Objective: We previously reported that dual injections of lipopolysaccharide (LPS) in mice constitute a valuable tool for investigating the contribution of inflammation to psychotic disorders. The present study investigated how immune activation affects the kynurenine pathway and rat behaviour of relevance for psychotic disorders.
Methods: Male Sprague Dawley rats were treated with either dual injections of LPS (0.5 mg/kg + 0.5 mg/kg, i.p.) or dual injections of saline. Twenty-four hours after the second injection, behavioural tests were carried out, including locomotor activity test, fear conditioning test, spontaneous alternation Y-maze test, and novel object recognition test. In a separate batch of animals, in vivo striatal microdialysis was performed, and tryptophan, kynurenine, quinolinic acid, and kynurenic acid (KYNA) in the dialysate were measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
Results: Dual-LPS treatment decreased spontaneous locomotion, exaggerated d-amphetamine-induced locomotor activity, and impaired recognition memory in male Sprague-Dawley rats. In vivo microdialysis showed that dual-LPS treatment elicited metabolic disturbances in the kynurenine pathway with increased extracellular levels of kynurenine and KYNA in the striatum.
Conclusion: The present study further supports the feasibility of using the dual-LPS model to investigate inflammation-related psychotic disorders and cognitive impairments.
Stress can have a significant impact on the daily lives of individuals and can increase vulnerability to a number of medical conditions. This study aims to estimate the ratio of male to female participants in acute social stress research in healthy individuals. We examined original research articles published over the last 20 years. Each article was screened to determine the total number of female and male participants. We extracted data from 124 articles involving a total of 9539 participants. A total of 4221 (44.2%) participants were female, 5056 (53.0%) were male and 262 (2.7%) were unreported. Articles incorporating only females were significantly underrepresented compared to articles incorporating only males. Forty articles (63.5%) which presented data from both females and males, failed to analyse and interpret the results by sex, a significant methodological limitation. In conclusion, in the literature published over the last 20 years, female participants are significantly underrepresented. In the studies where females are represented, severe methodological limitations are apparent. Researchers should be conscious of sexual dimorphism, menstrual phase and use of hormonal contraception, which may impact the interpretation of their results.
Objective: Although yoga shows some promise as an intervention for post-traumatic stress disorder (PTSD), little is known about how yoga reduces PTSD symptoms. The current study hypothesised that aspects of interoceptive awareness would mediate the effect of a yoga intervention on PTSD symptoms.
Methods: We used data from our recently completed randomised controlled trial of a 16-week holistic yoga programme for veterans and civilians diagnosed with PTSD (n = 141) that offered weekly 90-minute sessions. We conducted a mediation analysis using interoceptive awareness and other variables that were associated with PTSD symptom reduction at mid-treatment and treatment end.
Results: Although measures of anxiety, interoceptive awareness, and spirituality were identified in individual mediator models, they were no longer found to be significant mediators when examined jointly in multiple mediator models. When examining the multiple mediator models, the strongest mediator of the yoga intervention on PTSD symptoms was mental well-being at mid-treatment and stigma at the treatment end. The total effect of yoga on CAPS and PCL at the treatment end mediated by stigma was 37.1% (-1.81/-4.88) and 33.6% (-1.91/-5.68), respectively.
Conclusion: Investigation of mental well-being and mental illness stigma as potential mediators is warranted in future studies of yoga as a treatment for PTSD as they may prove to be important foci for yoga interventions.
Objective: The aim of this study was to examine the reliability and validity of the Male Post-coital Affect Scale (MPAS), which was developed to assess positive post-coital feelings in men.
Methods: After a pilot study, we validated our scale on a sample of American heterosexual men, who answered our questionnaire on the internet through Amazon Mechanical Turk. We tested the reliability using internal consistency. The validity was examined by assessing content, face and construct validity by testing the association between our scale, the Experience in Close Relationships Scale and other instruments.
Results: A total of 484 volunteers were included in the study. Cronbach's α for the scale was 0.83. Our scale was negatively correlated with attachment avoidance, r(482) = -0.36, p < 0.001) and Perceived Stress Scale, r(482) = -0.18, p < 0.001, and positively correlated with sexual satisfaction, r(482) = 0.18, p < 0.001.
Conclusion: The MPAS is a reliable and valid tool to assess positive post-coital feelings in men.
Objectives: Administration of antidepressant drugs - principally selective serotonin reuptake inhibitors (SSRIs) - may induce clinically significant 'apathy' which can affect treatment outcomes adversely. We aimed to review all relevant previous reports.
Methods: We performed a PUBMED search of English-language studies, combining terms concerning psychopathology (e.g. apathy) and classes of antidepressants (e.g. SSRI).
Results: According to certain inclusion (e.g. use of DSM/ICD diagnostic criteria) and exclusion (e.g. presence of a clinical condition that may induce apathy) criteria, 50 articles were eligible for review. Together, they suggest that administration of antidepressants - usually SSRIs - can induce an apathy syndrome or emotional blunting, i.e. a decrease in emotional responsiveness, to circumstances which would have triggered intense mood reactions prior to pharmacotherapy. The reported prevalence of antidepressant-induced apathy ranges between 5.8 and 50%, and for SSRIs ranges between 20 and 92%. Antidepressant-induced apathy emerges independently of diagnosis, age, and treatment outcome and appears dose-dependent and reversible. The main treatment strategy is dose reduction, though some data suggest the usefulness of treatment with olanzapine, bupropion, agomelatine or amisulpride, or the methylphenidate-modafinil-olanzapine combination.
Conclusion: Antidepressant-induced apathy needs careful clinical attention. Further systematic research is needed to investigate the prevalence, course, aetiology, and treatment of this important clinical condition.
Objective.: Anxiety can interfere with attention and working memory, which are components that affect learning. Statistical models have been designed to study learning, such as the Bayesian Learning Model, which takes into account prior possibilities and behaviours to determine how much of a new behaviour is determined by learning instead of chance. However, the neurobiological basis underlying how anxiety interferes with learning is not yet known. Accordingly, we aimed to use neuroimaging techniques and apply a Bayesian Learning Model to study learning in individuals with generalised anxiety disorder (GAD).
Methods.: Participants were 25 controls and 14 individuals with GAD and comorbid disorders. During fMRI, participants completed a shape-button association learning and reversal task. Using a flexible factorial analysis in SPM, activation in the dorsolateral prefrontal cortex, basal ganglia, and hippocampus was compared between groups during first reversal. Beta values from the peak of these regions were extracted for all learning conditions and submitted to repeated measures analyses in SPSS.
Results.: Individuals with GAD showed less activation in the basal ganglia and the hippocampus only in the first reversal compared with controls. This difference was not present in the initial learning and second reversal.
Conclusion.: Given that the basal ganglia is associated with initial learning, and the hippocampus with transfer of knowledge from short- to long-term memory, our results suggest that GAD may engage these regions to a lesser extent during early accommodation or consolidation of learning, but have no longer term effects in brain activation patterns during subsequent learning.
Cognitive consequences of hormonal contraceptives (HCs) are largely underexplored, despite the popularity of use. This study investigates the association between perseverance during cognitively challenging tasks and the use of HCs among Danish women. We hypothesised that women using HCs show decreased perseverance across tasks compared to their naturally cycling counterparts. We further hypothesised that HC using women would show decreased performance as a measure of accuracy (i.e. more incorrect answers) compared to naturally cycling women. The study used a cross-sectional repeated measures design, consisting of a Danish version of the Anagram Persistence Task and the Hagen Matrices Test, followed by an extensive survey documenting menstrual and HC history for each participant. The study was conducted online. Data processing was conducted on data from 129 participants. The former hypothesis was analysed through multilevel regression with a nested random effects structure on log-transformed data. The latter hypothesis was analysed through a multilevel generalised linear model with a nested random effects structure using the binomial family. No support was found for either of the hypotheses.
Objective: In sub-Saharan Africa, there are no validated screening tools for delirium in older adults, despite the known vulnerability of older people to delirium and the associated adverse outcomes. This study aimed to assess the effectiveness of a brief smartphone-based assessment of arousal and attention (DelApp) in the identification of delirium amongst older adults admitted to the medical department of a tertiary referral hospital in Northern Tanzania.
Method: Consecutive admissions were screened using the DelApp during a larger study of delirium prevalence and risk factors. All participants subsequently underwent detailed clinical assessment for delirium by a research doctor. Delirium and dementia were identified against DSM-5 criteria by consensus.
Results: Complete data for 66 individuals were collected of whom 15 (22.7%) had delirium, 24.5% had dementia without delirium, and 10.6% had delirium superimposed on dementia. Sensitivity and specificity of the DelApp for delirium were 0.87 and 0.62, respectively (AUROC 0.77) and 0.88 and 0.73 (AUROC 0.85) for major cognitive impairment (dementia and delirium combined). Lower DelApp score was associated with age, significant visual impairment (<6/60 acuity), illness severity, reduced arousal and DSM-5 delirium on univariable analysis, but on multivariable logistic regression only arousal remained significant.
Conclusion: In this setting, the DelApp performed well in identifying delirium and major cognitive impairment but did not differentiate delirium and dementia. Performance is likely to have been affected by confounders including uncorrected visual impairment and reduced level of arousal without delirium. Negative predictive value was nevertheless high, indicating excellent 'rule out' value in this setting.
Introduction: Cognitive dysfunction in schizophrenia may be assessed by measuring within-individual variability (WIV) in performance across a range of cognitive tests. Previous studies have found increased WIV in people with schizophrenia, but no studies have been conducted in low- to middle-income countries where the different sociocultural context may affect WIV. We sought to address this gap by exploring the relationship between WIV and a range of clinical and demographic variables in a large study of people with schizophrenia and matched controls in South Africa.
Methods: 544 people with schizophrenia and 861 matched controls completed an adapted version of The University of Pennsylvania Computerized Neurocognitive Battery (PennCNB). Demographic and clinical information was collected using the Structured Clinical Interview for DSM-IV Diagnoses. Across-task WIV for performance speed and accuracy on the PennCNB was calculated. Multivariate linear regression was used to assess the relationship between WIV and a diagnosis of schizophrenia in the whole sample, and WIV and selected demographic and clinical variables in people with schizophrenia.
Results: Increased WIV of performance speed across cognitive tests was significantly associated with a diagnosis of schizophrenia. In people with schizophrenia, increased speed WIV was associated with older age, a lower level of education and a lower score on the Global Assessment of Functioning scale. Increased accuracy WIV was significantly associated with a younger age in people with schizophrenia.
Conclusions: Measurements of WIV of performance speed can add to the knowledge gained from studies of cognitive dysfunction in schizophrenia in resource-limited settings.
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