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Comorbid mental disorders and quality of life of people with epilepsy attending primary health care clinics in rural Ethiopia.
BACKGROUND: Evidence from high-income countries demonstrates that co-morbid mental disorders in people with epilepsy adversely affect clinical and social outcomes. However, evidence from low-income countries is lacking. The objective of this study was to measure the association between co-morbid mental disorders and quality of life and functioning in people with epilepsy. METHODS: A facility-based, community ascertained cross-sectional survey was carried out in selected districts of the Gurage Zone, Southern Ethiopia. Participants were identified in the community and referred to primary health care (PHC) clinics. Those diagnosed by PHC workers were recruited. Co-morbid mental disorders were measured using a standardised, semi-structured clinical interview administered by mental health professionals. The main outcome, quality of life, was measured using the Quality of Life in Epilepsy questionnaire (QOLIE-10p). The secondary outcome, functional disability, was assessed using the 12-item World Health Organization Disability Assessment Schedule (WHODAS-2). RESULTS: The prevalence of comorbid mental disorders was 13.9%. Comorbid mental disorders were associated with poorer quality of life (Adjusted (Adj.) β -13.27; 95% CI -23.28 to-3.26) and greater disability (multiplier of WHODAS-2 score 1.62; 95% CI 1.05, 2.50) after adjusting for hypothesised confounding factors. Low or very low relative wealth (Adj. β = -12.57, 95% CI -19.94 to-5.20), higher seizure frequency (Adj.β coef. = -1.92, 95% CI -2.83 to -1.02), and poor to intermediate social support (Adj. β coef. = -9.66, 95% CI -16.51 to -2.81) were associated independently with decreased quality of life. Higher seizure frequency (multiplier of WHODAS-2 score 1.11; 95% CI 1.04, 1.19) was associated independently with functional disability. CONCLUSION: Co-morbid mental disorders were associated with poorer quality of life and impairment, independent of level of seizure control. Integrated and comprehensive psychosocial care is required for better health and social outcomes of people with epilepsy.
Onchocerca volvulus and epilepsy: A comprehensive review using the Bradford Hill criteria for causation.
BACKGROUND: The possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association. METHODS: PubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome. RESULTS: Onchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including nodding and Nakalanga syndromes. CONCLUSION: Applying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.
Childhood determinants of past-year anxiety and depression in recently transitioned military personnel.
BACKGROUND: Anxiety and depression may hamper a smooth transition from military to civilian life and may be important predictors of longer-term health and functioning. However, it is as yet unclear to what extent they are determined by childhood factors in a recently transitioned population. METHODS: We utilised logistic regression and Generalised Structural Equation Modelling to analyse associations of ICD-10 past-year anxiety and depression with childhood trauma and disorder in a recently transitioned population using detailed interview data from the ADF (Australian Defence Force) Transition and Wellbeing Research Programme. RESULTS: Past-year anxiety (including PTSD) was prevalent (36.4%, 95% CI, 31.9-41.1) and associated with childhood anxiety (but not other types of childhood disorder), childhood interpersonal trauma (but not other childhood trauma) and adult-onset trauma. Childhood anxiety had a direct and significant association with past-year anxiety. The pathway between childhood interpersonal trauma and past-year anxiety was fully mediated by childhood anxiety. Past-year depression was less prevalent (11.3%, 95% CI, 8.7-14.5) and had no association with childhood disorder or trauma variables. LIMITATIONS: The main predictor variables utilized in this analysis were childhood experiences recalled from adulthood, thus rendering the responses vulnerable to autobiographical bias. CONCLUSIONS: Past-year anxiety was highly prevalent in the period of transition and had strong associations with childhood and military factors, suggesting predictability and potentially preventability.
Trajectories of maternal depressive symptoms from the antenatal period to 24-months postnatal follow-up: findings from the 2015 Pelotas birth cohort.
BACKGROUND: Maternal depression may be chronic and recurrent, with negative effects both on the health of mothers and children. Many studies have shown trajectories of postnatal depressive symptoms but few studies in low- and middle-income countries have evaluated the trajectories of depressive symptoms starting during pregnancy. This study aims to identify the different trajectories of depressive symptoms among mothers in the Pelotas 2015 birth cohort, from pregnancy to the second year of the child's life. METHODS: This study used data from the 2015 Pelotas Birth Cohort, a longitudinal study of all live births occurred in 2015 in Pelotas, Brazil. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Mothers who completed the EPDS on at least three follow-up visits beginning to the antenatal follow-up visit were included in the analyses. The trajectory of maternal depressive symptoms was estimated through group-based trajectory modeling. RESULTS: A total of 3040 women were included in the present analysis. We identified five groups of maternal depressive symptoms trajectories, with 23.4% of the mothers presenting persistent depressive symptoms and 3.9% showing chronic high depressive symptoms throughout the study period. The probability of having persistent depressive symptoms increased among mothers with greater socioeconomic vulnerability. CONCLUSIONS: This study shown the persistence of maternal depressive symptoms since pregnancy until 2 years postnatal. Additionally, alongside the known risk factors, pre-gestational depression and antenatal depressive symptoms are important risk factors for the persistence and severity of depressive symptoms. These findings support the need to provide mental health evaluation and care for women from pregnancy to the late postnatal period.
Female infants are more susceptible to the effects of maternal antenatal depression; findings from the Pelotas (Brazil) Birth Cohort Study.
BACKGROUND: We utilised data from the 2015 Pelotas Birth Cohort, a large prospective cohort in southern Brazil, to examine the association of moderate and severe antenatal depression with child birth outcomes and explore interactions with sociodemographic characteristics. METHODS: Data was available for n = 3046 participants and their infants. We measured antenatal depression using the Edinburgh Postnatal Depression Scale (EPDS, ≥13 for moderate and ≥17 for severe depression). Outcome measures included gestational age, birth weight, length and head circumference, using the Intergrowth-21st standards. We controlled for known confounders including obstetric risk. RESULTS: We did not find differences in childbirth outcomes by maternal depression status for participants with at least moderate depression, although there was an increased risk for female offspring to be small for gestational age (SGA, OR 2.33[1.37,3.97]). For severe depression (EPDS≥17) we found an increased risk for lower APGAR scores (OR 1.63[1.02,2.60]) and being SGA (OR 1.77[1.06,2.97], with an increased risk for female offspring in particular to be in lower weight centiles (-10.71 [-16.83,-4.60]), to be SGA (OR 3.74[1.89, 7.44]) and in the lower 10th centile for length (OR 2.19[1.25,3.84]). LIMITATIONS: include the use of a maternal report questionnaire to ascertain depressive symptoms. CONCLUSIONS: In this recent large longitudinal cohort in Brazil we did not find independent effects of depression on adverse birth outcomes or interactions with sociodemographic characteristics. We found an increased risk of being SGA for female offspring of women with moderate and severe depression, in line with other research suggesting females may be more susceptible to antenatal disturbances. FUNDING: This work was supported by the Wellcome Trust, United Kingdom (095582), the Brazilian National Research Council (CNPq) and the Coordination for the Improvement of Higher Education Personnel (CAPES). EN was supported by the UK Economic and Social Research Council GCRF Postdoctoral Fellowship (ES/P009794/1).
Timing of onset of lithium relapse prevention in bipolar disorder: evidence from randomised trials.
Lithium is widely prescribed, but the timing of key effects remains uncertain. The timing of onset of its relapse prevention effects is clarified by placebo-controlled randomised trials (3 studies, n = 1120). Lithium reduced relapse into any mood episode over the first 2 weeks of treatment (hazard ratio 0.40, 95% CI 0.16-0.97). Fewer manic relapses were evident within the first 4 weeks, however, early effects on depressive relapse were not demonstrated. There is an early onset of lithium relapse prevention effects in bipolar disorder, particularly against manic relapse. Full effects against depressive relapse may develop over a longer period.Declaration of interestM.J.T. reports personal fees from Sunovion, Otsuka, Lundbeck, outside the submitted work.
Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study.
BACKGROUND: There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent studies of SNP in patients with psychosis have mixed results, and the drug has to be administered intravenously. Glyceryl trinitrate (GTN) is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. AIMS: We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis. METHODS: This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 7. The primary outcome was cognition (Jumping to Conclusions task), secondary outcomes were symptoms (Positive and Negative Syndrome Scale (PANSS)), verbal memory (Hopkins Verbal Learning task), and mood (Bond-Lader Visual Analogue Scales). RESULTS: Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms. CONCLUSIONS: We found no indication of an effect of GTN on symptoms of psychosis or cognition.
Tamoxifen for bipolar disorder: Systematic review and meta-analysis.
BACKGROUND: Tamoxifen is an oral medication that has been proposed as a potential treatment for bipolar disorder. Tamoxifen acts to inhibit the intracellular action of protein kinase C, which is also an action of well-established treatments such as lithium and valproate. Here we aimed to identify randomised controlled trials (RCTs) of tamoxifen in the treatment of bipolar disorder and synthesise their results using meta-analysis. METHODS: RCTs were identified by searching of electronic databases and from discussion with experts in the field. Data were extracted, and meta-analyses performed in R. RESULTS: Five placebo-controlled RCTs of tamoxifen in the treatment of acute mania were identified. There were no trials in the treatment of episodes of bipolar depression, or for relapse prevention. The studies of mania treatment were of between three and six weeks duration. Tamoxifen was studied either as monotherapy (two trials) or as augmentation of lithium or valproate (three trials). Change in mania scale scores favoured tamoxifen over placebo: SMD -2.14 (95% CI -3.39 to -0.89; 4 trials), as did endpoint mania scale scores SMD 1.23 (95% CI 0.60-1.87; 5 trials). Response rates were also higher: RR 4.35 (1.99-9.50; 4 trials). Acceptability was similar to placebo: RR 1.03 (0.94-1.13; 5 trials). CONCLUSIONS: Tamoxifen appears to be a promising potential treatment for episodes of mania. Future studies could investigate its effects as an adjunct to dopamine antagonists for improved anti-manic efficacy, and establish its longer term effects on mood, particularly depression and relapse.
Characteristics of severe life events, attachment style, and depression - Using a new online approach.
OBJECTIVES: Severe life events are established as provoking agents for depression in combination with vulnerability factors. Identifying features of severe events improves the prediction of disorder but are rarely utilized, mainly because life event research is increasingly dominated by self-report checklists with no capacity for inferring such characteristics. This paper investigates the association of severe life events' features with depression and insecure attachment styles using a new online measure of life events in a clinical and control sample. METHODS: A total of 202 participants (75 clinical and 127 matched control participants), taken from an earlier national Depression Case Control genetic study and followed up after 12 years, completed the Computerised Life Events Assessment Record to assess characteristics of life events, the Vulnerable Attachment Style Questionnaire to measure attachment insecurity, and the General Health Questionnaire to measure depression. RESULTS: The clinical group had higher self-reported depression, severe life events, and insecure attachment style. They also reported more loss, danger, humiliation, and trauma severe events. Intra-respondent analysis showed individuals experiencing these types of events were more likely to report depression. Insecure attachment style and severe life events were both significantly related to recent depression and history of depressive disorder. Anxious attachment style was significantly related to relationship events and bereavements, as well as severe loss or humiliation events, whereas avoidant style was not. CONCLUSIONS: Identifying salient features of severe life events improves associations with depression and insecure attachment style. Utilizing a new online approach can aid research and clinical approaches for depression at low cost. PRACTITIONER POINTS: Salient features of severe life events (e.g., loss, humiliation) give insight into the potential impact on attachment vulnerability and depression. Clinicians and researchers can use online methods to economically gain detailed life event information needed for clinical formulation and valid data on stressors. The self-reported scale for recent depression is only a proxy measure of clinical disorder, but the clinical group selection is a more robust criterion for depression history.
Is paliperidone palmitate more effective than other long-acting injectable antipsychotics?
BACKGROUND: Paliperidone palmitate is one of the most widely prescribed long-acting injectable (LAI) antipsychotics in the UK. However, it is relatively expensive and there are few data comparing its effectiveness to that of other LAI antipsychotics. We sought to address this issue by analyzing a large anonymized electronic health record (EHR) dataset from patients treated with LAI antipsychotics. METHODS: EHR data were obtained from 1281 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who started treatment with a LAI antipsychotic between 1 April 2011 and 31 January 2015. The number of days spent as a psychiatric inpatient and the number of admissions to a psychiatric hospital were analyzed in each of the 3 years before and after LAI prescription. RESULTS: Patients treated with paliperidone palmitate (n = 430; 33.6%) had a greater number of inpatient days and a greater number of admissions in the year prior to treatment than those treated with other LAI antipsychotics. Nevertheless, in the 3 years after initiation there were no significant differences between paliperidone and the other LAI antipsychotics in the number of days as an inpatient (B coefficient 5.4 days, 95% confidence interval (CI) -57.3 to 68.2, p = 0.86) or number of hospital admissions (Incidence rate ratio 1.07, 95% CI 0.62 to 1.83, p = 0.82). CONCLUSION: Paliperidone palmitate was more likely to be prescribed in patients with more frequent and lengthy hospital admissions prior to initiation. However, the absence of differences in outcomes after initiation indicates that paliperidone palmitate was not more effective than other cheaper LAI antipsychotics.
Nature of Glutamate Alterations in Schizophrenia: A Meta-analysis of Proton Magnetic Resonance Spectroscopy Studies.
IMPORTANCE: Alterations in glutamatergic neurotransmission may be fundamental to the pathophysiology of schizophrenia, and the glutamatergic system is a target for novel therapeutic interventions in the disorder. OBJECTIVE: To investigate the nature of brain glutamate alterations in schizophrenia by conducting a meta-analysis of glutamate proton magnetic resonance (MRS) spectroscopy studies. DATA SOURCES: The MEDLINE database was searched for studies published from January 1, 1980, to April 1, 2015. Search terms included magnetic resonance spectroscopy, schizophrenia, psychosis, clinical or genetic high risk, and schizoaffective. Inclusion criteria were single voxel 1H-MRS studies reporting glutamate, glutamine or Glx values for a patient or risk group in comparison to a healthy volunteer group. STUDY SELECTION: Fifty-nine studies were identified, which included 1686 patients and 1451 healthy individuals serving as controls. DATA EXTRACTION AND SYNTHESIS: A random-effects, inverse-weighted variance model was used to calculate the pooled effect size. Mean values were extracted and verified independently. Effect sizes were determined for glutamate, glutamine, and Glx in brain regions that had been examined in at least 3 different studies. A secondary analysis grouped studies into those examining patients at different stages of illness (high risk, first-episode psychosis, or chronic schizophrenia). Effects of age, antipsychotic dose, and symptom severity were determined using meta-regression. RESULTS: In schizophrenia, there were significant elevations in glutamate in the basal ganglia (Hedges g = 0.63; 95% CI, 0.15-1.11), glutamine in the thalamus (g = 0.56; 95% CI, 0.02-1.09), and Glx in the basal ganglia (g = 0.39; 95% CI, 0.09-0.70) and medial temporal lobe (g = 0.32; 95% CI, 0.12-0.52). No region showed a reduction in glutamate metabolites in schizophrenia. Secondary analyses revealed that elevated medial frontal Glx levels were evident in individuals at high risk for schizophrenia (g = 0.26; 95% CI, 0.05-0.46) but not in those with first-episode psychosis or chronic schizophrenia, whereas elevated Glx in the medial temporal lobe was seen with chronic schizophrenia (g = 0.40; 95% CI, 0.08-0.71) but not in the high-risk or first-episode groups. Meta-regression found no association with age, symptom severity, or antipsychotic dose. CONCLUSIONS AND RELEVANCE: Schizophrenia is associated with elevations in glutamatergic metabolites across several brain regions. This finding supports the hypothesis that schizophrenia is associated with excess glutamatergic neurotransmission in several limbic areas and further indicates that compounds that reduce glutamatergic transmission may have therapeutic potential.
Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia: A Systematic Review and Meta-analysis.
Importance: Ketamine hydrochloride is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like or psychotomimetic symptoms. Despite this risk, the consistency and magnitude of symptoms induced by ketamine or what factors are associated with these symptoms remain unknown. Objective: To conduct a meta-analysis of the psychopathological outcomes associated with ketamine in healthy volunteers and patients with schizophrenia and the experimental factors associated with these outcomes. Data Sources: MEDLINE, Embase, and PsychINFO databases were searched for within-participant, placebo-controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or the Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or patients with schizophrenia. Study Selection: Of 8464 citations retrieved, 36 studies involving healthy participants were included. Inclusion criteria were studies (1) including healthy participants; (2) reporting symptoms occurring in response to acute administration of subanesthetic doses of ketamine (racemic ketamine, s-ketamine, r-ketamine) intravenously; (3) containing a placebo condition with a within-subject, crossover design; (4) measuring total positive or negative symptoms using BPRS or PANSS; and (5) providing data allowing the estimation of the mean difference and deviation between the ketamine and placebo condition. Data Extraction and Synthesis: Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive, and negative BPRS and PANSS scores were extracted. Subgroup analyses were conducted examining the effects of blinding status, ketamine preparation, infusion method, and time between ketamine and placebo conditions. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Main Outcomes and Measures: Standardized mean differences (SMDs) were used as effect sizes for individual studies. Standardized mean differences between ketamine and placebo conditions were calculated for total, positive, and negative BPRS and PANSS scores. Results: The overall sample included 725 healthy volunteers (mean [SD] age, 28.3 [3.6] years; 533 [73.6%] male) exposed to the ketamine and placebo conditions. Racemic ketamine or S-ketamine was associated with a statistically significant increase in transient psychopathology in healthy participants for total (SMD = 1.50 [95% CI, 1.23-1.77]; P < .001), positive (SMD = 1.55 [95% CI, 1.29-1.81]; P < .001), and negative (SMD = 1.16 [95% CI, 0.96-1.35]; P < .001) symptom ratings relative to the placebo condition. The effect size for this association was significantly greater for positive than negative symptoms of psychosis (estimate, 0.36 [95% CI, 0.12-0.61]; P = .004). There was significant inconsistency in outcomes between studies (I2 range, 77%-83%). Bolus followed by constant infusion increased ketamine's association with positive symptoms relative to infusion alone (effect size, 1.63 [95% CI, 1.36-1.90] vs 0.84 [95% CI, 0.35-1.33]; P = .006). Single-day study design increased ketamine's ability to generate total symptoms (effect size, 2.29 [95% CI, 1.69-2.89] vs 1.39 [95% CI, 1.12-1.66]; P = .007), but age and sex did not moderate outcomes. Insufficient studies were available for meta-analysis of studies in schizophrenia. Of these studies, 2 found a statistically significant increase in symptoms with ketamine administration in total and positive symptoms. Only 1 study found an increase in negative symptom severity with ketamine. Conclusions and Relevance: This study found that acute ketamine administration was associated with schizophrenia-like or psychotomimetic symptoms with large effect sizes, but there was a greater increase in positive than negative symptoms and when a bolus was used. These findings suggest that bolus doses should be avoided in the therapeutic use of ketamine to minimize the risk of inducing transient positive (psychotic) symptoms.
BFKL approach and 2→5 maximally helicity violating amplitude in N=4 super-Yang-Mills theory
We study maximally helicity violating amplitude for the 2→5 scattering in the multi-Regge kinematics. The Mandelstam cut correction to the Bern-Dixon-Smirnov amplitude is calculated in the leading logarithmic approximation and the corresponding remainder function is given to any loop order in a closed integral form. We show that the leading logarithmic approximation remainder function at two loops for 2→5 amplitude can be written as a sum of two 2→4 remainder functions due to recursive properties of the leading order impact factors. We also make some generalizations for the maximally helicity violating amplitudes with more external particles. The results of the present study are in agreement with the all leg two-loop symbol derived by Caron-Huot as shown in a parallel paper of one of the authors with collaborators. © 2012 American Physical Society.
Multiparticle production in the mean field approximation of high density QCD
The generating functional is suggested for multiparticle generation processes. In mean field approximation of high density QCD two equations for new generating functional are derived: linear functional equation for an arbitrary initial condition and non-linear one for a specific initial condition. The non-linear equation has the form of Kovchegov-Levin equation for diffraction production and gives its generalization on the processes with fixed multiplicities of produced particles. © 2008 Elsevier B.V. All rights reserved.
On the nuclear modification factor at RHIC and LHC
We show that pQCD factorization incorporated with pre-hadronization energy-loss effect naturally leads to flatness of the nuclear modification factor RAA for produced hadrons at high transverse momentum pT. We consider two possible scenarios for the pre-hadronization: In scenario 1, the produced gluon propagates through dense QCD medium and loses energy. In scenario 2, all gluons first decay to quark-antiquark pairs and then each pair loses energy as propagating through the medium. We show that the estimates of the energy-loss in these two different models lead to very close values and is able to explain the suppression of high-pT hadrons in nucleus-nucleus collisions at RHIC. We show that the onset of the flatness of RAA for the produced hadron in central collisions at midrapidity is about pT≈15 and 25 GeV at RHIC and the LHC energies, respectively. We show that the smallness (RAA<0.5) and the high-pT flatness of RAA obtained from the kT factorization supplemented with the Balitsky-Kovchegov (BK) equation is rather generic and it does not strongly depend on the details of the BK solutions. We show that energy-loss effect reduces the nuclear modification factor obtained from the kT factorization about 30-50% at moderate pT. © 2011 Elsevier B.V.
A QCD motivated model for soft processes
In this talk we give a brief description of a QCD motivated model for both hard and soft interactions at high energies. In this model the long distance behaviour of the scattering amplitude is determined by the dipole scattering amplitude in the saturation domain. © 2009 American Institute of Physics.