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Background: OnabotulinumtoxinA (OnaA) injection in glabella area appears to be a promising treatment for major depression. However, one major concern of placebo‐controlled studies on botulinum toxin injections is to ensure adequate blinding. Patients and Methods: In this context, all subjects of this trial received the active product (OnaA). After randomization, 58 patients with resistant major depressive disorder (MDD) received OnaA either in the glabella area (N = 29) or in the crow's feet area (N = 29). Subjects were blinded to the supposedly effective area against resistant depression and the examiner was not aware of the injected area. The primary outcome measure was the proportion of responders (50% or greater decrease in MADRS [Montgomery and Asberg Depression Rating Scale] score from baseline) in glabella group versus crow's feet group at week 6 after the OnaA injection. Results: The number of responders was significantly higher in the glabella group than in the crow's feet group with 13 responders out of 29 patients (44.8%) in the glabella group and five out of 28 patients (17.9%) in the crow's feet group (p = 0.029). The rate of psychomotor agitation as measured by item 9 of the Hamilton Depression Rating Scale (HAM‐D), associated with a shorter span of psychiatric disorder, was a potent positive predictive factor of positive response to treatment. Conclusion: We conclude that OnaA injected in the glabella muscles is an effective and well‐tolerated treatment for MDD. We suggest that patients with a high score at item 9 of the HAM‐D might be a subgroup of best responders. We assume that OnaA may act as a modulator of the activity of the primary sensorimotor cortex and then of the amygdala. Trial Registration: ClinicalTrials.gov identifier: NCT03484754 [ABSTRACT FROM AUTHOR]

Background: Internalizing psychopathologies (IPs) are highly comorbid and exhibit substantial overlap, such as aberrant affective reactivity. Neural reactivity to emotional images, measured via the late positive potential (LPP) event-related potential (ERP) component, has been utilized to index affective reactivity in IPs. The LPP is often examined in isolation with a specific disorder, ignoring overlap between IPs. The current study examined how transdiagnostic IP symptom dimensions relate to neural affective reactivity in a highly comorbid patient sample.Methods: Participants (N = 99) completed a battery of IP symptom assessments as well as a target categorization task while viewing pleasant, unpleasant, and neutral images during electroencephalography recording. ERPs to each image valence were averaged from 400 to 1000 ms following picture onset at pooled centroparietal and occipital electrodes to calculate the LPP. A principal components analysis performed on the IP symptom measures resulted in two factors: affective distress/misery and fear-based anxiety.Results: Fear-based anxiety was associated with enhanced LPP reactivity to unpleasant, but not pleasant, images. Distress/misery was related to attenuated average LPP reactivity across images.Conclusions: Results revealed a dissociable effect of IP symptom factors in a transdiagnostic sample such that enhanced reactivity to negative images was specific to enhanced fear-based anxiety symptoms while distress/misery symptoms predicted blunted affective reactivity. Neural affective reactivity may serve as an objective biological marker to elucidate the nature of psychological concerns in individuals with comorbid IPs. [ABSTRACT FROM AUTHOR]

Background: The underlying mechanism between sensory impairments (SIs) and depressive symptoms among Chinese older adults is not well understood. This study aims to explore the mediating role of functional limitation on the longitudinal relationship between SIs and depressive symptoms among older adults in China. Methods: A total of 4130 older adults who participated in the 3‐year follow‐up China Health and Retirement Longitudinal Study (CHARLS) were included in the analysis. The hierarchical multiple linear regression model and nonparametric bootstrapping method were employed to explore the relationship between SIs and depressive symptoms, and the mediating role of functional limitation in this link. Results: The prevalence of self‐reported hearing impairment (HI) only, vision impairment (VI) only, and dual sensory impairment (DSI) at baseline were 5.7%, 22.2%, and 58.6%, respectively. After adjusting for controlling variables, older adults with DSI had significantly higher levels of depressive symptoms compared with those without SIs at baseline (β =.07, p =.005). The magnitude of mediation effect from DSI to depressive symptoms via functional limitation was a*b = 0.060 (BCa 95% confidence interval: 0.031–0.094). Conclusions: Functional limitation partially mediated the relationship between DSI and depressive symptoms among Chinese older adults. Interventions of DSI and functional limitation should be included in depressive symptoms prevention among older adults in China. [ABSTRACT FROM AUTHOR]

Background: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM‐5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. However, little is known about the neurobiological correlates of anxious distress in MDD. Methods: We probed the relation between the DSM‐5 ADS and task‐related reactivity to emotional faces, as well as resting‐state functional connectivity patterns of intrinsic salience and basal ganglia networks in unmedicated MDD patients with (MDD/ADS+, N = 24) and without ADS (MDD/ADS−, N = 48) and healthy controls (HC, N = 59). Both categorical and dimensional measures of ADS were investigated. Results: MDD/ADS+ patients had higher left amygdala responses to emotional faces compared to MDD/ADS− patients (p =.015)—part of a larger striato‐limbic cluster. MDD/ADS+ did not differ from MDD/ADS− or controls in resting‐state functional connectivity of the salience or basal ganglia networks. Conclusions: Current findings suggest that amygdala and striato‐limbic hyperactivity to emotional faces may be a neurobiological hallmark specific to MDD with anxious distress, relative to MDD without anxious distress. This may provide preliminary indications of the underlying mechanisms of anxious distress in depression, and underline the importance to account for heterogeneity in depression research. [ABSTRACT FROM AUTHOR]

Background: Cognitive remediation (CR) is a promising technique in the treatment of the cognitive dimension of depression. The present study evaluated the potential of CR in treating depressive symptoms and provides practical information about its usefulness in clinical settings. Methods: We performed two meta‐analyses of published randomized (and nonrandomized) clinical trials, comparing CR to control conditions in subjects with current depressive symptomatology. The superiority meta‐analysis aimed to determine the superiority of CR when compared with placebo/waiting list interventions and its efficacy when used as an augmentation therapy. The noninferiority meta‐analysis determined whether CR had noninferior efficacy compared with standard antidepressant interventions. Results: CR was found to significantly improve depressive symptomatology in the superiority meta‐analysis (CR: n = 466, control n = 478). Moreover, CR seemed to be noninferior to standard antidepressant interventions (CR: n = 230, control n = 235). CR was more effective when addressing hot (vs. cold) cognition, when involving younger patients (i.e., <30 years), and in the case of mild‐moderate (vs. severe) depression. Conclusions: CR should be considered an augmentation treatment to improve treatment outcomes in depressed subjects, especially among young individuals. Interventions addressing hot cognition seem to be the most promising. [ABSTRACT FROM AUTHOR]

Background: Despite evidence linking posttraumatic stress disorder (PTSD), depression, and head injury, separately, with worse cognitive performance, investigations of their combined effects on cognition are limited in civilian women. Methods: The Cogstate Brief Battery assessment was administered in 10,681 women from the Nurses' Health Study II cohort, mean age 64.9 years (SD = 4.6). Psychological trauma, PTSD, depression, and head injury were assessed using online questionnaires. In this cross‐sectional analysis, we used linear regression models to estimate mean differences in cognition by PTSD/depression status and stratified by history of head injury. Results: History of head injury was prevalent (36%), and significantly more prevalent among women with PTSD and depression (57% of women with PTSD and depression, 21% of women with no psychological trauma or depression). Compared to having no psychological trauma or depression, having combined PTSD and depression was associated with worse performance on psychomotor speed/attention (β = −.15, p =.001) and learning/working memory (β = −.15, p <.001). The joint association of PTSD and depression on worse cognitive function was strongest among women with past head injury, particularly among those with multiple head injuries. Conclusions: Head injury, like PTSD and depression, was highly prevalent in this sample of civilian women. In combination, these factors were associated with poorer performance on cognitive tasks, a possible marker of future cognitive health. Head injury should be further explored in future studies of PTSD, depression and cognition in women. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety disorders confer a significant public health concern for youth and their co‐occurrence places youth at a higher risk for poorer psychosocial outcomes. In the present study, we use network analysis to investigate the role of and interactions among individual depression and anxiety symptoms in a treatment‐seeking clinical sample. Methods: We estimate regularized partial correlation networks for youth‐ and parent reported symptoms in a transdiagnostic sample of youth (N = 417, ages 8–18). We examined features of the symptom‐level networks such as network stability, centrality, bridge symptoms, and communities in both youth‐ and parent‐reported networks. Results: Results indicate stable networks with disorder‐specific clustering, such that symptoms were more interconnected within compared to between disorders. Symptoms related to self‐comparison to peers and negative views of the future were most central in both networks. Symptoms of depression and anxiety were connected by worries for the future and hopelessness in the youth‐reported network, whereas self‐comparison to peers and low self‐efficacy were bridge symptoms in the parent network. Distinct symptom clusters emerged in the parent‐ and youth‐reported networks. Conclusions: Our findings indicate that negative self‐evaluation, negative views of the future, and repetitive negative thinking more generally are influential symptoms in the presentation and co‐occurrence of depression and anxiety and as such may be promising targets in the treatment and prevention of depression and anxiety in youth. [ABSTRACT FROM AUTHOR]

Background: Distinctions between major depressive disorder (MDD) and perinatal depression (PND) reflect varying views of PND, from a unique etiological subtype of MDD to an MDD episode that happens to coincide with childbirth. This case–control study investigated genetic differences between PND and MDD outside the perinatal period (non‐perinatal depression or NPD). Methods: We conducted a genome‐wide association study using PND cases (Edinburgh Postnatal Depression Scale score ≥ 13) from the Australian Genetics of Depression Study 2018 data (n = 3804) and screened controls (n = 6134). Results of gene‐set enrichment analysis were compared with those of women with non‐PND. For six psychiatric disorders/traits, genetic correlations with PND were evaluated, and logistic regression analysis reported polygenic score (PGS) association with both PND and NPD. Results: Genes differentially expressed in ovarian tissue were significantly enriched (stdBeta = 0.07, p = 3.3e−04), but were not found to be associated with NPD. The genetic correlation between PND and MDD was 0.93 (SE = 0.07; p = 3.5e−38). Compared with controls, PGS for MDD are higher for PND cases (odds ratio [OR] = 1.8, confidence interval [CI] = [1.7–1.8], p = 9.5e−140) than for NPD cases (OR = 1.6, CI = [1.5–1.7], p = 1.2e−49). Highest risk is for those reporting both antenatal and postnatal depression, irrespective of prior MDD history. Conclusions: PND has a high genetic overlap with MDD, but points of distinction focus on differential expression in ovarian tissue and higher MDD PGS, particularly for women experiencing both antenatal and postpartum PND. [ABSTRACT FROM AUTHOR]

Background: Health practitioners often meet older persons suffering both from pain and depression. The study aimed to examine the factors associated with pain among older individuals and its association with major depression. In addition, the interaction between self‐rated health (SRH), wealth status, and pain that is associated with depression are explored. Methods: We used data from the Longitudinal Aging Study in India (LASI). Participants included 15,098 male and 16,366 female adults aged 60 years or older. Univariate and bivariate analyses along with χ2 tests were conducted in the initial stage. Binary logistic regression analyses were performed to fulfill the objectives. Major depression was calculated using Short Form Composite International Diagnostic Interview. Results: A proportion of 39.6% older individuals (n = 12,686) reported pain and 8.7% older adults (n = 2657) suffered from depression. Older adults who suffered from pain frequently were more likely to be depressed than those who never suffered from pain (adjusted odds ratio [AOR]: 1.70; confidence interval [CI]: 1.38–2.09). The interaction of pain, SRH, and household wealth status on depression found that older adults with pain who reported poor SRH (AOR: 4.18; CI: 3.50–5.00) or belonged to rich households (AOR: 2.27; CI: 1.84–2.80) had higher odds of suffering from depression, compared to older adults with no pain and good SRH or no pain and belonged to poor households. Conclusion: It is highlighted that pain is quite common in older people, and is linked to depression especially among older people with poor SRH. Thus, routine evaluation of pain and associated symptoms of mental illnesses should be performed for ensuring healthy aging. [ABSTRACT FROM AUTHOR]

Background: Mindfulness‐based cognitive therapy (MBCT) is effective for relapse prevention in major depressive disorder (MDD). It reduces cognitive reactivity (CR) and rumination, and enhances self‐compassion and mindfulness. Although rumination and mindfulness after MBCT are associated with relapse, the association of CR, rumination, self‐compassion, and mindfulness with relapse before initiation of MBCT has never been investigated. Methods: Data were drawn from two randomized controlled trials, including a total of 282 remitted MDD participants (≥3 depressive episodes) who had been using maintenance antidepressant medication (mADM) for at least 6 months before baseline. All participants were offered MBCT while either their mADM was maintained or discontinued after MBCT. CR, rumination, self‐compassion, and mindfulness were assessed at baseline by self‐rated questionnaires and were used in Cox proportional hazards regression models to investigate their association with relapse. Results: CR and mindfulness were associated with relapse, independent of residual symptoms, previous depressive episodes, and mADM‐use. Higher CR and lower mindfulness increased the risk of relapse. Self‐compassion was not associated with relapse. For rumination, a significant interaction with mADM‐use was found. Rumination was associated with relapse in patients who discontinued their mADM, while this effect was absent if patients continued mADM. Conclusions: These results show that CR, rumination, and mindfulness are associated with relapse in remitted MDD‐patients before initiation of MBCT, independent of residual symptoms and previous depressive episodes. This information could improve decisions in treatment planning in remitted individuals with a history of depression. [ABSTRACT FROM AUTHOR]

Background: Depression is a highly prevalent, debilitating disorder that runs in families. Yet, empirical support for bidirectional mechanisms linking mother–adolescent depression symptoms remains limited. This study examined longitudinal bidirectional relations among emotion regulation (ER) constructs and depressive symptoms among mother–adolescent dyads over time. Pathways for girls and boys were explored separately, given extant research on sex differences in the intergenerational transmission of depression. Methods: Adolescent (n = 232; M = 15.02 years, SD = 0.95; 44% female)‐mother dyads, drawn from a longitudinal study on the development of risky behaviors, completed annual assessments of depressive symptoms and facets of ER over 4 years. Panel modeling examined lagged and cross‐lagged effects of mother–adolescent depressive symptoms and ER constructs over time, in a multigroup model of boys and girls. Results: Among girls, higher baseline maternal depression scores predicted increased adolescent ER difficulties (std. est. = −.42, p <.001) in turn, predicting increased adolescent depressive symptoms (std. est. = −.33, p =.002) and subsequent maternal ER difficulties (std. est. =.39, p =.002). The indirect effect of maternal depressive symptoms→adolescent ER→adolescent depressive symptoms→maternal ER was significant (ind. eff. =.10, 95% confidence interval [>.001,.19]) for girls, but not boys. Conclusion: Implications for interrupting intergenerational cycles of depressive symptoms and emotion dysregulation are discussed. [ABSTRACT FROM AUTHOR]

Introduction: The dynamic interplay between parent depressive symptoms and child internalizing behavior over time is not well understood. Methods: We used data from a prospective parent‐offspring adoption design (N = 561) to examine associations between adoptive parent depressive symptoms and child internalizing behavior when children were ages 18 months, 27 months, 4.5 years, and 6 years, and subsequent child psychiatric disorder symptoms when children were between the ages of 6–8 years. Models also accounted for the contributions of birth parent psychopathology, birth mother depressive symptoms during pregnancy, and infant negative emotionality. Bidirectional associations between adoptive parent depressive symptoms and child internalizing behavior were examined using a random‐intercept cross‐lagged panel model. Results: There was evidence for associations between child internalizing behavior and adoptive parent depressive symptoms over time, with mothers' depressive symptoms being a more salient risk factor for child internalizing behavior than fathers'. We found one significant cross‐lagged association from adoptive mother depressive symptoms at child age 18 months to child internalizing behavior at age 27 months. Infant negative emotionality (i.e., emotional liability) at age 9 months predicted both child internalizing behavior and adoptive parent depressive symptoms. Conclusion: Results suggest that postnatal maternal depressive symptoms confer specific risks for child internalizing behaviors in toddlerhood and childhood and depressive symptoms in childhood. [ABSTRACT FROM AUTHOR]

Methods: In a 2‐year longitudinal study of 220 families, we examined how youth gender and adrenocortical and parasympathetic activity moderated reciprocal, bidirectional relations between parent and youth anxiety and depression problems. Results: Maternal anxiety predicted subsequent youth anxiety and depression. Maternal depression predicted youth anxiety and, for daughters and youth with low adrenocortical reactivity, youth depression. Youth depression predicted maternal depression only for youth with high adrenocortical reactivity. There were no associations between paternal and youth psychopathology. Discussion: Examining youth gender and psychophysiological characteristics that shape the nature of bidirectional influences may inform efforts to identify families at heightened risk for intergenerational transmission of psychopathology. [ABSTRACT FROM AUTHOR]

Objectives: To study the effectiveness of attachment-based compassion therapy (ABCT) for reducing affective distress in a sample of outpatients with depressive, anxiety, or adjustment disorders, and to explore its mechanisms of action.Methods: This randomized controlled trial involved the assessment time points of pretreatment, posttreatment and 6-month follow-up. A total of 90 patients from three mental health units in Castellón, Spain, were recruited and randomly assigned to "ABCT + treatment as usual (TAU)," "Mindfulness-based stress reduction (MBSR) + TAU" or "TAU" alone. Affective distress, as measured by the "Depression, Anxiety and Stress Scales" (DASS-21) was the main outcome; self-compassion and mindfulness were also assessed. Multilevel mixed-effects models were used to estimate the effectiveness of the program, and path analyses were conducted to study the potential mechanistic role of mindfulness and self-compassion.Results: ABCT was not superior to MBSR in any outcome or at any assessment point. ABCT was superior to TAU alone both posttreatment (B = -13.20; 95% confidence interval [CI]: -19.57, -6.84) and at 6-month follow-up (B = -7.20; 95% CI: -13.63, -0.76) for reducing DASS-21, and MBSR was superior to TAU alone both posttreatment (B = -11.51; 95% CI: -17.97, -5.05) and at 6-month follow-up (B = -8.59; 95% CI: -15.09, -2.10), with large effects (d ≥ 0.90). Changes produced by ABCT in DASS-21 were mediated by self-compassion, whereas changes produced by MBSR were mediated by both mindfulness and self-compassion.Conclusion: ABCT is effective for reducing affective distress in patients with anxiety, depressive and adjustment disorders, although its effect is not superior to that offered by MBSR. Self-compassion seems to be a significant mediator of the effects of ABCT. [ABSTRACT FROM AUTHOR]

Objective: To conduct a systematic review of studies reporting prevalence rates of depression in women living in low‐income circumstances in developed countries. Methods: The published and unpublished literature was searched for studies reporting prevalence of depression in women with low income in developed countries. Searches, data extraction, and methodological appraisal were conducted twice independently. To perform the analysis, the meta and metafor packages in R, a random effect model to account for both between and within studies' variances, and the restricted maximum likelihood method for estimation were used. Results: One‐hundred sixty‐four studies, involving 218,035 participants, were located through the search process. The point prevalence of depression among women in low‐income circumstances using self‐report instruments in 134 studies was 37.4% (95% CI, 34.0%–40.7%). Additionally, the point prevalence according to depression diagnosis in 25 studies was 22.9% (95% CI, 17.8%–28.5%). Conclusions: The high rate of depression among women living in low‐income circumstances is of serious public health concern. Policy Implications: Women living in low‐income circumstances should receive screening and referral/treatment in not only medical service settings, but also in social service settings serving women receiving welfare benefits. [ABSTRACT FROM AUTHOR]

Background: Exposure to multiple psychosocial risk factors may increase vulnerability for mental health conditions during pregnancy. This analysis examined the relationship of a novel psychosocial adversity index with the co‐occurrence and persistence of depression and anxiety throughout pregnancy. Methods: This cross‐sectional analysis included 1797 pregnant women screened in the second/third trimesters for depression and anxiety symptoms and for eight contextual and individual psychosocial factors. The factors were summed to create a psychosocial adversity index; reporting four or more factors indicated high adversity. Elevated symptoms in both trimesters indicated persistent depression/anxiety and elevated symptoms at the same trimester indicated comorbid symptoms. The associations between the psychosocial adversity index and mental health were estimated. Results: Compared with a low psychosocial adversity index, women reporting a high level of psychosocial adversities had 2.06 (95% confidence interval [CI]: 1.51–2.82) times higher adjusted odds of only depressive or anxiety symptoms, and 5.57 (95% CI: 3.95–7.85) times higher adjusted odds of comorbid symptoms. The associations for persistent symptoms were of similar direction and magnitude. Conclusion: High psychosocial adversity was associated with persistent and comorbid depressive symptoms and anxiety during pregnancy. Assessing psychosocial adversity can help identify women at increased risk who would benefit from tailored mental health interventions. [ABSTRACT FROM AUTHOR]

Introduction: The major stressors associated with the COVID‐19 pandemic provide an opportunity to understand the extent to which protective factors against depression may exhibit gender‐specificity. Method: This study examined responses from multiple waves of a 50 states non‐probability internet survey conducted between May 2020 and January 2021. Participants completed the PHQ‐9 as a measure of depression, as well as items characterizing social supports. We used logistic regression models with population reweighting to examine association between absence of even mild depressive symptoms and sociodemographic features and social supports, with interaction terms and stratification used to investigate sex‐specificity. Results: Among 73,917 survey respondents, 31,199 (42.2%) reported absence of mild or greater depression—11,011/23,682 males (46.5%) and 20,188/50,235 (40.2%) females. In a regression model, features associated with greater likelihood of depression‐resistance included at least weekly attendance of religious services (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04–1.16) and greater trust in others (OR: 1.04 for a 2‐unit increase, 95% CI: 1.02–1.06), along with level of social support measured as number of social ties available who could provide care (OR: 1.05, 95% CI: 1.02–1.07), talk to them (OR: 1.10, 95% CI: 1.07–1.12), and help with employment (OR: 1.06, 95% CI: 1.04–1.08). The first two features showed significant interaction with gender (p <.0001), with markedly greater protective effects among women. Conclusion: Aspects of social support are associated with diminished risk of major depressive symptoms, with greater effects of religious service attendance and trust in others observed among women than men. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data show that having the eveningness associates with poor mental health. For preventive measures it is important to know which underlying factors mediate these associations and the burden posed to public health. This study examines at a population‐based level, whether (1) circadian type and the sleep‐wake behavior‐based phase entrainment similarly associate with mental health problems, (2) there are differences in hospital treatments due to mental disorders between chronotypes, and (3) the association of chronotype with mental health is mediated by insufficient sleep. Methods: The study sample (N = 18,039) consisted of population‐based sample of Finnish adults, aged 25–74 years, with information on their circadian type and sleep patterns, mental health symptoms, and diagnosis as reported in a health examination survey, as well as hospital treatments as recorded on the national Hospital Discharge Register. Results: All the mental health symptoms, diagnoses and hospital treatments were more pronounced among Evening‐types, especially when assessed by circadian type. Insufficient sleep mediated most but not all of the associations between eveningness and mental health. Conclusions: Eveningness does not increase mental health risks only on symptom or diagnosis level, but also on hospital admission level. A higher prevalence of insufficient sleep among the Evening‐types elevates the risk and severity for many of the mental health outcomes. Improving the sleep among Evening‐types could help to improve their mental health prospective and ease the health care burden. [ABSTRACT FROM AUTHOR]

Background: It is widely acknowledged that childhood adversities (CAs) and recent stress are potential risk factors for adult depression. However, the mechanism(s) by which interactions of CAs with recent stress affect adult depression remain unclear. Aims: To investigate the predictive association of the interaction among CAs and recent stress with early‐adult depression. Method: We conducted an annual survey of all freshmen for the period of 2016‐2018 in a Chinese comprehensive university, with a sample size of 23,206. An online questionnaire including standardized self‐report instruments was used to assess sociodemographic factors, childhood experiences of left‐behind (CELB), and maltreatments (CEMTs) including beating (CEB), neglect (CEN), sexual abuse (CESA), recent stress, and current depression (measured by the 9‐item Patient Health Questionnaire). Results: The correlation of Individual CAs and recent stress was significant. In addition to their significant independent/direct incremental effects, all surveyed CAs were associated with increased severity of early‐adult depression, and increased frequency of clinically significant depression (CSD), through significant associations with recent stress (mediation effect). History of CEMTs including CEB, CEN, and CESA significantly increased the effects of recent stress on depression (moderation effect). Conclusions: Chinese undergraduate students reported frequent history of exposure to CAs, which increased the likelihood of depression in early adulthood, not only directly but also through the increasing the likelihood (mediation effect) and impact (moderation effect) of recent stress on depression. These novel findings may help to extend our understanding of environmental determinants of depression, and to guide further research, clinical practice, and policy in this context. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of providing personalized depression risk information on self‐help and help‐seeking behaviors among individuals who are at high risk of having a major depressive episode (MDE). Materials and Methods: In a mixed methods randomized controlled trial, participants who were at high risk of having a MDE, were recruited from across Canada, and were randomized into intervention (n = 358) and control (n = 354) groups. Participants in the intervention group received their personalized depression risk estimated by sex‐specific risk prediction models for MDE. All participants were assessed at baseline, 6 and 12 months. Results: Repeated measure mixed effects modeling showed significant between group differences in self‐help scores. In the complete case analysis, the between group difference in mean self‐help change score was 1.13 at 12 months (effect size = 0.16). Among participants who reported "fair" or "poor health," the between group difference in mean self‐help change score was 2.78 at 12 months (effect size = 0.35). The qualitative data revealed three themes and the findings are consistent with the quantitative results. Conclusions: Providing personalized depression risk information has a positive impact on self‐help in high‐risk individuals, particularly in those with poor health. [ABSTRACT FROM AUTHOR]

Background: Physical activity is often associated with better mental health. However, there is evidence that the domain of physical activity influences the strength and direction of this association. Therefore, this study aimed to examine the associations between different domains of physical activity and depression among a large sample of adults living in the European Union. Methods: Cross‐sectional analyses were conducted on 261,121 adults, recruited in the European Health Interview Survey (wave 2). Validated items were used to assess physical activity domains (i.e., work‐related, transport‐related, leisure‐time aerobic, and muscle‐strengthening) and depression symptom severity (8‐item personal health questionnaire). Generalized linear models with Poisson regressions provided adjusted prevalence ratios (APR) of depressive symptom severity categories across the physical activity domains. Results: Compared to doing no physical activity, any physical effort at work (APR: 0.82–0.86), moderate, high, and very high levels of transport‐related (APR: 0.69–0.83) and aerobic leisure‐time activity (APR: 0.78–0.87), and 3 days/week of muscle‐strengthening (APR: 0.93) were associated with a lower prevalence of mild depressive symptom severity. Moreover, doing any level of physical activity in any domain was mostly associated with a lower prevalence of moderate (APR: 0.43–0.80), moderate–severe (APR: 0.34–0.82), and severe (APR: 0.26–0.56) depressive symptoms. Conclusion: Favorable associations were seen between any domain (leisure‐time, transport‐ and work‐related) of physical activity and depressive symptom severity. The more severe the symptoms, the stronger the associations. Both modalities of leisure‐time physical activity (aerobic and muscle‐strengthening) demonstrated beneficial associations with depression, but slightly more so for aerobic physical activity. [ABSTRACT FROM AUTHOR]

Background: Depression is a heterogeneous condition, with multiple possible symptom‐profiles leading to the same diagnosis. Descriptive depression subtypes based on observation and theory have so far proven to have limited clinical utility. Aim: To identify depression subtypes and to examine their time‐course and prognosis using data‐driven methods. Methods: Latent transition analysis was applied to a large (N = 8380) multi‐service sample of depressed patients treated with cognitive behavioral therapy (CBT) in outpatient clinics. Patients were classed into initial latent states based on their responses to the Patient Health Questionnaire‐9 of depression symptoms, and transition probabilities to other states during treatment were quantified. Qualitatively similar states were clustered into overarching depression subtypes and we statistically compared indices of treatment engagement and outcomes between subtypes using post hoc analyses. Results: Fourteen latent states were clustered into five depression subtypes: mild (2.7%), severe (9.8%), cognitive‐affective (23.7%), somatic (21.4%), and typical (42.4%). These subtypes had high temporal stability, and the most common transitions during treatment were from severe toward milder states within the same subtype. Differential response to treatment was evident, with the highest improvement rate (63.6%) observed in the cognitive‐affective subtype. Conclusion: Replicated evidence indicates that depression subtypes are temporally stable and associated with differential response to CBT. [ABSTRACT FROM AUTHOR]

Background: Depression is a common mental health problem causing significant disability globally, including in Canada. Prevalence estimates for depression within Black communities in Canada are unknown. This study determined the prevalence of depression in a sample of Black Canadians and the association between everyday racial discrimination experiences and depression. Methods: We analyzed data collected from the Black Community Mental Health project in Canada. Participants provided sociodemographic information and completed measures assessing depressive symptomology, everyday racial discrimination, and social support. The prevalence of depressive symptomatology was computed across sociodemographic variables and categories of everyday racial discrimination. Different regression models were conducted to examine the relationship between depressive symptoms and everyday racism controlling for sociodemographic factors. Results: In total, 65.87% of participants reported severe depressive symptoms, with higher rates among women, those who are employed, and those born in Canada. The linear regression models showed that everyday racial discrimination is the best predictor of depressive symptoms, with a final model explaining 25% of the variance. A logistic regression model demonstrated that those experiencing a high level of racial discrimination are 36.4 more likely to present severe depressive symptoms when compared to those reporting a low level of discrimination. Conclusions: Rates of depressive symptoms among Black individuals are nearly six times the 12‐month prevalence reported for the general population in Canada. Racial discrimination, which significantly predicts greater depressive symptomatology, is consistent with earlier studies in the United States and suggests that Canadian colorblind policies may inadvertently reinforce racial discrimination with detrimental effects on mental health. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines suggest that psychological interventions specifically aimed at reducing suicidality may be beneficial. We examined the impact of two depression treatments, cognitive therapy (CT) and interpersonal psychotherapy (IPT) on suicidal ideation (SI) and explored the temporal associations between depression and SI over the course of therapy. Methods: Ninety‐one adult (18–65) depressed outpatients from a large randomized controlled trial who were treated with CT (n = 37) and IPT (n = 54) and scored at least ≥1 on the Beck Depression Inventory II (BDI‐II) suicide item were included. Linear (two‐level) mixed effects models were used to evaluate the impact of depression treatments on SI. Mixed‐effects time‐lagged models were applied to examine temporal relations between the change in depressive symptoms and the change in SI. Results: SI decreased significantly during treatment and there were no differential effects between the two intervention groups (B = −0.007, p =.35). Depressive symptoms at the previous session did not predict higher levels of SI at the current session (B = 0.016, p =.16). However, SI measured at the previous session significantly predicted depressive symptoms at the current session (B = 2.06, p <.001). Conclusions: Both depression treatments seemed to have a direct association with SI. The temporal association between SI and depression was unidirectional with SI predicting future depressive symptoms during treatment. Our findings suggest that it may be most beneficial to treat SI first. [ABSTRACT FROM AUTHOR]

Background: A family history of major depressive disorder (MDD) increases the likelihood of a future depressive episode, which itself poses a significant risk for disruptions in reward processing and social cognition. However, it is unclear whether a family history of MDD is associated with alterations in the neural circuitry underlying reward processing and social cognition. Methods: We subdivided 279 participants from the Human Connectome Project into three groups: 71 with a lifetime history of MDD, 103 with a family history (FH) of MDD, and 105 healthy controls (HCs). We then evaluated task‐based functional magnetic resonance imaging data on a social cognition and a reward processing task and found a region of the ventromedial prefrontal cortex (vmPFC) that responded to both tasks, independent of the group. To investigate whether the vmPFC shows alterations in functional connectivity between groups, we conducted psychophysiological interaction analyses using the vmPFC as a seed region. Results: We found that FH (relative to HC) was associated with increased sadness scores, and MDD (relative to both FH and HC) was associated with increased sadness and MDD symptoms. Additionally, the FH group had increased vmPFC functional connectivity within the nucleus accumbens, left dorsolateral PFC, and subregions of the cerebellum relative to HC during the social cognition task. Conclusions: These findings suggest that aberrant neural mechanisms among those with a familial risk of MDD may underlie vulnerability to altered social cognition. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with a range of adverse daytime sequelae, including significantly higher rates of clinical depression than is seen in the general community. Improvements in depressive symptoms occur after treatment of the primary sleep disorder, suggesting that comorbid depression might be an intrinsic feature of OSA. However, there are limited data on whether treatment for OSA in patients diagnosed with clinical depression improves mood symptoms meaningfully enough to lead to the remission of the psychiatric diagnosis. Methods: N = 121 untreated OSA patients were randomized to either continuous positive airway pressure (CPAP) treatment or waitlist control, and depressive symptoms, sleepiness and clinical depression (using a structured clinical interview) were assessed at baseline and 4 months. Linear and logistic regression analyses were conducted, controlling for baseline scores, stratification factors and antidepressant use. Results: Depressive symptoms (odds ratio [OR] = −4.19; 95% confidence interval [CI] = −7.25, −1.13; p =.008) and sleepiness (OR = −4.71; 95% CI = −6.26, −3.17; p <.001) were significantly lower at 4 months in the CPAP group compared to waitlist. At 4 months, there was a significant reduction in the proportion of participants in the CPAP group meeting criteria for clinical depression, compared to the waitlist controls (OR = 0.06, 95% CI = 0.01, 0.37; p =.002). Conclusion: Treatment of OSA may be a novel approach for the management and treatment of clinical depression in those with comorbid sleep disordered breathing. Larger trials of individuals with clinical depression and comorbid OSA are needed. [ABSTRACT FROM AUTHOR]

Background: Use of social networking in later childhood and adolescence has risen quickly. The consequences of these changes for mental health are debated but require further empirical evaluation. Methods: Using data from the Childhood to Adolescence Transition Study (n = 1,156), duration of social networking use was measured annually at four time points from 11.9 to 14.8 years of age (≥1 h/day indicating high use). Cross‐sectional and prospective relationships between social networking use and depressive and anxiety symptoms were examined. Results: In adjusted (age, socioeconomic status, prior mental health history) cross‐sectional analyses, females with high social networking use had greater odds of depressive (odds ratio [OR]: 2.15; 95% confidence interval [CI]: 1.58–2.91) and anxiety symptoms (OR: 1.99; 95% CI: 1.32–3.00) than those that used a few minutes at most, while males with high social networking use had 1.60 greater odds of reporting depressive symptoms (95% CI: 1.09–2.35). For females, an increased odds of depressive symptoms at age 14.8 was observed for high social networking use at one previous wave and at two or three previous waves, even after adjustment (OR: 1.76; 95% CI: 1.11–2.78; OR: 2.06, 95% CI: 1.27–3.37, respectively) compared to no wave of high use. Conclusions: Our results suggest weak to moderate increased odds of depression and anxiety in girls and boys with high social networking use versus low/normal use. These findings indicate that prevention programs for early mental health problems might benefit from targeting social networking use in early adolescence. [ABSTRACT FROM AUTHOR]

Background: In recent years, a new framework for analyzing and understanding posttraumatic stress disorder (PTSD) was introduced; the network approach. Up until now, network analysis studies of PTSD were largely conducted on small to medium sample sizes (N < 1,000), which might be a possible cause of variability in main findings. Moreover, only a limited number of network studies investigated comorbidity.Methods: In this study, we utilized a large sample to conduct a network analysis of 17 symptoms of PTSD (DSM-IV), and compared it to the result of a second network consisting of symptoms of PTSD and depression (based on Patient Health Questionnaire-9 [PHQ-9]). Our sample consisted of 502,036 treatment-seeking veterans, out of which 158,139 had fully completed the assessment of symptoms of PTSD and a subsample of 32,841 with valid PCL and PHQ-9 that was administered within 14 days or less.Results: Analyses found that in the PTSD network, the most central symptoms were feeling distant or cut off from others, followed by feeling very upset when reminded of the event, and repeated disturbing memories or thoughts of the event. In the combined network, we found that concentration difficulties and anhedonia are two of the five most central symptoms.Conclusion: Our findings replicate the centrality of intrusion symptoms in PTSD symptoms' network. Taking into account the large sample and high stability of the network structure, we believe our study can answer some of the criticism regarding stability of cross-sectional network structures. [ABSTRACT FROM AUTHOR]

Background: Diagnostic delay contributes to morbidity in psychiatric disorders. Methods: Patients in an ambulatory psychiatry clinic were given patient‐reported outcome measures at an initial visit, and a subset (N = 493) were given a structured interview (MINI International Neuropsychiatric Interview, MINI), in addition to the clinical encounter (CLIN). Diagnostic agreement between MINI and CLIN was assessed at an initial and follow‐up visit. Diagnostic delay was identified if diagnostic disagreement between MINI and CLIN occurred at the initial visit and changed to an agreement at a follow‐up visit. Registry data was compiled by an honest broker. Results: Significant agreement occurred between MINI and CLIN diagnoses for major depressive disorder (MDD), bipolar disorder (BD), generalized anxiety disorder, and panic disorder. Diagnostic agreement for MDD occurred at initial visit for 63% of patients, and at follow‐up for 87% of those with initial diagnostic disagreement; for BD, 75% at initial visit and 28% at follow‐up. No demographic, socioeconomic, symptom severity or functioning measures predicted diagnostic agreement for the MDD group at the first visit, however initial psychopathological symptom complexity predicted diagnostic agreement in the diagnostic delay group. Initial diagnostic agreement for BD was predicted by lower symptom burden and better social, physical, and occupational functioning. No factors predicted additional diagnostic agreement at the second visit in the diagnostic delay group. Conclusion: Initial assessment by a structured interview aided physicians in identifying MDD by the second visit in patients with complex psychopathology. Patients with high complexity/severity of symptoms and more difficulty with functioning were less commonly identified with BD even with the assistance of a structured interview. Use of structured assessment tools may improve the detection of psychiatric illness by clinicians at the first visit. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant depression (TRD) is a debilitating chronic mental illness that confers increased morbidity and mortality, decreases the quality of life, impairs occupational, social, and offspring development, and translates into increased costs on the healthcare system. The goal of this study is to reach an agreement on the concept, definition, staging model, and assessment of TRD. Methods: This study involved a review of the literature and a modified Delphi process for consensus agreement. The Appraisal of Guidelines for Research & Evaluation II guidelines were followed for the literature appraisal. Literature was assessed for quality and strength of evidence using the grading, assessment, development, and evaluations system. Canadian national experts in depression were invited for the modified Delphi process based on their prior clinical and research expertize. Survey items were considered to have reached a consensus if 80% or more of the experts supported the statement. Results: Fourteen Canadian experts were recruited for three rounds of surveys to reach a consensus on a total of 27 items. Experts agreed that a dimensional definition for treatment resistance was a useful concept to describe the heterogeneity of this illness. The use of staging models and clinical scales was recommended in evaluating depression. Risk factors and comorbidities were identified as potential predictors for treatment resistance. Conclusions: TRD is a meaningful concept both for clinical practice and research. An operational definition for TRD will allow for opportunities to improve the validity of predictors and therapeutic options for these patients. [ABSTRACT FROM AUTHOR]

Background: Peripartum depression (PND) impairs mother-infant boding and perceived social support, yet limited research has examined if women at-risk for PND (AR-PND) also experience impairment. We examined if pregnant women AR-PND, women with PND, and healthy comparison women (HCW) differed in their mother-infant bonding and social support. As PND is highly comorbid with anxiety, we also examined if peripartum anxiety impacted postpartum diagnosis of PND. Methods: A total of 144 pregnant women AR-PND or euthymic were assessed twice antepartum and twice postpartum. We utilized regression models to examine the impact of PND risk group status and diagnostic status on mother-infant bonding and perceived social support postpartum. We conducted a sensitivity analysis using a generalized estimating equations model to determine if anxiety (Hamilton Anxiety Rating Scale, HAM-A) across all four time points was associated with the postpartum diagnosis of PND. Results: Women AR-PND experienced significantly worse mother-infant bonding compared to HCW (p = .03). Women diagnosed with PND experienced significantly worse mother-infant bonding and social support compared to HCW (p = .001, p = .002, respectively) and to those who were at-risk for but did not develop PND (p = .02, p = .008, respectively). HAM-A severity at each visit was associated with PND diagnosis status, where each increase in HAM-A was associated with 15% increased odds of being diagnosed with PND postpartum. Conclusions: Both women AR-PND and those with PND experience worse mother-infant bonding. Peripartum anxiety should also be assessed as it represents a marker for later PND. [ABSTRACT FROM AUTHOR]

Background: Comorbidities in mental disorders are often understood by assuming a common cause. The network theory of mental disorders offers an alternative to this assumption by understanding comorbidities as mutually reinforced problems. In this study, we used network analysis to examine bridge symptoms between anxiety and depression in a large sample. Method: Using data from a sample of patients diagnosed with both depression and an anxiety disorder before and after inpatient treatment (N = 5,614, mean age: 42.24, 63.59% female, average treatment duration: 48.12 days), network models of depression and anxiety symptoms are estimated. Topology, the centrality of nodes, stability, and changes in network structure are analyzed. Symptoms that drive comorbidity are determined by bridge node analysis. As an alternative to network communities based on categorical diagnosis, we performed a community analysis and propose empirically derived symptom subsets. Results: The obtained network models are highly stable. Sad mood and the inability to control worry are the most central. Psychomotor agitation or retardation is the strongest bridge node between anxiety and depression, followed by concentration problems and restlessness. Changes in appetite and suicidality were unique to depression. Community analysis revealed four symptom groups. Conclusion: The estimated network structure of depression and anxiety symptoms proves to be highly accurate. Results indicate that some symptoms are considerably more influential than others and that only a small number of predominantly physical symptoms are strong candidates for explaining comorbidity. Future studies should include physiological measures in network models to provide a more accurate understanding. [ABSTRACT FROM AUTHOR]

Background: Heightened attention allocation toward negative‐valanced information and reduced attention allocation toward positive‐valanced information represent viable targets for attention bias modification in major depressive disorder. Accordingly, we conducted a randomized controlled trial testing the efficacy of a novel gaze‐contingent attention bias modification procedure for major depressive disorder. Method: Sixty patients with major depressive disorder were randomly assigned to either eight training sessions of feedback‐based gaze‐contingent music reward therapy designed to divert patients' gaze toward positive over sad stimuli, or to a control condition which entailed eight sessions of gaze‐noncontingent music. Clinician‐rated and self‐reported measures of depression, and proportion of dwell‐time on sad faces, were assessed pretreatment, posttreatment, and at a 3‐month follow‐up. Results: Gaze‐contingent music reward therapy produced a greater reduction in dwell‐time on sad faces compared with the control condition, but it failed to generalize to novel faces. Both groups manifested similarly significant reductions in depression symptoms from pre‐ to posttreatment that were maintained at follow‐up. Exploratory analyses suggest that first‐episode patients may benefit more from this therapy than patients with a history of multiple episodes. Conclusions: Gaze‐contingent music reward therapy can modify attention biases in depression, but clear differential clinical effects did not emerge. Theoretical and practical implications are discussed. [ABSTRACT FROM AUTHOR]

Background: Adjunctive antidepressants are frequently used for bipolar depression but their clinical efficacy has been studied in few trials and little is known about how co‐occurring manic symptoms affect treatment response. Methods: Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (N = 482) and Lithium Treatment Moderate‐Dose Use Study (N = 281) were similar comparative effectiveness trials on outpatients with bipolar disorder comparing four different randomized treatment arms with adjunctive personalized guideline‐based treatment for 24 weeks. Adjunctive antidepressant treatment could be used if clinically indicated and was assessed at every study visit. Adjusted mixed effects linear regression analyses compared users of antidepressants to nonusers overall and in different subcohorts. Results: Of the 763 patients, 282 (37.0%) used antidepressant drugs during the study. Antidepressant users had less improvement compared to nonusers on the Clinical Global Impression Scale for Bipolar Disorder and on measures of depression. This was particularly true among patients with co‐occurring manic symptoms. Exclusion of individuals begun on antidepressants late in the study (potentially due to overall worse response) resulted in no differences between users and nonusers. We found no differences in treatment effects on mania scales. Conclusions: In this large cohort of outpatients with bipolar disorder, clinically indicated and guideline‐based adjunctive antidepressant treatment was not associated with lower depressive symptoms or higher mania symptoms. The treatment‐by‐indication confounding due to the nonrandomized design of the trials complicates causal interpretations, but no analyses indicated better treatment effects of adjunctive antidepressants. [ABSTRACT FROM AUTHOR]

Background: Theta burst stimulation (TBS) has recently been proposed as a novel treatment for youth depression. However, the impact of TBS on the youth brain and neurophysiological predictors of response to TBS in this population have not been investigated. Methods: Cortical reactivity was assessed at baseline and following 2 weeks of bilateral dorsolateral prefrontal cortex (DLPFC) TBS treatment in 16 youth with depression (aged 16–24 years old). In 16 age‐matched health youths, cortical reactivity was assessed twice, 2 weeks apart. Transcranial magnetic stimulation (TMS) combined with electroencephalography was used to assess TMS‐evoked potentials in bilateral DLPFC, motor cortices, and intraparietal lobules (IPL). Resting‐state functional magnetic resonance imaging (fMRI) data was also collected at baseline. Results: Left DLPFC pretreatment cortical reactivity, specifically the negativity at 45 ms (i.e., N45), which is related to GABAA neurotransmission, was associated with changes in depressive symptoms. Furthermore, TBS treatment was found to alter the N45 in the right IPL, a site distal to the treatment sites. The magnitude of the right IPL N45 modulation was correlated with the baseline fMRI connectivity between the right IPL and right DLPFC. Conclusions: TMS‐probed cortical inhibition at the site of TBS application may have potential as a predictor of treatment response in youth depression. Furthermore, pre‐treatment functional connectivity may predict the impact of TBS on the neurophysiology of regions distal to the stimulation site. Collectively, these results offer novel neurophysiological insights into the application of TBS for youth depression, which may facilitate its wider use in the youth population. [ABSTRACT FROM AUTHOR]

Objectives: To explore the anxiolytic effects of a 4‐month randomized, placebo‐controlled trial of exercise and antidepressant medication in patients with major depressive disorder (MDD), and to examine the potential modifying effects of anxiety in treating depressive symptoms. Materials and Methods: In this secondary analysis of the SMILE‐II trial, 148 sedentary adults with MDD were randomized to: (a) supervised exercise, (b) home‐based exercise, (c) sertraline, or (d) placebo control. Symptoms of state anxiety measured by the Spielberger Anxiety Inventory were examined before and after 4 months of treatment. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory‐II (BDI‐II). Analyses were carried out using general linear models. Results: Compared to placebo controls, the exercise and sertraline groups had lower state anxiety scores (standardized difference = 0.3 [95% CI = −0.6, −0.04]; p = 0.02) after treatment. Higher pretreatment state anxiety was associated with poorer depression outcomes in the active treatments compared to placebo controls for both the HAMD (p =.004) and BDI‐II (p =.02). Conclusion: Aerobic exercise as well as sertraline reduced symptoms of state anxiety in patients with MDD. Higher levels of pretreatment anxiety attenuated the effects of the interventions on depressive symptoms, however, especially among exercisers. Patients with MDD with higher comorbid state anxiety appear to be less likely to benefit from exercise interventions in reducing depression and thus may require supplemental treatment with special attention to anxiety. [ABSTRACT FROM AUTHOR]

Background: Stressful events due to the coronavirus disease‐2019 (COVID‐19) pandemic are likely to have profound effects on mental health, and validated methods for assessing these experiences and associations with psychopathology are needed. We developed the Pandemic Stress Questionnaire (PSQ) and tested its psychometric properties, characterized experiences in emerging adults, and examined associations with internalizing symptoms. Methods: Emerging adults (N = 450) completed the PSQ and measures of internalizing symptoms and perceived stress through an online platform in May 2020. One month later, 288 participants completed a follow‐up questionnaire to assess reliability of the PSQ and longitudinal associations between stress and internalizing symptoms. Results: Results supported the validity/reliability of PSQ total scores and indicated that stressful events were highly prevalent in May, particularly among younger, female, and Black emerging adults. Symptoms of depression and anxiety were high overall, but decreased at the follow‐up assessment. Pandemic‐related stress was moderately associated with both depression and anxiety at each assessment, but baseline stress did not predict change in symptoms when controlling for baseline symptoms. Conclusions: Results provide empirical evidence that emerging adults are at high risk for depression and anxiety related to the psychosocial effects of the COVID‐19 pandemic, and highlight specific types of experiences associated with greatest risk. Further, this study provides support for a questionnaire measure of experiences related to the COVID‐19 pandemic that can be applied in future work to advance understanding of risk and resilience in response to stressful events. [ABSTRACT FROM AUTHOR]

Objective: Increasing evidence supports the presence of an anhedonic endophenotype in major depressive disorder (MDD), characterized by impairments in various components of reward processing, particularly incentive motivation, effort‐based decision making, and reward learning. In addition to its prominent role in MDD, reward processing dysregulation has been proposed as a transdiagnostic risk and/or maintenance factor for a range of other forms of psychopathology. Individuals with social anxiety disorder (SAD)—a condition that frequently co‐occurs with MDD—demonstrate low trait positive affectivity and altered processing of rewards and positively valenced information. However, no studies to date have directly tested reward learning—the ability to modulate behavior in response to rewards—in this population. Materials and Methods: The current study evaluated reward learning in MDD, SAD, and healthy control subjects (N = 90) using a well‐validated signal detection task. Given increasing data supporting transdiagnostic features of psychopathology, we also evaluated associations between anhedonia and task performance transdiagnostically in the patient sample. Results: Contrary to expectations, results indicated no significant group differences in response bias in the full sample, suggesting no diagnostic differences in reward learning. However, dimensional analyses revealed that higher self‐reported anhedonia (but not general distress or anxious arousal) was associated with worse reward learning in both the MDD and SAD groups explaining about 11% of the variance. Conclusion: Deficits in implicit reward learning are associated with anhedonia but not necessarily with major depressive disorder as a diagnosis, which supports the use of transdiagnostic approaches to understanding psychopathology. [ABSTRACT FROM AUTHOR]

Introduction: Warzone participation is associated with increased risk of stress‐related psychopathology, including posttraumatic stress disorder (PTSD) and depression. Prior research suggests that the mental health of spouses of warzone veterans (WZVs) is linked to that of their partners. Additionally, PTSD among WZVs has been associated with marital dysfunction. Less is known about the effects of depression among WZVs on partner mental health and family relationships. We sought in this study to examine associations between WZV PTSD and depression and partner mental health and relationship outcomes. Methods: Using a nationally dispersed sample of Iraq and Afghanistan veterans and their married and unmarried intimate partners, 245 dyads completed structured psychiatric interviews and psychometric surveys assessing family functioning and relationship aggression. Results: Adjusted regression analyses indicated that depression among WZVs was associated with partner depression and anxiety disorders. WZV PTSD and depression were also associated with partner‐reported relationship dysfunction, dissatisfaction, and communication issues, and higher rates of intimate partner aggression victimization and perpetration. Conclusions: Mental health consequences of war extend beyond WZVs to the mental health of their intimate partners and their relationships with intimate partners. [ABSTRACT FROM AUTHOR]

Background: Energy drinks (EDs) claim to boost mental performance, however, few studies have examined the prospective effects of EDs on mental health. This study examined longitudinal associations between ED use and mental health symptoms in young adults aged 20 years over a 2‐year period. Methods: Data were drawn from Gen2 (Generation 2) of the Raine Study, a prospective population‐based study in Western Australia. Self‐report questionnaires assessed ED consumption and mental health symptoms (Depression Anxiety Stress Scale [DASS]‐21) when Gen2 participants were 20 and 22 years old. Changes in ED use and DASS‐21 scores over time were analyzed and results presented for the whole sample and by sex. Results: For the whole sample (n = 429), participants who changed from being a non‐ED user to an ED user had an average increase in stress scores of 2.30 (95% confidence interval [CI] = 0.04, 4.55) across the 2‐year follow‐up. Males, but not females who changed from being a non‐ED user to an ED user had an average increase in depression, anxiety, and stress scores of 6.09 (95% CI = 3.36, 8.81), 3.76 (95% CI = 1.82, 5.70), and 3.22 (95% CI = 0.47, 5.97), respectively. Conclusion: ED consumption may be a possible marker for mental health symptoms in young male adults. Practicing clinicians could consider screening for ED use in routine assessments of mental health, particularly for young males presenting with depression, anxiety, and stress symptoms. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety are well‐recognized comorbid health conditions among adults with migraine due to their humanistic and economic burden. This review was conducted to systematically assess the humanistic and economic burden of comorbid depression and/or anxiety disorder among adults with migraine. Methods: A systematic literature search was conducted using MEDLINE and CINAHL via EBSCO, EMBASE, and Cochrane Database of Systematic Reviews via OVID. Studies evaluating the humanistic burden and the economic burden of comorbid depression and anxiety among adults with migraine that were published in peer‐reviewed English language journals from inception until January 2020 were included. Results: Out of the 640 identified articles, 23 studies were found eligible and included in this review. Regarding the humanistic burden, health‐related quality of life (HRQoL) was examined by 11 studies, 7 studies examined disability, while 2 studies evaluated both HRQoL and disability measures. These studies reported an association between depression and/or anxiety and lower HRQoL and higher disability among adults with migraine. Regarding the economic burden, only three studies were identified and all concluded that depression and/or anxiety are significantly associated with higher healthcare expenditures and utilization among adults with migraine. Conclusions: Results of this review highlight the substantial burden of depression and/or anxiety for adults with migraine. Healthcare providers need to identify and treat anxiety and depression for patients living with migraine. [ABSTRACT FROM AUTHOR]

Background: Novel technologies make it possible to incorporate pharmacogenetic testing into the medical management of depression. However, previous studies indicate that there may be a subset of subjects who have concerns about genetic testing and may be psychologically vulnerable. If so, pharmacogenetic testing in depressed subjects could negatively impact their mental health and undermine treatment goals.Methods: In this study, we developed a standardized instrument to assess motivations and attitudes around pharmacogenetic testing in a cohort of 170 depressed Veterans participating in a multi-center clinic trial.Results: Testing reveals that subjects were largely positive about the use of genetic testing to guide pharmacological treatment and help plan their future. Most subjects showed only modest concerns about the impact on family, inability to cope with the results, and fear of discrimination. The severity of depression did not predict the concern expressed about negative outcomes. However, non-Caucasian subjects were more likely on average to endorse concerns about poor coping and fear of discrimination.Conclusions: These data indicate that while the overall risk is modest, some patients with depression may face psychosocial challenges in the context of pharmacogenetic testing. Future work should identify factors that predict distress and aim to tailor test results to different populations. [ABSTRACT FROM AUTHOR]

Background: Perinatal depression carries adverse effects on maternal health and child development, but genetic underpinnings remain unclear. We investigated the polygenic risk of perinatal depressive symptoms.Methods: About 742 women from the prospective Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction cohort were genotyped and completed the Center for Epidemiologic Studies Depression scale 14 times during the prenatal period and twice up to 12 months postpartum. Polygenic risk scores for major depressive disorder, bipolar disorder, schizophrenia, and cross-disorder were calculated using multiple p-value thresholds.Results: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder, but not bipolar disorder, were associated with higher prenatal and postpartum depressive symptoms (0.8%-1% increase per one standard deviation increase in polygenic risk scores). Prenatal depressive symptoms accounted for and mediated the associations between the polygenic risk scores and postpartum depressive symptoms (effect size proportions-mediated: 52.2%-88.0%). Further, the polygenic risk scores were associated with 1.24-1.45-fold odds to belong to the group displaying consistently high compared with consistently low depressive symptoms through out the prenatal and postpartum periods.Conclusions: Polygenic risk scores for major depressive disorder, schizophrenia, and cross-disorder in non-perinatal populations generalize to perinatal depressive symptoms and may afford to identify women for timely preventive interventions. [ABSTRACT FROM AUTHOR]

Background: Psychiatrists frequently struggle with how to sequence treatment for depressed adolescents who do not respond to an adequate trial of a selective serotonin reuptake inhibitor (SSRI). This study leveraged recent statistical and computational advances to create Bayesian hierarchal models (BHMs) of response in the treatment of SSRI-resistant depression in adolescents study to inform treatment planning.Methods: BHMs of individual treatment trajectories were developed and estimated using Hamiltonian Monte Carlo no u-turn sampling. From the Monte Carlo pseudorandom sample, 95% credible intervals, means, posterior tail probabilities, and so forth, were determined. Then, for the random effects model, posterior tail probabilities were used to create Bayesian two-tailed p values to evaluate the null hypotheses: no difference in efficacy between SSRIs and venlafaxine. The robustness of the results was examined using the fixed effects model of treatment comparisons.Results: In patients not receiving cognitive behavioral therapy (CBT; n = 168), SSRIs produced greater and faster improvement in depressive symptoms compared to venlafaxine (p = .015). No differences in response or trajectory of response for symptoms of anxiety were detected between SSRIs and venlafaxine (p = .168). For patients receiving CBT (n = 162), SSRIs and venlafaxine produced similar improvements in symptoms of anxiety and depression.Conclusions: Findings from this novel computational approach suggest that a second trial of an SSRI is warranted for depressed adolescents who fail to respond to initial SSRI treatment. [ABSTRACT FROM AUTHOR]

Background: Cohort and cost-effectiveness studies suggest that measuring variation in genes that influence metabolism of common drugs could improve antidepressant treatment outcomes. Prior randomized trials have yielded inconsistent results.Method: Multicenter randomized double-blind (subject and rater), controlled trial of pharmacogenomic testing among outpatients with nonpsychotic major depressive disorder. Study participants (n = 304) were randomized 1:1 to assay-guided treatment (AGT; N = 151) or treatment-as-usual (TAU; N = 153). Participants and raters were blinded to study arm; unblinded clinicians received results of a pharmacogenomic test and adjusted treatment in light of the test report. Primary outcome was change over 8 weeks in Hamilton Depression Rating Scale (SIGH-D-17).Results: For the primary comparison of interest, change in SIGH-D-17, no significant difference was detected between AGT and TAU at Week 8 (p = .53). Rates of study completion also did not differ between the arms (AGT 92.7%, TAU 92.2% (χ2  = 0.03, df = 1, p = .86). Exploratory analyses suggested significantly fewer individuals experienced worsening of depressive symptoms following AGT, and that treatment concordant with assay results was associated with greater likelihood of remission.Conclusion: Pharmacogenomic testing using a panel of pharmacokinetic and pharmacodynamic variants was not associated with significant improvement in the primary efficacy outcome when providers were unconstrained by the assay results. Further investigation is needed to understand the discordance with cost-effectiveness results and among randomized trials. [ABSTRACT FROM AUTHOR]

Background: Depression is common in patients with chronic heart failure (CHF) and is a predictor of rehospitalization and mortality. However, the complex bidirectional relationships between these two conditions are barely understood. We investigated the course of depression and markers of CHF (New York Heart Association [NYHA] functional class, N-terminal-prohormone B-type natriuretic peptide [NT-proBNP], and left ventricular ejection fraction [LVEF]) in a longitudinal study over a period of 2 years, using three assessment points.Methods: Data of n = 446 patients with documented CHF were analyzed using structural equation modeling. Specifically, a Bayesian cross-lagged structural equation model was applied.Results: Our study revealed that an aggravation of depression predicted an increase in NYHA functional class (significant cross-lagged effect γh  = 0.103, 95% confidence interval [CI] [0.017; 0.194]), whereas an increase in NYHA functional class did not predict an aggravation of depression (γd  = 0.002 95% CI [-0.057; 0.194]). This association was found only for NYHA functional class and depression-not for NT-proBNP and LVEF.Conclusions: Experiencing depression and associated symptoms, such as lack of energy and fatigue, may lead to a further decrease of functional capacity, and consequently to a higher NYHA functional class in CHF patients. As NYHA functional class is associated with higher mortality, this may be a critical development for affected patients. Further studies are required to investigate whether or not this association could be an essential key that explains the pathway from depression to increased mortality in heart failure patients. [ABSTRACT FROM AUTHOR]

Background: The application of experience sampling method/ecological momentary assessment (ESM/EMA) methods to individuals with major depressive disorder (MDD) seems promising, but evidence about their acceptability is still unclear. The aim of this systematic review and meta‐analysis (registration number CRD42017060438) was to investigate the acceptability of ESM/EMA techniques for health monitoring in patients with MDD, by examining the dropout rate and related‐reasons, and to explore the effects of individual, methodological, and technical features on dropping out. Method: According to PRISMA guidelines, after leading a systematic search on major electronic databases, a structured process for selecting and collecting data was followed. Results: A total of 19 studies were included in the analyses. From results, it emerged a dropout rate of 3.6%. Our findings showed that the use of paper and pencil tools in combination with electronic devices, the time‐based sampling method, and not providing monetary incentives significantly increase the dropout rate of patients with MDD during ESM/EMA monitoring. Age, gender, depression severity, duration of monitoring, number of assessments each day, and number of questions did not affect dropout rate. Conclusions: The results of this systematic review may assist clinicians and researchers in planning, implementing, or evaluating the use of ESM/EMA to assess the health status of community‐based individuals with MDD. [ABSTRACT FROM AUTHOR]

Background: Suicidality in youth is a major public health problem and objective methods for identifying those at greatest risk are critically needed. Suicidality has been associated with alterations in reward-related decision-making, but the extent to which measures of reward responsiveness (RR) can differentiate youth with and without suicidality in clinical samples remains unclear.Methods: We examined reliable and accessible neurophysiological (i.e., reward positivity [RewP] event-related potential) and self-report (Behavioral Activation System subscales) measures of RR in relation to active suicidality in 58 clinically depressed adolescents (14- to 18-year-olds).Results: Logistic regression analysis indicated that active suicidality in depressed adolescents was associated with heightened RR at both the self-report and neurophysiological levels. A relatively more positive RewP to win and a more negative RewP to loss uniquely predicted active suicidality beyond demographic, clinical, and self-report measures.Conclusions: Results support the utility of neurophysiological measures in differentiating clinically depressed adolescents with and without suicidality. Although depression is commonly characterized by reduced RR, depressed adolescents with active suicidality exhibited relatively enhanced neural responses to reward and loss feedback. Results highlight the need for consideration of heterogeneity in RR in depression and research on personalized depression treatment. [ABSTRACT FROM AUTHOR]

Background: Heterogeneity in major depressive disorder (MDD) is well recognized but not well understood. Core depressive features are reward and emotional symptoms, which reflect dysfunctions in the positive valence (PV) and negative valence (NV) systems, respectively. This study assessed whether PV and NV systems (based on selected symptoms) were associated with different clinical features, antidepressant response, and levels of immunomarkers in adults with MDD.Methods: These analyses used data from combining medications to enhance depression outcomes study (N = 665; n = 166 for immunomarkers). PV and NV symptom scores were extracted from the clinician-rated 30-item Inventory of Depressive Symptomatology. Correlational analyses were conducted.Results: PV and NV symptom scores were substantially associated with different clinical features. PV symptoms (impaired motivation, impaired energy, and anhedonia) were independently associated with female gender (p < .001), older age (p = .012), and higher cognitive and physical impairment (p < .001) according to the 7-item Cognitive and Physical Functioning Questionnaire. Conversely, NV symptoms (anxiety and interpersonal sensitivity) were independently associated with younger age (p = .013), more anxious comorbidities (p = .001 for generalized anxiety disorder and p = .002 for social phobia) and other commonly associated noncriterion symptoms (p < .001). Overall, PV symptoms were more responsive to antidepressants than NV symptoms (p < .0001; Cohen's d = .455). A PV symptom score was positively correlated with the concentration of three proinflammatory and one anti-inflammatory factor. In contrast, an NV symptom score was negatively associated with only one proinflammatory immunomarker.Conclusions: PV and NV system functions appear to be reflected in selected clinical symptoms that differentially relate to other clinical features, treatment outcomes, and immunological function. [ABSTRACT FROM AUTHOR]

Background: Maternal depression and anxiety have been associated with deleterious child outcomes. It is, however, unclear how the chronicity and timing of maternal mental health problems predict child development outcomes. The aim of the current study was to assess the effect of both chronicity and timing of maternal anxiety and depression in pregnancy, infancy, and the toddler period on children's internalizing and externalizing symptoms, as well as social and communication skills at age 5.Method: Participants were 1,992 mother-child pairs drawn from a large prospective pregnancy cohort. Mothers reported on anxiety and depression symptoms with clinical screening tools at six time points between <25 weeks gestation and 3 years postpartum. Child outcomes were assessed at age 5.Results: Effect sizes were small for brief incidents of depression/anxiety and increased for intermittent and chronic problems (i.e., three or more timepoints) compared with mothers who had never experienced clinical-level anxiety or depression. Maternal anxiety/depression during pregnancy, infancy, and toddlerhood predicted all child outcomes, even after controlling for depression/anxiety during the other timepoints. However, maternal anxiety and depression during toddlerhood had a stronger association with child internalizing/externalizing symptoms and communication skills than either prenatal or postpartum depression/anxiety.Conclusions: Increasing number of exposures to clinical-level anxiety and depression is related to poorer child outcomes. Neither prenatal nor postpartum periods emerged as "sensitive" periods. Rather, maternal depression and anxiety during toddlerhood was more strongly associated with child outcomes at age 5. Results highlight the need for continued support for maternal mental health across early childhood. [ABSTRACT FROM AUTHOR]