DSM-5 conduct disorder and symptoms in youths at high risk of psychosis in Kenya with DSM-5 mental disorders and substance use: towards integrated management.

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.

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

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

Personality Traits as Markers of Psychosis Risk in Kenya: Assessment of Temperament and Character.

Specific personality traits have been proposed as a schizophrenia-related endophenotype and confirmed in siblings at risk for psychosis. The relationship of temperament and character with psychosis has not been previously investigated in Africa. The study was conducted in Kenya, and involved participants at clinical high-risk (CHR) for psychosis (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 psychometric properties of the Washington Early Recognition Center Affectivity and Psychosis (WERCAP) screen in adults in the Kenyan context: Towards combined large scale community screening for affectivity and psychosis.

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.

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

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

Anterior thalamic radiation integrity in schizophrenia: a diffusion-tensor imaging study.

The anterior limb of the internal capsule (ALIC) is a white matter structure, the medial portion of which includes the anterior thalamic radiation (ATR) carrying nerve fibers between thalamus and prefrontal cortex. ATR abnormalities have a possible link with cognitive abnormalities and negative symptoms in schizophrenia. We aimed to study the fiber integrity of the ATR more selectively by isolating the medial portion of the ALIC using region-of-interest based methodology. Diffusion-tensor imaging was used to measure the anisotropy of total ALIC (tALIC) and medial ALIC (mALIC) in 39 schizophrenia and 33 control participants, matched for age/gender/handedness. Relationships between anisotropy, psychopathology, and cognitive performance were analyzed. Compared with controls, schizophrenia participants had 4.55% lower anisotropy in right tALIC, and 5.38% lower anisotropy in right mALIC. There were no significant group anisotropy differences on the left. Significant correlations were observed between right ALIC integrity and relevant domains of cognitive function (e.g., executive function, working memory). Our study suggests an asymmetric microstructural change in ALIC in schizophrenia involving the right side, which is only minimally stronger in mALIC, and which correlates with cognitive impairment. Microstructural changes in the ALIC may be linked to cognitive dysfunction in schizophrenia.

Elevated rates of substance use disorders in non-psychotic siblings of individuals with schizophrenia.

BACKGROUND: Individuals with schizophrenia use psychoactive substances more frequently than the general population. The genetic vulnerability to develop schizophrenia may also increase risk for the development of substance use disorders. We examine this hypothesis by assessing the rates of substance use disorders and nicotine use in non-psychotic siblings of individuals with schizophrenia. METHODS: Participants included 59 individuals with DSM-IV schizophrenia, 53 of their siblings, 80 community controls, and 75 of their siblings. Statistical regression was used to assess the rates of substance use disorders and nicotine use in study participants while controlling for age, gender, lifetime diagnosis of a mood or anxiety disorder, and a family history of substance use disorder. RESULTS: Individuals with schizophrenia and their non-psychotic siblings reported higher rates of alcohol and cannabis use disorders and nicotine use when compared to siblings of comparison subjects. CONCLUSIONS: The vulnerability to develop schizophrenia may also extend to substance use disorders. Future research is needed to investigate the neurobiological basis of increased substance use in non-psychotic siblings and the psychosocial mechanisms that may contribute to increased substance use in non-psychotic siblings.

Nuclear translocation of nuclear transcription factor-kappa B by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leads to transcription of p53 and cell death in dopaminergic neurons.

We describe a new molecular mechanism of cell death by excitotoxicity mediated through nuclear transcription factor kappa B (NF kappa B) in rat embryonic cultures of dopaminergic neurons. Treatment of mesencephalic cultures with alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) resulted in a number of changes that occurred selectively in dopaminergic neurons, including persistent elevation in intracellular Ca(2+) monitored with Fura-2, and a significant increase in intramitochondrial oxidation of dihydrorhodamine 123, probably associated with transient increase of mitochondrial permeability, cytochrome c release, nuclear translocation of NF kappa B, and transcriptional activation of the oncogene p53. Interruption of any of these steps by specific antagonists prevented neurite pruning and programmed cell death. In contrast, cell death was not prevented by caspase antagonists and only partly prevented by nitric-oxide synthase inhibitors. This signal transduction pathway might be a contributing mechanism in ongoing neuronal death in Parkinson disease.

T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase.

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.