Utility of Washington Early Recognition Center self-report screening questionnaires in the assessment of patients with schizophrenia and bipolar disorder

Early identification and treatment are associated with improved outcomes in bipolar disorder (BPD) and schizophrenia (SCZ). Screening for the presence of these disorders usually involves time-intensive interviews that may not be practical in settings where mental health providers are limited. Thus, individuals at earlier stages of illness are often not identified. The Washington Early Recognition Center Affectivity and Psychosis (WERCAP) screen is a self-report questionnaire originally developed to identify clinical risk for developing bipolar or psychotic disorders. The goal of the current study was to investigate the utility of the WERCAP Screen and two complementary questionnaires, the WERC Stress Screen and the WERC Substance Screen, in identifying individuals with established SCZ or BPD. Participants consisted of 35 BPD and 34 SCZ patients, as well as 32 controls (CON), aged 18–30 years. Univariate analyses were used to test for score differences between groups. Logistic regression and receiver operating characteristic (ROC) curves were used to identify diagnostic predictors. Significant group differences were found for the psychosis section of the WERCAP (pWERCAP; p < 0.001), affective section of the WERCAP (aWERCAP; p = 0.001), and stress severity (p = 0.027). No significant group differences were found in the rates of substance use as measured by the WERC Substance Screen (p = 0.267). Only the aWERCAP and pWERCAP scores were useful predictors of diagnostic category. ROC curve analysis showed the optimal cut point on the aWERCAP to identify BPD among our participant groups was a score of >20 [area under the curve (AUC): 0.87; sensitivity: 0.91; specificity: 0.71], while that for the pWERCAP to identify SCZ was a score of >13 (AUC: 0.89; sensitivity: 0.88; specificity: 0.82). These results indicate that the WERCAP Screen may be useful in screening individuals for BPD and SCZ and that identifying stress and substance-use severity can be rapidly done using self-report questionnaires. Larger studies in undiagnosed individuals will be needed to test the WERCAP Screen’s ability to identify mania or psychosis in the community

Longitudinal and cross-sectional validation of the WERCAP Screen for assessing psychosis risk and conversion

BACKGROUND: The Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen was developed to assess risk for developing psychosis. Its validity has not been investigated in a large population-based study or with longitudinal analyses. METHODS: 825 participants, aged 14-25, were recruited from Kenya. Symptoms were assessed using the WERCAP Screen, as experienced over the prior 3-months (3MO), 12-months (12MO) or lifetime (LIF). ROC curve analysis was used to determine the validity of the WERCAP Screen against the Structured Interview of Psychosis-Risk Syndromes. Longitudinal validity was assessed by comparing baseline p-WERCAP scores in psychotic disorder converters and non-converters, and using ROC curve analysis. Relationship of the p-WERCAP was examined against clinical variables. RESULTS: ROC curve analyses against SIPS showed an AUC of 0.83 for 3MO, 0.79 for 12MO and 0.65 for LIF psychosis scores. The optimal cut-point on 3MO was a score of \u3e12 (sens: 0.78; spec: 0.77; ppv: 0.41), and \u3e32 for 12MO (sens: 0.71; spec: 0.74; ppv: 0.24). Baseline 3MO scores (but not LIF scores) were higher in converters compared to high-risk non-converters (p = 0.02). 3MO scores against conversion status had an AUC of 0.75, with an optimal cutoff point of \u3e16 (sens: 1.0; spec: 0.53). All p-WERCAP scores significantly correlated with substance use and stress severity. 12 MO scores were most related to cognitive impairment. CONCLUSIONS: The WERCAP Screen is a valid instrument for assessing psychosis severity and conversion risk. It can be used in the community to identify those who may require clinical assessment and care, and for recruitment in psychosis-risk research

The co-morbidity of DSM-V gambling with DSM-V mental disorders and substance abuse in a Kenyan context of high risk schizophrenia

INTRODUCTION: There is evidence that gambling disorder shares similarities with other types of addictive behavior, such as occurs in substance abuse. In addition, co-morbidity of gambling with mental disorders has been established in school-going students. AIM: This study aimed at determining the comorbidity of DSM-V gambling disorder with DSM-V mental disorders and substance abuse in high school, college and university students in Kenya. METHODS: This was a cross-sectional study among 536 high school, college and university students. We collected data on socio-demographic characteristics, economic indicators, DSM-V diagnosis including DSM-V gambling disorder and substance use disorders using the WHO ASSIST tool. Descriptive and inferential analyses were done. RESULTS: A total of 536 students participated in the study, of which 11.4% (61 out of 536) had DSM-V gambling disorder. Male gender (AOR = 12.0, 95% CI: 4.99-34.3), antisocial personality disorder (AOR = 3.42, 95% CI: 1.34-8.54), tobacco use (AOR = 4.42, 95% CI: 1.15-18.3) and conduct disorder (AOR = 7.56, 95% CI: 2.34-25.1) were predictors of gambling disorder. CONCLUSION: Gambling is highly prevalent in Kenya learning institutions at 11.4% and is associated with mental disorders and substance use. There is a need for public awareness of gambling among Kenyan youths

Hippocampal shape and volume changes with antipsychotics in early stage psychotic illness

Progression of hippocampal shape and volume abnormalities has been described in psychotic disorders such as schizophrenia. However it is unclear how specific antipsychotic medications influence the development of hippocampal structure. We conducted a longitudinal, randomized, controlled, multisite, double-blind study involving 14 academic medical centers (United States 11, Canada 1, Netherlands 1, and England 1). 134 first-episode psychosis (receiving either haloperidol or olanzapine) patients and 51 healthy controls were treated and followed up for up to 104 weeks using magnetic resonance imaging and large-deformation high-dimensional brain mapping of the hippocampus. Changes in hippocampal volume and shape metrics (i.e., percentage of negative surface vertex slopes, and surface deformation) were evaluated. Mixed-models analysis did not show a significant group-by-time interaction for hippocampal volume. However, the cumulative distribution function of hippocampal surface vertex slopes showed a notable left shift with haloperidol treatment compared to olanzapine treatment and to controls. Olanzapine treatment was associated with a significantly lower percentage of large magnitude negative surface vertex slopes compared to haloperidol treatment (p=0.004). Surface deformation maps however did not localize any hippocampal regions that differentially contracted over time with olanzapine treatment, after FDR correction. These results indicate that surface analysis provides supplementary information to volumetry in detecting differential treatment effects of the hippocampus. Our results suggest that olanzapine is associated with less longitudinal hippocampal surface deformation than haloperidol, however the hippocampal regions affected appear to be variable across patients

Personality traits as markers of psychosis risk in Kenya: Assessment of temperament and character

Specific personality traits have been proposed as a schizophrenia-related endophenotype and confirmed in siblings at risk for psychosis. The relationship of temperament and character with psychosis has not been previously investigated in Africa. The study was conducted in Kenya, and involved participants at clinical high-risk (CHR) for psychosis

Functional reduction of SK3-mediated currents precedes AMPA-receptor-mediated excitotoxicity in dopaminergic neurons

In primary cultures of mesencephalon small-conductance calcium-activated potassium channels (SK) are expressed in dopaminergic neurons. We characterized SK-mediated currents (ISK) in this system and evaluated their role on homeostasis against excitotoxicity. ISK amplitude was reduced by the glutamatergic agonist AMPA through a reduction in SK channel number in the membrane. Blockade of ISK for 12 h with apamin or NS8593 reduced the number of dopaminergic neurons in a concentration-dependent manner. The effect of apamin was not additive to AMPA toxicity. On the other hand, two ISK agonists,1-EBIO and CyPPA, caused a significant reduction of spontaneous loss of dopaminergic neurons. 1-EBIO reversed the effects of both AMPA and apamin as well. Thus, ISK influences survival and differentiation of dopaminergic neurons in vitro, and is part of protective homeostatic responses, participating in a rapidly acting negative feedback loop coupling calcium levels, neuron excitability and cellular defenses. Fil: Benitez, Bruno A.. Harvard Medical School; Estados UnidosFil: Belálcazar, Helen M.. Harvard Medical School; Estados UnidosFil: Anastasia Gonzalez, Agustin. Washington University in St. Louis; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Mamah, Daniel. Washington University in St. Louis; Estados UnidosFil: Zorumski, Charles. Washington University in St. Louis; Estados UnidosFil: Masco, Daniel Hugo. Washington University in St. Louis; Estados Unidos. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Herrera, Daniel. Harvard Medical School; Estados UnidosFil: de Erausquin, Gabriel Alejandro. Harvard Medical School; Estados Unido

Evaluating brain damage in multiple sclerosis with simultaneous multi-angular-relaxometry of tissue

OBJECTIVE: Multiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination. METHODS: Twenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric was determined in normal-appearing cortical gray matter (NAGM), normal-appearing subcortical white matter (NAWM), and demyelinating lesions. MPF metric was evaluated for correlations with physical and cognitive test scores. Comparisons were made between HC and MS and between MS subtypes. Furthermore, correlations were determined between MPF and neuropathology in the biopsied person. RESULTS: SMART-derived MPF in NAGM and NAWM were lower in MS than HC (p \u3c 0.001). MPF in NAGM, NAWM and lesions differentiated RRMS from PMS (p \u3c 0.01, p \u3c 0.001, p \u3c 0.001, respectively), whereas lesion volumes did not. MPF in NAGM, NAWM and lesions correlated with the Expanded Disability Status Scale (p \u3c 0.01, p \u3c 0.001, p \u3c 0.001, respectively) and nine-hole peg test (p \u3c 0.001, p \u3c 0.001, p \u3c 0.01, respectively). MPF was lower in the histopathologically confirmed inflammatory demyelinating lesion than the contralateral NAWM and increased in the biopsied lesion over time, mirroring improved clinical performance. INTERPRETATION: SMART-derived MPF metric holds potential as a quantitative imaging biomarker of demyelination and remyelination

Three genetic-environmental networks for human personality

Phylogenetic, developmental, and brain-imaging studies suggest that human personality is the integrated expression of three major systems of learning and memory that regulate (1) associative conditioning, (2) intentionality, and (3) self-awareness. We have uncovered largely disjoint sets of genes regulating these dissociable learning processes in different clusters of people with (1) unregulated temperament profiles (i.e., associatively conditioned habits and emotional reactivity), (2) organized character profiles (i.e., intentional self-control of emotional conflicts and goals), and (3) creative character profiles (i.e., self-aware appraisal of values and theories), respectively. However, little is known about how these temperament and character components of personality are jointly organized and develop in an integrated manner. In three large independent genome-wide association studies from Finland, Germany, and Korea, we used a data-driven machine learning method to uncover joint phenotypic networks of temperament and character and also the genetic networks with which they are associated. We found three clusters of similar numbers of people with distinct combinations of temperament and character profiles. Their associated genetic and environmental networks were largely disjoint, and differentially related to distinct forms of learning and memory. Of the 972 genes that mapped to the three phenotypic networks, 72% were unique to a single network. The findings in the Finnish discovery sample were blindly and independently replicated in samples of Germans and Koreans. We conclude that temperament and character are integrated within three disjoint networks that regulate healthy longevity and dissociable systems of learning and memory by nearly disjoint sets of genetic and environmental influences

Characterizing psychosis risk traits in Africa: A longitudinal study of Kenyan adolescents

AbstractThe schizophrenia prodrome has not been extensively studied in Africa. Identification of prodromal behavioral symptoms holds promise for early intervention and prevention of disorder onset. Our goal was to investigate schizophrenia risk traits in Kenyan adolescents and identify predictors of psychosis progression.135 high-risk (HR) and 142 low-risk (LR) adolescents were identified from among secondary school students in Machakos, Kenya, using the structured interview of psychosis-risk syndromes (SIPS) and the Washington early recognition center affectivity and psychosis (WERCAP) screen. Clinical characteristics were compared across groups, and participants followed longitudinally over 0-, 4-, 7-, 14- and 20-months. Potential predictors of psychosis conversion and severity change were studied using multiple regression analyses.More psychiatric comorbidities and increased psychosocial stress were observed in HR compared to LR participants. HR participants also had worse attention and better abstraction. The psychosis conversion rate was 3.8%, with only disorganized communication severity at baseline predicting conversion (p=0.007). Decreasing psychotic symptom severity over the study period was observed in both HR and LR participants. ADHD, bipolar disorder, and major depression diagnoses, as well as poor occupational functioning and avolition were factors relating to lesser improvement in psychosis severity.Our results indicate that psychopathology and disability occur at relatively high rates in Kenyan HR adolescents. Few psychosis conversions may reflect an inadequate time to conversion, warranting longer follow-up studies to clarify risk predictors. Identifying disorganized communication and other risk factors could be useful for developing preventive strategies for HR youth in Kenya

Risk of autism spectrum disorder and association of its symptoms with psychiatric and substance use disorders in non-clinical student sample in Kenya: cross-sectional study

Background The prevalence and patterns of autism spectrum disorder (ASD) symptoms/traits and the associations of ASD with psychiatric and substance use disorders has not been documented in non-clinical students in Sub-Saharan Africa, and Kenya in particular. Aims To document the risk level of ASD and its traits in a Kenyan student population (high school, college and university) using the Autism-Spectrum Quotient (AQ); and to determine the associations between ASD and other psychiatric and substance use disorders. Method This was a cross-sectional study among students (n = 9626). We used instruments with sufficient psychometric properties and good discriminative validity to collect data. A cut-off score of ≥32 on the AQ was used to identify those at high risk of ASD. We conducted the following statistical tests: (a) basic descriptive statistics; (b) chi-squared tests and Fisher's exact tests to analyse associations between categorical variables and ASD; (c) independent t-tests to examine two-group comparisons with ASD; (d) one-way analysis of variance to make comparisons between categorical variables with three or more groups and ASD; (e) statistically significant (P < 0.05) variables fitted into an ordinal logistic regression model to identify determinants of ASD; (f) Pearson's correlation and reliability analysis. Results Of the total sample, 54 (0.56%) were at high risk of ASD. Sociodemographic differences were found in the mean scores for the various traits, and statistically significant (P < 0.05) associations we found between ASD and various psychiatric and substance use disorders. Conclusions Risk of ASD, gender characteristics and associations with psychiatric and substance use disorders are similar in this Kenyan sample to those found in Western settings in non-clinical populations