Adverse childhood experiences (ACEs) are associated with physical and mental health difficulties in adulthood. This study examines the associations of ACEs with functional impairment and life stress among military personnel, a population disproportionately affected by ACEs. We also evaluate the extent to which the associations of ACEs with functional outcomes are mediated through internalizing and externalizing disorders.

The sample included 4,666 STARRS Longitudinal Study (STARRS-LS) participants who provided information about ACEs upon enlistment in the US Army (2011–2012). Mental disorders were assessed in wave 1 (LS1; 2016–2018), and functional impairment and life stress were evaluated in wave 2 (LS2; 2018–2019) of STARRS-LS. Mediation analyses estimated the indirect associations of ACEs with physical health-related impairment, emotional health-related impairment, financial stress, and overall life stress at LS2 through internalizing and externalizing disorders at LS1.

ACEs had significant indirect effects via mental disorders on all functional impairment and life stress outcomes, with internalizing disorders displaying stronger mediating effects than externalizing disorders (explaining 31–92% vs 5–15% of the total effects of ACEs, respectively). Additionally, ACEs exhibited significant direct effects on emotional health-related impairment, financial stress, and overall life stress, implying ACEs are also associated with these longer-term outcomes via alternative pathways.

This study indicates ACEs are linked to functional impairment and life stress among military personnel in part because of associated risks of mental disorders, particularly internalizing disorders. Consideration of ACEs should be incorporated into interventions to promote psychosocial functioning and resilience among military personnel.

Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.

We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).

Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.

Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

Neuropsychiatric symptoms are common after traumatic brain injury (TBI) and often resolve within 3 months post-injury. However, the degree to which individual patients follow this course is unknown. We characterized trajectories of neuropsychiatric symptoms over 12 months post-TBI. We hypothesized that a substantial proportion of individuals would display trajectories distinct from the group-average course, with some exhibiting less favorable courses.

Participants were level 1 trauma center patients with TBI (n = 1943), orthopedic trauma controls (n = 257), and non-injured friend controls (n = 300). Trajectories of six symptom dimensions (Depression, Anxiety, Fear, Sleep, Physical, and Pain) were identified using growth mixture modeling from 2 weeks to 12 months post-injury.

Depression, Anxiety, Fear, and Physical symptoms displayed three trajectories: Stable-Low (86.2–88.6%), Worsening (5.6–10.9%), and Improving (2.6–6.4%). Among symptomatic trajectories (Worsening, Improving), lower-severity TBI was associated with higher prevalence of elevated symptoms at 2 weeks that steadily resolved over 12 months compared to all other groups, whereas higher-severity TBI was associated with higher prevalence of symptoms that gradually worsened from 3–12 months. Sleep and Pain displayed more variable recovery courses, and the most common trajectory entailed an average level of problems that remained stable over time (Stable-Average; 46.7–82.6%). Symptomatic Sleep and Pain trajectories (Stable-Average, Improving) were more common in traumatically injured groups.

Findings illustrate the nature and rates of distinct neuropsychiatric symptom trajectories and their relationship to traumatic injuries. Providers may use these results as a referent for gauging typical v. atypical recovery in the first 12 months post-injury.

Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.

This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.

The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).

Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.

Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).

This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.

Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.

The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.

Subjective well-being when on neuroleptic treatment (SWBN), has been established as a good predictor of adherence, early response and prognosis in patients with schizophrenia. The 20-item subjective well-being under neuroleptic treatment scale (SWN-K 20) is a self-rating scale that has been validated to measure SWBN. However the SWN-K20 has not been previously used to explore psychosocial and clinical factors influencing a low SWN-K20 score in an African population. This study uses the the SWN-K 20 scale among Xhosa speaking African patients with Schizophrenia to determine factors associated with SWBN in this population

To investigate and identify demographic and clinical predictors of subjective well-being in a sample of Xhosa people with schizophrenia on neuroleptic treatment.

As a part of a large genetic study, 244 study participants with a confirmed diagnosis of schizophrenia completed the translated SWN-K 20 scale. Internal consistency analysis was performed, and convergent analysis and exploratory analysis were conducted using Principal Component Analysis (PCA). Linear regression methods were used to determine predictors of SWBN in the sample population.

When translated into isiXhosa, the sasubscales of SWN-K 20 on their own were observed to be less reliable when compared to the scale in its entirety,internal consistency of 0.86 vs0. 59-0.47. The subscales were therefore noted to be not meaningful in measuring specific constructs but the full scale could be used to determine a single construct of general wellbeing.The validity of the SWN-K20 was further confirmed by moderate correlation scores with Global Assesment functioning scores (GAF), 0.44.There was a significant correlation between overall subjective well-being score with higher education level, and increased illness severity and GAF scores.

Patients’ perception of well-being while on neuroleptic treatment is an essential area of focus when aiming at improving patient centred treatment, compliance and overall treatment outcome. Treating individuals with SMI is difficult and made more complex when patient’s treatment experience and expectations are not elicited. Having a self-reported measurement like the SWN-K 20 available in a validated Xhosa language version provides helpful, possibly broad insights into the subjective well-being experiences of this patient group. Future studies should explore specific symptoms domains that are associated with a change in subjective wellbeing instead of general illness severity.

None Declared

To evaluate random effects of volume (patient days or device days) on healthcare-associated infections (HAIs) and the standardized infection ratio (SIR) used to compare hospitals.

A longitudinal comparison between publicly reported quarterly data (2014–2020) and volume-based random sampling using 4 HAI types: central-line–associated bloodstream infections, catheter-associated urinary tract infections, Clostridioides difficile infections, methicillin-resistant Staphylococcus aureus infections.

Using 4,268 hospitals with reported SIRs, we examined relationships of SIRs to volume and compared distributions of SIRs and numbers of reported HAIs to the outcomes of simulated random sampling. We included random expectations into SIR calculations to produce a standardized infection score (SIS).

Among hospitals with volumes less than the median, 20%–33% had SIRs of 0, compared to 0.3%–5% for hospitals with volumes higher than the median. Distributions of SIRs were 86%–92% similar to those based on random sampling. Random expectations explained 54%–84% of variation in numbers of HAIs. The use of SIRs led hundreds of hospitals with more infections than either expected at random or predicted by risk-adjusted models to rank better than other hospitals. The SIS mitigated this effect and allowed hospitals of disparate volumes to achieve better scores while decreasing the number of hospitals tied for the best score.

SIRs and numbers of HAIs are strongly influenced by random effects of volume. Mitigating these effects drastically alters rankings for HAI types and may further alter penalty assignments in programs that aim to reduce HAIs and improve quality of care.

Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.

To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.

We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.

The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75–1.32) and TIC IRR = 0.83 (95% CI, 0.49–1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.

In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking.

A multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups.

There were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4).

The study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.

This study investigates associations of several dimensions of childhood adversities (CAs) with lifetime mental disorders, 12-month disorder persistence, and impairment among incoming college students.

Data come from the World Mental Health International College Student Initiative (WMH-ICS). Web-based surveys conducted in nine countries (n = 20 427) assessed lifetime and 12-month mental disorders, 12-month role impairment, and seven types of CAs occurring before the age of 18: parental psychopathology, emotional, physical, and sexual abuse, neglect, bullying victimization, and dating violence. Poisson regressions estimated associations using three dimensions of CA exposure: type, number, and frequency.

Overall, 75.8% of students reported exposure to at least one CA. In multivariate regression models, lifetime onset and 12-month mood, anxiety, and substance use disorders were all associated with either the type, number, or frequency of CAs. In contrast, none of these associations was significant when predicting disorder persistence. Of the three CA dimensions examined, only frequency was associated with severe role impairment among students with 12-month disorders. Population-attributable risk simulations suggest that 18.7–57.5% of 12-month disorders and 16.3% of severe role impairment among those with disorders were associated with these CAs.

CAs are associated with an elevated risk of onset and impairment among 12-month cases of diverse mental disorders but are not involved in disorder persistence. Future research on the associations of CAs with psychopathology should include fine-grained assessments of CA exposure and attempt to trace out modifiable intervention targets linked to mechanisms of associations with lifetime psychopathology and burden of 12-month mental disorders.

Problematic anger is frequently reported by soldiers who have deployed to combat zones. However, evidence is lacking with respect to how anger changes over a deployment cycle, and which factors prospectively influence change in anger among combat-deployed soldiers.

Reports of problematic anger were obtained from 7298 US Army soldiers who deployed to Afghanistan in 2012. A series of mixed-effects growth models estimated linear trajectories of anger over a period of 1–2 months before deployment to 9 months post-deployment, and evaluated the effects of pre-deployment factors (prior deployments and perceived resilience) on average levels and growth of problematic anger.

A model with random intercepts and slopes provided the best fit, indicating heterogeneity in soldiers' levels and trajectories of anger. First-time deployers reported the lowest anger overall, but the most growth in anger over time. Soldiers with multiple prior deployments displayed the highest anger overall, which remained relatively stable over time. Higher pre-deployment resilience was associated with lower reports of anger, but its protective effect diminished over time. First- and second-time deployers reporting low resilience displayed different anger trajectories (stable v. decreasing, respectively).

Change in anger from pre- to post-deployment varies based on pre-deployment factors. The observed differences in anger trajectories suggest that efforts to detect and reduce problematic anger should be tailored for first-time v. repeat deployers. Ongoing screening is needed even for soldiers reporting high resilience before deployment, as the protective effect of pre-deployment resilience on anger erodes over time.

Trichotillomania (TTM) and skin picking disorder (SPD) are common and often debilitating mental health conditions, grouped under the umbrella term of body-focused repetitive behaviors (BFRBs). Recent clinical subtyping found that there were three distinct subtypes of TTM and two of SPD. Whether these clinical subtypes map on to any unique neurobiological underpinnings, however, remains unknown.

Two hundred and fifty one adults [193 with a BFRB (85.5% [n = 165] female) and 58 healthy controls (77.6% [n = 45] female)] were recruited from the community for a multicenter between-group comparison using structural neuroimaging. Differences in whole brain structure were compared across the subtypes of BFRBs, controlling for age, sex, scanning site, and intracranial volume.

When the subtypes of TTM were compared, low awareness hair pullers demonstrated increased cortical volume in the lateral occipital lobe relative to controls and sensory sensitive pullers. In addition, impulsive/perfectionist hair pullers showed relative decreased volume near the lingual gyrus of the inferior occipital–parietal lobe compared with controls.

These data indicate that the anatomical substrates of particular forms of BFRBs are dissociable, which may have implications for understanding clinical presentations and treatment response.

The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries.

Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents.

3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2–4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness.

ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Although non-suicidal self-injury (NSSI) is an issue of major concern to colleges worldwide, we lack detailed information about the epidemiology of NSSI among college students. The objectives of this study were to present the first cross-national data on the prevalence of NSSI and NSSI disorder among first-year college students and its association with mental disorders.

Data come from a survey of the entering class in 24 colleges across nine countries participating in the World Mental Health International College Student (WMH-ICS) initiative assessed in web-based self-report surveys (20 842 first-year students). Using retrospective age-of-onset reports, we investigated time-ordered associations between NSSI and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-IV) mood (major depressive and bipolar disorder), anxiety (generalized anxiety and panic disorder), and substance use disorders (alcohol and drug use disorder).

NSSI lifetime and 12-month prevalence were 17.7% and 8.4%. A positive screen of 12-month DSM-5 NSSI disorder was 2.3%. Of those with lifetime NSSI, 59.6% met the criteria for at least one mental disorder. Temporally primary lifetime mental disorders predicted subsequent onset of NSSI [median odds ratio (OR) 2.4], but these primary lifetime disorders did not consistently predict 12-month NSSI among respondents with lifetime NSSI. Conversely, even after controlling for pre-existing mental disorders, NSSI consistently predicted later onset of mental disorders (median OR 1.8) as well as 12-month persistence of mental disorders among students with a generalized anxiety disorder (OR 1.6) and bipolar disorder (OR 4.6).

NSSI is common among first-year college students and is a behavioral marker of various common mental disorders.

Epidemiological studies indicate that individuals with one type of mental disorder have an increased risk of subsequently developing other types of mental disorders. This study aimed to undertake a comprehensive analysis of pair-wise lifetime comorbidity across a range of common mental disorders based on a diverse range of population-based surveys.

The WHO World Mental Health (WMH) surveys assessed 145 990 adult respondents from 27 countries. Based on retrospectively-reported age-of-onset for 24 DSM-IV mental disorders, associations were examined between all 548 logically possible temporally-ordered disorder pairs. Overall and time-dependent hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Absolute risks were estimated using the product-limit method. Estimates were generated separately for men and women.

Each prior lifetime mental disorder was associated with an increased risk of subsequent first onset of each other disorder. The median HR was 12.1 (mean = 14.4; range 5.2–110.8, interquartile range = 6.0–19.4). The HRs were most prominent between closely-related mental disorder types and in the first 1–2 years after the onset of the prior disorder. Although HRs declined with time since prior disorder, significantly elevated risk of subsequent comorbidity persisted for at least 15 years. Appreciable absolute risks of secondary disorders were found over time for many pairs.

Survey data from a range of sites confirms that comorbidity between mental disorders is common. Understanding the risks of temporally secondary disorders may help design practical programs for primary prevention of secondary disorders.

Intermittent explosive disorder (IED) is characterised by impulsive anger attacks that vary greatly across individuals in severity and consequence. Understanding IED subtypes has been limited by lack of large, general population datasets including assessment of IED. Using the 17-country World Mental Health surveys dataset, this study examined whether behavioural subtypes of IED are associated with differing patterns of comorbidity, suicidality and functional impairment.

IED was assessed using the Composite International Diagnostic Interview in the World Mental Health surveys (n = 45 266). Five behavioural subtypes were created based on type of anger attack. Logistic regression assessed association of these subtypes with lifetime comorbidity, lifetime suicidality and 12-month functional impairment.

The lifetime prevalence of IED in all countries was 0.8% (s.e.: 0.0). The two subtypes involving anger attacks that harmed people (‘hurt people only’ and ‘destroy property and hurt people’), collectively comprising 73% of those with IED, were characterised by high rates of externalising comorbid disorders. The remaining three subtypes involving anger attacks that destroyed property only, destroyed property and threatened people, and threatened people only, were characterised by higher rates of internalising than externalising comorbid disorders. Suicidal behaviour did not vary across the five behavioural subtypes but was higher among those with (v. those without) comorbid disorders, and among those who perpetrated more violent assaults.

The most common IED behavioural subtypes in these general population samples are associated with high rates of externalising disorders. This contrasts with the findings from clinical studies of IED, which observe a preponderance of internalising disorder comorbidity. This disparity in findings across population and clinical studies, together with the marked heterogeneity that characterises the diagnostic entity of IED, suggests that it is a disorder that requires much greater research.

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.

This study assessed the efficacy of agomelatine (1,2,3), in the prevention of relapse in non-depressed out-patients with DSM-IV-TR defined Generalized Anxiety Disorder (GAD) and the tolerability.

GAD patients received open label agomelatine (25–50 mg/day). At week 4 the dose was increased for patients with insufficient improvement (blinded criteria). At week 16, responders were randomised to maintenance treatment with either agomelatine, or placebo for a 26 week period. Then, agomelatine treated-patients were re-randomised to an agomelatine arm or to a placebo arm, to confirm the lack of discontinuation symptoms (on the DESS check-list).

The primary outcome was the time to relapse (days) during the 26 week double-blind treatment period, as estimated using the Kaplan-Meier method. Relapse was defined as HAMA total score > = 15 or withdrawal for lack of efficacy (in the investigator's opinion, based on both HAM-A and CGI scores).

477 patients entered the open-label phase and 329 completed this period. 228 patients were randomly assigned to receive agomelatine (114 patients) or placebo (114 patients).

The incidence over time of relapse was significantly lower with agomelatine compared to placebo (19.7% versus 31.7% log rank test p = 0.046) during the double-blind treatment period.

During the double-blind treatment period 12.4% patients with agomelatine and 9.6% with placebo reported at least one emergent adverse event related to the study treatment. There was no discontinuation syndrome in agomelatine treated patients.

Agomelatine was efficacious in preventing relapse in GAD, with maintenance of efficacy over 6 months, and good tolerability.