Didi Rhebergen

The 7-year course of depression and anxiety in the general population

Rhebergen D, Batelaan NM, de Graaf R, Nolen WA, Spijker J, Beekman ATF, Penninx BWJH. The 7‐year course of depression and anxiety in the general population.

The three-year naturalistic course of major depressive disorder, dysthymic disorder and double depression

BACKGROUND Recent studies support a distinction between acute and chronic forms of depression, which contrasts the single-disease hypothesis for depressive disorders. Insight into the (determinants of) the 3-year naturalistic course of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD) may contribute to this debate. METHODS Data were derived from NEMESIS, an epidemiologic survey in the adult population of the Netherlands. 400 Respondents who met the Composite International Diagnostic Interview (CIDI) criteria of MDD and/or Dysth were selected. Cox proportional hazards analyses and Linear Mixed Models were conducted to examine 3-year course trajectories of MDD, Dysth and DD and determinants for course. RESULTS Adjusted analyses showed similar course trajectories for Dysth and DD, which were significantly worse than the course for MDD. Determinants of unfavorable course were neuroticism and poor functioning. LIMITATIONS Attrition was higher among persons with Dysth. However, since attrition is generally associated with poorer outcome, this would indicate that differences in course may even have been larger in reality. CONCLUSIONS Dysth and DD involve a similar course which is worse than the course of MDD only. These results do not support a distinction between Dysth and DD. Duration of symptoms and level of functioning may serve as two clinically relevant classifying dimensions within the broad category of depressive disorders.

Trajectories of recovery of social and physical functioning in major depression, dysthymic disorder and double depression: A 3-year follow-up

BACKGROUND Depressive disorders have a large impact on psychosocial functioning. Since lower functioning predicts recurrence of a depressive episode, insight into the post-morbid course of psychosocial functioning of persons with different depressive disorders may facilitate recurrence prevention. METHODS Data were derived from NEMESIS, an epidemiologic survey in the adult population in the Netherlands. Respondents, who met the CIDI criteria of major depression (MDD; n=102), dysthymic disorder (Dysth; n=66) or double depression (DD; n=73) at baseline, and recovered during three year follow-up, were included; as was a control group without any diagnosis (NoDiag, n=4140). Functioning was assessed using the Groningen Social Disability Schedule (GSDS) and the SF-36 physical health summary-scale. Linear Mixed Models were conducted to compare 3-year trajectories of functioning across depressive groups and with NoDiag group. RESULTS Compared to NoDiag, all depressed groups were significantly impaired on social and physical functioning. Dysth and DD had a lower level of post-morbid physical functioning compared to MDD (after 1 and 3 years respectively: Dysth: B=-13.8, p=.002 and B=-8.11, p=.09; DD: B=-8.9, p=.03 and B=-9.1, p=.05). Determinants for impaired social functioning (neuroticism) and for impaired physical functioning (age, comorbid somatic disorders and neuroticism) were identified. LIMITATIONS Attrition was higher among persons with a depression. Inclusion of the drop-outs would most likely have resulted in stronger associations, since we expect lower functioning among the drop-outs. CONCLUSION This study indicates the long-term debilitating effects of psychopathology, even after recovery of depressive disorders. Duration of the index symptoms appears to be associated with impaired functioning, since especially those with Dysthymia (either with or without a MDD) showed slower and less recovery of functioning.

Stability and transitions of depressive subtypes over a 2-year follow-up

BACKGROUND Identifying depressive subtypes is an important tool in reducing the heterogeneity of major depressive disorder. However, few studies have examined the stability of putative subtypes of depression over time. METHOD The sample included 488 persons from the Netherlands Study of Depression and Anxiety (NESDA) who had major depressive disorder at baseline and at the 2-year follow-up assessment. A latent transition analysis (LTA) was applied to examine the stability of depressive subtypes across time-points. Differences in demographic, clinical, psychosocial and health correlates between subtypes were evaluated in a subsample of persons with stable subtypes. RESULTS Three subtypes were identified at each time-point: a moderate subtype (prevalence T0 39%, T1 42%), a severe typical subtype (T0 30%, T1 25%), and a severe atypical subtype (T0 31%, T1 34%). The LTA showed 76% stability across the 2-year follow-up, with the greatest stability in the severe atypical class (79%). Analyses of correlates in the stable subtypes showed a predominance of women and more overweight and obesity in the severe atypical subtype, and a greater number of negative life events and higher neuroticism and functioning scores in the severe typical subtype. CONCLUSIONS Subtypes of major depressive disorder were found to be stable across a 2-year follow-up and to have distinct determinants, supporting the notion that the identified subtypes are clinically meaningful.

Course trajectories of unipolar depressive disorders identified by latent class growth analysis

BACKGROUND Current classification of unipolar depression reflects the idea that prognosis is essential. However, do DSM categories of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD=MDD+Dysth) indeed adequately represent clinically relevant course trajectories of unipolar depression? Our aim was to test DSM categories (MDD, Dysth and DD) in comparison with empirically derived prognostic categories, using a prospectively followed cohort of depressed patients. METHOD A large sample (n=804) of out-patients with unipolar depression were derived from a prospective cohort study, the Netherlands Study of Depression and Anxiety (NESDA). Using latent class growth analysis (LCGA), empirically derived 2-year course trajectories were constructed. These were compared with DSM diagnoses and a wider set of putative predictors for class membership. RESULTS Five course trajectories were identified, ranging from mild severity and rapid remission to high severity and chronic course trajectory. Contrary to expectations, more than 50% of Dysth and DD were allocated to classes with favorable course trajectories, suggesting that current DSM categories do not adequately represent course trajectories. The class with the most favorable course trajectory differed on several characteristics from other classes (younger age, more females, less childhood adversity, less somatic illnesses, lower neuroticism, higher extraversion). Older age, earlier age of onset and lower extraversion predicted poorest course trajectory. CONCLUSIONS MDD, Dysth and DD did not adequately match empirically derived course trajectories for unipolar depression. For the future classification of unipolar depression, it may be wise to retain the larger, heterogeneous category of unipolar depression, adopting cross-cutting dimensions of severity and duration to further characterize patients.

Psychiatric and Medical Comorbidities: Results from a Bipolar Elderly Cohort Study

OBJECTIVE Bipolar disorder is associated with concurrent mental and physical disorders. Although well studied among younger adults, less is known about concurrent morbidity among older patients. This is important because comorbidity may increase with age and optimal treatment requires awareness of medical and psychiatric comorbidities. This study analyzed psychiatric and medical comorbidity in a Dutch bipolar elderly cohort. METHODS This cross-sectional descriptive study included demographic and clinical data on 101 bipolar patients aged 60 and over (mean age: 68.9 ± 7.8 years); 53.4% were women. Psychiatric diagnoses were confirmed by semistructured diagnostic interviews. Somatic history, including current somatic complaints, was obtained by interview. Medication and indicators of metabolic syndrome were obtained via record review. RESULTS Most patients received outpatient care. Bipolar I disorder was diagnosed in 56.4% of patients, and 75.6% had an onset of first affective symptoms before age 50. The prevalence rates of psychiatric comorbidities were low, except for lifetime alcohol dependence (24.8%) and abuse (13.9%). On average, there were 1.7 (SD: 1.6) medical comorbid conditions, predominantly hypertension (27.8%), arthrosis (29.1%), and allergies (25.6%). Polypharmacy was found in 31.7% of patients and metabolic syndrome in 28.7%. CONCLUSION Psychiatric comorbidity (especially anxiety disorders) was relatively uncommon, except for substance use disorder. Geriatric bipolar patients had on average two comorbid medical conditions and relatively high medication use. Findings underline the need to assess for comorbid conditions in bipolar elders, thereby enabling tailored treatment to optimize the general condition of these patients.

Hypothalamic–pituitary–adrenal axis activity in older persons with and without a depressive disorder

BACKGROUND Altered functioning of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been associated with depression, but findings have been inconsistent. Among older depressed persons, both hyperactivity and hypo-activity of the HPA-axis were demonstrated. However, most studies were population-based studies, with single cortisol measurements, lacking insight into diurnal patterns of HPA-axis functioning. We aim to provide insight into functioning of the HPA-axis, assessed by various salivary cortisol samples, in depressed older adults and non-depressed controls. METHODS Data were derived from the Netherlands Study of Depression in Older Persons. Cortisol levels of older persons without a lifetime diagnosis of depression and/or anxiety (n=109) were compared with older persons with a 6-month major depression diagnosis (n=311). ANCOVA analyses and random coefficient analysis on the four morning cortisol samples were performed. A possible U-shaped association between cortisol and depression status was examined. RESULTS Depressed older persons showed higher morning cortisol levels at awakening (T1) and a less dynamic awakening response compared to non-depressed older persons. Dexamethasone suppression did not differ across groups. No U-shaped association between HPA-axis activity and depression was observed. CONCLUSION We demonstrated a hypercortisolemic state and a diminished ability to respond to the stress of awakening among depressed older persons. Previously it was shown, that hypercortisolemic states may indicate a lifelong biological vulnerability for depression. Our findings expand on previous literature by demonstrating that in older persons the HPA-axis may become less responsive to stress, culminating in a further dysregulation of the diurnal cortisol-rhythm, superimposed on - possibly lifelong - hypercortisolemic states.

Predicting the Naturalistic Course of Major Depressive Disorder Using Clinical and Multimodal Neuroimaging Information: A Multivariate Pattern Recognition Study

Background A chronic course of major depressive disorder (MDD) is associated with profound alterations in brain volumes and emotional and cognitive processing. However, no neurobiological markers have been identified that prospectively predict MDD course trajectories. This study evaluated the prognostic value of different neuroimaging modalities, clinical characteristics, and their combination to classify MDD course trajectories. Methods One hundred eighteen MDD patients underwent structural and functional magnetic resonance imaging (MRI) (emotional facial expressions and executive functioning) and were clinically followed-up at 2 years. Three MDD trajectories (chronic n = 23, gradual improving n = 36, and fast remission n = 59) were identified based on Life Chart Interview measuring the presence of symptoms each month. Gaussian process classifiers were employed to evaluate prognostic value of neuroimaging data and clinical characteristics (including baseline severity, duration, and comorbidity). Results Chronic patients could be discriminated from patients with more favorable trajectories from neural responses to various emotional faces (up to 73% accuracy) but not from structural MRI and functional MRI related to executive functioning. Chronic patients could also be discriminated from remitted patients based on clinical characteristics (accuracy 69%) but not when age differences between the groups were taken into account. Combining different task contrasts or data sources increased prediction accuracies in some but not all cases. Conclusions Our findings provide evidence that the prediction of naturalistic course of depression over 2 years is improved by considering neuroimaging data especially derived from neural responses to emotional facial expressions. Neural responses to emotional salient faces more accurately predicted outcome than clinical data.

Panic attacks as a dimension of psychopathology: evidence for associations with onset and course of mental disorders and level of functioning

OBJECTIVE One of the proposed revisions for DSM-5 is to rate panic attacks as a separate dimension across all mental disorders. The idea is that panic attacks occurring outside panic disorder are a dimension predicting important clinical outcomes. The aim of this study was to validate the proposition for DSM-5 that panic attacks have predictive value for overall psychopathology onset, course, and functioning. METHOD Data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), a prospective population-based study. Using the Composite International Diagnostic Interview (with classifications based on DSM-III-R), 5,571 subjects were selected who had (1) no panic history, (2) a history of panic attacks (but no panic disorder), (3) current panic attacks, or (4) current panic disorder. The impact of panic status on the prevalence of anxiety, affective, alcohol, and any mental disorders; on the onset and persistence of these disorders during 3-year follow-up; and on levels of functioning during 3-year follow-up (as assessed with the 36-Item Short-Form Health Survey) was examined. RESULTS Current panic attacks outside the realm of panic disorder were associated with increased prevalence of mental disorders (χ2(3) = 490.6; P < .001), increased onset of mental disorders (hazard ratio = 4.42; 95% CI, 2.88-6.80), persistence of mental disorders (odds ratio = 2.72; 95% CI, 1.53-4.82), and impaired functioning during 3-year follow-up (F = 69.67; P < .001). Although the impact was smaller than for panic disorder, the associations identified for panic attacks were consistent and significant and were, to a lesser extent, also found for a history of panic attacks. CONCLUSIONS Given the consistent impact of panic attacks on various aspects of psychopathology, the proposition to dimensionally rate panic attacks across all mental disorders may be of great value for clinical care.

Two-year course trajectories of anxiety disorders: do DSM classifications matter?

OBJECTIVE Anxiety disorders have been shown to differ in their course, but it is unknown whether DSM-categories represent clinically relevant course trajectories. We aim to identify anxiety course trajectories using a data-driven method and to examine whether these course trajectories correspond to DSM-categories or whether other clinical indicators better differentiate them. METHOD 907 patients with panic disorder with agoraphobia, panic disorder without agoraphobia , agoraphobia, social phobia, or generalized anxiety disorder according to DSM-IV criteria were derived from a prospective cohort study (Netherlands Study of Depression and Anxiety). Baseline data were collected between September 2004 and February 2007; follow-up data, between October 2006 and March 2009. Latent class growth analysis was conducted, based on symptoms of anxiety and avoidance assessed with the Life Chart Interview covering a 2-year time period. Identified course trajectories were compared with DSM-IV diagnoses and a wider set of predictors. RESULTS We identified a class with minimal symptoms over time (41.7%), a moderately severe chronic class (42.8%), and a severe chronic class (15.4%). Panic disorder with agoraphobia (OR = 2.14; 95% CI, 1.48-3.09) and social phobia (OR = 1.97; 95% CI, 1.46-2.68) predicted moderately severe chronicity; panic disorder with agoraphobia (OR = 2.70; 95% CI, 1.66-4.40), social phobia (OR = 2.46; 95% CI, 1.62-3.74), and generalized anxiety disorder (OR = 1.86; 95% CI, 1.23-2.82) predicted a severe chronic course. However, baseline severity, duration of anxiety, and disability better predicted severe chronic course trajectories than DSM-categories. Additionally, partner status, age at onset, childhood trauma, and comorbid depressive disorder predicted chronic courses. CONCLUSIONS Course of anxiety was pleomorphic with over 40% having a favorable course, thereby questioning the common notion of chronicity of anxiety disorders. Severity, duration of anxiety, and disability were able to better identify severe chronic course trajectories as compared with DSM-IV categories. These findings facilitate the identification of chronic course trajectories of anxiety disorders in clinical care and support current debates on staging and profiling of mental disorders.