Burden of Depression in Outpatient HIV-Infected adults in Sub-Saharan Africa; Systematic Review and Meta-analysis.

Despite the substantial burden of HIV in Africa, and the knowledge that depression causes worse HIV outcomes, the burden of depression in people living with HIV in Africa is unknown. We searched Pubmed and four other databases using key terms: depression, Africa, HIV, and prevalence from 2008 to 2018. We summarized depression prevalence by country. We estimated the burden of depression using our prevalence data and 2018 UNAIDS HIV estimates. Our search yielded 70 articles across 16 African countries. The overall prevalence of major depression in those HIV-infected using a diagnostic interview was 15.3% (95% CI 12.5-17.1%). We estimate that 3.63 million (99.7% CI 3.15-4.19 million) individuals with HIV in Sub-Saharan Africa have major depression and provide country-level estimates. We estimate that 1.57 million (99.7% CI 1.37-1.82 million) DALYs are lost among people with depression and HIV in Sub-Saharan Africa. There is a significant burden of depression in Africans with HIV. Further work to screen for and treat depression in Sub-Saharan Africa is needed to improve HIV outcomes and achieve the 90-90-90 UNAIDS goals.

Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial.

Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.

Lower cognitive functioning as a predictor of weight gain in bipolar disorder: a 12-month study.

OBJECTIVE: In cross-sectional studies, elevated body mass index (BMI) is associated with cognitive impairment in bipolar disorder (BD). We investigated the direction of this association by prospectively examining changes in BMI and cognition. METHOD: We measured BMI and performance in six cognitive domains over 12 months in 80 adolescent and young adult BD patients and 46 healthy comparison subjects (HS). Ninety-three percent of patients received pharmacotherapy and 84% were euthymic. We used repeated-measures ancova and longitudinal mixed models to investigate whether (i) higher BMI and increasing BMI over time predicted lower subsequent cognitive functioning, and (ii) lower cognitive functioning and changes in cognition predicted increasing BMI. RESULTS: Neither baseline BMI nor BMI change predicted lower cognitive functioning. Lower baseline scores in attention, verbal memory, working memory, and a composite measure of global cognition predicted increasing BMI in patients and HS. In patients, lower cognitive functioning remained associated with increasing BMI when clinical and treatment variables were adjusted for. Improvement in working memory predicted a smaller subsequent BMI increase in patients. CONCLUSION: Lower cognitive functioning in specific domains predicts increasing BMI in patients with BD and healthy young adults. Targeting cognition may be important for minimizing weight gain in BD.

A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes.

BACKGROUND: There is growing interest in glutamatergic agents in depression, particularly ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist. We aimed to assess the efficacy of ketamine in major depressive episodes. METHOD: We searched EMBASE, PsycINFO, CENTRAL, and Medline from 1962 to January 2014 to identify double-blind, randomized controlled trials with allocation concealment evaluating ketamine in major depressive episodes. Clinical remission, response and depressive symptoms were extracted by two independent raters. The primary outcome measure was clinical remission at 24 h, 3 days and 7 days post-treatment. Analyses employed a random-effects model. RESULTS: Data were synthesized from seven RCTs employing an intravenous infusion and one RCT employing intranasal ketamine, representing 73 subjects in parallel arms and 110 subjects in cross-over designs [n = 34 with bipolar disorder (BD), n = 149 with major depressive disorder (MDD)]. Ketamine was associated with higher rates of clinical remission relative to comparator (saline or midazolam) at 24 h [OR 7.06, number needed to treat (NNT) = 5], 3 days (OR 3.86, NNT = 6), and 7 days (OR 4.00, NNT = 6), as well as higher rates of clinical response at 24 h (OR 9.10, NNT = 3), 3 days (OR 6.77, NNT = 3), and 7 days (OR 4.87, NNT = 4). A standardized mean difference of 0.90 in favor of ketamine was observed at 24 h based on depression rating scale scores, with group comparisons revealing greater efficacy in unipolar depression compared to bipolar depression (1.07 v. 0.68). Ketamine was associated with transient psychotomimetic effects, but no persistent psychosis or affective switches. CONCLUSION: Our meta-analysis suggests that single administrations ketamine are efficacious in the rapid treatment of unipolar and bipolar depression. Additional research is required to determine optimal dosing schedules, route, treatment schedules, and the potential efficacy of other glutamatergic agents.

Relationship between cognitive functioning and 6-month clinical and functional outcome in patients with first manic episode bipolar I disorder.

BACKGROUND: Although cognitive deficits in bipolar disorder have been associated with diminished functional outcome, this relationship has been studied primarily through cross-sectional designs, and has not been studied in patients early in the course of illness. The purpose of this study was to evaluate the impact of cognitive functioning on longitudinal 6-month functional and clinical outcome in recently diagnosed clinically stable patients with bipolar disorder. METHOD: A total of 53 recently diagnosed patients with DSM-IV bipolar disorder type I were assessed within 3 months of their first manic episode using a neuropsychological battery measuring verbal/pre-morbid intellectual functioning, learning/memory, spatial/non-verbal reasoning, attention/processing speed and executive function. Functional outcome was assessed at baseline and 6 months using the Multidimensional Scale of Independent Functioning (MSIF) and DSM-IV Global Assessment of Functioning Scale (GAF). Clinical outcome was assessed with symptom ratings and by monitoring onset of new mood episodes. RESULTS: Memory, particularly verbal learning/memory, was robustly associated with 6-month functional outcome on the MSIF, even after partialling out the influence of mood symptoms and substance abuse co-morbidity. Depression ratings at 6 months, but not cognitive variables, were associated with 6-month GAF scores. Cognitive functioning was not associated with 6-month clinical outcome. CONCLUSIONS: Memory was associated with 6-month longitudinal functional but not clinical outcome in recently diagnosed patients with bipolar disorder. These data further support the distinction between clinical and functional outcome, and emphasize the need for identification of, and development of treatments for, cognitive impairments early in the course of bipolar disorder.

Diagnosis and body mass index effects on hippocampal volumes and neurochemistry in bipolar disorder.

We previously reported that higher body mass index (BMI) was associated with greater hippocampal glutamate+glutamine in people with bipolar disorder (BD), but not in non-BD healthy comparator subjects (HSs). In the current report, we extend these findings by examining the impact of BD diagnosis and BMI on hippocampal volumes and the concentrations of several additional neurochemicals in 57 early-stage BD patients and 31 HSs. Using 3-T magnetic resonance imaging and magnetic resonance spectroscopy, we measured bilateral hippocampal volumes and the hippocampal concentrations of four neurochemicals relevant to BD: N-acetylaspartate+N-acteylaspartylglutamate (tNAA), creatine+phosphocreatine (Cre), myoinositol (Ins) and glycerophosphocholine+phosphatidylcholine (Cho). We used multivariate factorial analysis of covariance to investigate the impact of diagnosis (patient vs HS) and BMI category (normal weight vs overweight/obese) on these variables. We found a main effect of diagnosis on hippocampal volumes, with patients having smaller hippocampi than HSs. There was no association between BMI and hippocampal volumes. We found diagnosis and BMI effects on hippocampal neurochemistry, with patients having lower Cre, Ins and Cho, and overweight/obese subjects having higher levels of these chemicals. In patient-only models that controlled for clinical and treatment variables, we detected an additional association between higher BMI and lower tNAA that was absent in HSs. To our knowledge, this was the first study to investigate the relative contributions of BD diagnosis and BMI to hippocampal volumes, and only the second to investigate their contributions to hippocampal chemistry. It provides further evidence that diagnosis and elevated BMI both impact limbic brain areas relevant to BD.

The Genetics of a Probable Insertional Translocation in SORDARIA BREVICOLLIS.

A chromosome rearrangement has been isolated and characterized in Sordaria brevicollis. Crosses to spore color mutants on each of the seven linkage groups have enabled the breakpoints to be mapped. The simplest hypothesis to account for the results is that a piece of linkage group VI has been translocated to linkage group V and inserted 2.7 map units from its centromere. Previous reports of markers on this linkage group with centromere distances greater than 2.7 units make it unlikely that the translocation is quasiterminal.

Preferential ascus discharge during cross maturation in Sordaria brevicollis.

Crosses involving spore color mutants of Sordaria brevicollis all showed a decline in the frequency of second division asymmetric asci (2:2:2:2's) as the cross matured. This decline was due to the preferential maturation and/or discharge of these asci. The proportion of spindle overlap and recombinational asci within the group did not change as shown by ascus dissection. The preferential discharge was also found to occur in two-point crosses where the asci did not contain wild-type spores.

Meiotic aneuploidy: its origins and induction following chemical treatment in Sordaria brevicollis.

A system suitable for the detection of meiotic aneuploidy is described in which various different origins of the aneuploidy can be distinguished. Aneuploid meiotic products are detected as black disomic spores held in asci containing all the products of a single meiosis. Aneuploidy may result from nondisjunction or from a meiosis in which an extra replica of one of the chromosomes has been generated in some other way, e.g., extra replication. By using this system it has been shown that pFPA treatment increase aneuploidy, primarily through an effect on nondisjunction. Preliminary results with trifluralin have indicated that this compound, too, may increase aneuploidy. There is a good possibility that the system can be further developed to permit a more rapid screening using a random plating method; this will allow a more efficient two-part analysis of the effects of compounds under test.

Childhood maltreatment and corpus callosum volume in recently diagnosed patients with bipolar I disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

Childhood trauma (CT) has been associated with abnormalities in the corpus callosum (CC). Decreased CC volumes have been reported in children and adolescents with trauma as well as adults with CT compared to healthy controls. CC morphology is potentially susceptible to the effects of Bipolar Disorder (BD) itself. Therefore, we evaluated the relationship between CT and CC morphology in BD. We using magnetic resonance imaging in 53 adults with BD recently recovered from their first manic episode, with (n = 23) and without (n = 30) CT, defined using the Childhood Trauma Questionnaire (CTQ) and 16 healthy controls without trauma. ANCOVA was performed with age, gender and intracranial volume as covariates in order to evaluate group differences in CC volume. The total CC volume was found to be smaller in BD patients with trauma compared to BD patients without trauma (p < .05). The differences were more pronounced in the anterior region of the CC. There was a significant negative correlation between CTQ scores and total CC volume in BD patients with trauma (p = .01). We did not find significant differences in the CC volume of patients with/without trauma compared to the healthy subjects. Our sample consists of patients recovered from a first episode of mania and are early in the course of illness and reductions in CC volume may occur late in the course of BD. It might mean there may be two sources of CC volume reduction in these patients: the reduction due to trauma, and the further reduction due to the illness.

The impact of childhood trauma on cognitive functioning in patients recently recovered from a first manic episode: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

BACKGROUND: Both bipolar disorder (BD) and childhood trauma are associated with cognitive impairment. People with BD have high rates of childhood trauma, which confer greater overall disease severity, but, it is unknown if childhood trauma is associated with greater neurocognitive impairment in BD patients early in the course of their illnesses. In this study, we investigated the impact of childhood trauma on specific cognitive dysfunction in patients who recently recovered from their first episode of mania. METHODS: Data were available for 64 patients and 28 healthy subjects matched by age, gender and pre-morbid IQ, recruited from a large university medical center. History of childhood trauma was measured using the Childhood Trauma Questionnaire. Cognitive function was assessed through a comprehensive neuropsychological test battery. RESULTS: Trauma was associated with poorer cognitive performance in patients on cognitive measures of IQ, auditory attention and verbal and working memory, and a different pattern was observed in healthy subjects. LIMITATIONS: We had a modest sample size, particularly in the group of healthy subjects with trauma. CONCLUSIONS: Childhood trauma was associated with poorer cognition in BD patients who recently recovered from a first episode of mania compared to healthy subjects. The results require replication, but suggest that the co-occurrence of trauma and bipolar disorder can affect those cognitive areas that are already more susceptible in patients with BD.

Depot antipsychotic medications in bipolar disorder: a review of the literature.

OBJECTIVE: To review the literature on the efficacy and safety of depot formulations of first- and second-generation antipsychotic medications (FGAs and SGAs) in patients with bipolar disorder. METHOD: We conducted a computer-aided MEDLINE search using the search terms 'depot antipsychotic', 'bipolar disorder' and 'compliance.' RESULTS: We identified eight published reports in bipolar patients regarding the use of depot FGAs, and six preliminary reports on the use of depot SGAs. These studies suggest that depots FGAs are efficacious in preventing manic episodes during the maintenance treatment of bipolar disorder. Several studies, however, indicate that depot FGAs may be associated with increased time with depressive symptoms, particularly in patients with a predominantly depressive course of illness. Preliminary data on the role of depot formulations of SGAs suggest that they reduce the frequency of both manic and depressive episodes during maintenance treatment, and are well tolerated by patients. CONCLUSION: After a careful risk-benefit analysis, depot antipsychotics may be considered for the long-term control of mood episodes in bipolar patients who have relapsed due to medication non-adherence or who have failed to respond to standard therapies. Depot FGAs should be avoided in patients with a high burden of illness from depressive symptoms and particularly in those judged to be at high risk of suicide. The available data on depot formulations of SGAs indicate that they are efficacious in the maintenance treatment of bipolar illness without increasing the burden of the depressive pole of the illness, but further systematic studies are required to definitively assess this.

Dimethylsulfoxide induces aneuploidy in a fungal test system.

Errors in chromosome segregation leading to numerical anomalies appear to be unusually frequent in Man and consequently a large proportion of conceptions in our species are aneuploid. Concern has been expressed that this frequency may be increased still further following exposure to inducing substances (trisomigens) present in the environment. We have been developing a fungal test system to screen for such trisomigens and in this paper we report its use in detecting induction following exposure to dimethylsulfoxide (DMSO). In our system DMSO induces segregational errors at both the first and second meiotic division. The results also show that increases in aneuploidy are proportional to the underlying spontaneous frequency. If this finding is generally true it will be especially important to avoid exposure to trisomigens as Man might be especially vulnerable to them.

Recent history of ischaemic heart disease and duodenal ulcer in doctors.

Data are presented on the incidence of ischaemic (coronary) heart disease and duodenal ulcer among the several thousand male medical practitioners aged 35-64 holding immediate sickness benefit policies with the Medical Sickness Annuity and Life Assurance Society Limited. Three periods are considered: 1947-50, 1957-60, and 1961-5.The incidence of first clinical episodes of ischaemic heart disease in the doctors altered little between 1947-50 and 1957-60 but increased in 1961-5. Comparison of the late 1940s with the early 1960s shows a 60% rise of incidence at ages 45-54 but little change at other ages. Cases first presenting as "sudden" death increased between 1947-50 and 1961-5 by 111% at 45-54, and again changed little at 55-64. In two other occupational groups that have been studied-bus conductors and insurance salesmen-the increase of incidence was greater than for the doctors at 45-54 and it occurred also over 55 years of age. The increase from 1947-50 to 1961-5 in mortality during all episodes of ischaemic heart disease was the same in the doctors as in the male population of England and Wales at 45-54, but at 55-64 it was less.The results in the doctors are not due to alterations over the period in length of sickness absence, or underwriting policy, or of the nomenclature used on the certificates.Well-documented changes in the smoking habits of doctors may be partly responsible for what appears to have been a relatively favourable experience of ischaemic heart disease from 1947-50 to 1961-5, especially at ages 55-64.Incidence of duodenal ulcer at ages 35-64 declined steadily in this population of doctors from 1947-50 to 1961-5. The decline is very likely to be real.