Neurobiology of Schizophrenia: A Comprehensive Review

Abstract

Schizophrenia is a debilitating disease that presents with both positive and negative symptoms affecting cognition and emotions. Extensive studies have analyzed the different factors that contribute to the disorder. There is evidence of significant genetic etiology involving multiple genes such as dystrobrevin binding protein 1 (DTNBP1) and neuregulin 1 (NRG1). There is no clear link between neurotransmitter changes and the pathophysiology of schizophrenia; however, studies have shown that subcortical dopamine dysfunction is the key mechanism. Specific regions of gray and white matter changes are observed in patients with schizophrenia; gray matter changes being more significant after the onset of psychosis. These pathological changes may be implicated in the impairment of executive functioning, attention, and working memory. The disease can be managed with pharmacological treatments based on individual patient profile, patient compliance, and disease severity. The challenge of disease management sometimes persists due to the side effects. A better understanding of the pathological processes in schizophrenia may lead to more specific and effective therapies.

Keywords: dopamine; negative symptom; neurobiology; positive symptom; schizophrenia; serotonin.

Figure 1. Network of direct and indirect pathways of basal ganglia involved in motor activity and psychotic symptoms; stimulation and increased activity of excessive D2 receptors in the associative striatum causing schizophrenia

Original image created by the authors. D1 - dopamine D1 receptor in the excitatory pathway; D2 - dopamine D2 receptor in the inhibitory pathway; SNc - substantia nigra pars compact; GPe - globus pallidus externus; GPi - globus pallidus internus; STN - subthalamic nucleus