Risk and protective factors associated with substance use disorders in adolescents with first-episode mania.

Adolescents with bipolar disorder (BD) are more likely to develop substance use disorders (SUDs) than adolescents without psychiatric disorders; however, to our knowledge, specific risk factors underlying this relationship have not been prospectively examined. The purpose of this study was to identify predictors of developing SUDs after a first manic episode.



Participants aged 12 to 20 years and hospitalized with their first manic episode associated with bipolar I disorder (BP-I) were recruited as part of the University of Cincinnati First-Episode Mania Study and prospectively evaluated for patterns of substance use. Follow-up ranged between 17 and 283 weeks (mean = 113 weeks, SD = 71.9 weeks). Demographic and clinical variables were compared between adolescents with and without SUDs.



Of the 103 adolescents with BD, 49 (48%) either had a SUD at baseline or developed one during follow-up. Of the 71 participants who did not have a SUD at study entry, 17 (24%) developed one during follow-up (median = 40 weeks). Later onset of BD, manic (versus mixed) mood episode, and comorbid disruptive behavior disorders were associated with an increased risk of developing a SUD in univariate analyses. Adolescents treated with psychostimulant treatment before their first manic episode were significantly less likely to develop a SUD independent of attention-deficit/hyperactivity disorder (ADHD) diagnosis. Comorbid posttraumatic stress disorder (PTSD) and psychotic symptoms were the strongest predictors of SUD development.



Our results confirm high rates of SUD in adolescents with BD. In addition, our findings identify potential risk factors associated with SUDs in adolescents with BD. These data are preliminary in nature and should be explored further in future studies.

Related papers:

title: Predictors of alcohol intake and heavy drinking in early adulthood: a 5-year follow-up of 15-19-year-old Finnish adolescents.
abstract: Relative contributions of earlier drinking and smoking vs mental health risk factors in predicting alcohol intake and heavy drinking in young adulthood were assessed. Higher average alcohol intake and heavy drinking (13 or more drinks on one occasion) in 1995 were significantly related to male gender and earlier high scores in 1990 of relief smoking, relief drinking, and their interaction. Parental alcohol problems, social group, perceived degree of social support, trait anxiety, number of negative life events, self-esteem, grade-point average, somatic symptoms score, or immature, neurotic, or mature defence style measured in 1990 did not predict alcohol intake or heavy drinking 5 years later. The findings suggest that alcohol intake and heavy drinking in young adulthood can be predicted by earlier self-reports on relief smoking and alcohol intake in adolescence.

title: Socioeconomic status and drinking patterns in young adults.
abstract: To investigate the relationship between several indicators of socioeconomic status and drinking patterns in young adulthood.



Data collected in a longitudinal study of young adults was analysed using repeated-measures models to examine the relationship between income, occupational activity and educational achievement and patterns of drinking.



These data were collected as part of a longitudinal study ofa birth cohort of New Zealanders. They were interviewed for the most part in a central location using a face-to-face method and a computer-assisted alcohol interview.



The participants were members of the Dunedin Multidisciplinary Health and Development study aged 18, 21 and 26 years. Nine hundred and sixty-nine study members contributed to the analysis. Study members have been found to be broadly representative of the New Zealand population and cross national studies suggest findings are generalizable to other similar market economies.



Three indicators of socioeconomic status were used; educational achievement, occupational activity and income. The educational achievement indicator at age 18 had three levels that ranged from no school qualifications to higher school qualifications. For age 21 two additional categories of tertiary educational achievement were included to make five categories and for age 26 higher tertiary degrees were included in the measure to make six categories. Five categories of occupational activity were used. Income data was also used. Two measures of alcohol consumption were used. These were the frequency of drinking and the typical quantity of alcohol consumed per drinking occasion in the past year.



Frequency of drinking increased over these early adult years and the quantities consumed peaked at age 21 and decreased thereafter for both males and females. Frequency of drinking was influenced by income with the higher income respondents drinking more often and this was persistent overtime. Quantity of drinking was most influenced by educational achievement. The less well-educated young adult drank significantly more during a drinking occasion and at all ages. There was also a relationship between educational achievement and frequency of drinking for males at age 18 and a relationship between women's occupational activity and the quantities they consumed.



The finding that the dimensions of drinking operate differently explains the lack of consistency in previous research, which has investigated socioeconomic status and the volumes of alcohol consumed. The findings of higher quantities consumed among those of lower social status may explain some of the reduced life expectancy found among those with lower socioeconomic status.

title: Parent, family, and neighborhood effects on the development of child substance use and other psychopathology from preschool to the start of adulthood.
abstract: We examined the long-term effects of childhood familial and neighborhood risk on adolescent substance use and psychiatric symptomatology.



This study used data from an ongoing 2-decade long study that recruited alcoholic and neighborhood control families through fathers' drunk-driving records and door-to-door canvassing in a four county area. The sample included 220 male, initially 3- to 5-year-old children of the participant families, who received in-home assessments at baseline and thereafter at 3-year intervals. Parental lifetime psychopathology and offspring symptomatology at ages 18-20 were assessed by semistructured diagnostic interviews. Census tract variables were used to indicate neighborhood characteristics.



The isomorphic parental symptomatology predicted offspring psychopathology. For marijuana-use disorder, major depressive disorder, and nicotine dependence, the other parental comorbidities were also significant predictors. Neighborhood residential instability in childhood contributed to the development of late adolescent alcohol-use disorder, marijuana-use disorder, major depressive disorder, antisocial personality disorder, and nicotine-dependence symptomatology. Although lower family socioeconomic status in childhood contributed to more adolescent marijuana-use disorder, major depressive disorder, and nicotine-dependence symptoms, neighborhood socioeconomic status did not predict adolescent psychopathology. Longitudinal changes in neighborhood environments from early childhood to adolescence had significant effects on alcohol-use disorder, marijuana-use disorder, and major depressive disorder symptoms in late adolescence. A higher frequency of family mobility from early childhood to adolescence predicted more nicotine-dependence symptoms in late adolescence.



Findings indicate that parental psychopathology, family socioeconomic status, and neighborhood residential instability are all important risk factors for the development of substance-use disorder and other comorbid psychopathology. Intervention programming might effectively use these early parental psychopathology indicators to identify risk and might target community activity to stabilize the social environment and provide youth services to counteract the effects of family transience.

title: The contextual role of alcohol outlet density in college drinking.
abstract: The objective of the study is to examine the relationship between the physical availability of off-campus alcohol and drinking outcomes among college students.



A multilevel analysis of students (N = 17,051) nested within college campuses (N = 32) was conducted. Four problem-drinking-related outcomes (i.e., average number of drinks when partying, frequency of drunkenness in past 2 weeks, 30-day frequency of drinking, and greatest number of drinks in one sitting) along with individual level covariates of drinking were introduced at the student level. The physical availability of alcohol was assessed as the number of on-premise and off-premise alcohol outlets within 3 miles of campus per 1,000 students enrolled.



Higher densities of on-premise alcohol outlets were strongly related to drinking outcomes even after controlling for individual predictors of college drinking. The association indicated that the campus means for the average number of drinks when partying and the number of drinking occasions in the past 30 days were, respectively, 1.13 drinks and 1.32 occasions greater when the outlet density was 2 SDs higher.



Off-campus, on-premise outlet density is strongly associated with college-drinking outcomes. Given the limited number of modifiable factors that affect college drinking, on-premise outlet density represents a potential modifiable means of addressing the problem.

title: The role of mental disorders in the risk and speed of transition to alcohol use disorders among community youth
abstract: Among adolescents and young adults with DSM-IV alcohol use disorders (AUDs), there are inter-individual differences in the speed of transition from initial alcohol use (AU) to AUD. AUDs are highly co-morbid with other mental disorders. The factors associated with rapid transition from first AU to AUD remain unknown and the role of mental disorders in rapid transitions is unclear. Given this background we examined (1) whether prior anxiety, mood, externalizing and non-alcohol substance use disorders are related to the risk and speed of transition from first AU to DSM-IV alcohol abuse (AA) and alcohol dependence (AD) and (2) whether early age of onset of prior mental disorders (PMDs) is a promoter of rapid transition.  A total of 3021 community subjects (97.7% lifetime AU) aged 14–24 years at baseline were followed up prospectively for up to 10 years. AU and mental disorders were assessed with the DSM-IV/M-CIDI.  Among subjects with lifetime AU, several PMDs, such as specific phobia, bipolar disorder and nicotine dependence, were associated with an increased risk of AUD independent of externalizing disorders. Associations of PMDs with the speed of transition to AUDs were mostly weak and inconsistent. Only social phobia and externalizing disorders were associated with faster transitions to AD even after adjustment for other PMDs. Earlier age of onset of PMD was not associated with rapid transition.  Mental disorders are associated with the risk of AUD. With the possible exception of social phobia and externalizing disorders, they do not promote rapid transition, even if they occur particularly early. Future research needs to identify factors relevant to rapid transition to AUD.

title: Does conduct disorder mediate the development of substance use disorders in adolescents with bipolar disorder? A case-control family study.
abstract: Recent work has highlighted important relationships among conduct disorder (CD), substance use disorders (SUD), and bipolar disorder in youth. However, because bipolar disorder and CD are frequently comorbid in the young, the impact of CD in mediating SUD in bipolar disorder youth remains unclear.



105 adolescents with DSM-IV bipolar disorder (mean +/- SD age = 13.6 +/- 2.50 years) and 98 controls (mean +/- SD age = 13.7 +/- 2.10 years) were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and SUD. The study was conducted from January 2000 through December 2004.



Among bipolar disorder youth, those with CD were more likely to report cigarette smoking and/or SUD than youth without CD. However, CD preceding SUD or cigarette smoking did not significantly increase the subsequent risk of SUD or cigarette smoking. Adolescents with bipolar disorder and CD were significantly more likely to manifest a combined alcohol plus drug use disorder compared to subjects with bipolar disorder without CD (chi(2) = 11.99, p < .001).



While bipolar disorder is a risk factor for SUD and cigarette smoking in a sample of adolescents, comorbidity with preexisting CD does not increase the risk for SUD. Further follow-up of this sample through the full risk of SUD into adulthood is necessary to confirm these findings.

title: Further evidence of an association between adolescent bipolar disorder with smoking and substance use disorders: a controlled study.
abstract: Although previous work suggests that juvenile onset bipolar disorder increases risk for substance use disorders and cigarette smoking, the literature on the subject is limited. We evaluated the association of risk for substance use disorders and cigarette smoking with bipolar disorder in adolescents in a case-control study of adolescents with bipolar disorder (n=105, age 13.6+/-2.5 years [mean]; 70% male) and without bipolar disorder ("controls"; n=98, age 13.7+/-2.1 years; 60% male). Rates of substance use and other disorders were assessed with structured interviews (KSADS-E for subjects younger than 18, SCID for 18-year-old subjects). Bipolar disorder was associated with a significant age-adjusted risk for any substance use disorder (hazard ratio[95% confidence interval]=8.68[3.02 25.0], chi(2)=16.06, p<0.001, df=1), alcohol abuse (7.66 [2.20 26.7], chi(2)=10.2, p=0.001, df=1), drug abuse (18.5 [2.46 139.10], chi(2)=8.03, p=0.005, df=1) and dependence (12.1 [1.54 95.50], chi(2)=5.61, p=0.02, df=1), and cigarette smoking (12.3 [2.83 53.69], chi(2)=11.2, p<0.001, df=1), independently of attention deficit/hyperactivity disorder, multiple anxiety, and conduct disorder (CD). The primary predictor of substance use disorders in bipolar youth was older age (BPD-SUD versus BPD+SUD, logistic regression: chi(2)=89.37, p<0.001). Adolescent bipolar disorder is a significant risk factor for substance use disorders and cigarette smoking, independent of psychiatric comorbidity. Clinicians should carefully screen adolescents with bipolar disorder for substance and cigarette use.

title: Clinical characteristics of psychiatrically referred adolescent outpatients with substance use disorder.
abstract: There is increasing interest in the developmental relationship of psychopathology and substance use disorders (SUD) in youths. Because the bulk of literature is focused in inpatient or incarcerated youths, inferences and generalizations are limited in outpatient settings. The clinical characteristics of psychiatrically referred outpatients were studied to determine whether differences existed in the nature and severity of comorbid psychiatric disorders when substance abuse was involved.



All diagnoses were derived from structured psychiatric interviews completed on all youths on intake assessment. Adolescents with an identified SUD (n = 38) were compared with those without SUD (n = 321) on a number of variables including past and current psychopathology, cognitive and school functioning, and overall impairment.



Eleven percent of referred outpatients (mean age = 15.9 +/- 1.3 years) met full criteria for a SUD by parental report. Controlling for age, adolescents with SUD had higher risk for mood and disruptive behavioral disorders compared with psychiatric controls. In the majority of cases, the onset of psychopathology preceded the onset of SUD by at least 1 year. The group with SUD also had lower overall functioning and more school dysfunction and psychiatric hospitalizations than their non-SUD peers.



Despite the small number of adolescents with SUD in this sample, these data indicate that SUD is common in outpatient psychiatry referrals. Youths with SUD appear to be at increased risk for more psychopathology and dysfunction in a number of domains.

title: Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study.
abstract: The prevalence of comorbid alcohol, other drug, and mental disorders in the US total community and institutional population was determined from 20,291 persons interviewed in the National Institute of Mental Health Epidemiologic Catchment Area Program. Estimated US population lifetime prevalence rates were 22.5% for any non-substance abuse mental disorder, 13.5% for alcohol dependence-abuse, and 6.1% for other drug dependence-abuse. Among those with a mental disorder, the odds ratio of having some addictive disorder was 2.7, with a lifetime prevalence of about 29% (including an overlapping 22% with an alcohol and 15% with another drug disorder). For those with either an alcohol or other drug disorder, the odds of having the other addictive disorder were seven times greater than in the rest of the population. Among those with an alcohol disorder, 37% had a comorbid mental disorder. The highest mental-addictive disorder comorbidity rate was found for those with drug (other than alcohol) disorders, among whom more than half (53%) were found to have a mental disorder with an odds ratio of 4.5. Individuals treated in specialty mental health and addictive disorder clinical settings have significantly higher odds of having comorbid disorders. Among the institutional settings, comorbidity of addictive and severe mental disorders was highest in the prison population, most notably with antisocial personality, schizophrenia, and bipolar disorders.

title: Substance abuse in bipolar disorder.
abstract: High rates of substance abuse have been reported in the general population, with males more often affected than females. Although high rates of substance abuse have also been reported in bipolar patients, the relationship between substance abuse and bipolar disorder has not been well characterized.



Substance abuse histories were obtained in 392 patients hospitalized for manic or mixed episodes of bipolar disorder and rates of current and lifetime abuse calculated. Analyses comparing sex, subtype (manic vs. mixed) and clinical history variables were conducted.



Rates of lifetime substance abuse were high for both alcohol (48.5%) and drugs (43.9%). Nearly 60% of the cohort had a history of some lifetime substance abuse. Males had higher rates of abuse than females, but no differences in substance abuse were observed between subjects in manic and mixed bipolar states. Rates of active substance abuse were lower in older age cohorts. Subjects with a comorbid diagnosis of lifetime substance abuse had more psychiatric hospitalizations.



Substance abuse is a major comorbidity in bipolar patients. Although rates decrease in older age groups, substance abuse is still present at clinically important rates in the elderly. Bipolar patients with comorbid substance abuse may have a more severe course. These data underscore the significance of recognition and treatment of substance abuse in bipolar disorder patients.

title: Substance abuse in first-episode bipolar I disorder: indications for early intervention.
abstract: This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder.



The authors evaluated substance use disorders, associated factors, and clinical course, prospectively, in the first 2 years of DSM-IV bipolar I disorder with standardized methods.



Baseline substance use disorder was found in 33% (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety disorders were more frequent in the patients with than without substance use disorder (30% and 13%, respectively). Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested. Patients using two or more substances had worse outcomes.



Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome, early interventions for substance use disorder and anxiety might improve later outcome.

title: Relation between childhood disruptive behavior disorders and substance use and dependence symptoms in young adulthood: individuals with symptoms of attention-deficit/hyperactivity disorder and conduct disorder are uniquely at risk.
abstract: Most prior literature examining the relations among attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and substance use and abuse suggests that CD fully account for the ADHD-substance abuse relation. This study sought to test an alternate theory that individuals with symptoms of both ADHD and CD are at a special risk for substance abuse. Relations between childhood ADHD and CD symptoms, and young adult tobacco, alcohol, marijuana, and hard drug use and dependence symptoms, were examined in a sample of 481 young adults. ADHD and CD symptoms interacted to predict marijuana dependence symptoms and hard drug use and dependence symptoms, such that individuals with high levels of both ADHD and CD had the highest levels of these outcomes.

title: Is ADHD a risk factor for psychoactive substance use disorders : Findings from a four-year prospective follow-up study
abstract: To evaluate whether attention-deficit hyperactivity disorder (ADHD) is a risk factor for psychoactive substance use disorders (PSUD), attending to issues of psychiatric comorbidity, family history, and adversity.  Using assessments from multiple domains, the authors examined 140 ADHD and 120 normal control subjects at baseline and 4 years later. Drug and alcohol abuse and dependence were operationally defined.  No differences were detected in the rates of alcohol or drug abuse or dependence or in the rates of abuse of individual substances between the groups; both ADHD and control probands had a 15% rate of PSUD. Conduct and bipolar disorders predicted PSUD, independently of ADHD status. Family history of substance dependence and antisocial disorders was associated with PSUD in controls but less clearly so in ADHD probands. Family history of ADHD was not associated with risk for PSUD. ADHD probands had a significantly shorter time period between the onsets of abuse and dependence compared with controls (1.2 years versus 3 years, p  Adolescents with and without ADHD had a similar risk for PSUD that was mediated by conduct and bipolar disorder. Since the risk for PSUD has been shown to be elevated in adults with ADHD when compared with controls, a sharp increase in PSUD is to be expected in grown-up ADHD children during the transition from adolescence to adulthood.

title: Substance Use Disorder and ADHD
abstract: To assess the pattern of substance use disorder (SUD) in adolescents with and without history of attention - deficit / hyperactivity disorder (ADHD) using an Iranian sample in the context of a cultural background and drug availability is differing from Western countries.  In this case- control study, the participants were interviewed by a child psychiatrist and the measures included: kiddie Schedule for Affective Disorder and Schizophrenia for school age children (K-SADS), Opium Treatment Index (OTI) and Global Assessment Functioning (GAF). Data were analyzed with chi square test and T test and fisher exact test by EPI.6 soft ware.  Adolescents with ADHD were younger at the time of starting cigarette smoking, substance use, abuse and dependency (p = 0.0001), a shorter period between their first-time substance use and substance dependence or abuse (p = 0.0001), more severe substance use (for cannabis, heroine, cigarette and drugs such as benzodiazepines p < 0.05) and more functional impairment (p = 0.0007). Average number of co morbid disorders were higher in ADHD group. (p = 0.03)  Although the pattern and type of substance use may be different in Iranian culture, our findings about the relationship between ADHD and SUD are similar to other western and non western countries. The presence of ADHD may over-ride cultural barriers and lower availability of drugs to the development of SUD in Iranian adolescents. Early diagnosis and treatment of ADHD may propose with better prognosis of SUD and subsequent decrease in the prevalence of SUD and the costs of SUD-related pathology in this population.

title: Substance use in a population-based clinic sample of people with first-episode psychosis
abstract: Substance use is implicated in the cause and course of psychosis.  To characterise substance and alcohol use in an epidemiologically representative treatment sample of people experiencing a first psychotic episode in south Cambridgeshire.  Current and lifetime substance use was recorded for 123 consecutive referrals to a specialist early intervention service. Substance use was compared with general population prevalence estimates from the British Crime Survey.  Substance use among people with first-episode psychosis was twice that of the general population and was more common in men than women. Cannabis abuse was reported in 51% of patients (n=62) and alcohol abuse in 43% (n=53). More than half (n=68, 55%) had used Class A drugs, and 38% (n=43) reported polysubstance abuse. Age at first use of cannabis, cocaine, ecstasy and amphetamine was significantly associated with age at first psychotic symptom.  Substance misuse is present in the majority of people with first-episode psychosis and has major implications for management. The association between age at first substance use and first psychotic symptoms has public health implications.

title: Demographic and clinical correlates of comorbid substance use disorders in psychosis: multivariate analyses from an epidemiological sample
abstract: While there has been substantial research examining the correlates of comorbid substance abuse in psychotic disorders, it has been difficult to tease apart the relative importance of individual variables. Multivariate analyses are required, in which the relative contributions of risk factors to specific forms of substance misuse are examined, while taking into account the effects of other important correlates.



This study used multivariate correlates of several forms of comorbid substance misuse in a large epidemiological sample of 852 Australians with DSM-III-R-diagnosed psychoses.



Multiple substance use was common and equally prevalent in nonaffective and affective psychoses. The most consistent correlate across the substance use disorders was male sex. Younger age groups were more likely to report the use of illegal drugs, while alcohol misuse was not associated with age. Side effects secondary to medication were associated with the misuse of cannabis and multiple substances, but not alcohol. Lower educational attainment was associated with cannabis misuse but not other forms of substance abuse.



The profile of substance misuse in psychosis shows clinical and demographic gradients that can inform treatment and preventive research.

title: The impact of substance use disorders on clinical outcome in 643 patients with first‐episode psychosis
abstract: Studies investigating the impact of comorbid substance use disorders (SUD) in psychosis have tended to focus on cross‐sectional data, with few studies examining the effects of substance use course on clinical outcome. The main aim of the present study was to assess the impact of baseline SUD and course of SUD on remission of positive symptoms.

title: Substance abuse and the onset of schizophrenia
abstract: Up to 60% of chronic schizophrenic patients are reported to abuse alcohol or drugs. This comorbidity raises the question whether one disorder is a consequence of the other. With the structured interview "IRAOS," the onset and course of schizophrenia and substance abuse were retrospectively assessed in a representative first-episode sample of 232 schizophrenic patients. Information by relatives validated the patients' reports. Alcohol abuse prior to first admission was found in 24%, drug abuse in 14%-twice the rates in the general population. Alcohol abuse more often followed than preceded the first symptom of schizophrenia. Drug abuse preceded the first symptom in 27.5%, followed it in 37.9%, and emerged within the same month in 34.6% of the cases. The study demonstrates a remarkable association between first-episode schizophrenia and substance abuse, but a unidirectional causality is not supported, nor is a specific psychotic disorder in comorbid cases.

title: Risk of substance use disorders in adolescents with bipolar disorder.
abstract: Previous work in adults and youths has suggested that juvenile onset bipolar disorder (BPD) is associated with an elevated risk of substance use disorders (SUD). Considering the public health importance of this issue, the authors now report on a controlled study of adolescents with and without BPD to evaluate the risk of SUD.



Probands with DSM-IV BPD (n=57, mean age +/- SD=13.3 +/- 2.4 years) and without DSM-IV BPD (n=46, 13.6 +/- 2.2 years) were studied. Structured psychiatric interviews and multiple measures of SUD were collected.



Bipolar disorder was associated with a highly significant risk factor for SUD (32% versus 7%, Z=2.9, p=.004) that was not accounted for by conduct disorder (adjusted odds ratio=5.4, p=.018). Adolescent-onset BPD (> or =13 years) was associated with a higher risk of SUD compared with those with child-onset BPD (chi1=9.3, p=.002).



These findings strongly indicate that BPD, especially adolescent onset, is a significant risk factor for SUD independently of conduct disorder.

title: Substance use disorders among adolescents with bipolar spectrum disorders.
abstract: We set out to examine the prevalence and correlates of substance use disorders (SUD) in a large sample of adolescents with bipolar disorder (BP).



Subjects were 249 adolescents ages 12 to 17 years old who fulfilled DSM-IV criteria for bipolar I disorder [(BPI), n = 154], or bipolar II disorder [(BPII), n = 25], or operationalized criteria for BP not otherwise specified [(BP NOS), n = 70], via the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). As part of the multi-site Course and Outcome of Bipolar Youth study, demographic, clinical, and family history variables were measured via intake clinical interview with the subject and a parent/guardian.



The lifetime prevalence of SUD among adolescents with BP was 16% (40/249). Results from univariate analyses indicated that subjects with, as compared to without, SUD were significantly less likely to be living with both biological parents, and that there was significantly greater lifetime prevalence of physical abuse, sexual abuse, suicide attempts, conduct disorder, and posttraumatic stress disorder among subjects with SUD. Subjects with SUD reported significantly greater 12-month prevalence of trouble with police, and females with SUD reported significantly greater 12-month prevalence of pregnancy and abortion. Significant predictors of SUD in a logistic regression model included living with both biological parents (lower prevalence), conduct disorder and suicide attempts (increased prevalence). In logistic regression analyses controlling for demographic differences and conduct disorder, SUD remained significantly associated with trouble with police, whereas the association of SUD with pregnancy and abortion was reduced to a statistical trend. The prevalence of SUD was not significantly different among child- versus adolescent-onset BP subjects.



SUD among adolescents with BP is associated with profound hazards including suicide attempts, trouble with police, and teenage pregnancy and abortion.

title: Comorbid substance use disorders among youth with bipolar disorder: opportunities for early identification and prevention.
abstract: The burden of substance use disorders (SUDs) among adults with bipolar disorder is well documented. Comparatively less is known regarding comorbid SUD among youth with bipolar disorder. This article aims to integrate the extant literature on this topic and to suggest strategies for delaying or preventing SUD among youth with bipolar disorder.



Relevant studies in English were identified using PubMed and MEDLINE (1950-February 2009). Search terms were bipolar disorder cross-referenced with child, adolescent, or youth, and alcohol, drug, or substance, and abuse, dependence, or disorder. Articles were selected on the basis of containing data regarding both bipolar disorder and SUD. The search was supplemented by manually reviewing reference lists from the identified publications.



Epidemiologic and clinical studies demonstrate that youth-onset bipolar disorder confers even greater risk of SUD in comparison with adult-onset bipolar disorder. Recent studies of youth with bipolar disorder have not identified childhood SUD (0%); however, the prevalence of SUD escalates during adolescence (16%-39%). Substance use disorder among bipolar youth is associated with legal and academic difficulties, pregnancy, and suicidality. Few studies have addressed interventions for this population, although studies are underway. Because bipolar disorder onset most commonly precedes SUD among youth (55%-83%), there is a window of opportunity for prevention.



Pending the results of ongoing treatment studies, several strategies are suggested for curtailing the burden of SUD in youth with bipolar disorder. These include screening for substance use among bipolar youth beginning at age 10 irrespective of other risk factors, education and intervention at the family level, and implementation of preventive interventions that have been successful in other populations.

title: Cannabis involvement in individuals with bipolar disorder
abstract: In a study of 471 bipolar disorder (BD) cases and 1761 controls, individuals with BD were 6.8 times more likely to report a lifetime history of cannabis use. Rates of DSM-IV cannabis use disorders in those with BD were 29.4% and were independently and significantly associated with increased suicide attempts, greater likelihood of mixed episodes and greater disability attributable to BD.

title: Risk factors for secondary substance use disorders in people with childhood and adolescent-onset bipolar disorder: opportunities for prevention.
abstract: Compared to other mental illnesses, bipolar disorder is associated with a disproportionately high rate of substance use disorders (SUDs), and the co-occurrence is associated with significant morbidity and mortality. Early diagnosis of primary bipolar disorder may provide opportunities for SUD prevention, but little is known about the risk factors for secondary SUD among individuals with bipolar disorder. The purposes of this study were to describe the population of people with childhood and adolescent-onset primary bipolar disorder, and to identify risk factors for secondary SUD in this population.



Using data collected from the National Comorbidity Survey Replication study, we identified 158 individuals with childhood-onset (<13 years) or adolescent-onset (13-18 years) primary bipolar disorder (I, II or subthreshold). Survival analysis was used to identify risk factors for SUD.



Compared to adolescent-onset, people with childhood-onset bipolar disorder had increased likelihoods of attention deficit hyperactivity disorder (ADHD) (adjusted odds ratio=2.81) and suicide attempt (aOR=3.61). Males were more likely than females to develop SUD, and did so at a faster rate. Hazard ratios of risk factors for SUD were: lifetime oppositional defiant disorder (2.048), any lifetime anxiety disorder (3.077), adolescent-onset bipolar disorder (1.653), and suicide attempt (15.424). SUD was not predicted by bipolar disorder type, family history of bipolar disorder, hospitalization for a mood episode, ADHD or conduct disorder.



As clinicians struggle to help individuals with bipolar disorder, this study provides information that might be useful in identifying individuals at higher risk for SUD. Future research can examine whether targeting these risk factors may help prevent secondary SUD.

title: Risk for substance use disorders in youths with child- and adolescent-onset bipolar disorder.
abstract: Previous work in adults has suggested that early-onset bipolar disorder (BPD) is associated with an elevated risk for substance use disorders (SUD). To this end, the authors assessed the risk for SUD in child- versus adolescent-onset BPD with attention to comorbid psychopathology.



All youths (aged 13-18 years) with available structured psychiatric interviews were studied systematically. From clinic subjects (N = 333), 86 subjects with DSM-III-R BPD were identified. To evaluate the risk for SUD and BPD while attending to developmental issues, the authors stratified the BPD sample into those with child-onset BPD (< or = 12 years of age, n = 50) and those with adolescent-onset BPD (13-18 years of age, n = 36).



In mid-adolescence, youths with adolescent-onset BPD were at significantly increased risk for SUD relative to those with child-onset BPD (39% versus 8%; p = .001). Compared with those with child-onset BPD, those with adolescent-onset BPD had 8.8 times the risk for SUD (95% confidence interval = 2.2-34.7; chi 7(2) = 9.7, p = .002). The presence of conduct disorder or other comorbid psychopathology within BPD did not account for the risk for SUD.



Adolescent-onset BPD is associated with a much higher risk for SUD than child-onset BPD, which was not accounted for by conduct disorder or other comorbid psychopathology. Youths with adolescent-onset BPD should be monitored and educated about SUD risk. The identification and treatment of manic symptomatology may offer therapeutic opportunities to decrease the risk for SUD in these high-risk youths.

title: Substance use disorders and suicide attempts in bipolar subtypes.
abstract: Bipolar disorder (BD) is associated with high rates of suicide attempt and completion. Substance use disorders (SUD) have been identified as potent risk factors for suicidal behavior in BD. However, little is known concerning differences between BD subtypes with regard to SUD as a risk factor for suicidal behavior. We studied previous suicidal behavior in adults with a major depressive episode in context of BD type I (BD-I; N=96) or BD type II (BD-II; N=42), with and without history of SUD. Logistic regressions assessed the association between SUD and suicide attempt history by BD type, and exploratory analyses examined the effects of other clinical characteristics on these relationships. SUD were associated with suicide attempt in BD-I but not BD-II, an effect not attributable to sample size differences. The higher suicide attempt rate associated with alcoholism in BD-I was mostly explained by higher aggression scores, and earlier age of BD onset increased the likelihood that alcohol use disorder would be associated with suicide attempt(s). The higher suicide attempt rate associated with other drug use disorders in BD-I was collectively explained by higher impulsivity, hostility, and aggression scores. The presence of both alcohol and drug use disorders increased odds of a history of suicide attempt in a multiplicative fashion: 97% of BD-I who had both co-morbid drug and alcohol use disorders had made a suicide attempt. A critical next question is how to target SUD and aggressive traits for prevention of suicidal behavior in BD-I.

title: Does recovery from substance use disorder matter in patients with bipolar disorder?
abstract: To examine the potential impact of recovery from substance use disorder (SUD) on the course of bipolar disorder among patients diagnosed with both bipolar and substance use disorders according to DSM-IV criteria.



As part of the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), we examined bipolar disorder status (i.e., whether the patient is recovering or recovered), role functioning, and quality of life in the first 1000 patients to enter the STEP-BD study. We compared patients with no history of SUD, current SUD, and past SUD (i.e., lifetime SUD, but no current SUD) on these parameters. Data were collected between November 1999 and April 2001.



A current clinical status of recovering or recovered from bipolar disorder was less likely among patients with current or past SUD compared to patients with no SUD (p < .002). Recovering/recovered status did not differ significantly between patients with current SUD versus past SUD. All 3 groups differed significantly on measures of role functioning as assessed by the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT), with poorest role functioning among patients with current SUD, followed by patients with past SUD (p = .0002). Patients with current or past SUD reported significantly lower quality of life as measured by the LIFE-RIFT and the Quality of Life Enjoyment and Satisfaction Questionnaire and more lifetime suicide attempts (p < .001) than patients without an SUD; patients with past versus current SUD did not differ significantly on these measures.



The results suggest that patients with bipolar disorder who experience sustained remission from an SUD fare better than patients with current SUD, but not as well as subjects with no history of SUD; differences among the 3 groups appear greatest in the area of role functioning.

title: Clinicians’ assessments of bipolar disorder and substance abuse as predictors of suicidal behavior in acutely hospitalized psychiatric inpatients
abstract: Suicide is a major risk for those with bipolar disorder, a risk amplified by comorbid substance abuse in some, but not all, previous studies. To further explore the relationships of substance abuse, suicide, and bipolarity as they present in clinical practice, we analyzed standardized clinical data from a large acute psychiatric inpatient service.



Standardized clinical evaluations of 7819 patients with diagnoses of bipolar depression (n=990), bipolar mania (n=948), unipolar depressive episode (n=3626), or schizophrenia-schizoaffective disorders (n=2255) were analyzed to evaluate the relationship between current substance-use problems, substance-induced symptoms, and a current suicide crisis, as well as lifetime suicide attempts, with logistic regressions adjusting for age, gender, and ethnicity.



Across the combined groups, current substance-use problems were significantly associated with a lifetime suicide attempt (odds ratios [ORs] 1.6-2.5) and to a lesser degree to the admission suicide crisis (ORs 1-2.2). Among bipolar (depressed/manic) patients, but not other diagnostic groups, those with both current substance-use problems and substance-induced symptoms had even higher rates of a recent suicide crisis (ORs 1.5-3.1) and of a lifetime attempt (ORs 2.5-3.4).



In bipolar patients, substance use disorder doubled and substance use disorder plus substance-induced symptoms tripled the suicidal risk. Implications for future research are discussed.

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



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.



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, chi2 = 4.33, df = 1, p = 0.037).



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.

title: Attempted suicide and alcoholism in bipolar disorder: clinical and familial relationships.
abstract: This study examined the clinical and familial relationships between comorbid alcoholism and attempted suicide in affectively ill relatives of probands with bipolar I disorder.



In 71 families ascertained for a genetic linkage study, 337 subjects with major affective disorder were assessed by using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version.



Subjects with bipolar disorder and alcoholism had a 38.4% lifetime rate of attempted suicide, whereas those without alcoholism had a 21.7% rate. Attempted suicide among subjects with bipolar disorder and alcoholism clustered in a subset of seven families. Families with alcoholic and suicidal probands had a 40.7% rate of attempted suicide in first-degree relatives with bipolar disorder, whereas other families had a 19.0% rate.



Comorbid alcoholism was associated with a higher rate of attempted suicide among family members with bipolar disorder. Attempted suicide and alcoholism clustered in a subset of families. These relationships may have a genetic origin and may be mediated by intoxication, mixed states, and/or temperamental instability.

title: Twelve-month outcome of adolescents with bipolar disorder following first hospitalization for a manic or mixed episode.
abstract: Although adolescent-onset bipolar disorder is associated with significant morbidity, there have been few prospective outcome studies of this population. The aim of this study was to examine the 12-month outcome of bipolar adolescents following an initial hospitalization for a manic or mixed episode.



Bipolar adolescents (N=71) were recruited during their first hospitalization for a manic or mixed episode and were evaluated using diagnostic, symptomatic, and functional assessments. Patients were also evaluated at 1, 4, 8, and 12 months after hospitalization to assess syndromic, symptomatic, and functional outcomes. Predictors of each type of outcome were identified.



Kaplan-Meier estimates of the cumulative probabilities of syndromal, symptomatic, and functional recovery and syndromic recurrence during the first 12 months following initial hospitalization were 0.86, 0.43, 0.41, and 0.54, respectively. Only 35% of bipolar adolescents reported full medication adherence. Individual predictors of poor syndromic recovery included co-occurring attention deficit hyperactivity disorder (ADHD), anxiety disorders, and disruptive behavior disorders as well as nonadherence to psychotropic medication and lower socioeconomic levels. Co-occurring alcohol use disorders, treatment with antidepressants, and the absence of psychotherapeutic intervention predicted syndromic recurrence. Boys were more than twice as likely as girls to experience symptomatic recovery.



Most bipolar adolescents experienced syndromic recovery following their first hospitalization. However, rates of symptomatic and functional recoveries were much lower. Future studies examining effective pharmacological and nonpharmacological treatment strategies for bipolar youth with co-occurring disorders and investigating factors that contribute to the development of substance use disorders and treatment adherence in bipolar youth are necessary to improve outcome.

title: Impact of substance use disorders on recovery from episodes of depression in bipolar disorder patients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).
abstract: Bipolar disorder is highly comorbid with substance use disorders, and this comorbidity may be associated with a more severe course of illness, but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined. The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder.



Subjects (N=3,750) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were followed prospectively for up to 2 years. Prospectively observed depressive episodes were identified for this analysis. Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic, hypomanic, or mixed episode.



During follow up, 2,154 subjects developed a new-onset major depressive episode; of these, 457 subjects switched to a manic, hypomanic, or mixed episode prior to recovery. Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity. However, those with current or past substance use disorder were more likely to experience switch from depression directly to a manic, hypomanic, or mixed state.



Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic, mixed, or hypomanic states. The mechanism conferring this increased risk merits further study.

title: Clinical features, response to treatment and functional outcome of bipolar disorder patients with and without co-occurring substance use disorder: 1-year follow-up.
abstract: Bipolar disorder patients (BP) with comorbid Substance Use Disorder (SUD) may present clinical features that could compromise adherence and response to pharmacological treatment. The purpose of this study was to examine clinical and psychopathological features of BP with and without comorbid SUD in a real-world setting.



The sample was composed by 131 affective patients. Sixty-five patients were affected by Bipolar Disorder I (BP-I, 49.2%), 29 by Bipolar Disorder II (BP-II, 22.3%) and 37 by Cyclothymic Disorder (CtD, 28.5%), according to DSM-IV. Sixty-six patients were diagnosed for a comorbid SUD. All patients have been submitted to psychometric assessment with Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), Young Mania Rating Scale (YMRS), Global Assessment Scale (GAS), Social Adjustment Self-reported Scale (SASS), Quality of Life Scale (QoL), at baseline and repeated follow-up periods (1, 3, 6, 12 months).



BP comorbid for SUD were more likely diagnosed as BP-II and CtD and were less likely to present a moderate-severe manic symptomatology. Furthermore, personality disorders were more frequent in SUD patients than in non-comorbid BP. BP with SUD were not different for primary outcome measure (HDRS, HARS, YMRS, GAS) from non-comorbid BP; however, BP with SUD were significantly more impaired in social functioning (SASS) at any stage of the follow-up and poor functioning increased the risk of relapse in substance use during treatment. Finally, SUD comorbidity did not represent a risk factor for treatment drop-out, while in our sample young age, low treatment dosage and BP-I diagnosis were significantly associated with drop-out.



The primary finding of this work is that BP with comorbid SUD are significantly more compromised in social functioning. Second, these patients were less likely to be diagnosed for BP-I and to present a severe manic symptomatology. Finally, we found that the diagnosis of SUD, but young age, low treatment dosage and BP-I diagnosis to be risk factors for treatment drop-out. Physicians should be alert to these differences in their clinical practice.

title: Presence of co-morbid substance use disorder in bipolar patients worsens their social functioning to the level observed in patients with schizophrenia
abstract: Bipolar disorder has been considered to have a better prognosis than schizophrenia at the very beginning of its definition. However, psychosocial functioning may vary not only because of the characteristics of the disorder, but also of co-morbid conditions, especially regarding substance use disorder (SUD). The purpose of this study was to compare the social adjustment level of patients with bipolar disorder with that observed in patients with schizophrenia, taking into account substance use disorder (SUD). Forty subjects with schizophrenia and 40 subjects with bipolar disorder, in the stable phase of the disorder, were matched for age, gender and presence of SUD (DSM-IV criteria). The social adjustment scale was completed with socio-demographic and clinical characteristics of illness. The global adaptation score of bipolar patients with SUD was poorer than bipolar patients without SUD, but was not observed as being significantly different from that of patients with schizophrenia, with or without associated SUD. Suicide attempts, poor compliance, longer hospitalisation, shorter remissions and criminal activity were also more frequently observed in the group of patients with bipolar disorder and SUD. Presence of substance use disorder seems to have a greater weight than the main diagnostic (schizophrenia versus bipolar disorder) to predict worse social adjustment and poorer outcome.

title: HIV risk behavior among patients with co-occurring bipolar and substance use disorders: associations with mania and drug abuse.
abstract: Bipolar and substance use disorders frequently co-occur, and both are associated with impulsivity, impaired judgment, and risk-taking.



This study aimed to: (1) describe the rates of HIV sexual and drug risk behaviors among patients with co-occurring bipolar and substance use disorders, (2) test whether acute mania, psychiatric severity, and drug severity independently predict HIV risk, and (3) examine the relationship between specific substance dependencies and sexual risk behaviors.



Participants (N=101) were assessed for psychiatric diagnoses, substance abuse, and HIV risk behavior using structured clinical interviews and self-report questionnaires.



The majority (75%) were sexually active in the past 6 months and reported high rates of sexual risk behaviors, including unprotected intercourse (69%), multiple partners (39%), sex with prostitutes (24%, men only), and sex trading (10%). In a multivariate linear regression model, recent manic episode, lower psychiatric severity, and greater drug severity were independent predictors of total HIV risk. Cocaine dependence was associated with increased risk of sex trading.



Results underscore the importance of HIV prevention for this population.

title: Cigarette smoking and its relationship to mood disorder symptoms and co‐occurring alcohol and cannabis use disorders following first hospitalization for bipolar disorder
abstract: Heffner JL, DelBello MP, Anthenelli RM, Fleck DE, Adler CM, Strakowski SM. Cigarette smoking and its relationship to mood disorder symptoms and co‐occurring alcohol and cannabis use disorders following first hospitalization for bipolar disorder. Bipolar Disord 2012: 14: 99–108.

title: Effects of co-occurring alcohol abuse on the course of bipolar disorder following a first hospitalization for mania.
abstract: Alcohol-use disorders are common co-occurring conditions affecting bipolar patients, and this co-occurrence is negatively associated with outcome.



The primary goal of this study was to identify how the relative onsets of alcohol-use and bipolar disorders affect the subsequent courses of illness in patients with both conditions.



Inception cohort at an academic medical center.



Patients meeting criteria for type I bipolar disorder, manic or mixed, with ages of 12 to 45 years, no prior hospitalizations, and minimal prior treatment. We enrolled 144 subjects who were followed up for up to 5 years, including 27 subjects in whom the onset of an alcohol-use disorder preceded the onset of bipolar disorder (Alcohol First), 33 subjects in whom bipolar disorder onset preceded or was concurrent with the onset of alcohol abuse (Bipolar First), and 83 subjects with bipolar disorder only (No Alcohol).



Symptomatic recovery and recurrence of both conditions and percentage of follow-up with affective episodes and affective and alcohol-use disorder symptoms.



The Alcohol First group was older and more likely to recover and recover more quickly than the other groups. Affective symptomatic recurrence curves were similar among groups. The Bipolar First group spent more time with affective episodes and symptoms of an alcohol-use disorder during follow-up than the Alcohol First group. Hospitalization was associated with a period of decreased alcohol abuse, although recurrence of the alcohol-use disorder was common.



The relative age at onset of alcohol-use and bipolar disorders is associated with differences in the course of both conditions. A first hospitalization for mania is associated with a period of recovery from comorbid alcohol abuse, suggesting this posthospital time may provide an opportunity to treat this co-occurring condition.

title: Effects of co-occurring cannabis use disorders on the course of bipolar disorder after a first hospitalization for mania.
abstract: Cannabis use disorders commonly co-occur in bipolar disorder; however, the effects of cannabis abuse on outcome have been minimally studied.



To identify how the sequence of the onsets of a cannabis use disorder and bipolar disorder is associated with the subsequent course of each condition.



Inception cohort.



Academic medical center.



Patients (N = 144) were studied who met criteria for bipolar I disorder (manic or mixed), were 12 to 45 years old, and had no previous hospitalizations and minimal previous treatment. Patients were followed up for up to 5 years and included 33 in whom the onset of a cannabis use disorder preceded the onset of bipolar disorder (cannabis first), 36 in whom bipolar disorder onset preceded the onset of cannabis abuse (bipolar first), and 75 with bipolar disorder only.



Symptomatic recovery and recurrence of both conditions and percentage of follow-up time with affective and cannabis use disorder symptoms.



The cannabis first group exhibited better recovery than the other groups, although when adjusted for potential mediator variables these results did not persist. Cannabis use was associated with more time in affective episodes and with rapid cycling. Most cannabis use disorders remitted immediately after hospitalization, followed by rapid rates of recurrence.



The effects of the sequence of onsets of bipolar and cannabis use disorders were less pronounced than observed in co-occurring alcohol and bipolar disorders. Aggressive drug abuse treatment immediately after a first psychiatric hospitalization might decrease rates of recurrence and new cases of cannabis use disorder in the course of bipolar disorder.

title: The Fifth Edition of the Addiction Severity Index.
abstract: The Addiction Severity Index (ASI) is 12 years old and has been revised to include a new section on family history of alcohol, drug, and psychiatric problems. New items were added in existing sections to assess route of drug administration; additional illegal activities; emotional, physical, and sexual abuse; quality of the recovery environment; and history of close personal relationships. No changes were made in the composite scoring to maintain comparability with previous editions. This article discusses the clinical and research uses of the ASI over the past 12 years, emphasizing some special circumstances that affect its administration. The article then describes the rationale for and description of the changes made in the ASI. The final section provides "normative data" on the composite scores and severity ratings for samples of opiate, alcohol, and cocaine abusers as well as drug abusing inmates, pregnant women, homeless men, and psychiatrically ill substance abusers.

title: Best estimate of lifetime psychiatric diagnosis: a methodological study.
abstract: It is important for genetic, epidemiologic, and nosological studies to determine accurate rates of lifetime psychiatric diagnoses in patient and nonpatient populations. As part of a case-control family study of major depression, lifetime psychiatric diagnoses were made for 1,878 individuals. Sources of information used in making diagnostic estimates included direct interview, medical records, and family history data systematically obtained from relatives. Diagnostic estimates were made by trained interviewers, experienced clinicians, and by computer program. The results indicate that it is possible to make lifetime best estimate diagnoses reliably among both interviewed and noninterviewed individuals for most diagnostic categories and that diagnoses based on interview data alone are an adequate substitute for best estimate diagnoses based on all available information in a limited number of diagnostic categories.

title: Predictors of first-onset substance use disorders during the prospective course of bipolar spectrum disorders in adolescents.
abstract: Substance use disorders (SUD) are common and problematic in bipolar disorder (BP). We prospectively examined predictors of first-onset SUD among adolescents with BP.



Adolescents (12-17 years old; N = 167) in the Course and Outcome of Bipolar Youth (COBY) study fulfilling criteria for BP-I, BP-II, or operationalized BP not otherwise specified, without SUD at intake, were included. Baseline demographic, clinical, and family history variables, and clinical variables assessed during follow-up, were examined in relation to first-onset SUD. Participants were prospectively interviewed every 38.5 ± 22.2 weeks for an average of 4.25 ± 2.11 years.



First-onset SUD developed among 32% of subjects, after a mean of 2.7 ± 2.0 years from intake. Lifetime alcohol experimentation at intake most robustly predicted first-onset SUD. Lifetime oppositional defiant disorder and panic disorder, family history of SUD, low family cohesiveness, and absence of antidepressant treatment at intake were also associated with increased risk of SUD, whereas BP subtype was not. Risk of SUD increased with increasing number of these 6 predictors: 54.7% of subjects with 3 or more predictors developed SUD vs. 14.1% of those with fewer than 3 predictors (hazard ratio = 5.41 95% confidence interval = 2.7-11.0 p < .0001). Greater hypo/manic symptom severity in the preceding 12 weeks predicted greater likelihood of SUD onset. Lithium exposure in the preceding 12 weeks predicted lower likelihood of SUD.



This study identifies several predictors of first-onset SUD in the COBY sample that, if replicated, may suggest targets for preventive interventions for SUD among youth with BP. Treatment-related findings are inconclusive and must be interpreted tentatively, given the limitations of observational naturalistic treatment data. There is a substantial window of opportunity between BP and SUD onset during which preventive strategies may be used.

title: Adolescent substance use disorder during the early stages of bipolar disorder: a prospective high-risk study.
abstract: There is a paucity of longitudinal data characterizing the relationship between substance use disorder (SUD) and the early clinical course of bipolar disorder (BD). We studied this relationship in a prospectively assessed cohort of high-risk offspring.



Eligible families had one parent with confirmed BD based on SADS-L interviews and best estimate diagnostic procedure. Offspring completed KSADS-PL interviews at baseline and were reassessed prospectively. DSM-IV diagnoses were made on blind consensus review using all available information. This analysis included 211 offspring ≥12 years, and used GEE and linear mixed models to determine clinical characteristics differentiating those with compared to those without SUD, and CPH models to assess the relationship between SUD and the early stages of BD.



Lifetime SUD was diagnosed in 24% of offspring; cannabis use being most common. The peak hazard of SUD was between 14 and 20 years of age. Male sex (HR 3.285; p=.0007), a prior mood disorder (HR 2.437; p=.0091) and parental history of SUD (HR 2.999; p=.0027) contributed to the risk of SUD in the offspring, while SUD predicted an increased risk of psychosis (HR 3.225; p=.0074). The estimated hazard of a major mood disorder in those offspring with compared to those without a prior SUD was almost 3-fold (HR 2.990 (p≤0.01).



The novel clinical staging model requires independent replication.



SUD is a common comorbidity arising during the early course of BD, even before the first activated episode. Further research is needed to understand causative factors and to develop effective early intervention and prevention strategies.

title: Post-traumatic stress disorder, depression and suicidality in inpatients with substance use disorders.
abstract: The international literature suggests that traumatic events are common for patients with substance use disorders (SUDs), and are often associated with the development of post-traumatic stress disorder (PTSD) and other psychiatric comorbidities. However, limited research has been conducted among Australian SUD patients. The aim of the present study was to examine the prevalence of these disorders in a group of Australian patients admitted for detoxification.



Data were collected from 253 inpatients using a modified version of the Composite International Diagnostic Interview, the 10-item Trauma Screening Questionnaire, the Zung Self-rating Depression Scale and questions from the PsyCheck.



Approximately 20% of inpatients experienced moderate to severe depressive symptoms, and 37% had a lifetime history of self-harm or attempted suicide. Approximately 80% of patients had experienced at least one traumatic event, most experiencing multiple traumas. The mean age of first trauma was 14years. Almost 45% of patients screened positive for current PTSD symptoms. Women were nine times more likely to have been raped and five times more likely to have been sexually molested than men. PTSD symptoms were associated with greater trauma exposure, younger age of first trauma, specific trauma types, moderate to severe depressive symptoms and a history of self-harm or attempted suicide. Despite their difficulties, patients with PTSD symptoms had high rates of retention in treatment.



Patients entering treatment for SUDs should be assessed for PTSD, depression and suicidality. These conditions impact significantly on treatment outcomes, and require the development of appropriate treatment strategies.

title: Childhood trauma among individuals with co-morbid substance use and post traumatic stress disorder.
abstract: Little is known about the impact of childhood trauma (CT) on the clinical profile of individuals with co-occurring substance use disorder (SUD) and post traumatic stress disorder (PTSD).  To compare the clinical characteristics of individuals with SUD+PTSD who have a history of CT with SUD+PTSD individuals who have experienced trauma during adulthood only.  Data were collected on 103 individuals as part of a randomised controlled trial examining the efficacy of an integrated psychosocial treatment for SUD+PTSD. Participants were recruited from substance use treatment services, community referrals and advertising. Data were collected on demographic characteristics, substance use and treatment histories, lifetime trauma exposure, and current physical and mental health functioning.  The vast majority (77%) of the sample had experienced at least one trauma before the age of 16, with 55% of those endorsing childhood sexual abuse. As expected individuals with a CT history, as compared to without, evidenced significantly longer duration of PTSD. Those with a CT history also had more extensive lifetime trauma exposure, an earlier age of first intoxication, and reported more severe substance use (e.g., a greater number of drug classes used in their lifetime, higher severity of dependence scores and greater number of drug treatment episodes).  Individuals with co-morbid SUD+PTSD who have experienced CT present with a more severe and chronic clinical profile in relation to a number of trauma and substance use characteristics, when compared to individuals with adulthood only trauma histories. It is therefore important for SUD+PTSD treatment planning that CT be carefully assessed.

title: Posttraumatic stress disorder and substance use disorder in adolescent bipolar disorder.
abstract: Anxiety disorders such as posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are increasingly recognized as comorbid disorders in children with bipolar disorder (BPD). This study explores the relationship between BPD, PTSD, and SUD in a cohort of BPD and non-BPD adolescents.



We studied 105 adolescents with BPD and 98 non-mood-disordered adolescent controls. Psychiatric assessments were made using the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiologic Version (KSADS-E), or Structured Clinical Interview for DSM-IV (SCID) if 18 years or older. SUD was assessed by KSADS Substance Use module for subjects under 18 years, or SCID module for SUD if age 18 or older.



Nine (8%) BPD subjects endorsed PTSD and nine (8%) BPD subjects endorsed subthreshold PTSD compared to one (1%) control subject endorsing full PTSD and two (2%) controls endorsing subthreshold PTSD. Within BPD subjects endorsing PTSD, seven (39%) met criteria for SUD. Significantly more SUD was reported with full PTSD than with subthreshold PTSD (chi(2) = 5.58, p = 0.02) or no PTSD (chi(2) = 6.45, p = 0.01). Within SUD, the order of onset was BPD, PTSD, and SUD in three cases, while in two cases the order was PTSD, BPD, SUD. The remaining two cases experienced coincident onset of BPD and SUD, which then led to trauma, after which they developed PTSD and worsening SUD.



An increased rate of PTSD was found in adolescents with BPD. Subjects with both PTSD and BPD developed significantly more subsequent SUD, with BPD, PTSD, then SUD being the most common order of onset. Follow-up studies need to be conducted to elucidate the course and causal relationship of BPD, PTSD and SUD.

title: Reasons for substance use among people with psychotic disorders: method triangulation approach.
abstract: Substance use disorders (SUD) are common among people with psychotic disorders and are associated with many negative consequences. Understanding the reasons for substance use in this population may allow for the development of more effective prevention and intervention strategies. We examined reasons for tobacco, alcohol, or cannabis use among people with psychotic disorders. Sixty-four participants with a diagnosed psychotic disorder completed a self-report reasons for use questionnaire. A subset of eight participants completed semi-structured qualitative interviews. Both the qualitative and quantitative data indicated that reasons for use of tobacco, alcohol, and cannabis differed considerably. Tobacco was primarily used for coping motives, alcohol for social motives, and cannabis for pleasure enhancement motives. Prevention and intervention strategies targeting coexisting psychotic disorders and SUD may improve in effectiveness if they address the perceived beneficial effects of tobacco use, the strong social pressures influencing alcohol use and if they encourage cannabis users to seek alternative pleasurable activities.

title: Do treatment improvements in PTSD severity affect substance use outcomes? A secondary analysis from a randomized clinical trial in NIDA's Clinical Trials Network.
abstract: The purpose of the analysis was to examine the temporal course of improvement in symptoms of posttraumatic stress disorder (PTSD) and substance use disorder among women in outpatient substance abuse treatment.



Participants were 353 women randomly assigned to 12 sessions of either trauma-focused or health education group treatment. PTSD and substance use assessments were conducted during treatment and posttreatment at 1 week and after 3, 6, and 12 months. A continuous Markov model was fit on four defined response categories (nonresponse, substance use response, PTSD response, or global response [improvement in both PTSD and substance use]) to investigate the temporal association between improvement in PTSD and substance use symptom severity during the study's treatment phase. A generalized linear model was applied to test this relationship over the follow-up period.



Subjects exhibiting nonresponse, substance use response, or global response tended to maintain original classification; subjects exhibiting PTSD response were significantly more likely to transition to global response over time, indicating maintained PTSD improvement was associated with subsequent substance use improvement. Trauma-focused treatment was significantly more effective than health education in achieving substance use improvement, but only among those who were heavy substance users at baseline and had achieved significant PTSD reductions.



PTSD severity reductions were more likely to be associated with substance use improvement, with minimal evidence of substance use symptom reduction improving PTSD symptoms. Results support the self-medication model of coping with PTSD symptoms and an empirical basis for integrated interventions for improved substance use outcomes in patients with severe symptoms.

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



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).



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.



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.

title: Reasons for substance use among adolescents with bipolar disorder.
abstract: We examined whether children and adolescents with bipolar disorder (BPD) "self-medicate" with cigarettes, alcohol, or other substances of abuse. One hundred and five adolescents with BPD and 98 controls were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and the Drug Use Screening Inventory (DUSI) for self-medication. Thirteen control (mean ± standard deviation [SD]= 15.31 ± 1.18 years) and 27 BPD (15.30 ± 2.09 years) subjects endorsed use of one of the listed drugs in the DUSI Section A within the past year and were included in all analyses. BPD adolescents were more likely than nonmood disordered, substance-using controls to report starting to use their preferred drug for mood-altering effects. There were no differences between groups in motivation for use with respect to starting substances to sleep better or get high, or in continuing substances to change mood, sleep better, or get high. These data may contribute to increased prevention of substance use disorders and to the treatment of adolescent BPD. Further studies clarifying the characteristics of self-medication are necessary.

title: Impulsivity: a link between bipolar disorder and substance abuse.
abstract: Substance abuse is present in most patients with bipolar disorder and associated with poor treatment outcome and increased risk of suicide. Increased impulsivity may be a link between bipolar disorder and substance abuse.



First, we compared impulsivity as a stable trait (Barratt Impulsiveness Scale, BIS) and as state-dependent behavioral laboratory performance (Immediate Memory-Delayed Memory task, derived from the Continuous Performance Task) in interepisode bipolar and non-bipolar subjects with and without substance abuse. Secondly, we compared impulsivity in interepisode and manic bipolar subjects with and without substance abuse.



The BIS scores were increased in interepisode bipolar disorder and in subjects with histories of substance abuse, and were increased further in interepisode bipolar subjects with substance abuse. Performance impulsivity was increased in subjects with substance abuse, regardless of whether they had bipolar disorder. Among subjects with bipolar disorder, after correction for age, BIS scores were increased in those with substance abuse. Performance impulsivity was increased in manic compared with interepisode subjects, regardless of substance abuse history, and was increased in interepisode subjects with substance abuse similarly to manic subjects without substance abuse. These differences could not be accounted for by age, gender, or course of illness.



Trait impulsivity is increased additively in bipolar disorder and substance abuse. Performance impulsivity is increased in interepisode bipolar disorder only if a history of substance abuse is present. This increased predisposition to impulsivity when not manic may contribute to the decrement in treatment outcome and compliance, and increased risk for suicide and aggression, in bipolar disorder with substance abuse.

title: Pharmacotherapy of Attention-deficit/Hyperactivity Disorder Reduces Risk for Substance Use Disorder
abstract: To assess the risk for substance use disorders (SUD) associated with previous exposure to psychotropic medication in a longitudinal study of boys with attention-deficit/hyperactivity disorder (ADHD).  The cumulative incidence of SUD throughout adolescence was compared in 56 medicated subjects with ADHD, 19 nonmedicated subjects with ADHD, and 137 non-ADHD control subjects.  Unmedicated subjects with ADHD were at a significantly increased risk for any SUD at follow-up compared with non-ADHD control subjects (adjusted OR: 6.3 ). Subjects with ADHD medicated at baseline were at a significantly reduced risk for a SUD at follow-up relative to untreated subjects with ADHD (adjusted OR: 0.15 . For each SUD subtype studied, the direction of the effect of exposure to pharmacotherapy was similar to that seen for the any SUD category.  Consistent with findings in untreated ADHD in adults, untreated ADHD was a significant risk factor for SUD in adolescence. In contrast, pharmacotherapy was associated with an 85% reduction in risk for SUD in ADHD youth.

title: Cocaine receptors on dopamine transporters are related to self-administration of cocaine.
abstract: Although cocaine binds to several sites in the brain, the biochemical receptor mechanism or mechanisms associated with its dependence producing properties are unknown. It is shown here that the potencies of cocaine-like drugs in self-administration studies correlate with their potencies in inhibiting [3H]mazindol binding to the dopamine transporters in the rat striatum, but not with their potencies in binding to a large number of other presynaptic and postsynaptic binding sites. Thus, the cocaine receptor related to substance abuse is proposed to be the one associated with dopamine uptake inhibition.