Cohen syndrome combined with psychiatric symptoms: a case report.

BACKGROUND: Cohen syndrome (CS) is a rare autosomal recessive inherited condition characterized by pathological changes affecting multiple systems. The extensive clinical variability associated with CS poses a significant diagnostic challenge. Additionally, there is limited documentation on the co-occurrence of CS with psychiatric symptoms. CASE REPORT: We report a case of a 30-year-old patient exhibiting characteristic physical features and psychiatric symptoms. Whole exome sequencing identified two heterozygous variants, a nonsense variation c.4336 C > T and a missense mutation c.4729G > A. Integrating clinical manifestations with genetic test results, we established the diagnosis of CS combined with psychiatric symptoms. CONCLUSIONS: This case introduces a novel missense variant as a candidate in the expanding array of VPS13B pathogenic variants. Its clinical significance remains unknown, and further investigation may broaden the spectrum of pathogenic variants associated with the VPS13B gene. Early diagnosis of CS is crucial for the prognosis of young children and holds significant importance for their families.

Computational markers of risky decision-making predict for relapse to alcohol.

BACKGROUND: Relapse remains the major challenge in treatment of alcohol use disorder (AUD). Aberrant decision-making has been found as important cognitive mechanism underlying relapse, but factors associated with relapse vulnerability are unclear. Here, we aim to identify potential computational markers of relapse vulnerability by investigating risky decision-making in individuals with AUD. METHODS: Forty-six healthy controls and fifty-two individuals with AUD were recruited for this study. The risk-taking propensity of these subjects was investigated using the balloon analog risk task (BART). After completion of clinical treatment, all individuals with AUD were followed up and divided into a non-relapse AUD group and a relapse AUD group according to their drinking status. RESULTS: The risk-taking propensity differed significantly among healthy controls, the non-relapse AUD group, and the relapse AUD group, and was negatively associated with the duration of abstinence in individuals with AUD. Logistic regression models showed that risk-taking propensity, as measured by the computational model, was a valid predictor of alcohol relapse, and higher risk-taking propensity was associated with greater risk of relapse to drink. CONCLUSION: Our study presents new insights into risk-taking measurement and identifies computational markers that provide prospective information for relapse to drink in individuals with AUD.

Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study.

BACKGROUND: The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. METHODS: Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. RESULTS: Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p<7.14×10-4), respectively. However, after performing multivariable MR, only age at first sexual intercourse has direct effects on five psychiatric disorders (Depression, Attention deficit or hyperactivity disorder, Bipolar disorder, Posttraumatic stress disorder and schizophrenia) when accounting for other reproductive behaviors with significant effects in univariable analyses. CONCLUSION: Our findings suggest that reproductive behaviors predominantly exert their detrimental effects on psychiatric disorders and age at first sexual intercourse has direct effects on psychiatric disorders.

Post-error slowing predicts for relapse in individuals with alcohol use disorder.

BACKGROUND: Relapse characterizes addiction. The cognitive phenotype underlying relapse in individuals with alcohol use disorder (AUD) remain unelucidated. Here we aimed to investigate the potential changes in behavioral adjustment in AUD, and the association with relapse. METHOD: Forty-seven subjects with AUD at Shandong Mental Health Center completed the stop-signal task, the PACS, the Beck Depression Inventory and the State-Trait anxiety questionnaires. Thirty age-matched male healthy subjects served as the control group (HC). In the follow-up, twenty-one subjects remained abstinent, while twenty-six subjects relapsed. Independent sample t-test was applied to measure differences between two groups and logistic regression analysis was conducted to explore the potential predictors on relapse. RESULTS: The results showed that there were significant differences in stop signal reaction time (SSRT) and trigger failure between the AUD and HC groups. Relapsed group showed longer post-error slowing (PES) when compared to the non-relapsed group. The PES could predict relapse in alcohol use disorder. CONCLUSION: Individuals with AUD showed impaired inhibitory control, which may predict relapse.

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence.

Poststroke depression (PSD) does not exist before and occurs after the stroke. PSD can appear shortly after the onset of stroke or be observed in the weeks and months after the acute or subacute phase of stroke. The pathogenesis of PSD is unclear, resulting in poor treatment effects. With research advancement, immunoactive cells in the central nervous system, particularly microglia, play a role in the occurrence and development of PSD. Microglia affects the homeostasis of the central nervous system through various factors, leading to the occurrence of depression. The research progress of microglia in PSD has been summarized to review the evidence regarding the pathogenesis and treatment target of PSD in the future.

Oxidative Stress and 4-hydroxy-2-nonenal (4-HNE): Implications in the Pathogenesis and Treatment of Aging-related Diseases.

Oxidative stress plays an important role in the development of aging-related diseases by accelerating the lipid peroxidation of polyunsaturated fatty acids in the cell membrane, resulting in the production of aldehydes, such as malondialdehyde and 4-hydroxy-2-nonenal (4-HNE) and other toxic substances. The compound 4-HNE forms adducts with DNA or proteins, disrupting many cell signaling pathways including the regulation of apoptosis signal transduction pathways. The binding of proteins to 4-HNE (4-HNE-protein) acts as an important marker of lipid peroxidation, and its increasing concentration in brain tissues and fluids because of aging, ultimately gives rise to some hallmark disorders, such as neurodegenerative diseases (Alzheimer's and Parkinson's diseases), ophthalmic diseases (dry eye, macular degeneration), hearing loss, and cancer. This review aims to describe the physiological origin of 4-HNE, elucidate its toxicity in aging-related diseases, and discuss the detoxifying effect of aldehyde dehydrogenase and glutathione in 4-HNE-driven aging-related diseases.

A Retrospective Analysis of Death Among Chinese Han Patients with Schizophrenia from Shandong.

Purpose: To describe the mortality rate and cause of death among Han Chinese schizophrenia patients and to explore the risk factors affecting survival. Methods: We performed a retrospective analysis of death among patients with schizophrenia from Jan 1, 2012, to Dec 31, 2019, using the Severe Mental Disorders Information System of Shandong Province (henceforth referred to as the SMDI system) in Shandong, China. The cohort included 72,102 patients, and 11,766 patients died during follow-up. The data in this cohort study were derived from the SMDI system. We calculated the crude mortality rate and standardized mortality rate (SMR, standardized according to the sex and age composition of the population in Shandong Province) for patients with schizophrenia. Cox regression analysis was used to analyze the risk factors affecting patient survival, and the statistical index was the hazard ratio (HR). Results: The mean age of the cohort patients was 47.21±14.05 years; 51.79% were males, and 48.21% were females. Among them, 68.98% (49,735) had only a primary education level, 85.36% (61,549) were farmers, 64.37% (46,413) were married, and 94.01% (67,775) received community management. A total of 16.32% of the cohort died. The SMR in patients with schizophrenia was 4.9, and it was higher for males than females (4.99 versus 4.82). Among the 6 registered causes of death, physical illness had the highest SMR (5.15), followed by other causes of death (4.86), mental illness-related complications (4.57), homicide (4.31), accidents (4.13), and suicide (3.87). Higher levels of education, employment (in-service status), marriage, and urban residence were protective factors for survival among patients with schizophrenia. Conclusion: In China, the SMR of schizophrenia is relatively high, and physical diseases are the main cause of death. We suggest that a variety of measures should be taken early to treat somatic diseases and reduce SMR in patients with schizophrenia.

Modulation of ultra-low-molecular-weight heparin on [Ca²âº]i in nervous cells.

Heparin is an effective competitive antagonist of inositol 1,4,5-trisphosphate receptors (IP(3)Rs). It binds to IP(3)Rs and affects calcium homeostasis. Ultra-low-molecular-weight heparin (ULMWH) is heparin's derivative, the present study was designed to test the effects of ULMWH on intracellular calcium concentration ([Ca(2+)]i) in primary cultured neurons. [Ca(2+)]i was measured by Multilabel Counter Victor-1420 using Fura-2/AM as the calcium fluorescent probe. The results indicated that ULMWH decreased the resting [Ca(2+)]i with or without extracellular Ca(2+). They had no effects on high K(+)-induced elevation of intracellular Ca(2+) level indicating that ULMWH had no effect on external Ca(2+) influx mediated by voltage-dependent calcium channels. However, they partially reduced the increase in [Ca(2+)]i induced by glutamate. Furthermore, ULMWH significantly inhibited the inositol 1,4,5-trisphosphate (IP(3))-induced increase in [Ca(2+)]i both in cellular and subcellular level. These results suggest that ULMWH may reduce [Ca(2+)]i in neurons through suppressing Ca(2+) release from IP(3)-sensitive stores.

Antagonistic effects of ultra-low-molecular-weight heparin on Aß25-35-induced apoptosis in cultured rat cortical neurons.

Low-molecular-weight heparin (LMWH) and ultra-low-molecular-weight heparin (ULMWH) are heparin's derivatives, having various pharmacological effects. The present study aims to investigate the effect of ULMWH on amyloid ß peptide (Aß25-35)-induced neurotoxicity in cultured rat cortical neurons, and LMWH was employed as a positive control agent. The neurons were incubated with Aß25-35 (35µM), Aß25-35 plus ULMWH (2, 10, 50 µg/ml) or LMWH (10 µg/ml) for 24h. The cell viability was assessed by MTT and LDH release. FITC-Annexin V/PI double staining, Hoechst 33258 staining, TUNEL and Western blotting for bcl-2 and caspase-3 were employed to measure the neuron apoptosis. Furthermore, the intracellular Ca(2+) concentration was measured by a fluorescent dye, Fura-2/AM. The results showed that ULMWH significantly increased cell viability and the protein expression levels of bcl-2 and decreased the LDH release, the number of apoptotic cells, the concentration of intracellular Ca(2+) and the protein expression levels of caspase-3 in cortical neurons, suggesting that ULMWH can obviously reduce Aß25-35-induced neurotoxic effects and might act as a potential agent for Alzheimer's disease.

Protective effect of ultra low molecular weight heparin on glutamate-induced apoptosis in cortical cells.

PURPOSE: To investigate the effect of ultra low molecular weight heparin (ULMWH) on glutamate induced apoptosis in rat cortical cells and to explore the possible mechanisms. MATERIALS AND METHODS: Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis was first analyzed with Hoechst 33258 and then confirmed by DNA fragmentation. The concentration of free intracellular calcium ([Ca(2+)](i)) was determined with fura-2/AM fluorometry. The expression of Bcl-2 family protein and caspase-3 were evaluated with Western blot. RESULTS: Typical apoptotic morphological change in rat cortical cells treated with 100 micromol/L glutamate for 24h was detected by Hoechst 33258 staining, which was then confirmed by the DNA ladder of agarose gel electrophoresis. The apoptotic rate of the glutamate treated cells was up to 33.21%, and 24 h of treatment with glutamate increased [Ca(2+)](i), down-regulated Bcl-2 expression, up-regulated Bax expression, and increased caspase-3 activation in rat cortical cells. Our research demonstrated that ULMWH pretreatment can prevent the glutamate-induced apoptosis, attenuate the increase of [Ca(2+)](i) not only in medium containing Ca(2+) but also in Ca(2+)-free medium, up-regulate the expression of Bcl-2, down-regulate the expression of Bax, and decrease caspase-3 activation. CONCLUSION: ULMWH has neuroprotective capacity to antagonize glutamate-induced apoptosis in cortical cells, through decrease of Ca(2+) release and modulation of apoptotic processes.