Dopaminergic system dysfunction is involved in schizophrenia (SCZ) pathogenesis and can mediate SCZ-related motor disorders. Recent studies have gradually revealed that SCZ susceptibility and the associated motor symptoms can be mediated by genetic factors, including dopaminergic genes. More importantly, polymorphisms in these genes are associated with both antipsychotic drug sensitivity and adverse effects. The study of genetic polymorphisms in the dopaminergic system may help to optimize individualized drug strategies for SCZ patients. This review summarizes the current progress about the involvement of the dopamine system in SCZ-associated motor disorders and the motor-related adverse effects after antipsychotic treatment, with a special focus on polymorphisms in dopaminergic genes. We hypothesize that the genetic profile of the dopaminergic system mediates both SCZ-associated motor deficits associated and antipsychotic drug-related adverse effects. The study of dopaminergic gene polymorphisms may help to predict drug efficacy and decrease adverse effects, thereby optimizing treatment strategies.
2019) Adjunct ketamine treatment effects on treatment-resistant depressive symptoms in chronic treatment-resistant schizophrenia patients are short-term and disassociated from regional homogeneity changes in key brain regions -a pilot study, Psychiatry and Clinical Psychopharmacology, 29:4, 907-915, ABSTRACT BACKGROUND: To investigate the effects of adjunct ketamine treatment on depressive symptoms and brain activity in chronic treatment-resistant schizophrenia (CTRS) patients with treatment-resistant depressive (TRD) symptoms. METHODS: Calgary Depression Scale for Schizophrenia (CDSS), positive and negative syndrome scale (PANSS), and regional homogeneity (ReHo) results were compared before versus after ketamine treatment in 12 CTRS patients with TRD symptoms. RESULTS: From 7 days to 14 days after the first ketamine administration, CDSS and PANSS total scores were reduced by 63.8% and 12.9%, respectively. By day 21, ReHo values had increased in the main components of the default mode network (DMN) and bilateral orbitofrontal cortex (OFC) after family-wise error correction. ReHo alterations did not correlate with TRD symptom changes. TRD symptoms relapsed by the 21-day time point, while increased ReHo was sustained. No adverse secondary effects (ASEs) necessitating medical intervention occurred. CONCLUSIONS: Adjunct ketamine alleviation of TRD symptoms lasted only a week, whereas increased ReHo in DMN regions and the OFC in CTRS patients was maintained beyond 2 weeks, indicating that adjunct ketamine is not well-suited for CTRS patients with TRD symptoms and that effects on functional activity dissociate from effects on TRD symptoms. This small-sample pilot study provides clues for further research into therapy for TRD symptoms in CTRS patients.
ARTICLE HISTORY
Objective To explore concomitant neuroimaging and genetic alterations in patients with schizophrenia with or without auditory verbal hallucinations (AVHs), and to discuss the use of pattern recognition techniques in the development of an objective index that may improve diagnostic accuracy and treatment outcomes for schizophrenia. Methods The pilot study included patients with schizophrenia with AVHs (SCH-AVH group) and without AVHs (SCH-no AVH group). High throughput sequencing (HTS) was performed to explore RNA networks. Global functional connectivity density (gFCD) analysis was performed to assess functional connectivity (FC) alterations of the default mode network (DMN). Quantitative long noncoding (lnc) RNA and mRNA expression data were related to peak T values of gFCDs using Pearson’s correlation coefficient analysis. Results Compared with the SCH-no AVH group ( n = 5), patients in the SCH-AVH group ( n = 5) exhibited differences in RNA expression in RNA networks that were related to AVH severity, and displayed alterations in FC (reflected by gFCD differences) within the DMN (posterior cingulate and dorsal-medial prefrontal cortex), and in the right parietal lobe, left occipital lobe, and left temporal lobe. Peak lncRNA expression values were significantly related to peak gFCD T values within the DMN. Conclusion Among patients with schizophrenia, there are concomitant FC and genetic expression alterations associated with AVHs. Data from pattern recognition studies may inform the development of an objective index aimed at improving early diagnostic accuracy and treatment planning for patients with schizophrenia with and without AVHs.
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