The interplay of dopamine metabolism abnormalities and mitochondrial defects in the pathogenesis of schizophrenia

Abstract

Dopamine (DA) is a major monoamine neurotransmitter in the brain and has essential roles in higher functions of the brain. Malfunctions of dopaminergic signaling have been implicated in various mental disorders such as addiction, attention deficit/hyperactivity disorder, Huntington’s disease, Parkinson’s disease (PD), and schizophrenia. The pathogenesis of PD and schizophrenia involves the interplay of mitochondrial defect and DA metabolism abnormalities. This article focuses on this issue in schizophrenia. It started with the introduction of metabolism, behavioral action, and physiology of DA, followed by reviewing evidence for malfunctions of dopaminergic signaling in patients with schizophrenia. Then it provided an overview of multiple facets of mitochondrial physiology before summarizing mitochondrial defects reported in clinical studies with schizophrenia patients. Finally, it discussed the interplay between DA metabolism abnormalities and mitochondrial defects and outlined some clinical studies showing effects of combination therapy of antipsychotics and antioxidants in treating patients with schizophrenia. The update and integration of these lines of information may advance our understanding of the etiology, pathogenesis, phenomenology, and treatment of schizophrenia.

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“…DA is a monoaminergic neurotransmitter responsible for regulating several functions including mood, motivation, pleasure, and reward . Dopaminergic neurons originating from the nuclei in the brain stem project to several cortical and subcortical brain regions, highlighting the mesocortical, mesolimbic, and nigrostriatal pathways .…”

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“…[7][8][9][10] Abnormal levels and lack of dopamine are associated with several psychiatric disorders, including Alzheimer's, drug addiction, aprosexia, Parkinson's, schizophrenia, Huntington's disease, and attention decit hyperactivity disorder (ADHD). 7,8,11 Conventional laboratorybased healthcare technologies demand patients to reach the hospitals causing detrimental effects from lengthy diagnosis time to delayed treatment. 12 The increasing need for diagnostic instruments that include improved analytical attributes such as sensitivity, selectivity, and short response time has prompted researchers to focus their efforts on the advancement of pointof-care (POC) devices.…”

“…7 It plays an essential role in the human central nervous system in the brain involving various brain functions like memory, motor control, motivation, arousal, sexual behaviour, reward and pleasure, emotions and mood, behavioural responses which include feeling, addiction and transduction responses, also influencing renal, hormonal and cardiovascular systems. 7–10 Abnormal levels and lack of dopamine are associated with several psychiatric disorders, including Alzheimer's, drug addiction, aprosexia, Parkinson's, schizophrenia, Huntington's disease, and attention deficit hyperactivity disorder (ADHD). 7,8,11 Conventional laboratory-based healthcare technologies demand patients to reach the hospitals causing detrimental effects from lengthy diagnosis time to delayed treatment.…”

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