Reconsidering the prognosis of major depressive disorder across diagnostic boundaries: full recovery is the exception rather than the rule.

BACKGROUND: Major depressive disorder (MDD) is often handled as an episodic and isolated disorder, resulting in an optimistic view about its prognosis. Herein, we test the idea that the prognosis of MDD changes if we vary the perspective in terms of (1) a longer time frame and (2) a broader diagnostic conceptualisation including dysthymia, (hypo)mania and anxiety disorders as relevant outcomes. METHODS: Patients with current MDD at baseline (n = 903) and available 2-, 4-, and/or 6-year follow-up assessments were selected from the Netherlands Study of Depression and Anxiety, a psychiatric cohort study. Combining psychiatric DSM-IV-based diagnoses and life-chart data, patient course trajectories were classified as (1) recovered (no diagnoses at 2-year follow-up or thereafter), (2) recurrent without chronic episodes, (3) recurrent with chronic episodes or (4) consistently chronic since baseline. A chronic episode was defined as having a current diagnosis at the follow-up assessment and consistent symptoms over 2 years. Proportions of course trajectories were provided moving from a short, narrow perspective (2-year follow-up, considering only MDD diagnosis) to a long, broad perspective (6-year follow-up, including MDD, dysthymia, (hypo)mania and anxiety diagnoses). RESULTS: With the short, narrow perspective, the recovery rate was 58% and 21% had a chronic episode. However, in the long, broad perspective the recovery rate was reduced to 17%, while 55% of the patients experienced chronic episodes. CONCLUSIONS: Results from a long and rigorous follow-up in a large cohort suggests that most MDD patients have an unfavourable prognosis. Longer follow-up and broader diagnostic conceptualisation show that the majority of patients have a disabling and chronic disorder. Conceptualising and handling MDD as a narrowly defined and episodic disorder may underestimate the prognosis of the majority of depressed patients and, consequently, the type of care that is appropriate.

Getting under the skin: Does biology help predict chronicity of depression?

BACKGROUND: Depressed patients are at risk of an unfavourable course including chronic episodes. Various psychiatric characteristics have shown to be predictive of depression's course trajectory, but whether indicators of somatic health further contribute to course prediction remains unclear. This study aimed to identify somatic health indicators (i.e. biomarkers, health status and lifestyle) that predict 2-year chronicity above and beyond an extensive list of sociodemographic and psychiatric characteristics. METHODS: Data are from patients with current depression at baseline (n = 903) and available 2-year follow-up participating in a longitudinal cohort study. Baseline demographic, psychiatric and somatic health indicators were associated with 2-year course trajectories, classified as non-chronic versus chronic RESULTS: At 2-year follow up, 40% of the patients showed a chronic course. Of the twenty tested somatic health indicators, short sleep and high interleukin-6 improved the regression model predicting chronicity with a significant, but modest, effect (ROC = 0.78; p = 0.03). LIMITATIONS: Due to the observational design we did not have the ability to reliably consider the impact of psychiatric treatment. More elaborate information on somatic health such as dietary patterns would strengthen the study. CONCLUSIONS: This study showed that short sleep duration and high interleukin-6 contributed significantly to the regression model as independent predictors, suggestive of clinical implications for patients with sleep disturbances and elevated inflammation levels. Other somatic health indicators did not add to the model. Overall, somatic health indicators showed modest additive value for predicting chronic course above and beyond sociodemographic and psychiatric indicators.

[Complete recovery from depression is the exception rather than the rule: prognosis of depression beyond diagnostic boundaries]. / Volledig herstel van depressie is eerder uitzondering dan regel.

OBJECTIVE: To investigate whether the course of depression changes when (a) follow-up duration is longer and (b) in addition to depression other mood and anxiety disorders are considered as outcome measures. DESIGN: Longitudinal observational cohort study. METHOD: We selected patients from the Netherlands Study of Depression and Anxiety (NESDA) who had active depression at baseline (n=903) and for whom data from the 2, 4 and/or 6 year measurements were available. Using DSM-IV diagnoses and data from the 'Life chart interview', we divided participants in one of the following four course categories: (1) recovered (no diagnosis at 2-year measurement or later), (2) recurring without chronic episodes, (3) recurring with chronic episodes or (4) consistent chronic depression since baseline. We looked at the distribution of patients over the course categories from a short, diagnostically narrow perspective (over 2 years, only looking at depression) to a long, diagnostically broad perspective (over 6 years, looking at depression, dysthymia, hypomania, mania and anxiety). RESULTS: In the short, diagnostically narrow perspective, 58% of participants had recovered and 21% met the criteria for a chronic episode. In the long, diagnostically broad perspective however, only 17% had recovered while 55% had chronic episodes. CONCLUSION: Monitoring patients with depression over a longer period and with broader outcome measures (depression and related psychiatric disorders belonging to the mood disorder spectrum) shows that the course of depression is unfavourable and chronic for the majority. Conceptualising depression as a defined episodic disorder underestimates the severity of the prognosis for many patients and, as a consequence, the type of care indicated.

Using Clinical Characteristics to Identify Which Patients With Major Depressive Disorder Have a Higher Genetic Load for Three Psychiatric Disorders.

BACKGROUND: Limited successes of gene finding for major depressive disorder (MDD) may be partly due to phenotypic heterogeneity. We tested whether the genetic load for MDD, bipolar disorder, and schizophrenia (SCZ) is increased in phenotypically more homogenous MDD patients identified by specific clinical characteristics. METHODS: Patients (n = 1539) with a DSM-IV MDD diagnosis and control subjects (n = 1792) were from two large cohort studies (Netherlands Study of Depression and Anxiety and Netherlands Twin Register). Genomic profile risk scores (GPRSs) for MDD, bipolar disorder, and SCZ were based on meta-analysis results of the Psychiatric Genomics Consortium. Regression analyses (adjusted for year of birth, sex, three principal components) examined the association between GPRSs with characteristics and GPRSs with MDD subgroups stratified according to the most relevant characteristics. The proportion of liability variance explained by GPRSs for each MDD subgroup was estimated. RESULTS: GPRS-MDD explained 1.0% (p = 4.19e-09) of MDD variance, and 1.5% (p = 4.23e-09) for MDD endorsing nine DSM symptoms. GPRS-bipolar disorder explained 0.6% (p = 2.97e-05) of MDD variance and 1.1% (p = 1.30e-05) for MDD with age at onset <18 years. GPRS-SCZ explained 2.0% (p = 6.15e-16) of MDD variance, 2.6% (p = 2.88e-10) for MDD with higher symptom severity, and 2.3% (p = 2.26e-13) for MDD endorsing nine DSM symptoms. An independent sample replicated the same pattern of stronger associations between cases with more DSM symptoms, as compared to overall MDD, and GPRS-SCZ. CONCLUSIONS: MDD patients with early age at onset and higher symptom severity have an increased genetic risk for three major psychiatric disorders, suggesting that it is useful to create phenotypically more homogenous groups when searching for genes associated with MDD.

Prevalence of ADHD symptoms across clinical stages of major depressive disorder.

BACKGROUND: Depression and ADHD often co-occur in clinical samples. Depression severity may be linked to ADHD symptomatology. We therefore assessed ADHD symptoms across clinical stages of major depressive disorder (MDD). METHODS: We used 4-year follow-up data of the Netherlands Study of Depression and Anxiety (September 2008 until April 2011), including healthy controls, groups with remitted and current MDD (N=2053; age range 21-69 years; 66.8% females). Probable ADHD was defined as having current ADHD symptoms on the Conners Adult ADHD Rating Scale and a positive score on childhood or early-adolescent ADHD indicators. We examined ADHD symptom rates across (i) those with and without lifetime MDD, (ii) clinical characteristics of MDD including severity, course and outcomes, (iii) clinical stages of MDD. RESULTS: (i) The prevalence of ADHD symptoms was 0.4% in healthy controls, 5.7% in remitted MDD and 22.1% in current MDD (OR=4.5; 95% CI 3.1-6.5). (ii) ADHD symptom rates and odds were significantly increased among those with more severe depression (29.4%; OR=6.8; 95% CI 2.9-16.1), chronic depression (21.8%; OR=3.8; 95% CI 2.5-5.7), earlier age of onset of depressive symptoms (9.9%; OR=1.5; 95% CI 1.0-2.3), and comorbid anxiety disorders (29.0%; OR=3.4; 95% CI 2.0-5.7). (iii) ADHD symptom rates increased across clinical stages of MDD, up to 22.5% in chronic MDD. LIMITATIONS: We used self-reports on ADHD symptoms. Also, clinical staging models have not yet been validated for mental disorders. CONCLUSIONS: ADHD symptoms are very common among MDD patients, especially among those in recurrent and chronic stages of MDD. Considering ADHD may be an important step forward in improving the treatment of depression.

Clinical staging of major depressive disorder: an empirical exploration.

OBJECTIVE: Clinical staging has been proposed to supplement psychiatric diagnoses. We examined the construct and predictive validity of a clinical staging model for major depressive disorder (MDD) that distinguishes 8 consecutive stages (0, 1A, 1B, 2, 3A, 3B, 3C, 4) based on symptom severity (Inventory of Depressive Symptomatology [IDS]) and duration (Life Chart Interview) and number of episodes (Composite International Diagnostic Interview [CIDI] based on DSM-IV criteria). METHOD: This study is a secondary data analysis based on baseline data (collected 2004-2007) and 2-year follow-up assessment (collected 2006-2009) from the Netherlands Study of Depression and Anxiety. 2,333 baseline participants were assigned to the 8 stages of the clinical staging model for MDD, and 2,012 participants were followed up after 2 years. For construct validity, differences between stages in clinical characteristics (eg, severity [IDS], age at onset [CIDI], and comorbid anxiety [CIDI]) were studied. Predictive validity was measured by the extent to which baseline stages predicted 2-year follow-up outcomes (eg, MDD presence [CIDI]). RESULTS: Later stages scored significantly poorer than early stages on most clinical characteristics and follow-up outcomes (all overall P values < .001), confirming validity of the model. This pattern was especially evident in mostly preclinical stages (0, 1A, 1B, 2). Among clinical stages (2, 3A, 3B, 3C, 4), stages characterized by long-lasting symptomatology had at baseline similar and the highest scores (IDS scores: stage 3A = 37.1; stage 4 = 39.0; disability scores: stage 3A = 36.7; stage 4 = 40.6) and compared to preclinical stages had increased probability of having MDD at 2-year follow-up (stage 3A: OR = 4.3; 95% CI, 2.8-6.7; stage 4: OR = 8.1; 95% CI, 5.7-11.5). CONCLUSIONS: This study showed reasonable validity for an MDD staging model that based its stages purely on clinical characteristics. Results suggest that, contrary to the number of episodes, duration of exposure to the depressed state best characterizes clinical (later) stages of MDD. Future studies should test whether modifications to these clinical stages improve the validity of the model.