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Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory.
One hundred and twenty-six persons aged 18–85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics.
Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model.
Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.
Studies about brain structure in bipolar disorder have reported conflicting findings. These findings may be explained by the high degree of heterogeneity within bipolar disorder, especially if structural differences are mapped to single brain regions rather than networks.
We aim to complete a systematic review and meta-analysis to identify brain networks underlying structural abnormalities observed on T1-weighted magnetic resonance imaging scans in bipolar disorder across the lifespan. We also aim to explore how these brain networks are affected by sociodemographic and clinical heterogeneity in bipolar disorder.
We will include case–control studies that focus on whole-brain analyses of structural differences between participants of any age with a standardised diagnosis of bipolar disorder and controls. The electronic databases Medline, PsycINFO and Web of Science will be searched. We will complete an activation likelihood estimation analysis and a novel coordinate-based network mapping approach to identify specific brain regions and brain circuits affected in bipolar disorder or relevant subgroups. Meta-regressions will examine the effect of sociodemographic and clinical variables on identified brain circuits.
Findings from this systematic review and meta-analysis will enhance understanding of the pathophysiology of bipolar disorder. The results will identify brain circuitry implicated in bipolar disorder, and how they may relate to relevant sociodemographic and clinical variables across the lifespan.
Women and gender-diverse people with early psychosis are at risk for suboptimal sexual health outcomes, yet little research has explored their sexual health experiences.
This study explored sexual health experiences and related priorities among women and gender-diverse people with early psychosis, to identify opportunities for improvements in sexual health and well-being.
Semi-structured individual qualitative interviews explored how patient participants (n = 19, aged 18–31 years, cisgender and transgender women and non-binary individuals) receiving clinical care from early psychosis programmes in Ontario, Canada, experienced their sexual health, including sexual function and behaviour. Thematic analysis was conducted, with triangulation from interviews/focus groups with clinicians (n = 36) who provide sexual and mental healthcare for this population.
Three key themes were identified based on patient interviews: theme 1 was the impact of psychotic illness and its treatments on sexual function and activity, including variable changes in sex drive, attitudes and behaviours during acute psychosis, vulnerability to trauma and medications; theme 2 related to intimacy and sexual relationships in the context of psychosis, with bidirectional effects between relationships and mental health; and theme 3 comprised autonomy, identity and intersectional considerations, including gender, sexuality, culture and religion, which interplay with psychosis and sexual health. Clinicians raised each of these priority areas, but emphasised risk prevention relative to patients’ more holistic view of their sexual health and well-being.
Women and non-binary people with early psychosis have wide-ranging sexual health priorities, affecting many facets of their lives. Clinical care should incorporate this knowledge to optimise sexual health and well-being in this population.
Frailty and late-life depression (LLD) often coexist and share several structural brain changes. We aimed to study the joint effect LLD and frailty have on brain structure.
Academic Health Center
Thirty-one participants (14 LLD+Frail and 17 Never-depressed+Robust)
LLD was diagnosed by a geriatric psychiatrist according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition for single episode or recurrent major depressive disorder without psychotic features. Frailty was assessed using the FRAIL scale (0–5), classifying subjects as robust (0), prefrail (1–2), and frail (3–5). Participants underwent T1-weighted magnetic resonance imaging in which covariance analysis of subcortical volumes and vertex-wise analysis of cortical thickness values were performed to access changes in grey matter. Participants also underwent diffusion tensor imaging in which tract-based spatial statistics was used with voxel-wise statistical analysis on fractional anisotropy and mean diffusion values to assess changes in white matter (WM).
We found a significant difference in mean diffusion values (48,225 voxels; peak voxel: pFWER=0.005, MINI coord. (X,Y,Z) = −26,−11,27) between the LLD-Frail group and comparison group. The corresponding effect size (f=0.808) was large.
We showed the LLD+Frailty group is associated with significant microstructural changes within WM tracts compared to Never-depressed+Robust individuals. Our findings indicate the possibility of a heightened neuroinflammatory burden as a potential mechanism underlying the co-occurrence of both conditions and the possibility of a depression–frailty phenotype in older adults.
Measurement-based care (MBC) in mental health improves patient outcomes and is a component of many national guidelines for mental healthcare delivery. Nevertheless, MBC is not routinely integrated into clinical practice. Several known reasons for the lack of integration exist but one lesser explored variable is the subjective perspectives of providers and patients about MBC. Such perspectives are critical to understand facilitators and barriers to improve the integration of MBC into routine clinical practice.
This study aimed to uncover the perspectives of various stakeholders towards MBC within a single treatment centre.
Researchers conducted qualitative semi-structured interviews with patients (n = 15), family members (n = 7), case managers (n = 8) and psychiatrists (n = 6) engaged in an early-psychosis intervention programme. Data were analysed using thematic analysis, informed by critical realist theory.
Analysis converged on several themes. These include (a) implicit negative assumptions; (b) relevance and utility to practice; (c) equity versus flexibility; and (d) shared decision-making. Providers assumed patients’ perspectives of MBC were negative. Patients’ perspectives of MBC were actually favourable, particularly if MBC was used as an instrument to engage patients in shared decision-making and communication rather than as a dogmatic and rigid clinical decision tool.
This qualitative study presents the views of various stakeholders towards MBC, providing an in-depth examination of the barriers and facilitators to MBC through qualitative investigation. The findings from this study should be used to address the challenges organisations have experienced in implementing MBC.
Little is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression.
Two hundred and sixty-nine men and women aged 18–85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse.
Higher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups.
PMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
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