A population-based study of the risk of schizophrenia and bipolar disorder associated with parent-child separation during development.

BACKGROUND: There is growing interest in the role of childhood adversities, including parental death and separation, in the etiology of psychotic disorders. However, few studies have used prospectively collected data to specifically investigate parental separation across development, or assessed the importance of duration of separation, and family characteristics. METHOD: We measured three types of separation not due to death: maternal, paternal, and from both parents, across the ages of 1-15 years among a cohort of 985 058 individuals born in Denmark 1971-1991 and followed to 2011. Associations with narrowly and broadly defined schizophrenia and bipolar disorder in the psychiatric register were assessed in terms of separation occurrence, age of separation, and number of years separated. Interactions with parental history of mental disorder were assessed. RESULTS: Each type of separation was associated with all three outcomes, adjusting for age, sex, birth period, calendar year, family history of mental disorder, urbanicity at birth and parental age. Number of years of paternal separation was positively associated with both schizophrenia and bipolar disorder. Associations between separation from both parents and schizophrenia were stronger when separation occurred at later ages, while those with bipolar disorder remained stable across development. The first occurrence of paternal separation appeared to increase risk more when it occurred earlier in childhood. Associations differed according to parental history of mental disorder, although in no situation was separation protective. CONCLUSIONS: Effects of parental separation may differ by type, developmental timing and family characteristics. These findings highlight the importance of considering such factors in studies of childhood adversity.

Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances.

Genotype scores that predict relevant clinical outcomes may detect other disease features and help direct prevention efforts. We report data that validate a previously established v1.0 smoking cessation quit success genotype score and describe striking differences in the score in individuals who display differing developmental trajectories of use of common addictive substances. In a cessation study, v1.0 genotype scores predicted ability to quit with P=0.00056 and area under receiver-operating characteristic curve 0.66. About 43% vs 13% quit in the upper vs lower genotype score terciles. Latent class growth analyses of a developmentally assessed sample identified three latent classes based on substance use. Higher v1.0 scores were associated with (a) higher probabilities of participant membership in a latent class that displayed low use of common addictive substances during adolescence (P=0.0004) and (b) lower probabilities of membership in a class that reported escalating use (P=0.001). These results indicate that: (a) we have identified genetic predictors of smoking cessation success, (b) genetic influences on quit success overlap with those that influence the rate at which addictive substance use is taken up during adolescence and (c) individuals at genetic risk for both escalating use of addictive substances and poor abilities to quit may provide especially urgent focus for prevention efforts.

Concordance between personality disorder assessment methods.

BACKGROUND: Studies have criticized the low level of agreement between the various methods of personality disorder (PD) assessment. This is an important issue for research and clinical purposes. METHOD: Seven hundred and forty-two participants in the Hopkins Epidemiology of Personality Disorders Study (HEPS) were assessed on two occasions using the Personality Disorder Schedule (PDS) and the International Personality Disorder Examination (IPDE). The concordance between the two diagnostic methods for all DSM-IV PDs was assessed using standard methods and also two item response analytic approaches designed to take account of measurement error: a latent trait-based approach and a generalized estimating equations (GEE)-based approach, with post-hoc adjustment. RESULTS: Raw criteria counts, using the intraclass correlation coefficient (ICC), κ and odds ratio (OR), showed poor concordance. The more refined statistical methods showed a moderate to moderately high level of concordance between the methods for most PDs studied. Overall, the PDS produced lower prevalences of traits but higher precision of measurement than the IPDE. Specific criteria within each PD showed varying endorsement thresholds and precision for ascertaining the disorder. CONCLUSIONS: Concordance in the raw measurement of the individual PD criteria between the two clinical methods is lacking. However, based on two statistical methods that adjust for differential endorsement thresholds and measurement error in the assessments, we deduce that the PD constructs themselves can be measured with a moderate degree of confidence regardless of the clinical approach used. This may suggest that the individual criteria for each PD are, in and of themselves, less specific for diagnosis, but as a group the criteria for each PD usefully identify specific PD constructs.

The effect of social networks and social support on common mental disorders following specific life events.

OBJECTIVE: This study examined the association between life events and common mental disorders while accounting for social networks and social supports. METHOD: Participants included 1920 adults in the Baltimore Epidemiologic Catchment Area Cohort who were interviewed in 1993-1996, of whom 1071 were re-interviewed in 2004-2005. Generalized estimating equations were used to analyze the data. RESULTS: Social support from friends, spouse or relatives was associated with significantly reduced odds of panic disorder and psychological distress, after experiencing specific life events. Social networks or social support had no significant stress-buffering effect. Social networks and social support had almost no direct or buffering effect on major depressive disorder, and no effect on generalized anxiety disorder and alcohol abuse or dependence disorder. CONCLUSION: The significant association between social support and psychological distress, rather than diagnosable mental disorders, highlights the importance of social support, especially when the severity of a mental health related problem is low.

Psychopathologic precursors and sociodemographic risk factors for the schizophrenia syndrome.

This article presents a prospective analysis of an antecedent psychopathologic features and sociodemographic risk factors in schizophrenia with data from five community sites in the National Institute of Mental Health Epidemiologic Catchment Area Program. Three nonoverlapping psychotic cases were defined using DSM-III definitions as implemented by the Diagnostic Interview Schedule (DIS): (1) DSM-III Schizophrenia Criterion A; (2) Criterion A and Affective Episode; and (3) full Schizophrenia. In a 1-year follow-up period, the cumulative incidence rate of Criterion A was 0.79 per 100, for Criterion A with Affective Episode it was 0.17 per 100, and for Schizophrenia the rate was 0.20 per 100. In multivariable logistic regression modeling, the patterns of associations between sociodemographic factors and DIS/DSM-III Schizophrenia resembled patterns in clinically based registry data. Male subjects had an earlier peak onset than female subjects, and marital status and employment were strongly related to odds of developing DIS/DSM-III Schizophrenia. An interaction between gender and never marrying showed never-married men at 50 times higher odds of developing DIS/DSM-III Schizophrenia, never-married women at 14 times higher odds, and married women at 2.5 times higher odds, relative to married men. Adjusting for sociodemographic factors, DIS/DSM-III Obsessive Compulsive Disorder and Social Phobia were both associated with more than 3.5 times increased odds of developing DIS/DSM-III Schizophrenia. Several other psychopathology items, including panic attacks, were associated with increased odds of developing DIS/DSM-III Schizophrenia. There were both similarities and differences in risk factor structure between DIS/DSM-III Schizophrenia and the other two defined categories of case.

Risk factors for the onset of Diagnostic Interview Schedule/DSM-III agoraphobia in a prospective, population-based study.

We analyzed the onset of agoraphobia in a large prospective study of the general population. The annual incidence of Diagnostic Interview Schedule/DSM-III agoraphobia is estimated at 22 per 1000 population per year. Latent class analysis of new cases in the at-risk population reveals the existence of two subtypes of agoraphobia. The relationship of the incidence of the two subtypes to sociodemographic and psychopathologic risk factors suggests different origins. The data also show that in two thirds of the 260 new cases of Diagnostic Interview Schedule/DSM-III agoraphobia, onset occurs without a history of panic attack. We analyzed the relationship of these epidemiologic results to earlier clinical findings in terms of possible measurement and sampling differences.

DSM-III-R generalized anxiety disorder in the National Comorbidity Survey.

BACKGROUND: Nationally representative general population data are presented on the current, 12-month, and lifetime prevalence of DSM-III-R generalized anxiety disorder (GAD) as well as on risk factors, comorbidity, and related impairments. METHODS: The data are from the National Comorbidity Survey, a large general population survey of persons aged 15 to 54 years in the noninstitutionalized civilian population of the United States. DSM-III-R GAD was assessed by lay interviewers using a revised version of the Composite International Diagnostic Interview. RESULTS: Generalized anxiety disorder was found to be a relatively rare current disorder with a current prevalence of 1.6% but was found to be a more frequent lifetime disorder affecting 5.1% of the US population aged 15 to 45 years. Generalized anxiety disorder was twice as common among women as among men. Multivariate logistic regression analysis showed that being older than 24 years, separated, widowed, divorced, unemployed, and a homemaker are significant correlates of GAD. Consistent with studies in treatment samples, we found that GAD was frequently associated with a wide spectrum of other mental disorders, with a lifetime comorbidity among 90.4% of the people who had a history of GAD. CONCLUSION: Contrary to the traditional view that GAD is a mild disorder, we found that the majority of people with GAD, whether they were comorbid or not, reported substantial interference with their life, a high degree of professional help seeking, and a high use of medication because of their GAD symptoms. Although lifetime GAD is highly comorbid, the proportion of current GAD that is not accompanied by any other current diagnosis is high enough to indicate that GAD should be considered an independent disorder rather than exclusively a residual or prodrome of other disorders.

A comparison of self-report and clinical diagnostic interviews for depression: diagnostic interview schedule and schedules for clinical assessment in neuropsychiatry in the Baltimore epidemiologic catchment area follow-up.

BACKGROUND: The field of psychiatric epidemiology continues to employ self-report instruments, but the low degree of agreement between diagnoses achieved using these instruments vs. that achieved by psychiatrists in the clinical modality threatens the credibility of the results. METHODS: In the Baltimore Epidemiologic Catchment Area follow-up, 349 individuals who had a Diagnostic Interview Schedule (DIS) interview were blindly examined by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Comparisons were made at the level of diagnosis, syndrome, and DSM-IV symptom group. Indexes of agreement were computed and characteristics of discrepant cases were identified. RESULTS: Agreement on diagnosis of major depressive disorder was only fair (kappa = 0.20), with the DIS missing many cases judged to meet criteria for diagnosis using the SCAN (29% sensitivity). A major source of discrepancy was respondents with false-negative diagnoses who repeatedly failed to report DIS symptoms attributed to life crises or medical conditions. Older age, male sex, and lower impairment were associated with underdetection by the DIS, using logistic regression analysis. In spite of the diagnostic discrepancy, there was substantial correlation in numbers of symptom groups in the 2 modalities (r = 0.49). Agreement was highest (about 55% sensitivity and 90% specificity) when both the SCAN and DIS thresholds were set at the level of depression syndrome instead of diagnosis. CONCLUSIONS: Weak agreement at the level of diagnosis continues to threaten the credibility of estimates of prevalence of specific disorders. A bias toward underreporting, as well as stronger agreement at the level of the depression syndrome and on ordinal measures of depressive symptoms, suggests that associations with risk factors are conservative.

Mental disorders and the incidence of migraine headaches in a community sample: results from the Baltimore Epidemiologic Catchment area follow-up study.

BACKGROUND: The cross-sectional relation between migraine headaches and affective disorders has been demonstrated in studies of clinical and community populations. Few studies have investigated the prospective relation between psychiatric disorders and migraine headaches. METHODS: A prospective follow-up of the Baltimore, Md, cohort of the Epidemiologic Catchment Area Study assessed psychopathologic features in 1981 and again between 1993 and 1996. Interviews included a history of headaches at baseline and self-reported assessment of migraine headaches at follow-up. Risk estimates for incident migraine headaches by 1981 demographic variables and psychopathologic features were calculated. The cross-sectional association between prevalent migraine and lifetime psychiatric diagnoses was estimated. RESULTS: In the at-risk population of 1343, there were 118 incident cases of migraine headaches. The age- and sex-specific incident rates of migraine headaches followed the expected patterns, with younger age and female sex identified as risk factors. In cross-sectional analyses, major depression (odds ratio, 3.14; 95% confidence interval, 2.03-4. 84) and panic disorder (odds ratio, 5.09; 95% confidence interval, 2. 65-9.79) had the strongest associations, and alcohol and other substance abuse were not associated. In logistic regression models including age, sex, and psychiatric illness in 1981, only phobia was predictive of incident migraines (odds ratio, 1.70; 95% confidence interval, 1.11-2.58). Affective disorders were not predictive of incident migraine headaches. Including a history of tricyclic antidepressant use did not change the results. CONCLUSIONS: There is a strong cross-sectional relation between affective disorders and migraine headaches in this cohort. However, there is no association between antecedent affective disorders and incident migraine headaches in this population-based prospective study.

Structure and course of positive and negative symptoms in schizophrenia.

BACKGROUND: This article focuses on the underlying structure and temporal course of the symptoms of schizophrenia. METHODS: Ratings of symptoms in 90 schizophrenic patients were made each month for 10 years following the first hospitalization. The analytic methods consisted of cross-tabulation, dichotomous factor analysis, and bivariate dichotomous time series. RESULTS: The factor analyses revealed positive and negative factors with a slight tendency to merge over time. The prevalence of positive and negative symptoms declined in the year following first hospitalization and was stable thereafter. Positive and negative symptoms in 1 month were highly predictive of the same type of symptoms in the next month. Neither type of symptom was strongly associated with the other type in the following month when both types were included in the model. The predictability of the process increased with time. CONCLUSIONS: With a few minor caveats, the results suggest that the positive and negative symptom clusters are independent, both cross-sectionally and longitudinally.

Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey.

BACKGROUND: Data are presented on the general population prevalences, correlates, comorbidities, and impairments associated with DSM-III-R phobias. METHODS: Analysis is based on the National Comorbidity Survey. Phobias were assessed with a revised version of the Composite International Diagnostic Interview. RESULTS: Lifetime (and 30-day) prevalence estimates are 6.7% (and 2.3%) for agoraphobia, 11.3% (and 5.5%) for simple phobia, and 13.3% (and 4.5%) for social phobia. Increasing lifetime prevalences are found in recent cohorts. Earlier median ages at illness onset are found for simple (15 years of age) and social (16 years of age) phobias than for agoraphobia (29 years of age). Phobias are highly comorbid. Most comorbid simple and social phobias are temporally primary, while most comorbid agoraphobia is temporally secondary. Comorbid phobias are generally more severe than pure phobias. Despite evidence of role impairment in phobia, only a minority of individuals with phobia ever seek professional treatment. CONCLUSIONS: Phobias are common, increasingly prevalent, often associated with serious role impairment, and usually go untreated. Focused research is needed to investigate barriers to help seeking.

Development of the Spanish-language version of the National Institute of Mental Health Diagnostic Interview Schedule.

The use of the National Institute of Mental Health Diagnostic Interview Schedule (DIS) to elicit DSM-III-defined mental disorders among Hispanic respondents in the Los Angeles site of the Epidemiologic Catchment Area project required development of a Spanish translation of the instrument that would be understood readily by persons of Mexican, Puerto Rican, and Cuban origin. The translation was carried out using back translation, bilingual test respondents, a bilingual translation staff, an extensive committee of experienced bilingual clinicians as translation consultants, and revision following clinical evaluation. A study of its reliability and comparison with clinical diagnoses obtained with Spanish-speaking psychiatric outpatients indicated satisfactory equivalence of the Spanish DIS to the English version. Early international use of the Spanish DIS promises new data on the cross-cultural validity and prevalence rates of DSM-III-diagnosed disorders.

Natural history of Diagnostic Interview Schedule/DSM-IV major depression. The Baltimore Epidemiologic Catchment Area follow-up.

BACKGROUND: Natural history can be characterized by incidence, recurrence, and duration of episodes. Research on the incidence of major depression is rare; studies of recurrence and duration are limited to clinical samples. METHODS: The Baltimore, Md, site of the Epidemiologic Catchment Area Program followed up its 1981 baseline cohort of 3481 respondents with an additional assessment in 1993 to 1996. Interviews were obtained from 1920 respondents (73% of the survivors). The Diagnostic Interview Schedule and the same survey procedures as in 1981 were used, augmented with a Life Chart Interview for dating the onset and duration of syndromes. RESULTS: There were 71 new cases of Diagnostic interview Schedule/DSM-IV major depression and 23,698 person-years of exposure, generating an estimated incidence of 3.0 per 1000 per year. Incidence peaked while subjects were in their 30s, with a smaller peak when they were in their 50s. Prodromal symptoms often occurred many years before the full criteria for diagnosis were met. Women were at higher risk for becoming new cases but had neither higher risk for recurrence nor longer episodes than men. Episodes of depression lasted for 12 weeks. The duration of an episode, and time to an episode-free year, was longer in the first episode than in recurrent episodes. CONCLUSIONS: The incidence estimated in this study is consistent with that found in the few other similar studies performed. The bimodality of onset suggests the value of further exploring the heterogeneity of depression via its natural history. Reported differences in prevalence between men and women seem to be due to differences in incidence, not chronicity.

The NIMH Epidemiologic Catchment Area program. Historical context, major objectives, and study population characteristics.

The National Institute of Mental Health multisite Epidemiologic Catchment Area (ECA) program is described in the context of four previous psychiatric epidemiologic surveys that included a combined total of 4,000 subjects from Stirling County, the Baltimore Morbidity Study, Midtown Manhattan, and the New Haven third-wave survey. The ECA program is distinguished by its sample size of at least 3,500 subjects per site (about 20,000 total); the focus on Diagnostic Interview Schedule--defined DSM-III mental disorders; the one-year reinterview-based longitudinal design to obtain incidence and service use data; the linkage of epidemiologic and health service use data; and the replication of design and method in multiple sites. Demographic characteristics of community and sample populations are provided for New Haven, Conn, Baltimore, and St Louis.

The design of the Epidemiologic Catchment Area surveys. The control and measurement of error.

Several methods are used to minimize and measure error in the NIMH Epidemiologic Catchment Area program. Sampling methods involve the inclusion of group quarters such as prisons, nursing homes, and mental hospitals in the sample frame and the use of probability sampling throughout. Interviewing, methods include use of identical diagnostic interview protocols, centralized training of interview supervisors, standard instructions to interviewers, and reinterview of a subsample by clinicians. In the area of completion, the methods include a 75% to 80% respondent completion rate, a 95% or greater completion rate for individual questions, use of informant interviews where necessary, and statistical adjustments to correct for low completion rates in some subgroups. Analytic methods include use of a computerized diagnostic algorithm, common estimation formulas on identically formatted data files, and estimation of exact variances that take account of the multistage sample design.

Depression and risk for onset of type II diabetes. A prospective population-based study.

OBJECTIVE: To determine whether depression is associated with an increased risk for onset of diabetes. RESEARCH DESIGN AND METHODS: In 1981, a total of 3,481 household-residing adults participated in the Epidemiologic Catchment Area (ECA) Program survey at the East Baltimore site. A follow-up of that cohort after 13 years completed 1,897 interviews, amounting to > 72% of survivors. In 1981, depression was assessed with the National Institutes of Mental Health (NIMH) Diagnostic Interview Schedule and diabetes, by self-report. This prospective analysis focused on subjects at risk for onset of diabetes by removing from the analysis individuals with diabetes in 1981. RESULTS: There were 89 new cases of diabetes among 1,715 individuals at risk, yielding a 13-year cumulative incidence of diabetes of 5.2%. In logistic models, major depressive disorder, but not milder forms of depression or other forms of psychiatric disorder, predicted the onset of diabetes (estimated relative risk, 2.23; 95% CI 0.90-5.55). Controlling for age, race, sex, socioeconomic status, education, use of health services, other psychiatric disorders, and body weight did not weaken the relationship. CONCLUSIONS: Major depressive disorder signals increased risk for onset of type II diabetes. Limitations of the findings arise from the difficulty in determining temporal order with two chronic conditions, even when the temporal order of measurement is clear. In addition, even though control variables were introduced for the use of health services, it is possible that the treatment for depression led to an earlier diagnosis of diabetes in this sample.

Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder.

Traumatic stress results in hypothalamic pituitary adrenal (HPA) axis abnormalities and an increased risk to both suicidal behaviors and post-traumatic stress disorder (PTSD). Previous work out of our laboratory identified SKA2 DNA methylation associations with suicidal behavior in the blood and brain of multiple cohorts. Interaction of SKA2 with stress predicted suicidal behavior with ~80% accuracy. SKA2 is hypothesized to reduce the ability to suppress cortisol following stress, which is of potentially high relevance in traumatized populations. Our objective was to investigate the interaction of SKA2 and trauma exposure on HPA axis function, suicide attempt and PTSD. SKA2 DNA methylation at Illumina HM450 probe cg13989295 was assessed for association with suicidal behavior and PTSD metrics in the context of Child Trauma Questionnaire (CTQ) scores in 421 blood and 61 saliva samples from the Grady Trauma Project (GTP) cohort. Dexamethasone suppression test (DST) data were evaluated for a subset of 209 GTP subjects. SKA2 methylation interacted with CTQ scores to predict lifetime suicide attempt in saliva and blood with areas under the receiver operator characteristic curve (AUCs) of 0.76 and 0.73 (95% confidence interval (CI): 0.6-0.92, P = 0.003, and CI: 0.65-0.78, P < 0.0001) and to mediate the suppression of cortisol following DST (ß = 0.5 ± 0.19, F = 1.51, degrees of freedom (df) = 12/167, P = 0.0096). Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.

Impairment in Holocaust survivors after 33 years: data from an unbiased community sample.

The authors compared the psychiatric status of 135 survivors of the Holocaust with that of control subjects. This study stands apart from most previous reports in that the two groups were generated by a random sample survey of all heads of households in a community (Montreal). Survivors were more likely to have mild psychiatric symptoms regardless of the age at which they experienced the Holocaust. The difference between survivors and controls in levels of mild psychiatric symptoms was greatly amplified in those respondents who perceived a recent increase in anti-Semitism in Montreal.

Prodromes and precursors: epidemiologic data for primary prevention of disorders with slow onset.

OBJECTIVE: The concepts of prodrome and precursor are used to show how epidemiologic data on age at onset can be used in timing preventive interventions and selecting target populations. METHODS: Data concerning onset of DSM-III major depression and panic disorder were taken from the Epidemiologic Catchment Area Program. Cumulative distributions of ages at onset of diagnosis and onset of precursors are presented, and the concept of attributable risk is introduced. Attributable risk is the maximum proportion of cases that would be prevented if an intervention were 100% effective in eliminating a specific precursor. RESULTS: Illustrative results for depression and panic are presented. Precursors vary in the degree to which they predict onset of the full disorder; 2 or more weeks of sad mood in the year before full-blown depression is a better predictor (relative odds, 7.0) than weight loss or gain (relative odds, 3.0). The formula for population attributable risk was applied to the precursor relative risks and prevalences to estimate the potential success of interventions for specific precursors in preventing the disorder. The precursor attributable risks indicate that sleep problems would identify 47% of the new cases of major depression occurring in the following year, and the question "Are you a nervous person?" would identify 60% of persons with onset of panic disorder in the following year. CONCLUSIONS: This conceptual framework links the early natural history of disorders with the search for syndromes. Knowledge of precursor prevalence and attributable risk, combined with other host characteristics and environmental risk factors, can be used in screening and prevention.