***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: BACKGROUND Substance abuse frequently complicates the course of bipolar illness , promotes mixed states , and contributes to poor outcome in mania . Preliminary open trials suggest that anticonvulsant mood stabilizers may enhance remission rates and outcome for bipolar patients with substance abuse . This study compared remission patterns for mixed or pure manic episodes among bipolar in patients with or without substance abuse histories . METHOD Hospital records were retrospectively review ed for 204 DSM-III-R bipolar I in patients . Clinical features were compared for those with or without substance abuse/dependence histories predating the index manic episode . Time until remission was analyzed by Kaplan-Meier survival analysis . Naturalistic treatment outcome with lithium or anticonvulsant mood stabilizers was compared for those with or without past substance abuse . RESULTS Past substance abuse was evident in 34 % of the bipolar sample and comprised most often alcoholism ( 82 % ) , followed by cocaine ( 30 % ) , marijuana ( 29 % ) , sedative-hypnotic or amphetamine ( 21 % ) , and opiate ( 13 % ) abuse . Substance abuse was more common among men ( p < .05 ) and those with mixed rather than pure mania ( p < .05 ) . Remission during hospitalization was less likely among patients with prior substance abuse ( p < .05 ) , especially alcohol or marijuana abuse , and among mixed manic patients with past substance abuse ( p < .05 ) . Bipolar patients with substance abuse histories who received divalproex or carbamazepine  remitted during hospitalization more often than did those who received lithium as the sole mood stabilizer ( p < .05 ) . CONCLUSION These findings support previous reports suggesting that bipolar patients with past substance abuse have poorer naturalistic treatment outcomes , but may show a better response to anticonvulsant mood stabilizers than lithium CONTEXT Although an association between mood disorders and substance use disorders has been well established , there is a lack of long-term prospect i ve data on the order of onset and subtypes of mood disorders associated with specific substances and their progression . OBJECTIVE To estimate the respective risks posed by subtypes of mood disorders or bipolar spectrum conditions for the subsequent development of substance use disorders . DESIGN Six waves of direct diagnostic interviews were administered to a sample of young adults during a 20-year period . Mood disorders and syndromes assessed at each interview were used to predict the cumulative incidences of substance use disorders at subsequent interview waves . PARTICIPANTS We followed up 591 individuals ( 292 men and 299 women ) who were selected at study enrollment from a representative sample of young adults in Zurich , Switzerl and . MAIN OUTCOME MEASURES Structured Diagnostic Interview for Psychopathologic and Somatic Syndromes , a semistructured clinical interview that collected data on the spectrum of expression of mood disorders and substance use and disorders for DSM-III-R and DSM-IV criteria . RESULTS Individuals having manic symptoms were at significantly greater risk for the later onset of alcohol abuse/dependence , cannabis use and abuse/dependence , and benzodiazepine use and abuse/dependence . Bipolar II disorder predicted both alcohol abuse/dependence and benzodiazepine use and abuse/dependence . In contrast , major depression was predictive only of later benzodiazepine abuse/dependence . CONCLUSIONS In comparison with major depression , bipolar II disorder was associated with the development of alcohol and benzodiazepine use and disorders . There was less specificity of manic symptoms that tended to predict all levels of the substances investigated herein . The different patterns of association between mood disorders and substance use trajectories have important implication s for prevention and provide lacking information about underlying mechanisms BACKGROUND The association between early childhood abuse and the course of illness , including psychiatric comorbidities , in adults with bipolar disorder has not been examined in a predominantly male or veteran population . METHODS As part of the VA Cooperative Study 430 , " Reducing the Efficacy-Effectiveness Gap in Bipolar Disorder , " 330 veterans ( 91 % male ) with bipolar I or II disorder who were enrolled in a 3-year prospect i ve study were examined for baseline data obtained at study entry . Diagnoses were determined by the use of the SCID . A semistructured interview design ed to elicit data about exposure to childhood physical , sexual , or combined abuse was conducted as part of baseline demographic and clinical information . Other reports from this data set have not addressed the issues of childhood adversity . RESULTS  Childhood abuse was reported by 48.3 % of the subjects ( 47.3 % of men ) .  Any abuse ( AA ) was reported by 48.3 % ; sexual abuse without physical abuse ( SA ) was reported by 8 % , physical abuse without sexual abuse ( PA ) by 20.7 % , and both types of abuse ( combined abuse , CA ) by 18.7 % of the male subjects . Female veterans reported more SA ( 27 % ) and less PA ( 6.7 % ) . AA subjects were more likely to have current PTSD and lifetime diagnoses of panic disorder and alcohol use disorders . CA was associated with lower SF-36 Mental scores , higher likelihood of current PTSD and lifetime diagnoses of alcohol use disorders , as well as more lifetime episodes of major depression and higher likelihood of at least one suicide attempt . Younger age at study entry was associated with AA and PA . LIMITATIONS Potential limitations include generalizability beyond the male , veteran population of patients with bipolar disorder and the methodology used to elicit abuse histories . CONCLUSIONS Similar to studies of predominantly female nonveteran sample s , this study extends the finding that a history of childhood abuse acts as a disease course modifier in male veterans with bipolar disorder . Clinicians should routinely seek information regarding abuse and be aware that these patients may be more difficult to treat than bipolar patients who have no abuse histories OBJECTIVE To evaluate the prevalence of substance abuse dependence and /or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry . METHOD One hundred r and omly selected registrants in a voluntary case registry for bipolar disorder were interviewed , using the Structured Clinical Interview for DSM-IV Axis I Disorders , to vali date the diagnosis of this registry . Corroborative information was obtained from medical records , family members and the treating psychiatrist . Eighty-nine adults ( 18 - 65 years ) met criteria for bipolar disorder ( bipolar I = 71 , bipolar II = 18 ) and were included in this analysis . RESULTS Forty-one ( 57.8 % ) subjects with bipolar I disorder abused , or were dependent on one or more substances or alcohol , 28.2 % abused , or were dependent on , two substances or alcohol , and 11.3 % abused or were dependent on three or more substances or alcohol . Nearly 39 % of bipolar II subjects abused or were dependent on one or more substances , nearly 17 % were dependent on two or more substances or alcohol , and 11 % were dependent on three or more substances or alcohol . Alcohol was the most commonly abused drug among either bipolar I or II subjects . CONCLUSIONS Consistent with other epidemiologic and hospital population studies , this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and /or substance abuse dependence . Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects ; however , as the number of bipolar II subjects was rather small , this suggestion needs confirmation 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 out patients 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 question naires . 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 prospect i ve study OBJECTIVE Previous work has shown that manic-depressive illness and alcohol abuse are linked . This study further explores the relationship of alcohol and drug abuse in bipolar I patients and unipolar depressives and a comparison group obtained through the acquaintance method .  METHOD Diagnosis was accomplished according to Research Diagnostic Criteria ( RDC ) : controls = 469 ; bipolars = 277 ; unipolar depressives = 678 . Systematic data were gathered using the SADS on lifetime and current drug abuse and alcoholism . Both patients and comparison subjects were then followed prospect ively for 10 years . First degree family members were interviewed using the RDC family history method . RESULTS The group of bipolar patients and the group of unipolar patients had higher rates of drug and alcohol abuse than the comparison group when primary and secondary affective disorder patients were combined . However , primary unipolar patients did not have higher rates of alcohol or drug abuse than the comparison group . In contrast , primary bipolar patients had higher rates of alcoholism , stimulant abuse , and ever having abused a drug than the primary unipolar group and the control group . In an evaluation of the bipolar patients , drug abusers were significantly younger at intake and had a significantly younger age of onset of bipolar disorder . There was a significant increase in family history of mania or schizoaffective mania in the drug-abusing bipolar patients as compared to the non-abusing bipolar patients . LIMITATION As in all adult sample s of patients with affective illness , the chronology of alcohol and substance problems vis-à-vis the onset of illness was determined retrospectively . CONCLUSIONS ( 1 ) Alcoholism and drug abuse are more frequent in bipolar than unipolar patients . ( 2 ) The drug abuse of bipolar patients tends toward the abuse of stimulant drugs . ( 3 ) In a bipolar patient , familial diathesis for mania is significantly associated with the abuse of alcohol and drugs . ( 4 ) More provocatively , these findings suggest the hypothesis of a common familial-genetic diathesis for a subtype of bipolar I , alcohol and stimulant abuse . CLINICAL IMPLICATION S The present analyses , coupled with two previous ones from the CDS , suggest that drug abuse may precipitate an earlier onset of bipolar I disorder in those who already have a familial predisposition for mania . Furthermore , in dually diagnosed patients with manic-depressive and alcohol/stimulant abuse history , mood stabilization of the bipolar disorder represents a rational approach to control concurrent alcohol and drug problems , and should be studied in systematic controlled trials In light of the established influence of substance use on the onset , course , and outcome of bipolar disorder , we performed a retrospective chart review of patients with bipolar I disorder participating in a r and omized controlled trial to further investigate the relationship between alcohol and substance use and first onset of mania . A total of 59.4 % ( N=101 ) of the 170 participants were determined to have a history of substance and /or alcohol use .  Among the 101 participants with SU , use was coded in 10 ( 9.9 % ) as immediately preceding , in 50 ( 49.5 % ) as preceding mania , in 7 ( 6.9 % ) as following mania , and in 34 ( 33.7 % ) as indeterminable . Of the 10 participants with immediately preceding use , 5 experienced their first manic episode immediately after discontinuing a substance . Our findings support earlier reports detailing the high prevalence of substance use among patients with bipolar disorder . Treatments targeting alcohol and substance use among individuals with bipolar disorder are clearly needed , as are prophylactic treatments targeting adolescents and young adults who are at risk for either bipolar disorder or alcohol and substance related disorders BACKGROUND There is a need for comparisons of long-term outcomes in bipolar disorder patients with predominantly manic symptoms vs. predominantly depressive symptoms , especially the course of comorbid alcohol/substance abuse . METHOD A naturalistic sample of bipolar I patients ( n=120 ) was followed prospect ively for up to 10years . At baseline , number and polarity of past episodes were used to classify patients as predominantly manic or predominantly depressive if there were more manic or more depressive episodes , respectively . 25 patients were excluded from the analyses . Outcomes including episodes , hospitalisations and suic 
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AUDs are highly prevalent in BD .
Our study revealed a substantial heterogeneity across studies .