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Background: Multiple studies point to the role of neuroinflammation in the pathophysiology of schizophrenia (SCZ), however, there have been few in vivo tools for imaging brain inflammation. Diffusion basis spectrum imaging (DBSI) is an advanced diffusion-based MRI method developed to quantitatively assess microstructural alternations relating to neuroinflammation, axonal fiber, and other white matter (WM) pathologies., Methods: We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n = 27), schizophrenia (SCZ, n = 21), and bipolar disorder (BPD, n = 21) participants aged 18-30. We applied Tract-based Spatial Statistics (TBSS) to allow whole-brain WM analyses and compare DBSI-derived isotropic and anisotropic diffusion measures between groups. Clinical relationships of DBSI metrics with clinical symptoms were assessed across SCZ and control participants., Results: In SCZ participants, we found a generalized increase in DBSI-derived cellularity (a putative marker of neuroinflammation), a decrease in restricted fiber fraction (a putative marker of apparent axonal density), and an increase in extra-axonal water (a putative marker of vasogenic edema) across several WM tracts. There were only minimal WM abnormalities noted in BPD, mainly in regions of the corpus callosum (increase in DTI-derived RD and extra-axonal water). DBSI metrics showed significant partial correlations with psychosis and mood symptoms across groups., Conclusion: Our findings suggest that SCZ involves generalized white matter neuroinflammation, decreased fiber density, and demyelination, which is not seen in bipolar disorder. Larger studies are needed to identify medication-related effects. DBSI metrics could help identify high-risk groups requiring early interventions to prevent the onset of psychosis and improve outcomes.

Background and Hypothesis: The Accelerating Medicines Partnership Schizophrenia (AMP SCZ) funds a longitudinal study of 43 research sites across 5 continents to develop tools to stratify developmental trajectories of youth at clinical high risk for psychosis (CHR) and identify homogenous targets for future clinical trials. However, there are no sites in Africa, leaving a critical gap in our knowledge of clinical and biological outcomes among CHR individuals., Study Design: We describe the development of the Kenya Psychosis-Risk Outcomes Study (KePROS), a 5-year NIH-funded project in Kenya designed to harmonize with AMP SCZ. The study will recruit over 100 CHR and 50 healthy participants and conduct multiple clinical and biomarker assessments over 2 years. Capacity building is a key component of the study, including the construction of an electroencephalography (EEG) laboratory and the upgrading of a local 3 T magnetic resonance imaging (MRI) machine. We detail community recruitment, study methodologies and protocols, and unique challenges with this pioneering research in Africa., Study Results: This paper is descriptive only. Planned future analyses will investigate possible predictors of clinical outcomes and will be compared to results from other global populations., Conclusions: KePROS will provide the research community with a rich longitudinal clinical and biomarker dataset from an African country in the developing Global South, which can be used alongside AMP SCZ data to delineate CHR outcome groups for future treatment development. Training in mental health assessment and investment in cutting-edge biomarker assessment and other technologies is needed to facilitate the inclusion of African countries in large-scale research consortia., Competing Interests: The authors have declared that there are no conflicts of interest in relation to the subject of this study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Background: Psychotic-like experiences (PLEs) and adverse life events (ALEs) are highly prevalent in sub-Saharan Africa where gendered practices are also common. There is, however, a paucity of data on how the relationship between PLEs and life adversities is influenced by gender. The current study addressed this gap., Method: Data were collected from 1886 school-based young people (1174 females) in Ghana, West Africa using a cross-sectional survey methodology and analyzed using Chi-square, independent t-test, Pearson correlation, and multivariate regression., Results: The results showed that victimization experiences, school stress and having a family member with mental illness were significantly associated with PLEs in both males and females. In contrast, substance misuse and experiences of head trauma correlated significantly with PLEs in females only., Conclusion: Life adversities constitute major risk factors for PLEs among school-based young people in Ghana, who could benefit from gender neutral and gender-sensitive intervention programming to remediate the effects of life adversities on PLEs., (© 2023 Association for Child and Adolescent Mental Health.)

Introduction: There are few psychiatric epidemiology studies among Kenyan youth and fewer among those at high psychosis risk (HR)., Methods: This study assessed the epidemiology of DSM-5 psychiatric disorders in HR and low-risk (LR) individuals to inform research and mental health services. 567 participants (aged 15-25) in HR (n = 246) and LR (n = 260) groups based on Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen scores. Diagnostic Interview Schedule, version 5 (DIS-5) assessed DSM-5 psychiatric disorder prevalence. Diagnostic comorbidity and demographic relationships were investigated., Results: A higher prevalence was observed for all DSM-5 disorders in the HR group, significantly for gambling disorder (13% vs. 5.8%), major depressive disorder (9.8% vs. 3.8%), antisocial personality disorder (5.7% vs. 2.3%), general anxiety disorder (4.9% vs. 0.4%), oppositional defiant disorder (3.3% vs. 0.4%), panic disorder (2.8% vs. 0.8%), and anorexia nervosa (2.8% vs. 0%). Gambling disorder was the most prevalent and showed significant gender effects (males>females)., Discussion: Psychiatric disorders occur at increased rates among HR compared to LR. Prevalence rates found are lower than in US studies, except for gambling disorder which was highly prevalent. Large-population-based epidemiology studies in Africa are needed to estimate rates, particularly of disorders such as schizophrenia, accurately., Competing Interests: Declaration of competing interest The authors do not have any conflicts to report. Data is available through the corresponding author., (Copyright © 2023. Published by Elsevier Inc.)

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS)., Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences., Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS., Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Introduction: Structural brain connectivity abnormalities have been associated with several psychiatric disorders. Schizophrenia (SCZ) is a chronic disabling disorder associated with accelerated aging and increased risk of dementia, though brain findings in the disorder have rarely been directly compared to those that occur with aging., Methods: We used an automated approach to reconstruct key white matter tracts and assessed tract integrity in five participant groups. We acquired one-hour-long high-directional diffusion MRI data from young control (CON, n =28), bipolar disorder (BPD, n =21), and SCZ (n =22) participants aged 18-30, and healthy elderly (ELD, n =15) and dementia (DEM, n =9) participants. Volume, fractional (FA), radial diffusivity (RD) and axial diffusivity (AD) of seven key white matter tracts (anterior thalamic radiation, ATR; dorsal and ventral cingulum bundle, CBD and CBV; corticospinal tract, CST; and the three superior longitudinal fasciculi: SLF-1, SLF-2 and SLF-3) were analyzed with TRACULA. Group comparisons in tract metrics were performed using multivariate and univariate analyses. Clinical relationships of tract metrics with recent and chronic symptoms were assessed in SCZ and BPD participants., Results: A MANOVA showed group differences in FA (λ=0.5; p=0.0002) and RD (λ=0.35; p<0.0001) across the seven tracts, but no significant differences in tract AD and volume. Post-hoc analyses indicated lower tract FA and higher RD in ELD and DEM groups compared to CON, BPD and SCZ groups. Lower FA and higher RD in SCZ compared to CON did not meet statistical significance. In SCZ participants, a significant negative correlation was found between chronic psychosis severity and FA in the SLF-1 (r= -0.45; p=0.035), SLF-2 (r= -0.49; p=0.02) and SLF-3 (r= -0.44; p=0.042)., Discussion: Our results indicate impaired white matter tract integrity in elderly populations consistent with myelin damage. Impaired tract integrity in SCZ is most prominent in patients with advanced illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mamah, Chen, Shimony and Harms.)

Little is known about the prevalence of Conduct Disorder (CD) and symptoms of CD in high risk psychosis persons at both clinical and community populations in LMICs and in particular Kenya. This study aimed to document (1) the prevalence of CD diagnosis and symptoms in youth who screened positive for psychosis and (2) the associated mental disorders and substance use in the same cohort in LMIC. The sample size was 536 students who had screened positive on the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) from a population of 9,742 high school, college and university students, but had not converted to a psychotic disorder. We collected data on socio-demographic characteristics and used the following tools: Economic indicators tool; the Diagnostic Interview Schedule (DIS) tool for DSM-5 diagnosis; World Health Organization (WHO) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Basic descriptive statistics, chi-square test, Fisher's exact test, Pearson correlation and Poisson regression were conducted. Five percent (5%) of the respondents met the criteria for DSM-5 CD. Indeterminate CD comprised 10.1%. Male gender, all substances except hallucinogens lifetime, obsessive compulsive disorder, psychosis, agoraphobia, social phobia, drug abuse/dependence, antisocial personality disorder, oppositional defiant disorder, suicidality, WERCAP screen for bipolar disorder and WERCAP screen for schizophrenia were significantly (p < 0.05) associated with CD. Deceitfulness or theft criteria symptoms showed that CD had no significant gender difference. Criteria symptoms in aggression to people and animals, destruction of property and serious violations of rules were more common among males. Our findings suggest the need to screen for and diagnose CD, mental disorders and substance use in high risk psychosis youths in Kenya. This will inform integrated management., (© 2023. The Author(s).)

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.

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., (© 2023. The Author(s).)

This study aimed at determining the prevalence of stress, different types of stress, their severity and their determinants in Kenyan university, college and high school students. The following tools were administered to 9741 students: (1) Researcher-designed socio-demographic tool, (2) Psychiatric Diagnostic Screening Questionnaire (PDSQ) for psychiatric disorders, (3) WERC Stress Screen for stress, (4) Washington Early Recognition Center Affectivity and Psychosis (WERCAP) screen for psychosis and affectivity, (5) Wealth Index Questionnaire for economic indicators. Descriptive analysis for the prevalence of different types of stress and inferential analysis for stress and independent variables were done. Significant variables (p < 0.05) were fitted into generalized linear model to determine independent predictors. The mean age of the respondents was 21.4 years (range 16-43). Money issues were the commonest stressors while alcohol and drug use were the least. The independent predictors of stress were females, college students and use of gas stove. In conclusion, up to 30% of the students suffer from mild to severe stress. The students experience a wide range of stressors. The most important stressors include money and finances, family related problems and concerns about their future. Our findings suggest a public health approach to create stress awareness in students., (© 2023. The Author(s).)

The risk for developing schizophrenia is increased among first-degree relatives of those with psychotic disorders, but the risk is even higher in those meeting established criteria for clinical high risk (CHR), a clinical construct most often comprising of attenuated psychotic experiences. Conversion to psychosis among CHR youth has been reported to be about 15-35% over three years. Accurately identifying individuals whose psychotic symptoms will worsen would facilitate earlier intervention, but this has been difficult to do using behavior measures alone. Brain-based risk markers have the potential to improve the accuracy of predicting outcomes in CHR youth. This narrative review provides an overview of neuroimaging studies used to investigate psychosis risk, including studies involving structural, functional, and diffusion imaging, functional connectivity, positron emission tomography, arterial spin labeling, magnetic resonance spectroscopy, and multi-modality approaches. We present findings separately in those observed in the CHR state and those associated with psychosis progression or resilience. Finally, we discuss future research directions that could improve clinical care for those at high risk for developing psychotic disorders., Competing Interests: CONFLICTS OF INTEREST The author declares that he has no conflicts of interest.

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 &lt; 0.001). MPF in NAGM, NAWM and lesions differentiated RRMS from PMS (p &lt; 0.01, p &lt; 0.001, p &lt; 0.001, respectively), whereas lesion volumes did not. MPF in NAGM, NAWM and lesions correlated with the Expanded Disability Status Scale (p &lt; 0.01, p &lt; 0.001, p &lt; 0.001, respectively) and nine-hole peg test (p &lt; 0.001, p &lt; 0.001, p &lt; 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., (© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: About a third of youth with suicidal ideation develop suicidal plans and about 60% of youth with suicidal plans make suicidal attempts. This study aimed to study different types of suicidal ideation and the risk factors in Kenyan youth., Methods: We studied a total of 9742 high school, college and university students using following self-administered instruments: - a researcher design socio-demographic questionnaire, Psychiatric Diagnostic Screening Questionnaire (PDSQ) to document psychiatric disorders and various types of suicidal ideas in previous two weeks, Washington Early Recognition Center Affectivity and Psychosis tool to assess stress, affectivity and psychosis, Wealth index questionnaire to document economic indicators based on household items for the families of the students. We used descriptive statistics, univariate analysis, bivariate logistic regression analysis and variables with a p-value of less than <.05 were entered into generalized linear models using logit links to identify independent predictors., Results: The overall prevalence of different types of suicidal ideation was (22.6%), major depression was found in 20.0%, affectivity, psychosis and stress was found in 10.4%, 8.7% and 26.0% respectively. Female gender, major depression, stress, affectivity and psychosis and being in high school were significant (p < 0.05) predictors of suicidal ideation., Limitations: This was a cross sectional study that focused only on suicidal ideas and associated economic factors and mental health disorders. It did not study suicidal behavior., Conclusion: Future studies are needed to study the progression from suicidal ideas to suicidal attempts and the factors associated with that progression., (Copyright © 2022. Published by Elsevier B.V.)

Background: The earlier younger people begin to use drugs, the more vulnerable they become to both their short term and long-term harmful effects. The overall aim of this study is to determine the prevalence of alcohol and drug abuse, the socio-demographic characteristic, perception of abuse and associated economic indicators and mental disorders and how they inform potential intervention in a cohort of Kenyan students., Methods: This was a cross-sectional study on a total of 9742 high school, college and university students. We used tools to document socio-demographic characteristics, economic indicators, drug and alcohol use and related perceptions and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) related psychiatric disorders. Basic descriptive statistics (means and standard deviations for numerical variables and frequencies for nominal and ordinal variables) were done. Logistic regression models were used to assess the association and odds ratios between the use of a given substance and the use of the other substances, as well as associations with the various available socio-demographic factors and economic indicators. Chi-squared tests were used in socio-economic characteristics disaggregated by current alcohol use., Results: The mean age was 21.4 ± 2.4; median = 21.3 (range 15-43) years. We found a wide range of different drugs of abuse. Alcohol abuse was the commonest and inhalants were the least, with different perceptions.Both alcohol and drug abuse were associated with various economic indicators and various mental disorders., Conclusion: This study has established for the first time in Kenya the multifaceted associations and predictors of alcohol and drug abuse in a cross-sectional student population ranging from high school to college and university levels. In the process, the study contributes to global data on the subject. These associations call for an integrated and multifaceted approach in addressing alcohol and substance abuse. This approach should take into account various associations and predictors as part of holistic approach in both public awareness and clinical interventions., (© 2022. The Author(s).)

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 >12 (sens: 0.78; spec: 0.77; ppv: 0.41), and >32 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 >16 (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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Kenya in particular and Africa in general lack data on Binge Eating Disorder (BED). The overarching objective of this study is to fill that gap. Kenyans may not be aware that BED exists when a "very good" appetite is considered a sign of good health, especially if food is available either at home, in fast food shops or when communally eating together, a very common cultural practice. On the other hand where there is relatively insufficient food, it is not expected that one could be having a problem of eating too much., Method: We administered the following tools and measurements to 9742 participants (high school, college and university students): 1) Researcher designed socio-demographic and economic indicator questionnaire; 2) An instrument documenting DSM-IV diagnostic criteria for BED and its various symptoms; 3) An instrument to determine DSM-IV psychiatric disorders and substance abuse;4) An instrument measuring high risk for psychosis ,affectivity and stress; 5) A WHO designed instrument measuring the severity of substance abuse for specific substances. We used descriptive and inferential analysis to determine the prevalence and association of the different variables. Independent predictors of BED were generated from a generalized linear model (p<0.05)., Results: We found a prevalence of 3.2% of BED and a wide range of prevalence for BED and BED related symptoms (8.1% to 19%). The least prevalent was "To prevent weight gain from eating binge did you force yourself to vomit, or used laxatives?". The most common was "Did you often go on eating binges (eating a very large amount of food very quickly over a short period of time)." Major depression, obsessive compulsive disorder, panic disorder, agoraphobia, generalized anxiety disorder ,a positive stress screen and drug abuse were independent predictors of BED (p<0.05)., Conclusion: Our findings on the prevalence of BED and significant associations with various psychiatric disorders and substance use disorders are similar to those obtained in High Income Countries (HIC) using similar large-scale samples in non-clinical populations. Our findings suggest the need fora public health approach to enhance awareness of BED and to promote health-seeking behaviour towards management of BED., (© 2022. The Author(s).)

Background: To date, there have been no large-scale population studies of autistic traits (AUT) conducted in Africa., Aim: The study aimed to estimate the prevalence and characteristics of autism spectrum disorders in a large sample of Kenyan adolescents and young adults., Setting: Tertiary academic institutions (87%) and directly from the community (13%)., Methods: Our study surveyed 8918 youths (aged 15-25 years) using the autism spectrum quotient (AQ). Based on AQ scores, we derived groups with low (L-AUT), borderline (B-AUT), and high (H-AUT) autistic traits. Relationships of AUT with demographic factors, psychosis, affectivity and stress were investigated., Results: Internal consistency of the AQ in the population was excellent (Cronbach's α = 0.91). Across all participants, 0.63% were estimated as having H-AUT, while 14.9% had B-AUT. Amongst community youth, prevalence of H-AUT was 0.98%. Compared to those with low and borderline traits, H-AUT participants were more likely to be males, to have lower personal and parental educational attainment, and to be of a lower socioeconomic status. The H-AUT group also had higher psychotic and affective symptoms as well as higher psychosocial stress than other groups., Conclusion: The prevalence of H-AUT amongst Kenyan youth is comparable to Autism spectrum disorder (ASD) rates in many countries. Autistic traits in Kenya are associated with worse social and clinical profiles. Further research on autism across Africa is needed to investigate cross-cultural heterogeneity of this disorder, and to guide healthcare policy., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2022. The Authors.)

There is growing evidence that schizophrenia and schizoaffective disorder represent closely related syndromes that vary in severity along a neurobiological continuum. In the present study, volume and shape of the basal ganglia was examined in people with schizophrenia and schizoaffective disorder relative to healthy controls and hypothesized that unique neuroanatomical differences would be observed in each patient group. Magnetic resonance 1.5T images were obtained from schizophrenia (n = 47), schizoaffective disorder (n = 15), and from healthy control (n = 42) participants, matched for age, gender, parental socioeconomic status, and race. The caudate, putamen, and globus pallidus were characterized using high-dimensional brain mapping procedures (Csernansky et al., 2004b). Results revealed significant shape deformations between schizophrenia and schizoaffective disorder that also differed from control subjects. Relative to schizophrenia, schizoaffective subjects showed exaggerated inward deformations indicative of localized volume loss in subregions of the caudate, putamen, and globus pallidus (all p < 0.001). These shape features correlated with mental flexibility and negative symptoms in schizophrenia (all p < 0.05), but not schizoaffective disorder. To the extent that differences in important basal ganglia substructures reflect biological heterogeneity among these two psychotic illnesses, this data could prove useful in improving diagnostic precision, as well as informing the affective component of mental illness., (Copyright © 2021. Published by Elsevier B.V.)

Objective: To investigate the prevalence and characteristics of psychotic-like experiences (PLE) in a large cohort of Kenyan adolescents and young adults., Method: The Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen was used to the study the 12-month prevalence of PLE's among 9,564 Kenyan youths (aged 15-25 yrs), and the rates of psychosis high-risk (HR) and medium-risk (MR) cases, based on cut-off scores. Relationships with clinical, demographic and economic profiles were investigated., Results: Across all participants, 72% reported having had at least one PLE over the last year. 4.6% and 30.6% were HR and MR based on symptom scores. There were similar PLE rates in females and males. PLE severity correlated with mood (r=0.67), stress (r=0.46), and autistic traits (r=0.18). PLE severity was also related to poverty, lower education attainment, and underemployment. Compared to controls, HR and MR youths were more likely to report lifetime substance use and to have more significant use., Conclusion: Psychosis screening can provide valuable information about individuals and may help identify those who may require clinical assessment and intervention to improve outcomes. This is particularly relevant in many parts of Africa where the resources are limited for treating more advanced illness., (Copyright © 2021. Published by Elsevier B.V.)

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., (© 2019. The Author(s).)

Introduction: Cognitive deficits are typically seen in schizophrenia and in the prodrome, and are a major predictor of functional outcomes in patients. In Africa, few studies have investigated neurocognition in psychosis, which presents a gap in our understanding of the heterogeneity of the illness. In this study, we assessed neurocognition among the largest sample of psychosis-risk participants recruited in the continent to date., Methods: The study was conducted in Kenya, and involved 295 psychiatric medication-naïve participants at clinical high-risk (CHR) for psychosis and healthy controls, aged 15-25 yrs. Psychosis-risk status was determined separately using the Structured Interview of Psychosis-Risk Syndromes (i.e. CHR) and by self-report with the Washington Early Recognition Center Affectivity and Psychosis Screen. Eleven tests were administered using the University of Pennsylvania Computerized Neurocognitive Battery. Test performance across groups were investigated, as well as demographic and clinical effects., Results: Fewer participants were designated as being at psychosis-risk with structured interview ( n  = 47; CHR) than with self-report ( n  = 155). A MANOVA of cognitive test performance was significant only when groups were ascertained based on self-report ( p  = 0.03), with decreased performance in the risk group on verbal intelligence ( p  = 0.003; d  = 0.39), emotion recognition (p = 0.003; d  = 0.36), sensorimotor processing ( p  = 0.01; d  = 0.31) and verbal memory ( p  = 0.035; d  = 0.21). Only verbal intelligence was significantly worse in the CHR group compared to controls ( p  = 0.036; d  = 0.45). There were no significant age and gender relationships., Conclusion: Deficits across multiple cognitive domains are present in Kenyan psychosis-risk youth, most significantly in verbal intelligence. The pattern of cognitive deficits and an absence of gender effects may represent ethnicity-specific phenotypes of the psychosis-risk state. Longitudinal studies of neurocognition in Kenyan patients who convert to psychosis may enhance risk prediction in this population, and facilitate targeted interventions., Competing Interests: The authors do not have any conflicts to report. This work was funded primarily by NIMH grant R56 MH111300. Additionally, Dr. Mamah has received funding from Taylor Family Institute, Dept. Psychiatry, Washington University; and the Center for Brain Research on Mood Disorders, Dept. Psychiatry, Washington University.

Background: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis., Method: Response to points of critique., Results: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not "extremely difficult"; e) the pattern of progression, although heterogenous, is discernible; f) "psychosis-like symptoms" are common but are not used to identify CHR; and g) on the point described as 'the real risk,' CHR diagnosis does not frequently cause harmful stigma., Discussion: Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the "real risk" of stigma associated with a CHR "label," however, our view is that avoiding words like "risk" and "psychosis" reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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 ( n = 268) and controls ( n = 251), aged 15-25 years. CHR status was estimated using the Structured Interview of Psychosis-Risk Syndromes (SIPS) and the Washington Early Psychosis Center Affectivity and Psychosis (WERCAP) Screen. Student's t -tests were used to assess group differences on the Temperament and Character Inventory (TCI). Neurocognitive functioning, stress severity, and substance use were correlated with the TCI, correcting for psychosis severity. CHR participants were more impulsive (ie, higher novelty seeking [NS]) and asocial (ie, lower reward dependence) than controls. They were also more schizotypal (ie, high self-transcendence [ST] and lower self-directedness [SD] and cooperativeness [CO] than controls). CO was related to logical reasoning, abstraction, and verbal memory. Stress severity correlated with high HA and schizotypal character traits. Lifetime tobacco use was related to NS, and lifetime marijuana use to high NS, low SD and high ST. Temperament and character of Kenyan CHR youth is similar to that observed in schizophrenia. Psychosis risk in Kenya is associated with impulsive, asocial, and schizotypal traits. CHR adolescents and young adults with schizophrenia-specific personality traits may be most at risk for developing a psychotic disorder and to require early intervention to improve outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

There is a need for screening for early symptoms of psychosis and affectivity at community level to promote early diagnosis and management. Any screening instrument should have good psychometric properties. One such instrument is the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) Screen that has been used in the USA, Kenya and Rwanda. However, its properties have not been studied outside the USA, and not in adults. The study aims to document the psychometric properties of the WERCAP Screen in Kenyan adults with positive screens on the WHO mental health treatment GAP- Intervention Guidelines (mhGAP-IG). We administered the WERCAP Screen and a gold standard - the Mini-International Neuropsychiatric Interview (MINI-Plus) section on psychosis to 674 Kenyan adults who had screened positive on the WHO mhGAP-IG. Out of these, 464 (68.84%) scored positive for both affectivity and psychosis sections on the MINI-Plus. The WERCAP affectivity and psychosis scales had good psychometric properties as screening measures, with a cut-off point of 22 for affectivity and 20 for psychosis. The WERCAP Screen has the potential for combined scale up screening for affectivity and psychosis in Kenyan population., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Diffusion imaging abnormalities have been associated with schizophrenia (SZ) and bipolar disorder (BD), indicating impaired structural connectivity. Newer methods permit the automated reconstruction of major white matter tracts from diffusion-weighted MR images in each individual's native space. Using high-definition diffusion data from SZ and BP subjects, we investigated brain white matter integrity using both an automated tract-based and voxel-based methods., Methods: Using a protocol matched to the NIH (Young-Adult) Human Connectome Project (and collected on the same customized 'Connectom' scanner), diffusion scans were acquired from 87 total participants (aged 18-30), grouped as SZ (n = 24), BD (n = 33) and healthy controls (n = 30). Fractional anisotropy (FA) of eighteen white matter tracks were analyzed using the TRACULA software. Voxel-wise statistical analyses of diffusion data was carried out using the tract-based spatial statistics (TBSS) software. TRACULA group effects and clinical correlations were investigated using analyses of variance and multiple regression., Results: TRACULA analysis identified a trend towards lower tract FA in SZ patients, most significantly in the left anterior thalamic radiation (ATR; p = .04). TBSS results showed significantly lower FA voxels bilaterally within the cerebellum and unilaterally within the left ATR, posterior thalamic radiation, corticospinal tract, and superior longitudinal fasciculus in SZ patients compared to controls (FDR corrected p < .05). FA in BD patients did not significantly differ from controls using either TRACULA or TBSS. Multiple regression showed FA of the ATR as predicting chronic mania (p = .0005) and the cingulum-angular bundle as predicting recent mania (p = .02) in patients. TBSS showed chronic mania correlating with FA voxels within the left ATR and corpus callosum., Conclusions: White matter abnormality in SZ varies in severity across different white matter tract regions. Our results indicate that voxel-based analysis of diffusion data is more sensitive than tract-based analysis in identifying such abnormalities. Absence of white matter abnormality in BD may be related to medication effects and age., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Schizophrenia shares some genetic risk and clinical symptoms with bipolar disorder. Clinical heterogeneity across subjects is thought to contribute to variable structural imaging findings across studies. The current study investigates cortical thickness in young adults diagnosed with schizophrenia or bipolar I disorder with a history of hyperthymic mania. We hypothesize that cortical thickness will be most similar between SCZ and the psychotic bipolar 1 disorder subtype., Methods: Patients with schizophrenia (n = 52), psychotic bipolar I disorder (PBD; n = 49) and non-psychotic bipolar I disorder (NPBD; n = 24) and healthy controls (n = 40) were scanned in a 3T Trio MRI. The thickness of 34 cortical regions was estimated with FreeSurfer, and analyzed using univariate analyses of variance. Relationships to psychotic (SAPS) and negative (SANS) symptoms were investigated using linear regression., Results: Cortical thickness showed significant group effects, after covarying for sex, age, and intracranial volume (p = 0.001). SCZ subjects had thinner paracentral, inferior parietal, supramarginal and fusiform cortices compared to CON. Caudal anterior cingulate cortical thickness was increased in SCZ, PBD and NPBD. Cortical thickness in PBD and NPBD were not significantly different from controls. Significant partial correlations were observed for SAPS severity with middle temporal (r = - 0.26; p = 0.001) and fusiform (- 0.26; p = 0.001) cortical thickness., Conclusions: Individuals with SCZ displayed significantly reduced cortical thickness in several cortical regions compared to both CON and bipolar. We found that SCZ participants had significant cortical thinning relative to CON and bipolar disorder most significantly in the frontal (i.e. paracentral), parietal (i.e. inferior parietal, supramarginal), and temporal (i.e. middle temporal, fusiform) cortices.

Task-based connectivity studies facilitate the understanding of how the brain functions during cognition, which is commonly impaired in schizophrenia (SZ). Our aim was to investigate functional connectivity during a working memory task in SZ. We hypothesized that the task-negative (default mode) network and the cognitive control (frontoparietal) network would show dysconnectivity. Twenty-five SZ patient and 31 healthy control scans were collected using the customized 3T Siemens Skyra MRI scanner, previously used to collect data for the Human Connectome Project. Blood oxygen level dependent signal during the 0-back and 2-back conditions were extracted within a network-based parcelation scheme. Average functional connectivity was assessed within five brain networks: frontoparietal (FPN), default mode (DMN), cingulo-opercular (CON), dorsal attention (DAN), and ventral attention network; as well as between the DMN or FPN and other networks. For within-FPN connectivity, there was a significant interaction between n -back condition and group ( p  = 0.015), with decreased connectivity at 0-back in SZ subjects compared to controls. FPN-to-DMN connectivity also showed a significant condition × group effect ( p  = 0.003), with decreased connectivity at 0-back in SZ. Across groups, connectivity within the CON and DAN were increased during the 2-back condition, while DMN connectivity with either CON or DAN were decreased during the 2-back condition. Our findings support the role of the FPN, CON, and DAN in working memory and indicate that the pattern of FPN functional connectivity differs between SZ patients and control subjects during the course of a working memory task.

Background: At least 50% of individuals with bipolar disorder (BD) present with psychosis during their lifetime. Psychotic symptoms have sometimes been linked to specific genetic and phenotypic markers. This study aims to explore potential differences between bipolar disorder subtypes by measuring white matter integrity of the brain and relationships with clinical measures., Methods: Diffusion tensor imaging and clinical measures were acquired from 102 participants, grouped as psychotic bipolar disorder (PBD) (n=48), non-psychotic bipolar disorder (NBD) (n=24), and healthy controls (n=30). We utilized a powerful, automated tool (TRACULA: Tracts Constrained by Underlying Anatomy) to analyze the fractional anisotropy (FA) and mean diffusivity (MD) of 18 white matter tracts., Results: Decreased FA in numerous tracts was observed in bipolar disorder groups compared to healthy controls: bilateral cingulum-cingulate gyrus bundles, corticospinal tracts, and superior longitudinal fasciculi as well as the right hemisphere cingulum-angular bundle. Only left uncinate fasciculus FA differed between PBD and NPBD groups. We found no group differences in MD. Positive symptoms correlated with FA in the superior (inversely) and inferior (directly) longitudinal fasciculi. Negative symptoms directly correlated with mean FA of the corticospinal tract and cingulum-angular bundle., Limitations: Neurotropic, mood-stabilizing medication prescribed for individuals with BD may interact with measures of white matter integrity in our BD participants., Conclusion: Our results indicate decreased white matter coherence in BD. Minimal differences in white matter FA between PBD and NPBD participants suggest related underlying neurobiology., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

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.

Background: Disorders within the schizophrenia spectrum genetically overlap with bipolar disorder, yet questions remain about shared biological phenotypes. Investigation of brain structure in disease has been enhanced by developments in shape analysis methods that can identify subtle regional surface deformations. Our study aimed to identify brain structure surface deformations that were common across related psychiatric disorders, and characterize differences., Methods: Using the automated FreeSurfer-initiated Large Deformation Diffeomorphic Metric Mapping, we examined volumes and shapes of seven brain structures: hippocampus, amygdala, caudate, nucleus accumbens, putamen, globus pallidus and thalamus. We compared findings in controls (CON; n = 40), and those with schizophrenia (SCZ; n = 52), schizotypal personality disorder (STP; n = 12), psychotic bipolar disorder (P-BP; n = 49) and nonpsychotic bipolar disorder (N-BP; n = 24), aged 15-35. Relationships between morphometric measures and positive, disorganized and negative symptoms were also investigated., Results: Inward deformation was present in the posterior thalamus in SCZ, P-BP and N-BP; and in the subiculum of the hippocampus in SCZ and STP. Most brain structures however showed unique shape deformations across groups. Correcting for intracranial size resulted in volumetric group differences for caudate (p < 0.001), putamen (p < 0.01) and globus pallidus (p < 0.001). Shape analysis showed dispersed patterns of expansion on the basal ganglia in SCZ. Significant clinical relationships with hippocampal, amygdalar and thalamic volumes were observed., Conclusions: Few similarities in surface deformation patterns were seen across groups, which may reflect differing neuropathologies. Posterior thalamic contraction in SCZ and BP suggest common genetic or environmental antecedents. Surface deformities in SCZ basal ganglia may have been due to antipsychotic drug effects.

Investigating brain tissue T2* relaxation properties in vivo can potentially guide the uncovering of neuropathology in psychiatric illness, which is traditionally examined post mortem. We use an MRI-based Gradient Echo Plural Contrast Imaging (GEPCI) technique that produces inherently co-registered images allowing quantitative assessment of tissue cellular and hemodynamic properties. Usually described as R2* (=1/T2*) relaxation rate constant, recent developments in GEPCI allow the separation of cellular-specific (R2*C) and hemodynamic (BOLD) contributions to the MRI signal decay. We characterize BOLD effect in terms of tissue concentration of deoxyhemoglobin, i.e. CDEOXY, which reflects brain activity. 17 control (CON), 17 bipolar disorder (BPD), 16 schizophrenia (SCZ), and 12 unaffected schizophrenia sibling (SIB) participants were scanned and post-processed using GEPCI protocols. A MANOVA of 38gray matter regions ROIs showed significant group effects for CDEOXY but not for R2*C. In the three non-control groups, 71-92% of brain regions had increased CDEOXY. Group effects were observed in the superior temporal cortex and the thalamus. Increased superior temporal cortex CDEOXY was found in SCZ (p=0.01), BPD (p=0.01) and SIB (p=0.02), with bilateral effects in SCZ and only left hemisphere effects in BPD and SIB. Thalamic CDEOXY abnormalities were observed in SCZ (p=0.003), BPD (p=0.03) and SIB (p=0.02). Our results suggest that increased activity in certain brain regions is part of the underlying pathophysiology of specific psychiatric disorders. High CDEOXY in the superior temporal cortex suggests abnormal activity with auditory, language and/or social cognitive processing. Larger studies are needed to clarify the clinical significance of relaxometric abnormalities., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Fractional anisotropy (FA) analysis of diffusion tensor-images (DTI) has yielded inconsistent abnormalities in schizophrenia (SZ). Inconsistencies may arise from averaging heterogeneous groups of patients. Here we investigate whether SZ is a heterogeneous group of disorders distinguished by distinct patterns of FA reductions. We developed a Generalized Factorization Method (GFM) to identify biclusters (i.e., subsets of subjects associated with a subset of particular characteristics, such as low FA in specific regions). GFM appropriately assembles a collection of unsupervised techniques with Non-negative Matrix Factorization to generate biclusters, rather than averaging across all subjects and all their characteristics. DTI tract-based spatial statistics images, which output is the locally maximal FA projected onto the group white matter skeleton, were analyzed in 47 SZ and 36 healthy subjects, identifying 8 biclusters. The mean FA of the voxels of each bicluster was significantly different from those of other SZ subjects or 36 healthy controls. The eight biclusters were organized into four more general patterns of low FA in specific regions: 1) genu of corpus callosum (GCC), 2) fornix (FX)+external capsule (EC), 3) splenium of CC (SCC)+retrolenticular limb (RLIC)+posterior limb (PLIC) of the internal capsule, and 4) anterior limb of the internal capsule. These patterns were significantly associated with particular clinical features: Pattern 1 (GCC) with bizarre behavior, pattern 2 (FX+EC) with prominent delusions, and pattern 3 (SCC+RLIC+PLIC) with negative symptoms including disorganized speech. The uncovered patterns suggest that SZ is a heterogeneous group of disorders that can be distinguished by different patterns of FA reductions associated with distinct clinical features., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this study, we examined the morphology of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ-S), and healthy controls (HC) with particular interest in differences related to the absence or presence of psychosis. Volumetric and shape analyses of the basal ganglia and thalamus were performed in 33 BP individuals [12 without history of psychotic features (NPBP) and 21 with history of psychotic features (PBP)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using FreeSurfer-initiated large deformation diffeomorphic metric mapping. Significant volume differences were found in the caudate and globus pallidus, with volumes smallest in the NPBP group. Shape abnormalities showing inward deformation of superior regions of the caudate were observed in BP (and especially in NPBP) compared with HC. Shape differences were also found in the globus pallidus and putamen when comparing BP and SCZ-S groups. No significant differences were seen in the nucleus accumbens and thalamus. In summary, structural abnormalities in the caudate and globus pallidus are present in BP and SCZ-S. Differences were more apparent in the NPBP subgroup. The findings herein highlight the potential importance of separately examining BP subgroups in neuroimaging studies., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Cannabis use is associated with working memory (WM) impairments; however, the relationship between cannabis use and WM neural circuitry is unclear. We examined whether a cannabis use disorder (CUD) was associated with differences in brain morphology between control subjects with and without a CUD and between schizophrenia subjects with and without a CUD, and whether these differences related to WM and CUD history. Subjects group-matched on demographics included 44 healthy controls, 10 subjects with a CUD history, 28 schizophrenia subjects with no history of substance use disorders, and 15 schizophrenia subjects with a CUD history. Large-deformation high-dimensional brain mapping with magnetic resonance imaging was used to obtain surface-based representations of the striatum, globus pallidus, and thalamus, compared across groups, and correlated with WM and CUD history. Surface maps were generated to visualize morphological differences. There were significant cannabis-related parametric decreases in WM across groups. Similar cannabis-related shape differences were observed in the striatum, globus pallidus, and thalamus in controls and schizophrenia subjects. Cannabis-related striatal and thalamic shape differences correlated with poorer WM and younger age of CUD onset in both groups. Schizophrenia subjects demonstrated cannabis-related neuroanatomical differences that were consistent and exaggerated compared with cannabis-related differences found in controls. The cross-sectional results suggest that both CUD groups were characterized by WM deficits and subcortical neuroanatomical differences. Future longitudinal studies could help determine whether cannabis use contributes to these observed shape differences or whether they are biomarkers of a vulnerability to the effects of cannabis that predate its misuse.

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., (© 2014.)

Background: Bipolar disorder (BPD) and schizophrenia (SCZ) share clinical characteristics and genetic contributions. Functional dysconnectivity across various brain networks has been reported to contribute to the pathophysiology of both SCZ and BPD. However, research examining resting-state neural network dysfunction across multiple networks to understand the relationship between these two disorders is lacking., Methods: We conducted a resting-state functional connectivity fMRI study of 35 BPD and 25 SCZ patients, and 33 controls. Using previously defined regions-of-interest, we computed the mean connectivity within and between five neural networks: default mode (DM), fronto-parietal (FP), cingulo-opercular (CO), cerebellar (CER), and salience (SAL). Repeated measures ANOVAs were used to compare groups, adjusting false discovery rate to control for multiple comparisons. The relationship of connectivity with the SANS/SAPS, vocabulary and matrix reasoning was investigated using hierarchical linear regression analyses., Results: Decreased within-network connectivity was only found for the CO network in BPD. Across groups, connectivity was decreased between CO-CER (p<0.001), to a larger degree in SCZ than in BPD. In SCZ, there was also decreased connectivity in CO-SAL, FP-CO, and FP-CER, while BPD showed decreased CER-SAL connectivity. Disorganization symptoms were predicted by connectivity between CO-CER and CER-SAL., Discussion: Our findings indicate dysfunction in the connections between networks involved in cognitive and emotional processing in the pathophysiology of BPD and SCZ. Both similarities and differences in connectivity were observed across disorders. Further studies are required to investigate relationships of neural networks to more diverse clinical and cognitive domains underlying psychiatric disorders., (Copyright © 2013 Elsevier B.V. All rights reserved.)