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.

The adenosine hypothesis of schizophrenia into its third decade: From neurochemical imbalance to early life etiological risks

“…Genetic deletion of CD73 in mice blunted the development of amphetamine sensitization and improved working memory performance (Augusto et al, 2013 ; Zlomuzica et al, 2013 ). While the former phenotype is indicative of a resilience against mesolimbic hyperdopaminergic signaling linked to the production of positive symptoms in schizophrenia (Laruelle, 2000 ), the later pro-cognitive phenotype is opposite to the memory impairment in schizophrenia attributed to cortical dopamine deficiency (Luvsannyam et al, 2022 ). One explanation of the anti-hyperdopaminergia phenotype is in terms of the colocalization of ADORA2A and CD73 in striatal neurons, whereby CD73 is the main source of adenosine that stimulates ADORA2A (Augusto et al, 2013 ).…”

Roles of the Oxytocin Receptor (OXTR) in Human Diseases

“…Among the numerous symptoms of this disease, one can distinguish psychotic (hallucinations, delusions, thought disorder, and movement disorder), negative (trouble with planning and sticking with activities, trouble with anticipating and feeling pleasure, talking in a dull voice, avoiding social interaction, severely decreased life energy), and cognitive (trouble with processing information and making decisions, inability to immediately use information, inability to focus or pay attention) ones. The description of this disease is broad, and recent review articles provide a great background for its causes, mechanisms (which are still only partially understood), and treatment possibilities [ 93 , 94 , 95 , 96 ].…”

The efficacy and safety of sodium nitroprusside in the treatment of schizophrenia: Protocol for an updated systematic review and meta-analysis

“…Since schizophrenia is a group of syndromes that includes multiple symptoms and dysfunction, treatment of the disorder is difficult [ 16 ]. Although antipsychotic drugs can control patients’ mental symptoms, they are relatively poor in the treatment of negative symptoms and cognitive impairment [ 2 ].…”