Situational major depressive disorder

Fifty-seven patients with situational major depression diagnosed by the Research Diagnostic Criteria were compared with 72 subjects with nonsituational major depression on demographic, clinical, and psychosocial variables. The situational patients tended to be younger and had fewer prior episodes of depression and fewer hospitalizations. No differences were found in categories of life events, in overall clinical picture, in social supports, or in family history.     

Tachyphylaxis in unipolar major depressive disorder

BACKGROUND: Major depressive disorder is usually a recurring illness, and maintenance treatment is used to forestall or prevent recurrent episodes of depression. This study describes recurrence of major depression despite maintenance pharmacotherapy, termed tachyphylaxis. METHOD: The study sample consisted of 103 subjects who participated in the NIMH Collaborative Depression Study, a multicenter longitudinal observational study of the mood disorders. Subjects diagnosed with unipolar major depressive disorder according to Research Diagnostic Criteria were enrolled from 1978-1981 and prospectively followed for up to 20 years. As an observational study, treatment was recorded but not controlled by anyone connected with the study. Subjects were selected for the present study if at some point during follow-up they received antidepressant medication for treatment of an episode of major depressive disorder, recovered from this episode, and subsequently received maintenance pharmacotherapy. Some subjects were successfully treated for multiple episodes of major depressive disorder and then received maintenance medication after each of these episodes, resulting in multiple maintenance treatment intervals. Data were collected using the Longitudinal Interval Follow-Up Evaluation, and mixed-effects logistic regression was used to test the association of sociodemographic and clinical variables with tachyphylaxis. RESULTS: For the 103 subjects, there were 171 maintenance treatment intervals in which a subject received maintenance pharmacotherapy after having recovered from an episode of major depressive disorder. The median duration of maintenance treatment was 20 weeks. Tachyphylaxis occurred during 43 (25%) of these 171 maintenance treatment intervals. The subtype of melancholic (endogenous) major depressive disorder significantly elevated the risk of tachyphylaxis during the subsequent maintenance treatment interval. CONCLUSIONS: Despite the use of maintenance pharmacotherapy, major depression recurs in a considerable number of patients. Improved prophylaxis for these patients requires other treatment strategies based upon a greater understanding of recurrence.     

Social functioning in major depressive disorder

Depression is associated with social risk factors, social impairments and poor social functioning. This paper gives an overview of these social aspects using the NIMH Research and Domain Criteria ‘Systems for Social Processes’ as a framework. In particular, it describes the bio-psycho-social interplay regarding impaired affiliation and attachment (social anhedonia, hyper-sensitivity to social rejection, competition avoidance, increased altruistic punishment), impaired social communication (impaired emotion recognition, diminished cooperativeness), impaired social perception (reduced empathy, theory-of-mind deficits) and their impact on social networks and the use of social media. It describes these dysfunctional social processes at the behavioural, neuroanatomical, neurochemical and genetic levels, and with respect to animal models of social stress. We discuss the diagnostic specificity of these social deficit constructs for depression and in relation to depression severity. Since social factors are importantly involved in the pathogenesis and the consequences of depression, such research will likely contribute to better diagnostic assessments and concepts, treatments and preventative strategies both at the diagnostic and transdiagnostic level.     

Lymphocyte function in major depressive disorder

Lymphocyte stimulation by phytohemagglutinin, concanavalin A, and pokeweed mitogen was significantly lower in a group of hospitalized depressed patients than in matched controls. The absolute number of T and B cells was lower in the depressed group, but the percentage of these cell types did not differ between the groups. These findings may be related to the altered neuroendocrine function found in patients with depressive disorders.     

Circadian genes in major depressive disorder

Abstract

Background: Sleep disturbances are a common symptom of major depressive disorder (MDD). Sleep is highly regulated by circadian rhythms, controlled by circadian genes, that act through a series of feedback loops to regulate the sleep-wake cycle.

Objectives: To the best of our knowledge, a systematic review regarding the core circadian genes and their role in MDD has not been published recently. Also, a review of these genes and their role in sleep disturbances in depressed individuals appears to have never been done. We decided to integrate both concepts into one comprehensive review.

Method: The review was done using the appropriate search terms in the following search engines: OVID Medline, Embase, PsycINFO and Pubmed.

Results: Based on the data reviewed, none of the circadian genes appear to be associated with MDD, but some are more promising than others. These genes are: CRY1, CRY2, PER2 and NPAS2. When investigating the role of circadian genes in sleep disturbances among individuals with MDD, the most promising candidate gene is TIMELESS. Although the results in this area are limited.

Conclusion: Given the promising leads from this review, future studies should investigate circadian genes in sleep disturbances among the depressed population.     

Executive dysfunction in major depressive disorder

Executive dysfunction is commonly seen in major depression. The types of executive deficits seen in depression include problems with planning, initiating and completing goal-directed activities. Executive dysfunction may vary as a function of the severity of depression. In addition, a subset of geriatric depression is also characterized by prominent deficits in executive functioning. The presence of executive dysfunction in depression is associated with vocational disability and possibly poorer treatment response. While few studies have examined the treatment of executive dysfunction in depression, preliminary work suggests that both pharmacologic interventions and psychosocial interventions such as problem solving therapy may be efficacious.     

Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = ?0.164 to ?0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = ?0.173 to ?0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.     

Seasonal variation of depressive symptoms in unipolar major depressive disorder

Objectives

Retrospective and cross-sectional studies of seasonal variation of depressive symptoms in unipolar major depression have yielded conflicting results. We examined seasonal variation of mood symptoms in a long-term prospective cohort – the Collaborative Depression Study (CDS).

Methods

The sample included 298 CDS participants from five academic centers with a prospectively derived diagnosis of unipolar major depression who were followed for at least ten years of annual or semi-annual assessments. Generalized linear mixed models were utilized to investigate the presence of seasonal patterns. In a subset of 271 participants followed for at least 20 years, the stability of a winter depressive pattern was assessed across the first two decades of follow-up.

Results

A small increase in proportion of time depressed was found in the months surrounding the winter solstice, although the greatest symptom burden was seen in December through April with a peak in March. The relative burden of winter depressive symptoms in the first decade demonstrated no relationship to that of the second decade. The onset of new episodes was highest October through January, peaking in January.

Conclusions

There exists a small but statistically significant peak in depressive symptoms from the month of the winter solstice to the month of the spring equinox. However, the predominance of winter depressive symptoms did not appear stable over the long-term course of illness.     

Compensatory pituitary-thyroid mechanisms in major depressive disorder

The thyrotropin-releasing hormone (TRH) stimulation test was administered to 47 patients meeting DSM-III criteria for major depressive disorder (with melancholia) and to 19 nondepressed patients. The wide variability of pituitary responses to TRH stimulation noted in the depressed patients provides evidence for the dysregulation of compensatory hypothalamic-pituitary-thyroid function in acute depression. Blunted thyroid-stimulating hormone (TSH) responses to TRH injection were found in 16 depressed (34%) and no nondepressed patients (p less than 0.01). Depressed patients who revealed blunted TSH responses also had blunted prolactin responses to TRH relative to other depressed and nondepressed patient groups (p less than 0.01). These patients (with blunted TSH and prolactin responses) may represent a psychobiologically distinct subgroup of endogenously depressed patients. Augmented (high normal) TSH responses to TRH stimulation were found in eight depressed patients (all women), in contrast to no nondepressed patients. These patients may have a subtle thyroidal dysfunction affecting the underlying endogenous depressive diathesis.     

Risks for suicidality in major depressive disorder

This investigation developed a hierarchical multiple regression model to assess the potential risk factors for suicidality in youths 7 to 17 years old. Variables were assessed in three domains: self-perceptions, demography and diagnosis, and home/environment. The model controlled for major depressive disorder (MDD), which has confounded previous investigations, by evaluating potential risks in a diagnostically heterogenous sample, and then evaluating these risks in a subsample with MDD. Conduct problems and depressive thinking emerged as the most powerful predictors in both samples. Hopelessness, life stress, and maternal psychopathology predicted suicidality only in the total sample. Separation anxiety protected MDD youths. These results suggest that suicidal MDD youths may comprise a distinct subgroup of depressed youths.     

Local contextual processing in major depressive disorder

ObjectiveThe study investigated local contextual processing in patients with major depressive disorder (MDD). This was defined as the ability to utilize predictive contextual information to facilitate detection of predictable versus random targets.MethodWe recorded EEG in 15 MDD patients and 14 age-matched controls. Recording blocks consisted of targets preceded by randomized sequences of standards and by sequences of standards that included a predictive sequence signaling the occurrence of a subsequent target event.ResultsBoth MDD patients and age-matched controls demonstrated a significant reaction time (RT) and P3b latency differences between predicted and random targets. However, patients demonstrated a specific prolongation of these measures during processing of predicted targets, as well as an attenuation of P3b amplitudes for the predictive sequence. In addition, patients target N1 amplitudes were attenuated compared with controls.ConclusionMDD patients were able to utilize predictive context in order to facilitate processing of deterministic targets, however, this ability was limited compared to controls, as demonstrated by context-dependent P3b deficits.SignificanceThese findings suggest that patients with major depression have altered processing of local contextual processing.     

Ego-rotation and object-rotation in major depressive disorder

Mental rotation (MR) performance provides a direct insight into a prototypical higher-level visuo-spatial cognitive operation. Previous studies suggest that progressive slowing with an increasing angle of orientation indicates a specific wing of object-based mental transformations in the psychomotor retardation that occurs in major depressive disorder (MDD). It is still not known, however, whether the ability of object-rotation is associated with the ability of ego-rotation in MDD. The present study was designed to investigate the level of impairment of mental transformation abilities in MDD. For this purpose we tested 33 MDD (aged 18–52 years, 16 women) and 30 healthy control subjects (15 women, age and education matched) by evaluating the performance of MDD subjects with regard to ego-rotation and object-rotation tasks. First, MDD subjects were significantly slower and made more errors than controls in mentally rotating hands and letters. Second, MDD and control subjects displayed the same pattern of response times to stimuli at various orientations in the letter task but not the hand task. Third, in particular, MDD subjects were significantly slower and made more errors during the mental transformation of hands than letters relative to control subjects and were significantly slower and made more errors in physiologically impossible angles than physiologically possible angles in the mental rotation hand task. In conclusion, MDD subjects present with more serious mental rotation deficits specific to the hand than the letter task. Importantly, deficits were more present during the mental transformation in outward rotation angles, thus suggesting that the mental imagery for hands and letters relies on different processing mechanisms which suggest a module that is more complex for the processing of human hands than for letters during mental rotation tasks. Our study emphasises the necessity of distinguishing different levels of impairment of action in MDD subjects.