactics are an effective strategy for the procurement of reinforcers. Strong dominance motivation facilitates learning of coercive tactics because dominant individuals are sensitive to reward [19]. Coercion is associated with negative emotions—trait anger and irritability (these often accompany trait dominance motivation [19]). According to Patterson, “It is the patterned irritable exchanges between the problem child, his mother, and his siblings that define the ‘basic training’ for coercion” [21]. Patterson brilliantly observed that not only is the problem child trained in coercion during these family interactions, but also parents are trained to submit to the child who uses coercive tactics: the externalizing child asks for something; parent refuses, child then escalates his/her demands until the parent submits. The difference between normative and problem children is that the former are not excessively driven to dominate their parents and problem children are not hampered in their demands by the presence of empathy [22]. Because problem children are deficient in (or dissociate from) emotional empathy, they are not concerned that their behavior distresses their parents.
Children’s coercive behavior and lack of rewarding child-parent interaction has negative effects on parents’ attributions and behavior [23]. Parents of problem children are more likely to view the motives of their children as malevolent. Negative parenting behavior results from the impact of the child’s externalizing disorder on the parent; it is not necessarily the sole cause of the problem child’s behavior. Because problem children emotionally drain their parents, they are robbed of the opportunity to learn enjoyment of affection and empathy in their relationships with them. Studies of the causes of psychopathy reveal that genes contribute about half of the risk; the rest of the risk primarily comes from a child’s unique environment [24]. Therefore, the dysfunctional relationships between problem children and their parents are likely to be important to developmental continuity of disorder. Treatment of externalizing children involves helping parents break the cycle of coercion and negativity, and cultivate affectionate interactions [25, 26].
While some parents of children with externalizing disorders also have psychopathic traits, many do not. These unaffected parents suffer a great deal trying to meet the needs of their disordered children who age to maturity but often are not independent (Table 1). Parents continue to give care and may be subjected to parasitism and abuse [12, 14]. In my work, I have interviewed many mothers and fathers who partnered and had children with psychopathic men and women. I discovered that when the children from these relationships develop psychopathy, it becomes impossible for these parents to escape the victimization experience that began with their psychopathic partner. In middle adulthood, they find that the life-energy expended parenting was spent on a child who now preys on others and is unable to assume adult roles. The golden years many dreamt of living, with grandchildren and mature relationships with adult sons and daughters are fraught with loneliness and stress.
Most children in Western countries have at least one sibling, therefore most psychopathic individuals have a sibling [27, 28]. Sibling abuse is the most common form of domestic abuse [29], and sibling sexual abuse is the most common form of familial sexual abuse [30]. Sibling violence reflects risk for violent behavior generally and hence may point to psychopathic traits [31]. Sibling assault leading to injury is linked to psychopathy [31]. Despite these statistics, the impact of children with externalizing disorders on their siblings and the extent to which sibling abuse is associated with morbidity in either perpetrators or victims is not well documented. Patterson [32], and his group described two ways older siblings increase risk for antisocial behavior in younger siblings. First, externalizing children train their siblings in coercion. This training results from both imitation of coercive interactions with parents and from direct practice in coercive behavior during sibling conflict. Second, externalizing siblings recruit their younger brothers and sisters into antisocial activities (Table 2) [33].
“Mary” describes life with her sister. This written account was provided by a woman who wanted her story shared to help others. The account is hers and illustrates the familial nature of psychopathy and the plight of those exposed to psychopathy in multiple family members; details were altered to further conceal “Mary’s” identity.
One study directly examined dyadic interactions between antisocial teens and a same sex sibling, friend, and romantic partner during problem-solving tasks. Negative dyadic interactions included: (a) negative verbal statements (e.g., disapproval) and (b) nonverbal behavior (e.g., negative facial expressions); (c) verbal attacks (e.g., name calling); (d) coercive and ambiguous coercive behavior (e.g., threatening directives that express a demand); (e) requests and ambiguous requests; (f) commands and ambiguous commands (e.g., directives); and (g) physical aggression (e.g., shoving) [34]. These interactions occurred at a relatively high rate, and interestingly, although the teens treated siblings and romantic partners coercively, they were less aggressive toward their friends. The researchers observed a high rate of talking about antisocial activities with siblings. Antisocial talk predicted persistence of antisocial behavior into adulthood. Such verbal exchanges reflect the assumption of an antisocial identity that may be imparted to younger siblings. Dominance relations in adolescent romantic relationships resemble familial relationships more than they do friendships—evidence that schemas of coercion learned in early family interactions are directly transferred to schemas regarding sexual partnerships (see Section 5).
In this discussion, the terms “friend” and “companion” are synonymous such that a friend is a preferred, familiar companion. In my role as professor of psychology and psychopathy researcher, I have been approached by members of the public, students, and staff who have shared their stories of friendship with psychopathic individuals. I am impressed by the level of lasting distress caused by abuse from psychopathic friends. It is not unexpected that psychopathic individuals maintain familial ties that serve their material needs; it is contrary to current theory that many also actively cultivate friendships. Current theory should be amended to account for sociability in psychopathic individuals. Studies by Kosson demonstrate that psychopathy is negatively associated with schizoid personality or a preference for solitary activities [35]. That psychopathic individuals report companions is further evidence for the idea that they do not prefer to be alone. Although psychopathic individuals may lack “affection,” there is some reward connected to the company of others. If psychopathy produced an indifference to companionship, theory would predict that psychopathic individuals would be loners and that they would be less likely than other offenders to join gangs. The social nature of psychopathy is evidenced by the positive association between gang membership and psychopathy and between gang leadership and the interpersonal features of psychopathy [36, 37]. The interpersonal features of psychopathy are also positively associated with social bonds in prison [38]. If psychopathic individuals are truly devoid of affection, these observations challenge the notion that affection and caring are necessary determinants of human social ties.
There are three sources of information regarding psychopathy and friendship: forensic studies, surveys of the general population, and anecdotal accounts. Forensic studies support the social nature of psychopathy indicating that it is associated with co-offending as opposed to solo-offending [39]. Accordingly, psychopathy does not reduce the likelihood of gang membership and gang membership appears to causally relate to callous-unemotional traits [36, 37]. Forensic studies demonstrate the interactive nature of friendship and personality traits. Psychopathy may predispose to the choice of antisocial friends and gang membership and in turn, these associations strengthen the stability of psychopathic personality traits [36]. In college students, DSM 5, Section 111 personality traits associated with ASPD including antagonism, correlate with attempts to be close to others and warm as opposed to cold dominant behavior (as reported by friends) [40]. There is also no negative association between psychopathy and the need to belong in young adults [41]. Community studies of psychopathy in adolescents demonstrate that youth high in psychopathic traits are “as likely as others to have important peers in their lives,” though these friendships may have less temporal stability [42]. Adolescents tend to associate with friends who have similar levels of psychopathy and friends engage in antisocial behavior (including substance abuse) together [39]. Psychopathy is associated with more reciprocated relationships in male adolescents, and does not affect levels of perceived support in relationships. As with adolescents, adults associate with others who have similar levels of psychopathy [43]. In contrast to forensic settings, psychopathy in college settings may not be associated with leadership [44]. Psychopathy is moderately associated with self-reports of not helping friends [31].
In summary, although psychopathy may cause friendships to have less temporal stability, psychopathic individuals seek out companionship and engage in their preferred activities with others. Researchers have labeled such relationships “shallow” and “lacking in depth” because psychopathy is associated with low closeness and reduced helping [31]. That psychopathic individuals cultivate friends to meet their material and companionship needs, receive admiration and attention, and to dominate others is supported by anecdotal accounts [2, 45]. Clinicians and researchers should work to better understand the nature of social reinforcement for psychopathic individuals. Informed application (or deprivation) of social reinforcement has the potential to enhance individual, group, and family therapy for psychopathic adolescents and adults.
Individuals with psychopathy seek relationships to meet material and companionship needs. They then abuse and often fail to help others. This dynamic creates difficulties for friends with low levels of psychopathic traits (who have different relationship expectations). I find that such friends are distressed and perplexed by abuse, betrayals, and lack of reciprocity (also noted in [6]). Friends are often very reluctant to sever ties with psychopathic individuals even those who have abused them. This reluctance reflects both effective manipulation on the part of the psychopathic friend and the presence of a social bond. I could not find any research regarding whether psychopathic individuals leave relationships on their own accord or whether relationships are terminated by abused friends. There is also no systematic data available regarding the time and energy psychopathic individuals invest in maintaining their friendships. Anecdotal data from spouses verify that even highly psychopathic individuals do invest energy into friendships [47].
Psychopathic individuals impact their friendship networks in addition to impacting individual friends. There is too little information regarding psychopathic traits and gangs to make definitive statements about the way individual psychopathy impacts the organization of the gang collective. Decker and Curry state that members murder their “brothers” and that gang murders are often related to intra- as opposed to intergang rivalry. They also suggest that gangs are not well organized [48]. Murder of associates and lack of organization could result from psychopathy in gang members. Poor organization could result from the impaired executive function in members related to the lifestyle facet of psychopathy [49]. Non-criminal organizations are also impacted by members’ psychopathy. In corporations, psychopathy is associated with passive leadership [50] and employee dissatisfaction with supervision [51]. Anecdotal evidence suggests that psychopathy is related to corporate crime and organizational dysfunction [52]. The impact of psychopathy on family organization is discussed below. In the family, facets of PCL-R psychopathy have differential effects on functional dynamics.
Sexual promiscuity and multiple short-term marital relationships are part of the definition of psychopathy [53, 54]. Psychopathy is associated with a ludic love style and self-reports of uncommitted sex (Table 3) [55]. These symptoms convey the impression that psychopathic individuals easily navigate from one relationship to the next without much investment. Lack of investment and ease of relationship mobility would be consistent with the view that psychopathy is associated with a lack of social bonds. Unfortunately for victims and theories of psychopathy, the behavior of many psychopathic individuals does not comport with this view. A survey of self-help message boards and clinical experience indicates that far more people are distressed by ongoing victimization and psychopathic individuals’ refusal to sever ties than by psychopathic partner abandonment [45]. Stalking by psychopathic former partners is also reported [56]. Psychopathic individuals may become vindictive when threatened with abandonment even when they have been unfaithful [6, 57]. If vindictiveness, stalking, and/or refusal to sever ties is connected to a specific variant of psychopathy (perhaps secondary psychopathy), then the relative prevalence of this variant should be determined.
One study of 1805 long-term married couples (average relationship length 19.6 years) found 49 (3%) women and 283 (16%) men reported three or more symptoms of APSD. Anecdotal reports also indicate that psychopathic individuals cultivate long-term romantic partnerships although infidelity is common [45, 47, 58]. Psychopathic individuals often con prospective partners by making misrepresentations regarding core aspects of their lives and identities. They then move the relationship along quickly, seeking early cohabitation and commitment [6, 45, 47, 58]. Partners meet in a variety of settings including through friends, work, place of worship, or school [58]. Passion is high early in the relationship when psychopathic individuals are noted to give material gifts and expressions of love and affection [58, 59]. Contrary to prevailing theory, partners report that even highly psychopathic individuals appear affectionate, especially in the beginning [47]. The beginning phase of the relationship can last several years depending on the circumstance and during this time, abuse is uncommon and the relationship may be harmonious [47]. In retrospect, partners can identify reasons why they were treated well in the beginning. Many say they were used as “cover” and that the psychopathic individual was trying to impress others or appear normal [45, 47, 58]. Others realize the motivation was parasitism. Pregnancy and childbirth are often the turning point where relationships become abusive. Boredom, infidelity, and escalation of substance use or gambling may also trigger partner abuse [60].
There is evidence for assortative mating for psychopathic characteristics (see Tables 3, 6–8) [61–63]. Assortative mating may contribute significantly to intergenerational transmission [64]. Partner’s personality type may be influenced by ACOA status as children of alcoholics may also tend to pair with psychopathic alcoholic individuals [65]. To test the hypothesis that women who partnered with psychopathic men might be temperamentally similar to their partners, the Temperament and Character Inventory was administered to a group of 35 women who were seeking support recovering from abusive relationships with psychopathic men. Narratives regarding the relationship were also collected from the women [58]. In common with psychopathic men, many women in the group had elevated Novelty Seeking scores. This elevation was due to Exploratory Excitability and not Impulsiveness, Extravagance or Disorderliness. In narrative accounts, many described being exhausted by the energy level of and chaos caused by their former partner. It may be that a certain need for excitement and tolerance for chaos is required by those who remain in a relationship with a highly psychopathic person. As one woman said, “It was the best and worst all rolled into one. I’ve never loved so much and in the same breath I’ve never hurt so much. Despite all his horrible qualities, he’s still the most exciting person I’ve ever known (p. 86).” The women also had elevated scores in Reward Dependence, Cooperativeness, and Self-Determination, traits that would tend to facilitate a person remaining in (but also recovering from) an abusive relationship. In this and two other surveys of people seeking to recover from abusive relationships, participants identified their own vulnerabilities, including losses just prior to meeting the psychopathic partner and a history of child abuse or prior sexual assault [45].
There is little doubt that many psychopathic individuals are highly abusive of partners (see below). Partners who are not subjected to high levels of abuse are often distressed by sexual infidelity and financial concerns. In long-term partnerships, psychopathy is associated with marital dissatisfaction [18]. The Cambridge Study in Delinquent Development examined relationship satisfaction and durability longitudinally in men, some with high PCL-SV scores and criminal involvement. In this study, psychopathy was negatively associated with relationship satisfaction and this was attributable to high scores in the affective facet [66]. However, at age 48, most men were cohabitating with a female partner (82%) and endorsed (88%) “gets on well with female partner.” These responses were not significantly associated with either criminality or psychopathy [67].
Twelve studies reveal a consistent negative influence of psychopathy on relationship quality (Table 3) [18, 59, 68–77]. Psychopathy is associated with reduced relationship satisfaction in both dating and cohabitating couples [59, 68]. Studies using the LSRP have found that secondary psychopathy impacts relationship quality more than primary psychopathy. The association between secondary psychopathy and decreased dyadic adjustment is not surprising, given high neuroticism and low conscientiousness in secondary psychopathy [71, 78] and the association between these and poor dyadic adjustment [71, 79]. Primary psychopathy is less robustly associated with low relationship satisfaction. In one study, primary psychopathy predicted a latent factor composed of passion, intimacy, and commitment [59]. Perhaps, individuals high in primary psychopathy are more adept at manipulating partners and using relationships for instrumental purposes [80]. The negative impact of psychopathy on well-being is mediated in part through poor quality of intimate relationships [68]. Turmoil in intimate relationships also predicts increases in self-reported psychopathy over time [71]. Poor parental dyadic adjustment also leads to increases in externalizing symptoms in children [18, 73–76, 81].
Studies of Psychopathy and Romantic Relationships | |||
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N | Definition of psychopathic traits | Study Findings | Study Publication year [Reference] |
431 (Individuals) | LSRP | Psychopathy associated with low well-being and ill-being. Psychopathy associated with relationship quality measures. Relationship quality measures mediated link between psychopathy and well (ill)-being. Effects stronger for women | 2010 [18] |
297 (Individuals) | LSRP | Primary psychopathy was positively associated with latent relationship factor. Secondary psychopathy was negatively associated with life satisfaction and intimacy. Psychopathy and sociosexual orientation equally related to commitment | 2016 [59] |
45 (Couples) | SRP-II | Psychopathy associated with assortative mating and decreased relationship satisfaction in dating couples | 2014 [68] |
140 (Couples) | LSRP | In men, primary and secondary psychopathy associated with own attachment anxiety and avoidance and partner’s attachment anxiety and attachment avoidance Psychopathic traits in women correlated with own and partner’s attachment anxiety and avoidance. Assortative mating was for primary psychopathic traits | 2015 [69] |
140 (Couples) | LSRP | Neuroticism linked to global, primary and secondary psychopathy. Perpetration of psychological aggression linked to global, primary and secondary psychopathy Relationship satisfaction negatively related to secondary psychopathy Assortative mating: primary > global > secondary psychopathic traits | 2011 [70] |
152 (Couples) | LSRP | Dyadic adjustment related to global and secondary psychopathy in men. Relationship distress at Time 1 associated with increases in men’s psychopathy scores a year later (Time 2) | 2006 [71] |
1805 (Couples) | DSM III-R | Adult antisocial behavior and CD linked to negative dyadic adjustment; effect not fully explained by low constraint | 2010 [72] |
1255 (Couples) | DSM III-R | Adult antisocial behavior associated with lower cohesion, satisfaction, consensus on important issues and affective expression | 2013 [73] |
1408 (Couples) | DSM III-R | Assortative mating for CD. History of CD linked to marital discord and decreased family adaptability | 2000 [74] |
1477 (Couples) | SCL-90 Hostility Subscale, Self-reported behavior | Antisocial behavior moderately associated with relationship conflict | 2012 [75] |
112 (Couples) | DSM III-R | Men’s ASPD predicted physical abuse, partner negative psychological adjustment and reduced marital satisfaction | 1999, 2003 [76, 77] |
Relationship variables, marital adjustment and psychopathic personality traits in available studies to date.
Psychopathy underlies community violence including violence toward partners and friends [82]. DSM III-R links ASPD to “spouse or child beating” [54, p. 342]. Psychopathy is associated with intimate partner violence perpetration [83, 84] and intimate partner terrorism [85]. In intimate partner terrorism, all forms of abuse serve the purpose of coercive control of partners [86–88]. Psychopathic men and women’s use of coercive control with partners is an extension of coercive familial behaviors learned during childhood and adolescence [34]. Learning of coercion occurs through both practice and modeling as witnessing domestic violence is a risk factor for the development of psychopathy [89]. Although some link coercive control to patriarchy [86], case histories of perpetrators suggest psychopathy [86, 90] and women perpetrate coercive control [87, 88]. It is likely that psychopathic personality traits associated with Factor 1 predispose to coercive control and also increase susceptibility to messages regarding patriarchy [91].
The extent to which psychopathy considered dimensionally is responsible for the public health problem of intimate partner violence has not been established. Certainly, the degree of psychopathy that increases risk for violence is far below that required for a categorical diagnosis [52]. In one study, abuse of partners was associated with psychopathy and this association was mediated by low Big Five Agreeableness [92]. Partners of psychopathic individuals endorse all forms of abuse including physical, sexual, psychological, emotional, social, financial, and legal [45]. The repercussions of financial abuse for victims have not been systematically investigated. Anecdotally, financial abuse causes poverty in middle age for people who otherwise would have been financially secure [42]. Interestingly, some highly psychopathic individuals contribute financially to their families [47]. Legal abuse occurs through the criminal court when psychopathic individuals recruit unwitting partners into their crimes and through civil court when partners attempt separation [6, 47]. Some psychopathic individuals are skilled at using the family courts to punish former partners [6, 93]. Social abuse occurs when psychopathic individuals spread rumors (a behavior victims have dubbed “the sociopath’s smear campaign” [94]) or behave in ways that damage their partner’s standing with others.
Couples present for couple therapy for reasons that “involve relational matters, such as emotional disengagement and waning commitment, power struggles, problem-solving and communication difficulties, jealousy and extramarital involvements, value and role conflicts, sexual dissatisfaction, and abuse and violence [95]”—all factors expected to be prevalent in the context of psychopathy. Given the association between psychopathy and relationship distress, this disorder is likely common in community couple therapy practice. Current guidelines stipulate that couple therapy not be offered to couples where: (1) the perpetrator of abuse lacks remorse, and does not take full responsibility for the abuse; (2) the perpetrator of abuse has a personality disorder; (3) the victim expresses fear; or (4) there is an ongoing threat of violence [96, 97]. Given that therapists are known not to adequately screen for these contraindications to couple therapy [98, 99], it is reasonable to hypothesize that many couples where these conditions are present do participate in couple therapy.
There are no published studies of couple therapy in the context of psychopathy or ASPD. In a preliminary study [60], 281 people (255 women, 26 men, all heterosexual) reporting relationships with a psychopathic partner (as assessed through DSM 5, Section III symptoms) answered an online survey regarding their experiences in couple therapy. All participants reported psychological abuse and most reported multiple other forms of abuse including physical, financial, and sexual. Although open-ended survey responses describing relationship and partner characteristics clearly pointed to the presence of psychopathy, disorder was identified by a minority of therapists even when abuse was severe. Sixty-two percent of therapists appeared to participants to lack knowledge of psychopathy. Some therapists were reported to have learned about psychopathy only after interacting with the participant’s partner. The combination of DSM 5, Section III Antagonism and Disinhibition symptoms, and therapist knowledge explained 60% of the variance in therapist identification of partner disorder. Therapist detection of partner symptoms was associated with the perceived helpfulness of treatment. One woman stated, "For the first time, someone wasn\'t manipulated by him to the point of thinking he was the victim instead of me. She called him on his ‘red herrings’ and got him back on track when he tried to talk about other things to pass the time.” Participant responses indicated that couple therapists attempted the same communication exercises with them that are recommended for non-personality disordered couples (Table 4). Abused partners feel invalidated during these exercises that may also place them in danger [100]. Therapists who helped participants understand the nature of their partner’s emotional deficits and manipulative behavior were judged most helpful. Only 11% of relationships continued; some therapists assisted participants in exiting the relationship. The responses of survey participants point to a gap in the literature that should be filled by more systematic investigation of community couple therapy practices.
Partner descriptions of communication exercises used in couple therapy |
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Example of open-ended response from two participants who described communication exercises used in couple therapy where partner had psychopathic personality traits.
At present, there are no evidence-supported interventions for partners or former partners of psychopathic individuals. A survey of 301 people, who had received individual psychotherapy for issues related to a long-term relationship with a psychopathic individual was conducted to determine interventions found most helpful and unhelpful by victims [101]. Also of interest was whether therapists were judged knowledgeable regarding the construct of psychopathy and the problem of psychopathy and the family. A minority of therapists were reported to have knowledge of psychopathy and its impact on the family. Participants reported invalidating responses, unhelpful, and harmful therapy when therapists lacked knowledge of psychopathy. In open-ended and Likert responses, participants stated that understanding their former partner’s personality disorder helped them make meaning of their experiences. Effective meaning making reduced self-blame and assisted in overcoming the distorted cognitions imparted to them by their abuser. Traditional approaches to family violence that attribute abuse to patriarchy as opposed to personality disorder may not be well suited for family members of psychopathic individuals. Such approaches do not assist with meaning making and risk of re-victimization related to pairing with another psychopathic individual. Furthermore, men victims of psychopathic partners require therapeutic assistance and do not fit the traditional model of domestic violence [88]. Former partners who share children with a psychopathic parent may not be able to cease having contact with their abuser. They need help learning effective strategies for dealing with the psychopathic co-parent (unfortunately, there are no data on effective strategies to provide them). These parents also need extensive support to provide the kind of nurturing parenting that will mitigate genetic risk for psychopathy [102].
Parenting behavior and the family environment caused by psychopathic traits are important in the intergenerational transmission of psychopathy [103]. When I was trained in psychiatry, neglectful parenting behavior was part of the definition of ASPD in DSM III-R (Table 4) [54]. We were taught that people with ASPD neglect and abandon their children. In response to my presentations at scientific meetings, colleagues have opined that “psychopaths2 [sic] are disinterested in parenting.” Several years ago, I sat in family court observing a custody case regarding a father I knew to be highly psychopathic. The father paid a psychologist to testify on his behalf to rebut the neutral forensic evaluator who had diagnosed psychopathy. The paid expert testified that since this father wanted a relationship with his children, he could not be “a psychopath.” The court transcript quotes the psychologist, “Robert Hare in his book says that psychopaths have no use for, or interest in children3…This man wants a relationship with his children and that is not typical for a psychopath.” This belief may be firmly ingrained in mental health professionals and may be the reason why parenting in relation to psychopathy is understudied. As with romantic partners, the problem of psychopathy and parenting is not abandonment [105]. It is psychopathic parents’ motivation to maintain ties with children who they neglect, abuse, and expose to antisocial activities.
A comprehensive list of studies of paternal [103, 105–115], maternal [116–122], and parental [73, 75, 93, 123–126] behavior in relation to psychopathic traits is provided in Tables 6–8. There is one large-scale study of parenting and psychopathic traits [123]. Dimensional Psychopathy correlates with reduced closeness, parenting stress, and unhappiness with the parenting role (Table 6). The three parenting studies that examined the correlation between paternal and maternal psychopathic traits found small to moderate correlations [107, 110, 126]. Psychopathy in fathers is associated with abandonment and IPV perpetration, especially in the context of maternal psychopathic features [110, 125, 126]. Outcome for children is worse when antisocial fathers maintain contact [105, 107, 110, 111, 127]. Psychopathic traits are associated with coercive, hostile and neglectful fathering, and low warmth. Paternal psychopathy impacts the structure of children’s lives due to poor marital quality, unstable housing, a chaotic home environment, and poverty [103]. Maternal psychopathy is associated with lower age at first birth [109, 125]. Regardless of age, psychopathic mothers may be abusive and neglectful, and show inappropriately low levels of monitoring and inconsistent discipline; their mothering tends to be hostile, coercive, and shaming with low levels of warmth (Tables 5 and 6). Outcome for children is related to the home environment and parenting practices of psychopathic mothers [117, 119, 120]. There are no studies examining whether there is a dose-effect of exposure to psychopathic mothers as there is with psychopathic fathers with respect to negative outcome.
Parenting behavior diagnostic of antisocial personality disorder (ASPD) |
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(4) repeatedly fails to honor financial obligations, as indicated by defaulting on debts or failing to provide child support or support other dependents on a regular basis. (8) if a parent or guardian, lacks ability to function as a responsible parent, as indicated by one or more of the following: (a) malnutrition of child (b) child’s illness resulting from lack of minimal hygiene (c) failure to obtain medical care for a seriously ill child (d) child’s dependence on neighbors or nonresident relatives for food or shelter (e) failure to arrange for a caretaker of a young child when parent is away from home (f) repeated squandering, on personal items, of money required for household necessities |
Parenting behavior in DSM III-R criteria for antisocial personality disorder.
Studies of Psychopathy and Fathering | |||
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N | Definition of psychopathic traits | Study Findings | Study Publication year [Reference] |
478 | PCL-SV | Paternal psychopathy linked to unstable employment, unstable housing and substance abuse, and psychopathy in offspring | 2015 [103] |
34 ASPD+/SD+ | SCID II; DSM III-R ASPD | Children of ASPD+/SD+ fathers had higher externalizing and internalizing psychopathology and association with deviant peers than both ASPD−/SD+ and ASPD−/SD−. | 2002 [106] |
161 | SCID II; DSM IV ASPD | ASPD associated with paternal abandonment. ASPD in mother and father correlated. | 2001 [107] |
20 | PSCAN; Partner report | Children exposed to IPV; father abused children by lying to them, ignoring them, failing to provide for them, bullying and terrifying them, breaking promises to them, and destroying their toys | 2005 [108] |
1116 | DSM IV ASPD | “When fathers engaged in high levels of antisocial behavior, the more time they lived with their children, the more conduct problems their children had” | 2003 [105] |
980 | DSM IV CD | CD was associated with earlier age at first birth, IPV, negative parenting practices and DBDs in children | 2006 [109] |
1626 | DSM III-R | Mother and father ASB correlated. Mother ASB negatively correlated with father residence. Father ASB correlated with non-residence. Child behavior problems increased with amount of time with father. “As the length of time that the father was present in the home increased, so too did the strength of the relationship between father and child antisocial behavior” | 2008 [110] |
230 | MMPI-TRI | Child behavior problems were associated with more time spent with antisocial fathers. Coercive fathering was predicted by antisocial personality features in fathers | 2010 [111] |
261 | ASB | ASB was associated with harsh discipline and low warmth. ASB associated with internalizing and externalizing symptoms that increased with the amount of contact between father and child | 2011 [112] |
543 | ASB | Father-child contact mediates intergenerational continuity of ASB, effect mediated by dysfunctional parenting | 2009 [113] |
96 | Antisocial behavior | Antisocial fathers with alcohol use disorders, family shows less engagement during interactions | 2000 [128] |
145 | PDQ-4 ASPD | Paternal ASPD and Borderline PD traits were correlated; ASPD traits correlated with psychological and physical aggression and predicted children’s overall psychosocial impairment and externalizing problems | 2014 [13] |
8 | IPV perpetration | Qualitative study of children’s lived experience. Children observed to dissociate. Had difficulty integrating conflicting observations of and feelings toward father. Children felt “trapped in conflict” and responsible for father’s “influence” | 2015 [14] |
66 | IPV perpetration | Greater contact with father, more externalizing problems and more exposure to IPV | 2016 [15] |
Parenting behavior and child outcomes for psychopathic fathers.
Anecdotal reports and qualitative studies provide first-hand accounts of the human suffering caused by parental psychopathy [6, 93]. Children and adults describe a confusing combination of loving and abusive experiences; this mix of experiences and the trauma associated with parental psychopathy produces disorganized attachment and dissociation of parental object representations [64, 83]. Children (who often carry genetic risk [105]) may develop internalizing and/or externalizing disorders. Psychopathic parents may select both favorites and targets for abuse from among the children of the family [93]. Favorites are overindulged and provided lax supervision, while targets are subjected to shaming and other abuse [93]. Psychopathic parents may enjoy inducing fear in their children and they may maintain poor sexual boundaries [93]. Psychoticism, defined as unusual beliefs and experiences, eccentricity, and perceptual dysregulation (DSM 5, Section III) is apparent in descriptions of parents provided by adult offspring and former partners [45, 47, 58, 93]; psychoticism manifests in the psychopathic individuals’ distorted worldview. The family takes on “cult-like” characteristics when psychopathic individuals demand that family members endorse their distorted views and unusual beliefs [93].
An examination of the complete quantitative and qualitative literature reveals consistent patterns in the relations between children’s experiences and the construct of parental psychopathy (Figure 1). Although most quantitative studies assessed primarily traits related to PCL-R Factor 2, there is sufficient evidence to conclude that Factor 1 traits also impact parenting and determine children’s experience. Pathological lying and the other interpersonal manifestations of psychopathy link to severe emotional and psychological abuse [93]. Invalidation and “gas-lighting” cause children to doubt their own perceptions of reality. Parental alienation (parental attempts to distance the child from a loving co-parent) may be one manifestation of “gas-lighting” [6]. Affective deficits and dominance needs cause parents to enjoy frightening and shaming children. Parents’ affective deficits produce guilt and confusion and impair trust [6, 93]. Lifestyle deficits cause unstable residence, neglect, and poverty [103] (see Tables 6–8). Early behavioral problems and juvenile delinquency may be markers for increased genetic risk in children. Criminal behavior and poor behavioral controls cause modeling of antisocial behavior, coercive control and physical abuse. The sexual symptoms of psychopathy cause exposure to multiple (perhaps psychopathic) stepparents, exposure to sexually inappropriate material, and sexual abuse [93].
The relationship between parental psychopathy and children’s lived experience. Symptoms of psychopathy are in the center of the circle, Factor 1 [Interpersonal (INT), Affective (AFF)] symptoms are on the left; Factor 2 [Lifestyle (LIFE), Antisocial (ANT)] are on the right, sexual symptoms are on top. Children’s lived experience is portrayed in Kristen ITC font in the outer circle adjacent to associated facets. Fear and shame are central to the experience of having a psychopathic parent.
Studies of Psychopathy and Mothering | |||
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N | Definition of psychopathic traits | Study Findings | Study Publication Year [Reference] |
141 | MMPI-2 ASP Scale | Pd scale of MMPI had poor predictive validity with respect to parenting measures. ASP scale antisocial mothers less understanding, more abusive, used shame, and coercion | 2014 [123] |
1116 | DSM IV ASPD | ASPD mothers’ home environment poor; chaotic; reduced happiness, reduced stimulation, parenting stress; ASPD mothers had less positive parenting less warmth and more negativity. Child neglect present in 16.2% ASPD only and 33.9% ASPD/Depression | 2012 [124] |
88 | PPI-R; PDQ-4 | ASPD symptoms linked to poor monitoring, inconsistent discipline, decreased involvement, boys’ CU, impulsive and narcissistic traits | 2012 [125] |
83 | LSRP | Primary and secondary psychopathy associated with parenting dysfunction and child conduct problems | 2013 [129] |
201 | C-DIS-IV (DSM IV) | Maternal ASPD associated with IPV exposure and child DBDs. Maternal ASPD not associated with parenting indices, impact of dysfunctional parenting mediated by IPV exposure and child temperament | 2010 [126] |
299 | Adult Self Report (ASR) | Maternal ASB associated with depression, hostile parenting, and child DBDs | 2012 [75] |
126 | Family Informant Schedule and Criteria (FISC) | Maternal ASB associated with poor monitoring; maternal CD associated with decreased punishment; other parenting variables not associated with either ASB or CD | 2013 [93] |
Parenting behavior and child outcomes for psychopathic mothers.
The clinical literature and the family courts may refer to couples where there is an abusive psychopathic parent and a victimized partner as “high conflict” [75, 128, 129]. Child victims are conceptualized as being caught up in “parental conflict” rather than in a situation where one parent has the burden of protecting them from abuse [130]. Such terminology conveys the impression that the non-psychopathic victimized co-parent is partly responsible for the family pathology. Although psychopathy in mothers and fathers is correlated, correlations are modest. Professionals involved with the family should therefore assess psychopathy dimensions in both partners using all available data. Evaluators should carefully consider the credibility of information they are given. If psychopathic traits are suspected, evaluators should document the presence of symptoms from all four facets of psychopathy and consider the differential impact of these on the child (Figure 1). The presence of mood, anxiety, and substance use disorders in parents should be assessed. Domestic violence including all forms of partner and child abuse should be documented. Clinicians should attempt to classify the family according to whether psychopathy is significant in one or both parents and as to whether abuse is primarily unidirectional. There are sufficient data (Tables 6–8) to recommend that if there is a relatively healthy parent, contact with the psychopathic parent should be limited. For further discussion of custody evaluations, see Refs. [5] and [6].
Studies of Psychopathy and Parenting | |||
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N | Definition of psychopathic traits | Study Findings | Study Publication year [Reference] |
15,701 | Big 5 facets associated with psychopathy | Reduced happiness with the parenting role; reduced closeness; increased stress from children; overwhelmed with role | 2014 [123] |
145 | IPDE-S | ASPD symptoms associated with lower quality responsiveness by mothers and child attempts to engage parent in social interaction. NPD symptoms associated with controlling parenting in both mothers and fathers | 2012 [124] |
99 mothers 72 fathers | ASB, arrest records and self-report | 3-generation study, mother and father ASB correlated; father ASB negatively correlated with contact with child; ASB in mother correlated with younger age of first birth | 2012 [125] |
1255 | DSM–III–R ASPD | Antisocial parents had significantly lower levels of cohesion and satisfaction, lower consensus on important issues, and a lower overall marital quality. Antisocial mothers and fathers dysfunctional parenting; fathers less involved | 2013 [128] |
489 | DSM IV ASPD | ASB in mother and father correlated. ASB correlated with adversity for children, parental neglect, and exposure to violence | 2010 [126] |
1477 | Antisocial behavior | Antisocial mothers and fathers more hostile parenting, these related to child ASB | 2012 [75] |
9 | PCL-R, DSM 5 | Qualitative study; psychopathic parents can be granted custody; psychopathy associated with abuse, neglect, exposure to multiple antisocial adults, chaotic home environment, unstable residence, poverty; children report: fear, confusion, shame, and anger; some given false information regarding their identity; children also report positive family experiences and feelings of love and loyalty toward psychopathic parent; family resembles a “cult” | 2013 [93] |
Parenting behavior and child outcomes for psychopathic fathers and mothers.
Relatively healthy parents should be referred for treatment of problems associated with any trauma they may have suffered. They should also be counseled regarding the detrimental impact disordered stepparents might have on children. The risk for revictimization by another psychopathic partner should be discussed. There are no data as to the frequency with which children are forced to spend time with or are placed by the courts in the custody of abusive psychopathic parents. My clinical experience and anecdotal evidence suggest this may be a serious problem in all Western democracies [93]. Professionals can assist children who have been victimized by recommending to the court that they be given truthful information as they can tolerate it (to counteract pathological lying and gas-lighting). Children may do better if the relatively healthy parent is coached as to how to provide them with direct truthful answers to questions [128] (although some localities have laws that prohibit parents from answering children’s questions truthfully [93]). Professionals should be aware of the possibility that if there is a marital separation, children may be jeopardized by a court decision to grant unsupervised parenting time to a psychopathic parent. Circumstances may dictate that a co-parent remain in an abusive relationship to protect (a) young child(ren).
Studies of families, relationship quality, conflict, and psychopathy show that marital problems and parent child problems worsen symptoms of psychopathy in mothers, fathers, sons, and daughters (Tables 3 and 6–8). Families may thus get caught in a positive feedback loop of worsening relations and psychopathic features. If therapy could reduce conflict and enhance relationship quality, symptoms of psychopathy in family members would likely decline. Evidence supported family therapy for adult psychopathy has not been developed though family therapies for adolescents with externalizing disorders do exist [131]. Studies of family therapy for youth with externalizing disorders should assess parental psychopathy to assess its impact on treatment effectiveness. Psychopathy is known to be a poor prognostic indicator for batterer intervention [132].
Anecdotal reports note that some family members assist psychopathic individuals in evading arrest and capture and others hold them accountable [47, 93]. Forensic experts report that marriage reduces criminal recidivism in psychopathic individuals [133]. In the case of “Frank” mentioned in the Introduction, the treating clinician stated, “Frank’s wife has indicated that she is invested in Frank’s recovery and remains connected to him. Her willingness to support his recovery should be explored. The possibility of a pharmacologic intervention may encourage her to remain supportive,
Psychopathy is clearly a familial disorder and a disorder of the family. Dysfunctional family relationships both worsen and are worsened by psychopathy. The long-standing belief that psychopathic individuals do not form lasting bonds with others has hindered therapeutic progress. While the nature of social reward for highly psychopathic individuals is yet to be determined, they do not prefer to be solitary. Forensic and community studies reveal that most psychopathic individuals maintain social ties over years and that these ties serve their psychological and material needs. Taken in its entirety, the psychopathy literature suggests that dominance reward [19] from both social power and material resource control [20] motivates sociability for highly psychopathic individuals. Couple and family therapy for psychopathy should be studied in the context of disorder severity. Also needed are evidence supported therapies for recovering adult sons and daughters and former partners of psychopathic persons.
Researchers have been attracted by the mystery of human neural development for hundreds of years. Numerous cellular and animal models have been explored to improve our understanding of neurogenesis in humans for hundreds of years. Although animal models have greatly improved our understanding of neural development, neurological disorders, cortical architecture, and functional regionalization, there are significant differences between the human and rodent brains. For example, the organization and behavior of neural progenitors during embryonic development determine the expansion and folding of the human neocortex to a large degree. Therefore, studying the development of the human brain requires models with human brain characteristics. Organoids are simply, self-organized three-dimensional (3D) tissue cultures that are derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which has gained great interest in simulating tissue development and disease. This technology opens a window to observe some of the most elusive aspects of human biology. Compared with animal models or two-dimensional (2D) cell culture systems, 3D-cultured organoids can overcome the differences between species and closely represent the realistic human-specific development features, which can be utilized to mimic the architecture and functionality of the human tissues, having great advantages in explaining the unique human developmental processes [1, 2]. In the field of neurodevelopment and regenerative medicine, neural organoids replicate human specific features of neurodevelopment, contributing to modeling neurogenesis and neurological diseases [3, 4]. Central nervous system (CNS) injury or damage initiates spatial and temporal neurodegeneration, resulting in irreversible neuronal loss and functional deficits. The vertebrate retina is an extension of the CNS that is composed of seven main types of neurons and glial cells. In recent years, emerging organoid-based research studies of brain and retina have made progress in understanding neural organogenesis, which facilitates successful application of 3D organoid systems in disease modeling and regenerative medicine. In this chapter, we summarize the application of neural organoids of the brain and retina in neurodevelopment and regenerative medicine.
CNS is generally regarded as the most complex system in human body. Limited by accessibility of living neural tissues and ethical challenges, human-specific features of neurodevelopment and neurological diseases remain largely unknown to us. Recent advances in stem cell technologies and 3D culture neural organoids have opened a new avenue in exploring the mechanisms of neurodevelopment. Early versions of the neural organoids range from complex neural epithelial structures to disorganized brain regions with large cellular diversity [5]. By supplementing exogenous factors and assembly of organoids during embryonic brain development, efforts have been made to gain the well-developed multilayer neural organoids and higher-order functions in terms of controlling patterning, morphogenesis, and function [6, 7].
Through the embryonic brain development, neural progenitors progressively follow precise orchestration and coordination to acquire their spatial identities, a process characterized by successive changes in cellular composition and cytoarchitecture (Figure 1a). Dysregulation of this process may affect neurogenesis, synaptogenesis, and myelination and induce neurological or psychiatric disorders. To better investigate the early formation and function of the human brain
Schematic depiction of brain and eye development
The 3D cultured brain organoids have been proven useful for many applications in basic research, for example, the development of the human brain cortex. It firstly begins with the expansion of the neuroepithelium, and then folds into six different layers. The main principles of the cortical layer formation are similar between mammals, such as primates and humans; however, the morphological differences are unneglectable. It is well known that neuronal number in primates massively increases in cortical surface, which eventually leads to the gyrification of the cortex (the generation of gyri and sulci) [11]. However, the mechanisms controlling the generation of gyrification are still not clear during the formation of cortical areas. The application of cortical organoids has helped us better understand the rapid expansion of human neocortex and the formation of cerebral cortical sulcus and gyrus. Karzbrun et al. revealed two opposing mechanical forces with the usage of the brain organoids-on-a-chip: the middle cytoskeletal contraction and peripheral cell-cycle-dependent nuclear expansion, physically leading to differential growth and folding into brain wrinkling [12], and the extracellular matrix (ECM) components are implicated in neocortical expansion [13].
For another example, brain organoids are used to investigate the development of cellular interactions in the human brain. The human CNS originated from several distinct vesicles and then after a range of progenitors migrate and integrate, it moves into areas to generate multiple intertwined regions, ultimately resulting in emerging complex networks, neurons branching, and projecting. To model the intricate cellular interactions in human brain, fusing regionalized organoids into assembloids recapitulates more elaborate biological processes of brain development. This approach has been applied to study forebrain axis establishment, interneuron migration, oligodendrogenesis, and neuronal projections like the fused dorsal-ventral cerebral organoids to model interneuron migration in [7, 14, 15].
The eye originates from the ventral diencephalon, where a group of eye field transcription factors (EFTFs) are highly expressed such as PAX6, RAX, SIX3, and OTX2, and becomes specified as the eye field [16]. The eye field region is firstly split into optic vesicles in pairs and subsequently forms the optic cup by experiencing the valgus and invagination of the optic vesicle. The outer layer of the optic cup develops into retinal pigment epithelium(RPE) while the inner layer develops into neural retina. The neural retina with multilayered structure undergoes different phases of development, with different types of cells differentiating and maturing over the time (Figure 1a).
However, the understandings of the function and development of the human retinal are limited by scarce human fetal retina sample and species differences between animals and human. Since 2011, Sasai et al. released a landmark study to generate a self-organized 3D optic cup with layered neuroepithelia from mouse pluripotent stem cells (mPSCs), which opened a window for generating retinal models [17]. Many research groups have subsequently optimized the protocol to generate human retinal organoids derived from hPSCs. During retinal organoid generation, stem cell patterns the eye field-like regions expressing a complete component of the EFTFs to mimic the optic vesicle in early development [18]. What is encouraging, these tiny retinal organoids even contain almost all relevant retinal cell types: retinal ganglion cells (RGCs), amacrine cells, horizontal cells, bipolar cells, Müller cells, and photoreceptors.
RGCs, the early-born neurons, transmit visual information between the eye and the brain, playing a critical role in retinal neuronal outputs. The loss of RGCs trends to result in a group of degenerative diseases such as glaucoma and optic nerve hypoplasia. Due to the specific time point of the RGC development, it is a challenge to obtain human fetus samples. In addition, the long-distance projection of neurites is the mostly important characteristic for RGC development as the extension of axons is regulated by extrinsic factors, including the ECM, growth factors, and glial cells. Recent several approaches have improved the capacity to differentiate hPSC-derived retinal organoids into RGCs that possess appropriate morphological and functional properties [19]. For example, Fligor et al. found that substrate composition including laminin and Matrigel shows the most conducive for RGC neurite outgrowth; similarly, the growth factors with Netrin-1 and BDNF have the ability to guide and direct RGC axons outgrowth [20]. Besides, single-cell RNA sequencing (RNA-seq) results proved that the ganglion cells of retinal organoids at day 60 give the similar clusters to the human fetal retina on day 59 [21]. Collectively, the established retinal organoids serve as effective models for investigations of RGC development and disease modeling and as a valuable tool for cell replacement.
Rod and cone photoreceptors are specialized neurons with functioning in the initial step of vision, which convert light stimuli into neurological responses. Rods are highly sensitive to light and operate under dim lighting conditions while the cones control color vision and high visual acuity. It is reported that the progressive loss of photoreceptors leads to blindness-associated inherited retinal diseases(IRDs), such as well-known retinitis pigmentosa (RP), congenital stationary night blindness(CSNB), and Leber congenital amaurosis (LCA). Therefore, it is particularly important to understand retinal progenitor fate choices toward rod photoreceptors and cone subtypes during retinogenesis. As such, the phototransduction mechanism requires a complicated cascade of gene regulatory networks. Aiming to induce hPCS-derived retinal organoids with mature photoreceptors, efforts of genetic manipulation and transcriptomic analysis have become the focal point for researchers [22]. Most recently, NRL (neural retina leucine zipper)-/- human-based 3D organoids were used to uncover the regulative role of MEF2C in cones’ development [22]. RNAseq analysis of hPCS-derived retinal organoids has identified certain molecular signatures related with human photoreceptors development [23]. In brief, these observations and datasets have enabled to reconstruct developmental trajectories and recapitulate dynamics
Neural organoids, which recapitulate the process of native neurogenesis in the development of CNS, have been applied in a large variety of areas including simulating brain development and retinogenesis. Moreover, emerging organoid-based cell transplantation has made considerable progress in reconstruction of lost neural circuits, damaged neural cortex and visual function, which facilitates the application of 3D organoid systems in disease modeling and regenerative medicine. Representative examples are involved in two aspects: (a) isolating neural progenitor cells (NPCs) from neural organoids; (b) transplanting neural organoids in immunodeficient animals. The stem cells in the organoids derived from hPSCs present a higher survival rate and closer connection with the surrounding tissues in the host. Distinct from conventional stem cell therapy usually focusing on specific populations of stem cells or NPCs, neural organoids offer an entire set of cell types of the human organs.
Brain disorders, such as Alzheimer\'s disease (AD), Parkinson\'s disease (PD), traumatic brain injury (TBI), and stroke, along with several other chronic neurodegenerative disorders, are debilitating diseases that have few treatment options. Stem cell therapy is likely to provide beneficial effects for the indications of these diseases. The current understanding of brain diseases is mainly based on traditional 2D monocultural cells, animal models, and postmortem examination. Because of the inherent species differences between animals and humans and the individual differences among genetic and environmental backgrounds, it remains a challenge to investigate brain development and associated disorders. To establish better models of human brain development, stem-cell-based 3D brain organoids systematically decipher the developmental rules, presenting the 3D architectures and physiology of the brain. These generated brain organoids show robust neuronal subtypes and glial subtypes and functionality to mimic
Recently, in two studies, scientists transplanted hPSC-derived cerebral organoids into mouse cerebral cortex and successfully generated vascularized organoids, which promoted the progressive neuronal differentiation and maturation and increased cell survival [26, 27]. They observed the widespread axonal extension and precise synaptic connectivity outside the graft area; however, the region-specific long projections and synaptogenesis mapping were not reported in the two studies. Previously, reported approaches produced brain organoids with large lumens and tubes, which results in insufficient oxygen and nutrients support in increasing metabolic needs, making them difficult to apply in transplantation therapy [10, 28]. Recently, an optimized culture protocol was developed to efficiently generate small human cerebral organoids, which presents the benefit of alleviating the risk of cell overgrowth and safety concerns after injecting into the mouse medial prefrontal cortex [29]. The transplanted cerebral organoids extended projections to basal brain regions and generated human glutamatergic neurons with mature electrophysiology [29]. Moreover, mice transplanted with cerebral organoids show potentiated auditory startle fear response, indicating that the organoids can be functionally integrated into preexisting host mouse neural circuits via building up bidirectional synaptic connections, which provides crucial therapeutic strategy for neurological diseases [29].
However, owing to the cellular composition of brain, organoids dramatically changes along the time course of the development, it is necessary to demonstrate which stage of the organoids is best suitable for transplantation. To address this limitation, Kitahara et al. transplanted hESC-derived cerebral organoids at 6w or 10w into mouse cerebral cortex and found that 6w-organoids extend more axons along corticospinal tracts but caused graft overgrowth with higher populations of proliferative cells while axonal extensions from 10w-organoids were smaller in number but enhanced after brain injury 1 week [30]. A similar study reported that 55d and 85d-cerebral organoids were transplanted into damaged motor cortex, indicating that 55d-cerebral organoids can be used as a better transplantation donor for traumatic brain injury (TBI) [31]. Cells from the transplanted cerebral organoids have the capability to support region-specific reconstruction of damaged brain cortex, upregulate hippocampal neural connection protein and neurotrophic factor, and improve of damaged motor cortex. It is also reported that cerebral organoids were transplanted at 55 days to explore the feasibility of organoid transplantation in stroke [32]. Cerebral organoids were transplanted at 6 h or 24 h after middle cerebral artery occlusion (MCAO) surgery, resulting in reducing brain infarct volume and improving neurological motor function. Furthermore, they also observed that the transplanted cerebral organoids were also related with increased neurogenesis, synaptic reconstruction, axonal regeneration and angiogenesis, decreased neural apoptosis, and rescued more survival neurons after stroke [32]. Although a few works with respect to transplanting brain organoid system were reported, it still has promising technologies in the future treatment of central nervous system diseases. Hence, the effects of the developmental organoid stage and host brain environment should be accurately evaluated when developing an organoid-replacement therapy for brain injury.
Retinal degenerative diseases, such as glaucoma, RP, and Age-Related Macular Degeneration (AMD), usually lead to irreversible blindness. So does the importance of finding a viable treatment. Regardless of the underlying etiology of retinal degeneration, the common endpoint is the loss of photoreceptors and underlying RPE. Cell replacement strategy provides a good solution for the treatment of retinal degeneration. Although plenty of studies have been made to understand the cellular and molecular mechanisms of retinal disorders, our knowledge is still in its infancy, and the immortalized retinal cell lines have not recapitulated the developmental stages of the human native retina. The new methodological advances in inducing hPSCs into human retina tissues have opened new possibilities for basic research on investigating the therapies or treatments in regenerative medicine [18, 33]. The generated retinal organoids closely resemble many aspects of the real human retina, including retina-specific ribbon synapse [34] and physiological-relevant response to light stimuli [35], which empower researchers to explore the pathogenesis of retinal diseases and pursue cell/tissue transplantation for developing novel treatment options. Because retinal organoids contain all the cell types of human retina, it plays a primary role in the field of transplantation therapy. In this section, we focus on single-cell suspensions isolated from retinal organoids and application of retinal organoids sheets transplantation used for cell therapies in regenerative medicine (Figure 1b).
During the previous decade, the aborted human fetal tissues and the hPSC-derived retinal progenitors were two cell sources for transplantation. Representative retinal cell replacement clinical trials are transplantation of hPSC-derived RPE for the treatment of retinal diseases, including AMD and Stargardt disease [36, 37, 38]. It has been proved that the mature mammalian retina lacks the ability to accept and incorporate stem cells or to promote photoreceptor differentiation. In 2006, stem-cell-derived precursor photoreceptors were first integrated into the outer retinal layer of degenerating retina and had success in improving vision [39, 40]. However, the strong ethical restrictions and limited cell sources remain a challenge in current transplantation therapies. The retinal organoids that contain abundant retinal progenitor cells (RPCs) can act as an ideal cell source transplantation in retinal degenerative diseases. Zou et al. transplanted effectively purifying RPCs with the surface markers (C-Kit+/SSEA4−) into the retinal degeneration models of rats and mice, showing benefits to the improvement of vision and preservation of the retinal structure [41]. The RGCs are the earliest differentiated cells closely associated with glaucoma. But the population of RGCs in retinal organoids is not substantial as they gradually degenerate following long-term culture time. Thus, prolonging the survival time of RGCs may provide the possibility for RGC replacement therapy. Several approaches have been taken to improve the short life of implanted RGCs and the length of axons, such as adding extrinsic growth factors [20], combining 2D and 3D protocols [42], and co-culturing with Müller glia [43]. In another animal study, by transplanting purified rod photoreceptors isolated from retinal organoids in defective S- and M- cone opsins, Nrl-/- mouse retinas can restore rod-mediated visual function and be incorporated into the host retina with forming synaptic-like structures in close apposition to mouse interneurons [44]. Interestingly, recent studies contradicted the common view that transplanted photoreceptors integrate into the photoreceptor layer of recipients. They demonstrated that the material transfer between donor rod photoreceptors and host photoreceptors leads to the acquisition of proteins originally expressed only by donor cells [45, 46]. Thus, the mechanism of the photoreceptor transplantation demands reinterpretation.
A retinal sheet derived from cultured retinal organoids or fetal retina is another approach to preserving the neural circuitries and improving visual function. Cell suspension strategies consist of transplanting purified photoreceptor precursor cells, whereas retinal sheet transplantations engraft retinal organoids containing both photoreceptor cells and inner retinal neurons. The inner neurons located in the transplanted retinal sheet, which serves as a scaffold and nurturing microenvironment, are conductive to outer layer retinal cells in differentiation and maturation, preserving normal lamination structures. It is reported that the retinal sheet graft can produce less immune activation that enhances life span and the survival rate of transplanted cells, providing suitability approach for therapies of late-stage retinal diseases.
Furthermore, several studies have demonstrated that the transplantation of hPSC-derived RPE cells in AMD patients shows promising outcomes in clinical trials, such as improvement in retinal integrity, maintainability in visual acuity, and increase in vision-related quality of life [47]. Currently, the transplantation of early-stage retinal organoid sheets is verified to establish connections more effectively with host retinal degeneration, and these connections show higher survival rate over time. A series of studies have been performed to investigate whether the transplantation of retinal organoid sheets can differentiate, integrate, and improve visual function in animal models with severe retinal degeneration [48, 49, 50]. In 2016, Shirai et al. dissected “retinas” from organoids to get transparent and continuous neural retina sheets and transplanted them into two primate models with retinal degeneration. In both monkey and rat, grafted hESC-retina differentiated into a range of retinal cell types, such as photoreceptors. The photoreceptors were proved to have migrated to the outer nuclear layer and the host-graft synaptic connections were established in those animal models [51]. Similar results were achieved in another study of transplanting the sheets dissected from hESC-derived retinal organoids into retinal degenerate rats [48]. In addition, to enhance functional integration of transplanted retinal sheet, a method in which a genetic modification was used to reduce ON-bipolar cells resulted in efficiently restoring RGC light responsiveness in degenerated retina [52]. However, in those studies, the absence of a well-defined RPE monolayer presents a main limiting factor for retinal sheet transplantation. To overcome this limitation, hESC-derived retinal organoids and RPE monolayer were combined using different bio-adhesives to transplant into immunodeficient Royal College of Surgeons (RCS) rats. The co-grafts were observed to reconstruct the severely damaged retina structure and improve visual function [53]. Those studies demonstrate the clinical feasibility of hPSC-derived retinal organoids sheet transplantation and provide practical tools to optimize transplantation strategies for future clinical applications.
In retinal tissue engineering, biomaterials are utilized to optimize the models of the human retina. A growing number of biomaterials, especially synthetic polymer scaffolds, such as biodegradable polycaprolactone (PCL) and polylactic-coglycolic acid (PLGA), have been widely used. The remarkable properties of defined synthetic polymer substrate are thin and biodegradable, which can be placed into the retinal subretinal space with minimal physical distortion [54]. In terms of the report, transplanting mouse RPCs cultured on biodegradable thin-film PCL scaffolds with varying surface topographies into the retinal subretinal space help newly integrated mRPCs exhibit potential to guide stem cell differentiation toward photoreceptor fate and to help cells localized to the outer nuclear layer [55]. Another study implanted the human retinal organoids, which are seeded on PLGA sheets into both normal and Chronic Ocular Hypertension (OHT) rhesus monkey retinas. They found that despite the need of immunosuppression for dexamethasone after transplantation, survival and differentiation into retinal tissue were successfully improved [56]. Subsequently, the same group proved again that with the support of PLGA sheets, retinal organoids showed active proliferation, migration and projection of axons into the host optic nerve after transplanting into OHT rhesus monkey eyes [57].
Development of neural organoid techniques has yielded rapid progress in clarifying the mechanisms of human neural development. Organoids display many characteristics of the organs from which they were made, including cellular anatomy and interaction, genetics, and specific tissue functions, advancing our understanding the neuro of biology, developmental science, and regeneration. Some of the limitations and challenges of neural organoids have been addressed, but emerging technologies are still required to be applied in further study. With respect to brain organoids, many points are needed to be improved, such as the maturation of neuronal and glial cells, reliable anatomical organization, long-range axonal projection and synaptic connections, and the precise construction of neuronal circuits. Providing a physiologically relevant microenvironment and the more complex whole-brain organoids to reproduce the developmental events of the human nervous systems may be needed in the future. Retinal organoids serve as an ideal choice for therapeutic transplantation, which still face many challenges as following: low yield, high heterogeneity, degenerative inner cell layers, and cancerogenesis. The next-generation retinal organoids would be anticipated to have an integrated vascular network, mature microglia system, and pigment layer wrapping around as well as the integration of bioengineering technologies. To achieve the goal, several engineering approaches may be useful: (1) engineered biomaterials to investigate cell-cell and cell-matrix interactions; (2) genetic engineering technology to study various aspects of organoids development and performance; (3) organoid-on-a-chip device to create an optimal microenvironment with the purpose of generating organoids with higher physiological relevance. Furthermore, the next generation of organoids probably needs to integrate more bioengineering technologies, aiming to overcome each approach’s limitation and provide a superior, synergistic approach for constructing more complex organoids in regenerative and precision medicine.
The authors declare no conflicts of interest.
This study was supported by the funding from the National Key Research and Development Program of China (Grant No. 2018YFA0107302); the National Natural Science Foundation of China (Grant No. 31930068); and the Military Key Program (Grant No. 20QNPY025).
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\n\nPolicy last updated: 2016-06-08
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This chapter is an updated overview of the signaling pathways going from external signals such as osmolarity and ionic concentration and their membrane reception to their transduction through the membrane and their final reception at the flagellar axoneme level. Additional factors such as energy management will be addressed as they constitute a limiting factor of the motility period of fish spermatozoa. Modern technologies used nowadays for quantitative description of fish sperm flagella in movement will be briefly described as they are more and more needed for prediction of the quality of sperm used for artificial propagation of many fish species used in aquaculture. The chapter will present some applications of these technologies and the information to which they allow access in some aquaculture species.",book:{id:"7912",slug:"biological-research-in-aquatic-science",title:"Biological Research in Aquatic Science",fullTitle:"Biological Research in Aquatic Science"},signatures:"Jacky Cosson",authors:[{id:"188281",title:"Dr.",name:"Jacky",middleName:null,surname:"Cosson",slug:"jacky-cosson",fullName:"Jacky Cosson"}]},{id:"20911",doi:"10.5772/19948",title:"The Significance of Suspended Sediment Transport Determination on the Amazonian Hydrological Scenario",slug:"the-significance-of-suspended-sediment-transport-determination-on-the-amazonian-hydrological-scenari",totalDownloads:4130,totalCrossrefCites:13,totalDimensionsCites:24,abstract:null,book:{id:"304",slug:"sediment-transport-in-aquatic-environments",title:"Sediment Transport in Aquatic Environments",fullTitle:"Sediment Transport in Aquatic Environments"},signatures:"Naziano Filizola, Jean-Loup Guyot, Hella Wittmann, Jean-Michel Martinez and Eurides de Oliveira",authors:[{id:"36890",title:"Dr.",name:"Naziano",middleName:null,surname:"Filizola",slug:"naziano-filizola",fullName:"Naziano Filizola"},{id:"60004",title:"Dr.",name:"Jean-Michel",middleName:null,surname:"Martinez",slug:"jean-michel-martinez",fullName:"Jean-Michel Martinez"},{id:"60005",title:"Dr.",name:"Jean-Loup",middleName:null,surname:"Guyot",slug:"jean-loup-guyot",fullName:"Jean-Loup Guyot"},{id:"102592",title:"Dr.",name:"Hella",middleName:null,surname:"Wittmann",slug:"hella-wittmann",fullName:"Hella Wittmann"},{id:"102593",title:"Mr.",name:"Eurides",middleName:null,surname:"De Oliveira",slug:"eurides-de-oliveira",fullName:"Eurides De Oliveira"}]},{id:"45198",doi:"10.5772/56105",title:"Stable Isotope Methods for the Study of the Nitrogen Cycle",slug:"stable-isotope-methods-for-the-study-of-the-nitrogen-cycle",totalDownloads:4680,totalCrossrefCites:11,totalDimensionsCites:18,abstract:null,book:{id:"3517",slug:"topics-in-oceanography",title:"Topics in Oceanography",fullTitle:"Topics in Oceanography"},signatures:"Evgenia Ryabenko",authors:[{id:"163463",title:"Dr.",name:"Evgenia",middleName:null,surname:"Ryabenko",slug:"evgenia-ryabenko",fullName:"Evgenia Ryabenko"}]}],mostDownloadedChaptersLast30Days:[{id:"60368",title:"Biological and Medicinal Importance of Sponge",slug:"biological-and-medicinal-importance-of-sponge",totalDownloads:2505,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Sponges are multicellular, heterotrophic parazoan organisms, characterized by the possession of unique feeding system among the animals. They are the most primitive types of animals in existence, featuring a cell-based organization where different cells have different tasks, but do not form tissues. Sponges (Porifera) are a predominantly marine phylum living from the intertidal to the abyssal (deepest ocean) zone. There are approximately 8500 described species of sponges worldwide with a prominent role in many reef coral communities. Several ecological studies reported have shown that secondary metabolites isolated from sponges often serve defensive purposes to protect them from threats such as predator attacks, biofouling, microbial infections, and overgrowth by other sessile organisms. In the recent years, interest in marine sponges has risen considerably due to presence of high number of interesting biologically active natural products. More than 5300 different natural products are known from sponges and their associated microorganisms, and every year hundreds of new substances are discovered. In addition to the unusual nucleosides, other classes of substances such as bioactive terpenes, sterols, fatty acids, alkaloids, cyclic peptides, peroxides, and amino acid derivatives (which are frequently halogenated) have been described from sponges or from their associated microorganisms. Many of these natural products from sponges have shown a wide range of pharmacological activities such as anticancer, antifungal, antiviral, anthelmintic, antiprotozoal, anti-inflammatory, immunosuppressive, neurosuppressive, and antifouling activities. This chapter covers extensive work published regarding new compounds isolated from marine sponges and biological activities associated with them.",book:{id:"6344",slug:"biological-resources-of-water",title:"Biological Resources of Water",fullTitle:"Biological Resources of Water"},signatures:"Musarat Amina and Nawal M. Al Musayeib",authors:[{id:"213049",title:"Dr.",name:"Musarat",middleName:null,surname:"Amina",slug:"musarat-amina",fullName:"Musarat Amina"},{id:"213050",title:"Dr.",name:"Nawal",middleName:null,surname:"M. Al Musayeib",slug:"nawal-m.-al-musayeib",fullName:"Nawal M. Al Musayeib"}]},{id:"59865",title:"Marine Fisheries in Nigeria: A Review",slug:"marine-fisheries-in-nigeria-a-review",totalDownloads:3853,totalCrossrefCites:8,totalDimensionsCites:10,abstract:"Fisheries production especially from marine is important for the socio-economic development of Nigerians and its contribution to the nation’s economic growth through the Gross Domestic Product (GDP). Nigeria is blessed with enough marine fisheries resources that could enhance increased fish production. Yet, fish supply from domestic production is far below the fish demand of her citizens. This chapter is therefore focused on marine fisheries in Nigeria. We adopted a desk review approach. This chapter is divided into different sections such as the Nigerian fisheries sector, marine fisheries resources in Nigeria, status of marine fisheries production in Nigeria, marine fisheries regulations, and constraints to optimal marine fisheries production in Nigeria. We concluded that the contribution of aquaculture to marine fisheries production has been low, compared to the marine capture fisheries production. Also, we noted that despite the availability of regulations, noncompliance by fisher folks has not helped to optimize marine fisheries production. We therefore recommended that the culture of marine fishes should be intensified. Marine waters should also be protected against destruction and pollution as a result of human activities. Available marine fisheries regulations should be enforced and violators of the regulations should be punished as stipulated in the regulations.",book:{id:"6266",slug:"marine-ecology-biotic-and-abiotic-interactions",title:"Marine Ecology",fullTitle:"Marine Ecology - Biotic and Abiotic Interactions"},signatures:"Olalekan Jacob Olaoye and Wahab Gbenga Ojebiyi",authors:null},{id:"57327",title:"Closed Aquaculture System: Zero Water Discharge for Shrimp and Prawn Farming in Indonesia",slug:"closed-aquaculture-system-zero-water-discharge-for-shrimp-and-prawn-farming-in-indonesia",totalDownloads:2465,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"This chapter focuses on the development and application of zero water discharge (ZWD) system, which has become an alternative solution to conventional methods of aquaculture production. With this system, it is expected to answer many issues in aquaculture cultivation, such as environmental damage, disease outbreak, and land-use change, and to create a sustainable aquaculture cultivation system. ZWD system is an improved batch system with an emphasis on microbial manipulation in rearing tank. The principle of microbial selection is based on the role of each microbial component in nutrient cycle in the rearing tank. This chapter contains in detail how methods and stages are performed in order to conduct this system, including design of construction system, cultivation of microbial components, initial conditioning of this system, and microbial manipulation. The performance of the system was tested in crustacean culture such as white shrimp and giant freshwater prawns, and it showed that the system can increase the average survival rate of 10–20%. In addition, the technical and economic feasibility of this system was evaluated to illustrate the production efficiency upon the application of this system in the industry.",book:{id:"6344",slug:"biological-resources-of-water",title:"Biological Resources of Water",fullTitle:"Biological Resources of Water"},signatures:"Gede Suantika, Magdalena Lenny Situmorang, Pingkan Aditiawati,\nDea Indriani Astuti, Fahma Fiqhiyyah Nur Azizah and Harish\nMuhammad",authors:[{id:"216920",title:"Dr.",name:"Gede",middleName:null,surname:"Suantika",slug:"gede-suantika",fullName:"Gede Suantika"},{id:"220079",title:"Dr.",name:"Magdalena Lenny",middleName:null,surname:"Situmorang",slug:"magdalena-lenny-situmorang",fullName:"Magdalena Lenny Situmorang"},{id:"220081",title:"Dr.",name:"Pingkan",middleName:null,surname:"Aditiawati",slug:"pingkan-aditiawati",fullName:"Pingkan Aditiawati"},{id:"220082",title:"Dr.",name:"Dea Indriani",middleName:null,surname:"Astuti",slug:"dea-indriani-astuti",fullName:"Dea Indriani Astuti"},{id:"220083",title:"MSc.",name:"Fahma Fiqhiyyah Nur",middleName:null,surname:"Azizah",slug:"fahma-fiqhiyyah-nur-azizah",fullName:"Fahma Fiqhiyyah Nur Azizah"}]},{id:"59973",title:"Genetic Applications in the Conservation of Neotropical Freshwater Fish",slug:"genetic-applications-in-the-conservation-of-neotropical-freshwater-fish",totalDownloads:1627,totalCrossrefCites:3,totalDimensionsCites:8,abstract:"Neotropical fish correspond to approximately 30% of all fish species worldwide. The diversity of fish species found in Neotropical basins reflects variations in life-history strategies and exhibition of particular morphological, physiological and ecological attributes. These attributes are mainly related to different forms of feeding, life maintenance and reproduction. Today, fish populations are being threatened by anthropogenic actions that are having a visible impact on the natural state of continental aquatic ecosystems. The main causes are overfishing, non-native species introduction, reservoir-dam systems, mining, pollution and deforestation. The biology and population dynamics of the species are still unclear due to lack of research. Genetic tools can be useful resources for the conservation of Neotropical fish species in several ways. Molecular genetic markers are considered powerful tools to identify cryptic and hybrid fish and also allow the evaluation of the genetic variability and structure of populations of Neotropical ichthyofauna. Several analyses of molecular markers have been performed on Neotropical fish, including allozyme analysis, restriction fragment length polymorphisms in regions of DNA (RFLP), randomly amplified polymorphic DNA (AFLP), randomly amplified polymorphic DNA (RAPD), microsatellites, single nucleotide polymorphisms (SNPs) and mitochondrial DNA (mtDNA) markers. In order to analyse a high number of markers, next generation sequencing has allowed researchers to generate a large amount of genomic information that can be applied to the conservation of Neotropical fish.",book:{id:"6344",slug:"biological-resources-of-water",title:"Biological Resources of Water",fullTitle:"Biological Resources of Water"},signatures:"Vito Antonio Mastrochirico Filho, Milena V. Freitas, Raquel B.\nAriede, Lieschen V.G. Lira, Natália J. Mendes and Diogo T.\nHashimoto",authors:[{id:"215385",title:"Dr.",name:"Diogo",middleName:null,surname:"Hashimoto",slug:"diogo-hashimoto",fullName:"Diogo Hashimoto"},{id:"226741",title:"MSc.",name:"Vito",middleName:null,surname:"Matrochirico-Filho",slug:"vito-matrochirico-filho",fullName:"Vito Matrochirico-Filho"},{id:"226743",title:"MSc.",name:"Milena",middleName:null,surname:"Freitas",slug:"milena-freitas",fullName:"Milena Freitas"},{id:"226744",title:"MSc.",name:"Raquel",middleName:null,surname:"Ariede",slug:"raquel-ariede",fullName:"Raquel Ariede"},{id:"226745",title:"MSc.",name:"Natália",middleName:null,surname:"Mendes",slug:"natalia-mendes",fullName:"Natália Mendes"},{id:"226746",title:"MSc.",name:"Lieschen",middleName:null,surname:"Lira",slug:"lieschen-lira",fullName:"Lieschen Lira"}]},{id:"62582",title:"Mangrove Species Distribution and Composition, Adaptive Strategies and Ecosystem Services in the Niger River Delta, Nigeria",slug:"mangrove-species-distribution-and-composition-adaptive-strategies-and-ecosystem-services-in-the-nige",totalDownloads:2139,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Mangroves of the Niger River Delta grade into several plant communities from land to sea. This mangrove is a biodiversity hot spot, and one of the richest in ecosystem services in the world, but due to lack of data it is often not mentioned in many global mangrove studies. Inland areas are sandy and mostly inhabited by button wood mangroves (Conocarpus erectus) and grass species while seaward areas are mostly inhabited by red (Rhizophora racemosa), black (Laguncularia racemosa) and white (Avicennia germinans) mangroves species. Anthropogenic activities such as oil and gas exploration, deforestation, dredging, urbanization and invasive nypa palms had changed the soil type from swampy to sandy mud soil. Muddy soil supports nypa palms while sandy soil supports different grass species, core mangrove soil supports red mangroves (R. racemosa), which are the most dominant of all species, with importance value (Iv) of 52.02. The red mangroves are adapted to the swampy soils. They possess long root system (i.e. 10 m) that originates from the tree stem to the ground, to provide extra support. The red mangrove trees are economically most viable as the main source of fire wood for cooking, medicinal herbs and dyes for clothes.",book:{id:"6411",slug:"mangrove-ecosystem-ecology-and-function",title:"Mangrove Ecosystem Ecology and Function",fullTitle:"Mangrove Ecosystem Ecology and Function"},signatures:"Aroloye O. Numbere",authors:[{id:"215285",title:"Dr.",name:"Aroloye O.",middleName:null,surname:"Numbere",slug:"aroloye-o.-numbere",fullName:"Aroloye O. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"