Agnes Nocon

Heterogeneity of DSM-IV Major Depressive Disorder as a Consequence of Subthreshold Bipolarity

CONTEXT There is growing evidence that major depressive disorder (MDD) might be overdiagnosed at the expense of bipolar disorder (BPD). OBJECTIVES To identify a subgroup of subthreshold BPD among DSM-IV MDD, which is distinct from pure MDD regarding a range of validators of bipolarity, and to examine the pattern of these validators among different groups with affective disorders. DESIGN Ten-year prospective longitudinal and family study including 3 follow-up waves. Data were assessed with the DSM-IV Munich Composite International Diagnostic Interview. SETTING Community sample in Munich, Germany. PARTICIPANTS A total of 2210 subjects (aged 14-24 years at baseline) who completed the third follow-up. MAIN OUTCOME MEASURES Cumulative incidence of pure MDD, BPD, and subthreshold BPD (defined as fulfilling criteria for MDD plus having manic symptoms but never having met criteria for [hypo]mania). RESULTS Among 488 respondents with MDD, 286 (58.6%) had pure MDD and 202 (41.4%) had subthreshold BPD (cumulative incidence, 9.3%). Compared with respondents who had pure MDD, respondents with subthreshold BPD were found to have a significantly increased family history of mania, considerably higher rates of nicotine dependence and alcohol use disorders, rates of panic disorder that were twice as high, and a tendency toward higher rates of criminal acts. Prospective analyses showed that subthreshold BPD converted more often into BPD during follow-up, with DSM-IV criterion D (symptoms observable by others) being of critical predictive relevance. With increasing severity of the manic component, rates for diverse validators accordingly increased (eg, alcohol use disorders, parental mania) or decreased (harm avoidance). CONCLUSIONS Data suggest that MDD is a heterogeneous concept including a large group with subthreshold BPD, which is clinically significant and shares similarities with BPD. Findings might support the need for a broader concept and a more comprehensive screening of bipolarity, which could be substantial for future research and adequate treatment of patients with bipolarity.

Interaction of FKBP5 gene variants and adverse life events in predicting depression onset: results from a 10-year prospective community study.

OBJECTIVE The binding protein FKBP5 is an important modulator of the function of the glucocorticoid receptor, the main receptor of the stress hormone system. This turns the FKBP5 gene into a key candidate for gene-environment interactions, which are considered critical for pathogenesis of stress-related disorders. The authors explored gene-environment interactions between FKBP5 gene variants and adverse life events in predicting the first occurrence of a major depressive episode. METHOD The analyses were based on 884 Caucasians in a 10-year prospective community study. At baseline, they were 14-24 years old and did not fulfill criteria for a major depressive episode. The DSM-IV-based Munich Composite International Diagnostic Interview was used to assess adverse life events preceding baseline and major depressive episodes during follow-up. On the basis of previous findings, five single-nucleotide polymorphisms (SNPs) within the FKBP5 gene were selected for genotyping. RESULTS While the authors did not observe genetic main effects, they found interactions between the five SNPs and traumatic (but not separation) events, with the strongest effect for severe trauma. The effect of trauma on incident major depressive episodes was evident among subjects homozygous for the minor alleles but not subjects with other genotypes. The findings were replicated in the U.K. Environmental Risk Longitudinal Twin Study. CONCLUSIONS These hypothesis-driven results suggest that an interaction between FKBP5 genotype and trauma is involved in the onset of depression. Subjects homozygous for the minor alleles of the investigated FKBP5 SNPs seem to be particularly sensitive to effects of trauma exposure in terms of triggering depression onset.

Agoraphobia and Panic

Background: The relationship of panic attacks (PA), panic disorder (PD) and agoraphobia (AG) is controversial. The aim of the current study is to prospectively examine the 10-year natural course of PA, PD and AG in the first three decades of life, their stability and their reciprocal transitions. Methods: DSM-IV syndromes were assessed via Composite International Diagnostic Interview – Munich version in a 10-year prospective-longitudinal community study of 3,021 subjects aged 14–24 years at baseline. Results: (1) Incidence patterns for PA (9.4%), PD (with and without AG: 3.4%) and AG (5.3%) revealed differences in age of onset, incidence risk and gender differentiation. (2) Temporally primary PA and PD revealed only a moderately increased risk for subsequent onset of AG, and primary AG had an even lower risk for subsequent PA and PD. (3) In strictly prospective analyses, all baseline groups (PA, PD, AG) had low remission rates (0–23%). Baseline PD with AG or AG with PA were more likely to have follow-up AG, PA and other anxiety disorders and more frequent complications (impairment, disability, help-seeking, comorbidity) as compared to PD without AG and AG without PA. Conclusions: Differences in incidence patterns, syndrome progression and outcome, and syndrome stability over time indicate that AG exists as a clinically significant phobic condition independent of PD. The majority of agoraphobic subjects in this community sample never experienced PA, calling into question the current pathogenic assumptions underlying the classification of AG as merely a consequence of panic. The findings point to the necessity of rethinking diagnostic concepts and DSM diagnostic hierarchies.

The interplay of familial depression liability and adverse events in predicting the first onset of depression during a 10-year follow-up

BACKGROUND The aim of the present article is to explore interaction and correlation effects between familial depression liability and selected adverse (separation and traumatic) events in predicting the first onset of a major depressive episode (MDE) in a 10-year prospective longitudinal community survey. METHODS Analyses are based on 1982 subjects (14 to 24 years at baseline) without baseline MDE who participated during the whole study period and for whom diagnostic information about psychopathology in both parents was available. The offsprings familial depression liability was determined by aggregating information on parental depressive symptoms obtained from family history data and direct interviews with parents. Data were assessed with the Munich-Composite International Diagnostic Interview according to its DSM-IV algorithms. RESULTS Adverse events predicted a substantially increased incidence of MDE among respondents with familial liability but not in those without familial liability. There was a significant interaction between familial liability and traumatic events with the strongest effect for the number of severe traumatic events (risk difference = 11.3%; 95% confidence interval = 3.55-19.15). Associations with familial liability were most pronounced for separation events. CONCLUSIONS Adverse events are particularly pathogenic in individuals with familial liability. The involvement of interactions and correlations between familial liability and adversity might depend on type, severity, and number of events. Both processes are suggested to be concomitant rather than exclusive.

Dual Diagnosis in an Inpatient Drug-Abuse Detoxification Unit

In Spain, detoxification in general hospitals plays an important role in the medical care of patients. We aim to provide clinicians with information on the prevalence and correlates of psychiatric co-morbidity in drug abusers in detoxification. A sample of 115 substance-abuse inpatients (mean age 31.9 ± 6.4 years) in a Detoxification Unit of a general university hospital was studied using the Spanish version of the PRISM. Most of the patients had multiple dependence diagnoses and co-morbid axis I or axis II psychiatric disorders. Patients with dual diagnosis showed lower psychosocial functioning than patients without co-morbidity and more dependence diagnoses due to cannabis and sedatives. A total of 80% of the patients successfully completed the detoxification process. The present results enhance the value of detoxification in a general hospital as a first step of the overall treatment strategy.

P01-82 - Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity

Context There is growing evidence that major depressive disorder (MDD) might be overdiagnosed at the expense of bipolar disorders (BPD). Aim To identify a subgroup of subthreshold BPD among DSM-IV MDD, which is distinct from pure MDD regarding validators of bipolarity. Method Data come from the ten-year prospective-longitudinal EDSP-Study, a community survey from Munich, and were assessed with the DSM-IV/M-CIDI. Subthreshold BPD was defined as fulfilling criteria for MDD plus presence of manic symptoms, but never having met criteria for hypomania. Results Among 488 respondents with MDD, about 60% had pure MDD and 40% subthreshold BPD. Compared to pure MDD, the subthreshold BPD group was found to have (a) an increased family history of mania, (b) considerably higher rates of nicotine dependence and alcohol use disorders, (c) twice as high rates of panic disorder, and (d) a tendency towards higher rates of criminal acts. (e) In prospective analyses, subthreshold BPD converted more often into BPD during follow-up with the criterion D (symptoms are observable by others) being of critical predictive relevance. Conclusion Data suggest that MDD is a heterogeneous concept including a large group of subthreshold BPD, which is clinically significant and shares similarities with BPD. Findings might support the need for a broader concept and a more comprehensive screening of bipolarity.

RE-EXAMINING THE DIFFERENTIAL FAMILIAL LIABILITY OF AGORAPHOBIA AND PANIC DISORDER

Controversy surrounds the question of whether agoraphobia (AG) exists as an independent diagnostic entity apart from panic. In favor of this position, AG without panic disorder (PD) in parents was found being unrelated to offsprings’ risk for AG or PD, albeit it may enhance the familial transmission of PD (Nocon et al., Depress Anxiety 2008;25:422–434). However, a recent behavioral genetic analysis (Mosing et al., Depress Anxiety 2009;26:1004–1011) found an increased risk for both PD and AG in siblings of those with AG without PD, casting doubt on whether AG exists independently of PD. Convincing evidence for either position notably requires considering also other anxiety disorders to establish the position of AG relative to the panic/anxiety spectrum.

P01-03 - Biomarkers for changes in self-regulation through cognitive behavioral therapy for depression

Depressed patients show a disturbed hypothalamic-pituitary-adrenal (HPA) axis regulation, resulting in increased cortisol levels, inadequate cortisol suppression following a low dose of dexamethasone, increased concentrations of corticotropin releasing hormone (CRH) in the cerebrospinal fluid, and a blunted adrenocorticotropic hormone (ACTH) response following CRH administration. Treatment with antidepressants, but seemingly also cognitive behavioral therapy (CBT), is associated with an improvement of a disturbed HPA-axis regulation, which can be most sensitively evaluated with the combined dexamethasone (dex)/CRH test. Favorable response to antidepressant treatment can be predicted at an early stage by determining the degree of normalization of HPA-axis function under treatment in a second dex/CRH test. We report about the predictive validity of HPA-axis normalization on the favorable response of CBT in medicated depressed patients. Medicated depressed patients receiving CBT at the Max-Planck-Institute of Psychiatry in Munich are studied using the State-Trait-Angstinventar (STAI), Beck Depression Inventory (BDI), Volitional-Components-Questionnaire (VCQ-3), Emotion-Regulation Questionnaire (EPQ) and the Self-Control and Self-Management Scale (SCMS). Neuroendocrine parameters including measures of HPA-axis regulation are measured before and after therapy via dex/CRH test. Up to the present moment data for N=38 depressed patients have been collected (N=21 male, 25-78 years; N=17 female, 21-80 years). The mean level of depression and anxiety showed a significant decrease between pre- and post-treatment measurement. Measures of perceived self-regulation and self-estimation increased and measures of perceived self-inhibition and inhibition of will decreased. The expected changes in depression, anxiety and self-regulation after treatment with antidepressants and CBT were observed. Endocrine data are currently under analysis.

P01-149 Different pathways into panic disorder, agoraphobia and specific phobia

Background In light of the ongoing debate whether agoraphobia [AG] should be viewed as a severe phobic disorder similar to specific phobia [SPE] or as a complication of panic disorder [PD] we aim to study the vulnerability structure of PD, AG and SPE. Methods 3021 14-24 year-olds from the general population were followed-up over 10 years. DSM-IV syndromes were assessed via computerized M-CIDI interview and vulnerability factors via questionnaires. Associations were assessed with odds ratios from logistic regression. Latent class analysis (LCA) regressed on vulnerability factors was used to derive classes that underlie panic and phobic syndromes and to assess their associations with vulnerability factors. Results 1. Vulnerability patterns were largely similar between PD, AG and SPE. 2. The LCA resulted in a best fitting model with 4 classes: a healthy class, a class with moderate frequency of phobias without PD, a class characterized by PD and AG and moderate frequency of SPE (PDAG class) and one class characterized by high frequency of AG and SPE situational type and lower frequency of PD (AGSIT class). 3. All classes showed different associations with multiple vulnerability measures. Subjects in the PDAG class reported less SPE in parents (OR=0.2; 95% CI=0.0-0.6) and older onset-age of any psychopathology (OR=2.0; 95% CI=1.07-3.6) than the AGSIT class. Discussion We found indications for separate latent classes underlying PD and phobias that were characterized by different vulnerability factors. We interprete the different classes as different vulnerability clusters and evidence of multiple pathways leading to panic and phobias.

P.6.c.007 Pathways into ecstasy use: the role of prior cannabis use and ecstasy availability

AIM To explore the role of cannabis use for the availability of ecstasy as a potential pathway to subsequent first ecstasy use. METHODS Baseline and 4-year follow-up data from a prospective-longitudinal community study of originally 3021 adolescents and young adults aged 14-24 years at baseline were assessed using the standardized M-CIDI and DSM-IV criteria. RESULTS Baseline cannabis users reported at follow-up more frequent access to ecstasy than cannabis non-users. Higher cannabis use frequencies were associated with increased ecstasy availability reports. Logistic regression analyses revealed that cannabis use and availability of ecstasy at baseline are predictors for incident ecstasy use during the follow-up period. Testing simultaneously the impact of prior cannabis use and ecstasy availability including potential confounders, the association with cannabis use and later ecstasy use was confirmed (OR=6.3; 95%CI=3.6-10.9). However, the association with ecstasy availability was no longer significant (OR=1.2; 95%CI=0.3-3.9). CONCLUSIONS Results suggest that cannabis use is a powerful risk factor for subsequent first onset of ecstasy use and this relation cannot be sufficiently explained by availability of ecstasy in the observation period.