Chapters authored
The Unique Properties of the Prefrontal Cortex and Mental Illness
Part of the book: When Things Go Wrong
The Convergence of Glutamate and GABA Dysregulation in Schizophrenia
Schizophrenia (SCZ) is a heterogeneous neurodevelopmental disorder that afflicts about 1% of the world population, imposing a huge financial and social burden on the community. Schizophrenia is characterized by three core features, positive (e.g., hallucinations, delusions) and negative symptoms (e.g., emotional blunting, reduced motivation), as well as cognitive impairments (i.e., working memory and attention deficits). Current antipsychotic treatments, which primarily target dopamine receptors, are effective at alleviating positive symptoms. However, dopamine‐specific therapies are insufficient to relieve negative symptoms and cognitive impairments, indicating other neuronal systems are involved in SCZ. Evidence for hypofunctioning glutamate and gamma‐aminobutyric acid (GABA) transmission in forebrain tissue has continued to culminate as major contributors to the onset of SCZ. Furthermore, recent genetic studies reveal disrupted mutations in neurodevelopmental proteins at glutamatergic and GABAergic synapses that are potentially responsible for the synaptic abnormalities seen in the disorder. Therefore, schizophrenia symptomatology is influenced by interactions of several neurotransmitter systems. In this chapter, we focus on how glutamatergic and GABAergic hypofunctioning contribute to the variety of symptoms presented in SCZ and its etiology. We also review the current treatment options with respect to their mechanism of action, side effects, and limitations and provide perspective of where research should be directed to move forward with treating this debilitating disease.
Part of the book: Schizophrenia Treatment