Reduction In Depressive Symptom Severity Research Articles

The long-term effect of bariatric surgery on depression and anxiety.

No previous review has comprehensively assessed long-term changes in anxiety and depressive symptoms in bariatric surgery patients. This systematic review assessed the effects of bariatric surgery on long-term reductions (≥ 24 months) in anxiety and depressive symptom severity in morbidly obese (≥ 35 BMI kg/m2) participants. Short term effects (< 24 months) are briefly reviewed for context. PsychINFO, Google Scholar and PubMed databases were systematically searched for prospective cohort studies published from inception to 14 June 2018 that evaluated long-term (≥ 24 months) changes in anxiety and depressive symptom severity in bariatric surgery patients with a BMI ≥ 35 kg/m2 using a combination of the following search terms: bariatric surgery (and surgical approaches included under this term), obesity, depression, depressive disorder, anxiety, anxious, psychiatric disorders, mood disorders. We reviewed 2058 articles for eligibility; 14 prospective studies were included in the systematic review. 13 studies (93%) reported significant reductions in depressive symptom severity 2-3 years after bariatric surgery. However, all studies recorded statistically significant reductions in depressive symptoms at the conclusion of the study. Similarly, there were reductions in overall anxiety symptom severity at ≥ 24 months follow-up (k = 8 studies, n = 1590 pooled). Pre-operative anxiety or depression scores did not predict outcomes of post-operative BMI. Similarly, post-surgery weight loss did not predict changes in anxiety symptoms. Very few studies assessed anxiety or depression as a primary outcome. Therefore, we cannot suggest bariatric surgery as a stand-alone therapeutic tool for anxiety and depression based on our findings. Currently available evidence suggests that bariatric surgery is associated with long-term reductions in anxiety and depressive symptoms. This supports existing literature showing that metabolic treatments may be a viable therapeutic intervention for mood disorders.

Effect of collaborative depression treatment on risk for diabetes: A 9-year follow-up of the IMPACT randomized controlled trial

Considerable epidemiologic evidence and plausible biobehavioral mechanisms suggest that depression is an independent risk factor for diabetes. Moreover, reducing the elevated diabetes risk of depressed individuals is imperative given that both conditions are leading causes of death and disability. However, because no prior study has examined clinical diabetes outcomes among depressed patients at risk for diabetes, the question of whether depression treatment prevents or delays diabetes onset remains unanswered. Accordingly, we examined the effect of a 12-month collaborative care program for late-life depression on 9-year diabetes incidence among depressed, older adults initially free of diabetes. Participants were 119 primary care patients [M (SD) age: 67.2 (6.9) years, 41% African American] with a depressive disorder but without diabetes enrolled at the Indiana sites of the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial. Incident diabetes cases were defined as diabetes diagnoses, positive laboratory values, or diabetes medication prescription, and were identified using electronic medical record and Medicare/Medicaid data. Surprisingly, the rate of incident diabetes in the collaborative care group was 37% (22/59) versus 28% (17/60) in the usual care group. Even though the collaborative care group exhibited greater reductions in depressive symptom severity (p = .024), unadjusted (HR = 1.29, 95% CI: 0.69–2.43, p = .428) and adjusted (HR = 1.18, 95% CI: 0.61–2.29, p = .616) Cox proportional hazards models indicated that the risk of incident diabetes did not differ between the treatment groups. Our novel preliminary findings raise the possibility that depression treatment alone may be insufficient to reduce the excess diabetes risk of depressed, older adults.

Preliminary Outcomes of a Computerized CBT/MET Intervention for Depressed Cannabis Users in Psychiatry Care.

Although depression is common among cannabis users, there is a paucity of targeted interventions addressing depression and cannabis use disorders concurrently. In the present pilot study, we examine the feasibility, acceptability, and preliminary outcomes of a computer-assisted intervention combining cognitive behavioral therapy (CBT) and motivational enhancement therapy (MET) techniques for adults with comorbid major depressive disorder (MDD) and cannabis use disorder (CUD) presenting for care in a psychiatric setting. Adults with MDD and CUD (N=26) recruited from mental health care settings were enrolled in a 10-week, computer-assisted psychosocial intervention: Self-Help for Alcohol and other Drug Use and Depression (SHADE). Feasibility, acceptability, perceived helpfulness, treatment retention, completion, and clinical outcomes including cannabis use and depression were assessed. Participants found the SHADE intervention to be acceptable and helpful in facilitating action towards their therapeutic goals concerning depression and cannabis use. Treatment completion, achieved by the majority (85%) of participants, was excellent. On average, participants reduced their past 30 day cannabis use from baseline (mean percentage of days using = 69%) to follow-up (M=44%) (t(22)= 2.3, p<0.05; Effect Size= 0.79). Concurrently, they evidenced reductions in depressive symptom severity, from the moderately severe range at baseline to the mild range at follow-up (t(24)=7.3, p<0.001; Effect Size=1.52). Addressing comorbid CUD and MDD using a computer-assisted, evidence-based treatment strategy is feasible in a psychiatric care setting, and may produce improvements in both depressive symptoms and cannabis use.

Treating late-life depression: Comparing the effects of internet-delivered cognitive behavior therapy across the adult lifespan

BackgroundThe burden attributable to late-life depression is set to increase with the ageing population. The size of the workforce trained to deliver psychogeriatric medicine is limited. Internet-delivered cognitive behavioral therapy (iCBT) is an efficacious and scalable treatment option for depression. Yet older adults are underrepresented in iCBT research. This study examines the effects of iCBT for depression across the adult lifespan among patients seeking help in routine clinical care (N = 1288). MethodsRegression analyses were used to examine the relationship between age group (e.g., 18-24years (n = 141); 25-34years (n = 289); 35–44years (n = 320); 45-54years (n = 289); 55-64years (n = 180); 65 +years (n = 69)) and presenting demographic and clinical characteristics, adherence to treatment, and rates of remission, recovery and reliable improvement. Linear mixed models were used to examine whether reductions in symptom severity, distress and impairment varied as a function of age. ResultsPatients aged 65+ years were more likely to be male compared to those aged 18–34 years and have been prescribed iCBT by their GP compared to those aged 55–64 years. Patients experiencing late-life depression experienced moderate to large effect size reductions in depressive symptom severity, psychological distress, and impairment, as did all other age groups. Rates of remission, recovery or reliable improvement were comparable across the adult lifespan. ConclusionsiCBT is an effective treatment option for depression including in later life, and can be used to scale evidenced-based medicine in routine clinical care. LimitationsNo follow-up data were collected. The long-term effects of treatment, particularly for those who did not experience remission, are unclear.

Major Depressive Disorder in Patients With Doctoral Degrees: Patient-reported Depressive Symptom Severity, Functioning, and Quality of Life Before and After Initial Treatment in the STAR*D Study.

This study examined patients with medical or doctoral degrees diagnosed with major depressive disorder (MDD) by analyzing patient-reported depressive symptom severity, functioning, and quality of life (QOL) before and after treatment of MDD. Analyses were conducted in a sample of 2280 adult outpatient participants with MDD from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study with complete entry and exit scores for the level 1 (citalopram monotherapy) trial. The sample contained 62 participants who had completed medical or doctoral degrees (DOCS) and 2218 participants without medical or doctoral degrees (non-DOCS). QOL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire, functioning was assessed with the Work and Social Adjustment Scale, and depressive symptom severity was assessed with the Quick Inventory of Depressive Symptomatology-Self Report. Both groups (DOCS and non-DOCS) had significant improvement in depressive symptom severity, functioning, and QOL following treatment (with equivalent improvements in mean change values). However, the DOCS group demonstrated larger effect sizes in symptom reduction for depression, increase in functioning, and improvement in QOL compared with the non-DOCS group. Participants who achieved remission from MDD at exit showed significantly greater improvement than nonremitters on functioning and QOL. Findings from this study indicated that, following citalopram monotherapy, the participants in the DOCS group achieved greater reductions in depressive symptom severity (based on effect sizes) than the participants in the non-DOCS group. For both treatment groups, the findings also showed the positive effect that remission status from MDD can have on QOL and functioning.

Effectiveness of Web- and Mobile-Based Treatment of Subthreshold Depression With Adherence-Focused Guidance: A Single-Blind Randomized Controlled Trial

Evidence for the impact of psychological Interventions for subthreshold depression (sD) is conflicting. Moreover, human resources to deliver such treatments are limited. This study aimed to evaluate the effectiveness of a web-based intervention with adherence-focused guidance in the treatment of sD. Participants with sD (CES-D≥ 16, no Major Depressive Disorder according to DSM-IV criteria, N = 204) recruited via a large health insurance were randomly allocated to a web-based mobile-supported cognitive-behavioral intervention or to a waitlist control condition with unrestricted access to usual care. The primary outcome was the reduction in depressive symptom severity as measured by blind diagnostic raters using the Quick Inventory of Depressive Symptomatology (QIDS) at posttreatment. There was a statistically significant between-group difference in QIDS scores at posttreatment in favor of the intervention group, F(1, 201) = 11.31, p = .001, corresponding to a medium effect size of d = 0.37 (95% CI 0.09–0.64) and a NNT of 7 (95%–CI 3.7–41.2). Significant effects in favour of the intervention group were also found for secondary outcomes such as quality of life, anxiety, and insomnia severity. Web-based self-help interventions with adherence-focused guidance could be an acceptable and effective approach to reduce a range of negative consequences associated with subclinical depression.

A pilot, open-label, 8-week study evaluating the efficacy, safety and tolerability of adjunctive minocycline for the treatment of bipolar I/II depression.

The objectives of the study were to determine if adjunctive minocycline mitigates depressive symptom severity and improves cognitive function in individuals with bipolar I/II disorder (BD). The study also aimed to determine if changes in depressive and/or cognitive symptoms over the course of treatment were associated with changes in circulating inflammatory cytokine levels. A total of 29 (intention-to-treat: n=27) adults meeting DSM-IV-TR criteria for a major depressive episode as part of bipolar I or II disorder (i.e. Hamilton Depression Rating Scale 17-item [HAMD-17] ≥20) were enrolled in an 8-week, open-label study with adjunctive minocycline (100mg bid). The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS). The HAMD-17, Clinical Global Impression-Severity (CGI-S), cognitive test composite scores and plasma cytokines were secondary outcome measures. Plasma cytokines were measured with the 30V-Plex Immunoassay from Meso Scale Discovery. Adjunctive minocycline was associated with a reduction in depressive symptom severity from baseline to week 8 on the MADRS (P<.001, d=0.835), HAMD-17 (P<.001, d=0.949) and CGI-S (P<.001, d=1.09). Improvement in psychomotor speed, but not verbal memory or executive function, was observed only amongst individuals exhibiting a reduction in depression severity (P=.007, d=0.826). Levels of interleukin (IL)-12/23p40 (P=.002) were increased, while levels of IL-12p70 (P=.001) and C-C motif chemokine ligand 26 (CCL26) (P<.001) were reduced from baseline to week 8. A reduction in CCL26 levels was associated with a less favourable treatment response (P<.001). Results from the pilot study suggest that adjunctive minocycline may exert antidepressant effects in individuals with bipolar depression, possibly by targeting inflammatory cytokines.

The Relation Between Catastrophizing and Occupational Disability in Individuals with Major Depression: Concurrent and Prospective Associations.

Background Catastrophic thinking has been associated with occupational disability in individuals with debilitating pain conditions. The relation between catastrophic thinking and occupational disability has not been previously examined in individuals with debilitating mental health conditions. The present study examined the relation between catastrophic thinking and occupational disability in individuals with major depression. Methods The study sample consisted of 80 work-disabled individuals with major depressive disorder (MDD) who were referred to an occupational rehabilitation service. Participants completed measures of depressive symptom severity, catastrophic thinking and occupational disability at admission and termination of a rehabilitation intervention. Return-to-work outcomes were assessed 1month following the termination of the rehabilitation intervention. Results Cross-sectional analyses of admission data revealed that catastrophic thinking contributed significant variance to the prediction of self-reported occupational disability, beyond the variance accounted for by depressive symptom severity. Prospective analyses revealed that reductions in catastrophic thinking predicted successful return to work following the rehabilitation intervention, beyond the variance accounted for by reductions in depressive symptom severity. Conclusions The findings suggest that catastrophic thinking is a determinant of occupational disability in individuals with major depressive disorder. The findings further suggest that interventions designed to reduce catastrophic thinking might promote occupational re-integration in individuals with debilitating mental health conditions.

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.

Effectiveness of group CBT in treating adolescents with depression symptoms: a critical review

Depression is among the most common psychological disorders of adolescents. Its management is based on pharmacological treatment, psychological therapy, or a combination thereof. Cognitive behavioral therapy (CBT) is the most extensively tested intervention for adolescent depression. A PubMed search was conducted for randomized controlled trials (RCT) of the efficacy of CBT in treating adolescents with depressive symptoms published in 2005-2015. Keywords were "cognitive behavioral therapy", "group therapy", "depression" and "adolescent". Of the 23 papers that were retrieved, only six met all inclusion criteria. Three of them reported a significant reduction in depressive symptom severity after either individual or group (G)-CBT compared with the control group, even with a small number of CBT sessions (six rather than 10-12), with a medium or medium-to-large effect size. One study reported improved self-awareness and a significantly greater increase in perceived friend social support compared with bibliotherapy and check with brochure. Two studies reported clinical symptom reduction without significant differences compared with the control group (activity contrast). This review highlighted primarily that very few RCT have applied CBT in adolescents; moreover, it confirmed the effectiveness of G-CBT, especially as psychotherapy, although it was not always superior to other interventions (e.g. other activities in prevention programs). Comparison showed that G-CBT and group interpersonal psychotherapy were both effective in reducing depressive symptoms. Successful G-CBT outcomes were related to the presence of peers, who were an important source of feedback and support to observe, learn, and practice new skills to manage depressive symptoms and improve social-relational skills.

Sleep Disturbances and Symptoms of Depression and Daytime Sleepiness in Pregnant Women.

Sleep disturbance, depression, and daytime sleepiness are among the most prevalent symptoms reported by women during pregnancy. However, available data on the association between sleep disturbances and symptoms of depression and daytime sleepiness in pregnant women are sparse and methodological limitations have been acknowledged. The purpose of the study was to examine objective and self-reported sleep disturbances and symptoms of depression and daytime sleepiness in a group of healthy pregnant women. A total of 274 third-trimester pregnant women wore a wrist actigraph continuously for 7 days to assess objective sleep quality and quantity. Self-reported sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), with self-reported poor sleep quality defined as a PSQI score more than 5. The Center for Epidemiologic Studies-Depression Scale (CES-D) and Epworth Sleepiness Scale were used to evaluate symptoms of depression and daytime sleepiness, respectively. Sixty-four (23.4%) women were at risk for clinical depression and 69 (25.2%) had daytime sleepiness. Risk of clinically meaningful depressive symptomatology was significantly increased in women with objective total nighttime sleep less than 6 hours (OR 2.53 [95% CI 1.26-5.08]) and self-reported poor sleep quality (OR 3.31 [95% CI 1.74-6.30]), even after multiple adjustment. Neither objective nor self-reported sleep disturbances increased daytime sleepiness in this group of pregnant women. Both objective nighttime sleep less than 6 hours and self-reported poor sleep quality in healthy third-trimester pregnant women is associated with significant risks for clinical depression. Improving sleep would likely be associated with a reduction in depression symptom severity and an attenuation of the prevalence of depression in pregnant women.

Effectiveness of a Web-Based Cognitive Behavioural Intervention for Subthreshold Depression: Pragmatic Randomised Controlled Trial

Background: Research on the effectiveness of treatments for subthreshold depression (sD) is still scarce. The aim of the study was to evaluate the efficacy of a web-based guided self-help intervention (GET.ON Mood Enhancer) in the treatment of sD. Methods: Participants with sD (n = 406) recruited from the general population via a large health insurance company were randomly allocated to a web-based cognitive behavioural intervention or to enhanced care-as-usual. The primary outcome was the reduction in depressive symptom severity as measured with the Center for Epidemiological Studies Depression Scale at post-treatment and at 6-month follow-up. Results: Participants in the intervention group showed a significantly greater pre-post reduction in depressive symptom severity (d = 1.06; 95% CI: 0.86-1.27) compared to the control condition (d = 0.29; 95% CI: 0.10-0.49). The corresponding between-group effect size was d = 0.69 (95% CI: 0.49-0.89). At 6-month follow-up the effect was reduced to d = 0.28 (95% CI: 0.09-0.48) but was still statistically significant (F_{1, 403} = 9.240, p = 0.003). Conclusions: This study lends support to the idea that problem solving coupled with behavioural activation is an effective treatment for sD. In addition, the delivery of this intervention over the Internet might be a promising strategy for the dissemination of psychological interventions for sD on a large scale.

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.

Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial.

Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression. We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point. The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period. The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.

Randomized Efficacy Trial of Two Psychotherapies for Depression in Youth With Inflammatory Bowel Disease

Pediatric inflammatory bowel disease (IBD) is associated with high rates of depression. This study compared the efficacy of cognitive behavioral therapy (CBT) to supportive nondirective therapy (SNDT) in treating youth with comorbid IBD and depression. Youth (51% female and 49% male; age 9-17 years, mean age 14.3 years) with depression and Crohn's disease (n = 161) or ulcerative colitis (n = 56) were randomly assigned to a 3-month course of CBT or SNDT. The primary outcome was comparative reduction in depressive symptom severity; secondary outcomes were depression remission, increase in depression response, and improved health-related adjustment and IBD activity. A total of 178 participants (82%) completed the 3-month intervention. Both psychotherapies resulted in significant reductions in total Children's Depression Rating Scale Revised score (37.3% for CBT and 31.9% for SNDT), but the difference between the 2 treatments was not significant (p = .16). There were large pre-post effect sizes for each treatment (d = 1.31 for CBT and d = 1.30 for SNDT). More than 65% of youth had a complete remission of depression at 3 months, with no difference between CBT and SNDT (67.8% and 63.2%, respectively). Compared to SNDT, CBT was associated with a greater reduction in IBD activity (p = .04) but no greater improvement on the Clinical Global Assessment Scale (p = .06) and health-related quality of life (IMPACT-III scale) (p = .07). This is the first randomized controlled study to suggest improvements in depression severity, global functioning, quality of life, and disease activity in a physically ill pediatric cohort treated with psychotherapy. Clinical trial registration information-Reducing Depressive Symptoms in Physically Ill Youth; http://clinical trials.gov; NCT00534911.

Telecounseling for the Linguistically Isolated: A Pilot Study With Older Korean Immigrants

Responding to the critical needs of the linguistically isolated, this pilot study tested the use of telehealth technology in providing access to culturally and linguistically appropriate mental health services. The goal of the study was to explore the feasibility and preliminary efficacy of a telecounseling program in the client's native language. Using a small sample of older Korean immigrants living in a low-income housing facility in Orlando, Florida, who had concerns about depressive moods (n = 14), the pilot telecounseling program was implemented via videoconferencing. Four weekly sessions were conducted by 4 Korean mental health counselors based in New York. A high level of completion (86%) and overall satisfaction with the program were observed. Participants also exhibited a significant reduction in depressive symptom severity shortly after completion of the program. At the 3-month follow-up, the participants' depressive symptom scores remained significantly lower than those at the initial assessment. The findings support the value of telecounseling for linguistically isolated populations and suggest further efforts to extend such programs.

Coenzyme Q10 Effects on Creatine Kinase Activity and Mood in Geriatric Bipolar Depression

Despite the prevalence, associated comorbidities, and functional consequences of bipolar depression (BPD), underlying disease mechanisms remain unclear. Published studies of individuals with bipolar disorder implicate abnormalities in cellular energy metabolism. This study tests the hypotheses that the forward rate constant (k(for)) of creatine kinase (CK) is altered in older adults with BPD and that CoEnzyme Q10 (CoQ10), known to have properties that enhance mitochondrial function, increases k(for) in elderly individuals with BPD treated with CoQ10 compared with untreated age- and sex-matched controls. Ten older adults (ages 55 and above) with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition [DSM IV]) bipolar disorder, current episode depressed and 8 older controls underwent two 4 Tesla (31)Phosphorus magnetic resonance spectroscopy ((31)PMRS) scans 8 weeks apart using a magnetization transfer (MT) acquisition scheme to calculate k(for). The BPD group was treated with open-label CoEnzyme Q10 400 mg/d titrated up by 400 mg/d every 2 weeks to a maximum of 1200 mg/d. The Montgomery Asberg Depression Rating Scale (MADRS) was used to measure depression symptom severity. Baseline k(for) and changes in k(for) were compared between individuals with BPD and controls, not receiving CoQ. Clinical ratings were compared across time and associated with k(for) changes using repeated measures linear regression. The k(for) of CK was nonsignificantly lower for BPD than healthy controls at baseline (BPD mean (standard deviation [SD]) = 0.19 (0.02), control mean (SD) = 0.20 (0.02), Wilcoxon rank sum exact P = .40). The k(for) for both CoQ10-treated BPD and controls increased after 8 weeks (mean increase (SD) = 0.03 (0.04), Wilcoxon signed rank exact P = .01), with no significant difference in 8-week changes between groups (BPD mean change (SD) = 0.03 (0.03), control mean change (SD) = 0.03 (0.05), Wilcoxon rank sum exact P = .91). In an exploratory analysis, depression severity decreased with CoQ10 treatment in the group with BPD (F (3,7) = 4.87, P = .04) with significant reductions in the MADRS at weeks 2 (t (9) = -2.40, P = .04) and 4 (t (9) = -3.80, P = .004). This study employing the novel MRS technique of MT did not demonstrate significance between group differences in the k(for) of CK but did observe a trend that would require confirmation in a larger study. An exploratory analysis suggested a reduction in depression symptom severity during treatment with high-dose CoEnzyme Q10 for older adults with BPD. Further studies exploring alterations of high-energy phosphate metabolites in geriatric BPD and efficacy studies of CoQ10 in a randomized controlled trial are both warranted.

Nonsuicidal Self-Injury as a Predictor of Suicidal Behavior in Depressed Adolescents

Nonsuicidal Self-Injury as a Predictor of Suicidal Behavior in Depressed Adolescents

Clinical value of early partial symptomatic improvement in the prediction of response and remission during short-term treatment trials in 3369 subjects with bipolar I or II depression

ObjectiveTo evaluate the clinical value of early partial symptomatic improvement in predicting the probability of response during the short-term treatment of bipolar depression. MethodsBlinded data from 10 multicenter, randomized, double-blind, placebo-controlled trials in bipolar I or II depression were used to determine if early improvement (≥20% reduction in depression symptom severity after 14days of treatment) predicted later short-term response or remission. Sensitivity, specificity, efficiency, and positive and negative predictive values (PPV, NPV) were calculated using an intent to treat analysis of individual and pooled study data. Results1913 patients were randomized to active compounds (aripiprazole, lamotrigine, olanzapine/olanzapine–fluoxetine, and quetiapine), and 1456 to placebo. In the pooled positive studies, early improvement predicted response and remission with high sensitivity (86% and 88%, respectively), but rates of false positives were high (53% and 59%, respectively). Pooled negative predictive values for response/remission (i.e. confidence in knowing the drug will not result in response or remission) were 74% and 82%, respectively, with low rates of false negatives (14% and 12%, respectively). ConclusionEarly improvement in an individual patient does not appear to be a reliable predictor of eventual response or remission due to an unacceptably high false positive rate. However, the absence of early improvement appears to be a highly reliable predictor of eventual non-response, suggesting that clinicians can have confidence in knowing when a drug is not going to work during short-term treatment. Patients who fail to demonstrate early improvement within the first two weeks of treatment may benefit from a change in therapy.

Randomized, double-blind, placebo-controlled trial of acetaminophen for preventing mood and memory effects of prednisone bursts

Corticosteroids are commonly associated with changes in mood, memory, and the hippocampus. Declarative memory decline occurs rapidly after corticosteroid administration. Minimal research has focused on interventions to prevent or reverse corticosteroid effects on the human brain and associated adverse psychiatric effects. Acetaminophen has neuroprotective properties in animal models. We examined acetaminophen add-on therapy in patients prescribed corticosteroids. Thirty outpatients prescribed oral high-dose prednisone therapy for asthma (n = 28) or allergic rhinitis (n = 2) were randomized to approximately 7 days of acetaminophen (4000 mg/day) or placebo in a double-blind fashion at the same time as prednisone. Mood was assessed with the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and Activation subscale of the Internal State Scale. Memory was assessed with the Rey Auditory Learning Test and asthma symptoms with the Asthma Control Questionnaire. Between-group differences were assessed using mixed ANCOVAs and within-group changes were examined with paired t-tests. Baseline mean depression scores were elevated. In the total sample, depressive and asthma symptoms improved significantly, while declarative memory worsened during prednisone therapy. No between treatment-group differences were found in mood or memory measures. Change in asthma symptoms with receiving prednisone was not related to change in mood or memory. Prednisone therapy was associated with a reduction in depressive symptom severity and decline in declarative memory that was not related to changes in asthma symptoms. This is consistent with prior research suggesting that prednisone impairs memory and may have antidepressant properties. Acetaminophen did not attenuate corticosteroid-induced mood or memory changes.