Changes In Depressive Symptom Severity Research Articles

Acute deep brain stimulation changes in regional cerebral blood flow in obsessive-compulsive disorder.

OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS. METHODS Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity. RESULTS Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = -0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact. CONCLUSIONS DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic-cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was associated with clinical changes in depressive symptom severity, but not OCD symptom severity.

Chronotype and Improved Sleep Efficiency Independently Predict Depressive Symptom Reduction after Group Cognitive Behavioral Therapy for Insomnia.

Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve both sleep and depressive symptoms, but predictors of depression outcome following CBT-I have not been well examined. This study investigated how chronotype (i.e., morningness-eveningness trait) and changes in sleep efficiency (SE) were related to changes in depressive symptoms among recipients of CBT-I. Included were 419 adult insomnia outpatients from a sleep disorders clinic (43.20% males, age mean ± standard deviation = 48.14 ± 14.02). All participants completed the Composite Scale of Morningness and attended at least 4 sessions of a 6-session group CBT-I. SE was extracted from sleep diary; depressive symptoms were assessed using the Beck Depression Inventory (BDI) prior to (Baseline), and at the end (End) of intervention. Multilevel structural equation modeling revealed that from Baseline to End, SE increased and BDI decreased significantly. Controlling for age, sex, BDI, and SE at Baseline, stronger evening chronotype and less improvement in SE significantly and uniquely predicted less reduction in BDI from Baseline to End. Chronotype did not predict improvement in SE. In an insomnia outpatient sample, SE and depressive symptoms improved significantly after a CBT-I group intervention. All chronotypes benefited from sleep improvement, but those with greater eveningness and/or less sleep improvement experienced less reduction in depressive symptom severity. This suggests that evening preference and insomnia symptoms may have distinct relationships with mood, raising the possibility that the effect of CBT-I on depressive symptoms could be enhanced by assessing and addressing circadian factors.

Emotionally biased cognitive processes: the weakest link predicts prospective changes in depressive symptom severity.

Emotional biases in attention, interpretation, and memory are predictive of future depressive symptoms. It remains unknown, however, how these biased cognitive processes interact to predict depressive symptom levels in the long-term. In the present study, we tested the predictive value of two integrative approaches to model relations between multiple biased cognitive processes, namely the additive (i.e., cognitive processes have a cumulative effect) vs. the weakest link (i.e., the dominant pathogenic process is important) model. We also tested whether these integrative models interacted with perceived stress to predict prospective changes in depressive symptom severity. At Time 1, participants completed measures of depressive symptom severity and emotional biases in attention, interpretation, and memory. At Time 2, one year later, participants were reassessed to determine depressive symptom levels and perceived stress. Results revealed that the weakest link model had incremental validity over the additive model in predicting prospective changes in depressive symptoms, though both models explained a significant proportion of variance in the change in depressive symptoms from Time 1 to Time 2. None of the integrative models interacted with perceived stress to predict changes in depressive symptomatology. These findings suggest that the best cognitive marker of the evolution in depressive symptoms is the cognitive process that is dominantly biased toward negative material, which operates independent from experienced stress. This highlights the importance of considering idiographic cognitive profiles with multiple cognitive processes for understanding and modifying effects of cognitive biases in depression.

Blood levels of S-100 calcium-binding protein B, high-sensitivity C-reactive protein, and interleukin-6 for changes in depressive symptom severity after coronary artery bypass grafting: prospective cohort nested within a randomized, controlled trial.

BackgroundCross-sectional and retrospective studies have associated major depressive disorder with glial activation and injury as well as blood–brain barrier disruption, but these associations have not been assessed prospectively. Here, we aimed to determine the relationship between changes in depressive symptom severity and in blood levels of S-100 calcium-binding protein B (S-100B), high-sensitivity C-reactive protein, and interleukin-6 following an inflammatory challenge.MethodsFifty unselected participants were recruited from a randomized, controlled trial comparing coronary artery bypass grafting procedures performed with versus without cardiopulmonary bypass for the risk of neurocognitive decline. Depressive symptom severity was measured at baseline, discharge, and six-month follow-up using the Beck Depression Inventory II (BDI-II). The primary outcome of the present biomarker study was acute change in depressive symptom severity, defined as the intra-subject difference between baseline and discharge BDI-II scores. Blood biomarker levels were determined at baseline and 2 days postoperative.ResultsChanges in S-100B levels correlated positively with acute changes in depressive symptom severity (Spearman ρ, 0.62; P = 0.0004) and accounted for about one-fourth of their observed variance (R2, 0.23; P = 0.0105). This association remained statistically significant after adjusting for baseline S-100B levels, age, weight, body-mass index, or β-blocker use, but not baseline BDI-II scores (P = 0.064). There was no statistically significant association between the primary outcome and baseline S-100B levels, baseline high-sensitivity C-reactive protein or interleukin-6 levels, or changes in high-sensitivity C-reactive protein or interleukin-6 levels. Among most participants, levels of all three biomarkers were normal at baseline and markedly elevated at 2 days postoperative.ConclusionsAcute changes in depressive symptom severity were specifically associated with incremental changes in S-100B blood levels, largely independent of covariates associated with either. These findings support the hypothesis that glial activation and injury and blood–brain barrier disruption can be mechanistically linked to acute exacerbation of depressive symptoms in some individuals.

Successful application of adaptive emotion regulation skills predicts the subsequent reduction of depressive symptom severity but neither the reduction of anxiety nor the reduction of general distress during the treatment of major depressive disorder.

ObjectiveDeficits in general emotion regulation (ER) skills have been linked to symptoms of depression and are thus considered a promising target in the treatment of Major depressive disorder (MDD). However, at this point, the extent to which such skills are relevant for coping with depression and whether they should instead be considered a transdiagnostic factor remain unclear. Therefore, the present study aimed to investigate whether successful ER skills application is associated with changes in depressive symptom severity (DSS), anxiety symptom severity (ASS), and general distress severity (GDS) over the course of treatment for MDD.MethodsSuccessful ER skills application, DSS, ASS, and GDS were assessed four times during the first three weeks of treatment in 175 inpatients who met the criteria for MDD. We computed Pearson correlations to test whether successful ER skills application and the three indicators of psychopathology are cross-sectionally associated. We then performed latent growth curve modelling to test whether changes in successful ER skills application are negatively associated with a reduction of DSS, ASS, or GDS. Finally, we utilized latent change score models to examine whether successful ER skills application predicts subsequent reduction of DSS, ASS, or GDS.ResultsSuccessful ER skills application was cross-sectionally associated with lower levels of DSS, ASS, and GDS at all points of assessment. An increase in successful skills application during treatment was associated with a decrease in DSS and GDS but not ASS. Finally, successful ER skills application predicted changes in subsequent DSS but neither changes in ASS nor changes in GDS.ConclusionsAlthough general ER skills might be relevant for a broad range of psychopathological symptoms, they might be particularly important for the maintenance and treatment of depressive symptoms.

Successful emotion regulation skills application predicts subsequent reduction of symptom severity during treatment of major depressive disorder.

Deficits in emotion regulation (ER) skills are considered a putative maintaining factor for major depressive disorder (MDD) and hence a promising target in the treatment of MDD. However, to date, the association between the successful application of arguably adaptive ER skills and changes in depressive symptom severity (DSS) has yet to be investigated over the course of treatment. Thus, the primary aim of this study was to clarify reciprocal prospective associations between successful ER skills application and DSS over the course of inpatient cognitive behavioral therapy for MDD. Additionally, we explored whether such associations would differ across specific ER skills. We assessed successful ER skills application and DSS 4 times during the first 3 weeks of treatment in 152 inpatients (62.5% women, average age 45.6 years) meeting criteria for MDD. We first tested whether successful skills application and depression were cross-sectionally associated by computing Pearson's correlations. Then, we utilized latent curve modeling to test whether changes in successful skills application were negatively associated with changes in DSS during treatment. Finally, we used latent change score models to clarify whether successful skills application would predict subsequent reduction of DSS. Cross-sectionally, successful ER skills application was associated with lower levels of DSS at all assessment times, and an increase of successful skills application during treatment was associated with a decrease of DSS. Moreover, successful overall ER skills application predicted subsequent changes in DSS (but not vice versa). Finally, strength of associations between successful application and DSS differed across specific ER skills. Among a broad range of potentially adaptive skills, only the abilities to tolerate negative emotions and to actively modify undesired emotions were significantly associated with subsequent improvement in DSS. Systematically enhancing health-relevant ER skills with specific interventions may help reduce DSS in patients suffering from MDD.

Prospective Relationship Between Obsessive–Compulsive and Depressive Symptoms During Multimodal Treatment in Pediatric Obsessive–Compulsive Disorder

The present study examined the prospective relationship between obsessive-compulsive and depressive symptoms during a multimodal treatment study involving youth with obsessive-compulsive disorder (OCD). Participants included fifty-six youth, aged 7-17 years (M = 12.16 years) who were enrolled in a two-site randomized controlled pharmacological and cognitive behavioral therapy treatment trial. Obsessive-compulsive severity was measured using the Children's Yale-Brown Obsessive-Compulsive Scale, and depressive symptoms were rated using the Children's Depression Rating Scale-Revised. Multi-level modeling analyses indicated that, on average over the course of treatment, variable and less severe obsessive-compulsive symptoms significantly predicted a decrease in depressive symptoms. Additionally, week-to-week fluctuations in OCD severity did not significantly predict weekly changes in depressive symptom severity. Level of baseline depressive symptom severity did not moderate these relationships. Findings suggest that when treating youth with OCD with co-occurring depression, therapists should begin by treating obsessive-compulsive symptoms, as when these are targeted effectively, depressive symptoms diminish as well.

The role of early symptom trajectories and pretreatment variables in predicting treatment response to cognitive behavioral therapy.

Research has focused on 2 different approaches to answering the question, "Which clients will respond to cognitive behavioral therapy (CBT) for depression?" One approach focuses on rates of symptom change within the 1st few weeks of treatment, whereas the 2nd approach looks to pretreatment client variables (e.g., hopelessness) to identify clients who are more or less likely to respond. The current study simultaneously examines these 2 lines of research (i.e., early symptom change and pretreatment variables) on the prediction of treatment outcome to determine the incremental utility of each potential predictor. The sample consists of 173 clients (66.47% female, 92.49% Caucasian), 18-64 years of age (M = 27.94, SD = 11.42), receiving treatment for depression and anxiety disorders in a CBT-oriented psychology training clinic. The rate of change in depressive symptom severity from baseline over the 1st 5 treatment sessions significantly predicted treatment outcome. A contemplative orientation to change and medication status positively predicted early symptom change, whereas student status negatively predicted early symptom change. Higher levels of baseline anxiety, precontemplative readiness to change, and global functioning predicted lower levels of depressive symptom severity at termination. The findings suggest achieving rapid symptom change early in treatment may be integral to overall success. As such, therapists may wish to target factors such as readiness to change to potentially maximize rapid rate of symptom change and subsequent treatment outcome.

The treatment of minor depression with St. John’s Wort or citalopram: Failure to show benefit over placebo

This paper presents new data addressing two important controversies in psychiatry: the construct of Minor Depression (MinD) and the efficacy of St. John’s Wort for milder forms of depressive disorders. Data are from a three-arm, 12 week, randomized clinical trial of investigating the efficacy of St. John’s Wort (810 mg/day), citalopram (20 mg/day), or placebo for acute treatment of MinD. Due to a high placebo response on all outcome measures, neither St. John’s Wort nor citalopram separated from placebo on change in depressive symptom severity, quality of life, or well-being. However, systematic assessment of potential adverse effects (AEs) led to three important observations: (1) prior to the administration of study compound, 60% of subjects endorsed items that would be characterized as AEs once study compound was administered, (2) St. John’s Wort and citalopram were each associated with a significant number of new or worsening AEs during treatment, and (3) using a structured interview for identifying AEs at baseline and during treatment is informative. MinD was not responsive to either a conventional antidepressant or a nutraceutical, and both compounds were associated with a notable side effects burden. Other treatment approaches for MinD should be investigated.

Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder

Background: While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder (MDD), the prevalence and importance of painful physical symptoms such as back pain, abdominal pain, and musculoskeletal pain is becoming increasingly appreciated. Antidepressants possessing dual serotonin/norepinephrine (5-HT/NE) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain. The efficacy of duloxetine, a balanced and potent dual reuptake inhibitor of 5-HT and NE, was evaluated within a cohort of depressed patients with associated painful physical symptoms. Methods: In this multicenter, double-blind, placebo-controlled study, patients meeting DSM-IV criteria for MDD were randomized to receive placebo ( N=141) or duloxetine 60 mg QD ( N=141). Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD 17) total score ⩾15, a Clinical Global Impression of Severity (CGI-S) score ⩾4, and a Brief Pain Inventory (BPI) Average Pain score ⩾2 at baseline. The primary efficacy measure was the BPI Average Pain score, while secondary measures included other BPI items, the HAMD 17 total score, CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQSS). Safety was evaluated by recording treatment-emergent adverse events (spontaneously reported), vital signs, and laboratory analytes. Results: Mean changes in BPI Average Pain for duloxetine- and placebo-treated patients differed significantly at most visits, but only approached significance at endpoint ( p=0.066). For the main effect of treatment (pooling all visits), significant advantages for duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and pain interference items, in addition to VAS overall pain and back pain. Mean changes in pain measures for duloxetine-treated patients corresponded to improvements of 25–50%, compared with 19–39% for placebo. Mean changes at endpoint in depression rating scales (HAMD 17, CGI-S, PGI-I) did not differ significantly between duloxetine and placebo treatment groups due to unusually high placebo response. The magnitude of placebo treatment effects (as measured by HAMD 17 total score and Maier subscale) was significantly smaller in patients with ⩾1 previous depressive episode, compared to those patients with no previous episodes. In patients with ⩾1 previous depressive episode the advantage of duloxetine over placebo was similar to previous studies. Rates of discontinuation due to adverse events were 14.2% vs. 2.1% for duloxetine and placebo, respectively ( p<0.001). Treatment-emergent adverse events reported at a significantly higher rate by duloxetine-treated patients included nausea, dry mouth, fatigue, and decreased appetite. Conclusions: In this study, duloxetine (60 mg QD) was shown to be an effective treatment for the painful physical symptoms which are frequently associated with depression. Improvements in pain severity occurred independently of changes in depressive symptom severity.