Recent Stressful Life Events and Suicidal Ideation in Schizophrenia: A 1-Year Follow-up Study.

ABSTRACT: Half of patients with schizophrenia experience suicidal ideation. Only few studies have examined the effects of recent stress on both current and emergent suicidal ideation.A cohort of 85 patients with schizophrenia spectrum disorders was assessed. The study was divided into a cross-sectional and longitudinal arms to test the effect of recent stress on suicidal ideation. Analysis was done using logistic regression models.After correcting for covariates, recent stress had no significant effect on current suicidal ideation. However, increased total stress (odds ratio [OR] = 1.099 [1.032-1.170], p = 0.003) and health-related stress (OR = 1.331 [1.074-1.650], p = 0.009) at follow-up were predictive of emergent suicidal ideation.With this sample size, we were unable to draw firm conclusions regarding the effect of specific life events on suicidal ideation. Further studies involving larger samples that investigate the interplay between several risk factors are needed.

Chromosome 22 Deletions and Suicidal Behavior in Schizophrenia.

BACKGROUND: Studies have shown that the overall copy number variant (CNV) load is associated with schizophrenia. Schizophrenia is a mental disorder that is frequently associated with suicidal behavior. METHODS: We recruited 263 patients with schizophrenia from the Centre for Addiction and Mental Health. The Columbia Suicide Severity Rating Scale was used to assess the presence of lifetime suicide attempt. Genotyping was completed using the Illumina Omni 2.5 chip. We tested the association between deletion events on chromosome 22 with suicide attempt in our schizophrenia sample. RESULTS: There was no significant difference between suicide attempters and non-attempters considering the presence/absence of deletion events on chromosome 22. CONCLUSION: Although our results did not show a significant association between deletions on chromosome 22 and suicide attempt in schizophrenia, CNV studies may reveal important, novel insights and open further investigation for the treatment of neuropsychiatric diseases.

Genome-wide methylation association with current suicidal ideation in schizophrenia.

In this study, we investigate the epigenetic mechanisms associated with current suicidal ideation. Gene expression changes have been found in post-mortem brain of suicide victims. However, it is not clear how in-vivo gene expression change confers risk for suicide. DNA methylation is a form of epigenetic modification that regulates gene expression. Our primary aim is to investigate genome-wide methylation in conferring risk for current suicidal ideation (SI) in schizophrenia. The presence of current SI and genome-wide methylation patterns were assessed in 107 patients with schizophrenia. DNA methylation has been measured in white blood cells as a possible peripheral biomarker of SI. SI was the primary outcome variable in a model including methylation status of white blood cells using the Illumina 450 array. We have tested the association with genome-wide methylation levels in 19 subjects with current SI and 88 subjects without current SI and we found that higher methylation level in the CpG cg06121808 located in the gene SLC20A1 on chromosome 2 was associated with current SI (p = 0.000003; beta difference = 0.06). Furthermore, the distal promoter analysis showed that the gene SMPD2 was hypermethylated in suicide ideators (p = 0.0001; beta difference = 0.02). Thus, molecular biomarkers could advance our understanding of the molecular mechanisms of stress-related SI. Furthermore, the methylation sites that we have identified should be replicated in other suicide related phenotypes to generate robust biomarkers with high translational value for proof of concept interventions aiming at reducing SI.

Astrocytes in the Neuropathology of Bipolar Disorder: Review of Current Evidence.

(1) Background: Approximately one-third of patients with bipolar disorder (BD) do not experience sustained remission with current treatments. Presently, astrocytes, i.e., glial cells that act as key regulators of neuroinflammation, have been a target for therapeutic development. Research regarding their role in the neuropathology of BD is limited. We conducted a scoping review on evidence linking astrocytes to the pathology of BD. (2) Methods: The search was conducted in MEDLINE for studies published from inception to August 2022. Studies of interest were data-extracted and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. (3) Results: Overall, 650 publications were identified, of which 122 full texts were evaluated and 12 included. Four were in vitro, seven were ex vivo, and one study was both in vitro and in vivo. In vitro investigations focused on plasma levels of neuroinflammatory biomarkers S100B and glial fibrillary acidic protein (GFAP). Ex vivo investigations were post-mortem brain studies assessing astrocytes in regions of interest (i.e., anterior cingulate cortex, dorsolateral prefrontal cortex) using phosphorylated GFAP and ASCT-1. The in vivo and in vitro study evaluated morphological and chemical variations of YKL-40 between cohorts. (4) Conclusions: Reports indicate an association between astrocyte dysfunction and BD although larger studies are required to validate this association.

Association Between the Visual N1-P2 Complex and Neuroticism.

Neuroticism is a personality trait associated with impaired attention, memory, and error detection. Thus, the present study investigated the visual N100 and P200 event-related potentials components associated with attention using a 2-back working memory task in healthy neurotic and nonneurotic participants, evaluated using the Neuroticism, Extraversion, Openness Five Factor Inventory. A total of 35 healthy participants were asked to perform the 2-back task while recording electroencephalographic activity from 64 electrodes on the scalp. Analysis of the N100 and P200 amplitude and latency in high neuroticism and low neuroticism subjects showed an increased P200 amplitude and latency for high neuroticism subjects in the frontal and parietal regions, respectively. However, there were no significant performance differences between the high and low neuroticism subjects for the 2-back working memory task. Therefore, the results suggest that neuroticism is associated with the P200 component elicited in the context of a working memory task.

Mediating effect of genome-wide DNA methylation on suicidal ideation induced by perceived stress.

Stress is an important risk factor for suicidal ideation, but the mechanisms that link stress, suicidal ideation and neurobiology remain unclear. Epigenetic mechanisms are involved in both vulnerability to suicidal behavior and stress. This is a pilot study of 60 patients with schizophrenia spectrum disorders (36 men and 24 women), with an average age of 43.75 ± 12.24 years. We analyzed the effects of (1) perceived stress and (2) the mediation of genome-wide methylation (~450 000 CpG sites) on suicidal ideation severity. The top CpG site mediating the effect of stress on suicidal ideation was the cg10782349 located in the ZNF701 gene on chromosome 19, facilitating the effect through DNA hypermethylation. These preliminary results indicate that DNA methylation in peripheral tissues can clarify the complex relationship between stress and suicidal ideation in schizophrenia.

Biological aging in schizophrenia and psychosis severity: DNA methylation analysis.

The physiological changes associated with normal aging are known to occur earlier in individuals with schizophrenia (SCZ). One of the phenomena linked with normal aging is the change in patterns of epigenetic modifications. We recruited 138 individuals with SCZ spectrum disorders and extracted DNA from white blood cells. The combinations of pre-selected DNA methylation sites were utilized to estimate the 'methylation age' (DNAm age) and evaluate evidence of epigenetic age acceleration. We investigated the correlation between the epigenetic age acceleration measures and psychosis severity; furthermore, we estimated blood cell counts based on DNA methylation levels. The extrinsic epigenetic age acceleration showed a significant correlation with the Brief Psychiatric Rating Scale (BPRS) disorganization subscale(r=0.222, p=0.039).Both Horvath age acceleration and Hannum age acceleration showed a significant correlation (r=0.221, p=0.029; r=0.242, p=0.017 respectively) with the Symptom Checklist 90 (SCL-90) psychotic domain. Overall, this study shows some evidence of epigenetic age acceleration associated with psychosis severity using two different algorithms for DNAm age analysis.

Global DNA methylation in suicidal ideation and suicide attempt in schizophrenia.

Suicidal behavior is influenced by many risk factors such as childhood trauma, stressful life events, genetic factors, and severe mental illnesses. Suicidal ideation is present in 50% of schizophrenia patients and is associated with an elevated risk of suicide attempt. Studies have shown that epigenetic mechanisms are associated with suicidal behavior in schizophrenia. Although several studies have suggested the importance of epigenetic factors in suicidal ideation and behavior, no studies have investigated global methylation in association with these two phenotypes. This study investigated global methylation level/change in association with current and emergent suicidal ideation and also with suicide attempt. Forty-seven schizophrenia patients were assessed for the association between global methylation and suicide attempt, and a subsample of these patients (n = 27) was assessed for current suicidal ideation. Afterwards, we performed a longitudinal analysis in which global methylation changes during a 3-month follow-up were compared between patients with and without emergent suicidal ideation. This methylation analysis did not find evidence for a significant association between global methylation and suicidal ideation or suicide attempt. To date, there are no robust biomarkers predicting suicidal ideation or behavior in psychotic patients. This study is the first to investigate global methylation in predicting suicidal ideation and behavior. Although we did not find evidence for an association between global methylation and these phenotypes, our findings may offer novel insights into the molecular mechanisms linked to suicide. Future investigation may measure global methylation in association with suicidal ideation or behavior in larger samples.

Effectiveness of Antipsychotics in Reducing Suicidal Ideation: Possible Physiologic Mechanisms.

Background: The aim of this study is to evaluate whether any specific antipsychotic regimen or dosage is effective in managing suicidal ideation in schizophrenia. Four comparisons were conducted between: (1) clozapine and other antipsychotics; (2) long-acting injectable and oral antipsychotics; (3) atypical and typical antipsychotics; (4) antipsychotics augmented with antidepressants and antipsychotic treatment without antidepressant augmentation. Methods: We recruited 103 participants diagnosed with schizophrenia spectrum disorders. Participants were followed for at least six months. The Beck Scale for Suicidal Ideation (BSS) was used to assess the severity of suicidal ideation at each visit. We performed a multiple linear regression model controlling for BSS score at study entry and other confounding variables to predict the change in the BSS scores between two visits. Results: Overall, there were 28 subjects treated with clozapine (27.2%), and 21 subjects with depot antipsychotics (20.4%). In our sample, 30 subjects experienced some suicidal ideation at study entry. When considering the entire sample, there was a statistically significant decrease in suicidal ideation severity in the follow-up visit compared to the study entry visit (p = 0.043). Conclusions: To conclude, our preliminary analysis implies that antipsychotics are effective in controlling suicidal ideation in schizophrenia patients, but no difference was found among alternative antipsychotics' classes or dosages.

Genome-wide association study of aggression and violence in schizophrenia.

Schizophrenia patients are at higher risk of engaging in violent behavior than the general population. Schizophrenia is also regarded as a highly heritable disorder. This study aimed to analyze genome-wide the effect of SNPs on violence in schizophrenia. We recruited 205 subjects between the age of 18-75 from the Centre for Addiction and Mental Health (CAMH), who had a diagnosis of schizophrenia or schizoaffective disorder. We recorded physical, verbal and lifetime violence scores indicating any violent actions to inflict pain, bodily harm, or death on another individual from the standardized scale, Modified Overt Aggression Scale (MOAS). We genotyped each participant's DNA using the Illumina Omni 2.5, and the SNPs were analyzed using the whole genome analysis tool-set, PLINK. We probed for single nucleotide polymorphisms (SNPs) correlated with violence in schizophrenia patients. We found one SNP (rs2188177) on chromosome 7 which showed a trend for association with physical violence (p = 7.80E-06). This study is the first of its kind to investigate genome-wide, the polymorphisms associated with violence in schizophrenia. The findings of this study may promote collaborative efforts to understand the genetic basis of violent behavior in psychosis.