Prediction of transition from common adolescent bipolar experiences to bipolar disorder: 10-year study.

BACKGROUND: Although (hypo)manic symptoms are common in adolescence, transition to adult bipolar disorder is infrequent. AIMS: To examine whether the risk of transition to bipolar disorder is conditional on the extent of persistence of subthreshold affective phenotypes. METHOD: In a 10-year prospective community cohort study of 3021 adolescents and young adults, the association between persistence of affective symptoms over 3 years and the 10-year clinical outcomes of incident DSM-IV (hypo)manic episodes and incident use of mental healthcare was assessed. RESULTS: Transition to clinical outcome was associated with persistence of symptoms in a dose-dependent manner. Around 30-40% of clinical outcomes could be traced to prior persistence of affective symptoms. CONCLUSIONS: In a substantial proportion of individuals, onset of clinical bipolar disorder may be seen as the poor outcome of a developmentally common and usually transitory non-clinical bipolar phenotype.

Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety disorder.

CONTEXT: Controversy surrounds the diagnostic categorization of generalized anxiety disorder (GAD). OBJECTIVES: To examine the incidence, comorbidity, and risk patterns for anxiety and depressive disorders and to test whether developmental features of GAD more strongly support a view of this condition as a depressive as opposed to an anxiety disorder. DESIGN: Face-to-face, 10-year prospective longitudinal and family study with as many as 4 assessment waves. The DSM-IV Munich Composite International Diagnostic Interview was administered by clinically trained interviewers. SETTING: Munich, Germany. PARTICIPANTS: A community sample of 3021 individuals aged 14 to 24 years at baseline and 21 to 34 years at last follow-up. MAIN OUTCOME MEASURES: Cumulative incidence of GAD, other anxiety disorders (specific phobias, social phobia, agoraphobia, and panic disorder), and depressive disorders (major depressive disorder, and dysthymia). RESULTS: Longitudinal associations between GAD and depressive disorders are not stronger than those between GAD and anxiety disorders or between other anxiety and depressive disorders. Survival analyses reveal that the factors associated with GAD overlap more strongly with those specific to anxiety disorders than those specific to depressive disorders. In addition, GAD differs from anxiety and depressive disorders with regard to family climate and personality profiles. CONCLUSIONS: Anxiety and depressive disorders appear to differ with regard to risk constellations and temporal longitudinal patterns, and GAD is a heterogeneous disorder that is, overall, more closely related to other anxiety disorders than to depressive disorders. More work is needed to elucidate the potentially unique aspects of pathways and mechanisms involved in the etiopathogenesis of GAD. Grouping GAD with depressive disorders, as suggested by cross-sectional features and diagnostic comorbidity patterns, minimizes the importance of longitudinal data on risk factors and symptom trajectories.

Generalized worry disorder: a review of DSM-IV generalized anxiety disorder and options for DSM-V.

BACKGROUND: Generalized anxiety disorder (GAD) has undergone a series of substantial classificatory changes since its first inclusion in DSM-III. The majority of these revisions have been in response to its poor inter-rater reliability and concerns that it may lack diagnostic validity. This article provides options for the revision of the DSM-IV GAD criteria for DSM-V. METHOD: First, searches were conducted to identify the evidence that previous DSM Work Groups relied upon when revising the DSM-III-R GAD and the overanxious disorder classifications. Second, the literature pertaining to the DSM-IV criteria for GAD was examined. CONCLUSIONS: The review presents a number of options to be considered for DSM-V. One option is for GAD to be re-labeled in DSM-V as generalized worry disorder. This would reflect its hallmark feature. Proposed revisions would result in a disorder that is characterized by excessive anxiety and worry generalized to a number of events or activities for 3 months or more. Worry acts as a cognitive coping strategy that manifests in avoidant behaviors. The reliability and validity of the proposed changes could be investigated in DSM-V validity tests and field trials.

Pain associated with specific anxiety and depressive disorders in a nationally representative population sample.

OBJECTIVE: To examine in a nationally representative sample (a) the differential association of specific anxiety and depressive disorders defined according to DSM-IV with pain disorder (PD) and pain symptoms, and (b) whether pain-associated anxiety and depressive disorders and their comorbidity have different implications in terms of impairment, disability, health care utilization, and substance use. METHOD: A nationally representative community study was conducted in Germany. Symptoms, syndromes and diagnoses of mental disorders, and pain were assessed in N = 4,181 participants aged 18-65 years using the DSM-IV/M-CIDI. RESULTS: Logistic regressions revealed that pain is associated with both specific anxiety and depressive disorders, with increasing significant odds ratios (OR) for medically explained pain symptoms (EPS; OR range: 1.9-2.0), to unexplained pain symptoms (UPS; OR range: 2.4-7.3), to PD (OR range: 3.3-14.8). PD and UPS persistently showed associations after adjusting for comorbid other anxiety and depressive disorders and physical illnesses. All types of pain, particularly PD/UPS, are associated with decreased quality of life, greater impairment in role functioning, disability, health care utilization, and substance use. Depressive disorders, even more so anxiety disorders and their comorbidity account for a substantial proportion of variance in these functional correlates. CONCLUSIONS: Pain is strongly associated with specific anxiety and depressive disorders. In light of the individual and societal burden due to pain, and the demonstrated role of comorbid anxiety or/and depression, our results call for further investigation of the underlying mechanisms for this association as well as targeted treatments for these comorbidities.

The position of anxiety disorders in structural models of mental disorders.

It has been suggested that the relationship between mental disorders can be summarized by a 3-factor model consisting of "anxious-misery," "fear," and "externalizing." This article examines the assumptions and predictions of this model, with particular emphasis on the anxiety disorders. Results indicate that the 3-factor model is not robust when additional diagnoses are included or when developmental factors are considered. Further, the assumption of a higher-order internalizing factor could not be consistently confirmed. Other factor solutions might fit the data equally as well. Further, the anxiety disorders did not load onto predicted factors as postulated in the 3-factor model. The authors results and considerations strongly suggest that caution is needed with this factor analytic approach in general and its use with classificatory issues. Extant results are not stable enough to form the basis of clinical diagnostic classification systems such as DSM and the International Classification of Diseases.

Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V.

This review summarizes findings on the epidemiology and etiology of anxiety disorders among children and adolescents including separation anxiety disorder, specific phobia, social phobia, agoraphobia, panic disorder, and generalized anxiety disorder, also highlighting critical aspects of diagnosis, assessment, and treatment. Childhood and adolescence is the core risk phase for the development of anxiety symptoms and syndromes, ranging from transient mild symptoms to full-blown anxiety disorders. This article critically reviews epidemiological evidence covering prevalence, incidence, course, and risk factors. The core challenge in this age span is the derivation of developmentally more sensitive assessment methods. Identification of characteristics that could serve as solid predictors for onset, course, and outcome will require prospective designs that assess a wide range of putative vulnerability and risk factors. This type of information is important for improved early recognition and differential diagnosis as well as prevention and treatment in this age span.

Mood episodes and mood disorders: patterns of incidence and conversion in the first three decades of life.

OBJECTIVES: Significant questions remain regarding both the incidence patterns of mood episodes in adolescents and young adults from the community and the conversion rate from unipolar to bipolar disorders. We addressed these issues by examining data from a prospective longitudinal community study to (i) determine the cumulative incidence of mood episodes and disorders in the first three decades of life; (ii) determine the risk for first onset of depression among individuals with a previous history of hypomanic/manic episodes and vice versa; and (iii) determine the clinical and treatment characteristics of these subjects. METHODS: Using the Munich-Composite International Diagnostic Interview, clinically trained interviewers assessed mood episodes and mental disorders in 3,021 community subjects (aged 14-24 at baseline and 21-34 at third follow-up). RESULTS: The estimated cumulative incidence at age 33 was 2.9% for manic, 4.0% for hypomanic, 29.4% for major depressive, and 19.0% for minor depressive episodes; overall, 26.0% had unipolar major depression, 4.0% bipolar depression, 1.5% unipolar mania, and 3.6% unipolar hypomania (no major depression). Overall, 0.6% and 1.8% had unipolar mania or hypomania, respectively, without indication for even minor depression. A total of 3.6% of the initial unipolar major depression cases subsequently developed (hypo)mania, with particularly high rates in adolescent onset depression (< 17 years: 9%). A total of 49.6% of the initial unipolar mania cases subsequently developed major depression and 75.6% major or minor depression. While bipolar cases had more adverse clinical and course depression characteristics and higher treatment rates than unipolar depressed cases, bipolar cases did not significantly differ in mania characteristics from unipolar mania cases. CONCLUSIONS: Unipolar and bipolar mood disorders are more frequent than previously thought in adolescence and young adulthood, a time period when both the recognition and the intervention rates by the healthcare system are rather low. 'Conversion' to bipolar disorder is limited in initial unipolar depression, but common in initial unipolar mania. The remaining unipolar mania cases appear to be significant in terms of clinical and course characteristics and thus require more research attention to replicate these findings.

Do parental psychopathology and unfavorable family environment predict the persistence of social phobia?

Parental psychopathology and unfavorable family environment are established risk factors for onset of offspring social phobia (SP), but their associations with the further course, e.g., persistence of the disorder, remain understudied. A community cohort of 1395 adolescents and their parents was followed-up over almost 10 years using the DIA-X/M-CIDI. Parental diagnostic interviews were supplemented by family history data. Parental rearing was retrospectively assessed by the Questionnaire of Recalled Parental Rearing Behavior in offspring, and family functioning by the Family Assessment Device in parents. Persistence measures (proportion of years affected since onset) were derived from diagnostic interviews, using age of onset, age of recency, and course information. Lack of emotional warmth and dysfunctional family functioning characteristics were associated with higher SP persistence, particularly in interaction with parental psychopathology. Predictors for SP persistence differ from those predicting SP onset. Unfavorable family environment alone and in interaction with parental disorders predict higher SP persistence.

The short- and long-term effect of duloxetine on painful physical symptoms in patients with generalized anxiety disorder: results from three clinical trials.

Generalized anxiety disorder (GAD) is associated with painful physical symptoms (PPS). These post hoc analyses of previous trial data assessed PPS and their response to duloxetine treatment in GAD patients. Studies 1 and 2 (n=840) were 9- to 10-week efficacy trials; study 3 (n=887) was a relapse prevention trial comprising a 26-week open-label treatment phase and a 26-week double-blind, placebo-controlled treatment continuation phase. Mean baseline visual analog scale scores (VAS, 0-100; n=1727) ranged from 26 to 37 for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake. In studies 1 and 2, improvement on all VAS scores was greater in duloxetine-treated than in placebo-treated patients (p

A typology of cannabis-related problems among individuals with repeated illegal drug use in the first three decades of life: Evidence for heterogeneity and different treatment needs.

BACKGROUND: Cannabis use (CU) and disorders (CUD) are highly prevalent among adolescents and young adults. We aim to identify clinically meaningful latent classes of users of cannabis and other illegal substances with distinct problem profiles. METHODS: N=3021 community subjects aged 14-24 at baseline were followed-up over a period ranging up to 10 years. Substance use (SU) and disorders (SUD) were assessed with the DSM-IV/M-CIDI. Latent class analysis (LCA) was conducted with a subset of N=1089 subjects with repeated illegal SU. The variables entered in the LCA were CU-related problems, CUD, other SUD, and other mental disorders. RESULTS: Four latent classes were identified: "Unproblematic CU" (class 1: 59.2%), "Primary alcohol use disorders" (class 2: 14.4%), "Delinquent cannabis/alcohol DSM-IV-abuse" (class 3: 17.9%), "CUD with multiple problems" (class 4: 8.5%). Range and level of CU-related problems were highest in classes 3 and 4. Comorbidity with other mental disorders was highest in classes 2 and 4. The probability of alcohol disorders and unmet treatment needs was considerable in classes 2-4. CONCLUSION: While the majority of subjects with repeated illegal SU did not experience notable problems over the 10-year period, a large minority (40.8%) experienced problematic outcomes, distinguished by clinically meaningful profiles. The data underline the need for specifically tailored interventions for adolescents with problematic CU and highlight the potentially important role of alcohol and other mental disorders.

Common and distinct amygdala-function perturbations in depressed vs anxious adolescents.

CONTEXT: Few studies directly compare amygdala function in depressive and anxiety disorders. Data from longitudinal research emphasize the need for such studies in adolescents. OBJECTIVE: To compare amygdala response to varying attention and emotion conditions among adolescents with major depressive disorder (MDD) or anxiety disorders, relative to adolescents with no psychopathology. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Eighty-seven adolescents matched on age, sex, intelligence, and social class: 26 with MDD (14 with and 12 without anxiety disorders), 16 with anxiety disorders but no depression, and 45 without psychopathology. MAIN OUTCOME MEASURES: Blood oxygen level-dependent signal in the amygdala, measured by means of event-related functional magnetic resonance imaging. During imaging, participants viewed facial expressions (neutral, fearful, angry, and happy) while attention was constrained (afraid, hostility, and nose-width ratings) or unconstrained (passive viewing). RESULTS: Left and right amygdala activation differed as a function of diagnosis, facial expression, and attention condition both when patients with comorbid MDD and anxiety were included and when they were excluded (group x emotion x attention interactions, P < or = .03). Focusing on fearful face-viewing events, patients with anxiety and those with MDD both differed in amygdala responses from healthy participants and from each other during passive viewing. However, both MDD and anxiety groups, relative to healthy participants, exhibited similar signs of amygdala hyperactivation to fearful faces when subjectively experienced fear was rated. CONCLUSIONS: Adolescent MDD and anxiety disorders exhibit common and distinct functional neural correlates during face processing. Attention modulates the degree to which common or distinct amygdala perturbations manifest in these patient groups, relative to healthy peers.

Association between generalized anxiety levels and pain in a community sample: evidence for diagnostic specificity.

BACKGROUND: It is unclear whether generalized anxiety disorder (GAD) has a specific relationship to pain syndromes, going beyond the established association of pain with anxiety syndromes in general. METHODS: Mental disorders were assessed in a community sample (N=4181; 18-65 years) using the DSM-IV/M-CIDI. Several threshold definitions were used to define GAD and medically unexplained pain. RESULTS: The association between pain and GAD (odds ratio, OR=5.8 pain symptoms; OR=16.0 pain disorder) is stronger than the association between pain and other anxiety disorders (OR=2.4 pain symptoms; OR=4.0 pain disorder). This association extends to subthreshold level definitions of GAD with some indication for a non-linear dose-response relationship. The GAD-pain link cannot sufficiently be explained by demographic factors, comorbid mental or physical disorders. CONCLUSIONS: The association of pain and generalized anxiety is not artifactual. Compared to other anxiety syndromes, it appears to be stronger and more specific suggesting the need to explore clinical and public health implications.

Worry exposure versus applied relaxation in the treatment of generalized anxiety disorder.

BACKGROUND: Worry exposure (WE) is a core element of cognitive-behavioral treatment for generalized anxiety disorder (GAD). Its efficacy as a stand-alone treatment method (without further cognitive-behavioral therapy interventions) has never been tested.We aimed to examine whether WE alone is as efficacious as the empirically supported stand-alone treatment for GAD, applied relaxation (AR). METHODS: In a randomized controlled study, 73 outpatients meeting DSM-IV criteria for GAD as primary diagnosis were allocated to either WE or AR or a waiting list control group; in a 2nd randomization procedure the waiting list subjects were reallocated to WE or AR. The treatment was manualized (15 sessions with WE or AR), included 6-month and 1-year follow-ups, as well as last observation carried forward and completer analyses, and was controlled for allegiance effects.The Hamilton Anxiety Rating Scale and the State-Trait Anxiety Scale were used as primary outcome measures. Self-report scales of anxiety, worrying and depression including negative metacognition about worrying and thought suppression served as secondary outcome measures. RESULTS: The dropout rate was moderate. The pre-/posttreatment effects were high for the Hamilton Anxiety Rating Scale (standardized mean difference >1) and for the State-Trait Anxiety Inventory (standardized mean difference >0.87). The proportion of patients reaching high end state functioning was 48% (WE) and 56% (AR). WE and AR did not differ with regard to dropout rate or treatment effects. The treatment effects were stable at 6 month and 1 year follow-up. CONCLUSION: This is the first study to show that a stand-alone exposure in sensu technique--WE--is efficacious in the treatment of GAD. Both AR and WE seem to represent effective principles of change in GAD.

Posttraumatic stress disorder: diagnostic and epidemiological perspectives.

We reviewed epidemiological findings for the diagnosis of posttraumatic stress disorder (PTSD) and its core diagnostic features, focusing on whether epidemiology has been helpful in clarifying some of the critical diagnostic issues relevant to the revision of the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases. Though epidemiology has provided increasingly rich data and knowledge regarding prevalence and incidence, patterns of onset and course, comorbidity, and risk factors for traumatic experiences and posttraumatic stress, little systematic research has been performed specifically addressing such critical diagnostic issues. Particularly, unresolved concerns remain regarding the definition of trauma, duration and impairment/distress criteria, the distinctiveness of the PTSD-syndrome, and even the position of PTSD in the classification system of mental disorders. A further exploitation of the existing data, and an improvement of existing epidemiological methods, strategies, and assessments are likely to substantially contribute to the clarification of unresolved diagnostic issues.

Associations of familial risk factors with social fears and social phobia: evidence for the continuum hypothesis in social anxiety disorder?

We examined parental psychopathology and family environment in subthreshold and DSM-IV threshold conditions of social anxiety disorder (SAD) in a representative cohort sample of 1,395 adolescents. Offspring and parental psychopathology was assessed using the DIA-X/M-CIDI; recalled parental rearing and family functioning via questionnaire. Diagnostic interviews in parents were supplemented by family history reports from offspring. The cumulative lifetime incidence was 23.07% for symptomatic SAD, and 18.38 and 7.41% for subthreshold and threshold SAD, respectively. The specific parent-to-offspring association for SAD occurred for threshold SAD only. For subthreshold and threshold SAD similar associations were found with other parental anxiety disorders, depression and substance use disorders. Parental rearing behaviour, but not family functioning, was associated with offspring threshold SAD, and although less strong and less consistent, also with subthreshold SAD. Results suggest a continued graded relationship between familial risk factors and offspring SAD. Parental psychopathology and negative parental styles may be used defining high-risk groups to assign individuals with already subthreshold conditions of SAD to early intervention programs.

The role of parental psychopathology and family environment for social phobia in the first three decades of life.

BACKGROUND: To examine the role of parental psychopathology and family environment for the risk of social phobia (SP) in offspring from childhood to early adulthood, encompassing the high risk period for SP. METHODS: A community sample of 1,395 adolescents was prospectively followed-up over 10 years. Offspring and parental psychopathology were assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) using the Munich Composite International Diagnostic Interview (M-CIDI), and direct diagnostic interviews in parents were supplemented by family history reports. Parental rearing was assessed by the Questionnaire of Recalled Rearing Behavior administered to offspring. Family functioning was assessed by the McMaster Family Assessment Device administered to parents. RESULTS: Parental SP was associated with offspring's risk to develop SP (OR=3.3, 95%CI:1.4-8.0). Other parental anxiety disorders (OR=2.9, 95%CI:1.4-6.1), depression (OR=2.6, 95%CI:1.2-5.4), and alcohol use disorders (OR=2.8, 95%CI:1.3-6.1) were also associated with offspring SP. Parental rearing styles of overprotection, rejection, and lack of emotional warmth were associated with offspring SP. Family functioning measures were not associated with offspring SP. Analyses of interaction of parental psychopathology and parental rearing indicated combined effects on the risk for offspring SP. CONCLUSIONS: Parental psychopathology and rearing were associated with offspring SP, independently as well as in their interaction. Further delineation of these associations is warranted as malleable components of these risk factors may provide potential targets for prevention programs. In addition, parent-to-offspring transmission of other internalizing disorders should be considered to examine the degree of diagnostic specificity.

Risk and speed of transitions to first alcohol dependence symptoms in adolescents: a 10-year longitudinal community study in Germany.

BACKGROUND: Although in many western countries alcohol use (AU) and symptoms of alcohol dependence (AD) are frequent in adolescence, temporal patterns and trajectories remain understudied. It is unclear whether early onset of AU is associated with the speed of transition to first AD symptoms and whether specific first AD symptoms and their timing are associated with AD. AIMS: To examine (i) the incidence patterns of self-reported first AD symptoms; (ii) whether early AU is associated with the risk and speed of transition to first AD symptoms; and (iii) whether first AD symptoms and their timing are associated with AD. DESIGN: A total of 3021 community subjects from Germany aged 14-24 years at baseline followed prospectively over 10 years. AU, AD symptoms and AD were assessed using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI). FINDINGS: Among first AD symptoms, tolerance (13.1%) and much time spent (5.0%) were most prevalent. Five to 30% of all first AD symptoms occurred during the first year after first AU. Early AU was not related to the risk of first AD symptoms. The speed of transition to first AD symptoms was greater among those with AU onset in later adolescence. Tolerance and loss of control were associated with AD development (risk difference 3.9% and 15.4%), as was early onset of tolerance, much time spent and loss of control. CONCLUSION: Early AU and early AD symptoms are frequent among adolescents. Early self-reported tolerance, much time spent and loss of control are particularly predictive for AD and important targets for early preventive interventions.

Psychometric properties of the Retrospective Self Report of Inhibition (RSRI) in a representative German sample.

The present study examined the internal consistency, factorial structure, and construct validity of the German version of the Retrospective Self Report of Inhibition (RSRI), a questionnaire measure of behavioral inhibition. The research was based on data from a German prospective-longitudinal community study of 3021 adolescents and young adults (aged 14-24 years at baseline). Diagnostic assessment was based on the DSM-IV/M-CIDI and general psychopathological distress was assessed with SCL-90-R. Results of confirmatory factor analysis indicated adequate fit of the two-factor model, suggested by the authors of the original version. Indices of internal consistency of the RSRI and its subscales 'social/school' and 'fear/illness' were shown to be sufficient for the total sample and even higher in subgroups of subjects with certain DSM-IV diagnoses. Associations with variables such as mental distress, parental psychopathology, and DSM-IV disorders were in line with theoretical assumptions and confirm different aspects of the validity (convergent, concurrent, predictive) of the instrument. The psychometric properties of the German RSRI were found to be comparable to those of the English version. The applicability of this questionnaire in German-speaking countries is therefore recommended for adolescents and young adults.

The natural course of cannabis use, abuse and dependence during the first decades of life.

AIMS: There has been little available information on the long-term natural course, persistence and remission of cannabis use, abuse and dependence. The current study estimated rates and risk factors associated with stability and variation in cannabis use patterns, cannabis abuse and cannabis dependence in a community sample over a 10-year period. DESIGN, SETTING AND PARTICIPANTS: Prospective longitudinal, epidemiological study with a 4- and 10-year follow-up of a community sample (n = 3021) aged 14-24 years at baseline in Munich, Germany. MEASUREMENTS: Cannabis use, abuse and dependence and associated risk factors were assessed by face-to-face interviews using the Munich Composite International Diagnostic Interview. Findings At baseline, one-third of the sample (34.2%) had used cannabis at least once. The cumulative incidence of cannabis use 10 years later was 50.7%. Fifty-six per cent of all repeated users (five times or more) at baseline reported cannabis use at 4-year follow-up. Ten years later, this proportion had decreased slightly to only 46.3%. Repeated (five times or more) users were almost three times more likely to report repeated use at 10-year follow up (OR = 2.8, 95% CI = 1.6-4.7), compared with those who had used cannabis fewer times. Peer use of cannabis, life-events and alcohol dependence also predicted use of cannabis at 10-year follow-up. CONCLUSIONS: Among youth who have used cannabis repeatedly (five times or more) cannabis use is fairly stable and rates of remission relatively low until age 34 years. Patterns of progression suggest that early targeted preventive measures should delay first use and reduce the number of experiences using cannabis, as these factors appear critical in progression to persistent cannabis use and cannabis dependence.