Search

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.)

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.)

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: 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).)

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.)

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.

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.)

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.

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.

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.

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). One hundred thirty-four first-episode psychosis patients (receiving either haloperidol [HAL] or olanzapine [OLZ]) and 51 healthy controls were followed 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 HAL treatment compared to OLZ treatment and to controls. OLZ treatment was associated with a significantly lower percentage of "large magnitude" negative surface vertex slopes compared to HAL treatment (p = 0.004). Surface deformation maps however did not localize any hippocampal regions that differentially contracted over time with OLZ 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 OLZ is associated with less longitudinal hippocampal surface deformation than HAL, however the hippocampal regions affected appear to be variable across patients.

We review demographic and mental health data from 1,729 youths aged 13 to 24 who attended the SPOT (Supporting Positive Opportunities with Teens), a free multi-resource drop-in youth center in St. Louis, within an 18-month period. Logistic regression analysis showed an association of increased mental health utilization and younger age, male gender, unemployment, lower educational attainment, having Medicaid, drug problems, and HIV positive status. Decreased mental health utilization was associated with black or mixed ethnicity, and living with a roommate.

Inflammatory bowel disease (IBD) is associated with mucosal T cell activation and diarrhea. We found that T cell activation with anti-CD3 mAb induces profound diarrhea in mice. Diarrhea was quantified by intestinal weight-to-length (wt/l) ratios, mucosal Na(+)/K(+)-ATPase activity was determined and ion transport changes were measured in Ussing chambers. Anti-CD3 mAb increased jejunal wt/l ratios by more than 50% at 3 hours, returning to base line after 6 hours. Fluid accumulation was significantly reduced in TNF receptor-1 (TNFR-1(-/-)), but not IFN-gamma knockout mice. Anti-CD3 mAb decreased mucosal Na(+)/K(+)-ATPase activity, which was blocked by anti-TNF mAb and occurred to a lesser degree in TNFR-1(-/-) mice. Neither alpha nor beta subunits of Na(+)/K(+)-ATPase decreased in abundance at 3 hours. Intestinal tissue from anti-CD3-treated mice exhibited increased permeability to mannitol at 1 hour and decreases in electroneutral Na(+) absorption, Na(+)-dependent glucose absorption, and cAMP-stimulated anion secretion at 3 hours. Furthermore, enteral fluid accumulation was observed in CFTR(-/-) mice, indicating a minor role of active anion secretion. These data suggest that diarrhea in IBD is due to TNF-mediated malabsorption rather than to secretory processes. T cell activation induces luminal fluid accumulation by increasing mucosal permeability and reducing epithelial Na(+)/K(+)-ATPase activity leading to decreased intestinal Na(+) and water absorption.