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BackgroundPanic disorder with agoraphobia is characterized by panic attacks and anxiety in situations where escape might be difficult. However, neuroimaging studies specifically focusing on agoraphobia are rare. Here we used functional magnetic resonance imaging (fMRI) with disorder-specific stimuli to investigate the neural substrates of agoraphobia.MethodWe compared the neural activations of 72 patients suffering from panic disorder with agoraphobia with 72 matched healthy control subjects in a 3-T fMRI study. To isolate agoraphobia-specific alterations we tested the effects of the anticipation and perception of an agoraphobia-specific stimulus set. During fMRI, 48 agoraphobia-specific and 48 neutral pictures were randomly presented with and without anticipatory stimulus indicating the content of the subsequent pictures (Westphal paradigm).ResultsDuring the anticipation of agoraphobia-specific pictures, stronger activations were found in the bilateral ventral striatum and left insula in patients compared with controls. There were no group differences during the perception phase of agoraphobia-specific pictures.ConclusionsThis study revealed stronger region-specific activations in patients suffering from panic disorder with agoraphobia in anticipation of agoraphobia-specific stimuli. Patients seem to process these stimuli more intensively based on individual salience. Hyperactivation of the ventral striatum and insula when anticipating agoraphobia-specific situations might be a central neurofunctional correlate of agoraphobia. Knowledge about the neural correlates of anticipatory and perceptual processes regarding agoraphobic situations will help to optimize and evaluate treatments, such as exposure therapy, in patients with panic disorder and agoraphobia.

BackgroundEarlier clinical studies have suggested consistent differences between anxious and non-anxious depression. The aim of this study was to compare parental pathology, personality and symptom characteristics in three groups of probands from the general population: depression with and without generalized anxiety disorder (GAD) and with other anxiety disorders. Because patients without GAD may have experienced anxious symptoms for up to 5 months, we also considered GAD with a duration of only 1 month to produce a group of depressions largely unaffected by anxiety.MethodDepressive and anxiety disorders were assessed in a 10-year prospective longitudinal community and family study using the DSM-IV/M-CIDI. Regression analyses were used to reveal associations between these variables and with personality using two durations of GAD: 6 months (GAD-6) and 1 month (GAD-1).ResultsNon-anxious depressives had fewer and less severe depressive symptoms, and higher odds for parents with depression alone, whereas those with anxious depression were associated with higher harm avoidance and had parents with a wider range of disorders, including mania.ConclusionsAnxious depression is a more severe form of depression than the non-anxious form; this is true even when the symptoms required for an anxiety diagnosis are ignored. Patients with non-anxious depression are different from those with anxious depression in terms of illness severity, family pathology and personality. The association between major depression and bipolar disorder is seen only in anxious forms of depression. Improved knowledge on different forms of depression may provide clues to their differential aetiology, and guide research into the types of treatment that are best suited to each form.

BackgroundAlthough several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients.MethodThe blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls.ResultsDifferential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation.ConclusionsThe results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.

BackgroundAmong adolescents and young adults with DSM-IV alcohol use disorders (AUDs), there are inter-individual differences in the speed of transition from initial alcohol use (AU) to AUD. AUDs are highly co-morbid with other mental disorders. The factors associated with rapid transition from first AU to AUD remain unknown and the role of mental disorders in rapid transitions is unclear. Given this background we examined (1) whether prior anxiety, mood, externalizing and non-alcohol substance use disorders are related to the risk and speed of transition from first AU to DSM-IV alcohol abuse (AA) and alcohol dependence (AD) and (2) whether early age of onset of prior mental disorders (PMDs) is a promoter of rapid transition.MethodA total of 3021 community subjects (97.7% lifetime AU) aged 14–24 years at baseline were followed up prospectively for up to 10 years. AU and mental disorders were assessed with the DSM-IV/M-CIDI.ResultsAmong subjects with lifetime AU, several PMDs, such as specific phobia, bipolar disorder and nicotine dependence, were associated with an increased risk of AUD independent of externalizing disorders. Associations of PMDs with the speed of transition to AUDs were mostly weak and inconsistent. Only social phobia and externalizing disorders were associated with faster transitions to AD even after adjustment for other PMDs. Earlier age of onset of PMD was not associated with rapid transition.ConclusionsMental disorders are associated with the risk of AUD. With the possible exception of social phobia and externalizing disorders, they do not promote rapid transition, even if they occur particularly early. Future research needs to identify factors relevant to rapid transition to AUD.

BackgroundIt has long been acknowledged that hearing impairment may increase the risk for psychotic experiences. Recent work suggests that young people in particular may be at risk, indicating a possible developmental mechanism.MethodThe hypothesis that individuals exposed to hearing impairment in early adolescence would display the highest risk for psychotic symptoms was examined in a prospective cohort study of a population sample of originally 3021 adolescents and young adults aged 14–24 years at baseline, in Munich, Germany (Early Developmental Stages of Psychopathology Study). The expression of psychosis was assessed at multiple time points over a period of up to 10 years, using a diagnostic interview (Munich Composite International Diagnostic Interview; CIDI) administered by clinical psychologists.ResultsHearing impairment was associated with CIDI psychotic symptoms [odds ratio (OR) 2.04, 95% confidence interval (CI) 1.10–3.81], particularly more severe psychotic symptoms (OR 5.66, 95% CI 1.64–19.49). The association between hearing impairment and CIDI psychotic symptoms was much stronger in the youngest group aged 14–17 years at baseline (OR 3.28, 95% CI 1.54–7.01) than in the older group aged 18–24 years at baseline (OR 0.82, 95% CI 0.24–2.84).ConclusionsThe finding of an age-specific association between hearing impairment and psychotic experiences suggests that disruption of development at a critical adolescent phase, in interaction with other personal and social vulnerabilities, may increase the risk for psychotic symptoms.

BackgroundReported rates of bipolar syndromes are highly variable between studies because of age differences, differences in diagnostic criteria, or restriction of sampling to clinical contacts.MethodIn 1395 adolescents aged 14–17 years, DSM-IV (hypo)manic episodes (manic and hypomanic episodes combined), use of mental health care, and five ordinal subcategories representing the underlying continuous score of (hypo)manic symptoms (‘mania symptom scale’) were measured at baseline and approximately 1.5, 4 and 10 years later using the Munich-Composite International Diagnostic Interview (DIA-X/M-CIDI).ResultsIncidence rates (IRs) of both (hypo)manic episodes and (hypo)manic symptoms (at least one DSM-IV core symptom) were far higher (714/105 person-years and 1720/105 person-years respectively) than traditional estimates. In addition, the risk of developing (hypo)manic episodes was very low after the age of 21 years [hazard ratio (HR) 0.031, 95% confidence interval (CI) 0.0050–0.19], independent of childhood disorders such as attention deficit hyperactivity disorder (ADHD). Most individuals with hypomanic and manic episodes were never in care (87% and 62% respectively) and not presenting co-morbid depressive episodes (69% and 60% respectively). The probability of mental health care increased linearly with the number of symptoms on the mania symptom scale. The incidence of the bipolar categories, in particular at the level of clinical morbidity, was strongly associated with previous childhood disorders and male sex.ConclusionsThis study showed, for the first time, that experiencing (hypo)manic symptoms is a common adolescent phenomenon that infrequently predicts mental health care use. The findings suggest that the onset of bipolar disorder can be elucidated by studying the pathway from non-pathological behavioural expression to dysfunction and need for care.

Background. The urban environment may increase the risk for psychotic disorder in interaction with pre-existing risk for psychosis, but direct confirmation has been lacking. The hypothesis was examined that the outcome of subclinical expression of psychosis during adolescence, as an indicator of psychosis-proneness, would be worse for those growing up in an urban environment, in terms of having a greater probability of psychosis persistence over a 3·5-year period.Method. A cohort of 918 adolescents from the Early Developmental Stages of Psychopathology Study (EDSP), aged 14–17 years (mean 15·1 years), growing up in contrasting urban and non-urban environments, completed a self-report measure of psychotic symptoms at baseline (Baseline Psychosis) and at first follow-up around 1 year post-baseline (T1). They were again interviewed by trained psychologists for the presence of psychotic symptoms at the second follow-up on average 3·5 years post-baseline (T2).Results. The rate of T2 psychotic symptoms was 14·2% in those exposed to neither Baseline Psychosis nor Urbanicity, 12·1% in those exposed to Urbanicity alone, 14·9% in those exposed to Baseline Psychosis alone and 29·0% in those exposed to both Baseline Psychosis and Urbanicity. The odds ratio (OR) for the combined exposure was 2·46 [95% confidence interval (CI) 1·46–4·14], significantly greater than that expected if Urbanicity and Baseline Psychosis acted independently.Conclusion. These findings support the suggestion that the outcome of the developmental expression of psychosis is worse in urban environments. The environment may impact on risk for psychotic disorder by causing an abnormal persistence of a developmentally common expression of psychotic experiences.

Background. We examined the association between parental alcohol use disorders and patterns of alcohol consumption and DSM-IV alcohol use disorders in their offspring in a community-based sample of young adults.Methods. Data are based on baseline and 4-year follow-up data of 2427 respondents aged 14–24 at baseline. Alcohol use and disorders in respondents were assessed using the Munich-Composite-International-Diagnostic-Interview with DSM-IV algorithms. Diagnostic information about parents was collected by family history information from the respondents, and by direct interview with one parent (cohort aged 14 to 17 years only).Results. Although the association between maternal and paternal alcohol use disorders and non-problematical drinking in offspring was minimal, there was a strong effect for the transition to hazardous use and for alcohol abuse and dependence; the effect of parental concordance for transition into hazardous use was particularly striking. Maternal history was associated with a higher probability of progression from occasional to regular use, whereas paternal history was associated with progression from regular to hazardous use. Parental alcoholism increased the risk for first onset of hazardous use and alcohol dependence between the ages of 14–17, and for an earlier onset of the alcohol outcomes in offspring. The impact of parental alcohol use disorders was comparable for male and female offspring.Conclusions. Parental alcoholism predicts escalation of alcohol use, development of alcohol use disorders and onset of alcohol outcomes in offspring.

Brugha and his colleagues in this issue raise important questions about the validity of standardized diagnostic interviews of mental disorders, such as the Composite International Diagnostic Interview (CIDI) (WHO, 1990). Although their concerns refer predominantly to the use of such instruments in epidemiological research, the authors' conclusions also have significant implications for diagnostic assessments in clinical practice and research. We agree with Brugha et al. that the inflexible approach to questioning used in standardized interviews can lead to an increased risk of invalidity with regard to some diagnoses. We also agree that the use of more semi-structured clinical questions has the potential to address this problem. However, we disagree with Brugha et al. in several other respects.First, we disagree with the authors' initial exclusive emphasis on diagnosis with regard to need assessment and consequences for the allocation of service resources. It is becoming increasingly clear that knowledge about diagnosis does not, in itself, whether assessed by clinical or non-clinical diagnostic interviews, provide sufficient information we need for policy purposes and the determination of societal costs, or to judge clinical management guidelines and treatment needs (Regier et al. 1998). Additional, preferably dimensional, data on associated disabilities and distress as well as a focused need evaluation for those psychosocial, psychological and drug interventions that characterize modern treatment strategies are also important. It also has become evident that a great many people in the general population carry more than one diagnosis. This ‘co-morbidity’ complicates further such simple equation of diagnosis prevalence with need assessment and policy decisions. Secondly, we disagree with the conclusion of Brugha et al. that the use of a semi-structured clinical interview, like the most current version of the Structured Clinical Assessment for Neuropsychiatry (SCAN), whether in the hands of clinical or non-clinical interviewers, is most closely approximating the ‘clinical gold standard’ and is the most feasible way to correct the problem of disagreement between semi-structured clinical diagnostic interviews and standardized diagnostic interviews. We believe that the practical reliability and validity problems associated with using such a clinical interviewing approach especially in large-scale community surveys as well as in cross-national research more than cancel out any theoretical advantage this approach might have in clarifying meaning. Thirdly, we disagree with the suggestion of Brugha et al. that the problem of validity is inherent in standardized non-clinician interviews. Indeed, as detailed below, there is no evidence that across all diagnoses clinical semi-structured interviews reveal more promising psychometric properties than standardized interviews. Also methodological research shows quite clearly that a substantial number of potential validity problems in standardized interviews can be overcome.

Background. General population data were used to study co-morbidities between lifetime social phobia and mood disorders.Methods. Data come from the US National Comorbidity Survey (NCS).Results. Strong associations exist between lifetime social phobia and major depressive disorder (odds ratio 2·9), dysthymia (2·7) and bipolar disorder (5·9). Odds ratios increase in magnitude with number of social fears. Reported age of onset is earlier for social phobia than mood disorders in the vast majority of co-morbid cases. Temporally-primary social phobia predicts subsequent onset of mood disorders, with population attributable risk proportions of 10–15%. Social phobia is also associated with severity and persistence of co-morbid mood disorders.Conclusions. Social phobia is a commonly occurring, chronic and seriously impairing disorder that is seldom treated unless it occurs in conjunction with another co-morbid condition. The adverse consequences of social phobia include increased risk of onset, severity and course of subsequent mood disorders. Early outreach and treatment of primary social phobia might not only reduce the prevalence of this disorder itself, but also the subsequent onset of mood disorders.

Background. The paper describes prevalence, impairments, patterns of co-morbidity and other correlates of DSM-IV social phobia in adolescents and young adults, separating generalized and non-generalized social phobics.Methods. Data are derived from the baseline investigation of the Early Developmental Stages of Psychopathology Study (EDSP), a prospective longitudinal community study of 3021 subjects, aged 14–24. Diagnoses were based on the DSM-IV algorithms of an expanded version of the Composite International Diagnostic Interview.Results. Lifetime prevalence of DSM-IV/CIDI social phobia was 9·5% in females and 4·9% in males, with about one-third being classified as generalized social phobics. Twelve-month prevalence was only slightly lower, indicating considerable persistence. Respondents with generalized social phobia reported an earlier age of onset, higher symptom persistence, more co-morbidity, more severe impairments, higher treatment rates and indicated more frequently a parental history of mental disorders than respondents with non-generalized social phobia.Conclusions. History of DSM-IV social phobia was found to be quite prevalent in 14–24 year-olds. The generalized subtype of social phobia was found to have different correlates and to be considerably more persistent, impairing and co-morbid than non-generalized social phobia. Although generalized social phobics are more likely than non-generalized social phobics to receive mental health treatments, the treatment rate in this sample was low despite the fact that mental health services are free in Germany.

Background. There are few cross-national comparisons of the rates of suicide ideation and attempts across diverse countries. Nine independently conducted epidemiological surveys using similar diagnostic assessment and criteria provided an opportunity to obtain that data.Methods. Suicide ideation and attempts were assessed on the Diagnostic Interview Schedule in over 40000 subjects drawn from the United States, Canada, Puerto Rico, France, West Germany, Lebanon, Taiwan, Korea and New Zealand.Results. The lifetime prevalence rates/100 for suicide ideation ranged from 2·09 (Beirut) to 18·51 (Christchurch, New Zealand). Lifetime prevalence rates/100 for suicide attempts ranged from 0·72 (Beirut) to 5·93 (Puerto Rico). Females as compared to males had only marginally higher rates of suicidal ideation in most countries, reaching a two-fold increase in Taiwan. Females as compared to males had more consistently higher rates for suicide attempts, reaching a two- to three-fold increase in most countries. Suicide ideation and attempts in most countries were associated with being currently divorced/separated as compared to currently married.Conclusions. While the rates of suicide ideation varied widely by country, the rates of suicide attempts were more consistent across most countries. The variations were only partly explained by variation in rates of psychiatric disorders, divorce or separation among countries and are probably due to cultural features that we do not, as yet, understand.

BackgroundLack of coordination between screening studies for common mental disorders in primary care and community epidemiological samples impedes progress in clinical epidemiology. Short screening scales based on the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), the diagnostic interview used in community epidemiological surveys throughout the world, were developed to address this problem.MethodExpert reviews and cognitive interviews generated CIDI screening scale (CIDI-SC) item pools for 30-day DSM-IV-TR major depressive episode (MDE), generalized anxiety disorder (GAD), panic disorder (PD) and bipolar disorder (BPD). These items were administered to 3058 unselected patients in 29 US primary care offices. Blinded SCID clinical reinterviews were administered to 206 of these patients, oversampling screened positives.ResultsStepwise regression selected optimal screening items to predict clinical diagnoses. Excellent concordance [area under the receiver operating characteristic curve (AUC)] was found between continuous CIDI-SC and DSM-IV/SCID diagnoses of 30-day MDE (0.93), GAD (0.88), PD (0.90) and BPD (0.97), with only 9–38 questions needed to administer all scales. CIDI-SC versus SCID prevalence differences are insignificant at the optimal CIDI-SC diagnostic thresholds (χ21 = 0.0–2.9, p = 0.09–0.94). Individual-level diagnostic concordance at these thresholds is substantial (AUC 0.81–0.86, sensitivity 68.0–80.2%, specificity 90.1–98.8%). Likelihood ratio positive (LR+) exceeds 10 and LR− is 0.1 or less at informative thresholds for all diagnoses.ConclusionsCIDI-SC operating characteristics are equivalent (MDE, GAD) or superior (PD, BPD) to those of the best alternative screening scales. CIDI-SC results can be compared directly to general population CIDI survey results or used to target and streamline second-stage CIDIs.

BackgroundAlthough positive effects of physical activity on mental health indicators have been reported, the relationship between physical activity and the development of specific mental disorders is unclear.MethodA cross-sectional (12-month) and prospective-longitudinal epidemiological study over 4 years in a community cohort of 2548 individuals, aged 14–24 years at outset of the study. Physical activity and mental disorders were assessed by the DSM-IV Composite International Diagnostic Interview (CIDI) with an embedded physical activity module. Multiple logistic regression analyses controlling for age, gender and educational status were used to determine the cross-sectional and prospective associations of mental disorders and physical activity.ResultsCross-sectionally, regular physical activity was associated with a decreased prevalence of any and co-morbid mental disorder, due to lower rates of substance use disorders, anxiety disorders and dysthymia. Prospectively, subjects with regular physical activity had a substantially lower overall incidence of any and co-morbid mental disorder, and also a lower incidence of anxiety, somatoform and dysthymic disorder. By contrast, the incidence of bipolar disorder was increased among those with regular physical activity at baseline. In terms of the population attributable fraction (PAF), the potential for preventive effects of physical activity was considerably higher for men than for women.ConclusionsRegular physical activity is associated with a substantially reduced risk for some, but not all, mental disorders and also seems to reduce the degree of co-morbidity. Further examination of the evidently complex mechanisms and pathways underlying these associations might reveal promising new research targets and procedures for targeted prevention.