The effect of an e-intervention on intellectual disability stigma among Nigerian and Kenyan internet users: a comparative randomised controlled trial.

Introduction: The negative consequences of stigma for the wellbeing of people with disabilities have raised public and global health concerns. This study assessed the impact of an e-intervention to reduce intellectual disability (ID) stigma among Nigerian and Kenyan internet-users. Method: Participants aged 18+ and citizens of Nigeria and Kenya were recruited through online advertising. Qualtrics, a web survey platform, randomly assigned (1:1) participants to watch either a short experimental or control film, while masked to their assignment. The experimental film featured education about ID and indirect contact. The control film was on an unrelated topic. Their attitudes were measured on three dimensions (affect, cognitions and behaviour) at three time points (baseline, post intervention and one-month follow-up). Between October 2016 and April 2017, 933 participants were randomised, 469 to the experimental condition and 464 to the control condition. Of these, 827 (89%) provided pre-and post-intervention data but only 287 (31%) were retained at follow-up. Results: An intent-to-treat analysis revealed that participants in the experimental but not the control condition showed a positive shift in their attitudes towards people with ID over time. Their willingness to interact with people with ID increased post-intervention. Discussion: A brief intervention that integrates education and indirect contact can make an effective contribution to efforts to reduce stigma faced by people with ID in Africa. Trial registered with the ISRCTN trial registry (number ISRCTN92574712).

Evolution of structural abnormalities in the rat brain following in utero exposure to maternal immune activation: A longitudinal in vivo MRI study.

Genetic and environmental risk factors for psychiatric disorders are suggested to disrupt the trajectory of brain maturation during adolescence, leading to the development of psychopathology in adulthood. Rodent models are powerful tools to dissect the specific effects of such risk factors on brain maturational profiles, particularly when combined with Magnetic Resonance Imaging (MRI; clinically comparable technology). We therefore investigated the effect of maternal immune activation (MIA), an epidemiological risk factor for adult-onset psychiatric disorders, on rat brain maturation using atlas and tensor-based morphometry analysis of longitudinal in vivo MR images. Exposure to MIA resulted in decreases in the volume of several cortical regions, the hippocampus, amygdala, striatum, nucleus accumbens and unexpectedly, the lateral ventricles, relative to controls. In contrast, the volumes of the thalamus, ventral mesencephalon, brain stem and major white matter tracts were larger, relative to controls. These volumetric changes were maximal between post-natal day 50 and 100 with no differences between the groups thereafter. These data are consistent with and extend prior studies of brain structure in MIA-exposed rodents. Apart from the ventricular findings, these data have robust face validity to clinical imaging findings reported in studies of individuals at high clinical risk for a psychiatric disorder. Further work is now required to address the relationship of these MRI changes to behavioral dysfunction and to establish thier cellular correlates.

Longitudinal in vivo maturational changes of metabolites in the prefrontal cortex of rats exposed to polyinosinic-polycytidylic acid in utero.

Proton magnetic resonance spectroscopy ((1)H MRS) studies in schizophrenia patients generally report decreased levels of N-acetyl-aspartate (NAA), glutamate and glutathione, particularly in frontal cortex. However, these data are inconsistent in part due to confounds associated with clinical samples. The lack of validated diagnostic biomarkers also hampers analysis of the neurodevelopmental trajectory of neurochemical abnormalities. Rodent models are powerful tools to address these issues, particularly when combined with (1)H MRS (clinically comparable technology). We investigated the trajectory of metabolic changes in the prefrontal cortex during brain maturation from adolescence to adulthood in vivo using (1)H MRS in rats exposed prenatally to polyinosinic-polycytidylic acid (POL), a rodent model of maternal immune activation (MIA), an epidemiological risk factor for several psychiatric disorders with a neurodevelopmental origin. Longitudinal in vivo (1)H MRS revealed a significant decrease in PFC levels of GSH and taurine in adult, but not adolescent rats. Significant age×MIA interactions for PFC levels of NAA were also observed. These data replicate some deficits observed in the PFC of patients with schizophrenia. There were no significant changes in the levels of glutamate or any other metabolite. These data suggest prenatal exposure to POL leads to subtle metabolic perturbations of the normal maturing PFC, which may be related to subsequent behavioural abnormalities. Further work is however required to examine any potential confound of shipping stress on the presumed imbalances in PFC metabolites in POL-exposed offspring. Testing the interactions between MIA with stress or genetic risk variants will also be an important advance.

Reduced cortical volume and elevated astrocyte density in rats chronically treated with antipsychotic drugs-linking magnetic resonance imaging findings to cellular pathology.

BACKGROUND: Increasing evidence suggests that antipsychotic drugs (APD) might affect brain structure directly, particularly the cerebral cortex. However, the precise anatomical loci of these effects and their underlying cellular basis remain unclear. METHODS: With ex vivo magnetic resonance imaging in rats treated chronically with APDs, we used automated analysis techniques to map the regions that show maximal impact of chronic (8 weeks) treatment with either haloperidol or olanzapine on the rat cortex. Guided by these imaging findings, we undertook a focused postmortem investigation with stereology. RESULTS: We identified decreases in the volume and thickness of the anterior cingulate cortex (ACC) after chronic APD treatment, regardless of the APD administered. Postmortem analysis confirmed these volumetric findings and demonstrated that chronic APD treatment had no effect on the total number of neurons or S100ß+ astrocytes in the ACC. In contrast, an increase in the density of these cells was observed. CONCLUSIONS: This study demonstrates region-specific structural effects of chronic APD treatment on the rat cortex, primarily but not exclusively localized to the ACC. At least in the rat, these changes are not due to a loss of either neurons or astrocytes and are likely to reflect a loss of neuropil. Although caution needs to be exerted when extrapolating results from animals to patients, this study highlights the power of this approach to link magnetic resonance imaging findings to their histopathological origins.