The role of genetic liability in the association of urbanicity at birth and during upbringing with schizophrenia in Denmark.

BACKGROUND: Studies have indicated that the association of urbanicity at birth and during upbringing with schizophrenia may be driven by familial factors such as genetic liability. We used a population-based nested case-control study to assess whether polygenic risk score (PRS) for schizophrenia was associated with urbanicity at birth and at age 15, and to assess whether PRS and parental history of mental disorder together explained the association between urbanicity and schizophrenia. METHODS: Data were drawn from Danish population registries. Cases born since 1981 and diagnosed with schizophrenia between 1994 and 2009 were matched to controls with the same sex and birthdate (1549 pairs). Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of a separate, large meta-analysis. RESULTS: Those with higher PRS were more likely reside in the capital compared with rural areas at age 15 [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01-1.40], but not at birth (OR 1.09, 95% CI 0.95-1.26). Adjustment for PRS produced almost no change in relative risks of schizophrenia associated with urbanicity at birth, but slightly attenuated those for urban residence at age 15. Additional adjustment for parental history led to slight attenuation of relative risks for urbanicity at birth [incidence rate ratio (IRR) for birth in capital = 1.54, 95% CI 1.18-2.02; overall p = 0.016] and further attenuation of relative risks for urbanicity at age 15 (IRR for residence in capital = 1.32, 95% CI 0.97-1.78; overall p = 0.148). CONCLUSIONS: While results regarding urbanicity during upbringing were somewhat equivocal, genetic liability as measured here does not appear to explain the association between urbanicity at birth and schizophrenia.

Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study.

BACKGROUND: There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders. METHODS: The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models. RESULTS: Current combined MDD [ß = 0.29, 95% confidence interval (CI) 0.03-0.55] and current atypical MDD (ß = 0.32, 95% CI 0.10-0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up. CONCLUSIONS: The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated.

Reexamining associations between mania, depression, anxiety and substance use disorders: results from a prospective national cohort.

Separate inheritance of mania and depression together with high rates of clinical overlap of mania with anxiety and substance use disorders provide a basis for re-examining the specificity of the prospective association of manic and depression episodes that is a hallmark of bipolar disorder. We analyzed information from 34 653 adults in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, a longitudinal nationally representative survey of US adults interviewed 3 years apart. Psychiatric disorders were assessed by a structured interview. We used logistic regression analyses to estimate the strength of associations between Wave 1 manic episodes and Wave 2 depression, anxiety and substance use disorders controlling for background characteristics and lifetime Wave 1 disorders. Corresponding analyses examined associations between Wave 1 major depressive episode with manic episodes and other psychiatric disorders. In multivariable models, Wave 1 manic episodes significantly increased the odds of Wave 2 major depressive episodes (adjusted odds ratio (AOR): 1.7; 95% confidence interval: 1.3-2.2) and any anxiety disorder (AOR: 1.8; 1.4-2.2), although not of substance use disorders (AOR: 1.2; 0.9-1.5). Conversely, Wave 1 major depressive episodes significantly increased risk of Wave 2 manic episodes (AOR: 2.2; 1.7-2.9) and anxiety disorders (AOR: 1.7; 1.5-2.0), although not substance use disorders (AOR: 1.0; 0.9-1.2). Adults with manic episodes have an approximately equivalent relative risk of developing depression episodes and anxiety disorders. Greater research and clinical focus is warranted on connections between manic episodes and anxiety disorders.

Bipolar spectrum in major depressive disorders.

Growing evidence for the spectrum concept of most mental disorders, particularly mood disorders, has challenged the arbitrary distinctions inherent in the contemporary categorical diagnostic classification system. Detection of manic symptoms in the context of episodes of depression is particularly important because of the implications for differential treatment of bipolar vs unipolar depression. The purpose of this study is to characterize the magnitude and clinical correlates of subthreshold manic syndromes or symptoms among people with major depressive disorder (MDD) compared to those without a history of manic symptoms. We defined two subthreshold manifestations-manic syndrome or symptoms-that did not include a criterion for duration. In the context of MDD, we found that the clinical correlates of those with the subthreshold manic syndrome were more similar to those with bipolar-II disorder than to MDD alone, whereas those with manic symptoms only were intermediate between those with subthreshold manic syndrome and MDD alone. These results confirm the spectrum concept of mania and suggest that a manic syndrome should be considered when evaluating people with MDD.

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.

Specificity of psychosis, mania and major depression in a contemporary family study.

There has been increasing attention to the subgroups of mood disorders and their boundaries with other mental disorders, particularly psychoses. The goals of the present paper were (1) to assess the familial aggregation and co-aggregation patterns of the full spectrum of mood disorders (that is, bipolar, schizoaffective (SAF), major depression) based on contemporary diagnostic criteria; and (2) to evaluate the familial specificity of the major subgroups of mood disorders, including psychotic, manic and major depressive episodes (MDEs). The sample included 293 patients with a lifetime diagnosis of SAF disorder, bipolar disorder and major depressive disorder (MDD), 110 orthopedic controls, and 1734 adult first-degree relatives. The diagnostic assignment was based on all available information, including direct diagnostic interviews, family history reports and medical records. Our findings revealed specificity of the familial aggregation of psychosis (odds ratio (OR)=2.9, confidence interval (CI): 1.1-7.7), mania (OR=6.4, CI: 2.2-18.7) and MDEs (OR=2.0, CI: 1.5-2.7) but not hypomania (OR=1.3, CI: 0.5-3.6). There was no evidence for cross-transmission of mania and MDEs (OR=.7, CI:.5-1.1), psychosis and mania (OR=1.0, CI:.4-2.7) or psychosis and MDEs (OR=1.0, CI:.7-1.4). The strong familial specificity of psychotic, manic and MDEs in this largest controlled contemporary family study challenges the growing assertion that the major types of mood disorders are manifestations of a common underlying diathesis.

Independence of familial transmission of mania and depression: results of the NIMH family study of affective spectrum disorders.

The goal of this study is to investigate the familial transmission of the spectrum of bipolar disorder in a nonclinical sample of probands with a broad range of manifestations of mood disorders. The sample included a total of 447 probands recruited from a clinically enriched community screening and their 2082 adult living and deceased first-degree relatives. A best estimate diagnostic procedure that was based on either direct semistructured interview or structured family history information from multiple informants regarding non-interviewed relatives was employed. Results revealed that there was specificity of familial aggregation of bipolar I (BP I; odds ratio (OR)=8.40; 3.27-20.97; h2=0.83) and major depressive disorder (OR=2.26; 1.58-3.22; h2=0.20), but not BP II. The familial aggregation of BP I was primarily attributable to the familial specificity of manic episodes after adjusting for both proband and relative comorbid anxiety and substance use disorders. There was no significant cross-aggregation between mood disorder subtypes suggesting that the familial transmission of manic and major depressive episodes is independent despite the high magnitude of comorbidity between these mood states. These findings confirm those of earlier studies of the familial aggregation of bipolar disorder and major depression in the first nonclinical sample, and the largest family study of bipolar disorder in the USA using contemporary nonhierarchical diagnostic criteria for mood and anxiety disorders. The results suggest that these major components of bipolar disorder may represent distinct underlying pathways rather than increasingly severe manifestations of a common underlying diathesis. Therefore, dissection of the broad bipolar phenotype in genetic studies could actually generate new findings that could index novel biologic pathways underlying bipolar disorder.

Threshold and subthreshold generalized anxiety disorder among US adolescents: prevalence, sociodemographic, and clinical characteristics.

BACKGROUND: Threshold and subthreshold forms of generalized anxiety disorder (GAD) are highly prevalent and impairing conditions among adults. However, there are few general population studies that have examined these conditions during the early life course. The primary objectives of this study were to: (1) examine the prevalence, and sociodemographic and clinical characteristics of threshold and subthreshold forms of GAD in a nationally representative sample of US youth; and (2) test differences in sociodemographic and clinical characteristics between threshold and subthreshold forms of the disorder. METHOD: The National Comorbidity Survey-Adolescent Supplement is a nationally representative face-to-face survey of 10,123 adolescents 13 to 18 years of age in the continental USA. RESULTS: Approximately 3% of adolescents met criteria for threshold GAD. Reducing the required duration from 6 months to 3 months resulted in a 65.7% increase in prevalence (5.0%); further relaxing the uncontrollability criterion led to an additional 20.7% increase in prevalence (6.1%). Adolescents with all forms of GAD displayed a recurrent clinical course marked by substantial impairment and co-morbidity with other psychiatric disorders. There were few significant differences in sociodemographic and clinical characteristics between threshold and subthreshold cases of GAD. Results also revealed age-related differences in the associated symptoms and clinical course of GAD. CONCLUSIONS: Findings demonstrate the clinical significance of subthreshold forms of GAD among adolescent youth, highlighting the continuous nature of the GAD construct. Age-related differences in the associated symptoms and clinical course of GAD provide further support for criteria that capture variation in clinical features across development.

Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression.

The hypothalamic-pituitary-adrenal (HPA) axis and the inflammatory response system have been suggested as pathophysiological mechanisms implicated in the etiology of major depressive disorder (MDD). Although meta-analyses do confirm associations between depression and these biological systems, effect sizes vary greatly among individual studies. A potentially important factor explaining variability is heterogeneity of MDD. Aim of this study was to evaluate the association between depressive subtypes (based on latent class analysis) and biological measures. Data from 776 persons from the Netherlands Study of Depression and Anxiety, including 111 chronic depressed persons with melancholic depression, 122 with atypical depression and 543 controls were analyzed. Inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-α), metabolic syndrome components, body mass index (BMI), saliva cortisol awakening curves (area under the curve with respect to the ground (AUCg) and with respect to the increase (AUCi)), and diurnal cortisol slope were compared among groups. Persons with melancholic depression had a higher AUCg and higher diurnal slope compared with persons with atypical depression and with controls. Persons with atypical depression had significantly higher levels of inflammatory markers, BMI, waist circumference and triglycerides, and lower high-density lipid cholesterol than persons with melancholic depression and controls. This study confirms that chronic forms of the two major subtypes of depression are associated with different biological correlates with inflammatory and metabolic dysregulation in atypical depression and HPA-axis hyperactivity in melancholic depression. The data provide further evidence that chronic forms of depressive subtypes differ not only in their symptom presentation, but also in their biological correlates. These findings have important implications for future research on pathophysiological pathways of depression and treatment.

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

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

Bipolar disorder with frequent mood episodes in the national comorbidity survey replication (NCS-R).

Virtually nothing is known about the epidemiology of rapid cycling bipolar disorder (BPD) in community samples. Nationally representative data are reported here for the prevalence and correlates of a surrogate measure of DSM-IV rapid cycling BPD from the National Comorbidity survey Replication (NCS-R), a national survey of the US household population. DSM-IV disorders were assessed in the NCS-R with the WHO Composite International Diagnostic Interview (CIDI). Although the CIDI did not assess rapid cycling, it did assess the broader category of 12-month BPD with frequent mood episodes (FMEs), having at least four episodes of mania/hypomania or major depression in the 12 months before interview. Roughly one-third of NCS-R respondents with lifetime DSM-IV BPD and half with 12-month BPD met criteria for FME. FME was associated with younger age-of-onset (of BP-I, but not BP-II) and higher annual persistence (73% of the years since first onset of illness with an episode) than non-FME BPD. No substantial associations of FME vs non-FME BPD were found with socio-demographics, childhood risk factors (parental mental disorders, other childhood adversities) or comorbid DSM-IV disorders. However, FME manic episodes had greater clinical severity than non-FME episodes (assessed with a fully structured version of the Young Mania Rating Scale) and FME hypomanic episodes had greater role impairment than non-FME episodes (assessed with the Sheehan Disability Scales). Whether these indicators of severity merely reflect attenuated effects of rapid cycling or independent effects of sub-threshold rapid cycling warrants further study given the high proportion of lifetime cases who met criteria for FME.

Mental disorders as risk factors for later substance dependence: estimates of optimal prevention and treatment benefits.

BACKGROUND: Although mental disorders have been shown to predict subsequent substance disorders, it is not known whether substance disorders could be cost-effectively prevented by large-scale interventions aimed at prior mental disorders. Although experimental intervention is the only way to resolve this uncertainty, a logically prior question is whether the associations of mental disorders with subsequent substance disorders are strong enough to justify mounting such an intervention. We investigated this question in this study using simulations to estimate the number of substance disorders that might be prevented under several hypothetical intervention scenarios focused on mental disorders. METHOD: Data came from the National Comorbidity Survey Replication (NCS-R), a nationally representative US household survey that retrospectively assessed lifetime history and age of onset of DSM-IV mental and substance disorders. Survival analysis using retrospective age-of-onset reports was used to estimate associations of mental disorders with subsequent substance dependence. Simulations based on the models estimated effect sizes in several hypothetical intervention scenarios. RESULTS: Although successful intervention aimed at mental disorders might prevent some proportion of substance dependence, the number of cases of mental disorder that would have to be treated to prevent a single case of substance dependence is estimated to be so high that this would not be a cost-effective way to prevent substance dependence (in the range 76-177 for anxiety-mood disorders and 40-47 for externalizing disorders). CONCLUSIONS: Treatment of prior mental disorders would not be a cost-effective way to prevent substance dependence. However, prevention of substance dependence might be considered an important secondary outcome of interventions for early-onset mental disorders.

Dysregulation of objectively assessed 24-hour motor activity patterns as a potential marker for bipolar I disorder: results of a community-based family study.

There has been a growing number of studies that have employed actigraphy to investigate differences in motor activity in mood disorders. In general, these studies have shown that people with bipolar disorders (BPDs) tend to exhibit greater variability and less daytime motor activity than controls. The goal of this study was to examine whether patterns of motor activity differ in euthymic individuals across the full range of mood disorder subtypes (Bipolar I (BPI), Bipolar II (BPII) and major depression (MDD)) compared with unaffected controls in a community-based family study of mood spectrum disorders. Minute-to-minute activity counts derived from actigraphy were collected over a 2-week period for each participant. Prospective assessments of the level, timing and day-to-day variability of physical activity measures were compared across diagnostic groups after controlling for a comprehensive list of potential confounding factors. After adjusting for the effects of age, sex, body mass index (BMI) and medication use, the BPI group had lower median activity intensity levels across the second half of the day and greater variability in the afternoon compared with controls. Those with a history of BPII had increased variability during the night time compared with controls, indicating poorer sleep quality. No differences were found in the average intensity, variability or timing of activity in comparisons between other mood disorder subgroups and controls. Findings confirm evidence from previous studies that BPI may be a manifestation of a rhythm disturbance that is most prominent during the second half of the day. The present study is the largest study to date that included the full range of mood disorder subgroups in a nonclinical sample that increases the generalizability of our findings to the general community. The manifestations of activity patterns outside of acute episodes add to the accumulating evidence that dysregulation of patterns of activity may constitute a potential biomarker for BPD.

The epidemiology of common mental disorders from age 20 to 50: results from the prospective Zurich cohort Study.

BACKGROUND: There are only a small number of prospective studies that have systematically evaluated standardised diagnostic criteria for mental disorder for more than a decade. The aim of this study is to present the approximated overall and sex-specific cumulative incidence of mental disorder in the Zurich cohort study, a prospective cohort study of 18-19 years olds from the canton of Zurich, Switzerland, who were followed through age 50. METHOD: A stratified sample of 591 participants were interviewed with the Structured Psychopathological Interview and Rating of the Social Consequences of Psychological Disturbances for Epidemiology, a semi-structured interview that uses a bottom-up approach to assess the past-year presence of 15 psychiatric syndromes. Seven interview waves took place between 1979 and 2008. Approximated cumulative incidence was estimated using Kaplan-Meier methods. RESULTS: Rates of mental disorder were considerably higher than those generally reported in cross-sectional surveys. We found rates ranging from 32.5% for major depressive disorder to 1.2% for Bipolar I disorder. The cumulative probability of experiencing any of the mental disorders assessed by age 50 was 73.9%, the highest reported to date. We also found that rates differed by sex for most disorders, with females generally reporting higher rates of mood, anxiety and phobic disorder, and males reporting higher rates of substance- and alcohol-related disorders. CONCLUSIONS: These findings confirm those of other long-term prospective studies that indicate the nearly universal nature of disturbances of emotion and behaviour across the life span. Greater community awareness of the normative nature of these experiences is warranted. An important area of future research is study long-term course and stability to determine who among those with such disturbances suffer from chronic disabling mental disorders. Such longitudinal studies may aid in directing services and intervention efforts where they are most needed.

Assortative mating for psychiatric disorders and psychological traits.

This article reviews the literature on assortative mating for psychological traits and psychiatric illness. Assortative mating appears to exist for personality traits, but to a lesser degree than that observed for physical traits, sociodemographic traits, intelligence, and attitudes and values. Concordance between spouses for psychiatric illness has also been consistently reported in numerous studies. This article examines alternative explanations for such observed concordance and discusses the effects of assortative mating on population genetics and the social environment.

Migraine and psychopathology. Results of the Zurich cohort study of young adults.

We present data regarding the association of psychiatric syndromes and migraine headache from a prospective epidemiologic cohort study of 27- and 28-year-olds in Zurich, Switzerland. The prevalence of migraine of 13.3% approximates estimates from previous epidemiologic studies in other regions of the world. Consistent with previous reports, there was a strong association between migraine and depression. However, this is the first study to demonstrate this association in an unselected epidemiologic sample with standardized assessment of psychiatric diagnoses by direct interview. The association between migraine and the anxiety disorders was even stronger than that for the affective disorders. The combination of anxiety disorder and major depression, but not pure anxiety disorders, nor pure depression, were significantly associated with migraine. Our data suggest that migraine with anxiety and depression may constitute a distinct syndrome comprising anxiety, often manifested in early childhood, followed by the occurrence of migraine headaches, and then by discrete episodes of depressive disorder in adulthood. Because of the prospective longitudinal design of this study, future assessments of this cohort will provide further information on the stability of these findings and the course of this cohort as subjects proceed through adulthood.

Linkage studies of bipolar disorder: methodologic and analytic issues. Report of MacArthur Foundation Workshop on Linkage and Clinical Features in Affective Disorders.

To review the findings of the linkage studies of affective disorders, a workshop, "Linkage and Clinical Features in Affective Disorders," was organized by the MacArthur Foundation Mental Health Research Network I on the Psychobiology of Depression meeting in Alexandria, Va, April 13 to 15, 1989. The major goals of the workshop for affective disorders were to explore the relationship between genetic and clinical heterogeneity, to identify major impediments to linkage studies, and to develop recommendations for the application of standardized methods of conducting linkage studies. The participants in the conference presented detailed demographic and clinical data from most of the published linkage studies of affective disorders. No systematic correspondence between genetic and clinical subtypes of bipolar disorder pedigrees was evident. The major problems hampering the linkage analyses of psychiatric disorders that were identified follow: (1) the major psychiatric disorders--the affective disorders in particular--constituting complex human disorders; (2) the lack of valid definitions of affective disorders; (3) comorbidity between the affective disorders with other disorders; (4) nonrandom mating; (5) a cohort effect, with younger birth cohorts exhibiting higher rates of affective disorders; and (6) the lack of replication of current linkage studies. The recommendations that were made for linkage study designs that incorporate some of the complexities of the affective disorders are reported.

Assortative mating, social adjustment, and course of illness in primary affective disorder.

Fifty-six married inpatients with primary affective disorders and their spouses participated in a 12- to 36-month follow-up study in which the relationship of assortative mating to social adjustment and course of illness was examined. At follow-up, the patients who were concordant with their spouses for psychiatric illness had poorer social adjustment than the group of patients with well spouses. This finding was confirmed by both relatives' ratings and clinicians' ratings of the patients' social adjustment. Measures of relapse since the target hospitalization and self-rated symptoms at the time of follow-up were not different for the two groups. The divorce rate, however, was significantly greater for the couples who were concordant for psychiatric illness when compared with the discordant couples.

Parental psychopathology, parenting styles, and the risk of social phobia in offspring: a prospective-longitudinal community study.

BACKGROUND: This article examines the associations between DSM-IV social phobia and parental psychopathology, parenting style, and characteristics of family functioning in a representative community sample of adolescents. METHODS: Findings are based on baseline and first follow-up data of 1047 adolescents aged 14 to 17 years at baseline (response rate, 74.3%), and independent diagnostic interviews with one of their parents. Diagnostic assessments in parents and adolescents were based on the DSM-IV algorithms of the Munich-Composite International Diagnostic Interview. Parenting style (rejection, emotional warmth, and overprotection) was assessed by the Questionnaire of Recalled Parental Rearing Behavior, and family functioning (problem solving, communication, roles, affective responsiveness, affective involvement, and behavioral control) was assessed by the McMaster Family Assessment Device. RESULTS: There was a strong association between parental social phobia and social phobia among offspring (odds ratio [OR], 4.7; 95% confidence interval [CI], 1.6-13.5). Other forms of parental psychopathology also were associated with social phobia in adolescents (depression: OR, 3.6; 95% CI, 1.4-9.1; any anxiety disorder other than social phobia: OR, 3.5; 95% CI, 1.4-8.8; and any alcohol use disorder: OR, 3.0; 95% CI, 1.1-7.8). Parenting style, specifically parental overprotection (OR, 1.4; 95% CI, 1.0-1.9) and rejection (OR, 1.4; 95% CI, 1.1-1.9), was found to be associated with social phobia in respondents. Family functioning was not associated with respondents' social phobia. CONCLUSIONS: Data suggest that parental psychopathology, particularly social phobia and depression, and perceived parenting style (overprotection and rejection) are both associated with the development of social phobia in youth.

Family-genetic studies of psychiatric disorders. Developing technologies.

During the past decade new concepts and technologies have improved the conduct of family-genetic studies in psychiatry. We compiled and critically evaluated these advances, including study design, pedigree collection, diagnostic procedures in adults and children, and epidemiologic and genetic approaches to data analysis. These approaches have improved the collection of accurate information on the nature and patterns of psychiatric illness in families. The data generated from well-designed and well-conducted family studies are useful for the identification of homogeneous subgroups of psychiatric disorders, for understanding the spectrum of psychiatric disorders, for examining the associations between psychiatric disorders, and for studying the continuity between adult and childhood manifestations of psychiatric disorders. Findings from these studies also may enhance our capacity to identify the mode of transmission of the psychiatric disorders and to select potentially informative families for future genetic linkage studies using the new recombinant DNA techniques. The adaptation of these methods to routine clinical practice and new directions in the application of family-genetic studies employing more refined assessments and analytic methods are also discussed.