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This study examined the associations between accelerometer-derived sedentary time (ST), lower intensity physical activity (LPA), higher intensity physical activity (HPA) and the incidence of depressive symptoms over 4 years of follow-up.
Methods
We included 2082 participants from The Maastricht Study (mean ± s.d. age 60.1 ± 8.0 years; 51.2% men) without depressive symptoms at baseline. ST, LPA and HPA were measured with the ActivPAL3 activity monitor. Depressive symptoms were measured annually over 4 years of follow-up with the 9-item Patient Health Questionnaire (PHQ-9). Cox regression analysis was performed to examine the associations between ST, LPA, HPA and incident depressive symptoms (PHQ-9 ⩾ 10). Analyses were adjusted for total waking time per day, age, sex, education level, type 2 diabetes mellitus, body mass index, total energy intake, smoking status and alcohol use.
Results
During 7812.81 person-years of follow-up, 203 (9.8%) participants developed incident depressive symptoms. No significant associations [Hazard Ratio (95% confidence interval)] were found between sex-specific tertiles of ST (lowest v. highest tertile) [1.13 (0.76–1.66], or HPA (highest v. lowest tertile) [1.14 (0.78–1.69)] and incident depressive symptoms. LPA (highest v. lowest tertile) was statistically significantly associated with incident depressive symptoms in women [1.98 (1.19–3.29)], but not in men (p-interaction <0.01).
Conclusions
We did not observe an association between ST or HPA and incident depressive symptoms. Lower levels of daily LPA were associated with an increased risk of incident depressive symptoms in women. Future research is needed to investigate accelerometer-derived measured physical activity and ST with incident depressive symptoms, preferably stratified by sex.
Eye-tracking-based attentional research implicates sustained attention to threat in posttraumatic stress disorder (PTSD). However, most of this research employed small stimuli set-sizes, small samples that did not include both trauma-exposed healthy participants and non-trauma-exposed participants, and generally failed to report the reliability of used tasks and attention indices. Here, using an established eye-tracking paradigm, we explore attention processes to different negatively-valenced cues in PTSD while addressing these limitations.
Methods
PTSD patients (n = 37), trauma-exposed healthy controls (TEHC; n = 34), and healthy controls (HC; n = 30) freely viewed three blocks of 30 different matrices of faces, each presented for 6 s. Each block consisted of matrices depicting eight negatively-valenced faces (anger, fear, or sadness) and eight neutral faces. Gaze patterns on negative and neural areas of interest were compared. Internal consistency and test-retest reliability were evaluated for the entire sample and within groups.
Results
The two trauma-exposed groups dwelled longer on negatively-valenced faces over neutral faces, while HC participants showed the opposite pattern. This attentional bias was more prominent in the PTSD than the TEHC group. Similar results emerged for first-fixation dwell time, but with no differences between the two trauma-exposed groups. No group differences emerged for first-fixation latency or location. Internal consistency and 1-week test-retest reliability were adequate, across and within groups.
Conclusions
Sustained attention on negatively-valenced stimuli emerges as a potential target for therapeutic intervention in PTSD designed to divert attention away from negatively-valenced stimuli and toward neutral ones.
High job demands, low job control, and their combination (job strain) may increase workers' risk of depression. Previous research is limited by small populations, not controlling for previous depression, and relying on the same informant for reporting exposure and outcome. This study aims to examine the relationship between objectively measured workplace factors and the risk of developing clinical depression among the Swedish working population while controlling for previous psychiatric diagnoses and sociodemographic factors.
Methods
Control, demands, and job strain were measured using the Swedish Job Exposure Matrix (JEM) measuring psychosocial workload linked to around 3 million individuals based on their occupational titles in 2005. Cox regression models were built to estimate associations between these factors and diagnoses of depression recorded in patient registers.
Results
Lower job control was associated with an increased risk of developing depression (HR 1.43, 95% CI 1.39–1.48 and HR 1.27, 95% CI 1.24–1.30 for men and women with the lowest control, respectively), and this showed a dose–response relationship among men. Having high job demands was associated with a slight decrease in depression risk for men and women. High strain and passive jobs (both low control jobs) were associated with an increased risk of depression among men, and passive jobs were associated with an increased risk among women.
Conclusion
High job control appears important for reducing the risk of developing depression even when accounting for previous psychiatric diagnoses and sociodemographic factors. This is an important finding concerning strategies to improve occupational and in turn mental health.
Posttraumatic stress disorder (PTSD) is highly prevalent within prison settings, yet is often unidentified and undertreated. Complex PTSD (CPTSD) has been recently formally recognised in the International Classification of Diseases 11th revision (ICD-11) diagnostic framework but has never been explored in prison settings. We aimed to establish the prevalence of ICD-11 PTSD and CPTSD in a UK prison sample using a validated instrument (the International Trauma Questionnaire). We also explored the associations of these two diagnoses with their traumatic antecedents and psychiatric comorbidities.
Method
Randomly selected male, sentenced prisoners in a large medium-security prison in south London (N = 221) took part in a clinical interview which assessed PTSD, CPTSD, trauma histories, and comorbid disorders. Multinomial logistic regression was performed to examine differences between those with PTSD or CPTSD, and those without symptoms.
Results
A total of 7.7% (95% CI 4.5–12) of the male sentenced prisoners met diagnostic criteria for ICD-11 PTSD and 16.7% (95% CI 12.1–22.3) for CPTSD. A diagnosis of PTSD was associated with more recent traumatic exposure, comorbid generalised anxiety disorder, alcohol dependence, and Cluster B personality disorder. A diagnosis of CPTSD was associated with complex trauma exposure antecedents (developmental, interpersonal, repeated, or multiple forms), and comorbid with anxiety, depression, substance misuse, psychosis, and ADHD.
Conclusions
This study confirms that CPTSD is a very common and comorbid condition in male prisoners. There is an urgent need to develop trauma-informed care in prisons.
Risk is an essential trait of most daily decisions. Our behaviour when faced with risks involves evaluation of many factors including the outcome probabilities, the valence (gains or losses) and past experiences. Several psychiatric disorders belonging to distinct diagnostic categories, including pathological gambling and addiction, show pathological risk-taking and implicate abnormal dopaminergic, opioidergic and serotonergic neurotransmission. In this study, we adopted a transdiagnostic approach to delineate the neurochemical substrates of decision making under risk.
Methods
We recruited 39 participants, including 17 healthy controls, 15 patients with pathological gambling and seven binge eating disorder patients, who completed an anticipatory risk-taking task. Separately, participants underwent positron emission tomography (PET) imaging with three ligands, [18F]fluorodopa (FDOPA), [11C]MADAM and [11C]carfentanil to assess presynaptic dopamine synthesis capacity and serotonin transporter and mu-opioid receptor binding respectively.
Results
Risk-taking behaviour when faced with gains positively correlated with dorsal cingulate [11C]carfentanil binding and risk-taking to losses positively correlated with [11C]MADAM binding in the caudate and putamen across all subjects.
Conclusions
We show distinct neurochemical substrates underlying risk-taking with the dorsal cingulate cortex mu-opioid receptor binding associated with rewards and dorsal striatal serotonin transporter binding associated with losses. Risk-taking and goal-directed control appear to dissociate between dorsal and ventral fronto-striatal systems. Our findings thus highlight the potential role of pharmacological agents or neuromodulation on modifying valence-specific risk-taking biases.
Borderline personality disorder (BPD) is characterized by instability in affective regulation that can result in a loss of cognitive control. Triggers may be neuronal responses to emotionally valenced context and/or stimuli. ‘Neuronal priming’ indexes the familiarity of stimuli, and may capture the obligatory effects of affective valence on the brain's processing system, and how such valence mediates responses to the repeated presentation of stimuli. We investigated the effects of affective valence of stimuli on neuronal priming (i.e. changes in activation to repeated presentation of stimuli), and if these effects distinguished BPD patients from controls.
Methods
Forty BPD subjects and 25 control subjects (age range: 18–44) participated in an episodic memory task during fMRI. Stimuli were presented in alternating epochs of encoding (six images of positive, negative, and neutral valence) and recognition (six images for ‘old’ v. ‘new’ recognition). Analyses focused on inter-group differences in the change in activation to repeated stimuli (presented during Encoding and Recognition).
Results
Relative to controls, BPD showed greater priming (generally greater decrease from encoding to recognition) for negatively valenced stimuli. Conversely, BPD showed less priming for positively valenced stimuli (generally greater increase from encoding to recognition).
Conclusion
Plausibly, the relative familiarity of negative valence to patients with BPD exerts an influence on obligatory responses to repeated stimuli leading to repetition priming of neuronal profiles. The specific effects of valence on memory and/or attention, and consequently on priming can inform the understanding of mechanisms of altered salience for affective stimuli in BPD.
Depression and overweight are each associated with abnormal immune system activation. We sought to disentangle the extent to which depressive symptoms and overweight status contributed to increased inflammation and abnormal cortisol levels.
Methods
Participants were recruited through the Wellcome Trust NIMA Consortium. The sample of 216 participants consisted of 69 overweight patients with depression; 35 overweight controls; 55 normal-weight patients with depression and 57 normal-weight controls. Peripheral inflammation was measured as high-sensitivity C-Reactive Protein (hsCRP) in serum. Salivary cortisol was collected at multiple points throughout the day to measure cortisol awakening response and diurnal cortisol levels.
Results
Overweight patients with depression had significantly higher hsCRP compared with overweight controls (p = 0.042), normal-weight depressed patients (p < 0.001) and normal-weight controls (p < 0.001), after controlling for age and gender. Multivariable logistic regression showed that comorbid depression and overweight significantly increased the risk of clinically elevated hsCRP levels ⩾3 mg/L (OR 2.44, 1.28–3.94). In a separate multivariable logistic regression model, overweight status contributed most to the risk of having hsCRP levels ⩾3 mg/L (OR 1.52, 0.7–2.41), while depression also contributed a significant risk (OR 1.09, 0.27–2). There were no significant differences between groups in cortisol awakening response and diurnal cortisol levels.
Conclusion
Comorbid depression and overweight status are associated with increased hsCRP, and the coexistence of these conditions amplified the risk of clinically elevated hsCRP levels. Overweight status contributed most to the risk of clinically elevated hsCRP levels, but depression also contributed to a significant risk. We observed no differences in cortisol levels between groups.
The aim of this study was to examine whether exposure to previous traumatic events is a risk factor for stress reactions during this pandemic. Capitalizing on a 29-year longitudinal study of Israeli ex-prisoners of war (ex-POWs) and combat veterans, we examined whether captivity is a risk factor for fear of coronavirus disease 2019 (COVID-19) and COVID-19-induced acute stress disorder (COVID-19 ASD) beyond the effects of combat exposure and other stressful life events. In addition, we examined the contribution of captivity experiences (severity of captivity, experience of solitary confinement, and suffering during captivity) and veterans' appraisal of the impact of their war-related experiences on adjustment to the current quarantine and isolation to fear of COVID-19 and COVID-19 ASD.
Methods
One-hundred-and-twenty Israeli ex-POWs from 1973 Yom Kippur War and 65 matched controls (combat veterans from the same war) filled out self-report questionnaires 18 (T1), 35 (T2), 42 (T3), and 47 (T4) years after the war.
Results
Findings revealed that although ex-POWs and controls did not differ in their level of exposure to COVID-19, ex-POWS reported higher levels of fear of COVID-19 and COVID-19 ASD than controls. Suffering during captivity, measured at 1991, and participants' appraisal of the extent to which their war-related experiences affected adjustment to COVID-19 were significantly associated with fear of COVID-19 and COVID-19 ASD.
Conclusions
The findings of the study demonstrate the long-term effects of exposure to traumatic experiences (captivity) during young adulthood on adjustment to an unrelated collective stress, such as COVID-19, 40 years later.
Cognitive mechanisms that characterize or precede depressive symptoms are poorly understood. We investigated cross-sectional and longitudinal associations between risk taking to obtain reward and adolescent depressive symptoms in a large prospective cohort, using the Cambridge Gambling Task (CGT). We also explored sex differences.
Methods
The Millennium Cohort Study (MCS) is an ongoing UK study, following the lives of 19 000 individuals born 2000/02. The CGT was completed at ages 11 (n = 12 355) and 14 (n = 10 578). Our main exposure was the proportion of points gambled, when the odds of winning were above chance (risk-taking to obtain reward). Outcomes were emotional symptoms (Strengths and Difficulties Questionnaire, SDQ) at age 11 and depressive symptoms (short Mood and Feelings Questionnaire, sMFQ) at age 14. We calculated cross-sectional and longitudinal associations, using linear regressions.
Results
In univariable models, there was evidence of cross-sectional associations between risk-taking and SDQ/sMFQ scores, but these associations disappeared after we adjusted for sex. Longitudinally, there was weak evidence of an association between risk-taking and depressive symptoms in females only [a 20-point increase in risk-taking at age 11 was associated with a reduction of 0.31 sMFQ points at age 14 (95% CI −0.60 to −0.02)]. At both time-points, females were less risk-taking than males.
Conclusions
We found no convincing evidence of a relationship between risk-taking to obtain reward and depressive symptoms. There were large sex differences in risk-taking, but these do not appear to contribute to the female preponderance of depressive symptoms in adolescence.
Animal studies have shown beneficial effects of probiotic supplementation on the hippocampus (HC) and cognitive performance. Evidence in humans is scarce. It was hypothesised that probiotic supplementation is associated with enhanced hippocampal (HC) regional grey matter volume (rGMV), as well as HC functional connectivity (FC). Relatedly improvements in mnestic and navigational performance, or emotional well-being, were expected to be observed in healthy human volunteers.
Methods
A randomised-controlled, double-blind trial (RCT) was conducted in N = 59 volunteers (age Mean = 27.1, s.d. = 6.7), applying a multi-strain probiotic (Vivomixx®) v. non-probiotic milk-powder placebo, each with 4.4 g/day, for 4 weeks. Volumetric data was extracted from 3T structural magnetic resonance images of total HC and -subfields. Voxel-based morphometry (VBM) and FreeSurfer-based analyses were performed. Potential neuroplastic change beyond HC was explored using whole-brain-VBM for white- and GMV. Seed-based FC was calculated based on HC. Cognitive tests included visual, map-based, object-location, and verbal memory, and spatial navigation. Mental health status (stress, anxiety, depression, and emotion-regulation) was assessed using self-reports.
Results
There were no changes in HC-total, -subfield GMV, or FC, through probiotics. VBM revealed no changes at a whole-brain-level. There were no effects on cognitive performance or mental health. Evidence in favor of the null-hypothesis, using Bayesian statistics, was consistent.
Conclusions
The applied multi-strain probiotic did not elicit any effects concerning hippocampal structural plasticity, cognition, or mental well-being in young, healthy adults. For future studies, longer application/observation RCTs, perhaps in stressed, otherwise psychologically/ cognitively vulnerable, or ageing groups, with well-founded strain selection and investigation of mechanism, are advised.
According to the cognitive neuropsychological model, antidepressants reduce symptoms of depression and anxiety by increasing positive relative to negative information processing. Most studies of whether antidepressants alter emotional processing use small samples of healthy individuals, which lead to low statistical power and selection bias and are difficult to generalise to clinical practice. We tested whether the selective serotonin reuptake inhibitor (SSRI) sertraline altered recall of positive and negative information in a large randomised controlled trial (RCT) of patients with depressive symptoms recruited from primary care.
Methods
The PANDA trial was a pragmatic multicentre double-blind RCT comparing sertraline with placebo. Memory for personality descriptors was tested at baseline and 2 and 6 weeks after randomisation using a computerised emotional categorisation task followed by a free recall. We measured the number of positive and negative words correctly recalled (hits). Poisson mixed models were used to analyse longitudinal associations between treatment allocation and hits.
Results
A total of 576 participants (88% of those randomised) completed the recall task at 2 and 6 weeks. We found no evidence that positive or negative hits differed according to treatment allocation at 2 or 6 weeks (adjusted positive hits ratio = 0.97, 95% CI 0.90–1.05, p = 0.52; adjusted negative hits ratio = 0.99, 95% CI 0.90–1.08, p = 0.76).
Conclusions
In the largest individual placebo-controlled trial of an antidepressant not funded by the pharmaceutical industry, we found no evidence that sertraline altered positive or negative recall early in treatment. These findings challenge some assumptions of the cognitive neuropsychological model of antidepressant action.
Lemborexant has demonstrated statistically significant improvements in sleep onset and sleep maintenance compared with placebo and zolpidem tartrate extended release, measured both objectively using polysomnography and subjectively using sleep diaries, in the phase 3 clinical trial SUNRISE 1. This study evaluated the cost-effectiveness of lemborexant compared with suvorexant, zolpidem immediate release (IR), and untreated insomnia.
Methods
A decision-tree model was developed for falls, motor vehicle collisions, and workplace accidents associated with insomnia and insomnia treatments from a Japanese healthcare perspective and with a 6-month time horizon. The model extracted subjective sleep onset latency treatment responses and disutility values for non-responders from SUNRISE 1. Cost-effectiveness was assessed using incremental cost per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were conducted to evaluate the impact of parameter uncertainty on the results.
Results
In the base-case analysis, the mean estimated QALYs for lemborexant, suvorexant, zolpidem-IR, and untreated insomnia were 0.4220, 0.4204, 0.4113, and 0.4163, and expected medical costs were JPY 34 034, JPY 38 371, JPY 38 139, and JPY 15 383, respectively. Lemborexant saved JPY 4337 and JPY 4105 compared with suvorexant or zolpidem-IR, respectively, while conferring QALY benefits. The incremental cost-effectiveness ratio (ICER) of lemborexant compared with that of untreated insomnia was JPY 3 220 975 /QALY. Lemborexant was dominant over suvorexant and zolpidem-IR and was cost-effective when compared with untreated insomnia. Sensitivity analyses supported the results' robustness.
Conclusions
In a Japanese clinical practice setting, lemborexant may represent a better investment for treating insomnia in the healthcare system in Japan.
The time of widespread outbreaks of infectious diseases can lead to elevated stress and mental health problems among all persons affected, and in particular those sub-groups of the population that are at an increased risk of mental health problems. One such vulnerable group constitutes university students. The aim of this study is to assess stress, depression, anxiety, and suicidality among different groups of university students (medical, psychology, and other).
Methods
Using a repeated cross-sectional study design, we collected survey data among a large sample of 7228 university students from Poland (mean age = 22.78, s.d. = 4.40; 81% female). Data were collected in five waves, during the first 2 months of the COVID-19 pandemic in Europe (March and April 2020).
Results
The results demonstrate a significant increase in depression levels as the pandemic was progressing. We also found that female students scored significantly higher than male students on depression, anxiety, and stress. Psychology students recorded the lowest scores on depression and anxiety. Young adult students (aged 18–24 years) had more symptoms of depression, anxiety, and suicidality than adult students (⩾25 years).
Conclusions
These results provide insights into stress and mental health among university students during the early stages of the COVID-19 pandemic. Findings can be used for a more effective identification of students who may struggle during next stages of the pandemic and future crises.