Moderators for the Relationship between Post-Traumatic Stress Disorder and Opioid Use Disorder.

Objective: Post-traumatic stress disorder (PTSD) is a common risk factor for opioid use disorder (OUD). However, not all individuals with PTSD develop OUD when exposed to opioids. As the underlying moderators remain unexplored, this analysis aimed to determine if non-traumatic adverse experiences and stressors prior to the age of 18 moderate the relationship between PTSD and OUD. Methods: In a matched dataset (n = 830) of individuals with or without PTSD who reported lifetime use of opioids, the following non-traumatic adverse experiences and stressors were assessed: emotional abuse, emotional neglect and physical neglect, parents' adverse experiences, and number of days jailed before the age of 18. Using the PROCESS macro in SAS for each factor, the conditional effects were estimated through simple slopes. Moderation was inferred through significant interaction effects. Results: The matched data were similar on age, gender, ethnicity, education, being born in the US, living with, or losing biological parents before age 18, and family history of depression, anxiety, and substance use disorder. Significantly more individuals in the preexisting PTSD group had preexisting psychiatric disorders, and preexisting substance use and schizotypal personality disorder. Childhood emotional abuse and neglect and physical neglect (effect: 0.03; 95%CI: 0.001-0.056; p = .039), and more than one event of adversity experienced by parents (effect: 0.34; 95%CI: 0.07-0.61; p = .013) significantly interacted with PTSD to lead to OUD. Conclusion: The conditional effect of PTSD on the development of OUD after exposure to opioids was dependent on the frequency and severity of childhood non-traumatic adverse experiences. To identify individuals with PTSD who are at a high risk of developing OUD, programs may focus on non-traumatic adverse childhood experiences that are not commonly explored. Future steps may include focusing on educational schemes to mitigate this higher risk of developing OUD in at-risk individuals, for example, by discussing the risks when prescribing opioids.

Early-life stressful events and suicide attempt in schizophrenia: Machine learning models.

Childhood abuse and neglect predicts suicide attempt. Furthermore, other early-life stressful events may predict lifetime suicide attempt in psychiatric disorders. We assessed 189 schizophrenics for suicide attempt and stressful life events. Early-life stressful events were used as predictors of lifetime suicide attempt in three machine learning models. In our sample, 38% of the schizophrenics had at least one suicide attempt lifetime. The machine learning models provided an overall significant prediction (accuracy range: 62-69%). Childhood sexual molestation and mental illness were important predictors of suicide attempt. Early-life stressful events should be included in models aiming at predicting suicide attempt in schizophrenia.

Childhood trauma predicts multiple, high lethality suicide attempts in patients with schizophrenia.

Childhood trauma has been shown to increase the risk of suicide attempts in individuals with schizophrenia. However, previous literature has been limited by considerable heterogeneity within the category of suicide attempters. Here we tested the predictive effect of childhood maltreatment on lifetime suicide attempt in a homogeneous sample of 650 patients with schizophrenia spectrum disorders. Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form and suicide history was measured using subjective and objective validated scales as well as medical chart reviews. We refined our sample into two homogenous groups: 1) suicide attempters: patients who had attempted suicide multiple times, with highly lethal results (medical hospitalization required) (n = 24); and 2) non-ideators: patients who had no personal history of suicide attempt or ideation, or family history of attempt (n = 25). Binary logistic regression models revealed that total childhood trauma (ß = 0.002; OR: 1.07; 95% CI: 1.00-1.14) and emotional abuse (ß = 0.04; OR: 1.38; 95% CI: 1.08-1.77), but not other trauma subtypes, significantly predicted lifetime multiple, high lethality suicide attempts after adjusting for demographic and clinical covariates. Thus, childhood trauma is a weak, independent risk factor for extreme suicide attempts in patients with schizophrenia spectrum disorders.

Correlation Between Violence and Antipsychotic Dosage in Schizophrenia: A Secondary Analysis of The Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) Dataset.

INTRODUCTION: Violent behavior is more common in individuals with schizophrenia, compared to the general population. Studies suggest higher psychotic symptoms are predictive of greater violent behavior. On the other hand, violent behaviors are reduced with antipsychotic treatment. However, the relationship between antipsychotic dosage and violence has not been studied to date. Thus, we aimed to determine if there exists an association between antipsychotic dosage and violence scores and whether the maximum violence would be predictive of the final antipsychotic dosage. We hypothesized that the violence scores at the final assessment in the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) would be correlated with the corresponding drug dosage and the maximum violence severity score would be predictive of the final dosage. METHODS: Antipsychotic dosage at the end of the trial was converted into defined daily dosage and chlorpromazine equivalents (CPZe). Final and maximum violence sum scores were analyzed from the final violence assessment interviews. Spearman's rank-order correlation and linear regression analyses were used to analyze the relationship between the violence scores and standardized antipsychotic dosages. RESULTS: The analysis was on 952 individuals with schizophrenia. There was a significant association between maximum violence severity score and the final CPZe dosage (p=0.049). Exploratory analysis of age and ethnicity revealed younger non-white individuals to be at a higher risk of engaging in violent activities. DISCUSSION: Violence in schizophrenia is associated with poor illness course. Further studies focusing on violence in younger non-white individuals are warranted.

The effect of ethnicity and immigration on treatment resistance in schizophrenia.

BACKGROUND: Treatment resistance is a common issue among schizophrenia patients undergoing antipsychotic treatment. According to the American Psychiatric Association (APA) guidelines, treatment-resistant status is defined as little or no symptom reduction to at least two antipsychotics at a therapeutic dose for a trial of at least six weeks. The aim of the current study is to determine whether ethnicity and migration are associated with treatment resistance. METHODS: In a sample of 251 participants with schizophrenia spectrum disorders, we conducted cross-sectional assessments to collect information regarding self-identified ethnicity, immigration and treatment history. Ancestry was identified using 292 markers overlapping with the HapMap project. Using a regression analysis, we tested whether a history of migration, ethnicity or genetic ancestry were predictive of treatment resistance. RESULTS: Our logistic regression model revealed no significant association between immigration (OR = 0.04; 95%CI = 0.35-3.07; p = 0.93) and treatment resistant schizophrenia. White Europeans did not show significant association with resistance status regardless of whether ethnicity was determined by self-report (OR = 1.89; 95%CI = 0.89-4.20; p = 0.105) or genetic analysis (OR = -0.73; 95%CI = -0.18-2.97; p = 0.667). CONCLUSION: Neither ethnicity nor migrant status was significantly associated with treatment resistance in this Canadian study. However, these conclusions are limited by the small sample size of our investigation.

No interaction between polygenic scores and childhood trauma in predicting suicide attempt in schizophrenia.

BACKGROUND: Approximately 5% of patients with schizophrenia commit suicide, and 20% to 40% of them have at least one suicide attempt during their lifetime. Previous research has identified childhood trauma as a potential risk factor for suicide attempt in schizophrenia. The Psychiatric Genetics Consortium found 108 common genetic risk loci associated with schizophrenia. Moreover, familial, adoption, and twin studies suggested that suicidal behaviour is under genetic influence. OBJECTIVE: Our objective was to determine the effect of childhood trauma and schizophrenia polygenic risk in leading to suicide attempt, as well as to determine any interaction effect between the polygenic scores with childhood trauma. METHODS: The study design was cross-sectional and retrospective considering lifetime suicide attempt as the main dependent variable. Childhood trauma was assessed using the Childhood Trauma Questionnaire. Polygenic Risk Score calculation was done using the genome-analysis toolkit, PLINK. The suicide attempts were recorded using the Columbia Suicide Severity Rating Scale. RESULTS: We included 224 subjects in our sample and 93 attempted suicide at least once in their lifetime. When comparing the weighted scores in attempters and non-attempters, we found no association (p > .05). CONCLUSION: Although our results do not support our hypothesis, the interaction analysis of genetic risk for schizophrenia in combination with the history of childhood trauma requires larger samples with high-quality suicide risk assessment.

Structural and functional alterations of the suicidal brain: An updated review of neuroimaging studies.

Brain imaging is a non-invasive and in vivo direct estimation of detailed brain structure, regional brain functioning and estimation of molecular processes in the brain. The main objective of this review was to analyze functional and structural neuroimaging studies of individuals at risk for suicide. We reviewed articles published between 2005 and 2018, indexed in PubMed and Medline, assessing structural and functional alterations of the brain of individuals at high risk for suicide and at low risk for suicide. We reviewed functional and structural neuroimaging studies which included individuals with a history of suicidal ideation or attempt in major depressive disorder (MDD), bipolar disorder (BD), psychosis, and borderline personality disorder (BPD). We selected 45 papers that focused on suicidality in MDD, 17 papers on BD, 11 papers on psychosis, and 5 papers on BPD. The suicidal brain across psychiatric diagnoses seems to heavily involve dysfunction of the fronto-temporal network, primarily involving reductions of gray and white matter volumes in the pre-frontal cortex (PFC), anterior cingulate, and superior temporal gyrus. Nonetheless, there are several ways to define suicidal behaviour and ideation. Therefore, it still remains difficult to combine the evidence from imaging studies that used different definitions of suicidality.