Correlates of suicide attempt history in bipolar disorder: a stress-diathesis perspective

Objectives:  Distinguishing clinical characteristics of bipolar patients who have made a suicide attempt may help to identify at-risk individuals. We sought to identify such factors and to consider them within a stress-diathesis model of suicidal behavior.
Methods:  Patients with bipolar disorder (N = 96) were compared with respect to the presence or absence at baseline evaluation of a history of suicide attempt. We used multiple logistic regression analysis to assess the unique associations of independent variables to history of a past suicide attempt.
Results:  The regression analysis showed that a history of suicide attempt in bipolar disorder was associated with greater recent suicidal ideation, more psychiatric hospitalizations, lifetime aggressive traits and an earlier age at onset of a first mood episode.
Conclusions:  Aggressive traits and early treatment of mood disorders, especially major depressive episodes, are potential targets for suicide prevention in bipolar disorder.     

Polarity at illness onset in bipolar I disorder and clinical course of illness

Objectives:  Studies have suggested that episode polarity at illness onset in bipolar disorder may be predictive of some aspects of lifetime clinical characteristics. We here examine this possibility in a large, well-characterized sample of patients with bipolar I disorder.
Methods:  We assessed polarity at onset in patients with bipolar I disorder (N = 553) recruited as part of our ongoing studies of affective disorders. Lifetime clinical characteristics of illness were compared in patients who had a depressive episode at first illness onset (n = 343) and patients who had a manic episode at first illness onset (n = 210).
Results:  Several lifetime clinical features differed between patients according to the polarity of their onset episode of illness. A logistic regression analysis showed that the lifetime clinical features significantly associated with a depressive episode at illness onset in our sample were: an earlier age at illness onset; a predominantly depressive polarity during the lifetime; more frequent and more severe depressive episodes; and less prominent lifetime psychotic features.
Conclusions:  Knowledge of pole of onset may help the clinician in providing prognostic information and management advice to an individual with bipolar disorder.     

Prevalence and clinical correlates of alcohol use disorders among bipolar disorder patients: Results from the Brazilian Bipolar Research Network

Objectives

To investigate prevalence rates and clinical correlates of alcohol use disorders (AUD) among bipolar disorder (BD) patients in a large sample from the Brazilian Bipolar Research Network.

Methods

Four hundred and eighty-three DSM-IV BD patients, divided according to the presence or absence of a lifetime AUD diagnosis (BD-AUD vs. BD-nonAUD), were included. Demographic and clinical characteristics of these two groups were compared. Logistic regression was performed to identify which characteristics were most strongly associated with a lifetime AUD diagnosis.

Results

Nearly 23% presented a lifetime AUD diagnosis. BD-AUD patients were more likely to be male, to present rapid cycling, post-traumatic stress disorder (PTSD), anorexia, other substance use disorders (SUD), family history of SUD, any substance misuse during the first mood episode, history of psychosis, suicide attempts, and younger age at onset of illness than BD-nonAUD patients. Logistic regression showed that the variables most strongly associated with a lifetime AUD diagnosis were SUD (non-alcohol), any substance misuse during the first mood episode, PTSD, male gender, suicide attempt, family history of SUD, and younger age at onset of BD.

Conclusions

BD-AUD patients begin their mood disorder earlier and present more suicidal behaviors than BD-nonAUD patients. Personal and family history of SUD may be good predictors of comorbid AUD among BD patients. These variables are easily assessed in the clinical setting and may help to identify a particularly severe subgroup of BD patients.     

Comorbid anxiety in bipolar disorder: does it have an independent effect on suicidality?

Objective:  Comorbid anxiety disorder is reported to increase suicidality in bipolar disorder. However, studies of the impact of anxiety disorders on suicidal behavior in mood disorders have shown mixed results. The presence of personality disorders, often comorbid with anxiety and bipolar disorders, may explain these inconsistencies. This study examined the impact of comorbid Cluster B personality disorder and anxiety disorder on suicidality in bipolar disorder.
Methods:  A total of 116 depressed bipolar patients with and without lifetime anxiety disorder were compared. Multiple regression analysis tested the association of comorbid anxiety disorder with past suicide attempts and severity of suicidal ideation, adjusting for the effect of Cluster B personality disorder. The specific effect of panic disorder was also explored.
Results:  Bipolar patients with and without anxiety disorders did not differ in the rate of past suicide attempt. Suicidal ideation was less severe in those with anxiety disorders. In multiple regression analysis, anxiety disorder was not associated with past suicide attempts or with the severity of suicidal ideation, whereas Cluster B personality disorder was associated with both. The results were comparable when comorbid panic disorder was examined.
Conclusions:  Comorbid Cluster B personality disorder appears to exert a stronger influence on suicidality than comorbid anxiety disorder in persons with bipolar disorder. Assessment of suicide risk in patients with bipolar disorder should include evaluation and treatment of Cluster B psychopathology.     

Rapid switching of mood in families with familial bipolar disorder

Objective:  Rapid switching of moods in bipolar disorder has been associated with early age at onset, panic comorbidity, and suicidality. This study aims to confirm these associations and investigate other potential correlates of rapid switching of mood using families from a multisite bipolar linkage study.
Methods:  The subjects were comprised of 1,143 probands and relatives with diagnosis of bipolar disorder. All subjects were interviewed directly with a standard diagnostic instrument, and all subjects who met criteria for bipolar disorder were asked if their moods had ever switched rapidly.
Results:  Individuals with rapid mood switching had significantly earlier age at onset (18 versus 21 years, p < 0.00001), higher comorbid anxiety (47% versus 26%, p < 0.00001) and substance use disorders (52% versus 42%, p = 0.0006), higher rate of violent behavior (6% versus 3%, p < 0.004), suicidal behavior (46% versus 31%, p < 0.00001), and nonsuicidal self-harm (13% versus 6%, p < 0.0002). Multiple logistic regression analysis found significant net effects on rapid mood switching for early emergence of symptoms [odds ratio (OR) = 0.62; 95% confidence interval (CI): 0.45–0.85]; anxiety comorbidity (OR = 2.31; 95% CI: 1.34–3.98); and hypersensitivity to antidepressants (OR = 2.05; 95% CI: 1.49–2.83) as the strongest predictors.
Conclusions:  This confirms earlier reports associating rapid switching with a more complex clinical course, in particular early emergence of bipolar symptomatology, antidepressant activation, and anxiety comorbidity. These results support a clinical differentiation of bipolar disorder into subtypes based on symptom stability.     

Bipolar-panic disorder comorbidity within bipolar disorder families: a study of siblings

Objectives:  Although anxiety disorders often co-occur with bipolar disorder in clinical settings, relatively few studies of bipolar disorder have looked specifically at panic comorbidity. This report examines lifetime panic comorbidity within a sample of families with a history of bipolar disorder.
Methods:  One hundred and nine probands with bipolar disorder and their 226 siblings were interviewed as part of a family-genetic study. Logistic regression was used to model bipolar disorder as a predictor of comorbid panic in those with affective disorder, with age at interview and gender included as covariates.
Results:  The percentage with panic attacks was low in those without affective disorder (3%) compared with those with unipolar depression (22%) or bipolar disorder (32%). Panic disorder was found only in those with affective disorder (6% for unipolar, 16% for bipolar). When bipolar disorder and unipolar disorder were compared, controlling for age and sex, having bipolar disorder was associated with panic disorder (OR = 3.0, 95% CI = 1.1, 7.8) and any panic symptoms (OR = 2.0, CI = 1.0,3.8) and more weakly with the combination of panic disorder and recurrent attacks (OR = 1.8, CI = 0.9, 3.5).
Conclusions:  The absence of panic disorder and the low prevalence of any panic symptoms in those without bipolar or unipolar disorder suggest that panic is associated primarily with affective disorder within families with a history of bipolar disorder. Furthermore, panic disorder and symptoms are more common in bipolar disorder than in unipolar disorder in these families.     

Suicide risk in bipolar patients: the role of co-morbid substance use disorders

Objective:  Bipolar disorder is associated with a high frequency of both completed suicides and suicide attempts. The primary aim of this study was to identify clinical predictors of suicide attempts in subjects with bipolar disorder.
Methods:  We studied 336 subjects with a diagnosis of bipolar I, bipolar II, or schizoaffective disorder (bipolar type). The Structured Clinical Interview for DSM-IV (SCID-I) was administered and subsequently two expert psychiatrists established a diagnosis. Predictors of suicide attempts were examined in attempters and non-attempters.
Results:  The lifetime rate of suicide attempts for the entire sample was 25.6%. A lifetime co-morbid substance use disorder was a significant predictor of suicide attempts: bipolar subjects with co-morbid substance use disorders (SUD) had a 39.5% lifetime rate of attempted suicide, while those without had a 23.8% rate (odds ratio=2.09, 95% CI=1.03–4.21, χ²=4.33, df=1, p=0.037).
Conclusions:  Lifetime co-morbid SUD were associated with a higher rate of suicide attempts in patients with bipolar disorder. This relationship may have a genetic origin and/or be explained by severity of illness and trait impulsivity.     

Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder

OBJECTIVE: Bipolar disorder often co-occurs with other axis I disorders, but little is known about the relationships between the clinical features of bipolar illness and these comorbid conditions. Therefore, the authors assessed comorbid lifetime and current axis I disorders in 288 patients with bipolar disorder and the relationships of these comorbid disorders to selected demographic and historical illness variables. METHOD: They evaluated 288 outpatients with bipolar I or II disorder, using structured diagnostic interviews and clinician-administered and self-rated questionnaires to determine the diagnosis of bipolar disorder, comorbid axis I disorder diagnoses, and demographic and historical illness characteristics. RESULTS: One hundred eighty-seven (65%) of the patients with bipolar disorder also met DSM-IV criteria for at least one comorbid lifetime axis I disorder. More patients had comorbid anxiety disorders (N=78, 42%) and substance use disorders (N=78, 42%) than had eating disorders (N=9, 5%). There were no differences in comorbidity between patients with bipolar I and bipolar II disorder. Both lifetime axis I comorbidity and current axis I comorbidity were associated with earlier age at onset of affective symptoms and syndromal bipolar disorder. Current axis I comorbidity was associated with a history of development of both cycle acceleration and more severe episodes over time. CONCLUSIONS: Patients with bipolar disorder often have comorbid anxiety, substance use, and, to a lesser extent, eating disorders. Moreover, axis I comorbidity, especially current comorbidity, may be associated with an earlier age at onset and worsening course of bipolar illness. Further research into the prognostic and treatment response implications of axis I comorbidity in bipolar disorder is important and is in progress.     

Comparison of manic and depressive symptoms between children and adolescents with bipolar spectrum disorders

Objective: To compare the most severe lifetime (current or past) mood symptoms, duration of illness, and rates of lifetime comorbid disorders among youth with bipolar spectrum disorders [BP (bipolar‐I, bipolar‐II and bipolar–not otherwise specified)]. Methods: A total of 173 children (<12 years) with BP, 101 adolescents with childhood‐onset BP, and 90 adolescents with adolescent‐onset BP were evaluated with standardized instruments. Results: Depression was the most common initial and frequent episode for both adolescent groups, followed by mania/hypomania. Adolescents with childhood‐onset BP had the longest illness, followed by children and then adolescents with adolescent‐onset BP. Adjusting for sex, socioeconomic status, and duration of illness, while manic, both adolescent groups showed more ‘typical’ and severe manic symptoms. Mood lability was more frequent in childhood‐onset and adolescents with early‐onset BP. While depressed, both adolescent groups showed more severe depressive symptoms, higher rates of melancholic and atypical symptoms, and suicide attempts than children. Depressed children had more severe irritability than depressed adolescents. Early BP onset was associated with attention‐deficit hyperactivity disorder, whereas later BP onset was associated with panic, conduct, and substance use disorders. Above‐noted results were similar when each BP subtype was analyzed separately. Conclusions: Older age was associated with more severe and typical mood symptomatology. However, there were differences and similarities in type, intensity, and frequency of BP symptoms and comorbid disorders related to age of onset and duration of BP and level of psychosocial development. These factors and the normal difficulties youth have expressing and modulating their emotions may explain existing complexities in diagnosing and treating BP in youth, particular in young children, and suggest the need for developmentally sensitive treatments.     

Impact of remitted substance use disorders on the future course of bipolar I disorder: findings from a clinical trial

Given the high lifetime prevalence rates of bipolar disorder and comorbid substance use disorders (SUDs), the aim of the study was to examine the effect of a remitted SUD on the future course of bipolar I disorder in patients taking part in a clinical trial. Patients with bipolar I disorder were enrolled in a larger study examining the effects of pharmacotherapy plus family interventions. These patients were recruited during an acute mood episode and their mood symptoms and substance abuse were assessed longitudinally for up to 28 months. Patients with a remitted SUD showed a poorer acute treatment response, a longer time to remission of their acute mood episode, and a greater percentage of time with subthreshold but clinically significant depression and manic symptoms over follow-up compared to those without this comorbidity pattern. Subsequent substance abuse during follow-up could not fully account for the poorer course of illness. As remitted SUDs appear to negatively predict treatment outcome, current findings have implications for both clinical trials of bipolar patients as well as clinical practice.     

Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study

Objective:  Symptoms of bipolar disorder are increasingly recognized among children and adolescents, but little is known about the course of bipolar disorder among adults who experience childhood onset of symptoms.
Methods:  We examined prospective outcomes during up to two years of naturalistic treatment among 3,658 adult bipolar I and II outpatients participating in a multicenter clinical effectiveness study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Age at illness onset was identified retrospectively by clinician assessment at study entry.
Results:  Compared to patients with onset of mood symptoms after age 18 years (n = 1,187), those with onset before age 13 years (n = 1,068) experienced earlier recurrence of mood episodes after initial remission, fewer days of euthymia, and greater impairment in functioning and quality of life over the two-year follow-up. Outcomes for those with onset between age 13 and 18 years (n = 1,403) were generally intermediate between these two groups.
Conclusion:  Consistent with previous reports in smaller cohorts, adults with retrospectively obtained early-onset bipolar disorder appear to be at greater risk for recurrence, chronicity of mood symptoms, and functional impairment during prospective observation.     

Childhood mania,attention deficit hyperactivity disorder and conduct disorder: a critical review of diagnostic dilemmas

Objectives:  Significant debate exists on whether early onset bipolar disorder is mistakenly attributed to attention deficit hyperactivity disorder (ADHD) or conduct disorder (CD), or whether ADHD and CD are frequently misdiagnosed as mania. We review the literature on the extent to which these disorders can be reliably differentiated, and describe the diagnostic confusion that may be the result of features common to both classes of disorders.
Methods:  The review focuses on research studies that have examined whether overlapping symptoms of bipolar disorder, ADHD, and CD contribute to misdiagnosis of the two classes of disorders, the prevalence of early onset bipolar disorder with comorbid ADHD or CD, and theories regarding the origins of this comorbidity.
Results:  Reliable and accurate diagnoses can be made despite the symptom overlap of bipolar disorder with ADHD and CD. Children with bipolar disorder and ADHD may have a distinct familial subtype of bipolar disorder. Some findings suggest that manic symptoms may represent `noise' that indicates the general severity of psychopathology in a child or adolescent.
Conclusions:  Further prospective studies may confirm whether early onset bipolarity can be successfully differentiated from ADHD or CD, whether all three types of disorders can be recognized in comorbid cases, or whether comorbid cases represent a distinct subtype of bipolar disorder.     

Health-related quality of life measures and psychiatric comorbidity in patients with migraine

Background and purpose:  The identification of factors associated to health-related quality of life (HRQoL) measures in patients with migraine has major implications in terms of prognosis and treatment. This study aimed at investigating associations between HRQoL and comorbid mood and anxiety disorders.
Methods:  Consecutive adult outpatients with a diagnosis of migraine with or without aura were assessed using the Mini International Neuropsychiatric Interview (M.I.N.I.) Plus version 5.0.0 and the Migraine-Specific Quality-of-Life Questionnaire (MSQ).
Results:  Data of 112 patients (82 females), 69 without aura, mean age 41.2 ± 13.3 years were analyzed. According to the M.I.N.I., 50% patients had a lifetime or current DSM-IV diagnosis of mood or anxiety disorder. There was no between-groups difference in MSQ total and subscale scores in relation to the presence/absence of psychiatric comorbidity, independently whether that was current or lifetime. In the group of subjects with psychiatric disorders, age at onset of migraine correlated with MSQ-total (rho = −0.407 P  = 0.002), and subscale scores (Role Function-Restrictive, rho = −0.397, P  = 0.002; Emotional Function, rho = −0.487, P  < 0.001).
Conclusions:  Our findings suggest that current and/or lifetime psychiatric comorbidities are not associated with HRQoL measures in patients with migraine. However, patients with migraine and psychiatric comorbidities may represent a specific subgroup deserving particular attention for targeted interventions.     

The spectrum of substance abuse in bipolar disorder: reasons for use, sensation seeking and substance sensitivity

OBJECTIVES: To examine the spectrum of alcohol and substance abuse, including reasons for use, in patients with bipolar I disorder, compared with patients with substance use disorder and healthy controls, with a specific focus on the relationship between substance use, substance sensitivity, other comorbid psychiatric symptoms and traits related to sensation seeking. METHODS: This study included 104 patients with bipolar I disorder (BPD I), of whom 57 (54.8%) met DSM-IV criteria for lifetime alcohol or substance use disorder (BPD + SUD), 35 patients with substance use disorder (SUD) and no psychiatric disorder and 50 healthy controls. Assessments included the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS). RESULTS: Patients with BPD + SUD and SUD had significantly higher scores on the SCI-SUBS domains of self-medication, substance sensitivity and sensation seeking compared with patients with BPD and healthy controls. Reasons for substance use did not differ between patients with BPD + SUD and patients with SUD. Those most frequently cited were: improving mood; relieving tension; alleviating boredom; achieving/maintaining euphoria; and increasing energy. CONCLUSIONS: Recourse to substances is associated with increased mood and anxiety symptoms, substance sensitivity, and sensation seeking among patients with BPD + SUD and SUD. Substance sensitivity and sensation seeking traits should be investigated in all patients with BPD as possible factors associated with a development of SUD, in order to warn patients of the specific risks related to improper use of medications and substances.     

Age at onset of bipolar disorder and risk for comorbid borderline personality disorder

Objectives: The relationship between bipolar disorder and cluster B personality disorders remains phenomenologically complex and controversial. We sought to examine the relationship between early age at onset of bipolar disorder and development of comorbid borderline personality disorder. Methods: A total of 100 adults in an academic specialty clinic for bipolar disorder underwent structured diagnostic interviews and clinical assessments to determine lifetime presence of comorbid borderline personality disorder, histories of childhood trauma, and clinical illness characteristics. Results: Logistic regression indicated that increasing age at onset of bipolar disorder was associated with a lower probability of developing comorbid borderline personality disorder (odds ratio = 0.91, 95% confidence interval: 0.83–0.99) while controlling for potential confounding factors, including a history of severe child trauma/abuse. Conclusion: Early onset of bipolar disorder increases the probability of developing comorbid borderline personality disorder, independent of the effects of severe childhood trauma/abuse. In patients with borderline personality disorder, prospective studies of new‐onset bipolar disorder may underestimate the prevalence of true comorbidity unless they capture the primary risk window for first‐episode mania arising before the end of adolescence.     

Approximate entropy of self-reported mood prior to episodes in bipolar disorder

Background:  Approximate entropy (ApEn) measures regularity in time series data, while traditional linear statistics measure variability. Using self-reported mood data from patients with bipolar disorder, this preliminary study addressed whether ApEn could distinguish (i) the 60 days prior to the start of a manic or depressed episode from the 60 days prior to a month of euthymia, and (ii) the 60 days prior to a manic episode from the 60 days prior to a depressed episode.
Methods:  Self-reported mood data from 49 outpatients with bipolar disorder receiving standard treatment were analysed. The data contained 27 episodes (12 manic and 15 depressed), and 43 periods of 1 month of euthymia. For the 60 days prior to episode or euthymia, the ApEn, linear statistics and the correlation between linear and non-linear measures were calculated.
Results:  ApEn was significantly greater in the 60 days prior to a manic or depressive episode than the 60 days prior to a month of euthymia. The onset of an episode was associated with greater irregularity in mood. Variability was also significantly larger and correlated with ApEn. ApEn was significantly greater in the 60 days prior to a manic episode than in the 60 days prior to a depressed episode, whereas measures of variability were not significantly different. Mood in the 60 days prior to mania was more irregular than prior to depression.
Conclusions:  Non-linear measures may complement traditional linear measures in the analysis of longitudinal data in bipolar disorder. A larger study is indicated.     

Missed bipolarity and psychiatric comorbidity in women with postpartum depression

Objective:  To investigate the diagnostic profile of women referred for postpartum depression.
Methods:  Fifty-six women seen consecutively with the referral diagnosis of postpartum depression were administered structured instruments to gather information about their DSM-IV Axis I diagnoses.
Results:  In terms of frequency of occurrence, the primary diagnoses in this sample were: major depressive disorder (46%), bipolar disorder not otherwise specified (29%), bipolar II disorder (23%), and bipolar I disorder (2%). A current comorbid disorder, with no lifetime comorbidity, occurred among 32% of the sample; by contrast, lifetime comorbidity alone (i.e., with no currently comorbid disorder) was found among 27%. Both a lifetime and a current comorbidity were found among 18% of the women, and 23% had no comorbid disorder. The most frequently occurring current comorbid disorder was an anxiety disorder (46%), with obsessive-compulsive disorder (62%) being the most common type of anxiety disorder. For lifetime comorbidity, substance use (20%) and anxiety disorders (12%) were the two most common. Over 80% of patients who scored positive on either the Highs Scale or the Mood Disorder Questionnaire met the diagnostic criteria for a bipolar disorder.
Conclusion:  The results suggest that postpartum depression is a heterogeneous entity and that misdiagnosis of bipolar disorder in the postpartum period may be quite common. The findings have important clinical implications, which include the need for early detection of bipolarity through the use of reliable and valid assessment instruments, and implementation of appropriate prevention and treatment strategies.     

Medical comorbidity in bipolar disorder: implications for functional outcomes and health service utilization

OBJECTIVE: This is the first cross-national population-based investigation exploring the prevalence and functional implications of comorbid general medical disorders in bipolar disorder. METHODS: Data were extracted from the Canadian Community Health Survey (N = 36,984). Analyses were conducted to ascertain the prevalence and prognostic implications of predetermined comorbid general medical disorders among persons who screened positive for a lifetime manic episode (indicative of a diagnosis of bipolar disorder). Within the subpopulation of people who screened positive for a manic episode, the effect of medical comorbidity on employment, functional role, psychiatric care, and medication use was examined. RESULTS: When the data were weighted to be representative of the household population of the ten provinces in 2002, an estimated 2.4 percent of respondents screened positive for a lifetime manic episode. Rates of chronic fatigue syndrome, migraine, asthma, chronic bronchitis, multiple chemical sensitivities, hypertension, and gastric ulcer were significantly higher in the bipolar disorder group (all p < .05). Chronic medical disorders were associated with a more severe course of bipolar disorder, increased household and work maladjustment, receipt of disability payments, reduced employment, and more frequent medical service utilization. CONCLUSIONS: Comorbid medical disorders in bipolar disorder are associated with several indices of harmful dysfunction, decrements in functional outcomes, and increased utilization of medical services.     

Clinical characteristics of unipolar disorder and bipolar disorder according to the lifetime presence of recurrent panic attacks

Objectives:  The frequent comorbidity of panic and affective disorders has been described in previous studies. However, it is not clear how panic disorder comorbidity in unipolar disorder and bipolar disorder is related to illness course.
Methods:  We compared lifetime clinical characteristics of illness and items of symptomatology in samples of individuals with bipolar I disorder (n = 290) and unipolar disorder (n = 335) according to the lifetime presence of recurrent panic attacks.
Results:  We found significant differences in clinical course of illness characteristics that were shared across the unipolar and bipolar samples according to the lifetime presence of panic attacks. We also found a number of differences according to the presence of panic attacks that may be specific to the diagnostic group.
Conclusions:  Distinguishing patients who have mood disorder diagnoses, especially bipolar I disorder, according to the lifetime presence of panic attacks may not only be of use in clinical practice, but may also be informative for aetiological research, such as molecular genetic studies.     

Psychiatric comorbidity in adult attention deficit hyperactivity disorder: findings from multiplex families

OBJECTIVE: Patterns of psychiatric comorbidity were assessed in adults with and without attention deficit hyperactivity disorder (ADHD) identified through a genetic study of families containing multiple children with ADHD. METHOD: Lifetime ADHD and comorbid psychopathology were assessed in 435 parents of children with ADHD. Rates and mean ages at onset of comorbid psychopathology were compared in parents with lifetime ADHD, parents with persistent ADHD, and those without ADHD. Age-adjusted rates of comorbidity were compared with Kaplan-Meier survival curves. Logistic regression was used to assess additional risk factors for conditions more frequent in ADHD subjects. RESULTS: The parents with ADHD were significantly more likely to be unskilled workers and less likely to have a college degree. ADHD subjects had more lifetime psychopathology; 87% had at least one and 56% had at least two other psychiatric disorders, compared with 64% and 27%, respectively, in non-ADHD subjects. ADHD was associated with greater disruptive behavior, substance use, and mood and anxiety disorders and with earlier onset of major depression, dysthymia, oppositional defiant disorder, and conduct disorder. Group differences based on Kaplan-Meier age-corrected risks were consistent with those for raw frequency distributions. Male sex added risk for disruptive behavior disorders. Female sex and oppositional defiant disorder contributed to risk for depression and anxiety. ADHD was not a significant risk factor for substance use disorders when male sex, disruptive behavior disorders, and socioeconomic status were controlled. CONCLUSIONS: Adult ADHD is associated with significant lifetime psychiatric comorbidity that is not explained by clinical referral bias.