Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia

STUDY OBJECTIVE: Insomnia impacts the course of major depressive disorder (MDD), hinders response to treatment, and increases risk for depressive relapse. This study is an initial evaluation of adding cognitive behavioral therapy for insomnia (CBTI) to the antidepressant medication escitalopram (EsCIT) in individuals with both disorders. DESIGN AND SETTING: A randomized, controlled, pilot study in a single academic medical center. PARTICIPANTS: 30 individuals (61% female, mean age 35 +/- 18) with MDD and insomnia. INTERVENTIONS: EsCIT and 7 individual therapy sessions of CBTI or CTRL (quasi-desensitization). Measurements and results: Depression was assessed with the HRSD17 and the depression portion of the SCID, administered by raters masked to treatment assignment, at baseline and after 2, 4, 6, 8, and 12 weeks of treatment. The primary outcome was remission of MDD at study exit, which required both an HRSD17 score < or =7 and absence of the 2 core symptoms of MDD. Sleep was assessed with the insomnia severity index (ISI), daily sleep diaries, and actigraphy. EsCIT + CBTI resulted in a higher rate of remission of depression (61.5%) than EsCIT + CTRL (33.3%). EsCIT + CBTI was also associated with a greater remission from insomnia (50.0%) than EsCIT + CTRL (7.7%) and larger improvement in all diary and actigraphy measures of sleep, except for total sleep time. CONCLUSIONS: This pilot study provides evidence that augmenting an antidepressant medication with a brief, symptom focused, cognitive-behavioral therapy for insomnia is promising for individuals with MDD and comorbid insomnia in terms of alleviating both depression and insomnia.     

The association between vasomotor symptoms and depression during perimenopause: A systematic review

There is a high incidence of depression in women presenting to menopause clinics. The aim of this review was to determine if there is an association between depressive symptoms or major depressive disorder (MDD) and vasomotor symptoms (VMS). A systematic review of the literature was conducted according to PRISMA guidelines. 33 relevant publications were found, 12 from three large studies. Overall, we found that there is a bidirectional association between VMS and depressive symptoms. This has been established in well-conducted, large observational studies. There does not appear to be a relationship between VMS and MDD. However, studies examining VMS and MDD were prone to bias making it difficult to draw any conclusions.     

Differential impact of isolated psychotic symptoms on treatment outcome of major depressive disorder in the STAR*D cohort of Whites,Blacks and Latinos

Objective

To determine whether isolated psychotic symptoms are more likely to be endorsed by depressed Latinos as opposed to other ethnic–racial groups; whether these symptoms affect Latinos similarly to other ethnic–racial groups in terms of treatment response; and whether they are more likely to be associated with anxiety disorders in depressed Latinos.

Methods

We analyzed data from STAR?D subjects who self identified as White, Black, or Latino. Rates of isolated psychotic symptoms were assessed by the self-rated Psychiatric Diagnostic Screening Questionnaire (PDSQ) and compared between ethnic–racial groups. Depressive remission outcomes were compared within each ethnic–racial group between subjects who endorsed psychotic symptoms versus no psychotic symptoms. Associations between isolated psychotic symptoms and anxiety disorders were also examined.

Results

Among 2597 eligible subjects with at least one post-baseline assessment and available PDSQ data excluding first-rank symptoms, the prevalence of auditory–visual hallucination was 2.5% in Whites (n=49/1928), 11.3% in Blacks (n=45/398) 6.3% in Latinos (n=17/270) (χ²=64.9; df=2; p<0.001). Prevalence of paranoid ideation was 15.5% in Whites (n=299/1927), 31.5% in Blacks (n=126/400), and 21.1% in Latinos (n=57/270) (χ²=57.3; df=2; p<0.001). Among Whites and Blacks but not Latinos, depressive remission rates were worse in subjects with auditory–visual hallucinations compared to those without them. Paranoid ideation had a significant negative impact on remission in Whites only. In all ethnic–racial groups, a significant association was found between auditory–visual hallucinations and PTSD and panic disorder.

Limitations

The STAR*D study did not include any structured clinician-based assessment of psychotic symptoms.

Conclusion

Latinos do not appear to have worse outcomes when treated for MDD with auditory–visual hallucinations, differently from Whites and Blacks.     

Remitted major depression is characterized by reduced prefrontal cortex reactivity to reward loss

Background

Major depression (MDD) is characterized by anhedonia. Although a growing body of literature has linked anhedonia in MDD to reduced frontostriatal activity during reward gains, relatively few studies have examined neural responsivity to loss, and no studies to date have examined neural responses to loss in euthymic individuals with a history of MDD. Methods: An fMRI monetary incentive delay task was administered to 19 participants with remitted MDD (rMDD) and 19 never depressed controls. Analyses examined group activation differences in brain reward circuitry during monetary loss anticipation and outcomes. Secondary analyses examined the association between self-reported rumination and brain activation in the rMDD group. Results: Compared to controls, the rMDD group showed less superior frontal gyrus activation during loss anticipation and less inferior and superior frontal gyri activation during loss outcomes (cluster corrected p’s<.05). Ruminative Responses Scale scores were negatively correlated with superior frontal gyrus activation (r=−.68, p=.001) during loss outcomes in the rMDD group. Limitations: Replication with a larger sample is needed. Conclusions: Euthymic individuals with a history of MDD showed prefrontal cortex hypoactivation during loss anticipation and outcomes, and the degree of superior frontal gyrus hypoactivation was associated with rumination. Abnormal prefrontal cortex responses to loss may reflect a trait-like vulnerability to MDD, although future research is needed to evaluate the utility of this functional neural endophenotype as a prospective risk marker.     

Self-reported versus clinician-rated symptoms of depression as outcome measures in psychotherapy research on depression: A meta-analysis

It is not well-known whether self-report measures and clinician-rated instruments for depression result in comparable outcomes in research on psychotherapy. We conducted a meta-analysis in which randomized controlled trials were included examining the effects of psychotherapy for adult depression. Only studies were included in which both a self-report and a clinician-rated instrument were used. We calculated the effect size (Hedges' g) based on the self-report measures, the effect size based on the clinician-rated instruments, and the difference between these two effect sizes (Δg). A total of 48 studies including a total of 2462 participants was included in the meta-analysis. The differential effect size was Δg = 0.20 (95% CI: 0.10–0.30), indicating that clinician-rated instruments resulted in a significantly higher effect size than self-report instruments from the same studies. When we limited the effect size analysis to those studies comparing the HRSD with the BDI, the differential effect was somewhat smaller, but still statistically significant (Δg = 0.15; 95% CI: 0.03–0.27). This meta-analysis has made it clear that clinician-rated and self-report measures of improvement following psychotherapy for depression are not equivalent. Different symptoms may be more suitable for self-report or ratings by clinicians and in clinical trials it is probably best to include both.     

Group interpersonal psychotherapy for patients with major depression disorder - pilot study

Background: This study evaluated the effectiveness of group interpersonal psychotherapy (IPT-G) for patients suffering from moderate to severe major depressive disorder (MDD), and who responded to antidepressant drugs during the acute phase treatment. Method: Subjects were allocated into two groups: in the study group subjects entered IPT-G while in the comparison group subjects continued with standard treatment. All subjects were assessed five times during and 6 months after the termination of the IPT-G in a double-blind, matched-control design. Results: Subjects who participated in the IPT-G demonstrated significant improvement of their depressive symptoms compared to those who received the standard treatment both during the group therapy and in a 6-month follow-up period. Conclusions: Our preliminary results suggest that IPT in a group setting might be effective for a subset of patients who respond to antidepressant medication. Limitation: Small group of patients, lack of different types of treatment as control groups.     

Persistence of chronic major depression: A national prospective study

Background

Chronic major depressive disorder (CMDD) is highly prevalent and associated with high personal and societal cost. Identifying risk factors for persistence and remission of CMDD may help in developing more effective treatment and prevention interventions.

Methods

Prospective cohort study of individuals participating in the National Epidemiologic Survey on Alcohol and Related Conditions (Wave 1; n=43,093) and its 3-year follow-up (Wave 2; n=34,653) who met a diagnosis of CMDD at the Wave 1 assessment.

Results

Among the 504 respondents who met criteria for present CMDD at Wave 1, only 63 (11.52%) of them continued to meet criteria of CMDD. A history of childhood sexual abuse, earlier onset of MDD, presence of comorbidity and a history of treatment-seeking for depression predicted persistence of CMDD three years after the baseline evaluation.

Limitations

Our sample is limited to adults, our follow-up period was only three-years and the diagnosis of CMDD at baseline was retrospective.

Conclusions

CMDD shows high rates of remission within three years of baseline assessment, although some specific risk factors predict a persistent course. Given the high personal and societal cost associated with CMDD, there is a need to develop and disseminate effective interventions for CMDD.     

Effects of an antidepressant on neural correlates of emotional processing in patients with major depression

We measured brain activation in patients with major depressive disorder when exposed to emotional pictures before and after antidepressant treatment. The participants included 18 first-episode unmedicated patients with current major depressive disorder and 18 age- and gender-matched control subjects. All subjects performed an emotional task during functional magnetic resonance imaging scanning at baseline and after 8 weeks of fluoxetine treatment. Unmedicated depressed patients showed lower accuracy rates (0.53 ± 0.26) than did subjects in the control group (0.71 ± 0.18) while viewing positive pictures. During exposure to positive stimuli, decreased activations were seen in the right insula (BA13) and left anterior cingulate cortex (BA32) in patients after antidepressant treatment. After antidepressant treatment, patients exhibited greater activation in the right middle frontal gyrus (BA8,9) in response to negative stimuli. Our results suggest that the prefrontal cortex, anterior cingulate cortex and insula may play key roles as biological markers for treatment response and as predictors of therapeutic success.     

Differences in functional connectivity in major depression versus bipolar II depression

Background

Objective methods of differentiating unipolar versus bipolar depression would enhance our ability to treat these disorders by providing more accurate diagnoses. One first step towards developing diagnostic methodology is determining whether brain function as assessed by functional MRI (fMRI) and functional connectivity analyses might differentiate the two disorders.

Methods

Fourteen subjects with bipolar II depression and 26 subjects with recurrent unipolar depression were studied using fMRI and functional connectivity analyses.

Results

The first key finding of this study was that functional connectivity of the right posterior cingulate cortex differentiates bipolar II and unipolar depression. Additionally, results suggest that functional connectivity of this region is associated with suicidal ideation and depression severity in unipolar but not bipolar II depression.

Limitations

The primary limitation is the relatively small sample size, particularly for the correlational analyses.

Conclusions

The functional connectivity of right posterior cingulate cortex may differential unipolar from bipolar II depression. Further, connectivity of this region may be associated with depression severity and suicide risk in unipolar but not bipolar depression.     

Plasma NPY concentrations during tryptophan and sham depletion in medication-free patients with remitted depression

BACKGROUND: Neuropeptide Y (NPY) and serotonergic systems have been implicated in the pathophysiology of depression but have not yet been linked together. METHODS: In a randomized, double-blind crossover study, 28 medication-free patients with remitted depression and 26 healthy control subjects underwent tryptophan depletion (TD) and sham depletion. Plasma NPY concentrations were determined at baseline and at +5, +7, and +24 h during TD and sham depletion, respectively. Hamilton Depression Rating Scale (HDRS, 24-item) scores were assessed at baseline and at +7 and +24 h after TD and sham depletion, respectively. RESULTS: There was no difference between healthy subjects and patients with remitted depression in baseline plasma NPY concentrations and in plasma NPY concentrations during TD and sham depletion, respectively. Plasma NPY concentrations did not differ between TD and sham depletion. At no time point there was an association between HDRS scores and plasma NPY concentrations in patients with remitted depression. LIMITATIONS: Plasma NPY concentrations in rMDD patients were not obtained during the symptomatic phase of the illness. Only peripheral measurements of NPY were used. CONCLUSIONS: Decreased plasma NPY concentrations, as described previously during a spontaneous episode of major depression, appear as state but not as trait marker in depression. No evidence was found for an involvement of plasma NPY in relapse during TD. There appears no direct functional link between serotonergic neurotransmission and plasma NPY concentrations.     

Assessment of depression by questionnaire compared to DSM-III diagnosis

The LPD, a self-report questionnaire which provides a quantitative and qualitative measure of depression, was examined in relation to a criterion-based system of diagnosis, the DSM-III. Results from 190 psychiatric inpatients suggest that the LPD distinguishes depressive from non-depressive syndromes in terms of severity of depression and that patients with melancholic major depression are more severely depressed than those with non-melancholic major depression. Furthermore, major depression with melancholia and major depression without melancholia, both conform to the LPD profile of endogenous depression whereas other depressive syndromes do not. A comparison of the two systems of categorizing depression also suggests that the LPD is a relatively sensitive predictor of the diagnosis of major depressive disorder.     

Medial temporal lobe abnormalities in pediatric unipolar depression

In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age +/- S.D.=13.0 +/- 2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age +/- S.D.=13.9 +/- 2.9 years) were studied using a 1.5T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89 +/- 0.16 cm(3) versus 1.99 +/- 0.18 cm(3), respectively; F=5.0, d.f.=1/39, p=0.03; effect size: eta2(p) =0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F=2.8, d.f.=2/38, p=0.07; effect size: eta2(p) =0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction.     

Life events in depression. Relationship to subtypes

Life events that had occurred in the 6 months before the onset of depression were recorded in 40 depressed patients and 41 normal controls. The depressed patients had experienced significantly more life events and significantly more undesirable life events than the controls. The 20 patients with a DSM-III diagnosed major depressive episode (MDE) without melancholia had experienced significantly more life events in the 6 months before the onset of depression than the 20 patients with a major depressive episode with melancholia. The patients with MDE without melancholia, but not the MDE with melancholia patients, had also experienced significantly more life events than a group of age- and sex-matched normal controls.     

EEG patterns in various subgroups of endogenous depression

Twenty-three patients with major depressive disorders were examined clinically, biochemically and electroencephalographically before antidepressive treatment was initiated. EEG characteristics were related to clinical items and to a serotonin re-uptake indicator. The results suggested that at least three definable EEG patterns were associated with certain specific features of major depressive disorders. Thus, an EEG pattern characterised by increased beta activity was associated with the recurrent type of depression. Another EEG pattern, with signs of decreased alertness, was present in patients with insomnia, agitation and in those without depression in their families. A significant correlation was also found between the alertness indicator and the serotonin accumulation rate. The third type of EEG feature was represented by interhemispheric asymmetry in the EEG which could be seen in patients with high scores of anxiety. The results suggest that the EEG findings may be helpful in defining various subgroups of major depressive disorders.     

Prevalence and correlates of depression among HIV-infected and -affected older people in rural South Africa

Background

Little is known about depression in older people in sub-Saharan Africa, the associated impact of HIV, and the influence on health perceptions.

Objectives

Examine the prevalence and correlates of depression; explore the relationship between depression and health perceptions in HIV-infected and -affected older people.

Methods

In 2010, 422 HIV-infected and -affected participants aged 50+ were recruited into a cross-sectional study. Nurse professionals interviewed participants and a diagnosis of depressive episode was derived from the Composite International Diagnostic Interview (Depression module) using the International Classification of Diseases diagnostic criteria and categorised as major (MDE) or brief (BDE).

Results

Overall, 42.4% (n=179) had a depressive episode (MDE: 22.7%, n=96; BDE: 19.7%, n=83). Prevalence of MDE was significantly higher in HIV-affected (30.1%, 95% CI 24.0–36.2%) than HIV-infected (14.8%, 95% CI 9.9–19.7%) participants; BDE was higher in HIV-infected (24.6%, 95% CI 18.7–30.6%) than in HIV-affected (15.1%, 95% CI 10.3–19.8%) participants. Being female (aOR 3.04, 95% CI 1.73–5.36), receiving a government grant (aOR 0.34, 95% CI 0.15–0.75), urban residency (aOR 1.86, 95% CI 1.16–2.96) and adult care-giving (aOR 2.37, 95% CI 1.37–4.12) were significantly associated with any depressive episode. Participants with a depressive episode were 2–3 times more likely to report poor health perceptions.

Limitations

Study limitations include the cross-sectional design, limited sample size and possible selection biases.

Conclusions

Prevalence of depressive episodes was high. Major depressive episodes were higher in HIV-affected than HIV-infected participants. Psycho-social support similar to that of HIV treatment programmes around HIV-affected older people may be useful in reducing their vulnerability to depression.     

A meta-analysis of the relation of intolerance of uncertainty to symptoms of generalized anxiety disorder, major depressive disorder, and obsessive-compulsive disorder

Intolerance of uncertainty (IU) has been suggested to reflect a specific risk factor for generalized anxiety disorder (GAD), but there have been no systematic attempts to evaluate the specificity of IU to GAD. This meta-analysis examined the cross-sectional association of IU with symptoms of GAD, major depressive disorder (MDD), and obsessive-compulsive disorder (OCD). Random effects analyses were conducted for two common definitions of IU, one that has predominated in studies of GAD (56 effect sizes) and another that has been favored in studies of OCD (29 effect sizes). Using the definition of IU developed for GAD, IU shared a mean correlation of .57 with GAD, .53 with MDD, and .50 with OCD. Using the alternate definition developed for OCD, IU shared a mean correlation of .46 with MDD and .42 with OCD, with no studies available for GAD. Post-hoc significance tests revealed that IU was more strongly related to GAD than to OCD when the GAD-specific definition of IU was used. No other differences were found in the magnitude of associations between IU and the three syndromes. We discuss implications of these findings for models of shared and specific features of emotional disorders and for future research efforts.     

Meta-analytic evidence for neuroimaging models of depression: State or trait?

Background

Major Depressive Disorder (MDD) is a leading cause of disease burden worldwide. With the rapid growth of neuroimaging research on relatively small samples, meta-analytic techniques are becoming increasingly important. Here, we aim to clarify the support in fMRI literature for three leading neurobiological models of MDD: limbic–cortical, cortico–striatal and the default mode network.

Methods

Searches of PubMed and Web of Knowledge, and manual searches, were undertaken in early 2011. Data from 34 case-control comparisons (n=1165) and 6 treatment studies (n=105) were analysed separately with two meta-analytic methods for imaging data: Activation Likelihood Estimation and Gaussian-Process Regression.

Results

There was broad support for limbic–cortical and cortico–striatal models in the case-control data. Evidence for the role of the default mode network was weaker. Treatment-sensitive regions were primarily in lateral frontal areas.

Limitations

In any meta-analysis, the increase in the statistical power of the inference comes with the risk of aggregating heterogeneous study pools. While we believe that this wide range of paradigms allows identification of key regions of dysfunction in MDD (regardless of task), we attempted to minimise such risks by employing GPR, which models such heterogeneity.

Conclusions

The focus of treatment effects in frontal areas indicates that dysregulation here may represent a biomarker of treatment response. Since the dysregulation in many subcortical regions in the case-control comparisons appeared insensitive to treatment, we propose that these act as trait vulnerability markers, or perhaps treatment insensitivity. Our findings allow these models of MDD to be applied to fMRI literature with some confidence.     

Pattern of impaired working memory during major depression

BACKGROUND: The aim of this study was to assess working memory (WM) in patients with major depressive disorder (MDD), using a robust parametric WM task (the n-back task). METHODS: Twenty patients with MDD and twenty healthy controls completed a visual version of the paradigm, comprising four levels of task difficulty (i.e. 0-, 1-, 2-, and 3-back). Performance accuracy and reaction time (RT) were measured at each difficulty level. RESULTS: In comparison with controls, patients with MDD exhibited slower RTs (F((1,38)) = 25.16, p < 0.001), and reduced accuracy (F((1,38)) = 5.93, p < 0.001). There was no diagnosis-specific effect of task difficulty on performance accuracy. However, the faster response to memory (1-3-back) than to shadowing (0-back) tasks observed in controls was not as pronounced in patients. CONCLUSIONS: These observations support a relatively specific impairment of WM/central executive function in MDD, which may potentially mediate the diverse pattern of cognitive dysfunction noted in MDD. The parametric n-back task is applicable to subjects with MDD and yields results interpretable across the dimensions of task difficulty and performance in controls and patients.     

Subtyping depression in the medically ill by cluster analysis

Background

There is increasing awareness of the need of subtyping major depressive disorder, particularly in the setting of medical disease. The aim of this investigation was to use both DSM-IV comorbidity and the Diagnostic Criteria for Psychosomatic Research (DCPR) for characterizing depression in the medically ill.

Methods

1700 patients were recruited from 8 medical centers in the Italian Health System and 1560 agreed to participate. They all underwent a cross-sectional assessment with DSM-IV and DCPR structured interviews. 198 patients (12.7%) received a diagnosis of major depressive disorder. Data were submitted to cluster analysis.

Results

Two clusters were identified: depressed somatizers and irritable/anxious depression. The somatizer cluster included 58.6% of the cases and was characterized by DCPR somatization syndromes (persistent somatization, functional somatic symptoms secondary to a psychiatric disorder, conversion symptoms, and anniversary reactions) and DCPR alexithymia. The anxious/irritable cluster had 41.4% of the total sample and included DCPR irritable mood and type A behavior and DSM-IV anxiety disorders.

Limitations

The study has limitations due to its cross-sectional nature. Further, these findings require additional validation in another sample.

Conclusions

The findings indicate the need of expanding clinical assessment in the medically ill to include the various manifestations of somatization, irritable mood, type A behavior and alexithymia, as encompassed by the DCPR. Subtyping major depressive disorder may yield improved targets for psychosomatic research and treatment trials.     

Duloxetine for major depressive disorder and daytime and nighttime hot flashes associated with the menopausal transition

Background

We sought to obtain preliminary data regarding the efficacy of duloxetine for major depressive disorder (MDD) during the menopausal transition. The secondary outcomes were vasomotor symptoms (VMS, or hot flashes), specifically assessed as daytime or nighttime, and anxiety.

Methods

After a single-blind placebo lead-in, peri- and postmenopausal women with MDD (n = 19) received eight weeks of open-label treatment with duloxetine (60 mg/day). The Hamilton Rating Scale for Depression (17-item) (HAM-D) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries, the Greene Climacteric Scale (GCS), and the Hot Flash-Related Daily Interference Scale (HFRDIS). Anxiety was measured with the Generalized Anxiety Disorder scale (GAD-7).

Results

Of 19 participants treated with duloxetine, 16 (84.2%) were evaluable (returned for ≥1 follow up), and 13 (68.4%) completed the study. Three discontinued due to side effects. The pre-treatment and final median HAM-D scores were 15 (interquartile range [IQR] 14–18), and 6.5 (IQR 4–11.5), respectively, reflecting a significant decrease (p = .0006). The response and remission rates were 56.3% (all responders were also remitters, having ≥50% decrease in HAM-D scores and final scores ≤7). Anxiety improved with treatment (p = .012). GCS and HFRDIS scores decreased significantly. Among those who reported hot flashes at baseline, number and severity of hot flashes improved significantly overall (p = .009 and p = .008, respectively). Daytime but not nighttime hot flashes improved significantly.

Conclusions

These data support further study of duloxetine for the treatment of a spectrum of symptoms associated with the menopausal transition.