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MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood.
We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness.
The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing.
Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.
Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
Unit cohesion may protect service member mental health by mitigating effects of combat exposure; however, questions remain about the origins of potential stress-buffering effects. We examined buffering effects associated with two forms of unit cohesion (peer-oriented horizontal cohesion and subordinate-leader vertical cohesion) defined as either individual-level or aggregated unit-level variables.
Longitudinal survey data from US Army soldiers who deployed to Afghanistan in 2012 were analyzed using mixed-effects regression. Models evaluated individual- and unit-level interaction effects of combat exposure and cohesion during deployment on symptoms of post-traumatic stress disorder (PTSD), depression, and suicidal ideation reported at 3 months post-deployment (model n's = 6684 to 6826). Given the small effective sample size (k = 89), the significance of unit-level interactions was evaluated at a 90% confidence level.
At the individual-level, buffering effects of horizontal cohesion were found for PTSD symptoms [B = −0.11, 95% CI (−0.18 to −0.04), p < 0.01] and depressive symptoms [B = −0.06, 95% CI (−0.10 to −0.01), p < 0.05]; while a buffering effect of vertical cohesion was observed for PTSD symptoms only [B = −0.03, 95% CI (−0.06 to −0.0001), p < 0.05]. At the unit-level, buffering effects of horizontal (but not vertical) cohesion were observed for PTSD symptoms [B = −0.91, 90% CI (−1.70 to −0.11), p = 0.06], depressive symptoms [B = −0.83, 90% CI (−1.24 to −0.41), p < 0.01], and suicidal ideation [B = −0.32, 90% CI (−0.62 to −0.01), p = 0.08].
Policies and interventions that enhance horizontal cohesion may protect combat-exposed units against post-deployment mental health problems. Efforts to support individual soldiers who report low levels of horizontal or vertical cohesion may also yield mental health benefits.
Recent data support the view that the neurodegeneration underlying sporadic Alzheimer's Disease (AD) is in part related to brain insulin deficiency and brain insulin resistance. There is a higher incidence of AD in patients with diabetes mellitus type II (T2D) and both diseases show a decline in memory function. In a preceding trial intranasal insulin improved memory function in healthy volunteers so that an increase of central-nervous insulin concentration may improve cognitive function in both amnestic patient groups.
We want to analyse the effects of intranasal insulin on patients with early Alzheimers's disease (eAD) and patients with T2D in the state of amnestic mild cognitive impairment (aMCI).
Recruitment of 30 patients with eAD, 30 patients with T2D in aMCI state and 30 age-matched healthy controls. All patients undergo a run-in period of 2 weeks with 4 × daily administration of placebo. It follows a double blinded trial with daily intranasal administration of 4 × 40 I.U. insulin vs. placebo for 8 weeks and another 8 weeks of follow-up. At 4 defined time points memory function is assessed by word lists comprising 30 items of emotional, nutritional and neutral content which have to be memorized and are recalled after one week. To assess structural changes of the brain, a quantitative analysis for hippocampal N-acetyl-aspartate, choline and creatine is performed by 3 Tesla magnetic resonance spectroscopy.
Results: Since the study has not finished yet, we present experiences from the initiation and the beginning phase.
Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.
The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.
There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.
These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.
Obsessive-compulsive disorder (OCD) is a highly disabling condition, with frequent early onset. Adult/adolescent OCD has been extensively investigated, but little is known about prevalence and clinical characterization of geriatric patients with OCD (G-OCD = 65 years). The present study aimed to assess prevalence of G-OCD and associated socio-demographic and clinical correlates in a large international sample.
Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age < vs = 65 years, and then divided on the basis of the median age of the sample (age < vs = 42 years). Socio-demographic and clinical variables were compared between groups (Pearson Chi-squared and t tests).
G-OCD compared with younger patients represented a significant minority of the sample (6% vs 94%, P < .001), showing a significantly later age at onset (29.4 ± 15.1 vs 18.7 ± 9.2 years, P < .001), a more frequent adult onset (75% vs 41.1%, P < .001) and a less frequent use of cognitive-behavioural therapy (CBT) (20.8% vs 41.8%, P < .05). Female gender was more represented in G-OCD patients, though not at a statistically significant level (75% vs 56.4%, P = .07). When the whole sample was divided on the basis of the median age, previous results were confirmed for older patients, including a significantly higher presence of women (52.1% vs 63.1%, P < .05).
G-OCD compared with younger patients represented a small minority of the sample and showed later age at onset, more frequent adult onset and lower CBT use. Age at onset may influence course and overall management of OCD, with additional investigation needed.
Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.
Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.
Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.
Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors.
The WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.
20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2–0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66–55% v. 43%) and later-recovery (75–68% v. 39%).
We found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.
Sleep problems are associated with increased risk of physical and mental illness. Identifying risk factors is an important method of reducing public health impact. We examined the association between maternal postnatal depression (PND) and offspring adolescent sleep problems.
The sample was derived from Avon Longitudinal Study of Parents and Children (ALSPAC) participants. A sample with complete data across all variables was used, with four outcome variables. A sensitivity analysis imputing for missing data was conducted (n = 9633).
PND was associated with increased risk of sleep problems in offspring at ages 16 and 18 years. The most robust effects were sleep problems at 18 years [adjusted odds ratio (OR) for a 1 s.d. increase in PND, 1.26, 95% confidence interval (CI) 1.15–1.39, p < 0.001] and waking more often (adjusted OR 1.14, 95% CI 1.05–1.25, p = 0.003). This remained after controlling for confounding variables including antenatal depression and early sleep problems in infancy.
PND is associated with adolescent offspring sleep problems. Maternal interventions should consider the child's increased risk. Early sleep screening and interventions could be introduced within this group.
This is the first cross-national study of intermittent explosive disorder (IED).
A total of 17 face-to-face cross-sectional household surveys of adults were conducted in 16 countries (n = 88 063) as part of the World Mental Health Surveys initiative. The World Health Organization Composite International Diagnostic Interview (CIDI 3.0) assessed DSM-IV IED, using a conservative definition.
Lifetime prevalence of IED ranged across countries from 0.1 to 2.7% with a weighted average of 0.8%; 0.4 and 0.3% met criteria for 12-month and 30-day prevalence, respectively. Sociodemographic correlates of lifetime risk of IED were being male, young, unemployed, divorced or separated, and having less education. The median age of onset of IED was 17 years with an interquartile range across countries of 13–23 years. The vast majority (81.7%) of those with lifetime IED met criteria for at least one other lifetime disorder; co-morbidity was highest with alcohol abuse and depression. Of those with 12-month IED, 39% reported severe impairment in at least one domain, most commonly social or relationship functioning. Prior traumatic experiences involving physical (non-combat) or sexual violence were associated with increased risk of IED onset.
Conservatively defined, IED is a low prevalence disorder but this belies the true societal costs of IED in terms of the effects of explosive anger attacks on families and relationships. IED is more common among males, the young, the socially disadvantaged and among those with prior exposure to violence, especially in childhood.
Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms.
One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood.
During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship.
Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.
The aim of this study was to examine cross-sectionally whether higher cardiorespiratory fitness (CRF) might favorably modify amyloid-β (Aβ)-related decrements in cognition in a cohort of late-middle-aged adults at risk for Alzheimer’s disease (AD). Sixty-nine enrollees in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. They completed a comprehensive neuropsychological exam, underwent 11C Pittsburgh Compound B (PiB)-PET imaging, and performed a graded treadmill exercise test to volitional exhaustion. Peak oxygen consumption (VO2peak) during the exercise test was used as the index of CRF. Forty-five participants also underwent lumbar puncture for collection of cerebrospinal fluid (CSF) samples, from which Aβ42 was immunoassayed. Covariate-adjusted regression analyses were used to test whether the association between Aβ and cognition was modified by CRF. There were significant VO2peak*PiB-PET interactions for Immediate Memory (p=.041) and Verbal Learning & Memory (p=.025). There were also significant VO2peak*CSF Aβ42 interactions for Immediate Memory (p<.001) and Verbal Learning & Memory (p<.001). Specifically, in the context of high Aβ burden, that is, increased PiB-PET binding or reduced CSF Aβ42, individuals with higher CRF exhibited significantly better cognition compared with individuals with lower CRF. In a late-middle-aged, at-risk cohort, higher CRF is associated with a diminution of Aβ-related effects on cognition. These findings suggest that exercise might play an important role in the prevention of AD. (JINS, 2015, 21, 841–850)
Two experiments were conducted to investigate if adjustments in diet formulations either based on total analysed amino acids or standardized ileal digestible (SID) amino acids may be used to eliminate negative effects of including heat-damaged soybean meal (SBM) or heat-damaged corn distillers dried grains with solubles (DDGS) in diets fed to weanling pigs. In Experiment 1, four corn–SBM diets were formulated. Diet 1 contained non-autoclaved SBM (315 g/kg), and this diet was formulated on the basis of analysed amino acid concentrations and using SID values from the AminoDat® 4.0 database. Diet 2 was similar to Diet 1 in terms of ingredient composition, except that the non-autoclaved SBM was replaced by autoclaved SBM at 1 : 1 (weight basis). Diet 3 was formulated using autoclaved SBM and amino acid inclusions in the diet were adjusted on the basis of analysed total amino acid concentrations in the autoclaved SBM and published SID values for non-autoclaved SBM (AminoDat® 4.0). Diet 4 also contained autoclaved SBM, but the formulation of this diet was adjusted on the basis of analysed amino acids in the autoclaved SBM and SID values that were adjusted according to the degree of heat damage in this source of SBM. Pigs (160; initial BW: 10.4 kg) were allotted to the four treatments with eight replicate pens per treatment in a randomized complete block design. Diets were fed to pigs for 21 days. The gain to feed ratio (G : F) was greater (P<0.05) for pigs fed Diet 1 compared with pigs fed the other diets and pigs fed Diet 4 had greater (P<0.05) G : F than pigs fed Diet 2. In Experiment 2, 144 pigs (initial BW: 9.9 kg) were allotted to four diets with eight replicate pens per diet. The four diets contained corn, SBM (85 g/kg) and DDGS (220 g/kg), and were formulated using the concepts described for Experiment 1, except that heat-damaged DDGS, but not heat-damaged SBM, was used in the diets. Pigs fed Diet 1 had greater (P<0.05) G : F than pigs fed Diet 2, but no differences were observed for G : F among pigs fed diets containing autoclaved DDGS. Results demonstrate that the negative effects of heat damage of SBM or DDGS may be ameliorated if the reduced concentration and digestibility of amino acids in heat-damaged SBM or DDGS is taken into account in diet formulation. Further research is needed to improve the prediction of the ileal digestibility of amino acids in heat-processed ingredients used in practical diet formulations.
To examine barriers to initiation and continuation of mental health treatment among individuals with common mental disorders.
Data were from the World Health Organization (WHO) World Mental Health (WMH) surveys. Representative household samples were interviewed face to face in 24 countries. Reasons to initiate and continue treatment were examined in a subsample (n = 636 78) and analyzed at different levels of clinical severity.
Among those with a DSM-IV disorder in the past 12 months, low perceived need was the most common reason for not initiating treatment and more common among moderate and mild than severe cases. Women and younger people with disorders were more likely to recognize a need for treatment. A desire to handle the problem on one's own was the most common barrier among respondents with a disorder who perceived a need for treatment (63.8%). Attitudinal barriers were much more important than structural barriers to both initiating and continuing treatment. However, attitudinal barriers dominated for mild-moderate cases and structural barriers for severe cases. Perceived ineffectiveness of treatment was the most commonly reported reason for treatment drop-out (39.3%), followed by negative experiences with treatment providers (26.9% of respondents with severe disorders).
Low perceived need and attitudinal barriers are the major barriers to seeking and staying in treatment among individuals with common mental disorders worldwide. Apart from targeting structural barriers, mainly in countries with poor resources, increasing population mental health literacy is an important endeavor worldwide.
Remoras (echeneid fish) reversibly attach and detach to marine hosts, almost instantaneously, to “hitchhike” and feed. The adhesion mechanisms that they use are remarkably insensitive to substrate topology and quite different from the latching and suction cup-based systems associated with other species at similar length scales. Remora adhesion is also anisotropic; drag forces induced by the swimming host increase adhesive strength, while rapid detachment occurs when the remora reverses this shear load. In this work, an investigation of the adhesive system’s functional morphology and tissue properties was carried out initially through dissection and x-ray microtomographic analyses. Resulting finite element models of these components have provided new insights into the adaptive, hierarchical nature of the mechanisms and a path toward a wide range of engineering applications.
Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10·4 nmol/l; women, 10·7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north–south gradient. Vitamin B2 concentrations were highest in Northern Europe (men, 22·2 nmol/l; women, 26·0 nmol/l) and decreased towards Southern Europe (Ptrend< 0·001). Vitamin B6 concentrations were highest in Central Europe in men (77·3 nmol/l) and highest in the North among women (70·4 nmol/l), with decreasing concentrations towards Southern Europe in women (Ptrend< 0·001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.