Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. Funding: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

Two Neuroanatomical Signatures in Schizophrenia: Expression Strengths Over the First 2 Years of Treatment and Their Relationships to Neurodevelopmental Compromise and Antipsychotic Treatment.

BACKGROUND AND HYPOTHESIS: Two machine learning derived neuroanatomical signatures were recently described. Signature 1 is associated with widespread grey matter volume reductions and signature 2 with larger basal ganglia and internal capsule volumes. We hypothesized that they represent the neurodevelopmental and treatment-responsive components of schizophrenia respectively. STUDY DESIGN: We assessed the expression strength trajectories of these signatures and evaluated their relationships with indicators of neurodevelopmental compromise and with antipsychotic treatment effects in 83 previously minimally treated individuals with a first episode of a schizophrenia spectrum disorder who received standardized treatment and underwent comprehensive clinical, cognitive and neuroimaging assessments over 24 months. Ninety-six matched healthy case-controls were included. STUDY RESULTS: Linear mixed effect repeated measures models indicated that the patients had stronger expression of signature 1 than controls that remained stable over time and was not related to treatment. Stronger signature 1 expression showed trend associations with lower educational attainment, poorer sensory integration, and worse cognitive performance for working memory, verbal learning and reasoning and problem solving. The most striking finding was that signature 2 expression was similar for patients and controls at baseline but increased significantly with treatment in the patients. Greater increase in signature 2 expression was associated with larger reductions in PANSS total score and increases in BMI and not associated with neurodevelopmental indices. CONCLUSIONS: These findings provide supporting evidence for two distinct neuroanatomical signatures representing the neurodevelopmental and treatment-responsive components of schizophrenia.

Antipsychotic treatment effects and structural MRI brain changes in schizophrenia.

BACKGROUND: Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia. METHODS: A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest. RESULTS: The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms. CONCLUSIONS: We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.

The 3-year progression of clinically significant psychotic-like experiences in a general adult population in Lagos, Nigeria.

PURPOSE: The study assessed the 3-year progression of clinically significant psychotic-like experience (CS-PLE) symptoms in an adult general population in terms of stability or remission of symptoms and transition to psychosis. METHODS: Participants (n = 1292) aged 18-65 years with CS-PLE were assessed at baseline for sociodemographic details, family history of mental illness, functioning status, common mental disorders, alcohol, and substance use disorders. Three years later they were reassessed for diagnosis of psychosis, presence or remission of PLE symptoms, and contact with mental health services. RESULTS: The mean age of the participants at baseline in years was 36.56 (SD = 11.66) and there were 855 (66.2%) females. By the 3rd year follow-up, 95 (7.3%) had transited to psychosis, while 850 (65.5%) had persistent CS-PLE symptoms and the rest 347 (27.2%) were in remission. Only history of mental illness in the immediate family (HR 4.81, 95% CI 1.40-16.47, P = 0.013) and regular use of cannabis at less than 18 years of age (HR 0.65, 95% CI 0.55-0.77, P < 0.001) were the independent predictors of conversion to psychosis at 3 years. CONCLUSION: The rate of TTP in the non-clinical population with elevated risk may be lower than that earlier reported in the western literature. Interventions aimed at preventing transition to psychosis in high risk groups must pay attention to early onset users of cannabis and those with family history of mental illness.

Healthcare Utilization 12 Months Prior to Fatal and Non-fatal Suicidal Behaviour in Cape Town, South Africa.

The purpose of this study was to characterize healthcare use for general care and mental health one year before suicidal behavior among individuals with fatal and non-fatal suicidal behavior (NFSB) in Cape Town, South Africa. We linked electronic health records of 484 participants from a case series of 93 completed suicides on whom forensic autopsies were performed at a mortuary in Cape Town, between August 2014 and January 2016; and 391 patients admitted to hospital following NFSB between June 2014 and March 2015, and between August 2015 and August 2017. Time from last healthcare visit to date of suicidal behavior (fatal or non-fatal) was calculated, and Kaplan Meier curves were used to compare the differences by psychiatric diagnoses and study group. Overall, 64.5% of completed suicides and 65.9% of NFSB patients sought general healthcare in the year before suicidal behavior. Most of these visits occurred at hospital outpatient clinics (40.8%) and primary healthcare facilities (31.3%). The prevalence of preexisting psychiatric diagnoses and the use of mental healthcare services was lower for individuals who completed suicide compared to NFSB patients. Common reasons for a healthcare visit among individuals who completed suicide were chronic disease and assault; and psychiatric illness (depression, bipolar, and/or substance use disorders), chronic disease and HIV among NFSB patients. A large proportion of individuals with fatal and NFSB interacted with the healthcare system before suicidal behavior. These findings suggest opportunities for suicide prevention at primary healthcare facilities, antiretroviral treatment centers and emergency departments.HIGHLIGHTSHealthcare access is common among individuals with fatal and NFSB in the year before suicidal behavior.The prevalence of mental disorder diagnoses is higher among NFSB patients than among individuals who completed suicide.A greater proportion of NFSB patients accessed mental healthcare services compared to individuals who completed suicide.

Differences in white matter microstructure in first-episode schizophrenia spectrum disorders vs healthy volunteers and their association with cognition.

OBJECTIVE: Both cognitive impairment and alterations in white matter tissue microstructure are well recognised in schizophrenia. We investigated whether differences in white matter microstructure underpin cognitive impairments in patients with first-episode schizophrenia spectrum disorders when controlling for multiple confounding factors. METHODS: We employed a cross-sectional study design and compared fractional anisotropy (FA) between individuals diagnosed with first- episode schizophrenia spectrum disorders (FES) (n = 68) and matched healthy controls (n = 120). We conducted multiple analyses of covariance (ANCOVAs) to compare the mean FA values for patients and controls across 27 white matter tracts. We conducted exploratory correlation analyses to determine if white matter tract differences were associated with global cognitive impairment as well as deficits across seven cognitive domains. RESULTS: We found widespread reductions in FA in patients compared to controls, after controlling for confounding variables, such as age, biological sex, education, substances, and childhood adversities. We found a significant positive correlation between the attention/vigilance domain and the splenium of the corpus collosum and external capsule after correction for multiple comparisons. In the control group we found no significant correlations between FA and cognition. CONCLUSION: Our findings provide a neurobiological basis for attentional cognitive deficits in schizophrenia, highlighting a potential role for the splenium of the corpus collosum and external capsule.

Depressive symptoms and quality of life prior to metabolic surgery in Cape Town, South Africa.

Background: Depression has been shown to have a negative impact on the outcomes of metabolic surgery and quality of life (QOL). Currently, there are limited data on mental distress and QOL in metabolic surgery candidates in South Africa. Aim: This study aimed to determine the prevalence of depressive symptoms at the time of presurgical assessment in participants undergoing metabolic surgery. Setting: The Obesity and Metabolic Surgery Initiative at Tygerberg Hospital. Methods: We conducted pre-operatively a retrospective cross-sectional study on patients who underwent metabolic surgery from September 2017 to September 2019. Participants were profiled in terms of metabolic parameters, depressive symptoms and QOL. Results: Of the 157 participants assessed, 88% were female with a body mass index in the super obese range. Twenty-two percent of participants had depressive symptoms. Metabolic surgery candidates with depressive symptoms had a significantly poorer overall QOL score compared with those without depressive symptoms. When controlling for all other variables, an increase in QOL score was shown to decrease the odds of current depressive symptoms, whilst back pain on non-narcotic medication and having had a stroke were found to increase the odds of current depressive symptoms. Conclusion: This study highlights the complex interplay between metabolic, clinical and psychiatric factors in patients undergoing metabolic surgery. The study highlights the vital role of a psychiatrist as part of a multidisciplinary team pre- and post-operatively in the early identification of depressive symptoms. Psychiatrists may have an important role to play as part of the multidisciplinary team in metabolic surgery, including screening for mental health problems pre- and post-operatively, providing psychoeducation and relevant pharmacological treatment and psychotherapy where needed. Contribution: This study expands our limited knowledge of psychiatric comorbidity (in particular depressive symptoms and associated factors) in people undergoing metabolic surgery in low- and middle-income countries.

Childhood trauma exposure and reward processing in healthy adults: A functional neuroimaging study.

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire-Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults.

Sex and gender associations with indicators of neurodevelopmental compromise in schizophrenia spectrum disorders.

BACKGROUND: It has been proposed that sex and gender differences described in schizophrenia can be explained from a neurodevelopmental perspective. AIM: In this study, we examined the associations of biological sex and gender role endorsement with putative indicators of neurodevelopmental compromise. METHODS: We used the Bem Sex Role Inventory to calculate masculinity scores in 77 patients with a first episode of a schizophrenia spectrum disorder, and selected the following indicators of neurodevelopmental compromise: family history of schizophrenia, obstetric complications, premorbid functioning, neurological soft signs, and cognitive function. Secondary objectives included the moderating effects of age of onset of illness, substance use and negative symptoms on these associations. RESULTS: There were no significant sex differences across any of the indicators of neurodevelopmental compromise. However, lower masculinity scores correlated significantly with poorer premorbid adjustment, sensory integration deficits and worse overall cognitive performance. Stepwise linear regression identified poorer premorbid adjustment in early adolescence and lower verbal learning scores as independent predictors of lower masculinity scores. In contrast to sex, gender showed several associations with indicators of neurodevelopmental compromise. CONCLUSIONS: Lower masculinity scores may represent part of a phenotype for a neurodevelopmental anomaly that places some individuals on a pathway to schizophrenia.

The trajectories and correlates of two negative symptom subdomains in first-episode schizophrenia.

BACKGROUND: Recent studies suggest a two-factor structure for negative symptoms as assessed by the Positive and Negative Syndrome Scale (PANSS) in schizophrenia, namely experiential and expressive subdomains. Little is known about their clinical correlates and treatment trajectories. OBJECTIVES: We sought to replicate the two factor-analysis derived subdomains for PANSS negative symptoms in schizophrenia and to assess their independent demographic, premorbid and treatment-related characteristics. METHODS: This was a longitudinal study of 106 minimally treated participants with a first episode of a schizophrenia spectrum disorder who received treatment with flupenthixol decanoate 2-weekly injections over two years. Factor analysis was used to characterize the PANSS negative symptom subdomains and linear mixed-effect models for continuous repeated measures were constructed to assess the temporal relations between the negative symptom subdomains and premorbid and treatment related variables. RESULTS: Factor analysis confirmed a two-factor solution for experiential and expressive subdomains of negative symptoms, although they were strongly correlated. The treatment response trajectories for the two subdomains did not differ significantly, and neither subdomain was significantly associated with our premorbid variables. We found significant main effects for disorganised symptoms and extrapyramidal symptoms on the expressive subdomain, and for disorganised symptoms and depressive symptoms on the experiential subdomain. Post-hoc testing indicated that reductions in HDL-cholesterol levels were associated with less improvement in both expressive and experiential subdomain scores. CONCLUSION: The two negative symptom subdomains are closely related, have similar premorbid correlates and respond similarly to antipsychotic treatment. Depression affects the experiential subdomain, whereas extrapyramidal symptoms affect the expressive subdomain.

The associations of cannabis and methamphetamine use with cognitive performance over the first 2 years of treatment in schizophrenia spectrum disorders.

AIM: Cognitive deficits are a core feature of schizophrenia, and comorbid substance use may be a contributory factor. Methamphetamine use has been associated with cognitive impairment in schizophrenia, while associations with cannabis use are less clear-cut. This study aimed to investigate the associations of cannabis and methamphetamine use with cognitive performance in first-episode schizophrenia spectrum disorders over the first 2 years of treatment. METHODS: This was a longitudinal cohort study in 81 patients treated with flupenthixol decanoate according to a standardized protocol over 24 months. Cognitive performance was assessed with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Cognitive Consensus Battery at four time points, and urine testing for cannabis and methamphetamine was conducted at six time points. We used linear mixed-effect models for repeated measures to assess visit-wise changes in composite cognitive scores in patients (n = 91) compared to matched controls without psychiatric or medical disorders (n = 100). Linear regression models were constructed to examine pre-treatment and end-point effects in patients. RESULTS: Compared to controls, patients exhibited greater cognitive impairments at baseline, which improved with treatment, but remained significantly lower throughout. The number of positive methamphetamine, but not cannabis, tests predicted less cognitive improvement in patients. CONCLUSIONS: Our findings suggest a negative association between methamphetamine and cognition, but not cannabis.

Considerations for improving diversity, equity and inclusivity within research designs and teams.

This article addresses the growing movement towards greater diversity, equity and inclusivity (DEI) within the research community. We present the case for increasing DEI among research teams and participants, discussing the benefits of this, as well as some of the current hindrances to achieving better DEI, particularly implicit biases. Lastly, we present some interventions that can be implemented within four key aspects of the research process: research methods, the research team, funding access and scientific dissemination. It is contingent on all players to engage in efforts to improve DEI in research settings, as they each are a critical step to improving the scientific method, rigor and accuracy of research outcomes.

Organophosphate pesticide exposure as a risk factor for attempted suicide in Cape Town, South Africa: A case-control study.

Pesticides are a commonly used agent for suicide in many Low- and Middle-Income countries (LMICs). However, accumulating evidence suggests that exposure to organophosphate (OP) pesticide may also increase the risk of suicide. We conducted a hospital-based case-control study to investigate whether prior household, garden or occupational OP exposure were associated with attempted suicide using conditional logistic regression modeling. Participants who attempted suicide with any means and were admitted to two Western Cape Province hospitals in South Africa were compared to a sample of controls matched by age, sex and time of admission with unrelated conditions, between August 2015 and August 2017. The means of attempted suicide was not recorded. OP exposure was determined by dialkyl phosphate (DAP) metabolites detected in hair and by environmental and occupational history. Approximately 85% of participants reported using pesticides in the home or garden and 15% of participants reported current or past occupational exposure while working on a farm. Attempted suicide was not associated with reported home or garden OP use (Odds ratio [OR] = 0.59, 95%CI 0.33-1.04), hair DAP metabolites (OR = 1.00, 95%CI 0.98-1.02) or current or past agricultural work (OR = 1.08, 95%CI 0.62-1.87), but was associated with hazardous drinking and unemployment with no household income. We found no evidence that attempted suicide was associated with environmental or occupational pesticide use in an urban South African population attending an emergency center.

Erratum: Extrapyramidal side effects in first-episode schizophrenia treated with flupenthixol decanoate.

[This corrects the article DOI: 10.4102/sajpsychiatry.v27i0.1568.].

Associations of premorbid adjustment with type and timing of childhood trauma in first-episode schizophrenia spectrum disorders.

BACKGROUND: Childhood trauma may contribute to poorer premorbid social and academic adjustment which may be a risk factor for schizophrenia. AIM: We explored the relationship between premorbid adjustment and childhood trauma, timing of childhood trauma's moderating role as well as the association of clinical and treatment-related confounders with premorbid adjustment. SETTING: We conducted a secondary analysis in 111 patients with first-episode schizophrenia (FES) disorders that formed part of two parent studies, EONKCS study (n =73) and the Shared Roots study (n =38). METHODS: Type of childhood trauma was assessed with the Childhood Trauma Questionnaire, short-form and premorbid adjustment using the Premorbid Adjustment Scale. Timing of childhood trauma was assessed using the Life Events Checklist and life events timeline. Linear regression analyses were used to assess the moderating effect of timing of childhood trauma. Clinical and treatment-related confounders were entered into sequential hierarchical regression models to identify independent predictors of premorbid adjustment across key life stages. RESULTS: Childhood physical neglect was associated with poorer premorbid academic functioning during childhood and early adolescence, and poorer premorbid social functioning during early and late adolescence. By hierarchical regression modelling (r 2 = 0.13), higher physical neglect subscale scores (p = 0.011) independently predicted poorer premorbid social adjustment during early adolescence. Timing of childhood trauma did not moderate the relationship between childhood trauma and premorbid functioning. CONCLUSION: In patients with FES, childhood physical neglect may contribute to poorer premorbid social functioning during early adolescence. This may provide us with an opportunity to identify and treat at-risk individuals earlier.

Cannabis use and clinical outcome in people with first-episode schizophrenia spectrum disorders over 24 months of treatment.

Cannabis use is associated with an unfavourable course of illness in schizophrenia, although several factors may confound this association. In this longitudinal study, we explored the influence of cannabis use on baseline symptom severity and treatment outcomes in 98 patients with first-episode schizophrenia spectrum disorders treated with a long acting injectable antipsychotic over 24 months. Using mixed models for repeated measures, we compared visit-wise changes in psychopathology, social and occupational functioning and quality of life between recent/current cannabis users (n=45) and non-users (n=53). There were no significant group by time interactions for any of our outcomes, and with the exception of poorer functionality in cannabis users at baseline, no significant differences in these domains at baseline or month 24. Also, remission rates were similar. However, more cannabis users met our operationally defined relapse criteria compared to non-users, and more frequent cannabis use over the course of treatment, as assessed by positive urine toxicology testing, predicted relapse. Our results suggest that cannabis users do not have poorer treatment response than non-users in terms of symptom reduction over the 24 months of treatment. However, dose-related risk of relapse remains with ongoing cannabis use, possibly by directly reducing the threshold for psychotic breakthrough.

Prevalence and associated factors of depression among older adults in rural Tanzania.

OBJECTIVES: Depression is the commonest mental disorder in older adults worldwide, affecting 7% of the world's older population and accounting for 5.7% of years lived with disability among adults aged over 60 years. We conducted a secondary data analysis to determine the point prevalence, associated risk factors and treatment gap for DSM-IV depression among older adults in the Hai District, rural Tanzania. METHODS: The primary data source was a cross-sectional two-stage community-based dementia study where older adults aged ≥70 years (n = 296) were fully-assessed for dementia and depression in the second stage. Age-adjusted prevalence of depression was determined based on the WHO standard population using the Direct Method. Univariate and multivariate logistic regression models were performed. RESULTS: Of the 296 older adults assessed for depression, 48 were diagnosed with depression based on Diagnostic and Statistical Manual of Mental Disorders-IV criteria. The median (Inter Quartile Range; QR) age was 80 (75-88) years. Age-adjusted point prevalence of depression was 21.2% (95% CI: 16.6-21.9) and the treatment gap for depression was 100%. There was reduced odds of depression in older adults who rated their physical health as good or very good (adjusted odds ratio [AOR] = 0.22; 95%CI: 0.10-0.46; p < 0.001), or moderate (AOR 0.26; 95%CI: 0.10-0.66; p = 0.005). CONCLUSIONS: Depression in older adults is associated with physical health status and there is an alarmingly high treatment gap. Future research on depression in older adults should focus on effective interventions to address physical morbidity, psychosocial factors and the treatment gap.