The WERCAP Screen and the WERC Stress Screen: psychometrics of self-rated instruments for assessing bipolar and psychotic disorder risk and perceived stress burden.

BACKGROUND: Identification of individuals in the prodromal phase of bipolar disorder and schizophrenia facilitates early intervention and promises an improved prognosis. There are no current assessment tools for clinical risk symptoms of bipolar disorder, and psychosis-risk assessment generally involves semi-structured interviews, which are time consuming and rater dependent. We present psychometric data on two novel quantitative questionnaires: the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen for assessing bipolar and psychotic disorder risk traits, and the accompanying WERC Stress Screen for assessing individual and total psychosocial stressor severities. METHODS: Prevalence rates of the WERCAP Screen were evaluated among 171 community youth (aged 13-24 years); internal consistency was assessed and k-means cluster analysis was used to identify symptom groups. In 33 participants, test-retest reliability coefficients were assessed, and ROC curve analysis was used to determine the validity of the psychosis section of the WERCAP Screen (pWERCAP) against the Structured Interview of Psychosis-Risk Symptoms (SIPS). Correlations of the pWERCAP, the affectivity section of the WERCAP Screen (aWERCAP) and the WERC Stress Screen were examined to determine the relatedness of scores with cognition and clinical measures. RESULTS: Cluster analysis identified three groups of participants: a normative (47%), a psychosis-affectivity (18%) and an affectivity only (35%) group. Internal consistency of the aWERCAP and pWERCAP resulted in alphas of 0.87 and 0.92, and test-retest reliabilities resulted in intraclass correlation coefficients of 0.76 and 0.86 respectively. ROC curve analysis showed the optimal cut-point on the pWERCAP as a score of >30 (sensitivity: 0.89; specificity: 1.0). There was a significant negative correlation between aWERCAP scores and total cognition (R=-0.42), and between pWERCAP scores and sensorimotor processing speed. Total stress scores correlated significantly with scores on the aWERCAP (R=0.88), pWERCAP (R=0.62) and total cognition (R=-0.44). CONCLUSIONS: Our results show that the WERCAP Screen and the WERC Stress Screen are easy to administer and derived scores are related to cognitive and clinical traits. This suggests that their use could have particular benefits for epidemiologic studies and in busy clinical settings. Longitudinal studies would be required to evaluate clinical outcomes with high questionnaire scores.

Validation of a modified version of the PRIME screen for psychosis-risk symptoms in a non-clinical Kenyan youth sample.

BACKGROUND: The PRIME screen is a self-administered questionnaire designed to quickly assess individuals at risk for developing a psychotic disorder. It is shorter in both length and administration time compared to the Structured Interview for Psychosis-Risk Syndromes (SIPS)-a standard instrument for psychosis prodromal risk assessment. Validation of the PRIME against the SIPS has not been reported in large non-clinical populations. METHODS: A culturally modified version of the PRIME screen (mPRIME) was administered to Kenyan youth between the ages of 14 and 29. 182 completed both the SIPS and mPRIME. Validation measures (sensitivity, specificity, positive predictive value, negative predictive value) were calculated and the study sample was then broken down into true positives, false positives, and false negatives for comparison on different quantitative measures. RESULTS: Using previously suggested thresholds for a positive screen, the mPRIME had a sensitivity of 40% and a specificity of 64.8% for our entire sample. Positive predictive value (PPV) and negative predictive value (NPV) were 12.3% and 89.7%, respectively. Breaking the sample down by questionnaire outcome showed that true-positive individuals scored higher on average rate and intensity of endorsement of mPRIME items compared to false-positive and false-negatives, while false-negatives on average registered disagreement on all mPRIME questionnaire items. CONCLUSIONS: The mPRIME does not appear to be an effective screener of at-risk individuals for psychosis in our non-clinical sample. Further validation efforts in other general populations are warranted.

Classes of psychotic experiences in Kenyan children and adolescents.

Psychotic-like experiences (PLEs) have been observed worldwide in both adults and children outside the context of a clinical disorder. In the current study, we investigate the prevalence and patterns of PLEs among children and adolescents in Kenya. Among 1,971 students from primary and secondary schools around Nairobi (aged 8-19), 22.1 % reported a lifetime history of a psychotic experience, and 16.3 % reported this unrelated to sleep or drugs. Psychotic experiences were more common in males compared to females. LCA resulted in a three-class model comprised of a normative class (83.3 %), a predominately hallucinatory class (Type 1 psychosis: 9.6 %), and a pan-psychotic class (Type 2 psychosis: 7.2 %). These results indicate that PLEs are prevalent in children and adolescents, and the distributions of symptom clusters are similar to that found in adulthood. The relationship of specific PLEs to the future development of psychotic disorder, functional impairment or distress will require further study.

Prevalence and characteristics of psychotic-like experiences in Kenyan youth.

Current evidence suggests that there may be significant differences in psychotic symptom prevalence in Africa compared with other cultures. However, there have been few studies evaluating these symptoms in the continent. We conducted a cross-sectional survey of psychotic-like experiences (PLEs) in 2963 Kenyan students from seven tertiary academic institutions spread across Kenya, using a self-administered psychosis questionnaire evaluating psychotic experiences and demographic variables. Logistic regression was used to evaluate relationship between PLEs and demographic variables. Latent class analysis (LCA) was used to determine specific classes of psychotic experiences. Twenty-three percent of respondents reported having at least one PLE, and 19% reported this unrelated to drug use or sleep. Compared to students identifying as Protestant Christians, Catholics had a lower likelihood of having any PLE or visual hallucinations. Other demographic variables were not significantly associated with PLEs. LCA of PLEs resulted in a three-class model that comprised 1) a non-psychotic class (83.8%), 2) a predominantly hallucinatory class ("type I PLE"; 12.7%), and 3) a multiple symptom class ("type II PLE"; 3.5%). Both psychotic classes had a predominance of male students. Further studies are required to clarify functionality and clinical progression associated with observed patterns of psychosis, as well as the generalizability of our findings.

Angiogenic proteins are expressed by brain blood vessels in Alzheimer's disease.

Data are emerging to support the idea that mediators of angiogenesis are found in the Alzheimer's disease (AD) brain. The objective of this study is to compare the expression of the angiogenic mediators vascular endothelial growth factor (VEGF), angiopoietin, and matrix metalloproteinases (MMPs) in the microcirculation of AD patients and age-matched controls. Our results indicate that angiopoietin-2 and VEGF are expressed by AD- but not control-derived microvessels. AD-derived microvessels also release higher levels of MMP-2 and MMP-9 compared to controls. The data show that despite high levels of MMP-9, assessed by western blot, MMP-9 activity is not detectable in AD microvessels. In this regard we find high levels of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in AD, but not control vessels. Furthermore, we explore the ability of thrombin, previously shown to be present in AD microvessels, to affect TIMP expression in cultured brain endothelial cells and find that thrombin causes up regulation of TIMP-1. These data show that angiogenic changes occur in the microcirculation of the AD brain and suggest that if these changes are contributory to disease pathogenesis, targeting the abnormal brain endothelial cell would provide a novel therapeutic approach for the treatment of this disease.

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

The 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.