Major depressive disorder (MDD) is a disabling psychiatric condition for which effective treatment remains an outstanding need. Antidepressants are currently the mainstay of treatment for depression; however, almost two-thirds of patients will fail to achieve remission with initial treatment. As a result, a range of augmentation and combination strategies have been used in order to improve outcomes for patients. Despite the popularity of these approaches, limited data from double-blind, randomized, placebo-controlled studies are available to allow clinicians to determine which are the most effective augmentation options or which patients are most likely to respond to which options. Recently, evidence has shown that adjunctive therapy with atypical antipsychotics has the potential for beneficial antidepressant effects in the absence of psychotic symptoms. In particular, aripiprazole has shown efficacy as an augmentation option with standard antidepressant therapy in two, large, randomized, double-blind studies. Based on these efficacy and safety data, aripiprazole was recently approved by the FDA as adjunctive therapy for MDD. The availability of this new treatment option should allow more patients with MDD to achieve remission and, ultimately, long-term, successful outcomes.

Objective

Little is known about mental health service use by adults with prior suicidal behavior and current mood or anxiety disorders. This study determined nationally representative prevalence estimates of current mental health service use by these adults, examining racial-ethnic, age, and gender differences.

Methods

Service use across the life course was examined with Collaborative Psychiatric Epidemiology Survey data from 1,139 adults with a history of suicidal behavior and current mood or anxiety disorders.

Results

Overall service use was 47.3%. Across the life course, African Americans showed increasing service use that paralleled use by non-Hispanic whites, Hispanics, and others, whereas use by these three groups decreased in the latter half of the life course (p interaction=.01).

Conclusions

Adults with prior suicidal behavior and current mood or anxiety disorders have low mental health service use. Findings of racial-ethnic disparities in use can help identify those in need of care.

Background

Less than half of patients with major depressive disorder (MDD) respond to their first antidepressant trial. Our understanding of the underlying mechanisms of selective serotonin reuptake inhibitors (SSRIs) remains poor, and there is no reliable method of predicting treatment response.

Methods

Thirty-seven MDD subjects and 41 healthy controls, somatically healthy and medication-free for at least six weeks, were recruited, and plasma serotonin (5-HT) levels were assessed at baseline. Twenty-six of the MDD subjects were then treated in an open-label manner with clinically appropriate doses of sertraline for 8 weeks, after which plasma 5-HT levels were again assessed. Response to treatment was defined as an improvement of 50% or more on the Hamilton Depression Rating Scale.

Results

Non-responders to sertraline treatment had significantly lower pre-treatment 5-HT levels compared to both healthy controls and responders (F = 4.4, p = 0.004 and p = 0.036, respectively). There was a significant decrease in 5-HT levels over treatment in all MDD subjects (t = 6.2, p = 0.000003). The decrease was significantly more prominent in responders compared to non-responders (t = 2.1, p = 0.047). There was no significant difference in post-treatment 5-HT levels between responders and non-responders.

Limitations

The study had a modest sample size. 5-HT levels in plasma may not reflect 5-HT levels in the brain.

Conclusions

The results indicate that SSRI response may be facilitated by adequate baseline plasma 5-HT content and that successful SSRI treatment is associated with greater decreases in circulating 5-HT. Plasma 5-HT content may be a predictor of SSRI treatment outcome. Potential underlying mechanisms are discussed.

Objective

To evaluate the association between changes in functional disability and suicide ideation among older adults following psychotherapy for depression.

Methods

Sixty-five participants (65-91 years old, 72% White, and 66% female) with depression completed 12 sessions of problem solving therapy (PST) and completed measures of disability (WHO Disability Assessment Schedule 2.0) and suicide ideation (Geriatric Suicide Ideation Scale [GSIS]) at baseline and post-treatment.

Results

Hierarchical linear regressions found that reductions in functional disability were associated with overall reductions in suicide ideation on the GSIS (F[4,60] = 4.06, p < 0.01), particularly with the Loss of Worth GSIS subscale (F[4,60] = 7.86, p < 0.001, ΔR² = 0.140).

Conclusions

Results suggest decreased functional disability following depression treatment is associated with decreased suicide ideation, especially thoughts regarding loss of worth. These results highlight the potential for treatments that reduce functional disability (e.g., PST) to reduce risk of suicide among older adults.

Objective

The purpose of this study was to determine the impact of psychotherapy on cognitive functioning in older adults with late-life depression (LLD) and executive dysfunction.

Methods

Two hundred twenty-one adults aged 60 years and older participated in a randomized clinical trial comparing the efficacy of Problem Solving Therapy (PST) and Supportive Therapy (ST) for LLD. Cognitive performance on seven tests of executive functioning, verbal learning, and memory was evaluated at baseline, after 12 weeks of treatment, and at 24 weeks after the completion of treatment.

Results

Performance on a measure of executive functioning with a significant information processing speed component (Stroop Color and Word Test) improved after treatment, F (1, 312) = 8.50, p = 0.002, and improved performance was associated with a reduction in depressive symptoms but not treatment type. Performance on other measures of executive functioning, verbal learning, and memory did not change significantly after 12 weeks of psychotherapy treatment.

Conclusion

Our results suggest that improvements in cognitive functioning after psychotherapy treatment for depression in older adults with executive dysfunction are likely focal and not distributed across all cognitive domains. Although previous analyses reported that PST was superior to ST in the treatment of depression, this analysis indicated no difference between the two treatments with regard to improvements in cognitive functioning.

Background

Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD.

Methods

This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission.

Results

We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes.

Conclusions

MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD.

Objective

To compare patterns of cognitive performance in older adults with late-onset depression (LOD; ≥65 years of age) with that of older adults with early-onset depression (EOD; <65 years).

Methods

Participants were 171 adults aged 60 years or older with major depression and executive dysfunction who were participating in a randomized psychotherapy trial. Participants included 72 LOD and 99 EOD individuals. Cognitive performance on measures of verbal learning, memory, and executive functioning were evaluated. Demographic and clinical characteristics, severity of cerebrovascular risk factors, and disability ratings were also compared between groups.

Results

The LOD group was older and had fewer previous episodes of depression and lower severity of depression compared with EOD participants. The LOD group demonstrated poorer performance on measures of verbal learning (F(1,161) = 4.28, p = 0.04) and memory (F(1,160) = 4.65, p = 0.03) than the EOD group. Linear regression analysis demonstrated that LOD and fewer years of education were significant predictors of poorer verbal learning (F(7,114) = 6.25, p <0.001) and memory (F(7,113)=7.24, p <0.001). Performance on measures of executive functioning, severity of vascular risk factors, and disability ratings did not differ between the two groups.

Conclusion

In older adults with depression and executive dysfunction, LOD was associated with poorer performance on measures of verbal learning and memory. Aging-related brain changes associated with LOD may play a more important role, leading to dysfunction in these cognitive domains than a history of recurrent depressive episodes in older adults with a dysexecutive syndrome.

Objective

Cortical atrophy has been associated with late-life depression (LLD) and recent findings suggest that reduced right hemisphere cortical thickness is associated with familial risk for major depressive disorder, but cortical thickness abnormalities in LLD have not been explored. Furthermore, cortical atrophy has been posited as a contributor to poor antidepressant treatment response in LLD, but the impact of cortical thickness on psychotherapy response is unknown. This study was conducted to evaluate patterns of cortical thickness in LLD and in relation to psychotherapy treatment outcomes.

Methods

Participants included 22 individuals with LLD and 12 age-matched comparison subjects. LLD participants completed 12 weeks of psychotherapy and treatment response was defined as a 50% reduction in depressive symptoms. All participants underwent magnetic resonance imaging of the brain, and cortical mapping of gray matter tissue thickness was calculated.

Results

LLD individuals demonstrated thinner cortex than controls prominently in the right frontal, parietal, and temporal brain regions. Eleven participants (50%) exhibited positive psychotherapy response after 12 weeks of treatment. Psychotherapy nonresponders demonstrated thinner cortex in bilateral posterior cingulate and parahippocampal cortices, left paracentral, precuneus, cuneus, and insular cortices, and the right medial orbitofrontal and lateral occipital cortices relative to treatment responders.

Conclusions

Our findings suggest more distributed right hemisphere cortical abnormalities in LLD than have been previously reported. In addition, our findings suggest that reduced bilateral cortical thickness may be an important phenotypic marker of individuals at higher risk for poor response to psychotherapy.

Background

Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of "accelerated aging" in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD), whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation.

Methodology

Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio) and inflammation (IL-6). Analyses were controlled for age and sex.

Principal findings

The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05). Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration) was 281 base pairs shorter than that in controls (p<0.05), corresponding to approximately seven years of "accelerated cell aging." Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01) and in the controls (p<0.05) and with inflammation in the depressed subjects (p<0.05).

Conclusions

These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression and is not an intrinsic feature. Rather, telomere shortening may progress in proportion to lifetime depression exposure.

Short leukocyte telomere length (LTL) may be associated with several psychiatric disorders, including major depressive disorder (MDD). Short LTL has previously been associated with poor response to psychiatric medications in bipolar disorder and schizophrenia, but no studies have prospectively assessed the relationship of LTL to SSRI response in MDD. We assessed pre-treatment LTL, depression severity (using the Hamilton Depression Rating Scale [HDRS]), and self-reported positive and negative affect in 27 healthy, unmedicated adults with MDD. Subjects then underwent open-label treatment with a selective serotonin reuptake inhibitor (SSRI) antidepressant for eight weeks, after which clinical ratings were repeated. Analyses were corrected for age, sex and BMI. "Non-responders" to treatment (HDRS improvement <50%) had significantly shorter pre-treatment LTL, compared to "Responders" (p=0.037). Further, shorter pre-treatment LTL was associated with less improvement in negative affect (p<0.010) but not with changes in positive affect (p=0.356). This preliminary study is the first to assess the relationship between LTL and SSRI response in MDD and among the first to prospectively assess its relationship to treatment outcome in any psychiatric illness. Our data suggest that short LTL may serve as a vulnerability index of poorer response to SSRI treatment, but this needs examination in larger samples.