The new-generation antipsychotics -integrating the neuropathology and pharmacology of schizophrenia

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OBJECTIVE: Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to investigate the effects of HIV infection on reward processing by examining the function of the ventral-striatal reward system during a monetary incentive delay task. DESIGN: This is a cross-sectional case-control study. METHODS: Eighteen combined antiretroviral therapy-naive HIV-positive (HIV+) participants, as well as 16 matched healthy controls, performed a monetary incentive delay task. This paradigm assesses behaviour as well as functional brain activity-associated reward anticipation and reward outcome. RESULTS: HIV+ participants showed a general decrease in activation associated with both neutral as well as potentially rewarding cues in their ventral striatum. We found normal activity related to reward outcome in the orbito-frontal cortex. Despite HIV+ participants' reaction times being significantly slower when independently measured from the reward paradigm, this performance deficit normalized during the performance of the reward task. CONCLUSION: HIV caused a decrease in activity during cue processing in the ventral striatum, with normal cortical functioning during reward outcome processing. Our results therefore suggest that HIV not only has an impact on fronto-striatal systems involved in executive functioning, but also has a direct impact on the function of the ventral-striatal reward system

A new model for the pathophysiology of Alzheimer's disease: Aluminium toxicity is exacerbated by hydrogen peroxide and attenuated by an amyloid protein fragment and melatonin

Objectives. Although Alzheimer's disease (AD) is the leading cause of dementia in developed countries, there is an as yet unexplained lower prevalence of the disease in parts of Africa. AD is characterised by a catastrophic loss of neurons; free radicals (oxidative toxins) have been implicated in the destruction of the cells through the process of lipid peroxidative damage of cell membranes. Previously aluminium (Al) and a fragment of beta amyloid (Aβ 25 - 35) were shown to exacerbate tree-radical damage, while melatonin reduced this effect. The aim of the present study was: (i) to investigate the conditions detennining the toxicity of Al and Aβ 25 - 35; and (ii) to assess whether melatonin could attenuate the damage done by both aluminium and the amyloid fragment, thus suggesting a pathway for the aetiology of AD.Design. An in vitro model system was used in which free radicals were generated, causing lipid peroxidation of platelet membranes, thus simulating the disease process found in the brain.Results. 1. Al and Aβ 25 - 35 caused lipid peroxidation in the presence of the iron (II) ion (Fe2+, Al being more toxic than Aβ 25 - 35. 2. Aβ 25 - 35 attenuated the lipid peroxidation promoted by Al. 3. Hydrogen peroxide (H2O2 greatly exacerbated the toxicity of Al and Aβ 25 - 35. 4. Melatonin prevented lipid peroxidation by Al and Aβ 25 - 35 in the absence of H2O2, but only reduced the process when H2O2 was present.Conclusions. In the light of the results obtained from the present study, the following hypotheses are formulated. 1. In AD, excessive quantities of Al are taken up into the  brain, where the Al exacerbates iron-induced lipid peroxidatian in the Iysosomes. 2. In response, the normal synthetic pathway of amyloid protein is altered to produce Aβ fragments which attenuate the toxicity of Al. In the process of sequestering the Al and iron, immature plaques are formed in the brain. 3. Microglia are activated, in an attempt to destroy the plaques by secreting reactive oxygen species such as H2O2. At this point in the disease process, lipid peroxidation causes a catastrophic loss of brain cells. 4. Melatonin, together with other free radical scavengers in the brain, reduces the free-radical damage caused by Al and Aβ, except in the latter stages of the disease process. Since melatonin is produced by the pineal gland only in the dark, the excess of electric light in developed countries may help explain why AD is more prevalent in these countries than in rural Africa

Sub-specialties in psychiatry: Towards parity in mental health training and services

Neuropsychiatric disorders account for 5 of the 10 most disabling medical disorders worldwide,1 and for a particularly large component of the burden of disease in South Africa.2 Unfortunately, as elsewhere, training and services in psychiatry have lagged behind those of other major disciplines, and much additional work is needed to achieve parity. We focus in particular on the status of psychiatric sub-specialties in South Africa, considering the pros and cons of their recognition in a developing country

Obsessive compulsive disorder- prevalence in Xhosaspeaking schizophrenia patients

Obsessive compulsive disorder (OCD) has been reported in up to 31% of  schizophrenia sufferers. This study evaluated the presence of OCD in a  Xhosa-speaking schizophrenia group. Xhosa patients (N = 509, including 100  sibships) with schizophrenia were recruited from hospital and community settings. The patients underwent a structured clinical interview for the presence  of lifetime co-morbid schizo-phrenia and OCD. Only 3 patients (0.5%) fulfilled criteria for OCD. No concordance for OCD was noted in the  sibship group. Our findings differ from those in other parts of the world, and if replicated, might suggest unique protective environmental or genetic factors  for OCD in certain ethnic groups

Associations of premorbid adjustment with type and timing of childhood trauma in first-episode schizophrenia spectrum disorders

CITATION: Smit, A. M. et al. 2021. Associations of premorbid adjustment with type and timing of childhood trauma in first-episode schizophrenia spectrum disorders. South African Journal of Psychiatry, 27:a1639, doi:10.4102/sajpsychiatry.v27i0.1639.The original publication is available at https://sajp.org.zaBackground: Childhood trauma may contribute to poorer premorbid social and academic adjustment which may be a risk factor for schizophrenia. Aim: We explored the relationship between premorbid adjustment and childhood trauma, timing of childhood trauma’s moderating role as well as the association of clinical and treatment-related confounders with premorbid adjustment. Setting: We conducted a secondary analysis in 111 patients with first-episode schizophrenia (FES) disorders that formed part of two parent studies, EONKCS study (n =73) and the Shared Roots study (n =38). Methods: Type of childhood trauma was assessed with the Childhood Trauma Questionnaire, short-form and premorbid adjustment using the Premorbid Adjustment Scale. Timing of childhood trauma was assessed using the Life Events Checklist and life events timeline. Linear regression analyses were used to assess the moderating effect of timing of childhood trauma. Clinical and treatment-related confounders were entered into sequential hierarchical regression models to identify independent predictors of premorbid adjustment across key life stages. Results: Childhood physical neglect was associated with poorer premorbid academic functioning during childhood and early adolescence, and poorer premorbid social functioning during early and late adolescence. By hierarchical regression modelling (r2 = 0.13), higher physical neglect subscale scores (p = 0.011) independently predicted poorer premorbid social adjustment during early adolescence. Timing of childhood trauma did not moderate the relationship between childhood trauma and premorbid functioning. Conclusion: In patients with FES, childhood physical neglect may contribute to poorer premorbid social functioning during early adolescence. This may provide us with an opportunity to identify and treat at-risk individuals earlier.https://sajp.org.za/index.php/sajp/article/view/1639Publisher's versio

Chromosome 22q11 in a Xhosa schizophrenia population

Chromosome 22q11 aberrations substantially increase the risk for developing schizophrenia. Although micro-deletions in this region have been extensively investigated in different populations across the world, little is known of their prevalence in African subjects with schizophrenia. We screened 110 African Xhosa-speaking participants with schizophrenia for the presence of micro-deletions. As further verification for the presence or absence of 22q11 microdeletions, we screened 238 Xhosa schizophrenia patients and 240 healthy Xhosa individuals from a larger schizophrenia candidate 22q11 gene study using molecular analyses. Data from molecular and cytogenetic analyses confirmed the absence of 22q11 microdeletions in the Xhosa schizophrenia samples. Although the absence of chromosome 22q11 micro-deletions in this group of patients does not exclude the possibility that it may occur in Xhosa schizophrenia patients, we concluded an extremely low prevalence. Our findings suggest that unique susceptibility loci may be present in this group