Neurocognition and Depressive Symptoms have Unique Pathways to Predicting Different Domains of Functioning in Major Depressive Disorder.

BACKGROUND: Research has established the independent relationships between depressive symptoms to cognition and functioning in depression; however, little is known about the role of mediators in this relationship. We explored the role of neurocognitive abilities, depressive symptom severity, dysfunctional attitudes, and functional capacity in predicting two dimensions of daily functioning in individuals with major depressive disorder (MDD). METHODS: One hundred and twenty-four participants (mean age = 46.26, SD = 12.27; 56% female) with a diagnosis of MDD were assessed on a standard neurocognitive battery, self-reported depressive symptoms, dysfunctional attitudes, and clinician-rated functional impairment. They completed a performance-based assessment of functional competence. RESULTS: Confirmatory path analyses were used to model the independent and mediated effects of variables on two domains of functioning: social (relationships and social engagement) and productive (household and community activities). Cognition and depressive symptoms both predicted productive functioning, and dysfunctional attitudes mediated each of these relationships. Functional competence was a significant mediator in the relationship between neurocognition and productive functioning. Depressive symptoms and cognition were direct predictors of social functioning with no significant mediators. CONCLUSIONS: There are divergent pathways to different dimensions of daily functioning in MDD. Measurement implications include the consideration of multiple levels of predicting productive activities and more direct relationships with social outcomes. Treatments that directly target depressive symptoms and cognition might not generalize to improvements in everyday functioning if additional pathways to functioning are not addressed.

Currencies of recognition: What rewards and recognition do Canadian distributed medical education preceptors value?

Background: Medical schools spend considerable time, effort, and money on recognition initiatives for rural and distributed medical education (DME) faculty. Previous literature has focused on intrinsic motivation to teach and there is little in the literature to guide institutional recognition efforts or to predict which items or types of recognition will be most appreciated. Methods: To better understand how rural and DME faculty in Canada value different forms of recognition, we asked faculty members from all Canadian medical schools to complete a bilingual, national online survey evaluating their perceptions of currently offered rewards and recognition. The survey received a robust response in both English and French, across nine Canadian provinces and one territory. Results: Our results indicated that there were three distinct ways that preceptors looked at recognition; these perspectives were consistent across geographic and demographic variables. These "clusters" or "currencies of recognition" included: i) Formal institutional recognition, ii) connections, growth and development, and iii) tokens of gratitude. Financial recognition was also found to be important but separate from the three clusters. Some preceptors did value support of intrinsic motivation most important, and for others extrinsic motivators, or a mix of both was most valued. Conclusions: Study results will help medical schools make effective choices in efforts to find impactful ways to recognize rural and DME faculty.

Mixed symptoms in major depressive and bipolar disorders: A systematic review.

BACKGROUND: The DSM-5 mixed features specifier for mood disorders encourages renewed interest in mixed states and led us to pool research findings regarding prevalence of mixed features in episodes of major depressive (MDD) and bipolar disorders (BD). METHODS: We systematically searched to July 2017 for reports on mixed symptoms in depressive episodes of MDD and in depression and mania or hypomania in types I and II BD. For primary mood-states and diagnostic groups we compared rates of the presence of mixed symptoms: as defined by DSM-5 (≥3 features opposite to the dominant mood-polarity but not overlapping those of the primary disorder) or as having any ≥3 features of opposite polarity. RESULTS: We identified 17 reports, from 13 world regions involving 19,198 participants meeting standard diagnostic criteria for an index major depressive or [hypo]manic episode. Prevalence of cases with ≥3 features of opposite polarity averaged 27.8% [CI: 27.2-28.5] overall, and differed significantly between BD and MDD disorders, ranking: BD-depressed (35.2% [33.8-36.5]) = BD-[hypo]manic (35.1% [32.9-37.3]) > MDD-depressed (23.8% [23.0-24.5]). LIMITATIONS: Available findings were limited to mood disorders with mixed features by particular criteria, with few comparisons to other criteria or to their prognostic or therapeutic implications. CONCLUSIONS: Prevalence of ≥3 features of opposite polarity ranked: depressive = [hypo]manic episodes of BD > depression in MDD.

Sleep architecture and cognitive changes in olanzapine-treated patients with depression: a double blind randomized placebo controlled trial.

BACKGROUND: Disturbance in sleep quality is a symptom of Major Depressive Disorder (MDD) and Bipolar Disorder (BD) and thus improving quality of sleep is an important aspect of successful treatment. Here, a prospective, double-blind, randomized, placebo-controlled study examined the effect of olanzapine (an atypical antipsychotic) augmentation therapy on sleep architecture, specifically slow wave sleep (SWS), in the treatment of depression. The effect of olanzapine augmentation therapy on other features of sleep (e.g., sleep continuity) and depression (e.g., illness severity and cognitive function) were also determined. METHODS: Patients currently experiencing a major depressive episode and who were on a stable medication were included. Sleep architecture was measured by overnight ambulatory polysomnography. Illness severity was determined using the Montgomery-Asberg Depression Rating Scale (MADRS). Cognitive function was examined using Cambridge Neuropsychological Test Automated Battery (CANTAB): Spatial Working Memory (SWM), Spatial Span (SSP), and Reaction Time (RTI) tasks. Polysomnographs, clinical measures and cognitive tests were administered at baseline, after 2-4 days of treatment and after 28-31 days of treatment. Twenty-five patients participated in the study (N = 10, N = 15 for placebo and olanzapine treated groups respectively). RESULTS: The primary objective of the study was to assess the objective (polysomnographic) changes in sleep quality, defined as changes in SWS, following olanzapine treatment for depression. Latency to but not duration of SWS was found to significantly differ between olanzapine- and placebo-treated participants (Hedge's g: 0.97, 0.13 respectively). A significant improvement in olanzapine-treated participants over placebo-treated participants was observed in secondary outcome measures, including sleep efficiency, total sleep time, and sleep latency. Secondary objectives assessed the subjective changes in sleep quality parameters and correlated them with measures of illness severity and changes in cognition. MADRS scores were significantly improved in olanzapine-treated participants over time but not more than placebo treatment. There was no significant difference between olanzapine- and placebo-treated participants in SWM, SSP or RTI tasks. CONCLUSIONS: Olanzapine augmentation treatment generally did not improve SWS but did improve sleep continuity and depression. Olanzapine may be one of few medications that improve sleep continuity, thus directly targeting symptoms of depression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00520507.

Sleep architecture in ziprasidone-treated bipolar depression: a pilot study.

OBJECTIVES: This study investigated the effect of ziprasidone augmentation therapy on sleep architecture in bipolar depression. METHODS: We conducted a double-blind, randomized, placebo-controlled clinical pilot trial of ziprasidone versus placebo in Diagnostic and Statistical Manual of Mental Disorders, fourth edition bipolar disorder with current major depressive episode. The effects during acute (2-5 days) and continuation treatment (28-31 days) were measured. Main outcomes were sleep architecture variables including rapid eye movement sleep (REM) and slow wave sleep (SWS) measured by polysomnography. Secondary outcomes included subjective sleep quality measures and illness severity measures including the 17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery Asberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAMA) and Clinical Global Illness Severity (CGI-S) scores. RESULTS: The completer analysis comprised of 14 patients (ziprasidone, N = 8 and placebo, N = 6). Latency to REM, duration of SWS, duration of stage 2 sleep, total sleep time, onset to sleep latency, number of awakenings and overall sleep efficiency significantly improved in ziprasidone-treated participants over placebo. CGI-S and HAMA scores also significantly improved. No significant difference between treatment groups was seen on the HAMD-17, MADRS or in self-reported sleep quality. Increase in SWS duration significantly correlated with improvement in CGI-S, however, this finding did not withstand Bonferroni correction. CONCLUSION: Adjunctive ziprasidone treatment alters sleep architecture in patients with bipolar depression, which may partially explain its mechanism of action and merits further investigation.

Cognitive remediation for treatment-resistant depression: effects on cognition and functioning and the role of online homework.

Neurocognitive impairments are observed in depression and associated with poor functioning. This study examined the efficacy and the effectiveness of cognitive remediation with supplemental Internet-based homework in treatment-resistant depression. Participants were randomized to treatment or wait list control conditions. Treatment consisted of 10 weeks of weekly group sessions and daily online cognitive exercises completed at home. The participants were assessed on cognitive, mood, motivation, and functioning measures. There was a significant time by treatment interaction for attention/processing speed and verbal memory. Changes in functioning were not significant, although improved cognition predicted improvements in functioning. Number of minutes of online exercise was associated with greater cognitive improvements. Cognitive deficits are malleable with behavioral treatment in a mood disorder characterized by severe and persistent symptoms.

Utility of the Berlin questionnaire for predicting obstructive sleep apnea in individuals with treatment-resistant depression.

PURPOSE: Obstructive sleep apnea is a disabling sleep disorder characterized by obstructions or near obstructions of the upper airway. Sleep apnea shares many common features with major depressive disorder, which is a serious psychiatric disorder that can persist despite multiple treatment attempts. The current study utilizes baseline data from a study designed to evaluate the effectiveness of continuous positive airway pressure treatment in patients with comorbid treatment-resistant depression and sleep apnea. The aim of this study is to examine the effectiveness of the Berlin questionnaire in predicting which individuals with treatment-resistant depression have obstructive sleep apnea. METHODS: Eighty-two outpatients with treatment-resistant depression completed the Berlin questionnaire and underwent overnight polysomnography to determine whether they were suffering from undiagnosed obstructive sleep apnea. RESULTS: Scoring in the high-risk category on the Berlin questionnaire predicted an apnea/hypopnea index greater than 5 with a sensitivity of 25 % and a specificity of 85.4 %, an apnea/hypopnea index greater than 10 with a sensitivity of 24.5 % and a specificity of 91.7 %, and an apnea/hypopnea index greater than 15 with a sensitivity of 22.2 % and a specificity of 92.9 %. The Berlin questionnaire was better at predicting the presence of sleep apnea in our sample of predominantly pre-menopausal women than men, and category 2 of the questionnaire (daytime somnolence) was the poorest predictor of sleep apnea. CONCLUSIONS: The Berlin questionnaire appears to be a valid instrument for ruling out obstructive sleep apnea in treatment-resistant depression and may be a helpful tool in assisting with the allocation of diagnostic resources.

Relationships among neurocognition, symptoms, and functioning in treatment-resistant depression.

Treatment-resistant depression (TRD) refers to a condition where individuals with major depressive disorder have inadequate or no response to treatment. Although functional disability is a prominent and costly feature of treatment resistance, very little is known about the factors that contribute to and maintain functional impairment in TRD. This is the first study to report the neurocognitive profile of TRD and the relationships among neurocognition, symptoms, and functioning in this syndrome. Results indicated that patients with TRD (N = 33) exhibit mildly reduced performance across all neurocognitive domains with a superimposed moderate impairment in verbal working memory. Neurocognition was associated with functional competence (what one can do), whereas depressive symptoms were associated with functional performance (what one actually does). Understanding the psychological mechanisms related to functioning may help us move toward recovery in this chronically ill group.

Effects of electroconvulsive therapy and repetitive transcranial magnetic stimulation on serum brain-derived neurotrophic factor levels in patients with depression.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) levels are decreased in individuals with depression and increase following antidepressant treatment. The objective of this study is to compare pre- and post-treatment serum BDNF levels in patients with drug-resistant major depressive disorder (MDD) who received either electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS). It is hypothesized that non-pharmacological treatments also increase serum BDNF levels. METHODS: This was a prospective, single-blind study comparing pre- and post-treatment serum BDNF levels of 29 patients with drug-resistant MDD who received ECT or rTMS treatment. Serum BDNF levels were measured 1 week prior to and 1 week after treatment using the sandwich ELISA technique. Depression severity was measured 1 week before and 1 week after treatment using the Hamilton Depression Rating Scale. Two-sided normal distribution paired t-test analysis was used to compare pre- and post-treatment BDNF concentration and illness severity. Bivariate correlations using Pearson's coefficient assessed the relationship between post-treatment BDNF levels and post-treatment depression severity. RESULTS: There was no significant difference in serum BDNF levels before and after ECT, although concentrations tended to increase from a baseline mean of 9.95-12.29 ng/ml after treatment (p = 0.137). Treatment with rTMS did not significantly alter BDNF concentrations (p = 0.282). Depression severity significantly decreased following both ECT (p = 0.003) and rTMS (p < 0.001). Post-treatment BDNF concentration was not significantly correlated with post-treatment depression severity in patients who received either ECT (r = -0.133, p = 0.697) or rTMS (r = 0.374, p = 0.126). It is important to note that these results are based on the small number of patients included in this study. CONCLUSION: This study suggests that ECT and rTMS may not exert their clinical effects by altering serum BDNF levels in patients with drug-resistant MDD. Serum BDNF concentration may not be a biomarker of ECT or rTMS treatment response.

Effects of quetiapine on sleep architecture in patients with unipolar or bipolar depression.

OBJECTIVE: To determine the effect of adjunctive quetiapine therapy on the sleep architecture of patients with bipolar or unipolar depression. METHODS: This is a prospective, single-blind, repeated measures polysomnographic study. Sleep architecture was analyzed by overnight polysomnography, and subjective sleep quality was measured using the Pittsburgh Sleep Quality Index. The Hamilton Rating Scale for Depression, Montgomery Asberg Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impression-Severity Scale were employed to quantify changes in illness severity with adjunctive quetiapine treatment. Polysomnographs and clinical measures were administered at baseline, after 2-4 days of treatment, and after 21-28 days of quetiapine treatment. The average dose of quetiapine was 155 mg, ranging from 100-200 mg. RESULTS: Adjunctive quetiapine therapy did not significantly alter sleep efficiency, sleep continuity, or Pittsburgh Sleep Quality Index scores. Respiratory Disturbance Index and percentage of total time in rapid eye movement (REM) sleep significantly decreased and the percentage of total time in non-REM sleep, and duration of Stage 2 and non-REM sleep significantly increased after 2-4 days of quetiapine treatment. Illness severity significantly decreased over time. CONCLUSIONS: Adjunctive quetiapine treatment alters sleep architecture in patients with major depressive disorder or bipolar disorder, which may partially explain its early antidepressant properties. Changes in sleep architecture are more robust and significant within two to four days of starting treatment.

Outcomes of home-based diagnosis and treatment of obstructive sleep apnea.

BACKGROUND: Home diagnosis and therapy for obstructive sleep apnea (OSA) may improve access to testing and continuous positive airway pressure (CPAP) treatment. We compared subjective sleepiness, sleep quality, quality of life, BP, and CPAP adherence after 4 weeks of CPAP therapy in subjects in whom OSA was diagnosed and treated at home and in those evaluated in the sleep laboratory. METHODS: A randomized trial was performed consisting of home-based level 3 testing followed by 1 week of auto-CPAP and fixed-pressure CPAP based on the 95% pressure derived from the auto-CPAP device, and in-laboratory polysomnography (PSG) (using mostly split-night protocol) with CPAP titration; 102 subjects were randomized (age, 47.4 +/- 11.4 years; 63 men; BMI, 32.3 +/- 6.3 kg/m(2); Epworth Sleepiness Scale [ESS]: 12.5 +/- 4.3). The outcome measures were daytime sleepiness (ESS), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), quality of life (Calgary Sleep Apnea Quality of Life Index [SAQLI], 36-Item Short-Form Health Survey [SF-36], BP, and CPAP adherence after 4 weeks. RESULTS: After 4 weeks of CPAP therapy, there were no significant differences in ESS (PSG 6.4 +/- 3.8 vs home monitoring [HM] 6.5 +/- 3.8, P = .71), PSQI (PSG 5.4 +/- 3.1 vs HM 6.2 +/- 3.4, P = .30), SAQLI (PSG 4.5 +/- 1.1 vs HM 4.6 +/- 1.1, P = .85), SF-36 vitality (PSG 62.2 +/- 23.3 vs HM 64.1 +/- 18.4, P = .79), SF-36 HM (PSG 84.0 +/- 10.4 vs HM 81.3 +/- 14.9, P = .39), and BP (PSG 129/84 +/- 11/0 vs HM 125/81 +/- 13/9, P = .121). There was no difference in CPAP adherence (PSG 5.6 +/- 1.7 h/night vs HM 5.4 +/- 1.0 h/night, P = .49). CONCLUSIONS: Compared with the home-based protocol, diagnosis and treatment of OSA in the sleep laboratory does not lead to superior 4-week outcomes in sleepiness scores, sleep quality, quality of life, BP, and CPAP adherence. TRIAL REGISTRATION: clinicaltrials.gov; Identifier: NCT00139022.

Repetitive transcranial magnetic stimulation for treatment of elderly patients with depression - an open label trial.

BACKGROUND: RTMS has been developed as a novel tool for treating depression but the clinical significance of this treatment has been variable, especially in the older depressed subjects. METHODS: Medication-resistant depressed patients 60 years or older were treated for two weeks (10 sessions) with high-frequency rTMS delivered to the left dorsolateral prefrontal cortex at 100% of motor threshold. Each session consisted of 20 trains at 10Hz delivered in 8-second duration. The patients continued taking their psychotropic medications throughout the study. RESULTS: Nineteen of the 20 subjects completed the trial. One subject dropped out after 8 sessions because of discomfort. The average age of our patients was 66.8 years (6 males and 14 females). Six patients responded and there was a 31.6% mean reduction in Hamilton Depression Rating Scale (HDRS) scores from baseline at the end of the treatment. There was statistically significant decrease from baseline in both HDRS and HARS scores at the end of treatment. rTMS was generally well tolerated. CONCLUSION: These preliminary finding suggests that rTMS may be an effective treatment alternative to a subpopulation of medication resistant older depressed patients.