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Background Both Major Depressive Disorder (MDD) and Primary Insomnia (PI) have been linked to deficiencies in cortical γ-aminobutyric acid (GABA) and glutamate (Glu) thus suggesting a shared neurobiological link between these two conditions. The extent to which comorbid insomnia contributes to GABAergic or glutamatergic deficiencies in MDD remains unclear. Methods We used single-voxel proton magnetic resonance spectroscopy (1H MRS) at 4 Tesla to examine GABA+ and Glu relative to creatine (Cr) in the dorsal anterior cingulate cortex (dACC) and in the parieto-occipital cortex (POC) of 51 non-medicated adults with MDD, 24 adults with Primary Insomnia (PI), and 25 age- and sex-matched good sleeper controls (HC). Measures of depression severity and subjective and objective sleep quality were compared with 1H MRS metabolite measures. Results MDD subjects exhibited a 15% decrease in Glu/Cr in the dACC compared to HC. Within the MDD group, there was a trend inverse correlation between dACC Glu/Cr and anhedonia ratings. We observed no significant association between measures of sleep quality with dACC Glu/Cr in those with MDD. Limitations The protocol and data interpretation would have been enhanced by the recruitment of MDD subjects with a broader range of affect severity and a more comprehensive assessment of clinical features. Conclusions These findings support the role of cortical glutamatergic mechanisms in the pathophysiology of MDD. Insomnia severity did not further contribute to the relative deficiency of glutamatergic measures in MDD.

Background Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. Methods 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300 mg/day], aripiprazole [≤2.5 mg/day], or sertraline [≥150 mg/day]) were randomized to naltrexone 1 mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. Results All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN, from 30.7±4.3 to 22.8±8.5) for placebo (d=1.45; p=0.035). MADRS-15 item scores decreased from 36.6±6.2 to 13.2±8.8 for LDN, from 36.7±4.2 to 26.0±10.0 for placebo (d=1.49; p=0.035). Clinical Global Improvement Scale-Severity (CGI-S) scores decreased from 4.3±0.5 to 3.0±1.1 for LDN, from 4.3±0.5 to 4.0±0.6 for placebo (d=1.22; p=0.064). Limitations Small study; restrictions on allowed antidepressants. Conclusion LDN augmentation showed some benefit for MDD relapse on dopaminergic agents. Confirmation in larger studies is needed.

Previously, we found an anxiolytic effect of ziprasidone augmentation to escitalopram (compared with placebo augmentation) in patients with depression in an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial. Here, we carried out a post-hoc analysis, comparing changes in the Hamilton Depression and Anxiety Rating Scales between patients with anxious depression versus nonanxious depression, using a moderator analysis. Hamilton Depression Rating Scales total change scores from baseline and endpoint were not significantly different (interaction term P=0.91) in patients with anxious depression on ziprasidone augmentation (n=19; -9.1±4.9) or placebo (n=19; -6.1±8.9) versus patients without anxious depression on ziprasidone (n=52; -5.5±6.7) or placebo (n=49; -2.3±4.5). There was a trend toward statistical significance (interaction term P=0.1) in favor of patients without anxious depression for a difference in Hamilton Anxiety Rating Scale total change scores from baseline to endpoint [patients with anxious depression on ziprasidone augmentation (n=19; -2.7±5.3) or placebo (n=19; -3.3±5.8) versus patients without anxious depression on ziprasidone (n=51; -3.9±6.6) or placebo (n=44; -0.9±4.7)]. Ziprasidone augmentation was equally efficacious in treating depression in patients with versus without anxious depression. However, the observed anxiolytic effect for patients with higher anxiety was not clinically significant.

Scrupulosity is a subtype of obsessive-compulsive disorder (OCD) defined by religious or moral fears. Although the relationship between personality and OCD has been extensively studied, it remains unclear how personality relates specifically to religious obsessions and scrupulous fears. In the current study, we examined the association between scrupulosity and personality characteristics, including the Five Factor Model (FFM) and obsessive-compulsive personality disorder (OCPD), in a sample of individuals with self-reported obsessive-compulsive (OC) symptoms. Seventy-nine participants completed an anonymous online survey. FFM traits did not, but OCPD traits did, explain a significant amount of variance in scrupulosity. We also replicated previous findings showing that individuals with greater OC symptoms score lower on Extraversion and higher on Neuroticism. These findings suggest that scrupulous symptoms may not be specifically linked with any of the FFM personality factors, but may be associated with OC...

BACKGROUND: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. METHODS: Between April 2012 and October 2013, 14 outpatients with DSM-IV-diagnosed major depressive disorder were recruited for the presence of current, stable (≥ 3 months) suicidal thoughts. They received open-label ketamine infusions over 3 weeks (0.5 mg/kg over 45 minutes for the first 3 infusions; 0.75 mg/kg over 45 minutes for the last 3). In this secondary analysis, the primary outcome measures of suicidal ideation (Columbia-Suicide Severity Rating Scale [C-SSRS] and the Suicide Item of the 28-item Hamilton Depression Rating Scale [HDRS28-SI]) were assessed at 240 minutes postinfusion and for 3 months thereafter in a naturalistic follow-up. RESULTS: Over the course of the infusions (acute treatment phase), 7 of 14 patients (50%) showed remission of suicidal ideation on the C-SSRS Ideation scale (even among patients whose depression did not remit). There was a significant linear decrease in this score over time (P CONCLUSIONS: In this preliminary study, repeated doses of open-label ketamine rapidly and robustly decreased suicidal ideation in pharmacologically treated outpatients with treatment-resistant depression with stable suicidal thoughts; this decrease was maintained for at least 3 months following the final ketamine infusion in 2 patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01582945.© Copyright 2016 Physicians Postgraduate Press, Inc. Language: en

Background: Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone’s safety and efficacy as an augmentation agent in outpatients with partially remitted major depressive disorder (MDD) with residual symptoms of anger and irritability. Methods: A total of 13 outpatients with partially remitted MDD [currently treated with selective serotonin reuptake inhibitors (SSRIs)] received four weeks of iloperidone or placebo, followed by one week of washout. Patients were then crossed over to the other treatment arm for 4 weeks. Treatment arms were randomized and double blind; and two sites were used for the study. Analyses compared treatment response using the Symptom Questionnaire (SQ) Anger/Hostility Subscale as the primary outcome measure. Results: There was no significant differential effect of iloperidone × weeks on the SQ Anger/Hostility Subscore over the course of the study, compared with placebo × weeks, regardless of administration order ( p = 0.77). Conclusions: Iloperidone did not significantly outperform placebo on measures of anger or irritability in patients with partially remitted MDD and residual anger/irritability.

Background Despite the development of effective pharmacologic and cognitive behavioral treatments for obsessive-compulsive disorder (OCD), some patients continue to be treatment-refractory and severely impaired. Fiber tracts connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical nuclei have been the target of neurosurgical lesions as well as deep brain stimulation in these patients. We report on the safety and efficacy of ventral gamma capsulotomy for patients with intractable OCD. Methods Fifty-five patients with severely disabling, treatment-refractory OCD received bilateral lesions in the ventral portion of the anterior limb of the internal capsule over a 20-year period using the Leksell Gamma Knife. The patients were prospectively followed over 3 years with psychiatric, neurologic, and neuropsychological assessments of safety and efficacy, as well as structural neuroimaging. Results Thirty-one of 55 patients (56%) had an improvement in the primary efficacy measure, the Yale-Brown Obsessive Compulsive Scale, of ≥35% over the 3-year follow-up period. Patients had significant improvements in depression, anxiety, quality of life, and global functioning. Patients tolerated the procedure well without significant acute adverse events. Five patients (9%) developed transient edema that required short courses of dexamethasone. Three patients (5%) developed cysts at long-term follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally conscious state. Conclusions Gamma Knife ventral capsulotomy is an effective radiosurgical procedure for many treatment-refractory OCD patients. A minority of patients developed cysts at long-term follow-up, 1 of whom had permanent neurological sequelae.

Background Several studies indicate that ketamine has rapid antidepressant effects in patients with treatment-resistant depression (TRD). The extent to which repeated doses of ketamine (versus placebo) reduce depression in the short and long term among outpatients with TRD and chronic, current suicidal ideation remains unknown. Methods Twenty-six medicated outpatients with severe major depressive disorder with current, chronic suicidal ideation were randomized in a double-blind fashion to six ketamine infusions (0.5 mg/kg over 45 minutes) or saline placebo over three weeks. Depression and suicidal ideation were assessed at baseline, 240 min post-infusion, and during a three-month follow-up phase. Results During the infusion phase, there was no differences in depression severity or suicidal ideation between placebo and ketamine (p = 0.47 and p = 0.32, respectively). At the end of the infusion phase, two patients in the ketamine group and one in the placebo group met criteria for remission of depression. At three-month follow-up, two patients in each group met criteria for remission from depression. Limitations Limitations include the small sample size, uncontrolled outpatient medication regimens, and restriction to outpatients, which may have resulted in lower levels of suicidal ideation than would be seen in emergency or inpatient settings. Conclusions Repeated, non-escalating doses of ketamine did not outperform placebo in this double-blind, placebo controlled study of patients with severe TRD and current, chronic suicidal ideation. This result may support our previously published open-label data that, in this severely and chronically ill outpatient population, the commonly used dose of 0.5 mg/kg is not sufficient.

BACKGROUND Children whose parents have cancer are at risk for psychosocial difficulties; however, the mechanisms are not well understood. This cross-sectional study sought support for a model connecting parental cancer to child distress through its impact on parenting self-efficacy beliefs and parenting behaviors by examining relations among parental illness, quality of life/parent functioning, parenting efficacy beliefs, and concerns about children's emotional distress. METHODS One hundred ninety-four adult oncology outpatients with children who were 18 years old or younger completed questionnaires assessing their health-related quality of life (Functional Assessment of Cancer Therapy–General), depression and anxiety symptoms (Hospital Anxiety and Depression Scale), overall distress (Distress Thermometer), and parenting efficacy beliefs and parenting concerns (Parenting Concerns Questionnaire). RESULTS Parenting efficacy scores for parents and coparents declined significantly after diagnosis. This decline correlated with more visits to a medical clinic, treatment with intravenous chemotherapy in the past month, poorer health-related quality of life, and more depression and distress. Parents experiencing the most concern about the impact of mood, physical limitations, and changes in routines on their children experienced the biggest declines in their own sense of efficacy as parents and in their belief in their coparent's efficacy. Finally, declines in parenting efficacy beliefs correlated with parental concerns about children's emotional distress about aspects of the parent's illness. CONCLUSIONS This study highlights the importance of identifying and addressing parenting concerns to alleviate patient distress, and it may help to guide future intervention efforts. Cancer 2015;121:3435–43. © 2015 American Cancer Society.

Despite their prevalence, depression and suicidal ideation (SI) are relatively unaddressed problems in the college student population. There are limited individual treatment studies targeting this population. Nine students (M = 19.33 years of age; SD ± .87) with depressive symptoms and/or SI were enrolled in 6-weeks of individual cognitive behavioral therapy (CBT) with a individually tailored manual-based treatment delivery. Measures were given before and after treatment. Primary results, presented as a case series, suggested decreases in depression across students and an overall downward trend in SI. As a secondary analysis, paired samples t tests showed significant decreases in both depression and SI. In summary, short-term, individually tailored manual-based CBT may be beneficial for reducing depressive symptoms and SI among college students. More research is needed to determine the best clinical interventions and targeted treatments for this vulnerable population.

We have previously shown an association between patient belief and treatment response in the Hypericum Depression Trial Study Group's 2002 study. We re-examined these data to determine whether clinical improvement was associated with physician belief about assigned therapy.Three hundred and forty adults with major depression and baseline scores ≥20 on the 17-item Hamilton Depression Scale (HDRS-17) were randomized to Hypericum 900-1500mg/day, sertraline 50-100mg/day, or placebo for 8 weeks. At week 8, physicians guessed their patients' treatment. We analyzed 277 subjects with at least one post-baseline visit and physician guess data. We examined association between guess and improvement in HDRS-17 and whether treatment assignment moderated the effect of belief on remission (final HDRS-17 score8).Patient and doctor guesses agreed at 53% for sertraline, 68% for Hypericum, and 52% for placebo (kappa=0.37). Doctors guessed placebo correctly (38%) more than sertraline (18%) or Hypericum (19%) (p=0.001). Adverse event scores were significantly greater among subjects for which the clinicians guessed Hypericum (p0.001) or sertraline (p=0.005) compared to placebo. Significant improvements in HDRS-17 score were found when comparing the Hypericum-guess (p0.001) or the sertraline-guess group (p0.001) against the placebo-guess group. Remission rates were significantly greater for subjects whose clinicians guessed sertraline (p0.001) or Hypericum (p0.001) versus placebo.Doctors tended to guess placebo more easily than Hypericum or sertraline, and their guesses tended to favor active therapies when improvement was more robust. Results show association but not causation, and merit more careful investigation.

Suicide is the third leading cause of death in college students, but there is limited consensual evidence to guide clinicians’ assessment and management of suicide. The aim of the current study was to assess the capability of a simple and practical measure, the Beck Depression Inventory (BDI) suicide item, to identify college students at high risk of suicide. Exploration of this research question could have important implications in this vulnerable population for identifying those at risk for suicide. Six-hundred-and-fifty-seven college students participated in a mental health screening and completed the BDI and the Suicidal Behaviors Questionnaire-Revised (SBQ-R), which is a detailed measure of suicide risk. We dichotomized the BDI suicide item, which measures suicidal ideation within the past week (presence vs. absence of suicidal ideation) as well as the SBQ-R total score (low vs. high risk of suicide). We computed the kappa statistic for the examination of agreement between these two measures. The kappa coefficient for the BDI suicide item and the SBQ-R was 0.57 for dichotomized scores. The BDI suicide item had a positive predictive value of 74 %, and a negative predictive value of 93 %. In a hierarchical linear regression, the BDI suicide item alone significantly predicted elevated scores on the SBQ-R [Chi square (1) = 128.427, p

Purpose National initiatives, such as the UK Improving Access to Psychological Therapies program (IAPT), demonstrate the feasibility of conducting empirical mental health assessments on a large scale, and similar initiatives exist in other countries. However, there is a lack of international consensus on which outcome domains are most salient to monitor treatment progress and how they should be measured. The aim of this project was to propose (1) an essential set of outcome domains relevant across countries and cultures, (2) a set of easily accessible patient-reported instruments, and (3) a psychometric approach to make scores from different instruments comparable. Methods Twenty-four experts, including ten health outcomes researchers, ten clinical experts from all continents, two patient advocates, and two ICHOM coordinators worked for seven months in a consensus building exercise to develop recommendations based on existing evidence using a structured consensus-driven modified Delphi technique. Results The group proposes to combine an assessment of potential outcome predictors at baseline (47 items: demographics, functional, clinical status, etc.), with repeated assessments of disease-specific symptoms during the treatment process (19 items: symptoms, side effects, etc.), and a comprehensive annual assessment of broader treatment outcomes (45 items: remission, absenteeism, etc.). Further, it is suggested reporting disease-specific symptoms for depression and anxiety on a standardized metric to increase comparability with other legacy instruments. All recommended instruments are provided online (www.ichom.org). Conclusion An international standard of health outcomes assessment has the potential to improve clinical decision making, enhance health care for the benefit of patients, and facilitate scientific knowledge. Electronic supplementary material The online version of this article (doi:10.1007/s11136-017-1659-5) contains supplementary material, which is available to authorized users.

In treated patients with major depressive disorder (MDD), residual symptoms are common and challenging to disentangle from possible antidepressant side effects. Our objective was to prospectively differentiate between rates of residual symptoms and treatment-emergent side effects.Participants in an episode of MDD were enrolled in a 6-week trial of an antidepressant. Assessments occurred at baseline and after 6 weeks of treatment, using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR) and the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH CPFQ). Among treatment responders, residual symptoms were those that remained the same or improved. Side effects were defined as newly emergent or worsening symptoms.Of 403 participants, 284 completed (70.5%) the trial; 93 (32.7%) were treatment responders. Residual symptoms were common and represented a substantially greater burden than side effects at end point. This was true across symptoms of depression broadly, as captured by items with the QIDS-SR and the MGH CPFQ.Prospective assessment is crucial to discriminate between residual symptoms and side effects during antidepressant treatment. This study demonstrated that after 6 weeks of active treatment, symptoms are likely to persist despite response to treatment and are much less likely to represent side effects of medication treatment.

Background Failed treatment trials are common in major depressive disorder and treatment-resistant depression, and remotely performed multifaceted, centralized structured interviews can potentially enhance signal detection by ensuring that enrolled patients meet eligibility criteria. Methods We assessed the use of a specific remote structured interview that validated the diagnosis, level of treatment resistance, and depression severity. The objectives were to (1) assess the rate at which patients who were deemed eligible for participation in trials by site investigators were ineligible, (2) assess the reasons for ineligibility, (3) compare rates of ineligibility between academic and nonacademic sites, (4) compare eligibility between US and non-US sites, and (5) report the placebo response rates in trials utilizing this quality assurance approach, comparing its placebo response rates with those reported in the literature. Methods included a pooled analysis of 9 studies that utilized this methodology (SAFER interviews). Results Overall, 15.33% of patients who had been deemed eligible at research sites were not eligible after the structured interviews. The most common reason was that patients did not meet the study requirements for level of treatment resistance. Pass rates were significantly higher at non-US compared with US sites (94.6% vs 83.3%, respectively; P < 0.001). There was not a significant difference between academic and nonacademic sites (87.8% vs 82.4%; P = 0.08). Placebo response rates were 13.0% to 27.3%, below the 30% to 40% average in antidepressant clinical trials, suggesting a benefit of the quality assurance provided by these interviews. Conclusions The use of a remotely structured interview by experienced clinical researchers was feasible and possibly contributed to lower-than-average placebo response rates. The difference between US and non-US sites should be the subject of further research.

The aim of this study was to evaluate efficacy of ziprasidone monotherapy for major depressive disorder (MDD) with and without psychomotor symptoms. In accordance with the sequential parallel comparison design, 106 MDD patients (age 44.0±10.7 years; female, 43.4%) were recruited and a post-hoc analysis was carried out on 12-week double-blind treatment with either ziprasidone (40-160 mg/day) or placebo, divided into two phases of 6 weeks each to the assigned treatment sequences, drug/drug, placebo/placebo, and placebo/drug. Psychomotor symptoms were evaluated on the basis of the Mini-International Neuropsychiatric Interview at baseline. Efficacy assessments, on the basis of the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Quick Inventory of Depressive Symptomatology Scale, Self-Rated (QIDS-SR), were performed every week throughout the trial. In phase I, ziprasidone monotherapy produced significant improvement in patients with psychomotor symptoms compared with placebo on the basis of HDRS-17 (F=5.95, P=0.017) and QIDS-SR (F=5.26, P=0.025) scores, whereas no significant changes were found in HDRS-17 (F=2.32, P=0.15) and QIDS-SR (F=3.70, P=0.074) scores in patients without psychomotor symptoms. In phase II, ziprasidone monotherapy produced no significant differences compared with placebo. In the pooled analysis, ziprasidone monotherapy showed significance according to QIDS-SR (Z=2.00, P=0.046) and a trend toward statistical significance according to the HDRS-17 (Z=1.66, P=0.10) in patients with psychomotor symptoms. Ziprasidone monotherapy may produce significant improvement compared with placebo in MDD patients with psychomotor symptoms.

Objective This pilot, randomized clinical trial investigates the effectiveness of tai chi as the primary treatment for Chinese Americans with major depressive disorder (MDD). Methods 67 Chinese Americans with DSM-IV MDD and no treatment for depression were recruited between March 2012 and April 2013 and randomized (1:1:1) into a tai chi intervention, an education program, or a waitlisted group for 12 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇); positive response for this outcome was defined as a decrease in total score of 50% or more, and remission was defined as HDRS₁₇ ≤ 7. Results Participants (N = 67) were 72% female with a mean age of 54 ± 13 years. No serious adverse events were reported. After the end of the 12-week intervention, response rates were 25%, 21%, and 56%, and remission rates were 10%, 21%, and 50% for the waitlisted, education, and tai chi intervention groups, respectively. The tai chi group showed improved treatment response when compared to both the waitlisted group (odds ratio [OR] = 2.11; 95% CI, 1.01-4.46) and to the education group (OR = 8.90; 95% CI, 1.17-67.70). Tai chi intervention showed significantly improved remission rate over the waitlisted group (OR = 3.01; 95% CI, 1.25-7.10), and a trend of improved remission compared to the education group (OR = 4.40; 95% CI, 0.78-24.17). Conclusions As the primary treatment, tai chi improved treatment outcomes for Chinese Americans with MDD over both passive and active control groups. Trial registration ClinicalTrials.gov identifier: NCT01619631.

Objective To examine motoric, cardiovascular, endocrine, and metabolic effects of adjunctive ziprasidone in adults with major depressive disorder (MDD) and prior nonresponse to 8 weeks of open-label escitalopram. Methods A multicenter, parallel, randomized, double-blind, placebo-controlled trial was conducted at 3 US academic medical centers from July 2008 to October 2013. Recruited were 139 outpatients with persistent DSM-IV MDD following an 8-week open-label trial of escitalopram. Subjects were then randomized to adjunctive ziprasidone (escitalopram + ziprasidone, n = 71) or placebo (escitalopram + placebo, n = 68) for 8 additional weeks. Cardiac and metabolic measures were obtained at each treatment visit. Barnes Akathisia Scale and Abnormal Involuntary Movement Scale (AIMS) scores were also obtained. Changes in outcome measures for each treatment group were compared by independent-samples t test. Results A trend toward significance (P = .06) in corrected QT interval (QTc) increase was observed for ziprasidone (mean [SD] = 8.8 [20.2] milliseconds) versus placebo (-0.02 [25.5] milliseconds). Ziprasidone-treated patients had a significantly greater increase in global akathisia scores (P = .01) and significant weight increase (mean [SD] = 3.5 [11.8] kg, or 7.7 [26.1] lb) compared to placebo (1.0 [6.4] kg, or 2.2 [14.1] lb) (P = .03). No significant changes in AIMS scores were observed for either treatment group. Conclusions Adjunctive ziprasidone, added to escitalopram, led to a greater weight gain and greater but modest akathisia compared to placebo. The effect of ziprasidone on QTc showed a trend toward significance, and therefore caution should be used in the administration of ziprasidone. While ziprasidone augmentation in patients with MDD appears safe, precautions should be taken in practice, specifically regular monitoring of electrocardiogram, weight, extrapyramidal symptoms, and involuntary movements. Trial registration ClinicalTrials.gov identifier: NCT00633399​​.

Purpose The purpose of this study was to assess the association of obsessive-compulsive symptoms (OCS) with suicide risk among college students. Methods Subjects were 474 college students who attended mental health screenings at two private universities and completed multiple self-report questionnaires. Results Presence of one or more OCS was associated with an increased odds ratio of suicide risk of approximately 2.4, although this was no longer a significant risk factor when controlling for depressive symptoms. Of the OCS assessed, only obsessions about speaking or acting violently remained an independent risk factor for suicidality over and above depression. Conclusions Although our study was cross-sectional in nature and thus cannot determine causality, increased burden of particular OCS symptom clusters, such as violent or aggressive obsessions, may increase risk among college students, for suicidal ideation.

The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Participants were 139 outpatients with persistent symptoms of major depression after an 8-week open-label trial of escitalopram (phase 1), randomly assigned in a 1:1 ratio to receive adjunctive ziprasidone (escitalopram plus ziprasidone, N=71) or adjunctive placebo (escitalopram plus placebo, N=68), with 8 weekly follow-up assessments. The primary outcome measure was clinical response, defined as a reduction of at least 50% in score on the 17-item Hamilton Depression Rating Scale (HAM-D). The Hamilton Anxiety Rating scale (HAM-A) and Visual Analog Scale for Pain were defined a priori as key secondary outcome measures.Rates of clinical response (35.2% compared with 20.5%) and mean improvement in HAM-D total scores (-6.4 [SD=6.4] compared with -3.3 [SD=6.2]) were significantly greater for the escitalopram plus ziprasidone group. Several secondary measures of antidepressant efficacy also favored adjunctive ziprasidone. The escitalopram plus ziprasidone group also showed significantly greater improvement on HAM-A score but not on Visual Analog Scale for Pain score. Ten (14%) patients in the escitalopram plus ziprasidone group discontinued treatment because of intolerance, compared with none in the escitalopram plus placebo group.Ziprasidone as an adjunct to escitalopram demonstrated antidepressant efficacy in adult patients with major depressive disorder experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram.

Psychosocial treatments and medications both have been shown to be effective in treating major depressive disorder. We hypothesized that cognitive-behavioral therapy (CBT) would outperform medication on measures of cognitive change.We randomized depressed individuals to 12 weeks of CBT (n = 15) or escitalopram (n = 11). In an intent-to-treat analysis (n = 26), we conducted a repeated measures analysis of variance to examine changes in depressive symptoms (ie, 17-item Hamilton Depression Rating Scale, Beck Depression Inventory), anhedonia (ie, Snaith-Hamilton Pleasure Scale), cognitive measures (ie, Dysfunctional Attitudes Scale, Automatic Thoughts Questionnaire, Perceived Stress Scale), and quality of life (ie, Quality of Life Enjoyment and Satisfaction Questionnaire) at 4 time points: baseline, week 4, week 8, and week 12. Treatment for both groups started at baseline, and patients received either 12 weeks of individual CBT or 12 weeks of escitalopram with flexible dosing (10 to 20 mg).Collapsing the escitalopram and CBT groups, there were statistically significant pre-post changes on all outcome measures. However, there were no statistically significant differences between treatment groups on any of the outcome measures, including cognitive measures across time points.Our results suggest that both CBT and escitalopram have similar effects across a variety of domains and that, in contrast to our a priori hypothesis, CBT and escitalopram were associated with comparable changes on cognitive measures.

We examined whether fatigue was associated with greater symptomatic burden and functional impairment in college students with depressive symptoms.Using data from the self-report Beck Depression Inventory (BDI), we stratified a group of 287 students endorsing significant symptoms of depression (BDI score ≥ 13) into 3 levels: no fatigue, mild fatigue, or moderate/severe fatigue. We then compared the 3 levels of fatigue across a battery of psychiatric and functional outcome measures.Approximately 87% of students endorsed at least mild fatigue. Students with moderate/severe fatigue had significantly greater depressive symptom severity compared with those with mild or no fatigue and scored higher on a suicide risk measure than those with mild fatigue. Students with severe fatigue evidenced greater frequency and intensity of anxiety than those with mild or no fatigue. Reported cognitive and functional impairment increased significantly as fatigue worsened.Depressed college students with symptoms of fatigue demonstrated functional impairment and symptomatic burden that worsened with increasing levels of fatigue. Assessing and treating symptoms of fatigue appears warranted within this population.

Objective To compare asthma care roles of maternal and paternal caregivers, and examine associations between caregiver involvement and the outcomes of adherence, morbidity, and parental quality of life (QoL). Methods Mothers and fathers in 63 families of children, ages 5-9 years, with persistent asthma completed semistructured interviews and questionnaires. Adherence was measured via electronic monitoring. Paired t tests compared parental asthma care roles, and analysis of covariance, controlling for socioeconomic status, evaluated associations of asthma outcomes with caregiver involvement scores. Results Mothers had higher scores on measures of involvement, beliefs in medication necessity, and on four subscales of the Family Asthma Management System Scale interview (Asthma Knowledge, Relationship with Provider, Symptom Assessment, and Response to Symptoms). Maternal QoL was lowest when both maternal and paternal involvement was high. Paternal involvement was associated with increased morbidity. Conclusions There is room for enhancement of fathers' asthma care roles. Higher levels of paternal involvement may be driven by family need.

Objective Skills for Life (SFL) is the largest school-based mental health program in the world, screening and providing services to more than 1,000,000 students in Chile over the past decade. This is the first external evaluation of the program. Method Of the 8,372 primary schools in Chile in 2010 that received public funding, one-fifth (1,637) elected to participate in SFL. Each year, all first- and third-grade students in these schools are screened with validated teacher- and parent-completed measures of psychosocial functioning (the Teacher Observation of Classroom Adaptation–Re-Revised [TOCA-RR] and the Pediatric Symptom Checklist–Chile [PSC-CL]). Students identified as being at risk on the TOCA-RR in first grade are referred to a standardized 10-session preventive intervention in second grade. This article explores the relationships between workshop participation and changes in TOCA-RR and PSC-CL scores, attendance, and promotion from third to fourth grades. Results In all, 16.4% of students were identified as being at-risk on the TOCA-RR. Statistically significant relationships were found between the number of workshop sessions attended and improvements in behavioral and academic outcomes after controlling for nonrandom selection into exposure and loss to follow-up. Effect sizes for the difference between attending most (7–10) versus fewer (0–6) sessions ranged from 0.08 to 0.16 standard deviations. Conclusion This study provides empirical evidence that a large-scale mental health intervention early in schooling is significantly associated with improved behavioral and academic outcomes. Future research is needed to implement more rigorous experimental evaluation of the program, to examine longer-term effects, and to investigate possible predictors of heterogeneity of treatment response.

The Pediatric Symptom Checklist (PSC) is a widely-used, parent-completed measure of children’s emotional and behavioral functioning. Previous research has shown that the PSC and its subscales are generally responsive to patient progress over the course of psychiatric treatment. In this naturalistic study, we examined the performance and utility of the five-item PSC Internalizing Subscale (PSC-IS) as an assessment of routine treatment in outpatient pediatric psychiatry. Parents and clinicians of 1,593 patients aged 17 or younger completed standardized measures at intake and three-month follow-up appointments. Comparisons between PSC-IS scores and clinician-reported diagnoses, internalizing symptoms, and overall functioning showed acceptable levels of agreement. Change scores on the PSC-IS were also larger among patients with internalizing diagnoses than those with non-internalizing diagnoses. As a brief measure of internalizing symptoms, the PSC may be particularly useful to mental health clinicians treating youth with depression and anxiety as a quality assurance or treatment outcome measure.

In medicine, it is critical that clinicians demonstrate both empathy (perceived as warmth) and competence. Perceptions of these qualities are often intuitive and are based on nonverbal behavior. Emphasizing both warmth and competence may prove problematic, however, because there is evidence that they are inversely related in other settings. We hypothesize that perceptions of physician competence will instead be positively correlated with perceptions of physician warmth and empathy, potentially due to changing conceptions of the physician’s role. We test this hypothesis in an analog medical context using a large online sample, manipulating physician nonverbal behaviors suggested to communicate empathy (e.g. eye contact) and competence (the physician’s white coat). Participants rated physicians displaying empathic nonverbal behavior as more empathic, warm, and more competent than physicians displaying unempathic nonverbal behavior, adjusting for mood. We found no warmth/competence tradeoff and, additionally, no significant effects of the white coat. Further, compared with male participants, female participants perceived physicians displaying unempathic nonverbal behavior as less empathic. Given the significant consequences of clinician empathy, it is important for clinicians to learn how nonverbal behavior contributes to perceptions of warmth, and use it as another tool to improve their patients’ emotional and physical health.

OBJECTIVE Obsessive-compulsive symptoms (OCS) may be underrecognized in patients suffering from major depressive disorder. These patients may not receive optimal psychopharmacologic or psychological treatment if their OCS are not attended to. We performed a secondary analysis of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial database, the largest effectiveness study of "real-world" depression ever conducted, to determine the frequency of OCS and their effects on depression outcome. METHOD 3,984 adult subjects without a previous selective serotonin reuptake inhibitor trial for their current major depressive episode, per DSM-IV diagnostic criteria, had data for rating scales of interest at entry into Level 1 of the STAR*D trial, a 12-week open trial of citalopram at a dose of 20-60 mg/d to assess rates of depression remission. Our primary interest was the OCD subscale of the Psychiatric Diagnostic Screening Questionnaire. RESULTS At study entry, 53% of the STAR*D sample (which excluded patients with primary obsessive-compulsive disorder) endorsed ≥ 1 OCS, and 14% endorsed ≥ 4 OCS. Subjects endorsing ≥ 4 OCS had significantly lower corrected odds of depression remission on both the 17-item Hamilton Depression Rating Scale (HDRS-17) (OR = 0.61) and the Quick Inventory of Depressive Symptomatology (odds ratio [OR] = 0.51). Number of OCS endorsed was positively correlated with HDRS-17 score (r = 0.26, P < .0001). Consistent with findings from the Dunedin, New Zealand Community Study, the most common obsessions were doubts of having inadvertently caused harm and violent obsessions. CONCLUSIONS OCS are common in depressed outpatients and are often not attended to. They impact clinical recovery from depression and should be screened for since sufferers are often reluctant to disclose these symptoms. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00021528.

The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) was developed to assess clinically relevant cognitive and physical symptoms associated with depression that are not adequately assessed by traditional measures. Although the CPFQ has been shown previously to be a reliable and valid measure, the purpose of the present study was to provide additional evidence using larger samples from 4 independent clinical trials that were designed to test the efficacy and safety of different antidepressants.The psychometric analyses were based on data from 4 independent clinical trials that were designed to test the safety and efficacy of different antidepressants. Reliability of the items and of the overall questionnaire was evaluated with principal components analysis, whereas validity was assessed by associations of the questionnaire scores with convergent and divergent external criteria.Overall, the results have replicated previous findings that the CPFQ has good internal reliability. Validation also is strengthened by the demonstration of predictive differences among known groups as well as a sensitivity to change with antidepressant treatment.Results support the use of the CPFQ as a valuable instrument for the detection of clinically relevant symptoms that are not captured by typical measures of depression used for the assessment of treatment outcomes.

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus nonanxious depression. One hundred and twenty outpatients were enrolled in a 12-week study that was divided into two 6-week periods according to the sequential parallel comparison design. Patients were randomized in a 2:3:3 multi-ratio to receive ziprasidone for 12 weeks, placebo for 6 weeks, followed by ziprasidone for 6 weeks, or placebo for 12 weeks. Efficacy was measured according to the 17-item Hamilton Depression Rating Scale (HRDS-17), Quick Inventory of Depressive Symptomatology SelfRated (QIDS-SR). Anxious depression was defined as a score of 7 on the HDRS-17 anxiety/somatization subscale. In phase I and II, ziprasidone monotherapy led to no significant changes compared with placebo on the HDRS-17 and QIDS-SR scores in patients with both anxious and non-anxious depression. In the pooled analysis, ziprasidone monotherapy also produced no significance on the HDRS-17 (Z 1⁄4 0.25, P 1⁄4 0.80) and QIDS-SR (Z 1⁄4 0.43, P 1⁄4 0.67) in patients with anxious depression. In conclusion, treatment with ziprasidone monotherapy may produce no significant improvement compared with placebo in patients with in anxious depression. Trial registration: ClinicalTrials.gov identifier: NCT00555997. © 2015 Elsevier Ltd. All rights reserved.