Disentangling the Social Context of Nonmedical Use of Prescription Stimulants in College Students.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the social context of nonmedical use of prescription stimulants (NMUPS) among college students who endorsed NMUPS with co-occurring substance use disorders (SUD) compared with those without co-occurring SUDs. METHODS: Presented here are new analyses based on data previously collected from college students aged 18 to 28 years derived from the Boston metropolitan area who endorsed NMUPS (N = 100) at least once in their lifetime. Differences between those with lifetime history of SUD (N = 46) and without a history of SUD (N = 54) on the Massachusetts General Hospital ADHD Medication Misuse and Diversion Assessment were analyzed using the Student t test, the Pearson χ2 test, and the Wilcoxon rank-sum test. RESULTS: College students who endorsed NMUPS with co-occurring SUD were more likely than those without SUD to have bought or traded stimulants, bought or traded in their car, used at parties with drugs/alcohol, or used intranasally (all P < .05). Intranasal administration was common (38% of all students endorsing NMUPS) and was associated with misuse at a party and simultaneous use with cocaine (P = .04), marijuana (P < .001), and alcohol (P < .001), compared with only oral use. DISCUSSION AND CONCLUSIONS: Notable characteristics were identified among individuals who engaged in NMUPS in the type, amount, cost, and ascertainment of stimulants. SCIENTIFIC SIGNIFICANCE: The concurrence of SUD and/or intranasal administration appear to represent a more severe phenotype of NMUPS that should be considered in the implementation of future prevention and intervention protocols on college campuses. (Am J Addict 2020;29:476-484).

Recovery From Malnutrition Among Refugee Children Following Participation in the Special Supplemental Nutrition for Women, Infants, and Children (WIC) Program in Massachusetts, 1998-2010.

OBJECTIVES: (1) To examine patterns of catch-up growth and anemia correction in refugee children younger than 5 years after participation in the Special Supplemental Nutrition for Women, Infants, and Children (WIC) program, and (2) to identify factors associated with recovery from growth abnormalities. DESIGN: Records on 1731 refugee children younger than 5 years who arrived in Massachusetts between 1998-2010 were matched to WIC program records and then restricted to 779 children who had at least 2 WIC visits. Kaplan-Meier curves and Cox proportional hazards models were used to examine how sex affected time to recovery from malnutrition and anemia. Factors associated with recovery were analyzed in SAS using multivariate logistic regression. SETTING: Massachusetts. PARTICIPANTS: Refugee children younger than 5 years on arrival, who visited a WIC program at least twice between 1998 and 2010. MAIN OUTCOME MEASURES: (1) Proportion of children who recovered from low height-for-age (stunting), low weight-for-age, low weight-for-height (wasting), and anemia; (2) odds ratios for factors associated with recovery; and (3) Kaplan-Meier curves showing recovery over time from low height-for-age, low weight-for-age, and low weight-for-height. RESULTS: The number of WIC visits was associated with recovery from stunting, wasting, low weight-for-age, and anemia; results reached statistical significance for stunting (odds ratio [OR] = 8.64; 95% confidence interval [CI], 2.25-33.19), low weight-for-age (OR = 5.28; 95% CI, 1.35-20.73), and anemia (OR = 6.50; 95% CI, 2.69-15.69). Female sex was associated with recovery from stunting, wasting, and low weight-for-age, whereas male sex was associated with recovery from anemia; the associations were statistically significant between female sex and stunting (OR = 9.14; 95% CI, 1.93-43.29), wasting (OR = 14.78; 95% CI, 1.57-138.85), and low weight-for-age (OR = 4.29; 95% CI, 1.09-16.79). CONCLUSIONS: Children who remained engaged in WIC may recover better from malnutrition than children with fewer WIC visits, although there are limitations to the available data.These findings suggest that those working with refugee families should prioritize outreach toward initiating and maintaining WIC program enrollment for eligible refugee children.

Neuropsychological functioning in college students who misuse prescription stimulants.

BACKGROUND AND OBJECTIVES: Relatively little is known about the neuropsychological profiles of college students who misuse prescription stimulant medications. METHODS: Data presented are from college students aged 18-28 years who misused prescription stimulants prescribed for attention-deficit/hyperactivity disorder and controls (no prescription stimulant misuse). Students were assessed neuropsychologically using the self-report Behavioral Rating Inventory of Executive Functioning (BRIEF-A), the Cambridge Automated Neuropsychological Test and Battery (CANTAB), and other tests of cognitive functioning. The analyses included 198 controls (age 20.7 ± 2.6 years) and 100 prescription stimulant misusers (age 20.7 ± 1.7 years). RESULTS: On the BRIEF-A, misusers were more likely than controls to endorse greater dysfunction on 8 of 12 measures including Inhibition, Self Monitor, Initiation, Working Memory, and Plan/Organize, when adjusting for race and sex (all p's < .05). Similarly, when dichotomizing the BRIEF-A as abnormal (T score ≥ 65), misusers had more abnormalities on five of nine subscales, as well as all major indices (p's < .05). Misusers also performed worse on several subtests of the CANTAB and standardized cognitive battery (p's < .05). A proxy of prescription stimulant misuse frequency was positively correlated with greater executive dysfunction on the BRIEF-A. DISCUSSION AND CONCLUSIONS: These data demonstrate elevated risk for neuropsychological dysfunction among students who misuse prescription stimulants compared to non-misusing peers. The presence of ADHD contributed significantly to these cognitive findings. Students who misuse prescription stimulants should be screened for neuropsychological dysfunction. SCIENTIFIC SIGNIFICANCE: These data may better elucidate the neuropsychological profile of college-aged prescription stimulant misusers. (Am J Addict 2017;26:379-387).

Parental history of substance use disorders (SUD) and SUD in offspring: a controlled family study of bipolar disorder.

BACKGROUND AND OBJECTIVES: Adolescents with bipolar disorder (BPD) have been previously shown to be at very high risk for substance use disorders (SUD). We now examine the influence of a parental history of substance use disorders on SUD risk in offspring with and without BPD. METHODS: We studied 190 parents ascertained through 104 adolescent BPD probands and 189 parents ascertained through 98 control probands using structured interviews. We compared the prevalence of SUD using logistic regression. RESULTS: While adjusting for BPD in our combined sample, probands with a parental history of SUD were more likely to have an alcohol use disorder compared to probands without a parental history. Probands with a parental history of SUD were not more likely to have a drug use disorder or overall SUD compared to probands without a parental history. BPD in the offspring did not pose any additional risk between parental history of SUD and offspring SUD. CONCLUSION: Alcohol use disorders were more common in the offspring of parents with a SUD history compared to parents without SUD and the risk was not influenced by offspring BPD. SCIENTIFIC SIGNIFICANCE: Clarifying the mechanisms linking parental SUD to offspring SUD, particularly in children and adolescents with BPD, would help clinicians to educate and monitor high-risk families, which would facilitate strategies to mitigate risks associated with parental substance abuse.

Are obstetrical, perinatal, and infantile difficulties associated with pediatric bipolar disorder?

OBJECTIVES: Despite increasing acknowledgement of bipolar disorder (BD) in childhood, there is a paucity of literature that has investigated obstetrical, perinatal, and infantile difficulties and their potential link with BD. To this end, we examined difficulties during delivery, immediate post-birth, and infancy and the association with BD in childhood. METHODS: From two similarly designed, ongoing, longitudinal, case-control family studies of pediatric BD (N = 327 families), we analyzed 338 children and adolescents [mean (± standard deviation) age: 12.00 ± 3.37 years]. We stratified them into three groups: healthy controls (N = 98), BD probands (N = 120), and their non-affected siblings (N = 120). All families were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and substance use. Mothers were directly questioned regarding the pregnancy, delivery, and infancy difficulties that occurred with each child using a module from the Diagnostic Interview for Children and Adolescents-Parent Version (DICA-P). RESULTS: Mothers of BD subjects were more likely to report difficulties during infancy than mothers of controls [odds ratio (95% confidence interval) = 6.6 (3.0, 14.6)]. Specifically, children with BD were more likely to have been reported as a stiffened infant [7.2 (1.1, 47.1)] and more likely to have experienced 'other' infantile difficulties [including acting colicky; 4.9 (1.3, 18.8)] compared to controls. We found no significant differences between groups in regards to obstetrical or perinatal difficulties (all p values > 0.05). CONCLUSIONS: While our results add to previous literature on obstetrical and perinatal difficulties and BD, they also highlight characteristics in infancy that may be prognostic indicators for pediatric BD.

Reasons for substance use among adolescents with bipolar disorder.

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.

Does exposure to parental substance use disorders increase offspring risk for a substance use disorder? A longitudinal follow-up study into young adulthood.

OBJECTIVE: The main aim of this study was to examine the risk of exposure to parental substance use disorders (SUD; alcohol or drug abuse or dependence) on the risk for SUD in offspring with and without attention deficit hyperactivity disorder (ADHD) followed into young adult years. METHODS: Subjects were derived from two longitudinal case-control studies of probands of both sexes, 6-17 years, with and without DSM-III-R ADHD and their parents. Probands were followed for ten years into young adulthood. Probands with a parental history of non-nicotine SUD were included in this analysis. Exposure to SUD was determined by active non-nicotine parental SUD while the parent was living with their child after birth. Cox proportional hazard models were used to calculate the risk of non-nicotine SUD in offspring. RESULTS: 171 of the 404 probands reassessed at ten-year follow up had a family history of parental SUD. 102 probands were exposed to active parental SUD. The average age of our sample was 22.2 ±â€¯3.5 years old. Exposure to maternal but not paternal SUD increased offspring risk for an alcohol use disorder in young adulthood independently of ADHD status (OR: 2.7; 95% CI: 1.1, 6.9; p = 0.04). CONCLUSION: Exposure to maternal SUD increases the risk for an alcohol use disorder in offspring ten years later in young adult years irrespective of ADHD status.

Is Maternal Smoking During Pregnancy a Risk Factor for Cigarette Smoking in Offspring? A Longitudinal Controlled Study of ADHD Children Grown Up.

OBJECTIVE: This study examined whether exposure to maternal smoking during pregnancy in children with and without ADHD is associated with smoking in offspring and whether this association is selective to ADHD children. METHOD: Ninety-six exposed and 400 unexposed participants were derived from two longitudinal studies of boys and girls with and without ADHD. Maternal smoking during pregnancy was defined by interviews with participants' mothers. RESULTS: A significant association was observed between exposure to maternal smoking in pregnancy and cigarette smoking in offspring ( p = .02). Exposed offspring were also more likely to have higher rates of major depression ( p = .04), bipolar disorder ( p = .04), and conduct disorder ( p = .04), and lower IQ ( p = .01), lower Global Assessment of Functioning (GAF) score ( p = .02), and more impaired Social Adjustment Inventory for Children and Adolescents (SAICA) scores versus unexposed offspring, adjusting for social class. CONCLUSION: Maternal smoking during pregnancy was found to increase the risk for smoking and a wide range of adverse psychiatric, cognitive, and functional outcomes in youth.

Examining the association between attention deficit hyperactivity disorder and substance use disorders: A familial risk analysis.

OBJECTIVE: The main aim of this study was to use familial risk analysis to examine the association between attention deficit hyperactivity disorder (ADHD) and substance use disorders (SUDs) attending to sex effects and the specificity of alcohol and drug use disorder risks. METHODS: Subjects were derived from two longitudinal case-control family studies of probands aged 6-17 years with and without DSM-III-R ADHD of both sexes and their first degree relatives followed from childhood onto young adult years. Cox proportional hazard models were used to estimate rates of ADHD and SUDs (any SUD, alcohol dependence, and drug dependence). Logistic regression was used to test both co-segregation and assortative mating. RESULTS: Our sample included 404 probands (ADHD: 112 boys and 96 girls; Control: 105 boys and 91 girls) and their 1336 relatives. SUDs in probands increased the risk for SUDs in relatives irrespective of ADHD status. The risk for dependence to drug or alcohol in relatives was non-specific. There was evidence that even in the absence of a SUD in the proband, ADHD by itself increased the risk of SUDs in relatives. Proband sex did not moderate the familial relationship between ADHD and SUDs. There was evidence of co-segregation between ADHD and SUD. CONCLUSIONS: Findings indicate that various independent pathways are involved in the transmission of SUD in ADHD and that these risks were not moderated by proband sex. ADHD children and siblings should benefit from preventive and early intervention strategies to decrease their elevated risk for developing a SUD.

Branding Asklepios and the Traditional and Variant Serpent Symbol Display Among Health Professional Schools in the United States, Puerto Rico, and Canada: A Cross-Sectional Survey.

BACKGROUND: History supports the staff and single serpent, the asklepian, as the symbol of healing and medicine, yet its confusion with the caduceus (a winged staff with two snakes wrapped around it) persists. No population-based information on serpent symbol use exists. OBJECTIVE: To determine the prevalence of asklepian and caduceus display among Internet images of medical and health professional schools' emblems, and to compare asklepian and caduceus display between medical and health professional schools, examining the effects of school longevity and geographic location on symbol display. METHODS: This cross-sectional survey examined Internet websites and Google Images associated with medical and other health professional schools in the United States, Puerto Rico, and Canada from 2013 to 2015. The primary outcome was display of a traditional or variant asklepian or caduceus among current and past emblems in Google Images. Odds ratios (ORs) and 95% confidence intervals for the comparison of medical versus other health professional schools were calculated by logistic regression. Differences among schools' longevity were assessed with Student's t-tests and linear regression. RESULTS: Among images of current and past emblems of 482 schools-159 medical schools and 323 health professional schools-107 (22.2%) emblems displayed only the traditional, and 205 (42.5%) any, asklepian. Adjusting for geographic region and longevity, medical schools were 59% less likely than health professional schools to display the traditional asklepian (OR 0.41, 95% CI 0.24-0.71, P=.001), and were 7.7 times more likely than health professional schools to display the traditional caduceus. Medical schools were 8% less likely than health professional schools to display any asklepian (OR 0.92, 95% CI 0.62-1.38, P=.70), and were 3.3 times more likely than health professional schools to display any caduceus. CONCLUSIONS: Schools' preference of the asklepian over the caduceus confirmed historical origins. Less asklepian and more caduceus display by medical schools suggests an educational opportunity for the medical profession to define for itself and the public the correct symbol of an interdisciplinary mission of healing.

Nonmedical Stimulant Use in College Students: Association With Attention-Deficit/Hyperactivity Disorder and Other Disorders.

Objective: The nonmedical use of stimulants (misuse) in the college setting remains of utmost public health and clinical concern. The objective of this study was to evaluate comprehensively the characteristics of college students who misused stimulants, attending to rates of attention-deficit/hyperactivity disorder (ADHD), other psychopathology, and substance use disorders. Methods: The data presented are from a cross-sectional study of college students who misused prescription stimulant medications (not including cocaine or methamphetamine) and controls (college students without stimulant misuse). Between May 2010 and May 2013, college students were assessed blindly for psychopathology and substance use disorder by way of Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P) and completion of self-report questionnaires. Results: The analysis included 198 controls (mean ± SD age = 20.7 ± 2.6 years) and 100 stimulant misusers (20.7 ± 1.7 years). Misusers, when compared to controls, were more likely to endorse alcohol, drug, alcohol + drug, and any substance use disorder (all P values < .01). When a subset of stimulant misusers (n = 58) was examined, 67% had a full or subthreshold prescription stimulant use disorder. Misusers also had higher rates of conduct disorder (10% vs 3%; P = .02) and ADHD (including subthreshold cases; 27% vs 16%; P = .02) in addition to lower Global Assessment of Functioning score (P < .01). Higher rates of misuse of immediate-release­relative to extended-release­stimulants were reported. Conclusions: Our data suggest that, compared to controls, college students who misuse stimulant medications are more likely to have ADHD, conduct disorder, stimulant and other substance use disorder, and overall dysfunction.

Further Evidence for Smoking and Substance Use Disorders in Youth With Bipolar Disorder and Comorbid Conduct Disorder.

OBJECTIVE: Bipolar disorder (BPD) is a highly morbid disorder increasingly recognized in adolescents. The aim of this study was to examine the relative risk for substance use disorders (SUDs; alcohol or drug abuse or dependence) and cigarette smoking in adolescents with BPD. METHODS: We evaluated the relative risk for SUDs and cigarette smoking in a case-controlled, 5-year prospective follow-up of adolescents with (n = 105, mean ± SD baseline age = 13.6 ± 2.5 years) and without ("controls"; n = 98, baseline age = 13.7 ± 2.1 years) BPD. Seventy-three percent of subjects were retained at follow-up (BPD: n = 68; controls: n = 81; 73% reascertainment). Our main outcomes were assessed by blinded structured interviews for DSM-IV criteria. RESULTS: Maturing adolescents with BPD, compared to controls, were more likely to endorse higher rates of SUD (49% vs 26%; hazard ratio [HR] = 2.0; 95% confidence interval (CI), 1.1-3.6; P = .02) and cigarette smoking (49% vs 17%; HR = 2.9; 95% CI, 1.4-6.1; P = .004), as well as earlier onset of SUD (14.9 ± 2.6 [SD] years vs 16.5 ± 1.6 [SD] years; t = 2.6; P = .01). Subjects with conduct disorder (CD) were more likely to have SUD and nicotine dependence than subjects with BPD alone or controls (all P values < .05). When we added conduct disorder to the model with socioeconomic status and parental SUD, all associations lost significance (all P values > .05). Subjects with the persistence of a BPD diagnosis were also more likely to endorse cigarette smoking and SUD in comparison to those who lost a BPD diagnosis or controls at follow-up. CONCLUSIONS: The results provide further evidence that adolescents with BPD, particularly those with comorbid CD, are significantly more likely to endorse cigarette smoking and SUDs when compared to their non-mood disordered peers. These findings indicate that youth with BPD should be carefully monitored for comorbid CD and the development of cigarette smoking and SUDs.

Further evidence that severe scores in the aggression/anxiety-depression/attention subscales of child behavior checklist (severe dysregulation profile) can screen for bipolar disorder symptomatology: a conditional probability analysis.

BACKGROUND: Previous work shows that children with high scores (2SD, combined score≥210) on the Attention Problems, Aggressive Behavior, and Anxious-Depressed (A-A-A) subscales of the Child Behavior Checklist (CBCL) are more likely than other children to meet criteria for bipolar (BP)-I disorder. However, the utility of this profile as a screening tool has remained unclear. METHODS: We compared 140 patients with pediatric BP-I disorder, 83 with attention deficit hyperactivity disorder (ADHD), and 114 control subjects. We defined the CBCL-Severe Dysregulation profile as an aggregate cutoff score of ≥210 on the A-A-A scales. Patients were assessed with structured diagnostic interviews and functional measures. RESULTS: Patients with BP-I disorder were significantly more likely than both control subjects (Odds Ratio [OR]: 173.2; 95% Confidence Interval [CI], 21.2 to 1413.8; P<0.001) and those with ADHD (OR: 14.6; 95% CI, 6.2 to 34.3; P<0.001) to have a positive CBCL-Severe Dysregulation profile. Receiver Operating Characteristics analyses showed that the area under the curve for this profile comparing children with BP-I disorder against control subjects and those with ADHD was 99% and 85%, respectively. The corresponding positive predictive values for this profile were 99% and 92% with false positive rates of <0.2% and 8% for the comparisons with control subjects and patients with ADHD, respectively. LIMITATIONS: Non-clinician raters administered structured diagnostic interviews, and the sample was referred and largely Caucasian. CONCLUSIONS: The CBCL-Severe Dysregulation profile can be useful as a screen for BP-I disorder in children in clinical practice.

Difficulties in emotional regulation and substance use disorders: a controlled family study of bipolar adolescents.

BACKGROUND: Self-regulatory mechanisms appear etiologically operant in the context of both substance use disorders (SUD) and bipolar disorder (BD), however, little is known about the role of deficits in emotional self-regulation (DESR) as it relates to SUD in context to mood dysregulation. To this end, we examined to what extent DESR was associated with SUD in a high-risk sample of adolescents with and without BD. METHODS: 203 families were assessed with a structured psychiatric interview. Using the Child Behavior Checklist (CBCL), a subject was considered to have DESR when he or she had an average elevation of 1 standard deviation (SD) above the norm on 3 clinical scale T scores (attention, aggression, and anxiety/depression; scores: 60 × 3 ≥ 180). RESULTS: Among probands and siblings with CBCL data (N=303), subjects with DESR were more likely to have any SUD, alcohol use disorder, drug use disorder, and cigarette smoking compared to subjects with scores <180 (all p values <0.001), even when correcting for BD. We found no significant differences in the risk of any SUD and cigarette smoking between those with 1SD and 2SD above the mean (all p values >0.05). Subjects with cigarette smoking and SUD had more DESR compared to those without these disorders. CONCLUSIONS: Adolescents with DESR are more likely to smoke cigarettes and have SUD. More work is needed to explore DESR in longitudinal samples.

Further evidence that pediatric-onset bipolar disorder comorbid with ADHD represents a distinct subtype: results from a large controlled family study.

We used familial risk analysis to clarify the diagnostic comorbidity between pediatric BP-I disorder and ADHD, testing the hypothesis that pediatric-BP-I disorder comorbid with ADHD represents a distinct subtype. Structured diagnostic interviews were used to obtain DSM-IV psychiatric diagnoses on first-degree relatives (n = 726) of referred children and adolescents satisfying diagnostic criteria for BP-I disorder (n = 239). For comparison, diagnostic information on the first-degree relatives (N = 511) of non-bipolar ADHD children (N = 162) and the first degree relatives (N = 411) of control children (N = 136) with neither ADHD nor BP-I disorder were examined. BP-I disorder and ADHD in probands bred true irrespective of the comorbidity with the other disorder. We also found that the comorbid condition of BP-I disorder plus ADHD also bred true in families, and the two disorders co-segregated among relatives. This large familial risk analysis provides compelling evidence that pediatric BP-I disorder comorbid with ADHD represents a distinct familial subtype.

Personal and familial correlates of bipolar (BP)-I disorder in children with a diagnosis of BP-I disorder with a positive child behavior checklist (CBCL)-severe dysregulation profile: a controlled study.

BACKGROUND: Although the DSM-IV provides explicit criteria for the diagnosis of BP-I disorder, this is a complex diagnosis that requires high levels of clinical expertise. Previous work shows children with a unique profile of the CBCL of high scores (2SD) on the attention problems (AP), aggressive behavior (AGG), and anxious-depressed (AD) (A-A-A) subscales are more likely than other children to meet criteria for BP-I disorder in both epidemiological and clinical samples. However, since not all BP-I disorder children have a positive profile questions remain as to its informativeness, particularly in the absence of an expert diagnostician. METHODS: Analyses were conducted comparing personal and familial correlates of BP-I disorder in 140 youth with a structured interview and an expert clinician based DSM-IV diagnosis of BP-I disorder with (N=80) and without (N=60) a positive CBCL- Severe Dysregulation profile, and 129 controls of similar age and sex without ADHD or a mood disorder. Subjects were comprehensively assessed with structured diagnostic interviews and wide range of functional measures. We defined the CBCL-severe dysregulation profile as an aggregate cut-off score of ≥ 210 on the A-A-A scales. RESULTS: BP-I probands with and without a positive CBCL-severe dysregulation profile significantly differed from Controls in patterns of psychiatric comorbidity, psychosocial and psychoeducational dysfunction, and cognitive deficits, as well as in their risk for BP-I disorder in first degree relatives. LIMITATIONS: Because the sample was referred and largely Caucasian, findings may not generalize to community samples and other ethnic groups. CONCLUSION: A positive CBCL-severe dysregulation profile identifies a severe subgroup of BP-I disorder youth.

Further evidence for robust familiality of pediatric bipolar I disorder: results from a very large controlled family study of pediatric bipolar I disorder and a meta-analysis.

OBJECTIVE: To determine the risk for bipolar I disorder in first-degree relatives of children with DSM-IV bipolar I disorder via meta-analysis and expanded controlled study. DATA SOURCES AND EXTRACTION: For the meta-analysis, PubMed was searched for scientific articles published in the world literature in English through 2011. The keywords searched were bipolar disorder, first-degree relatives, family study, and control. All online abstracts were reviewed, and relevant full manuscripts were collected and reviewed. Citations were also examined for other potentially relevant articles. The analysis included only controlled family studies that examined rates of bipolar I disorder in all first-degree relatives (parents and siblings) of pediatric bipolar I probands and that had age- and sex-matched controls. Family history studies were excluded, as were studies that were not in English, did not report bipolar I rates for all first-degree relatives, or reported only bipolar spectrum rates. Also excluded were family studies that included only adult probands. A meta-analysis was conducted of the 5 controlled family studies of pediatric bipolar I probands that met the search criteria using the random-effects model of DerSimonian and Laird. METHOD: For the family study, our previous sample of DSM-IV bipolar I probands was greatly expanded using structured diagnostic interviews. The new study included 239 children aged 6-17 years who satisfied full DSM-IV diagnostic criteria for bipolar I disorder (n = 726 first-degree relatives), 162 attention-deficit/hyperactivity disorder (ADHD) probands (without bipolar I disorder; n = 511 first-degree relatives), and 136 healthy control probands (without ADHD or bipolar I disorder; n = 411 first-degree relatives). The Kaplan-Meier cumulative failure function was used to calculate survival curves and cumulative lifetime risk in relatives. Cox proportional hazard models were used to calculate the risk of bipolar I disorder in relatives. RESULTS: The pooled odds ratio for bipolar I disorder in relatives was estimated to be 6.96 (95% confidence interval [CI], 4.8-10.1). First-degree relatives of bipolar I probands were also significantly more likely than first-degree relatives of both ADHD probands (hazard ratio [HR] = 3.02; 95% CI, 1.85-4.93; P < .001) and control probands (HR = 2.83; 95% CI, 1.65-4.84; P < .001) to have bipolar I disorder. CONCLUSIONS: Our results document an increased familial risk for bipolar I disorder in relatives of pediatric probands with DSM-IV bipolar I disorder.

Do executive function deficits predict later substance use disorders among adolescents and young adults?

OBJECTIVE: There is increasing interest regarding the risk and overlap of executive function deficits (EFDs) in stable cigarette smoking and substance use disorders (SUD). Therefore, we examined whether earlier EFD was a risk factor for subsequent cigarette smoking and SUD and further explored the relationship between EFD and SUD. METHOD: We assessed 435 subjects at the 5-year follow-up (232 subjects with attention-deficit/hyperactivity disorder [ADHD], mean age ± SD: 15.4 ± 3.43 years; and 203 controls: 16.3 ± 3.42 years) and again 4 to 5 years later as part of a prospective family study of youth with ADHD. Individuals were assessed by structured psychiatric interview for psychopathology and SUD. EFD was categorically defined in an individual who had abnormal results on at least two of six neuropsychological tests of executive functioning. RESULTS: At the final follow-up period, ADHD was found to be a significant predictor of stable cigarette smoking (p < .01) and SUD into late adolescence and young adult years (p < .01). However, EFDs were not associated with an increase in subsequent substance use outcomes. New-onset stable cigarette smoking, but not SUD, was associated with subsequent EFD (p < .01). CONCLUSIONS: Our results do not support the hypothesis that EFDs predicts later stable cigarette smoking or SUD in children with ADHD growing up. However, stable cigarette smoking is associated with subsequent EFD.

Psychosocial functioning, familiality, and psychiatric comorbidity in bipolar youth with and without psychotic features.

OBJECTIVE: Few studies have examined the correlates of psychosis in children and adolescents with bipolar disorder (BPD). We examined psychiatric comorbidity, familiality, and psychosocial functioning in multiple domains in BPD children and adolescents with and without psychotic features. METHOD: As part of 2 ongoing family-based studies of children and adolescents with DSM-IV-defined BPD, we compared youth and their families with psychotic symptoms (BPD+P) and without psychotic symptoms (BPD-P). All youth and family members were assessed using indirect and direct structured psychiatric interviews (Kiddie Schedule for Affective Disorders-Epidemiologic Version and DSM-IV Structured Clinical Interview) in a blinded manner. One study was conducted from January 2000 through December 2004, and the other study was conducted from February 1997 through September 2006. RESULTS: Of the 226 youth with BPD, 33% manifested psychotic symptoms, as defined by the presence of hallucinations or delusions. We found that BPD+P youth had a greater number of BPD episodes (P < .01), more psychiatric hospitalizations (P < .01), and significantly higher rates of psychiatric comorbidity compared to BPD-P youth (all P values < .05). Additionally, a higher percentage of BPD+P youth had a family history of psychosis (P = .01). There was a lower processing speed (P = .03) and lower arithmetic scaled score (P = .04) in BPD+P youth, but no other meaningful differences in cognitive variables were identified between the 2 BPD groups. Psychosis in BPD was also associated with decreased family cohesion (P = .04) and poorer overall global functioning (P < .01). CONCLUSIONS: In children and adolescents with BPD, those who manifest psychotic features have higher rates of comorbid psychopathology, family history of psychosis, and poorer overall functioning in multiple domains than BPD children without psychosis. Future studies should examine neuroimaging correlates, medication response, and longitudinal course of children and adolescents with BPD who manifest psychosis as part of their clinical picture.

Does ADHD predict substance-use disorders? A 10-year follow-up study of young adults with ADHD.

OBJECTIVE: High rates of substance-use disorders (SUD) have been found in samples of adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Predictors of SUD in children with ADHD who are at risk for the development of SUDs remain understudied. The main aims of this study were to identify clinically meaningful characteristics of children that predicted the future development of SUDs and to see whether the role of these characteristics varied by sex. METHOD: Subjects were children and adolescents with (n = 268; mean age ± standard deviation = 10.9 ± 3.2 years) and without (n = 229; mean age 11.9 ± 3.3 years) DSM-III-R ADHD followed prospectively and blindly over a 10-year follow-up period onto young adult years. Subjects were assessed with structured diagnostic interviews for psychopathology and SUDs. RESULTS: Over the 10-year follow-up period, ADHD was found to be a significant predictor of any SUD (hazards ratio 1.47; 95% confidence interval 1.07-2.02; p = .01) and cigarette smoking (2.38; 1.61-3.53; p < .01). Within ADHD, comorbid conduct disorder (2.74; 1.66-4.52; p < .01) and oppositional defiant disorder (2.21; 1.40-3.51; p < .01) at baseline were also found to be significant predictors of SUDs. Similar results were found for cigarette-, alcohol-, and drug-use disorders. There were few meaningful sex interaction effects. No clinically significant associations were found for any social or family environment factors or for cognitive functioning factors (p > .05 for all comparisons). CONCLUSIONS: These results indicate that ADHD is a significant risk factor for the development of SUDs and cigarette smoking in both sexes.