Clinical correlates of subsyndromal depression in African American individuals with psychosis: The relationship with positive symptoms and comorbid substance dependence.
ABSTRACT: Patients with psychosis exhibit subsyndromal depressive symptoms during the course of illness and yet the clinical correlates of these symptoms remain under-investigated. We aimed to investigate the clinical correlates of subsyndromal depression in psychosis including the extent to which they mediate commonly observed comorbid substance dependence. We developed a model of depression in a non-clinical sample recruited via Amazon's Mechanical Turk (N?=?266), and confirmed that model in a locally recruited African-American clinical sample comprising psychotic and non-psychotic individuals (N?=?256). Using scores from this model we tested: the strength of relationships between depressive symptomatology and positive, negative and disorganized symptoms in a range of psychotic disorders; whether depressive symptoms were higher in individuals with affective psychoses versus schizophrenia; and if depressive symptomatology mediated the relationship between psychosis and substance dependence. Subsyndromal depressive symptomatology was significantly higher in individuals with psychosis than without psychosis, but did not significantly differ between affective and non-affective psychotic groups. Depressive symptomatology was significantly related to positive (but not negative or disorganized) psychotic symptoms, and mediated the relationship between psychosis and substance dependence. The present study underlines the importance of assessing subsyndromal depression in patients with psychosis, and generates a number of testable predictions for future work. In particular, the examination of the relationships between comorbid psychopathology, namely depression and substance abuse, may improve insight into the neurobiology of psychosis.
Project description:Emotion dysfunction has long been considered a cardinal feature across psychotic disorders, including schizophrenia and affective psychosis. However, few studies have used objective markers of emotional function to compare psychotic disorders to one another, and fewer studies have examined such markers within a longitudinal framework. Here, we examine one objective marker of emotional responsivity, the late positive potential (LPP), which is a centro-parietal event-related potential (ERP) that tracks the dynamic allocation of attention to emotional vs. neutral stimuli. We used the LPP to characterize abnormal emotional responsivity by relating it to negative, depressive, and psychotic symptoms among two clinical groups: individuals diagnosed with affective psychosis and individuals with schizophrenia. We also used a long-term longitudinal framework, examining concurrent associations between LPP amplitude and symptom severity, as well as prospective associations with symptoms 4 years later. Participants were 74 individuals with psychotic illness: 37 with schizophrenia spectrum disorders and 37 with a primary affective disorder (psychotic bipolar disorder, psychotic depression). There were no mean-level differences in LPP amplitude between the schizophrenia spectrum and primary affective psychosis group. In the primary affective psychosis group, reduced LPP amplitude was associated with greater depressive, negative, and psychotic symptom severity, both concurrently and at follow-up; associations between LPP and symptoms were not observed within the schizophrenia spectrum group. This pattern of results suggests that the neural correlates of emotion dysfunction may differ across psychotic disorders. One possibility is that schizophrenia is characterized by a decoupling of symptom severity and emotional processing. Such findings underscore the importance of analyzing transdiagnostic samples to determine common or specific symptom relationships across various patient populations.
Project description:PURPOSE:To investigate whether psychotic experiences and depressive symptoms at ages 12 and 18 years are associated with adverse life outcomes across a range of functional domains between 16 and 20 years of age. METHODS:Data were gathered from ALSPAC, a UK birth cohort. Individuals were assessed with the semi-structured Psychosis-Like Symptoms Interview and the Short Mood and Feeling Questionnaire at ages 12 and 18 years. Logistic regression was used to explore associations with outcomes in education, occupation, social functioning, substance use (alcohol, cannabis, smoking, and other drugs), and illegal behaviour between the ages of 16 and 20 years. All associations were adjusted for socio-demographic and childhood confounders and for comorbid psychotic experiences or depressive symptoms. RESULTS:Psychotic experiences and depression at age 12 were associated with poorer educational, occupational, and social outcomes between the ages of 16 and 20; these withstood adjustment for confounding. Depressive symptoms at age 12 were also associated with harmful drinking. Psychotic experiences and depression at age 18 were additionally associated with other forms of substance use and illegal behaviour. Comorbidity had little impact at age 12, but was associated with significantly worse educational, social, and substance use outcomes at age 18. CONCLUSIONS:Adolescent psychotic experiences and depression represent a risk marker for a number of later adverse outcomes, most consistently with education and employment, but also social impairment, harmful drinking, and substance use. This highlights the importance of recognizing adolescent psychopathology, so that support can be provided to try and minimize adverse outcomes.
Project description:Cross-sectional studies of the signs and symptoms of psychosis yield dimensional phenotypes. However, the validity and clinical utility of such dimensions remain debated. This study investigated the structure of psychotic symptomatology, the stability of the structure over time, and the concordance between symptom dimensions and categorical diagnoses.Sample consisted of 500 first-episode psychotic patients. A cross-sectional study (N = 500) investigated the organizational structure of symptom dimensions at the onset of psychosis and its concordance with categorical diagnoses; next, a nested longitudinal study (N = 100) examined the stability of the symptom dimensions structure after 5-10 years of follow-up.Factor analyses identified 6 first-order factors (mania, negative, disorganization, depression, hallucinations, and delusions) and 2 high-order factors (affective and nonaffective psychoses). Cumulative variance accounted for by the first and high-order factors was 63%: 31% by the first-order factors and 32% by the high-order factors. The factorial structure of psychotic symptoms during first episode remained stable after 5-10 years of follow-up. The overall concordance between 4 categorical diagnostic groups (schizophrenia, mania with psychosis, psychotic depression and schizoaffective disorder) and dimensional symptom ranged from 62.2% to 73.1% (when the schizoaffective group was excluded).Symptoms of psychosis assume a multidimensional hierarchical structure. This hierarchical model was stable over time and showed good concordance with categorical diagnoses. The combined use of dimensional and categorical approach to psychotic disorders would be of clinical and research utility.
Project description:Although depressive symptoms in first episode psychosis have been associated with cannabis abuse, their influence on the long-term functional course of FEP patients who abuse cannabis is unknown. The aims of the study were to examine the influence of subclinical depressive symptoms on the long-term outcome in first episode-psychosis patients who were cannabis users and to assess the influence of these subclinical depressive symptoms on the ability to quit cannabis use.64 FEP patients who were cannabis users at baseline were followed-up for 5 years. Two groups were defined: (a) patients with subclinical depressive symptoms at least once during follow-up (DPG), and (b) patients without subclinical depressive symptoms during follow-up (NDPG). Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms using the Hamilton Depression Rating Scale (HDRS)-17, and psychosocial functioning was assessed using the Global Assessment of Functioning (GAF). A linear mixed-effects model was used to analyze the combined influence of cannabis use and subclinical depressive symptomatology on the clinical outcome.Subclinical depressive symptoms were associated with continued abuse of cannabis during follow-up (β= 4.45; 95% confidence interval [CI]: 1.78 to 11.17; P = .001) and with worse functioning (β = -5.50; 95% CI: -9.02 to -0.33; P = .009).Subclinical depressive symptoms and continued cannabis abuse during follow-up could be predictors of negative outcomes in FEP patients.
Project description:Psychotic symptoms in Alzheimer disease (AD + P) identify a heritable phenotype associated with a more severe course. We recently found an association of AD + P with depression symptom severity. Reports have shown an association of a serotonin-2A receptor (HTR2A) gene T102C polymorphism with AD + P and with depression during AD. We examined the interaction of this common genetic polymorphism with depression and increased psychosis risk. Subjects with possible or probable AD or mild cognitive impairment (MCI) without psychosis at study entry were genotyped for the HTR2A T102C polymorphism and reassessed every 6 months until psychosis onset. Psychotic and depressive symptoms were rated using the CERAD behavioral rating scale (CBRS). Cox proportional hazard models with time-dependent covariates were used to examine associations with psychosis onset. A total of 324 Caucasian subjects completed at least one follow-up exam. Depressive symptom severity was a strong predictor of psychosis onset. Neither psychosis onset nor depression severity was associated with the HTR2A genotype. Genotype interacted with depression severity to moderate the risk of AD + P onset. This did not result from an interaction of HTR2A genotype with antidepressant use. Psychosis onset in AD is strongly associated with severity of depressive symptoms, an association that may be modified by HTR2A genotype.
Project description:Individuals with at-risk mental state for psychosis (ARMS) often suffer from depressive and anxiety symptoms, which are clinically similar to the negative symptomatology described for psychosis. Thus, many ARMS individuals are already being treated with antidepressant medication.To investigate clinical and structural differences between psychosis high-risk individuals with or without antidepressants.We compared ARMS individuals currently receiving antidepressants (ARMS-AD; n = 18), ARMS individuals not receiving antidepressants (ARMS-nonAD; n = 31) and healthy subjects (HC; n = 24), in terms of brain structure abnormalities, using voxel-based morphometry. We also performed region of interest analysis for the hippocampus, anterior cingulate cortex, amygdala and precuneus.The ARMS-AD had higher 'depression' and lower 'motor hyperactivity' scores than the ARMS-nonAD. Compared to HC, there was significantly less GMV in the middle frontal gyrus in the whole ARMS cohort and in the superior frontal gyrus in the ARMS-AD subgroup. Compared to ARMS-nonAD, the ARMS-AD group showed more gray matter volume (GMV) in the left superior parietal lobe, but less GMV in the left hippocampus and the right precuneus. We found a significant negative correlation between attenuated negative symptoms and hippocampal volume in the whole ARMS cohort.Reduced GMV in the hippocampus and precuneus is associated with short-term antidepressant medication and more severe depressive symptoms. Hippocampal volume is further negatively correlated with attenuated negative psychotic symptoms. Longitudinal studies are needed to distinguish whether hippocampal volume deficits in the ARMS are related to attenuated negative psychotic symptoms or to antidepressant action.
Project description:BACKGROUND:Ethnic inequalities in health outcomes are often explained by socioeconomic status and concentrated poverty. However, ethnic disparities in psychotic experiences are not completely attenuated by these factors. AIMS:We investigated whether disparities are better explained by interactions between individual risk factors and place-based clustering of disadvantage, termed a syndemic. METHOD:We performed a cross-sectional survey of 3750 UK men, aged 18-34 years, oversampling Black and minority ethnic (BME) men nationally, together with men residing in London Borough of Hackney. Participants completed questionnaires covering psychiatric symptoms, substance misuse, crime and violence, and risky sexual health behaviours. We included five psychotic experiences and a categorical measure of psychosis based on the Psychosis Screening Questionnaire. RESULTS:At national level, more Black men reported psychotic experiences but disparities disappeared following statistical adjustment for social position. However, large disparities for psychotic experiences in Hackney were not attenuated by adjustment for social factors in Black men (adjusted odds ratio, 3.24; 95% CI 2.14-4.91; P < 0.002), but were for South Asian men. A syndemic model of joint effects, adducing a four-component latent variable (psychotic experiences and anxiety, substance dependence, high-risk sexual behaviour and violence and criminality) showed synergy between components and explained persistent disparities in psychotic experiences. A further interaction confirmed area-level effects (Black ethnicity × Hackney residence, 0.834; P < 0.001). CONCLUSIONS:Syndemic effects result in higher rates of non-affective psychosis among BME persons in certain inner-urban settings. Further research should investigate how syndemics raise levels of psychotic experiences and related health conditions in Black men in specific places with multiple deprivations.
Project description:The presence of depressive subsyndromal symptoms (SS) in bipolar disorder (BD) increases the risk of affective relapse and worsens social, cognitive functioning, and quality of life. Nonetheless, there are limited data on how to optimize the treatment of subthreshold depressive symptoms in BD. Mindfulness-Based Cognitive Therapy (MBCT) is a psychotherapeutic intervention that has been shown effective in unipolar depression. The assessment of its clinical effectiveness and its impact on biomarkers in bipolar disorder patients with subsyndromal depressive symptoms and psychopharmacological treatment is needed.A randomized, multicenter, prospective, versus active comparator, evaluator-blinded clinical trial is proposed. Patients with BD and subclinical or mild depressive symptoms will be randomly allocated to: 1) MBCT added to psychopharmacological treatment; 2) a brief structured group psychoeducational intervention added to psychopharmacological treatment; 3) standard clinical management, including psychopharmacological treatment. Assessments will be conducted at screening, baseline, post-intervention (8 weeks) and 4 month follow-up post-intervention. The aim is to compare MBCT intervention versus a brief structured group psychoeducation. Our hypothesis is that MBCT will be more effective in reducing the subsyndromal depressive symptoms and will improve cognitive performance to a higher degree than the psychoeducational treatment. It is also hypothesized that a significant increase of BDNF levels will be found after the MBCT intervention.This is the first randomized controlled trial to evaluate the effects of MBCT compared to an active control group on depressive subthreshold depressive symptoms in patients with bipolar disorder.ClinicalTrials.gov: NCT02133170. Registered 04/30/2014.
Project description:BACKGROUND:The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment. METHOD:This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions. RESULTS:A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions. CONCLUSIONS:Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
Project description:A subgroup of individuals with mood and psychotic disorders shows evidence of inflammation that leads to activation of the kynurenine pathway and the increased production of neuroactive kynurenine metabolites. Depression is hypothesized to be causally associated with an imbalance in the kynurenine pathway, with an increased metabolism down the 3-hydroxykynurenine (3HK) branch of the pathway leading to increased levels of the neurotoxic metabolite, quinolinic acid (QA), which is a putative N-methyl-d-aspartate (NMDA) receptor agonist. In contrast, schizophrenia and psychosis are hypothesized to arise from increased metabolism of the NMDA receptor antagonist, kynurenic acid (KynA), leading to hypofunction of GABAergic interneurons, the disinhibition of pyramidal neurons and striatal hyperdopaminergia. Here we present results that challenge the model of excess KynA production in affective psychosis. After rigorous control of potential confounders and multiple testing we find significant reductions in serum KynA and/or KynA/QA in acutely ill inpatients with major depressive disorder (N=35), bipolar disorder (N=53) and schizoaffective disorder (N=40) versus healthy controls (N=92). No significant difference was found between acutely ill inpatients with schizophrenia (n=21) and healthy controls. Further, a post hoc comparison of patients divided into the categories of non-psychotic affective disorder, affective psychosis and psychotic disorder (non-affective) showed that the greatest decrease in KynA was in the affective psychosis group relative to the other diagnostic groups. Our results are consistent with reports of elevations in proinflammatory cytokines in psychosis, and preclinical work showing that inflammation upregulates the enzyme, kynurenine mono-oxygenase (KMO), which converts kynurenine into 3-hydroxykynurenine and quinolinic acid.