Showing papers in "Depression and Anxiety in 2019"

Developing an optimal short‐form of the PTSD Checklist for DSM‐5 (PCL‐5)

Abstract: Background Although several short-forms of the posttraumatic stress disorder (PTSD) Checklist (PCL) exist, all were developed using heuristic methods. This report presents the results of analyses designed to create an optimal short-form PCL for DSM-5 (PCL-5) using both machine learning and conventional scale development methods. Methods The short-form scales were developed using independent datasets collected by the Army Study to Assess Risk and Resilience among Service members. We began by using a training dataset (n = 8,917) to fit short-form scales with between 1 and 8 items using different statistical methods (exploratory factor analysis, stepwise logistic regression, and a new machine learning method to find an optimal integer-scored short-form scale) to predict dichotomous PTSD diagnoses determined using the full PCL-5. A smaller subset of best short-form scales was then evaluated in an independent validation sample (n = 11,728) to select one optimal short-form scale based on multiple operating characteristics (area under curve [AUC], calibration, sensitivity, specificity, net benefit). Results Inspection of AUCs in the training sample and replication in the validation sample led to a focus on 4-item integer-scored short-form scales selected with stepwise regression. Brier scores in the validation sample showed that a number of these scales had comparable calibration (0.015-0.032) and AUC (0.984-0.994), but that one had consistently highest net benefit across a plausible range of decision thresholds. Conclusions The recommended 4-item integer-scored short-form PCL-5 generates diagnoses that closely parallel those of the full PCL-5, making it well-suited for screening.

The prevalence and predictors of mental health diagnoses and suicide among U.S. college students: Implications for addressing disparities in service use.

Abstract: Background The college years represent a period of increased vulnerability for a wide range of mental health (MH) challenges. The onset of common psychiatric conditions occurs during this period of development. Increases in depression, anxiety, and suicidality among U.S. college students have been observed. This study identified prevalence and correlates of MH diagnoses and suicidality in a recent sample of U.S. college students. Methods The Spring 2015 American College Health Association-National College Health Assessment (ACHA-NCHA) survey assessed MH diagnoses and suicidality from U.S. undergraduate students (n = 67,308) across 108 institutions. Results Stress was strongly associated with a greater likelihood of suicide attempts and MH diagnoses, even among students reporting 1-2 stressful events (OR [odds ratio] range 1.6-2.6, CI [confidence interval] = 1.2-3.2). Bisexual students were more likely to report MH diagnoses and suicidality, compared to heterosexual and gay/lesbian students (OR range 1.5-3.9, CI = 1.8-4.3), with over half engaging in suicidal ideation and self-harm, and over a quarter reporting suicide attempts. Transgender students reported a higher rate of MH diagnoses and suicidality relative to females (OR range 1.9-2.4, CI = 1.1-3.4). Racial/ethnic minority students were generally less likely to report MH diagnoses relative to Whites, although the likelihood for suicidality was mixed. Conclusions The high rate of multiple stress exposures among the U.S. college population and the high impacts of stress on MH and suicidality point to an urgent need for service utilization strategies, especially among racial/ethnic, sexual, or gender minorities. Campuses must consider student experiences to mitigate stress during this developmental period.

Physical activity protects from incident anxiety: A meta-analysis of prospective cohort studies.

Abstract: Background Prospective cohorts have suggested that physical activity (PA) can decrease the risk of incident anxiety. However, no meta-analysis has been conducted. Aims To examine the prospective relationship between PA and incident anxiety and explore potential moderators. Methods Searches were conducted on major databases from inception to October 10, 2018 for prospective studies (at least 1 year of follow-up) that calculated the odds ratio (OR) of incident anxiety in people with high PA against people with low PA. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was conducted and heterogeneity was explored using subgroup and meta-regression analysis. Results Across 14 cohorts of 13 unique prospective studies (N = 75,831, median males = 50.1%) followed for 357,424 person-years, people with high self-reported PA (versus low PA) were at reduced odds of developing anxiety (adjusted odds ratio [AOR] = 0.74; 95% confidence level [95% CI] = 0.62, 0.88; crude OR = 0.80; 95% CI = 0.69, 0.92). High self-reported PA was protective against the emergence of agoraphobia (AOR = 0.42; 95% CI = 0.18, 0.98) and posttraumatic stress disorder (AOR = 0.57; 95% CI = 0.39, 0.85). The protective effects for anxiety were evident in Asia (AOR = 0.31; 95% CI = 0.10, 0.96) and Europe (AOR = 0.82; 95% CI = 0.69, 0.97); for children/adolescents (AOR = 0.52; 95% CI = 0.29, 0.90) and adults (AOR = 0.81; 95% CI = 0.69, 0.95). Results remained robust when adjusting for confounding factors. Overall study quality was moderate to high (mean NOS = 6.7 out of 9). Conclusion Evidence supports the notion that self-reported PA can confer protection against the emergence of anxiety regardless of demographic factors. In particular, higher PA levels protects from agoraphobia and posttraumatic disorder.

Aerobic exercise for adult patients with major depressive disorder in mental health services: A systematic review and meta-analysis

Abstract: Although exercise is associated with depression relief, the effects of aerobic exercise (AE) interventions on clinically depressed adult patients have not been clearly supported. The purpose of this meta-analysis was to examine the antidepressant effects of AE versus nonexercise comparators exclusively for depressed adults (18-65 years) recruited through mental health services with a referral or clinical diagnosis of major depression. Eleven e-databases and bibliographies of 19 systematic reviews were searched for relevant randomized controlled clinical trials. A random effects meta-analysis (Hedges' g criterion) was employed for pooling postintervention scores of depression. Heterogeneity and publication bias were examined. Studies were coded considering characteristics of participants and interventions, outcomes and comparisons made, and study design; accordingly, sensitivity and subgroup analyses were calculated. Across 11 eligible trials (13 comparisons) involving 455 patients, AE was delivered on average for 45 min, at moderate intensity, three times/week, for 9.2 weeks and showed a significantly large overall antidepressant effect (g = -0.79, 95% confidence interval = -1.01, -0.57, P < 0.00) with low and nonstatistically significant heterogeneity (I2 = 21%). No publication bias was found. Sensitivity analyses revealed large or moderate to large antidepressant effects for AE (I2 ≤ 30%) among trials with lower risk of bias, trials with short-term interventions (up to 4 weeks), and trials involving individual preferences for exercise. Subgroup analyses revealed comparable effects for AE across various settings and delivery formats, and in both outpatients and inpatients regardless symptom severity. Notwithstanding the small number of trials reviewed, AE emerged as an effective antidepressant intervention.

Internet- and mobile-based interventions for anxiety disorders: A meta-analytic review of intervention components.

Abstract: Background Although the efficacy of Internet- and mobile-based interventions (IMIs) for anxiety is established, little is known about the intervention components responsible for therapeutic change. We conducted the first comprehensive meta-analytic review of intervention components of IMIs for adult anxiety disorders. Methods Randomized controlled trials (RCTs) comparing IMIs for anxiety disorders to active online control groups, or IMIs to dismantled variations of the same intervention (± specific components) were identified by a systematic literature search in six databases. Outcomes were validated observer-rated or self-report measures for anxiety symptom severity and treatment adherence (number of completed modules and completer rate). This meta-analytic review is registered with PROSPERO (CRD42017068268). Results We extracted the data of 34 RCTs (with 3,724 participants) and rated the risk of bias independently by two reviewers. Random-effects meta-analyses were performed on 19 comparisons of intervention components (i.a., different psychotherapeutic orientations, disorder-specific vs. transdiagnostic approaches, guidance factors). IMIs had a large effect when compared to active online controls on symptom severity (standardized mean difference [SMD] of -1.67 [95% CI: -2.93, -0.42]; P = 0.009). Thereby, guided IMIs were superior to unguided interventions on symptom severity (SMD of -0.39 [95% CI: -0.59, -0.18]; P = 0.0002) and adherence (SMD of 0.38 [95% CI: 0.10, 0.66]; P = 0.007). Conclusions Overall, the results of this meta-analysis lend further support to the efficacy of IMIs for anxiety, pointing to their potential to augment service supplies. Still, future research is needed to determine which ingredients are essential, as this meta-analytic review found no evidence for incremental effects of several single intervention components apart from guidance.

Risk factors and comorbidity of ICD‐11 PTSD and complex PTSD: Findings from a trauma‐exposed population based sample of adults in the United Kingdom

Abstract: BACKGROUND: Following the recently published 11th version of the WHO International Classification of Diseases (ICD-11), we sought to examine the risk factors and comorbidities associated with posttraumatic stress disorder (PTSD) and complex PTSD (CPTSD). METHOD: Cross-sectional and retrospective design. The sample consisted of 1,051 trauma-exposed participants from a nationally representative panel of the UK adult population. RESULTS: A total of 5.3% (95% confidence interval [CI] = 4.0-6.7%) met the diagnostic criteria for PTSD and 12.9% (95% CI = 10.9-15.0%) for CPTSD. Diagnosis of PTSD was independently associated with being female, being in a relationship, and the recency of traumatic exposure. CPTSD was independently associated with younger age, interpersonal trauma in childhood, and interpersonal trauma in adulthood. Growing up in an urban environment was associated with the diagnosis of PTSD and CPTSD. High rates of physical and mental health comorbidity were observed for PTSD and CPTSD. Those with CPTSD were more likely to endorse symptoms reflecting major depressive disorder (odds ratio [OR] = 21.85, 95 CI = 12.51-38.04) and generalized anxiety disorder (OR = 24.63, 95 CI = 14.77-41.07). Presence of PTSD (OR = 3.13, 95 CI = 1.81-5.41) and CPTSD (OR = 3.43, 95 CI = 2.37-4.70) increased the likelihood of suicidality by more than three times. Nearly half the participants with PTSD and CPTSD reported the presence of a chronic illness. CONCLUSIONS: CPTSD is a more common, comorbid, debilitating condition compared to PTSD. Further research is now required to identify effective interventions for its treatment.

Sleep, circadian rhythm, and physical activity patterns in depressive and anxiety disorders: A 2-week ambulatory assessment study.

Abstract: BACKGROUND: Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the association with depression/anxiety and their clinical characteristics. METHODS: Fourteen-day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day-time and night-time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate-to-vigorous PA (MVPA). Self-reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA. RESULTS: Compared to controls, individuals with current depression/anxiety had a significantly different objective, but not self-reported, PA and CR: lower GMA (23.83 vs. 27.4 milli-gravity/day, p = .022), lower MVPA (35.32 vs. 47.64 min/day, p = .023), lower RA (0.82 vs. 0.83, p = .033). In contrast, self-reported, but not objective, sleep differed between people with current depression/anxiety compared to those without current disorders; people with current depression/anxiety reported both shorter and longer SD and more insomnia. More depressive/anxiety symptoms and number of depressive/anxiety diagnoses were associated with larger disturbances of the actigraphy measures. CONCLUSION: Actigraphy provides ecologically valid information on sleep, CR, and PA that enhances data from self-reported questionnaires. As those with more severe or comorbid forms showed the lowest PA and most CR disruptions, the potential for adjunctive behavioral and chronotherapy interventions should be explored, as well as the potential of actigraphy to monitor treatment response to such interventions.

Measurement invariance of the patient health questionnaire-9 (PHQ-9) depression screener in U.S. adults across sex, race/ethnicity, and education level: NHANES 2005-2016.

Abstract: BACKGROUND Despite its popularity, little is known about the measurement invariance of the Patient Health Questionnaire-9 (PHQ-9) across US sociodemographic groups Use of a screener shown not to possess measurement invariance could result in under/over-detection of depression, potentially exacerbating sociodemographic disparities in depression Therefore, we assessed the factor structure and measurement invariance of the PHQ-9 across major US sociodemographic groups METHODS US population representative data came from the 2005-2016 National Health and Nutrition Examination Survey (NHANES) cohorts We conducted a measurement invariance analysis of 31,366 respondents across sociodemographic factors of sex, race/ethnicity, and education level RESULTS Considering results of single-group confirmatory factor analyses (CFAs), depression theory, and research utility, we justify a two-factor structure for the PHQ-9 consisting of a cognitive/affective factor and a somatic factor (RMSEA = 0034, TLI = 0985, CFI = 0989) On the basis of multiple-group CFAs testing configural, scalar, and strict factorial invariance, we determined that invariance held for sex, race/ethnicity, and education level groups, as all models demonstrated close model fit (RMSEA = 0025-0025, TLI = 0985-0992, CFI = 0986-0991) Finally, for all steps ΔCFI was <-0004, and ΔRMSEA was <001 CONCLUSIONS We demonstrate that the PHQ-9 is acceptable to use in major US sociodemographic groups and allows for meaningful comparisons in total, cognitive/affective, and somatic depressive symptoms across these groups, extending its use to the community This knowledge is timely as medicine moves towards alternative payment models emphasizing high-quality and cost-efficient care, which will likely incentivize behavioral and population health efforts We also provide a consistent, evidence-based approach for calculating PHQ-9 subscale scores

Prediction of major depressive disorder onset in college students

Abstract: Background Major depressive disorder (MDD) in college students is associated with substantial burden. Aims To assess 1-year incidence of MDD among incoming freshmen and predictors of MDD-incidence in a representative sample of students. Method Prospective cohort study of first-year college students (baseline: n = 2,519, 1-year follow-up: n = 958) RESULTS: The incidence of MDD within the first year of college was 6.9% (SE = 0.8). The most important individual-level predictors of onset were prior suicide plans and/or attempts (OR = 9.5). The strongest population-level baseline predictors were history of childhood-adolescent trauma, stressful experience in the past 12 months, parental psychopathology, and other 12-month mental disorder. Multivariate cross-validated prediction (cross-validated AUC = 0.73) suggest that 36.1% of incident MDD cases in a replication sample would occur among the 10% of students at highest predicted risk (24.5% predicted incidence in this highest-risk subgroup). Conclusions Screening at college entrance is a promising strategy to identify students at risk of MDD onset, which may improve the development and deployment of targeted preventive interventions.

The accuracy of passive phone sensors in predicting daily mood.

Abstract: Background Smartphones provide a low-cost and efficient means to collect population level data. Several small studies have shown promise in predicting mood variability from smartphone-based sensor and usage data, but have not been generalized to nationally recruited samples. This study used passive smartphone data, demographic characteristics, and baseline depressive symptoms to predict prospective daily mood. Method Daily phone usage data were collected passively from 271 Android phone users participating in a fully remote randomized controlled trial of depression treatment (BRIGHTEN). Participants completed daily Patient Health Questionnaire-2. A machine learning approach was used to predict daily mood for the entire sample and individual participants. Results Sample-wide estimates showed a marginally significant association between physical mobility and self-reported daily mood (B = -0.04, P 0.50) for 80.6% of participants and very strong prediction in a subset (median AUC > 0.80) for 11.8% of participants. Conclusions Passive smartphone data with current features may not be suited for predicting daily mood at a population level because of the high degree of intra- and interindividual variation in phone usage patterns and daily mood ratings. Personalized models show encouraging early signs for predicting an individual's mood state changes, with GPS-derived mobility being the top most important feature in the present sample.

Speech-based markers for posttraumatic stress disorder in US veterans

Abstract: Background The diagnosis of posttraumatic stress disorder (PTSD) is usually based on clinical interviews or self-report measures. Both approaches are subject to under- and over-reporting of symptoms. An objective test is lacking. We have developed a classifier of PTSD based on objective speech-marker features that discriminate PTSD cases from controls. Methods Speech samples were obtained from warzone-exposed veterans, 52 cases with PTSD and 77 controls, assessed with the Clinician-Administered PTSD Scale. Individuals with major depressive disorder (MDD) were excluded. Audio recordings of clinical interviews were used to obtain 40,526 speech features which were input to a random forest (RF) algorithm. Results The selected RF used 18 speech features and the receiver operating characteristic curve had an area under the curve (AUC) of 0.954. At a probability of PTSD cut point of 0.423, Youden's index was 0.787, and overall correct classification rate was 89.1%. The probability of PTSD was higher for markers that indicated slower, more monotonous speech, less change in tonality, and less activation. Depression symptoms, alcohol use disorder, and TBI did not meet statistical tests to be considered confounders. Conclusions This study demonstrates that a speech-based algorithm can objectively differentiate PTSD cases from controls. The RF classifier had a high AUC. Further validation in an independent sample and appraisal of the classifier to identify those with MDD only compared with those with PTSD comorbid with MDD is required.

Detecting PTSD in a traumatically injured population: The diagnostic utility of the PTSD Checklist for DSM-5.

Abstract: Background The posttraumatic stress disorder (PTSD) Checklist for DSM-5 (PCL-5) is among few validated measures of PTSD severity in line with the DSM-5. Validation efforts among veteran samples have recommended cut scores of 33 and 38 to indicate PTSD; cut scores vary across populations depending on factors such as trauma type. The purpose of this study was to evaluate the diagnostic utility of and identify optimal cut scores for the PCL-5 in relation to the gold standard Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) among traumatically injured individuals 6 months after discharge from a level I trauma center. Methods A total of 251 participants completed the PCL-5 and CAPS-5 6 months after discharge from a level I trauma center following traumatic injury. Receiver operating characteristic curve analyses detailed diagnostic accuracy of the PCL-5 and identified the optimal cut score via Youden's J index. Cut scores were also broken down by intentional versus nonintentional injury. Results The PCL-5 produces satisfactory diagnostic accuracy, with adequate sensitivity and specificity, in a traumatically injured population. Estimates indicate the optimal cut score as >30; the optimal cut score for intentional injuries was >34 and >22 for nonintentional injuries. Conclusions This investigation provides support for the PCL-5 in detection of PTSD among injured individuals 6 months after discharge from a level I trauma center. PCL-5 specificity and sensitivity suggest clinicians working with this population can feel confident in using this measure over more onerous structured interviews (e.g., CAPS-5). This study signifies a move toward ensuring those experiencing mental health difficulties after traumatic injury are identified and connected to resources.

Social anxiety is associated with BNST response to unpredictability.

Abstract: Background Anxiety disorders are highly prevalent and cause substantial suffering and impairment. Whereas the amygdala has well-established contributions to anxiety, evidence from rodent and nonhuman primate models suggests that the bed nucleus of the stria terminalis (BNST) may play a critical, and possibly distinct, role in human anxiety disorders. The BNST mediates hypervigilance and anticipatory anxiety in response to an unpredictable or ambiguous threat, core symptoms of social anxiety, yet little is known about the BNST's role in social anxiety. Methods Functional magnetic resonance imaging was used to measure neural responses during a cued anticipation task with an unpredictable, predictable threat, and predictable neutral cues followed by threat or neutral images. Social anxiety was examined using a dimensional approach (N = 44 adults). Results For unpredictable cues, higher social anxiety was associated with lower BNST-amygdala connectivity. For unpredictable images, higher social anxiety was associated with greater connectivity between the BNST and both the ventromedial prefrontal cortex and the posterior cingulate cortex and lower connectivity between the BNST and postcentral gyrus. Social anxiety moderated the BNST-amygdala dissociation for unpredictable images; higher social anxiety was associated with BNST > amygdala response to unpredictable threat relative to unpredictable neutral images. Conclusions Social anxiety was associated with alterations in BNST responses to unpredictability, particularly in the BNST's interactions with other brain regions, including the amygdala and prefrontal cortex. To our knowledge, these findings provide the first evidence for the BNST's role in social anxiety, which may be a potential new target for prevention and intervention.

Residual symptoms following prolonged exposure and present-centered therapy for PTSD in female veterans and soldiers.

Abstract: Background Despite the effectiveness of evidence-based treatments for posttraumatic stress disorder (PTSD), some symptoms, such as sleep disturbance, can be difficult to treat regardless of treatment type. Methods We examined residual PTSD symptoms in 235 female veterans and soldiers who were randomized to receive 10 weekly sessions of either Prolonged Exposure (PE) or Present-Centered Therapy (PCT). PTSD symptoms were assessed using the Clinician-Administered PTSD Scale. Analyses examined the effects of PE and the effects of clinically significant improvement (loss of diagnosis, operationalized as meaningful symptom reduction and no longer meeting diagnostic criteria). Results Both treatments resulted in reductions in PTSD symptoms. PE had lower conditional probabilities than PCT of retaining intrusive memories, avoidance of people/places, detachment/estrangement, and restricted range of affect. Loss of diagnosis had lower conditional probabilities of almost all symptoms, although hyperarousal symptoms-especially irritability/anger (60.7%) and sleep difficulties (50.9%)-were the most likely to remain. Conclusions Results are consistent with previous findings on sleep difficulties being difficult to treat, but also show that hyperarousal symptoms overall may not be resolved even after substantial improvement. Additional strategies may be needed to treat the full range of PTSD symptoms in some patients.

Systematic review and meta-analysis: Dose–response curve of SSRIs and SNRIs in anxiety disorders

Abstract: Background We aimed to examine the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) for anxiety disorders examining overall symptom improvement, likelihood of treatment response, time course of treatment response, individual pharmacological agent, diagnostic indication dose, and tolerability. Methods We searched PubMed and Cochrane Central Register of Controlled Trials. We included randomized placebo-controlled clinical trials of SSRIs/SNRIs in adult patients with anxiety disorders that provided data at three or more time points. Extracted data included trial duration, weekly/biweekly anxiety scores for 12 weeks. Results Meta-analysis included 57 trials (N = 16,056). A linear mixed model analysis based on weekly outcome data suggested that for SNRI a logarithmic model offered the best fit compared to placebo (indicating the greatest incremental improvement from baseline occurred early in treatment); whereas for SSRI a linear model provided the best fit (indicating a similar improvement over the duration of the acute treatment phase). There were no significant differences in efficacy between pharmacological agents within each class or when comparing SSRIs to SNRIs. The greatest treatment benefits were observed for social anxiety disorder for both medication classes. Higher doses of SSRIs, but not SNRIs, were associated with significantly greater symptom improvement and likelihood of treatment response. For both medical classes, higher doses were associated with an increased likelihood of dropout due to side effects. Conclusions SSRIs and SNRIs are effective in treating anxiety disorders. Higher doses of SSRIs within the therapeutic range are associated with greater treatment benefit, whereas higher doses of SNRIs are not.

Differences between chronic and nonchronic depression: Systematic review and implications for treatment.

Abstract: Background There is still uncertainty if and to what extent chronic depression (CD) presents with specific features especially in contrast to the nonchronic course of major depressive disorder (non-CD). This systematic review aims to summarize the existing literature regarding sociodemographic factors, psychopathology, and course of disease in patients with CD in comparison to patients with non-CD. Methods A structured database search (MEDLINE, PsycINFO, Web of Science, CENTRAL) was performed. All studies comparing CD with non-CD patients were included. Twenty-eight studies, including cohort studies, cross-sectional studies, and observational studies, were identified in which both subgroups were diagnosed according to DSM-IV or DSM-5, respectively. Primary outcome were group comparisons focused on sociodemographic factors, childhood adversity, onset of the disorder, comorbidities, severity and course of the depressive symptoms, and specific psychopathology. Results Patients with CD had an earlier onset of depressive symptoms, higher rates of psychiatric comorbidities, and a complicated treatment course (e.g., higher rates of suicidality) compared to non-CD. We also found some evidence for specific features in the psychopathology of CD patients (submissive and hostile interpersonal styles) in contrast to non-CD patients. Results were inconsistent with regard to childhood maltreatment. No differences were found regarding the severity of depressive symptoms and most sociodemographic factors. Conclusion Despite some inconsistencies, the results of this review verified important differences between CD and non-CD. However, future research is needed to characterize especially the specific psychopathology of CD in comparison to non-CD patients to develop more tailored treatment strategies.

Bipolar disorder and depression in early adulthood and long‐term employment, income, and educational attainment: A nationwide cohort study of 2,390,127 individuals

Abstract: Background Mood disorders are known to be associated with poor socioeconomic outcomes, but no study has examined these associations across the entire worklife course. Our goal was to estimate the associations between bipolar disorder and depression in early adulthood and subsequent employment, income, and educational attainment. Methods We conducted a nationwide prospective cohort study including all individuals (n = 2,390,127; 49% female) born in Denmark between 1955 and 1990. Hospital-based diagnoses of depression and bipolar disorder before age 25 were obtained from the Danish psychiatric register. Yearly employment, earnings, and education status from ages 25 to 61 were obtained from the Danish labor market and education registers. We estimated both absolute and relative proportions. Results Population rates of hospital-diagnosed depression and bipolar between ages 15-25 were 1% and 0.12%, respectively. Compared to individuals without mood disorders, those with depression and particularly bipolar disorder had consistently poor socioeconomic outcomes across the entire work-life span. For example, at age 30, 62% of bipolar and 53% of depression cases were outside the workforce compared to 19% of the general population, and 52% of bipolar and 42% of depression cases had no higher education compared to 27% of the general population. Overall, individuals with bipolar disorder or depression earned around 36% and 51%, respectively, of the income earned by individuals without mood disorders. All associations were smaller for individuals not rehospitalized after age 25. Conclusions Severe mood disorders with onset before age 25, particularly bipolar disorder, are associated with persistent poor socioeconomic outcomes across the entire work-life course.

Structural imaging biomarkers for bipolar disorder: Meta-analyses of whole-brain voxel-based morphometry studies

Abstract: Background Bipolar disorder (BD) is a common and destructive psychiatric illness worldwide. Although it is known that BD is associated with morphological abnormalities of the brain, the regions implicated in BD remain unclear. Therefore, we aimed to update current knowledge on potential structural imaging biomarkers of BD. Methods Studies published up to January 31, 2018, were identified by a comprehensive literature search of PubMed, EBSCO, and BrainMap voxel-based morphometry (VBM) database. Whole-brain VBM studies that examined gray matter (GM) abnormalities of group comparisons between BD and healthy controls (HC) and reported results as coordinates in a standard reference space were included. Different meta-analyses were performed by activation likelihood estimation (ALE) algorithm. Results A total of 46 studies with 56 experiments, including 1720 subjects and 268 foci were included. Seven different meta-analyses were calculated separately across experiments reporting decreased or increased GM volume among BD, BDΙ, BD-adults, and BD-youths groups. Fifteen regions of significantly different GM volume between four groups and HC were identified. There were extensive GM deficits in the prefrontal and temporal cortex, and enlargements in the putamen, cingulate cortex, and precuneus. Conclusions The results revealed that the thinning of prefrontal cortex was a key region in the pathophysiology of BD. The enlargement of the cingulate cortex may be implicated in a compensatory mechanism. It underscored important differences between BD-adults and BD-youths and specific biomarkers of three subgroups.

Differentiating PTSD from anxiety and depression: Lessons from the ICD-11 PTSD diagnostic criteria.

Abstract: Objective: Posttraumatic stress disorder (PTSD) is frequently associated with depression and anxiety, but the nature of the relationship is unclear. By removing mood and anxiety diagnostic criteria, the 11th edition of the International Classification of Diseases (ICD-11) aims to delineate a distinct PTSD phenotype. We examined the effect of implementing ICD-11 criteria on rates of codiagnosed depression and anxiety in survivors with recent PTSD. Method: Participants were 1,061 survivors of traumatic injury admitted to acute care centers in Israel. ICD-10 and ICD-11 diagnostic rules were applied to the Clinician-Administered PTSD Scale for DSM-IV. Co-occurring disorders were identified using the Structured Clinical Interview for DSM-IV (SCID). Depression severity was measured by the Beck Depression Inventory-II (BDI-II). Assessments were performed 0–60 (“wave 1”) and 90–240 (“wave 2”) days after trauma exposure. Results: Participants identified by ICD-11 PTSD criteria were equally or more likely than those identified by the ICD-10 alone to meet depression or anxiety disorder diagnostic criteria (for wave 1: depressive disorders, OR [odds ratio] = 1.98, 95% CI [confidence interval] = [1.36, 2.87]; anxiety disorders, OR = 1.04, 95% CI = [0.67, 1.64]; for wave 2: depressive disorders, OR = 1.70, 95% CI = [1.00, 2.91]; anxiety disorders, OR = 1.04, 95% CI = [0.54, 2.01]). ICD-11 PTSD was associated with higher BDI scores (M = 23.15 vs. 17.93, P < 0.001 for wave 1; M = 23.93 vs. 17.94, P < 0.001 for wave 2). PTSD symptom severity accounted for the higher levels of depression in ICD-11 PTSD. Conclusions: Despite excluding depression and anxiety symptom criteria, the ICD-11 identified equal or higher proportion of depression and anxiety disorders, suggesting that those are inherently associated with PTSD.

Consistency of trajectories of suicidal ideation and depression symptoms: Evidence from a randomized controlled trial.

Abstract: Background Depression is a risk factor for suicidal ideation. However, suicidal ideation can occur in the absence of depression and treating depression may not reduce suicidal thinking. This study tested whether trajectories of suicidal thinking are concordant with trajectories of depressive symptoms and sought to identify factors associated with these trajectories. Methods Participants were community-based Australian adults (N = 418, 77% female) enrolled in a randomized controlled trial evaluating the effectiveness of an online cognitive-behavioral intervention for suicidal ideation. Separate linear growth mixture models were estimated across 12 months of follow-up to identify longitudinal trajectories of suicidal ideation and depression symptoms. Predictors of latent class membership were tested using logistic regression models. Results Two-class models were found to have optimal fit for both suicidal thinking and depressive symptoms. Trajectory classes of suicidal ideation were: (1) moderate severity decreasing over time; and (2) high severity remaining stable over time. Depression trajectories were: (1) moderate severity with a small decrease over time; and (2) high severity that decreased moderately over time. Lower perceived burdensomeness was associated with having a greater decrease in both suicidal thinking and depression. More severe mental health symptoms were associated with less decrease in depression symptoms but not with suicidal ideation trajectory. Conclusion Class membership across the two outcomes and predictors of class membership were found to be largely independent. The lack of coupling in trajectories and predictors suggests that changes in suicidal thinking may occur independently of changes in depression.

Heart rate variability as a biomarker of anxious depression response to antidepressant medication

Abstract: Background There is a need to identify biomarkers of treatment outcomes for major depressive disorder (MDD) that can be disseminated. We investigated the predictive utility of pretreatment heart rate variability (HRV) for outcomes of antidepressant medication in MDD, with pretreatment anxious depression as a hypothesized moderator of HRV effects. Methods A large, randomized, multicenter practical trial (International Study to Predict Optimized Treatment in Depression) in patients with current nonpsychotic MDD (N = 1,008; 722 completers) had three arms: escitalopram, sertraline, and venlafaxine-extended release. At pretreatment, patients were defined as having anxious (N = 309) versus nonanxious (N = 413) depression and their resting high-frequency HRV (root mean square of successive differences) was assessed. Patients' usual treating clinicians managed medication. At 8 weeks, primary outcomes were clinician-rated depressive symptom response and remission; secondary outcomes were self-reported response and remission. Results Pretreatment HRV predicted antidepressant outcomes as a function of anxious versus nonanxious depression. In anxious depression, patients with higher HRV had better outcomes, whereas patients with lower HRV had poorer outcomes. In nonanxious depression, patients with lower HRV had better outcomes, whereas patients with higher HRV had poorer outcomes. Some simple effects were not significant. Results did not differ by treatment arm and remained significant when controlling for important covariates. Conclusions These findings inform a precision medicine approach in which clinical and biological assessments may be integrated to facilitate treatment outcome prediction. Knowing about HRV may help determine which patients with anxious depression could benefit from antidepressants and which patients may require a different treatment approach.

Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression.

Abstract: Objective To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment-resistant depression (TRD). Methods In a multisite, double-blind, placebo-controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was change in the six-item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety-Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion. Results N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73). Conclusion In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.

Is rTMS effective for anxiety symptoms in major depressive disorder? An efficacy analysis comparing left-sided high-frequency, right-sided low-frequency, and sequential bilateral rTMS protocols.

Abstract: BACKGROUND Anxiety symptoms are common in major depressive disorder. Whilst therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression is well-established, minimal research has investigated rTMS's efficacy in treating anxiety symptoms in depression. METHODS This study investigates the effectiveness of rTMS in treating anxiety symptoms in depression, specifically the relative efficacy of the three rTMS protocols commonly used in clinical practice: left-sided high-frequency, right-sided low-frequency and sequential bilateral rTMS. Antidepressant efficacy of each rTMS protocol is also investigated. Treatment data for 697 patients were pooled from three studies across five sites. Changes in Beck's Anxiety Inventory (BAI) and the Hamilton Depression Rating Scale over 4-week rTMS courses were analysed using latent growth curve modelling. RESULTS All rTMS protocols were effective in treating anxiety symptoms (mean BAI reduction, 8.13 points; p < 0.001) and depressive symptoms. Near therapeutic equivalence was seen across the three protocols. Improvement in depressive severity positively correlated with improvement in anxiety. Both high- and low-baseline anxiety scores showed overall symptom reduction. CONCLUSIONS This study addresses the clinical knowledge gap pertaining to rTMS's therapeutic efficacy in treating anxiety symptoms in depression and the relative efficacy of three commonly used stimulation protocols. Our findings suggest therapeutic equivalence across left-sided high-frequency, right-sided low-frequency, and sequential bilateral rTMS approaches.

Transdiagnostic neural correlates of volitional emotion regulation in anxiety and depression.

Abstract: Background Individuals who suffer from anxiety and/or depression face difficulty in adaptively managing emotional responses, while accumulating evidence suggests impaired emotion regulation is a transdiagnostic feature of psychopathology. Effectual regulation in the context of negative stimuli is characterized by engagement of the prefrontal cortex (PFC) coupled with reduced amygdala reactivity. In anxiety disorders and major depression, PFC underengagement and atypical PFC-amygdala connectivity has been observed, although patient findings based on case-control studies have been mixed with regard to magnitude, locality, and extent of dysfunction. As anxiety disorders and major depression are heterogeneous disorders and frequently comorbid with one another, delineating relationships between reappraise-related substrates and symptoms may advance our understanding of emotion dysregulation in these populations. Methods We examined PFC activation and its functional connectivity (FC) to the amygdala using functional magnetic resonance imaging in a large sample of patients (N = 174) with primary generalized anxiety disorder (n = 47), social anxiety disorder (n = 78), or major depressive disorder (n = 49) during a reappraisal-based emotion regulation task. Comorbidity was permitted and the majority of participants had a concurrent psychiatric illnesses. Results Across participants, whole-brain results showed that (1) greater anxiety and depression symptom severity was related to less engagement of the dorsal anterior cingulate cortex (ACC) and (2) less FC between the amygdala and ventrolateral PFC. Results were driven by anxiety, while depression symptoms were not significant. Conclusion These findings demonstrate that individual differences in anxiety and depression may help explain ACC and PFC dysfunction during emotion regulation observed across anxiety and depressive disorders.

Hoarding: A meta‐analysis of age of onset

Abstract: Hoarding disorder is present in 2-6% of the population and can have an immense impact on the lives of patients and their families. Before its inclusion the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, pathological hoarding was often characterized as a symptom of obsessive-compulsive disorder, and several different diagnostic assessment methods were used to identify and characterize it. Although the age of onset of pathological hoarding is an important epidemiological measure, as clarifying the age of onset of hoarding symptoms may allow for early identification and implementation of evidence-based treatments before symptoms become clinically significant, the typical age of onset of hoarding is still uncertain. To that end, this study is a systematic review and meta-analysis of research published in English between the years 1900 and 2016 containing information on age of onset of hoarding symptoms. Twenty-five studies met inclusion criteria. The mean age of onset of hoarding symptoms across studies was 16.7 years old, with evidence of a bimodal distribution of onset. The authors conclude by discussing practice implications for early identification and treatment.

Resting-state brain fluctuation and functional connectivity dissociate moral injury from posttraumatic stress disorder.

Abstract: Moral injury is closely associated with posttraumatic stress disorder (PTSD) and characterized by disturbances in social and moral cognition. Little is known about the neural underpinnings of moral injury, and whether the neural correlates are different between moral injury and PTSD. A sample of 26 U.S. military veterans (two females: 28-55 years old) were investigated to determine how subjective appraisals of morally injurious events measured by Moral Injury Event Scale (MIES) and PTSD symptoms are differentially related to spontaneous fluctuations indexed by amplitude of low frequency fluctuation (ALFF) as well as functional connectivity during resting-state functional magnetic resonance imaging scanning. ALFF in the left inferior parietal lobule (L-IPL) was positively associated with MIES subscores of transgressions, negatively associated with subscores of betrayals, and not related with PTSD symptoms. Moreover, functional connectivity between the L-IPL and bilateral precuneus was positively related with PTSD symptoms and negatively related with MIES total scores. Our results provide the first evidence that morally injurious events and PTSD symptoms have dissociable neural underpinnings, and behaviorally distinct subcomponents of morally injurious events are different in neural responses. The findings increase our knowledge of the neural distinctions between moral injury and PTSD and may contribute to developing nosology and interventions for military veterans afflicted by moral injury.

Anomalous functional connectivity of amygdala subregional networks in major depressive disorder.

Abstract: Objective Amygdala-based network dysfunction has been found to be centrally implicated in major depressive disorder (MDD). However, relatively little is known about how different forms of effective or cognitive dysfunction are modulated in MDD. Therefore, in the current study, we aimed to examine the alteration of amygdala subregional networks in adult patients with MDD to explore whether different parts of the amygdala that are functionally connected to different regions contribute differently to the cerebral network mechanism of depression. Methods Resting-state fMRI scans were obtained from 70 medication-free adults with MDD and 70 age- and sex-matched healthy controls (HC). Functional connectivity maps of four distinct regions of the amygdala, including the amygdalostriatal transition area (AStr) and the basolateral (BLA), centromedial (CM) and superficial (SF) amygdala, were generated and compared between the two groups. Results Compared with HC, patients with MDD showed hypoconnectivity between the AStr/BLA and the orbitofrontal cortex (OFC), between the CM/SF and the brainstem/cerebellum, and within AStr/CM/SF-thalamic/striatal networks. Hyperconnectivity was observed between the left AStr/BLA and the fusiform gyrus. There was no difference in the gray matter volume of the amygdala or any of its subregions between the two groups. Conclusions These findings suggest that amygdala subregional-network dysfunction in MDD is independent of structural changes and, more important, that hypoconnectivity and hyperconnectivity in different subregional networks may reflect imbalanced network function, which may modulate different forms of emotional and cognitive dysfunction in MDD.

Association between posttraumatic stress disorder severity and amygdala habituation to fearful stimuli.

Abstract: Background Amygdala hyperreactivity to threat has been proposed to be a causal contributor to posttraumatic stress disorder (PTSD). However, emerging literature in healthy samples shows higher test-retest reliability for amygdala habituation (the change over time in response to repeated stimuli) than for its reactivity to threat. Amygdala habituation has received relatively little attention in relationship to PTSD, despite the key role of this region in the etiology of the disorder. Thus, we investigated habituation to repeated fearful face stimuli and PTSD, in a large sample of trauma exposed African American women. Methods African American women (N = 100) were recruited from a nonprofit hospital serving a largely low-income population with a high risk of trauma exposure. Participants underwent functional magnetic resonance imaging, passively viewing fearful and neutral face stimuli, and reported their history of trauma exposure and current PTSD symptoms. We examined associations between PTSD symptom severity and amygdala reactivity (fearful > neutral) and habituation (early > late) to fearful faces. Secondary analyses tested whether amygdala habituation to fearful faces mediated the association between childhood trauma and PTSD. Results PTSD symptom severity and PTSD status (based on self-report measure) were both positively associated with amygdala habituation to repeated fearful face stimuli. Whole-brain analysis showed that this association extended to the bilateral hippocampus and left fusiform gyrus. The association held when controlling for trauma history and depressive symptoms. Amygdala habituation to fearful faces partially mediated the association between childhood trauma severity and PTSD symptom severity. Conclusion Individuals with greater PTSD symptom severity showed greater amygdala habituation to social threat cues (fearful faces), and greater habituation may partly explain the association between childhood trauma exposure and current PTSD symptoms. Further examination of the dynamics of the amygdala response to threat cues may lead to new insights in the understanding and treatment of stress-related disorders.

Early response to psychological therapy as a predictor of depression and anxiety treatment outcomes: A systematic review and meta-analysis

Abstract: Background: Previous studies indicate that early symptomatic improvement, typically observed during the first 4 weeks of psychological therapy, is associated with positive treatment outcomes for a range of mental health problems. However, the replicability, statistical significance and magnitude of this association remains unclear. Aim: The present study reviewed the literature on early response to psychological interventions for adults with depression and anxiety symptoms. Methods: A systematic review and random effects meta-analysis was conducted, including studies found in Medline, PsychINFO, SCOPUS, Web of Science, and through reference lists and reverse citations. Results: Twenty-five eligible studies including 11091 patients measured early response and examined associations with post-treatment outcomes. It was possible to extract and/or calculate effect size data from 15 studies to conduct a meta-analysis. A large pooled effect size (g = 0.87 [95 % CI: 0.63, 1.10] p < .0001) indicated that early responders had significantly better post-treatment outcomes compared to cases without early response, and this effect was larger in anxiety (g = 1.37) compared to depression (g = 0.76) measures. Most studies were of good quality and there was no evidence of publication bias. The main limitations concerned insufficient statistical reporting in some studies, which meant that the meta-analysis only included 60% of reviewed studies, and it was not possible to examine effect sizes according to different outcome questionnaires. Conclusions: There is robust and replicated evidence that early response to therapy is a reliable prognostic indicator for depression and anxiety treatment outcomes.

Depression increases the genetic susceptibility to high body mass index: Evidence from UK Biobank

Abstract: Background This study aimed to explore the association between depression and body mass index (BMI), and to investigate whether genetic susceptibility to high BMI is different among individuals with or without depression. Methods We used data on 251,125 individuals of white British ancestry from the UK Biobank. We conducted Mendelian randomization (MR) analysis to test for a causal association between depression and BMI using a major depressive disorder (MDD)‐related genetic risk score (GRSMDD) as an instrument for depression. We also examined whether depression modifies genetic susceptibility to high BMI, by investigating the interaction between depression and the BMI‐related GRSBMI. Results We found observational and genetic evidence for an association between depression and BMI (MR beta: 0.09, 95% confidence interval [CI] 0.04–0.13). Further, the contribution of genetic risk to high BMI was higher among individuals with depression compared to controls. Carrying 10 additional BMI increasing alleles was associated with 0.24 standard deviation (SD; 95%CI 0.23–0.25) higher BMI among depressed individuals compared to 0.20 SD (95%CI 0.19–0.21) higher in controls, which corresponds to 3.4 kg and 2.8 kg extra weight for an individual of average height. Amongst the individual loci, the evidence for interaction was most notable for a variant near MC4R, a gene known to affect both appetite regulation and the hypothalamic‐pituitary adrenal axis (pinteraction = 5.7 × 10−5). Conclusion Genetic predisposition to high BMI was higher among depressed than to nondepressed individuals. This study provides support for a possible role of MC4R in the link between depression and obesity.