Hendrick V, Altshuler LL, Gitlin MJ, Delrahim S, Hammen C.
Gender and bipolar illness.
J Clin Psychiatry 2000 May;61(5):393-6; quiz 397
"BACKGROUND: For major depression and schizophrenia, gender differences have been reported in symptom expression and course of illness. Gender differences in bipolar disorder are becoming increasingly apparent, but have been less studied. Research data on these differences will help determine whether gender is important in influencing illness variables such as course, symptom expression, and likelihood of comorbidity. METHOD: Charts of 131 patients (63 women and 68 men) with a DSM-IV diagnosis of bipolar disorder admitted to the University of California Los Angeles Mood Disorders Program over a 3-year period were reviewed to gather data on demographic variables and course of illness and to assess differences in the illness across genders. RESULTS: No significant gender differences were found in the rate of bipolar I or bipolar II diagnoses, although women were overrepresented in the latter category. Also, no significant gender differences emerged in age at onset, number of depressive or manic episodes, and number of hospitalizations for depression. Women, however, had been hospitalized significantly more often than men for mania. Further, whereas bipolar men were significantly more likely than bipolar women to have a comorbid substance use disorder, women with bipolar disorder had 4 times the rate of alcohol use disorders and 7 times the rate of other substance use disorders than reported in women from community-derived samples. CONCLUSION: For bipolar disorder, course of illness variables such as age at onset and number of affective episodes of each polarity do not seem to differ across genders. Women, however, may be more likely than men to be hospitalized for manic episodes. While both men and women with the illness have high rates of comorbidity with alcohol and other substance use disorders, women with bipolar disorder are at a particularly high risk for comorbidity with these conditions." [Abstract]

Arnold LM.
Gender differences in bipolar disorder.
Psychiatr Clin North Am. 2003 Sep;26(3):595-620.
"The presentation and course of bipolar disorder differs between women and men. The onset of bipolar disorder tends to occur later in women than men, and women more often have a seasonal pattern of the mood disturbance. Women experience depressive episodes, mixed mania, and rapid cycling more often than men. Bipolar II disorder, which is predominated by depressive episodes, also appears to be more common in women than men. Comorbidity of medical and psychiatric disorders is more common in women than men and adversely affects recovery from bipolar disorder more often in women. Comorbidity, particularly thyroid disease, migraine, obesity, and anxiety disorders occur more frequently in women than men, whereas substance use disorders are more common in men. Although the course and clinical features of bipolar disorder differ between women and men, there is no evidence that gender affects treatment response to mood stabilizers. However, women may be more susceptible to delayed diagnosis and treatment. Treatment of women during pregnancy and lactation is challenging because available mood stabilizers pose potential risks to the developing fetus and infant. Pregnancy neither protects nor exacerbates bipolar disorder, and many women require continuation of medication during the pregnancy. The postpartum period is a time of high risk for onset and recurrence of bipolar disorder in women, and prophylaxis with mood stabilizers might be needed. Individualized risk/benefit assessments of pregnant and postpartum women with bipolar disorder are required to promote the health of the woman and avoid or limit exposure of the fetus or infant to potential adverse effects of medication." [Abstract]

Benazzi F.
Gender differences in bipolar II and unipolar depressed outpatients: a 557-case study.
Ann Clin Psychiatry 1999 Jun;11(2):55-9
"The aim of the present report was to study gender differences in bipolar II and in unipolar depressed outpatients. Consecutive 557 bipolar II and unipolar outpatients presenting for treatment of depression were interviewed with the Structured Clinical Interview for DSM-IV, the Montgomery Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale. Atypical features were significantly more common in bipolar II and in unipolar females than in males, in bipolar II females than in unipolar females, and in bipolar II males than in unipolar males. Female gender was significantly associated with atypical features, but not with diagnosis. Age at intake/onset, duration of illness, severity, recurrences, psychosis, and chronicity were not significantly different in bipolar II and in unipolar females and males (apart from comorbidity). Age at onset was significantly lower in bipolar II females than in unipolar females. This difference was not related to the higher prevalence of atypical features in bipolar II females." [Abstract]

Robb JC, Young LT, Cooke RG, Joffe RT.
Gender differences in patients with bipolar disorder influence outcome in the medical outcomes survey (SF-20) subscale scores.
J Affect Disord 1998 Jun;49(3):189-93
"BACKGROUND: The importance of gender on the course and outcome in bipolar disorder (BD) has been widely acknowledged. The limited data suggest that the prevalence is similar between sexes but that the course of illness may be different. This study investigated gender differences in a clinic sample of patients with BD including a measure of subjects' perception of well-being and functioning. METHODS: Euthymic outpatients attending a mood disorders clinic were systematically assessed. Measurements obtained included SADS-LV, Hamilton Depression Ratings scores, Young Mania Rating scores, and Medical Outcome Survey Short Form 20 items and Global Assessment of Functioning. RESULTS: Women with BD have a later onset of mania, are more likely to have a rapid cycling course, experience mixed episodes, experience more depressive episodes and report more overall impairment in all MOS subscale scores with significant impairment in physical health and pain. CONCLUSIONS: Further investigation and replication of these differences need to be addressed including non-euthymic patients and during a longer period of systematic follow-up." [Abstract]

Cassidy F, Carroll BJ.
The clinical epidemiology of pure and mixed manic episodes.
Bipolar Disord 2001 Feb;3(1):35-40
"INTRODUCTION: Few large clinical epidemiological studies have been undertaken comparing subjects meeting criteria for mixed and pure states of bipolar disorder. In part, the difficulty comparing these states emanates from confusion in their diagnostic separation. In the current report, we use a definition derived from receiver operating characteristic (ROC) curve analysis as an alternative to the DSM-IIIR/IV definition, and we compare the two subtypes of manic episodes. METHODS: Three hundred and sixty-six patients meeting DSM-IIIR criteria for bipolar disorder, manic or mixed, were categorized using newly described criteria for mixed states. The two subtypes were compared on demographic variables and clinical history variables, using multiple analysis of variance with post hoc univariate F tests. The same analyses were conducted using the DSM-IIIR-defined subtypes. RESULTS: Using the ROC criteria, 79 subjects (21.6%) were characterized as mixed, in contrast to 51 subjects (13.9%) using DSM-IIIR criteria for bipolar disorder, mixed. The ROC-defined mixed manic group comprised more Caucasians and more females. Age of first psychiatric hospitalization was earlier and duration of illness longer in the mixed group. First episodes were unlikely to be categorized as mixed (< 5%). When the DSM-IIIR definition was employed, differences were not demonstrated. CONCLUSIONS: An earlier age of first psychiatric hospitalization and increased duration of illness, as well as a lower frequency of mixed subtype of manic episode during first hospitalization, are compatible with the view that mixed manic episodes occur more frequently later in the course of bipolar disorder. Moreover, differences in race, sex, and clinical histories of subjects in mixed episodes tend to support the separation of mixed mania as a diagnostic subtype of bipolar disorder." [Abstract]

Arnold LM, McElroy SL, Keck PE Jr.
The role of gender in mixed mania.
Compr Psychiatry 2000 Mar-Apr;41(2):83-7
"This article reviews the literature regarding possible gender differences in adults with mixed mania. Studies examining gender differences in the prevalence of mixed mania, biological abnormalities, suicidality, long-term outcome, and treatment response were analyzed. Data from these studies suggest that mixed mania may occur more commonly in women than in men, especially when defined by narrow criteria. There were no significant differences between men and women with mixed mania in biological abnormalities, suicidality, outcome, and treatment response." [Abstract]

Maj M, Pirozzi R, Formicola AM, Tortorella A.
Reliability and validity of four alternative definitions of rapid-cycling bipolar disorder.
Am J Psychiatry 1999 Sep;156(9):1421-4
"OBJECTIVE: This study tested the reliability and validity of four definitions of rapid cycling. METHOD: Two trained psychiatrists, using the Schedule for Affective Disorders and Schizophrenia, independently assessed 210 patients with bipolar disorder. They checked whether each patient met four definitions of rapid cycling: one consistent with DSM-IV criteria, one waiving criteria for duration of affective episodes, one waiving such criteria and requiring at least one switch from mania to depression or vice versa during the reference year, and one waiving duration criteria and requiring at least 8 weeks of fully symptomatic affective illness during the reference year. The interrater reliability was calculated by Cohen's kappa statistic. Patients who met each definition according to both psychiatrists were compared to those who did not meet any definition (nonrapid-cycling group) on demographic and clinical variables. All patients were followed up for 1 year. RESULTS: Kappa values were 0.93, 0.73, 0.75, and 0.80, respectively, for the four definitions of rapid cycling. The groups meeting the second and third definitions included significantly more female and bipolar II patients than did the nonrapid-cycling group. Those two groups also had the lowest proportion of patients with a favorable lithium prophylaxis outcome and the highest stability of the rapid-cycling pattern on follow-up. The four groups of rapid-cycling patients did not differ significantly among themselves on any of the assessed variables. CONCLUSIONS: The expression "rapid cycling" encompasses a spectrum of conditions. The DSM-IV definition, although quite reliable, covers only part of this spectrum, and the conditions that are excluded are very typical in terms of key validators and are relatively stable over time." [Abstract]

Rasgon N, Bauer M, Glenn T, Elman S, Whybrow PC.
Menstrual cycle related mood changes in women with bipolar disorder.
Bipolar Disord. 2003 Feb;5(1):48-52.
"OBJECTIVES: A relationship between affective symptoms and menstrual cycle in women with bipolar disorder (BPD) has been suggested. This study investigates the influence of the menstrual cycle on mood in women with BPD who are taking medication, but not selected for menstrual abnormalities. METHODS: Data from women with BPD (n = 17) consecutively enrolled into a ChronoRecord validation study were included in the current analysis. All women received medication for BPD, in addition, 35% received oral contraceptives (OC). Participants entered mood, menstrual data, psychiatric medications, and life events daily for a 3-month period using a computerized version (ChronoRecord) of an established paper based form for self-reporting (ChronoSheet). RESULTS: The majority of women treated for BPD (65%) reported significant mood changes across the menstrual cycle. Long menstrual cycle was present in 59% of subjects, including those taking OC. CONCLUSIONS: Women with BPD taking medication report a high rate of long menstrual cycles, and significant mood changes in relation to menstrual cycle phase." [Abstract]

Chaudron LH, Pies RW.
The relationship between postpartum psychosis and bipolar disorder: a review.
J Clin Psychiatry. 2003 Nov;64(11):1284-92.
"BACKGROUND: The evidence for a spectrum of bipolar disorders is mounting. Of particular interest and importance is the evolution and recurrence of bipolar disorder in the postpartum period and its relationship to postpartum psychosis. Understanding whether such a phenomenological link exists has diagnostic, prognostic, and treatment implications. OBJECTIVES: A comprehensive review of (1) the literature regarding the relationships between postpartum psychosis and bipolar affective disorder, (2) the data regarding prophylactic treatment and acute management of postpartum psychosis and bipolar disorder in the puerperium, and (3) critical areas for future research. STUDY DESIGN: MEDLINE and PubMed (1966-2002) databases were searched for English-language articles using the keywords postpartum/puerperal depression, puerperal/postpartum psychosis, bipolar disorder, lithium, anticonvulsants, antipsychotics, and breastfeeding. RESULTS: Evidence from studies of women with a history of bipolar disorder, longitudinal studies of women with puerperal episodes of psychosis, and family studies support a link between postpartum psychosis and bipolar disorder. CONCLUSIONS: Understanding the relationship between postpartum psychosis and bipolar disorder has implications for perinatal and long-term treatment. Prophylactic treatment of women with bipolar disorder and/or a history of postpartum psychosis may be indicated. Epidemiological, genetic, and pharmacologic research must be completed to understand, prevent, and adequately treat postpartum psychosis." [Abstract]

Jones I, Craddock N.
Do puerperal psychotic episodes identify a more familial subtype of bipolar disorder? Results of a family history study.
Psychiatr Genet. 2002 Sep;12(3):177-80.
"Bipolar women have a marked vulnerability to puerperal psychosis, an episode of mania or psychosis following childbirth. We have conducted a family history study to examine the question of whether a vulnerability to puerperal episodes of illness is a marker for a more familial form of bipolar disorder. A consecutive series of 103 bipolar disorder probands were recruited in a lithium clinic and given a semi-structured interview, including a detailed family history. For the 52 female probands, information was also obtained about the relationship of episodes to childbirth. The morbid risk of affective disorder in first-degree relatives of bipolar women who had suffered an episode of mania, hypomania or schizoaffective mania with onset within 6 weeks of childbirth was significantly higher than that in relatives of parous bipolar women with no episodes in relation to childbirth (P = 0.0077). Despite relatively small numbers, this study provides evidence to support the hypothesis that puerperal episodes identify a more familial subtype of bipolar disorder." [Abstract]

Frye MA, Altshuler LL, McElroy SL, Suppes T, Keck PE, Denicoff K, Nolen WA, Kupka R, Leverich GS, Pollio C, Grunze H, Walden J, Post RM.
Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder.
Am J Psychiatry. 2003 May;160(5):883-9.
"OBJECTIVE: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study. METHOD: The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires. RESULTS: As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder. CONCLUSIONS: This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study." [Abstract]

Christensen EM, Gjerris A, Larsen JK, Bendtsen BB, Larsen BH, Rolff H, Ring G, Schaumburg E.
Life events and onset of a new phase in bipolar affective disorder.
Bipolar Disord. 2003 Oct;5(5):356-61.
"BACKGROUND: There is an increasing focus on the impact of psychosocial factors and stressors on the course of bipolar affective disorder. The life event research has revealed many biases and the results are conflicting. In a prospective study we examined the relationship between life events and affective phases in a group of bipolar patients with a long duration of the disease. METHODS: A group of patients with at least three admissions to hospital for bipolar disorder was followed every 3 months for up to 3 years. At each examination an evaluation of affective phase was made according to the Hamilton Depression Scale, the Newcastle Depression Rating Scale and the Bech-Rafaelsen Mania Rating Scale. Moreover, the patients were rated according to the Paykel Life Events Scale. Their current medical treatment was noted. RESULTS: Fifty-six patients (19 men and 37 women) were included in the study. Women experienced a significantly higher number of life events than men. In 21% of the 353 examinations of women, a new phase was preceded by life events whereas this was the case only in 8% of the 152 examinations of men. In 13% of the male examinations the patients were in a manic phase and in 5% in a depressive phase. In 5% of the female examinations the patients were in a manic phase and in 15% in a depressive phase. Half of the women's depressive phases were preceded by life events, but none of the depressive phases of men. The categories of life events preceding the depressive phases presented a significant overweight of somatic ill health and conflicts in the family. CONCLUSION: We found a gender difference in the course of bipolar affective disorder, as women had a significantly higher number of depressive episodes than men and men had a higher number of manic episodes than women. In bipolar patients with long duration of disease a significant number of depressive episodes in women were preceded by negative life events. Somatic health problems and conflicts in the family were significant factors preceding new depressive phases." [Abstract]

Calabrese JR, Shelton MD, Rapport DJ, Kujawa M, Kimmel SE, Caban S.
Current research on rapid cycling bipolar disorder and its treatment.
J Affect Disord 2001 Dec;67(1-3):241-55
"Rapid cycling is a pattern of presentation of bipolar disorder that specifies the course of the illness and is associated with a greater morbidity. The validity of rapid cycling as a distinct course modifier for bipolar disorder has been demonstrated and the term has been incorporated into the DSM-IV. The phenomenon of rapid cycling tends to appear late in the course of the disorder, occurs more frequently among females, and is more frequently seen in patients with bipolar type II disorder." [Abstract]

Raymont V, Bettany D, Frangou S.
The Maudsley bipolar disorder project. Clinical characteristics of bipolar disorder I in a Catchment area treatment sample.
Eur Psychiatry. 2003 Feb;18(1):13-7.
"The clinical characteristics of bipolar I disorder (BD1) have prognostic and therapeutic importance. The aim of this study was to examine the effect of demographic and clinical variables on the course of BD1. We reviewed the case notes of all BD1 patients (n = 63) receiving treatment in a London psychiatric service during a 1-month period. Depressive and manic onsets were equally likely without any gender difference. The earlier the age of onset, the more likely it was for patients to experience psychotic features. Only depressive onsets predicted a higher number of episodes of the same polarity. Male gender and substance abuse were associated with younger age at first presentation, while women with co-morbid substance abuse had more manic episodes. Male patients were more likely than females to be unemployed or single." [Abstract]

Akiskal HS, Hantouche EG, Bourgeois ML, Azorin JM, Sechter D, Allilaire JF, Lancrenon S, Fraud JP, Chatenet-Duchene L.
Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN).
J Affect Disord 1998 Sep;50(2-3):175-86
"BACKGROUND: This research derives from the French national multisite collaborative study on the clinical epidemiology of mania (EPIMAN). Our aim is to establish the validity of dysphoric mania along a "spectrum of mixity" extending into mixed mania with subthreshold depressive manifestations; to demonstrate the feasibility of obtaining clinically meaningful data on this entity on a national level; and to characterize the contribution of temperamental attributes and gender in its origin. METHODS: EPIMAN involves training 23 French psychiatrists in four different sites, representing four regions of France; to rigorously apply a common protocol deriving from the criteria of DSM-IV and McElroy et al.; the use of such instruments as the Beigel-Murphy, Ahearn-Carroll, modified HAM-D; and measures of affective temperaments based on the Akiskal-Mallya criteria; obtaining data on comorbidity, and family history (according to Winokur's approach as incorporated into the FH-RDC); and prospective follow-up for at least 12 months. The present report concerns the clinical and temperamental features of 104 manic patients during the acute hospital phase. RESULTS: Dysphoric mania (DM defined conservatively with fullblown depressive admixtures of five or more symptoms) occurred in 6.7%; the rate of dysphoric mania defined broadly (DM, presence of > or = 2 depressive symptoms) was 37%. Depressed mood and suicidal thoughts had the best positive predictive values for mixed mania. In comparison to pure mania (0-1 depressive symptoms), DM was characterized by female over-representation; lower frequency of such typical manic symptomatology as elation, grandiosity, and excessive involvement; higher prevalence of associated psychotic features; higher rate of mixed states in first episodes; and complex temperamental dysregulation along primarily depressive, but also cyclothymic, and irritable dimensions; such irritability was particularly apparent in mixed mania at the lowest threshold of depressive admixtures of two symptoms only. LIMITATION: In a study involving hospitalized affectively unstable psychotic patients, it was difficult to assure that psychiatrists making the clinical diagnoses would be blind to the temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. CONCLUSIONS: Mixed mania, defined cross-sectionally by the simultaneous presence of at least two depressive symptoms, represents a prevalent and clinically distinct form of mania. Subthreshold depressive admixtures with mania actually appear to represent the more common expression of dysphoric mania. Moreover, an irritable dimension appears to be relevant to the definition of the expression of mixed mania with the lowest threshold of depressive symptoms. Neither an extreme, nor an endstage of mania, "mixity" is best conceptualized as intrusion of mania into its "opposite" temperament - especially that defined by lifelong depressive traits - and favored by female gender. These data suggest that reversal from a temperament to an episode of "opposite" polarity represents a fundamental aspect of the dysregulation that characterizes bipolar disorder. In both men and women with hyperthymic temperament, there appears "protection" against depressive symptom formation during a manic episode which, accordingly, remains relatively "pure". Because men have higher rates of this temperament, pure mania is overrepresented in men; on the other hand, the depressive temperament in manic women seems to be a clinical marker for the well-known female tendency for depression, hence the higher prevalence of mixed mania in women." [Abstract]

Visscher PM, Yazdi MH, Jackson AD, Schalling M, Lindblad K, Yuan QP, Porteous D, Muir WJ, Blackwood DH.
Genetic survival analysis of age-at-onset of bipolar disorder: evidence for anticipation or cohort effect in families.
Psychiatr Genet 2001 Sep;11(3):129-37
"Age-at-onset (AAO) in a number of extended families ascertained for bipolar disorder was analysed using survival analysis techniques, fitting proportional hazards models to estimate the fixed effects of sex, year of birth, and generation, and a random polygenic genetic effect. Data comprised the AAO (for 171 affecteds) or age when last seen (ALS) for 327 unaffecteds, on 498 individuals in 27 families. ALS was treated as the censored time in the statistical analyses. The majority of individuals classified as affected were diagnosed with bipolar I and II (n = 103) or recurrent major depressive disorder (n = 68). In addition to the significant effects of sex and year of birth, a fitted 'generation' effect was highly significant, which could be interpreted as evidence for an anticipation effect. The risk of developing bipolar or unipolar disorder increased twofold with each generation descended from the oldest founder. However, although information from both affected and unaffected individuals was used to estimate the relative risk of subsequent generations, it is possible that the results are biased because of the 'Penrose effect'. Females had a twofold increased risk in developing depressive disorder relative to males. The risk of developing bipolar or unipolar disorder increased by approximately 4% per year of birth. A polygenic component of variance was estimated, resulting in a 'heritability' of AAO of approximately 0.52. In a family showing strong evidence of linkage to chromosome 4p (family 22), the 'affected haplotype' increased the relative risk of being affected by a factor of 46. In this family, there was strong evidence of a time trend in the AAO. When either year of birth or generation was fitted in the model, these effects were highly significant, but neither was significant in the presence of the other. For this family, there was no increase in trinucleotide repeats measured by the repeat expansion detection method in affected individuals compared with control subjects. Proportional hazard models appear appropriate to analyse AAO data, and the methodology will be extended to map quantitative trait loci (QTL) for AAO." [Abstract]

Leboyer M, Bellivier F, McKeon P, Albus M, Borrman M, Perez-Diaz F, Mynett-Johnson L, Feingold J, Maier W.
Age at onset and gender resemblance in bipolar siblings.
Psychiatry Res 1998 Nov 16;81(2):125-31
"In order to measure the intrafamilial correlation for age at onset and to examine gender resemblance among bipolar siblings, we assessed a sample of 130 bipolar patients belonging to 59 multiple affected sibships. To study the intrafamilial resemblance for age at onset and gender, we used the intraclass correlation and the sibship method, respectively. Within the whole sample, age at onset for affected siblings was correlated (rho = 0.42, P = 0.0001). Gender was randomly distributed among bipolar sibships, demonstrating the absence of gender resemblance among affected siblings. The existence of an intrafamilial correlation for age at onset among bipolar siblings suggests that this variable may assist in the identification of more heritable forms of the illness. No intrafamilial correlation was found for the gender of affected siblings, suggesting that familial vulnerability factors are not gender-specific." [Abstract]

Lish JD, Gyulai L, Resnick SM, Kirtland A, Amsterdam JD, Whybrow PC, Price RA.
A family history study of rapid-cycling bipolar disorder.
Psychiatry Res 1993 Jul;48(1):37-46
"Previous studies have yielded mixed evidence as to whether rapid-cycling bipolar disorder (four or more episodes per year) is associated with a distinctive pattern of patient characteristics and familial aggregation of affective disorder. In this study, Family History Research Diagnostic Criteria (FH-RDC) were used to interview 165 patients with rapid-cycling bipolar disorder, non-rapid-cycling bipolar disorder, or recurrent unipolar depressive disorder about the psychiatric history of 812 adult first-degree relatives. In a validity study, FH-RDC diagnoses were demonstrated to agree reasonably well with best-estimate diagnoses by two psychiatrists/psychologists, based on direct interviews with the Structured Clinical Interview for DSM-III-R. Relatives of patients with recurrent unipolar depression were less likely to have bipolar disorder and more likely to have unipolar depression than were relatives of rapid-cycling or non-rapid-cycling bipolar patients. Rapid-cycling patients were younger and more likely to be female than non-rapid-cycling patients. The relatives of rapid cyclers did not differ significantly from those of non-rapid cyclers in the prevalence of bipolar disorder, unipolar disorder, rapid-cycling bipolar disorder, or substance abuse. However, there were nonsignificant trends for the relatives of rapid-cycling bipolar patients, compared with those of non-rapid-cycling bipolar patients, to have more substance abuse and less bipolar disorder given the presence of affective disorder." [Abstract]