MaryKate Martelon

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.

Presenting ADHD Symptoms, Subtypes, and Comorbid Disorders in Clinically Referred Adults with ADHD

OBJECTIVE Despite the increasing presentation of attention-deficit/hyperactivity disorder (ADHD) in adults, many practitioners remain reluctant to assess individuals for ADHD, in part related to the relative lack of data on the presenting symptoms of ADHD in adulthood. Comorbidity among adults with ADHD is also of great interest due to the high rates of psychiatric comorbidity, which can lead to a more persistent ADHD among adults. METHOD We assessed 107 adults with ADHD of both sexes (51% female; mean +/- SD of 37 +/- 10.4 years) using structured diagnostic interviews. Using DSM-IV symptoms, we determined DSM-IV subtypes. The study was conducted from 1998 to 2003. RESULTS Inattentive symptoms were most frequently endorsed (> 90%) in adults with ADHD. Using current symptoms, 62% of adults had the combined subtype, 31% the inattentive only subtype, and 7% the hyperactive/impulsive only subtype. Adults with the combined subtype had relatively more psychiatric comorbidity compared to those with the predominately inattentive subtype. Women were similar to men in the presentation of ADHD. CONCLUSION Adults with ADHD have prominent inattentive symptoms of ADHD, necessitating careful questioning of these symptoms when evaluating these individuals.

An Open Study of Adjunct OROS-Methylphenidate in Children and Adolescents Who Are Atomoxetine Partial Responders: I. Effectiveness

OBJECTIVE This study evaluated the effectiveness of adding OROS methylphenidate (MPH) to children who are partial responders to atomoxetine (ATMX) in the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS This is a two-phase, 7-week, open study in children aged 6-17 years. Phase I initiated ATMX for a minimum of 4 weeks. Phase II entered partial responders to ATMX and added up to 54 mg of OROS MPH to their regimen. Subjects were assessed on multiple outcomes, including ADHD, executive functioning, and adverse effects. All analyses were intent to treat, with last observation carried forward. RESULTS Fifty subjects who were partial responders to ATMX were treated with the combination therapy, with 41 subjects completing the entire protocol. There was a 40% reduction in their ADHD Rating Scale from the start of phase II through the end of study (from 21.14 +/- 9.9 to 12.8 +/- 9.7, t = 6.5, p < 0.0001). In addition, there was a clinically significant reduction in the Clinical Global Index of ADHD severity from moderate to mild ADHD (start of phase II, 3.7; end of phase II, 2.7, 27%, t = 6.5, p < 0.0001), as well as improvements in executive functioning. CONCLUSION These results suggest that OROS MPH added to the regimen of partial responders to ATMX improves ADHD and executive functioning, necessitating further controlled trials.

An open study of adjunct OROS-methylphenidate in children who are atomoxetine partial responders: II. Tolerability and pharmacokinetics.

OBJECTIVE The aim of this study was to evaluate the tolerability of adding OROS methylphenidate (MPH) to children who are partial responders to atomoxetine (ATMX) in the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS This was a two-phase, 7-week, open study in children aged 6-17 years. Phase 1 initiated ATMX for a minimum of 4 weeks. Phase 2 entered partial responders to ATMX and added OROS MPH to their regimen. Safety was assessed using blood pressure and heart rate measurements, electrocardiogram readings, AEs, laboratories, and ATMX levels. RESULTS Fifty subjects who were partial responders to ATMX received the combination therapy, with 41 subjects completing the entire protocol. As reported elsewhere (Wilens et al., 2009 ), OROS MPH added to partial responders of ATMX was accompanied by a 40% reduction in the ADHD rating scale score and improvements in executive functioning. However, the combination of ATMX plus OROS MPH was associated with greater rates of insomnia, irritability, and loss of appetite compared to ATMX alone. A small significant increase in diastolic blood pressure was observed during adjunctive OROS MPH, with no clinically meaningful changes in electrocardiogram (ECG) parameters during the study. ATMX levels and liver function tests did not significantly change during the combination treatment. CONCLUSION Adjunct OROS MPH in ATMX partial responders yielded an additive adverse effect burden in this short-term study. Further controlled research with larger samples of children is warranted.

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.

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 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.

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 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.

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.