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Showing papers in "Depression and Anxiety in 2016"


Journal ArticleDOI
TL;DR: Social media use is increasing among U.S. young adults, and its association with mental well‐being remains unclear, and this study assessed the association between SM use and depression in a nationally representative sample of young adults.
Abstract: BACKGROUND: Social media (SM) use is increasing among U.S. young adults, and its association with mental well-being remains unclear. This study assessed the association between SM use and depression in a nationally representative sample of young adults. METHODS: We surveyed 1,787 adults ages 19 to 32 about SM use and depression. Participants were recruited via random digit dialing and address-based sampling. SM use was assessed by self-reported total time per day spent on SM, visits per week, and a global frequency score based on the Pew Internet Research Questionnaire. Depression was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Scale Short Form. Chi-squared tests and ordered logistic regressions were performed with sample weights. RESULTS: The weighted sample was 50.3% female and 57.5% White. Compared to those in the lowest quartile of total time per day spent on SM, participants in the highest quartile had significantly increased odds of depression (AOR = 1.66, 95% CI = 1.14-2.42) after controlling for all covariates. Compared with those in the lowest quartile, individuals in the highest quartile of SM site visits per week and those with a higher global frequency score had significantly increased odds of depression (AOR = 2.74, 95% CI = 1.86-4.04; AOR = 3.05, 95% CI = 2.03-4.59, respectively). All associations between independent variables and depression had strong, linear, dose-response trends. RESULTS were robust to all sensitivity analyses. CONCLUSIONS: SM use was significantly associated with increased depression. Given the proliferation of SM, identifying the mechanisms and direction of this association is critical for informing interventions that address SM use and depression. Language: en

588 citations


Journal ArticleDOI
TL;DR: Current clinical practice guidelines for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first‐line treatment.
Abstract: BACKGROUND: Current clinical practice guidelines (CPGs) for posttraumatic stress disorder (PTSD) offer contradictory recommendations regarding use of medications or psychotherapy as first-line treatment. Direct head-to-head comparisons are lacking. METHODS: Systemic review of Medline, EMBASE, PILOTS, Cochrane Central Register of Controlled Trials, PsycINFO, and Global Health Library was conducted without language restrictions. Randomized clinical trials ≥8 weeks in duration using structured clinical interview-based outcome measures, active-control conditions (e.g. supportive psychotherapy), and intent-to-treat analysis were selected for analyses. Independent review, data abstraction, and bias assessment were performed using standardized processes. Study outcomes were grouped around conventional follow-up time periods (3, 6, and 9 months). Combined effect sizes were computed using meta-analyses for medication versus control, medication pre-/posttreatment, psychotherapy versus control, and psychotherapy pre-/posttreatment. RESULTS: Effect sizes for trauma-focused psychotherapies (TFPs) versus active control conditions were greater than medications versus placebo and other psychotherapies versus active controls. TFPs resulted in greater sustained benefit over time than medications. Sertraline, venlafaxine, and nefazodone outperformed other medications, although potential for methodological biases were high. Improvement following paroxetine and fluoxetine treatment was small. Venlafaxine and stress inoculation training (SIT) demonstrated large initial effects that decreased over time. Bupropion, citalopram, divalproex, mirtazapine, tiagabine, and topiramate failed to differentiate from placebo. Aripiprazole, divalproex, guanfacine, and olanzapine failed to differentiate from placebo when combined with an antidepressant. CONCLUSIONS: Study findings support use of TFPs over nontrauma-focused psychotherapy or medication as first-line interventions. Second-line interventions include SIT, and potentially sertraline or venlafaxine, rather than entire classes of medication, such as SSRIs. Future revisions of CPGs should prioritize studies that utilize active controls over waitlist or treatment-as-usual conditions. Direct head-to-head trials of TFPs versus sertraline or venlafaxine are needed.© 2016 Wiley Periodicals, Inc. Language: en

260 citations


Journal ArticleDOI
TL;DR: About 10% of trauma‐exposed individuals develop PTSD and a growing number of studies have investigated resting‐state abnormalities in PTSD, but inconsistent results suggest a need for a meta‐analysis and systematic review.
Abstract: BACKGROUND: About 10% of trauma-exposed individuals develop PTSD. Although a growing number of studies have investigated resting-state abnormalities in PTSD, inconsistent results suggest a need for a meta-analysis and a systematic review. METHODS: We conducted a systematic literature search in four online databases using keywords for PTSD, functional neuroimaging, and resting-state. In total, 23 studies matched our eligibility criteria. For the meta-analysis, we included 14 whole-brain resting-state studies, reporting data on 663 participants (298 PTSD patients and 365 controls). We used the activation likelihood estimation approach to identify concurrence of whole-brain hypo- and hyperactivations in PTSD patients during rest. Seed-based studies could not be included in the quantitative meta-analysis. Therefore, a separate qualitative systematic review was conducted on nine seed-based functional connectivity studies. RESULTS: The meta-analysis showed consistent hyperactivity in the ventral anterior cingulate cortex and the parahippocampus/amygdala, but hypoactivity in the (posterior) insula, cerebellar pyramis and middle frontal gyrus in PTSD patients, compared to healthy controls. Partly concordant with these findings, the systematic review on seed-based functional connectivity studies showed enhanced salience network (SN) connectivity, but decreased default mode network (DMN) connectivity in PTSD. CONCLUSIONS: Combined, these altered resting-state connectivity and activity patterns could represent neurobiological correlates of increased salience processing and hypervigilance (SN), at the cost of awareness of internal thoughts and autobiographical memory (DMN) in PTSD. However, several discrepancies between findings of the meta-analysis and systematic review were observed, stressing the need for future studies on resting-state abnormalities in PTSD patients. Language: en

229 citations


Journal ArticleDOI
TL;DR: The evidence for positive affect as a symptom cluster, and its neural underpinnings, is reviewed, and a novel psychological treatment for anxiety and depression that targets appetitive responding is introduced that targets deficits in reward sensitivity.
Abstract: Anhedonia, or loss of interest or pleasure in usual activities, is characteristic of depression, some types of anxiety, as well as substance abuse and schizophrenia. Anhedonia is a predictor of poor long-term outcomes, including suicide, and poor treatment response. Because extant psychological and pharmacological treatments are relatively ineffective for anhedonia, there is an unmet therapeutic need for this high-risk symptom. Current psychological and drug treatments for anxiety and depression focus largely on reducing excesses in negative affect rather than improving deficits in positive affect. Recent advances in affective neuroscience posit that anhedonia is associated with deficits in the appetitive reward system, specifically the anticipation, consumption, and learning of reward. In this paper, we review the evidence for positive affect as a symptom cluster, and its neural underpinnings, and introduce a novel psychological treatment for anxiety and depression that targets appetitive responding. First, we review anhedonia in relation to positive and negative valence systems and current treatment approaches. Second, we discuss the evidence linking anhedonia to biological, experiential, and behavioral deficits in the reward subsystems. Third, we describe the therapeutic approach for Positive Affect Treatment (PAT), an intervention designed to specifically target deficits in reward sensitivity.

209 citations


Journal ArticleDOI
TL;DR: There is no rigorous research to support the views that: (1) a phase‐based approach is necessary for positive treatment outcomes for adults with cPTSD, (2) front‐line trauma‐focused treatments have unacceptable risks or that adults with bpTSD do not respond to them, and (3) adults with pTSD profit significantly more from trauma‐ focused treatments when preceded by a stabilization phase.
Abstract: According to current treatment guidelines for Complex PTSD (cPTSD), psychotherapy for adults with cPTSD should start with a “stabilization phase.” This phase, focusing on teaching self-regulation strategies, was designed to ensure that an individual would be better able to tolerate trauma-focused treatment. The purpose of this paper is to critically evaluate the research underlying these treatment guidelines for cPTSD, and to specifically address the question as to whether a phase-based approach is needed. As reviewed in this paper, the research supporting the need for phase-based treatment for individuals with cPTSD is methodologically limited. Further, there is no rigorous research to support the views that: (1) a phase-based approach is necessary for positive treatment outcomes for adults with cPTSD, (2) front-line trauma-focused treatments have unacceptable risks or that adults with cPTSD do not respond to them, and (3) adults with cPTSD profit significantly more from trauma-focused treatments when preceded by a stabilization phase. The current treatment guidelines for cPTSD may therefore be too conservative, risking that patients are denied or delayed in receiving conventional evidence-based treatments from which they might profit.

197 citations


Journal ArticleDOI
TL;DR: This study aims to examine the association between chronotype and depressive (major depressive disorder), dysthymia and anxiety (generalized anxiety disorder, panic disorder, agoraphobia, and social phobia) disorders diagnosed using clinical interviews, while taking into account relevant sociodemographic, clinical, somatic health, and sleep parameters.
Abstract: BACKGROUND: The chronotype, being a morning or an evening type, can influence an individual's psychological health. Studies have shown a link between depressed mood and being an evening type; however, most studies have used symptom scales and not diagnostic criteria, and confounding factors such as sleep patterns and somatic health factors have often not been considered. This study aims to examine the association between chronotype and depressive (major depressive disorder (MDD), dysthymia) and anxiety (generalized anxiety disorder, panic disorder, agoraphobia, and social phobia) disorders diagnosed using clinical interviews, while taking into account relevant sociodemographic, clinical, somatic health, and sleep parameters. METHODS: Data from a large cohort, the Netherlands Study of Depression and Anxiety were used (n = 1,944), which included 676 currently depressed and/or anxious patients, 831 remitted patients, and 437 healthy controls. Chronotype was assessed using the Munich Chronotype Questionnaire. RESULTS: Our results showed that current depressive and/or anxiety disorders were associated with a late chronotype (β =.10, P =.004) even when adjusting for sociodemographic, somatic health, and sleep-related factors (β =.09, P =.03). When examining each type of disorder separately, MDD only, but not dysthymia or specific anxiety disorders, was associated with the late chronotype. The late chronotype also reported significant diurnal mood variation (worse mood in the morning). CONCLUSIONS: Our findings show a clear association between MDD and late chronotype (being an evening type), after controlling for a range of pertinent factors. A late chronotype is therefore associated with a current status of MDD and deserves the relevant clinical attention when considering treatments. Language: en

170 citations


Journal ArticleDOI
TL;DR: Internet‐delivered cognitive behavioral therapy is a relatively novel treatment method that may improve the accessibility of mental health care for individuals with posttraumatic stress disorder (PTSD).
Abstract: BACKGROUND: Internet-delivered cognitive behavioral therapy (iCBT) is a relatively novel treatment method that may improve the accessibility of mental health care for individuals with posttraumatic stress disorder (PTSD). The aim of this meta-analysis was to evaluate the effectiveness of iCBT compared to inactive (waitlist control and treatment-as-usual (TAU)) and active other interventions in reducing PTSD symptoms. METHODS: A meta-analysis of 12 randomized controlled trials (14 comparisons) and 1,306 participants was conducted. RESULTS: The pooled effect size of the 11 comparisons (10 studies, 1,139 participants) that compared iCBT to waitlist and TAU control was moderate (g = 0.71, 95% CI [0.49-0.93], P CONCLUSION: The findings of this systematic review and meta-analysis show that iCBT is an effective treatment for individuals with PTSD and comorbid depressive symptoms. However, further research is needed for effective dissemination of iCBT in clinical practice.© 2016 Wiley Periodicals, Inc. Language: en

156 citations


Journal ArticleDOI
TL;DR: Examination of potential neural correlates of mindfulness training using a novel group therapy (mindfulness‐based exposure therapy (MBET) in combat veterans with PTSD deployed to Afghanistan and/or Iraq is examined.
Abstract: BACKGROUND: Recent studies suggest that mindfulness may be an effective component for posttraumatic stress disorder (PTSD) treatment. Mindfulness involves practice in volitional shifting of attention from "mind wandering" to present-moment attention to sensations, and cultivating acceptance. We examined potential neural correlates of mindfulness training using a novel group therapy (mindfulness-based exposure therapy (MBET)) in combat veterans with PTSD deployed to Afghanistan (OEF) and/or Iraq (OIF). METHODS: Twenty-three male OEF/OIF combat veterans with PTSD were treated with a mindfulness-based intervention (N = 14) or an active control group therapy (present-centered group therapy (PCGT), N = 9). Pre-post therapy functional magnetic resonance imaging (fMRI, 3 T) examined resting-state functional connectivity (rsFC) in default mode network (DMN) using posterior cingulate cortex (PCC) and ventral medial prefrontal cortex (vmPFC) seeds, and salience network (SN) with anatomical amygdala seeds. PTSD symptoms were assessed at pre- and posttherapy with Clinician Administered PTSD Scale (CAPS). RESULTS: Patients treated with MBET had reduced PTSD symptoms (effect size d = 0.92) but effect was not significantly different from PCGT (d = 0.46). Increased DMN rsFC (PCC seed) with dorsolateral dorsolateral prefrontal cortex (DLPFC) regions and dorsal anterior cingulate cortex (ACC) regions associated with executive control was seen following MBET. A group × time interaction found MBET showed increased connectivity with DLPFC and dorsal ACC following therapy; PCC-DLPFC connectivity was correlated with improvement in PTSD avoidant and hyperarousal symptoms. CONCLUSIONS: Increased connectivity between DMN and executive control regions following mindfulness training could underlie increased capacity for volitional shifting of attention. The increased PCC-DLPFC rsFC following MBET was related to PTSD symptom improvement, pointing to a potential therapeutic mechanism of mindfulness-based therapies.© 2016 Wiley Periodicals, Inc. Language: en

147 citations


Journal ArticleDOI
TL;DR: A review of stress‐related neurobiology of depression and the safety, tolerability, and efficacy of ketamine for MDD, along with a review ofketamine's mechanism of action and prospective predictors of treatment response are discussed.
Abstract: Major depressive disorder (MDD) is a common and debilitating psychiatric disorder. Traditional antidepressants are of limited efficacy and take weeks to months to yield full therapeutic effects. Thus, there is a clear need for effective rapid-acting antidepressant medications. The N-methyl-d-aspartate receptor (NMDA-R) antagonist, ketamine, has received a great deal of attention over the last 20 years due to the discovery that a single subanesthetic dose leads to a rapid antidepressant effect in individuals with treatment-resistant depression. Animal and human research suggest that ketamine's antidepressant effects are mediated by a glutamate surge that leads to a cascade of events that result in synaptogenesis and reversal of the negative effects of chronic stress and depression, particularly within the prefrontal cortex (PFC). Preclinical and clinical data have provided compelling insights into the mechanisms underlying the rapid-acting antidepressant effects of ketamine. This review discusses stress-related neurobiology of depression and the safety, tolerability, and efficacy of ketamine for MDD, along with a review of ketamine's mechanism of action and prospective predictors of treatment response. Research limitations and future clinical prospects are also discussed.

146 citations


Journal ArticleDOI
TL;DR: The scarcity of cross‐national reports and the changes in Diagnostic and Statistical Manual version 5 (DSM‐5) regarding panic disorder (PD) and panic attacks (PAs) call for new epidemiological data on PD and PAs and its subtypes in the general population.
Abstract: Context The scarcity of cross-national reports and the changes in Diagnostic and Statistical Manual version 5 (DSM-5) regarding panic disorder (PD) and panic attacks (PAs) call for new epidemiological data on PD and PAs and its subtypes in the general population Objective To present representative data about the cross-national epidemiology of PD and PAs in accordance with DSM-5 definitions Design and setting Nationally representative cross-sectional surveys using the World Health Organization Composite International Diagnostic Interview version 30 Participants Respondents (n = 142,949) from 25 high, middle, and lower-middle income countries across the world aged 18 years or older Main outcome measures PD and presence of single and recurrent PAs Results Lifetime prevalence of PAs was 132% (SE 01%) Among persons that ever had a PA, the majority had recurrent PAs (665%; SE 05%), while only 128% fulfilled DSM-5 criteria for PD Recurrent PAs were associated with a subsequent onset of a variety of mental disorders (OR 20; 95% CI 18–22) and their course (OR 13; 95% CI 12–24) whereas single PAs were not (OR 11; 95% CI 09–13 and OR 07; 95% CI 06–08) Cross-national lifetime prevalence estimates were 17% (SE 00%) for PD with a median age of onset of 32 (IQR 20–47) Some 804% of persons with lifetime PD had a lifetime comorbid mental disorder Conclusions We extended previous epidemiological data to a cross-national context The presence of recurrent PAs in particular is associated with subsequent onset and course of mental disorders beyond agoraphobia and PD, and might serve as a generic risk marker for psychopathology

132 citations


Journal ArticleDOI
TL;DR: S‐ketamine, an enantiomer in racemic ketamine, has been shown to be hepatotoxic in vitro and is considered the mainstay of treatment.
Abstract: Ketamine was discovered in the 1960s and released for public use in 1970. Originally developed as a safer alternative to phencyclidine, ketamine is primarily used in clinical settings for analgesia and sedation. In recent years, other uses have been developed, including pain management and treatment of asthma and depression. Clinical use of ketamine causes dissociation and emergence delirium. These effects have led to recreational abuse. Although death from direct pharmacologic effects appears rare, the disinhibition and altered sensory perceptions caused by ketamine puts users at risk of environmental harm. Ketamine has also been implicated in nonconsensual sexual intercourse. Data continue to build that chronic ketamine use may lead to morbidity. Impairment of memory and persistent dissociative, depressive, and delusional thinking has also been reported with long-term use. Lower urinary tract symptoms, including cystitis have been described. Gastric and hepatic pathology have also been noted, including abnormal liver function tests, choledochal cysts and dilations of the common bile duct. S-ketamine, an enantiomer in racemic ketamine, has been shown to be hepatotoxic in vitro. Abstinence from ketamine may reduce the adverse effects of chronic use and is considered the mainstay of treatment. Specialized urine drug testing may be required to detect use, as not all point of care urine drug screens include ketamine.

Journal ArticleDOI
TL;DR: Comparing relative noninferiority of evidence‐based psychotherapies for PTSD and MD, specifically Behavioral Activation and Therapeutic Exposure (BA‐TE), when delivered via HBT versus in person, in clinic delivery is compared.
Abstract: Objective Combat veterans returning to society with impairing mental health conditions such as PTSD and major depression (MD) report significant barriers to care related to aspects of traditional psychotherapy service delivery (e.g., stigma, travel time, and cost). Hence, alternate treatment delivery methods are needed. Home-based telehealth (HBT) is one such option; however, this delivery mode has not been compared to in person, clinic-based care for PTSD in adequately powered trials. The present study was designed to compare relative noninferiority of evidence-based psychotherapies for PTSD and MD, specifically Behavioral Activation and Therapeutic Exposure (BA-TE), when delivered via HBT versus in person, in clinic delivery. Method A repeated measures (i.e., baseline, posttreatment, 3-, 6-month follow-up) randomized controlled design powered for noninferiority analyses was used to compare PTSD and MD symptom improvement in response to BA-TE delivered via HBT versus in person, in clinic conditions. Participants were 232 veterans diagnosed with full criteria or predefined subthreshold PTSD. Results PTSD and MD symptom improvement following BA-TE delivered by HBT was comparable to that of BA-TE delivered in person at posttreatment and at 3- and 12-month follow-up. Conclusion Evidence-based psychotherapy for PTSD and depression can be safely and effectively delivered via HBT with clinical outcomes paralleling those of clinic-based care delivered in person. HBT, thereby, addresses barriers to care related to both logistics and stigma.

Journal ArticleDOI
TL;DR: If successful, KOR antagonists would represent a unique example in psychiatry where the therapeutic mechanism of a drug class is understood before it is shown to be efficacious in humans.
Abstract: Kappa-opioid receptor (KOR) antagonists are currently being considered for the treatment of a variety of neuropsychiatric conditions, including depressive, anxiety, and substance abuse disorders. A general ability to mitigate the effects of stress, which can trigger or exacerbate these conditions, may explain their putative efficacy across such a broad array of conditions. The discovery of their potentially therapeutic effects evolved from preclinical research designed to characterize the molecular mechanisms by which experience causes neuroadaptations in the nucleus accumbens (NAc), a key element of brain reward circuitry. This research established that exposure to drugs of abuse or stress increases the activity of the transcription factor CREB (cAMP response element binding protein) in the NAc, which leads to elevated expression of the opioid peptide dynorphin, which in turn causes core signs of depressive- and anxiety-related disorders. Disruption of KORs—the endogenous receptors for dynorphin—produces antidepressant- and anxiolytic-like actions in screening procedures that identify standard drugs of these classes, and reduces stress effects in tests used to study addiction and stress-related disorders. Although interest in this target is high, prototypical KOR antagonists have extraordinarily persistent pharmacodynamic effects that complicate clinical trials. The development of shorter-acting KOR antagonists together with more rapid designs for clinical trials may soon provide insight on whether these drugs are efficacious as would be predicted by preclinical work. If successful, KOR antagonists would represent a unique example in psychiatry where the therapeutic mechanism of a drug class is understood before it is shown to be efficacious in humans.

Journal ArticleDOI
TL;DR: Considerable research has demonstrated the efficacy of repetitive transcranial magnetic stimulation treatment in patients with depression, but limited research has described the pattern of response or explored possible predictors of the likelihood of treatment response.
Abstract: BACKGROUND: Considerable research has demonstrated the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment in patients with depression. However, limited research has described the pattern of response to rTMS treatment or explored possible predictors of the likelihood of treatment response. METHODS: Data from 11 clinical trials (n = 1,132) was pooled and we described the pattern of response to rTMS, rate of response, and remission as well as potential clinical and demographic predictors of response. RESULTS: There was a bimodal pattern of response to rTMS with the response-associated peak at 57% reduction in depression rating scale scores. About 46% of patients achieved response criteria, with 31% completing rTMS treatment in remission. A greater likelihood of response was seen for patients who had less severe depression at baseline, a shorter duration of the current episode, and recurrent rather than single episode of depression. Greater response was also seen in patients treated at higher stimulation intensity. CONCLUSIONS: A meaningful percentage (>40%) of patients respond to a course of rTMS treatment. Response does vary with a number of clinical and demographic variables but none of these variables exert a sufficiently strong influence on response rates to warrant using these criteria to exclude patients from treatment.© 2016 Wiley Periodicals, Inc. Language: en

Journal ArticleDOI
TL;DR: A GWAS and genome‐wide by environment interaction study of depressive symptoms and considers gene–environment interaction (GxE) might improve efficiency for gene discovery.
Abstract: Background Genome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene–environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms. Methods Using data from the SHARe cohort of the Women's Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts. Results No SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 × 10−8) and rs75407252 (intronic to CACNA2D3, P = 6.99 × 10−7). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 × 10−7) and rs4542757 (intronic to DCC, P = 7.31 × 10−7). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 × 10−10; located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self-reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample. Conclusions Our results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities.

Journal ArticleDOI
TL;DR: There is a need of brief psychotherapeutical treatment alternative for suicide prevention in specialized outpatient clinics for adults with borderline personality disorder.
Abstract: Background Many psychological treatments have shown effect on reducing self-harm in adults with borderline personality disorder. There is a need of brief psychotherapeutical treatment alternative for suicide prevention in specialized outpatient clinics. Methods/Design The DiaS trial was designed as a pragmatic single-center, two-armed, parallel-group observer-blinded, randomized clinical superiority trial. The participants had at least two criteria from the borderline personality disorder diagnosis and a recent suicide attempt (within a month). The participants were offered 16 weeks of dialectical behavior therapy (DBT) versus up to 16 weeks of collaborative assessment and management of suicidality (CAMS) treatment. The primary composite outcome was the number of participants with a new self-harm (nonsuicidal self-injury [NSSI] or suicide attempt) at week 28 from baseline. Other exploratory outcomes were: severity of borderline symptoms, depressive symptoms, hopelessness, suicide ideation, and self-esteem. Results At 28 weeks, the number of participants with new self-harm in the DBT group was 21 of 57 (36.8%) versus 12 of 51 (23.5%) in the CAMS treatment (OR: 1.90; 95% CI: 0.80–4.40; P = .14). When assessing the effect of DBT versus CAMS treatment on the individual components of the primary outcome, we observed no significant differences in the number of NSSI (OR: 1.60; 95% CI: 0.70–3.90; P = .31) or number of attempted suicides (OR: 2.24; 95% CI: 0.80–7.50; P = .12). Conclusion In adults with borderline personality traits and disorder and a recent suicide attempt, DBT does not seem superior compared with CAMS for reduction of number of self-harm or suicide attempts. However, further randomized clinical trials may be needed.

Journal ArticleDOI
TL;DR: The impact of childhood maltreatment on the methylation status of the 5‐HT3AR and its association with clinical severity outcomes in relation with a functional genetic polymorphism is studied.
Abstract: BACKGROUND: Serotonin 3A receptor (5-HT3A R) is associated at the genetic and epigenetic levels with a variety of psychiatric disorders and interacts with early-life stress such as childhood maltreatment. We studied the impact of childhood maltreatment on the methylation status of the 5-HT3A R and its association with clinical severity outcomes in relation with a functional genetic polymorphism. METHODS: Clinical severity indexes of 346 bipolar, borderline personality, and adult attention deficit hyperactivity disorders patients were tested for association with the DNA methylation status of eight 5-HT3A R gene CpGs. Relationship between the functional variant rs1062613 (C > T) and methylation status on severity of the disorders were also assessed. RESULTS: Childhood maltreatment was associated with higher severity of the disease (higher number of mood episodes, history of suicide attempts, hospitalization, and younger age at onset) across disorders and within each individual disorder. This effect was mediated by two 5-HT3A R CpGs. Compared to T allele carriers, CC carriers had higher methylation status at one CpG located 1 bp upstream of this variant. CONCLUSIONS: This study shows that epigenetic modification of the 5-HT3A R is involved in the mechanism underlying the relationship between maltreatment in childhood and the severity of several psychiatric disorders in adulthood. Language: en

Journal ArticleDOI
TL;DR: In this article, a clinical review of the use of ketamine in the treatment of depression and bipolar disorder has been presented, with the initial clinical implications of further development of a potentially novel treatment for rapid reduction of symptoms in depressed patients.
Abstract: There is an urgent need for more rapidly effective pharmacotherapies for major depressive disorder and bipolar disorder (BP) that are efficacious and tolerable for depressed patients who respond poorly to conventional treatments. Multiple controlled trials have now demonstrated a rapid, nonsustained antidepressive response to a single intravenous infusion of ketamine. Early controlled studies of intranasal or serial infusion therapy appear promising. The effective dose for depression is lower than the typical anesthetic doses, and side-effects are generally mild and transient. The data investigating the adjunctive use of concurrent ketamine in the course of electroconvulsive therapy (ECT) for depression do not suggest efficacy or tolerability. The therapeutic potential of ketamine has stimulated considerable excitement among clinicians, patients, and industry, and has led to the increasing use of ketamine as an off-label substitute for ECT and other antidepressive treatments. This clinical review of ketamine will assess the evidence-based use of ketamine and initial clinical implications of further development of a potentially novel treatment for rapid reduction of symptoms in depressed patients.

Journal ArticleDOI
TL;DR: This study identified courses ofPTG over a 2‐year period in a contemporary, nationally representative sample of U.S. military veterans, and examined sociodemographic, military, trauma, medical, and psychosocial predictors of PTG course.
Abstract: BACKGROUND: Posttraumatic growth (PTG) is increasingly recognized as an important psychosocial phenomenon, but few studies have evaluated the longitudinal course of PTG. This study identified courses of PTG over a 2-year period in a contemporary, nationally representative sample of U.S. military veterans, and examined sociodemographic, military, trauma, medical, and psychosocial predictors of PTG course. METHODS: Data were based on a Web-based survey of a nationally representative sample of 1,838 U.S. veterans who reported at least one potentially traumatic event and provided data at two time points (October-December 2011 and September-October 2013). RESULTS: Five different courses of PTG were identified-Consistently Low (33.6%), Moderately Declining (19.4%), Increasing PTG (16.8%), Dramatically Declining (15.7%), and Consistently High (14.5%). More than half (59.4%) of veterans who reported at least "moderate" PTG maintained that level of PTG 2 years later. Posttraumatic stress disorder symptoms, medical conditions, purpose in life, altruism, gratitude, religiosity, and an active reading lifestyle predicted maintenance or increase in PTG. CONCLUSIONS: PTG has a heterogeneous course and is not only common, but can persist over time especially in the presence of posttraumatic stress and certain psychosocial factors. Clinicians and researchers should consider the personal growth that can result from trauma and help trauma survivors find ways to maintain this growth over time. Language: en

Journal ArticleDOI
TL;DR: It is not clear whether evidence‐based depression therapies are as effective in college students as in other adult populations, but the higher levels of cognitive functioning and IQ and higher proportions of first‐onset cases might lead to treatment effects being different among college students relative to the larger adult population.
Abstract: BACKGROUND: Expanded efforts to detect and treat depression among college students, a peak period of onset, have the potential to bear high human capital value from a societal perspective because depression increases college withdrawal rates. However, it is not clear whether evidence-based depression therapies are as effective in college students as in other adult populations. The higher levels of cognitive functioning and IQ and higher proportions of first-onset cases might lead to treatment effects being different among college students relative to the larger adult population. METHODS: We conducted a metaanalysis of randomized trials comparing psychological treatments of depressed college students relative to control groups and compared effect sizes in these studies to those in trials carried out in unselected populations of depressed adults. RESULTS: The 15 trials on college students satisfying study inclusion criteria included 997 participants. The pooled effect size of therapy versus control was g = 0.89 (95% CI: 0.66∼1.11; NNT = 2.13) with moderate heterogeneity (I(2) = 57; 95% CI: 23∼72). None of these trials had low risk of bias. Effect sizes were significantly larger when students were not remunerated (e.g. money, credit), received individual versus group therapy, and were in trials that included a waiting list control group. No significant difference emerged in comparing effect sizes among college students versus adults either in simple mean comparisons or in multivariate metaregression analyses. CONCLUSIONS: This metaanalysis of trials examining psychological treatments of depression in college students suggests that these therapies are effective and have effect sizes comparable to trials carried out among depressed adults. Language: en

Journal ArticleDOI
TL;DR: The aim of this study is to investigate the effects of an individualized yoga intervention for reducing depression and anxiety in patients with a history of depression.
Abstract: BACKGROUND: Depression and anxiety are leading causes of disability worldwide. Current treatments are primarily pharmaceutical and psychological. Questions remain about effectiveness and suitability for different people. Previous research suggests potential benefits of yoga for reducing depression and anxiety. The aim of this study is to investigate the effects of an individualized yoga intervention. METHODS: A sample of 101 people with symptoms of depression and/or anxiety participated in a randomized controlled trial comparing a 6-week yoga intervention with waitlist control. Yoga was additional to usual treatment. The control group was offered the yoga following the waitlist period. Measures included Depression Anxiety Stress Scale (DASS-21), Kessler Psychological Distress Scale (K10), Short-Form Health Survey (SF12), Scale of Positive and Negative Experience (SPANE), Flourishing Scale (FS), and Connor-Davidson Resilience Scale (CD-RISC2). RESULTS: There were statistically significant differences between yoga and control groups on reduction of depression scores (-4.30; 95% CI: -7.70, -0.01; P =.01; ES -.44). Differences in reduced anxiety scores were not statistically significant (-1.91; 95% CI: -4.58, 0.76; P =.16). Statistically significant differences in favor of yoga were also found on total DASS (P =.03), K10, SF12 mental health, SPANE, FS, and resilience scores (P CONCLUSION: Yoga plus regular care was effective in reducing symptoms of depression compared with regular care alone. Further investigation is warranted regarding potential benefits in anxiety. Individualized yoga may be particularly beneficial in mental health care in the broader community.© 2016 Wiley Periodicals, Inc. Language: en

Journal ArticleDOI
TL;DR: The reward positivity (RewP) event‐related potential (ERP) component was used to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression and comorbid anxiety and depression.
Abstract: BACKGROUND: Cognitive behavioral therapy (CBT) is a well-established treatment for anxiety and depression; however, response to CBT is heterogeneous across patients and many remain symptomatic after therapy, raising the need to identify prospective predictors for treatment planning. Altered neural processing of reward has been implicated in both depression and anxiety, and improving hedonic capacity is a goal of CBT. However, little is known about how neural response to reward relates to CBT outcomes in depression and anxiety. The current study used the reward positivity (RewP) event-related potential (ERP) component to examine whether neural reactivity to reward would predict CBT response in a sample of patients with anxiety without depression (n = 30) and comorbid anxiety and depression (CAD, n = 22). METHODS: Participants completed a guessing reward ERP paradigm before completing 12 weeks of standard CBT. RESULTS: The majority of the sample (68%; 35 out of 52 patients) responded to treatment, and those with a reduced RewP at baseline were more likely to respond to treatment. A reduced RewP was also associated with a greater pre-to-post CBT reduction in depressive symptoms among individuals with CAD, but not among individuals with pure anxiety. CONCLUSIONS: CBT may be most beneficial in reducing depressive symptoms for individuals who demonstrate decreased reward reactivity prior to treatment. CBT may target reward brain function, leading to greater improvement in symptoms. These effects may be strongest, and therefore most meaningful, for individuals with reward-processing deficits prior to treatment.© 2016 Wiley Periodicals, Inc. Language: en

Journal ArticleDOI
TL;DR: Considering the polarity‐dependent effects on cortical excitability of transcranial direct current stimulation (tDCS), cathodal and/or anodal tDCS is applied to the pre‐SMA of OCD patients to test which current polarity might better improve symptoms.
Abstract: Background Presupplementary motor area (pre-SMA) hyperactivity has been detected in obsessive–compulsive disorder (OCD) patients. However, it is not understood whether this is a putative primary cause or a compensatory mechanism in OCD pathophysiology. Considering the polarity-dependent effects on cortical excitability of transcranial direct current stimulation (tDCS), we applied cathodal and/or anodal tDCS to the pre-SMA of OCD patients to test which current polarity might better improve symptoms. Methods Twelve OCD patients received initially 10 anodal (n = 6) or cathodal (n = 6) daily consecutive 2 mA/20 min tDCS sessions with the active electrode placed bilaterally on the pre-SMA. In case of improvement or no change in symptoms severity, the subjects were maintained on the same current polarity for 10 more sessions. In case of symptoms worsening after the first 10 sessions they were switched to the other polarity for 10 more sessions to test the hypothesis of a polarity-dependent effect. Therefore, each subject received 20 tDCS sessions. The Yale-Brown Obsessive–Compulsive Scale (Y-BOCS) and the Sheehan Disability Scale (SDS) were administered biweekly to assess changes in symptoms severity. Results After 10 sessions, 50% of patients who initially received anodal stimulation were switched to cathodal, while 100% of patients initially assigned to cathodal stimulation continued on the same polarity. At the end of the study, a statistically significant decrease was observed in the mean Y-BOCS scores of those patients who underwent cathodal tDCS. No pre–post difference was found in the scores of patients following anodal tDCS. Conclusions Cathodal but not anodal tDCS over the pre-SMA significantly improved OCD symptoms.

Journal ArticleDOI
TL;DR: Whether sensitive parenting is impaired in mothers with depression in remission, and whether among these mothers childhood abuse has an additional impact, is investigated.
Abstract: BACKGROUND: The association between maternal depression and adverse outcomes in children is well established. Similar links have been found for maternal childhood abuse. One proposed pathway of risk transmission is reduced maternal emotional availability. Our aim was to investigate whether sensitive parenting is impaired in mothers with depression in remission, and whether among these mothers childhood abuse has an additional impact. METHODS: The mother-child interaction of 188 dyads was assessed during a play situation using the Emotional Availability Scales, which measure the overall affective quality of the interaction: maternal sensitivity, structuring, nonhostility, and nonintrusiveness. Mothers with depression in remission were compared to healthy mothers. Children were between 5 and 12 years old. Group differences and impact of additional childhood abuse were analyzed by one-factorial analyses of covariance and planned contrasts. RESULTS: Mothers with depression in remission showed less emotional availability during mother-child interaction compared to healthy control mothers. Specifically, they were less sensitive and, at trend-level, less structuring and more hostile. Among these mothers, we found an additional effect of severe maternal childhood abuse on maternal sensitivity: Mothers with depression in remission and a history of severe childhood abuse were less sensitive than remitted mothers without childhood abuse. CONCLUSIONS: Our data suggest that depression impacts on maternal emotional availability during remission, which might represent a trait characteristic of depression. Mothers with depression in remission and additional severe childhood abuse were particularly affected. These findings may contribute to the understanding of children's vulnerability to develop a depressive disorder themselves. Language: en

Journal ArticleDOI
TL;DR: Metabolic syndrome components—waist circumference, high‐density lipoprotein cholesterol (HDL‐C), triglycerides, systolic blood pressure and fasting glucose—are cross‐sectionally associated with depression and anxiety with differing strength.
Abstract: BACKGROUND: Metabolic syndrome components-waist circumference, high-density lipoprotein cholesterol (HDL-C), triglycerides, systolic blood pressure and fasting glucose-are cross-sectionally associated with depression and anxiety with differing strength. Few studies examine the relationships over time or whether antidepressants have independent effects. METHODS: Participants were from the Netherlands Study of Depression and Anxiety (NESDA; N = 2,776; 18-65 years; 66% female). At baseline, 2- and 6-year follow-up, participants completed diagnostic interviews, depression and anxiety symptom inventories, antidepressant use assessment, and measurements of the five metabolic syndrome components. Data were analyzed for the consistency of associations between psychopathology indicators and metabolic syndrome components across the three assessment waves, and whether psychopathology or antidepressant use at one assessment predicts metabolic dysregulation at the next and vice versa. RESULTS: Consistently across waves, psychopathology was associated with generally poorer values of metabolic syndrome components, particularly waist circumference and triglycerides. Stronger associations were observed for psychopathology symptom severity than diagnosis. Antidepressant use was independently associated with higher waist circumference, triglycerides and number of metabolic syndrome abnormalities, and lower HDL-C. Symptom severity and antidepressant use were associated with subsequently increased number of abnormalities, waist circumference, and glucose after 2 but not 4 years. Conversely, there was little evidence that metabolic syndrome components were associated with subsequent psychopathology outcomes. CONCLUSIONS: Symptom severity and antidepressant use were independently associated with metabolic dysregulation consistently over time and also had negative consequences for short-term metabolic health. This is of concern given the chronicity of depression and anxiety and prevalence of antidepressant treatment.© 2016 The Authors. Depression and Anxiety published by Wiley Periodicals, Inc. Language: en

Journal ArticleDOI
TL;DR: Data from a randomized clinical trial of psychotherapy for PTSD in female military veterans and active duty personnel is used to examine the correspondence between benchmarks of improvement in PTSD symptoms and changes in quality of life.
Abstract: Background Although research has shown that PTSD symptom change relates to improved quality of life, the question of how much improvement in PTSD symptoms is necessary to result in meaningful improvements in quality of life remains unanswered. We used data from a randomized clinical trial of psychotherapy for PTSD in female military veterans and active duty personnel to examine the correspondence between benchmarks of improvement in PTSD symptoms and changes in quality of life. Methods Participants were 235 female veterans and Army soldiers who were randomized to 10 weekly sessions of Prolonged Exposure or Present-Centered Therapy. We operationalized PTSD symptom change in terms of four progressively stringent mutually exclusive definitions—No Response, Response, Loss of Diagnosis, and Remission—successively comparing each category to the prior one: No Response versus Response, Response versus Loss of Diagnosis, and Loss of Diagnosis versus Remission. Outcomes were clinically meaningful improvements and good endpoints in domains of clinician-rated and self-reported quality of life. Results Response was associated with improvement on almost all measures, but with only one good endpoint. Loss of Diagnosis was associated with improvement on all measures except self-rated social functioning and with achieving a good endpoint on all measures. Remission was associated with improvement in clinician-rated social impairment and a good endpoint in clinician-rated occupational impairment. Conclusions For most domains of quality of life, treating a patient until the patient no longer meets diagnostic criteria would be optimal. For some domains, further improvements may result by helping a patient achieve remission.

Journal ArticleDOI
TL;DR: Whether abnormal ACC–hippocampal connectivity is associated with genetic variability, particularly for polymorphisms of a gene that has been previously associated with PTSD, FKBP5, is examined.
Abstract: BACKGROUND: The integrity of connections between the hippocampus and the anterior cingulate cortex (ACC) is critical for adaptive cognitive and emotional processing; these connections may be compromised in posttraumatic stress disorder (PTSD). However, there is a lack of PTSD research that combines structural and functional connectivity data, and no studies have examined whether abnormal ACC-hippocampal connectivity is associated with genetic variability, particularly for polymorphisms of a gene that has been previously associated with PTSD, FKBP5. This was the goal of the present study. METHODS: Fifty-four women with and without PTSD underwent diffusion tensor imaging and resting-state MRI. Probabilistic tractography was used to examine ACC-hippocampal structural connectivity; mean fractional anisotropy (FA) values were extracted from connectivity streamlines, which represent the cingulum bundle. Genotype data were collected for a single nucleotide polymorphism (SNP) of FKBP5, rs1360780. RESULTS: Participants with PTSD demonstrated poorer structural connectivity (lower cingulum FA) compared to traumatized controls (F1, 50 = 6.77, P CONCLUSIONS: Individuals with PTSD demonstrated compromised structural connectivity of the hippocampus-ACC pathway. Altered hippocampus-ACC connectivity may represent a highly salient intermediate neural phenotype for PTSD.© 2016 Wiley Periodicals, Inc. Language: en

Journal ArticleDOI
TL;DR: The aims of the study were to explore the direct and indirect links between child sexual abuse and cyberbullying, bullying, and mental health problems and to study maternal support as a potential protective factor.
Abstract: BACKGROUND: Child sexual abuse is associated with adverse outcomes, including heightened vulnerability that may translate into risk of revictimization. The aims of the study were: (1) to explore the direct and indirect links between child sexual abuse and cyberbullying, bullying, and mental health problems and (2) to study maternal support as a potential protective factor. METHODS: Teenagers involved in the two first waves of the Quebec Youths' Romantic Relationships Survey (N = 8,194 and 6,780 at Wave I and II, respectively) completed measures assessing child sexual abuse and maternal support at Wave I. Cyberbullying, bullying, and mental health problems (self-esteem, psychological distress, and suicidal ideations) were evaluated 6 months later. RESULTS: Rates of cyberbullying in the past 6 months were twice as high in sexually abused teens compared to nonvictims both for girls (33.47 vs. 17.75%) and boys (29.62 vs. 13.29%). A moderated mediated model revealed a partial mediation effect of cyberbullying and bullying in the link between child sexual abuse and mental health. Maternal support acted as a protective factor as the conditional indirect effects of child sexual abuse on mental health via cyberbullying and bullying were reduced in cases of high maternal support. CONCLUSIONS: Results have significant relevance for prevention and intervention in highlighting the heightened vulnerability of victims of child sexual abuse to experience both bullying and cyberbullying. Maternal support may buffer the risk of developing mental health distress, suggesting that intervention programs for victimized youth may profit by fostering parent involvement.© 2016 Wiley Periodicals, Inc. Language: en

Journal ArticleDOI
TL;DR: The effect of childhood malt treatment on predicting the 4‐year course of depressive and anxiety disorders and the possible mediating role of personality characteristics in the association between childhood maltreatment and illness course are investigated.
Abstract: BACKGROUND: We investigated the effect of childhood maltreatment on predicting the 4-year course of depressive and anxiety disorders and the possible mediating role of personality characteristics in the association between childhood maltreatment and illness course. METHODS: Longitudinal data in a large sample of participants with baseline depressive and/or anxiety disorders (n = 1,474, 18-65 years) were collected in the Netherlands Study of Depression and Anxiety. At baseline, childhood maltreatment was assessed with a semistructured interview. Personality trait questionnaires (Neuroticism-Extroversion-Openness Five Factor Inventory, Mastery scale, and Leiden Index of Depression Sensitivity), recent stressful life events (List of Threatening Experiences Questionnaire), and psychosocial variables were administered. The Life Chart Interview was used to determine the time to remission of depressive and/or anxiety disorders. RESULTS: At baseline, 846 participants (57.4%) reported any childhood maltreatment. Childhood maltreatment had a negative impact on psychosocial functioning and was predictive of more unfavorable personality characteristics and cognitive reactivity styles (P CONCLUSIONS: Certain personality characteristics are key players in the mechanism linking childhood maltreatment to an adverse illness course of depressive and anxiety disorders. Early interventions-reducing neuroticism and hopelessness, and enhancing extraversion and locus of control-might contribute to a better prognosis in a "high-risk" group of depressive and anxiety disorders. Language: en

Journal ArticleDOI
TL;DR: The present study seeks to identify factors that influence PTSD symptom load across pregnancy and early post partum, and study its impact on postpartum adaptation.
Abstract: BACKGROUND: Little is known about trajectories of PTSD symptoms across the peripartum period in women with trauma histories, specifically those who met lifetime PTSD diagnoses prior to pregnancy. The present study seeks to identify factors that influence PTSD symptom load across pregnancy and early postpartum, and study its impact on postpartum adaptation. METHOD: The current study is a secondary analysis on pregnant women with a Lifetime PTSD diagnosis (N = 319) derived from a larger community sample who were interviewed twice across pregnancy (28 and 35 weeks) and again at 6 weeks postpartum, assessing socioeconomic risks, mental health, past and ongoing trauma exposure, and adaptation to postpartum. RESULTS: Using trajectory analysis, first we examined the natural course of PTSD symptoms based on patterns across peripartum, and found four distinct trajectory groups. Second, we explored factors (demographic, historical, and gestational) that shape the PTSD symptom trajectories, and examined the impact of trajectory membership on maternal postpartum adaptation. We found that child abuse history, demographic risk, and lifetime PTSD symptom count increased pregnancy-onset PTSD risk, whereas gestational PTSD symptom trajectory was best predicted by interim trauma and labor anxiety. Women with the greatest PTSD symptom rise during pregnancy were most likely to suffer postpartum depression and reported greatest bonding impairment with their infants at 6 weeks postpartum. CONCLUSIONS: Screening for modifiable risks (interpersonal trauma exposure and labor anxiety) and /or PTSD symptom load during pregnancy appears critical to promote maternal wellbeing. Language: en