Astroglial dysregulation and gliotransmitter imbalance in schizophrenia

Schizophrenia is a neuropsychiatric illness characterized by progressive deterioration of thought processes and marked behavioral abnormalities arising from an unknown pathogenesis underlying the false perceptions, primarily hallucinations and delusions. The clinical symptoms of schizophrenia also include apathy, communication disorders and suicidal thoughts. Although the etiopathogenesis of schizophrenia remains not fully elucidated, the development of schizophrenia has been linked to adverse pregnancy, obstetric complications, neurodevelopmental disorders, neurotransmission imbalance and aberrant neurogenic events. Astrocytes are the most predominant glial cell type in the central nervous system (CNS), where they provide metabolic support, regulate neuroimmune mechanisms, facilitate neurotransmitter reuptake, and sustain synaptic homeostasis. Abnormal neural transmission is considered central to the pathogenesis of schizophrenia. Recent studies have highlighted that malformations in glial cells, particularly dysfunctional or reactive astrocytes, play a crucial role in the pathophysiology. Astrocytic dysregulation in schizophrenia is likely to result in synaptic dysfunction due to altered levels of key gliotransmitters such as glutamate, gamma-aminobutyric acid (GABA) and D-serine leading to altered neurobehavioral outcomes. Thus, insight into the scientific concepts that interrelate the pathophysiology of schizophrenia with astroglia dysregulation at the level of gliotransmitter imbalance could provide innovative hints for developing therapeutic strategies for the treatment of schizophrenia. This chapter describes the key roles of astrocytes and emphasizes imbalances in gliotransmitters as main contributors to the pathophysiology of schizophrenia.