Major Depressive Disorder Illness Research Articles

359. Effects of Developmental Age and Length of Illness in Major Depressive Disorder: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies

359. Effects of Developmental Age and Length of Illness in Major Depressive Disorder: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies

Which biomarkers are associated with response to antidepressants and severity of illness in major depressive disorder? Preliminary results

Which biomarkers are associated with response to antidepressants and severity of illness in major depressive disorder? Preliminary results

Individual variation in brain network topology is linked to course of illness in major depressive disorder.

Major depressive disorder (MDD) is a chronic and highly recurrent disorder. The functional connectivity in depression is affected by the cumulative effect of course of illness. However, previous neuroimaging studies on abnormal functional connection have not mainly focused on the disease duration, which is seen as a secondary factor. Here, we used a data-driven analysis (multivariate distance matrix regression) to examine the relationship between the course of illness and resting-state functional dysconnectivity in MDD. This method identified a region in the anterior cingulate cortex, which is most linked to course of illness. Specifically, follow-up seed analyses show this phenomenon resulted from the individual differences in the topological distribution of three networks. In individuals with short-duration MDD, the connection to the default mode network was strong. By contrast, individuals with long-duration MDD showed hyperconnectivity to the ventral attention network and the frontoparietal network. These results emphasized the centrality of the anterior cingulate cortex in the pathophysiology of the increased course of illness and implied critical links between network topography and pathological duration. Thus, dissociable patterns of connectivity of the anterior cingulate cortex is an important dimension feature of the disease process of depression.

White matter fiber microstructure is associated with prior hospitalizations rather than acute symptomatology in major depressive disorder.

Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness. A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects. Disease state (pFWE < 0.042) and number of hospitalizations (pFWE< 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF. Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.

Social cognitive abilities predict psychosocial dysfunction in major depressive disorder.

Major depressive disorder (MDD) is associated with social cognitive deficits (e.g., poor affect recognition and impaired theory of mind). However, the contribution of social cognitive issues to psychosocial dysfunction in MDD (e.g., occupational functioning and interpersonal relationships) has not been investigated. The current study evaluated the relationship between specific social cognitive domains (e.g., prosody interpretation) and psychosocial dysfunction in subjects with lifetime MDD, as well as currently depressed, remitted, and healthy controls (HCs) subjects. Data were obtained from 213 participants in the Cognitive Function and mood study (CoFaMS), a cross-sectional study of mood, social cognition, cold cognition, and psychosocial functioning in mood disorders. Participants' (current MDD n=42, remitted MDD n=69, and HCs n=102) social cognitive abilities were assessed using the Social Perception subtest of the Wechsler Adult Intelligence Scale, and psychosocial dysfunction was clinically evaluated with the Functioning Assessment Short Test (FAST). The results indicated that prosody interpretation, but not facial affect or meaning interpretation, was associated with psychosocial dysfunction in subjects with lifetime MDD, as well as remitted MDD subjects relative to HCs. In contrast, social cognition was not associated with functioning in participants with current MDD or in HCs. These results suggest that the relationship between social cognition and psychosocial functioning differs between the acute and remitted stage of illness in MDD, and that prosody interpretation should be considered a treatment target in patients with residual psychosocial issues.

Epidemiology and Heritability of Major Depressive Disorder, Stratified by Age of Onset, Sex, and Illness Course in Generation Scotland: Scottish Family Health Study (GS:SFHS).

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD.

Cognitive impairment in euthymic major depressive disorder: a meta-analysis

There is evidence to suggest that cognitive deficits might persist beyond the acute stages of illness in major depressive disorder (MDD). However, the findings are somewhat inconsistent across the individual studies conducted to date. Our aim was to conduct a systematic review and meta-analysis of existing studies that have examined cognition in euthymic MDD patients. Following a systematic search across several publication databases, meta-analyses were conducted for 27 empirical studies that compared euthymic adult MDD patients (895 participants) and healthy controls (997 participants) across a range of cognitive domains. The influence of demographic variables and confounding factors, including age of onset and recurrent episodes, was examined. Compared with healthy controls, euthymic MDD patients were characterized by significantly poorer cognitive functions. However, the magnitude of observed deficits, with the exception of inhibitory control, were generally modest when late-onset cases were excuded. Late-onset cases demonstrated significantly more pronounced deficits in verbal memory, speed of information processing and some executive functions. Cognitive deficits, especially poor response inhibition, are likely to be persistent features, at least of some forms, of adult-onset MDD. More studies are necessary to examine cognitive dysfunction in remitted psychotic, melancholic and bipolar spectrum MDD. Cognitive deficits overall appear to be more common among patients with late-onset depression, supporting the theories suggesting that possible vascular and neurodegenerative factors play a role in a substantial number of these patients.

Duration of untreated illness in anxiety and mood disorders

A prolonged duration of untreated illness (DUI) has been indicated as a negative prognostic factor of clinical outcome in schizophrenia(1),affective(2) and anxiety disorders(3). The present study analyzes DUI in anxiety/mood disorders. Study sample included 729 patients:181 Major Depressive Disorder, 115 Bipolar I Disorder, 186 Bipolar II Disorder, 100 Generalized Anxiety Disorder, 96 Panic Disorder and 51 Obsessive-Compulsive Disorder. The main demographic and clinical (age at onset, age at first treatment, DUI) variables were compared between groups using oneway ANOVA, t-tests or chi-squared tests. DUI was defined as the interval between the onset of the disorder and the first adequate treatment.Patients with MDD showed a shorter DUI (F= 25.159; p> 0.0001) whereas patient with BDII showed a longer DUI (F= 12.680; p> 0.0001) compared to the other groups. Present findings indicate that patients with affective/anxiety disorders present significant differences in DUI. It is of clinical interest to assess the extent to which delays until beginning an appropriate treatment influence the course of these disorders.1. Altamura AC, Bassetti R, Sassella F, Salvatori D, Mundo E. Duration of untreated psychosis as a predictor of outcome in first-episode schizophrenia: a retrospective study. Schizophr Res, 2001; 52 (1-2): 29-36.2. Altamura AC, Dell'Osso B, Mundo E, Dell'Osso L. Duration of untreated illness in major depressive disorder: a naturalistic study. Int J Clin Pract 2007 b, 61(10): 1697-700.3. Altamura AC, Santini A, Salvadori D, Mundo E. Duration of untreated illness in panic disorders: a poor outcome risk factor? Neuropsychiatric disease and treatment 2005, 1(4): 345-347.

Duration of untreated illness in major depressive disorder: a naturalistic study

Most of the studies on the duration of untreated illness (DUI) as a possible predictor of the clinical outcome and the course have focused on the psychotic disorders. The present naturalistic study was aimed to evaluate the possible relationship between the DUI and some clinical characteristics of a sample of patients with major depressive disorder (MDD). Sixty-eight patients with MDD, according to the Diagnostic and Statistical Manual of Mental Disorders, IV Edition, Text Revision (DSM-IV-TR) criteria, followed-up for 4 years, were selected, interviewed and their clinical charts reviewed. The DUI was defined as the interval between the onset of the first major depressive episode and the first adequate antidepressant treatment. The sample was divided in two groups according to a DUI <or= 12 months (n = 45) and > 12 months (n = 23). The main demographic and clinical course variables were compared between the two groups using t-tests or chi-squared tests. Patients with a DUI > 12 months were more frequently women (chi2 = 4.005, p = 0.045), had an earlier onset (t = 2.515, p = 0.014), a longer duration of illness (t = -2.483, p = 0.016), a higher number of recurrences (t = -2.262, p = 0.027) and had more frequently comorbid Axis I disorders with onset later than MDD (chi2 = 5.595, p = 0.05). These findings suggest that a longer DUI may negatively influence the clinical course of MDD. Further studies on larger samples are warranted to confirm these preliminary results.

Randomized, Placebo-Controlled Trial of Fluoxetine for Acute Treatment of Minor Depressive Disorder

OBJECTIVE: Minor depressive disorder is both common and associated with significant psychosocial impairment. This study examined antidepressant treatment efficacy in a large group of patients with minor depressive disorder. METHOD: One hundred sixty-two patients with minor depressive disorder were randomly assigned to receive fluoxetine or placebo in a 12-week, double-blind study; 73% (59 of 81) of the patients in each treatment group completed the study. Patients were evaluated weekly with standard depression rating instruments and measures of psychosocial impairment. Hypotheses were tested by last-observation-carried-forward analysis of variance (ANOVA) and confirmed by mixed (random-effects) regression analysis. RESULTS: At baseline, minor depressive disorder patients were mildly to moderately depressed, with a corresponding degree of functional impairment. Over 12 weeks of treatment, both ANOVA and mixed regression showed fluoxetine to be superior to placebo as indicated by significantly greater improvement of fluoxetine-treated patients in scores on the 30-item clinician-rated Inventory of Depressive Symptomatology, the 17-item and 21-item Hamilton Depression Rating Scale, the Beck Depression Inventory, and the Clinical Global Impression severity scale. Improvement in Global Assessment of Functioning Scale score was significantly greater for the fluoxetine group in mixed regression analysis only. Patients in both treatment groups reported a similar number and severity of adverse events during the 12-week treatment period. CONCLUSIONS: Clinicians frequently encounter minor depressive disorder either as a prodromal or residual phase of illness in major depressive disorder or as de novo minor depressive disorder episodes. Fluoxetine is significantly superior to placebo in reducing minor depressive disorder symptoms within a 12-week period. Improvement in psychosocial function with fluoxetine may take longer than 12 weeks.