Molecular Evidence Underlying Dopamine Hypothesis of Schizophrenia
Molecular Evidence Underlying Dopamine Hypothesis of Schizophrenia

Summary/Abstract: Schizophrenia is a chronic psychiatric disorder characterized by positive symptoms such as delusions and hallucinations, and negative symptoms like alogia and avolition. Affecting approximately 1% of the population, its etiology remains unclear, but it is believed to arise from the interaction of genetic and environmental factors, primarily impacting the frontal and temporal lobes. The dopamine hypothesis, a leading theory in explaining schizophrenia’s pathophysiology, is based on observations that dopamine-enhancing substances like amphetamines can induce psychotic symptoms. Postmortem brain studies showing increased dopamine levels and D2 receptor density further support this hypothesis. Changes in D2R expression and dimerization are significant in schizophrenia’s molecular basis. However, the dopamine hypothesis faces criticism due to inconsistencies between dopamine levels and symptoms, and the limited efficacy of antipsychotics in addressing negative and cognitive symptoms. Other neurotransmitter systems, including glutamate, GABA, and serotonin, also contribute to schizophrenia. Notably, NMDA receptor hypofunction is linked to neurodevelopmental and neurodegenerative processes. Genetic studies highlight variations in genes like ZNF804A, BDNF, and HLA as risk factors. Epigenetic mechanisms further influence gene expression, contributing to the disorder’s pathophysiology. Schizophrenia requires a multifactorial model beyond dopamine dysfunction, with promising new treatments targeting glutamatergic, serotonergic, and immune pathways. This study discusses the validity of the dopamine hypothesis by reviewing molecular evidence and relevant findings from the literature.

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