Abstract
Schizophrenia is a disease that affects many areas of the brain. The dopamine hypothesis is one of the most widely-accepted ideas in the pathophysiology of schizophrenia. Besides alterations in the dopaminergic system in the central nervous system, there have been several reports of changes in dopaminergic systems in the peripheral blood of schizophrenic patients. Several reports have shown that dopamine receptor expression by lymphocytes is altered in patients with schizophrenia, but the results have been conflicting. We therefore re-assessed D3R and D4R mRNA levels in 11 patients with schizophrenia and 12 healthy subjects and correlated levels with severity of symptoms. D3R and D4R expression in lymphocytes and granulocytes was measured by quantitative RT-PCR and the severity of symptoms and cognitive impairment were assessed using the PANSS and BACS-J. There were no significant differences in mean D3R or D4R mRNA levels in lymphocytes from schizophrenic patients and controls and no significant difference in mean D4R mRNA levels in granulocytes (D3R mRNA undetectable). In patients with schizophrenia, D3R expression was inversely correlated with the total PANSS score (r = 0.768, p = 0.009), while D4R expression was positively correlated with working memory scales (r = 0.895, p = 0.001). In conclusion, these results imply that lymphocyte D3R and D4R are involved in the mechanisms of the disorder and could be used as target markers in the treatment of schizophrenia.
Highlights
Schizophrenia is a disease that affects diverse brain regions, causing patients to show a variety of clinical manifestations, such as psychopathologies and cogni- tive deficits [1]
D3R and D4R mRNA levels in lymphocytes or D4R mRNA levels (D3R mRNA levels were undetectable) in granulocytes measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were not influenced by age or sex
D2R, D3R, and D4R mRNA levels were measured in granulocytes and lymphocytes, but D2R mRNA levels in lymphocytes and granulocytes and D3R mRNA levels in
Summary
Schizophrenia is a disease that affects diverse brain regions, causing patients to show a variety of clinical manifestations, such as psychopathologies and cogni- tive deficits [1]. Intensive study for more than 30 years has led to the proposal that alteration of dopaminergic neurotransmission is implicated in the pathophysiology of schizophrenia [2,3]. The dopamine hypothesis of schizophrenia postulates that excessive dopaminergic neurotransmission in the limbic cortex is responsible for positive symptoms, such as hallucinations and delusions, while limited dopaminergic activity in the frontal cortex results in negative symptoms, such as avolition and anhednia, and in cognitive dysfunction [4]. A major neurotransmitter in the central nervous system (CNS), regulates motor coordination, cognition, mood, and reward, and acts on the endocrine and cardiovascular systems. D2-like receptors have attracted pharmacological interest for the design of antipsychotics, Published Online July 2011 in SciRes. http://www.scirp.org/journal/OJPsych
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