Schizophrenia and bipolar disorder are severe mental disorders with a major component of genetic factors in their etiology. Rare mutations play a significant role in these two disorders, and they are highly heterogeneous and personalized. Identification of personalized mutations is essential for the establishment of molecular diagnosis, providing insight into pathogenesis and guiding the personalized treatment for each affected patient. We conducted whole-genome sequencing analysis of families with schizophrenia and bipolar disorder to search for their genetic underpinnings. This report identified a rare missense mutation Arg1087Gln of BSN (bassoon presynaptic cytomatrix protein) co-segregating with schizophrenia in a family with multiple affected members. Furthermore, we identified the rare missense mutation Ser1535Leu of PCLO (piccolo presynaptic cytomatrix protein) in two sisters with bipolar disorder and another rare missense mutation, His5142Arg in PCLO, in a patient with schizophrenia. These three missense mutations were very rare and were predicted to be pathogenic. The BSN and PCLO genes encode two structurally related proteins of the presynaptic cytomatrix at the active zone that regulates neurotransmission at the presynaptic neuronal terminal. Our findings suggest the involvement of the presynaptic matrix in the pathogenesis of schizophrenia and bipolar disorder, and BSN and PCLO are the risk genes for schizophrenia and bipolar disorder.
Background: Synthetic cathinones are the most used novel psychoactive substances in Taiwan because they exhibit psychoactive effects similar to those of methamphetamine, inducing acute psychosis, violence, and selfharm. However, the differences in the clinical characteristics of patients with synthetic cathinone and methamphetamine intoxication admitted to psychiatric emergency departments (EDs) remain unclear.Methods: This study recruited patients with stimulant intoxication who were admitted to a psychiatric ED from April 2019 to May 2020. Sociodemographic, lifestyle, and psychopathological data were collected through face-to-face interviews and evaluated. Immunoassay tests and liquid chromatography-quadrupole time-of-flight mass spectrometry were performed to detect substances in urine specimens. The patients were matched by sex and age (in 5-year intervals). The associations between the 2 groups and physical complications were analyzed through logistic regression.Results: Twenty-four patients with synthetic cathinone intoxication were identified and matched with 48 patients with methamphetamine intoxication. The 2 groups exhibited similar clinical severity of psychotic symptoms and high risks of violence and self-harm. Both groups were predominated by unmarried patients, unemployed patients, and habitual smokers and drinkers. However, family histories of substance use and criminal records were less prevalent among the patients with synthetic cathinone intoxication, but they had a higher rate of physical complications (odds ratio, 8.55; 95% confidence interval, 2.15-34.03), compared with patients with methamphetamine intoxication.
Conclusions:Compared with patients intoxicated with methamphetamine, those intoxicated with synthetic cathinones may have similar tendencies toward psychosis, violence, and self-harm but higher risks of physical complications, which are prioritized in psychiatric EDs.
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