Anxiety Disorders: Biederman J

Biederman J. · Department of Pediatric Psychopharmacology Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. · Biol Psychiatry. · Pubmed #15949990 No free full text.

Abstract: Attention-deficit/hyperactivity disorder (ADHD) is a multifactorial and clinically heterogeneous disorder that is associated with tremendous financial burden, stress to families, and adverse academic and vocational outcomes. Attention-deficit/hyperactivity disorder is highly prevalent in children worldwide, and the prevalence of this disorder in adults is increasingly recognized. Studies of adults with a diagnosis of childhood-onset ADHD indicate that clinical correlates--demographic, psychosocial, psychiatric, and cognitive features--mirror findings among children with ADHD. Predictors of persistence of ADHD include family history of the disorder, psychiatric comorbidity, and psychosocial adversity. Family studies of ADHD have consistently supported its strong familial nature. Psychiatric disorders comorbid with childhood ADHD include oppositional defiant and conduct disorders, whereas mood and anxiety disorders are comorbid with ADHD in both children and adults. Pregnancy and delivery complications, maternal smoking during pregnancy, and adverse family environment variables are considered important risk factors for ADHD. The etiology of ADHD has not been clearly identified, although evidence supports neurobiologic and genetic origins. Structural and functional imaging studies suggest that dysfunction in the fronto-subcortical pathways, as well as imbalances in the dopaminergic and noradrenergic systems, contribute to the pathophysiology of ADHD. Medication with dopaminergic and noradrenergic activity seems to reduce ADHD symptoms by blocking dopamine and norepinephrine reuptake. Such alterations in dopaminergic and noradrenergic function are apparently necessary for the clinical efficacy of pharmacologic treatments of ADHD.

Biederman J. · Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Department of Psychiatry, Harvard Medical School, Boston, USA. · J Clin Psychiatry. · Pubmed #15046528 No free full text.

Abstract: Persistence of attention-deficit/hyperactivity disorder (ADHD) into adulthood and male-to-female ratios of this disorder in childhood and adulthood have been controversial issues in the ADHD diagnosis in adults. Research has resolved these controversies and in turn provided support for the validity of the diagnosis in adults. Support for the diagnosis can also be found in data that show the lifetime prevalence rate for comorbid conditions such as antisocial disorders, mood and anxiety disorders, and substance abuse disorders to be consistent across pediatric and adult populations with ADHD. These coexisting conditions add not only to the impairment associated with ADHD in adults but also to the disorder's economic burden, the extent of which is currently unknown. However, adults with the disorder, like children, probably have higher health care use and costs than people without the disorder. Little, too, is known about the social cost of ADHD, but if left untreated, the impact may be substantial. Research to determine the occupational costs associated with ADHD is ongoing, but until that and other cost-of-illness data are available, studies on the economic costs of the comorbid conditions depression, anxiety, and substance abuse and dependence may be used to make suppositions about the economic impact of ADHD in adults. More studies are needed on the outcomes of adults with this disorder, especially cost-of-illness studies.

Hirshfeld-Becker DR, Biederman J, Calltharp S, Rosenbaum ED, Faraone SV, Rosenbaum JF. · Pediatric Psychopharmacology Program, Massachusetts General Hospital, Cambridge, Massacusetts 02138, USA. · Biol Psychiatry. · Pubmed #12788244 No free full text.

Abstract: Attention has been devoted over the past two decades to the identification of temperamental risk factors for child psychopathology. These qualities, evident in toddlerhood or earlier, have the advantage of being measurable in standardized laboratory observations well before children reach the age of onset or diagnosis of psychiatric disorders. Our group's programmatic research over the past 15 years, and that of others, has provided evidence linking "behavioral inhibition to the unfamiliar" in toddlerhood or early childhood with later social anxiety disorder. In addition, recent results by our group have suggested that "behavioral disinhibition" in early childhood, measured by the same laboratory methods, may be linked with later disruptive behavior and comorbid mood disorders. In this article, we discuss our approach to the study of temperamental precursors to disorders in high-risk children, summarize the literature linking behavioral inhibition and disinhibition to later psychopathology, and suggest directions to take in applying this methodology to the search for temperamental precursors to pediatric bipolar disorder.

Biederman J, Faraone SV. · Pediatric Psychopharmacology Unit of the Child Psychiatry Service, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA. · J Atten Disord. · Pubmed #12685515 No free full text.

Abstract: Attention-Deficit/Hyperactivity Disorder (ADHD) is an early onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. In contrast to the widespread acceptance of ADHD as a childhood diagnosis, Its prevalence In adults and its implications for clinical practice remain a source of controversy. Throughout the lifecycle, a key clinical feature observed in ADHD patients is comorbidity with Conduct Depressive, Bipolar, and Anxiety disorders. Family studies consistently support the assertion that ADHD runs in families. Heritability data from twin studies of ADHD attribute about 80 percent of the etiology of ADHD to genetic factors. Adoption studies of ADHD also implicate genes in its etiology. Molecular genetic data are bolstered by considerations suggesting that DRD4 and DAT genes may be relevant for ADHD. Independently of genes, prenatal exposure to nicotine and psychosocial adversity have also been identified as risk factors for ADHD. Structural and functional imaging studies consistently implicate catecholamine-rich fronto-subcortical systems in the pathophysiology of ADHD. The effectiveness of stimulants, along with animal models of hyperactivity, point to catecholamine disruption as at least one source of ADHD brain dysfunction. Although not entirely sufficient, changes in dopaminergic and noradrenergic function appear necessary for the clinical efficacy of pharmacological treatments for ADHD, providing support for the hypothesis that alteration of monoaminergic transmission in critical brain regions may be the basis for therapeutic action in ADHD.

Wilens TE, Biederman J, Spencer TJ. · Clinical Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital and Harvard Medical School, 15 Parkman Street, Boston, Massachusetts 02114, USA. · Annu Rev Med. · Pubmed #11818466 No free full text.

Abstract: Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder presenting for treatment in youth. ADHD is often chronic with prominent symptoms and impairment spanning into adulthood. ADHD is often associated with co-occurring anxiety, mood, and disruptive disorders, as well as substance abuse. The diagnosis of ADHD by careful review of symptoms and impairment is both reliable and valid. Recent genetic, imaging, neurochemistry, and neuropsychological data support the biological underpinning of the disorder. All aspects of an individual's life must be considered in the diagnosis and treatment of ADHD. Pharmacotherapy, including stimulants, antidepressants, and antihypertensives, plays a fundamental role in the management of ADHD across the lifespan.

Biederman J, Mick E, Faraone SV, Spencer T, Wilens TE, Wozniak J. · Pediatric Psychopharmacology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114-3139, USA. · Biol Psychiatry. · Pubmed #11018219 No free full text.

Abstract: Despite ongoing controversy, the view that pediatric mania is rare or nonexistent has been increasingly challenged not only by case reports, but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: 1) its pattern of comorbidity may be unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder, aggression, and conduct disorder; 2) its overlap with substance use disorders; 3) its association with trauma and adversity; and 4) its response to treatment is atypical by adult standards.

Faraone SV, Biederman J, Spencer T, Wilens T, Seidman LJ, Mick E, Doyle AE. · Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114-3139, USA. · Biol Psychiatry. · Pubmed #10913503 No free full text.

Abstract: To assess the validity of adult attention-deficit/hyperactivity disorder (ADHD), we reviewed clinical, family, psychopharmacologic, neurobiological, and outcome studies. We found multiple reports describing adults with clinical features highly reminiscent of the childhood ADHD. These adults, who are impulsive, inattentive, and restless, have the clinical "look and feel" of ADHD children. As with their childhood counterparts, many adults with ADHD suffer from antisocial, depressive, and anxiety disorders. They also show clinically significant impairments--histories of school failure, occupational problems, and traffic accidents. Studies of biological features show correspondences between child and adult cases of ADHD. Both show familial aggregation and a characteristic profile of neuropsychologic deficits; an emerging neuroimaging literature suggests that abnormalities in the same brain regions underlie both the child and adult forms of the disorder. Although these converging lines of evidence support the validity of ADHD in adults, follow-up studies of ADHD children have yielded ambiguous results. This ambiguity is in part due to differences in how researchers define the persistence of ADHD, a problem that suggests future research focus on how best to diagnose ADHD in adulthood.

Spencer T, Biederman J, Wilens T. · Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, USA. · Pediatr Clin North Am. · Pubmed #10570696 No free full text.

Abstract: Studies of children with ADHD consistently document high rates of comorbid psychiatric conditions, including conduct disorders, depression and other mood disorders, anxiety disorders, and tic disorders. In diagnosing children with ADHD, one must be careful not to dismiss other symptomatology as secondary. Poor social skills, problems with parents, low academic functioning, and other correlates of ADHD can be construed as causal factors. Although these should not be ignored, neither should the possibility that a child suffers from another psychiatric disorder that might respond to appropriate pharmacotherapy. A variety of behavior rating scales are available to the practitioner as the first steps in this process.

Mrakotsky C, Masek B, Biederman J, Raches D, Hsin O, Forbes P, de Moor C, DeMaso DR, Gonzalez-Heydrich J. · Department of Psychiatry, Children's Hospital Boston, 300 Longwood Avenue, Fegan 8, Boston, MA 02115, United States. · J Anxiety Disord. · Pubmed #17419001 No free full text.

Abstract: Mirtazapine is indicated for major depression and used for anxiety in adults; however, little is known about its application in pediatric populations. This is an 8-week open-label pilot study of mirtazapine in children with social phobia age 8-17 years. Primary outcomes were symptom improvement based on clinician rating and self-report, as well as tolerability based on rates of discontinuation due to adverse effects. Fifty-six percent (10/18) responded to treatment, 17% (3/18) achieved full remission. Social phobia symptoms improved significantly during the first 2 weeks of treatment, as did comorbid symptoms of depression and anxiety. Eleven patients (61%) did not complete all 8 weeks of treatment; four patients (22%) discontinued due to adverse effects including fatigue and irritability. The others discontinued due to study burden (28%), insufficient response (6%), or to pursue herbal treatment (6%). Significant weight gain was observed. Larger controlled trials are needed to further evaluate efficacy and safety.

Henin A, Biederman J, Mick E, Sachs GS, Hirshfeld-Becker DR, Siegel RS, McMurrich S, Grandin L, Nierenberg AA. · Pediatric Psychopharmacology Unit and Harvard Bipolar Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02138, USA. · Biol Psychiatry. · Pubmed #16112654 No free full text.

Abstract: BACKGROUND: To examine the risk for psychopathology in offspring at risk for bipolar disorder and the course of psychiatric disorders in these youth. METHODS: Using structured diagnostic interviews (Structured Clinical Interview for DSM-IV [SCID] and Kiddie Schedule for Affective Disorders and Schizophrenia [K-SADS]), psychiatric diagnoses of 117 nonreferred offspring of parents with diagnosed bipolar disorder were compared with those of 171 age- and gender-matched offspring of parents without bipolar disorder or major depression. RESULTS: Compared with offspring of parents without mood disorders, high-risk youth had elevated rates of major depression and bipolar disorder, anxiety, and disruptive behavior disorders. High-risk offspring also had significantly more impaired Global Assessment of Functioning (GAF) scores, higher rates of psychiatric treatment, and higher rates of placement in special education classes. Disruptive behavior disorders, separation anxiety disorder, generalized anxiety disorder (GAD), social phobia, and depression tended to have their onset in early or middle childhood, whereas bipolar disorder, obsessive-compulsive disorder (OCD), panic disorder, and substance use disorder had onset most frequently in adolescence. CONCLUSIONS: These findings support the hypothesis that offspring of parents with bipolar disorder are at significantly increased risk for developing a wide range of severe psychiatric disorders and accompanying dysfunction. Early disruptive behavior and anxiety disorders, as well as early-onset depression, may be useful markers of risk for subsequent bipolar disorder in high-risk samples.

Spencer T, Biederman J, Wilens T. · Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston, MA 02114, USA. · Psychiatr Clin North Am. · Pubmed #15064002 No free full text.

Abstract: Though only recently recognized as a valid disorder in adults, the clinical picture of adult ADHD is highly reminiscent of childhood ADHD,with continued associated occupational failure and academic deficits. Similarly, many adults with ADHD suffer from antisocial, depressive, and anxiety disorders. Recent work clearly documents that when therapeutic doses of MPH and amphetamine treatment are used in the treatment of adults with ADHD, they can lead to a robust clinical response that is highly consistent with that observed in pediatric studies using equipotent daily doses. As in childhood ADHD, medication remains a key component of treatment for adults with ADHD. More studies are needed to evaluate the efficacy and safety of stimulants over the long-term and their impact on quality of life.

Wilens TE, Biederman J, Forkner P, Ditterline J, Morris M, Moore H, Galdo M, Spencer TJ, Wozniak J. · Johnson and Johnson Center for the Study of Pediatric Psychopathology, Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. · J Child Adolesc Psychopharmacol. · Pubmed #14977462 No free full text.

Abstract: OBJECTIVE: Despite its common onset in preschool years, few studies have examined the characteristics of bipolar disorder (BPD) in preschoolers. This study reports on the clinical characteristics, psychiatric comorbidity, and functioning of preschoolers identified with BPD who were referred to a pediatric psychiatric clinic. METHODS: Structured psychiatric interviews assessing lifetime psychopathology by Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) criteria were completed with parents about their children and confirmed by clinical interview of the child. Family, social, and overall functioning were also assessed at intake. Findings from preschoolers ages 4 to 6 years were compared with a group of children ages 7 to 9 years (school age). RESULTS: We identified 44 preschoolers and 29 consecutively ascertained school-age youth with BPD. Preschoolers had similar rates of comorbid psychopathology compared to school-age youth with BPD. Preschoolers and school-age children with BPD typically manifest symptoms of mania and major depression simultaneously (mixed states). Both preschoolers and school-age children had substantial impairment in school, social, and overall functioning. CONCLUSIONS: These results suggest that clinically referred preschoolers with BPD share with school-age children with BPD high rates of comorbid psychopathology and impaired functioning. Follow-up of these clinically referred preschoolers with BPD evaluating the stability of their diagnoses, treatment response, and their long-term outcome is necessary.

Mick E, Biederman J, Faraone SV, Murray K, Wozniak J. · Pediatric Psychopharmacology Unit of the Child Psychiatry Service, Massachusetts General Hospital, Boston, Massachusetts, USA. · J Child Adolesc Psychopharmacol. · Pubmed #14977458 No free full text.

Abstract: OBJECTIVE: To test the hypothesis that the age at onset of bipolar disorder would identify a developmental subtype of bipolar disorder in adults characterized by increased levels of irritability, chronic course, rapid cycling, and comorbidity with attention deficit hyperactivity disorder. METHODS: Forty-four adult subjects diagnosed with bipolar disorder were selected from large family studies of youth with and without attention deficit hyperactivity disorder. These subjects were stratified by the age at onset in childhood (younger than 13 years; n = 8, 18%), adolescence (13-18 years; n = 12, 27%, or adulthood (older than 19 years; n = 24, 55%). All subjects were administered structure diagnostic interviews and a brief cognitive battery. RESULTS: In contrast with adult-onset bipolar disorder, child-onset bipolar disorder was associated with a longer duration of illness, more irritability than euphoria, a mixed presentation, a more chronic or rapid-cycling course, and increased comorbidity with childhood disruptive behavior disorders and anxiety disorders. CONCLUSION: Stratification by age at onset of bipolar disorder identified subgroups of adult subjects with differing clinical correlates. This pattern of correlates is consistent with findings documented in children with pediatric bipolar disorder and supports the hypothesis that child-onset bipolar disorder may represent a developmental subtype of the disorder.

Geller DA, Biederman J, Stewart SE, Mullin B, Farrell C, Wagner KD, Emslie G, Carpenter D. · Obsessive Compulsive Disorder Program, Pediatric Psychopharmacology Research Program, Massachusetts General Hospital, & Harvard Medical School, Boston, Massachusetts 02114, USA. · J Child Adolesc Psychopharmacol. · Pubmed #12880497 No free full text.

Abstract: OBJECTIVE: To examine the influence of psychiatric comorbidity on response and relapse rates in children and adolescents treated with paroxetine for obsessive-compulsive disorder (OCD). METHODS: Patients responding following 16 weeks of treatment (phase I) were randomized to continued paroxetine or to placebo for 16 additional weeks (phase II). OCD response (phase I) and relapse (phase II) criteria were based on the Clinical Global Impression-Improvement Scale and the Children's Yale-Brown Obsessive Compulsive Scale. The presence of OCD and other psychiatric disorders was ascertained using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version interview. RESULTS: At entry, 193 of 335 (57.6%) patients had at least one psychiatric disorder in addition to OCD, and 102 of 335 (30.4%) had multiple other disorders. Although the response rate to paroxetine in the overall population was high (71%), the response rates in patients with comorbid attention deficit hyperactivity disorder, tic disorder, or oppositional defiant disorder (56%, 53%, and 39%, respectively) were significantly less than in patients with OCD only (75%) (intent-to-treat population, last observation carried forward analysis, p < 0.05). Psychiatric comorbidity was associated with a greater rate of relapse in the total patient population (46% for one or more comorbid disorders [p = 0.04] and 56% for two or more comorbid disorders [p < 0.05] vs. 32% for no comorbidity). CONCLUSIONS: The results of these post hoc analyses show that comorbid illness adversely impacted response to pharmacotherapy with paroxetine in pediatric OCD and significantly increased risk of relapse following withdrawal from treatment. Continued paroxetine treatment reduced the relapse rates in all groups compared with placebo, including those with comorbid illness. Because pediatric OCD is frequently comorbid with other psychiatric disorders, results of randomized, controlled pediatric OCD trials that use multiple exclusion criteria may not generalize to more naturalistic OCD samples.

Cook EH, Wagner KD, March JS, Biederman J, Landau P, Wolkow R, Messig M. · Department of Psychiatry and Pediatrics, University of Chicago, IL 60637, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #11589530 No free full text.

Abstract: OBJECTIVE: To evaluate the safety and effectiveness of sertraline in the long-term treatment of pediatric obsessive-compulsive disorder (OCD). METHOD: Children (6-12 years; n= 72) and adolescents (13-18 years; n = 65) with DSM-III-R-defined OCD who had completed a 12-week, double-blind, placebo-controlled sertraline study were given open-label sertraline 50 to 200 mg/day in this 52-week extension study. Concomitant psychotherapy was allowed during the extension study Outcome was evaluated by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), National Institute of Mental Health Global Obsessive-Compulsive Scale, and Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores. RESULTS: Significant improvement (p < .0001) was demonstrated on all four outcome parameters on an intent-to-treat analysis for the overall study population (n = 132), as well as the child and the adolescent samples. At endpoint, 72% of children and 61% of adolescents met response criteria (>25% decrease in CY-BOCS and a CGI-I score of 1 or 2). Significant (p < .05) improvements were also demonstrated from the extension study baseline to endpoint on all outcome parameters in those patients who received sertraline during the 12-week, double-blind acute study. Long-term sertraline treatment was well tolerated, and there were no discontinuations due to changes in vital signs, laboratory values, or electrocardiograms. CONCLUSION: Sertraline (50-200 mg/day) was effective and generally well tolerated in the treatment of childhood and adolescent OCD for up to 52 weeks. Improvement was seen with continued treatment.

Wilens TE, Spencer TJ, Biederman J, Girard K, Doyle R, Prince J, Polisner D, Solhkhah R, Comeau S, Monuteaux MC, Parekh A. · Pediatric Psychopharmacology Clinic, Massachusetts General Hospital, Boston, MA 02114, USA. · Am J Psychiatry. · Pubmed #11156812 links to  free full text

Abstract: OBJECTIVE: Despite the increasing recognition of attention deficit hyperactivity disorder (ADHD) in adults, there is a paucity of controlled pharmacological trials demonstrating the effectiveness of compounds used in treatment, particularly nonstimulants. The authors report results from a controlled investigation to determine the anti-ADHD efficacy of bupropion in adult patients with DSM-IV ADHD. METHOD: This was a double-blind, placebo-controlled, randomized, parallel, 6-week trial comparing patients receiving sustained-release bupropion (up to 200 mg b.i.d.) (N=21) to patients receiving placebo (N=19). The authors used standardized structured psychiatric instruments for diagnosis of ADHD. To measure improvement, they used separate assessments of ADHD, depression, and anxiety symptoms at baseline and each weekly visit. RESULTS: Of the 40 subjects (55% male) enrolled in the study, 38 completed the study. Bupropion treatment was associated with a significant change in ADHD symptoms at the week-6 endpoint (42% reduction), which exceeded the effects of placebo (24% reduction). In analyses using a cutoff of 30% or better reduction to denote response, 76% of the subjects receiving bupropion improved, compared to 37% of the subjects receiving placebo. Similarly, in analyses using Clinical Global Impression scale scores, 52% of the subjects receiving bupropion reported being "much improved" to "very improved," compared to 11% of the subjects receiving placebo. CONCLUSIONS: These results indicate a clinically and statistically significant effect of bupropion in improving ADHD in adults. The results suggest a therapeutic role for bupropion in the armamentarium of agents for ADHD in adults, while further validating the continuity of pharmacological responsivity of ADHD across the lifespan.

Wilens TE, Biederman J, March JS, Wolkow R, Fine CS, Millstein RB, Faraone SV, Geller D, Spencer TJ. · Department of Psychiatry, Massachusetts General Hospital, Boston 02114, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #10230189 No free full text.

Abstract: OBJECTIVE: In a 12 week, placebo-controlled, parallel-design, multicenter study of sertraline for obsessive-compulsive disorder in 107 children and 80 adolescents, the authors prospectively assessed cardiovascular effects to doses of sertraline of < or = 200 mg/day. METHOD: Vital signs (blood pressure and heart rate) and electrocardiograph parameters (ECGs) were systematically evaluated at baseline and again throughout treatment. RESULTS: There were no clinically significant cardiovascular adverse events in any of the subjects enrolled in the study. Moreover, compared with baseline and placebo, sertraline treatment at an average dose of 167 mg did not result in any clinically meaningful changes in any ECG indices (PR, QRS, and QTc intervals), cardiac rhythm, blood pressure, or heart rate. CONCLUSIONS: These prospectively derived results support the cardiovascular safety of sertraline at doses up to 200 mg in children and adolescents.

Biederman J, Monuteaux MC, Spencer T, Wilens TE, Faraone SV. · Psychiatry Department,Massachusetts General Hospital, Clinical and Research Programs in PediatricPsychopharmacology and Adult ADHD, Boston, Massachusetts 02114, USA. · Pediatrics. · Pubmed #19564285 No free full text.

Abstract: OBJECTIVE: Little is known about the effect of stimulant treatment in youth with attention-deficit/hyperactivity disorder (ADHD) on the subsequent development of comorbid psychiatric disorders. We tested the association between stimulant treatment and the subsequent development of psychiatric comorbidity in a longitudinal sample of patients with ADHD. METHODS: We conducted a case-control, 10-year prospective follow-up study into young-adult years of youth with ADHD. At baseline, we assessed consecutively referred white male children with (n = 140) and without (n = 120) ADHD, aged 6 to 18 years. At the 10-year follow-up, 112 (80%) and 105 (88%) of the children in the ADHD and control groups, respectively, were reassessed (mean age: 22 years). We examined the association between stimulant treatment in childhood and adolescence and subsequent comorbid disorders and grade retention by using proportional hazards survival models. RESULTS: Of the 112 participants with ADHD, 82 (73%) were previously treated with stimulants. Participants with ADHD who were treated with stimulants were significantly less likely to subsequently develop depressive and anxiety disorders and disruptive behavior and less likely to repeat a grade compared with participants with ADHD who were not treated. CONCLUSIONS: We found evidence that stimulant treatment decreases the risk for subsequent comorbid psychiatric disorders and academic failure in youth with ADHD.

Geller DA, Wieland N, Carey K, Vivas F, Petty CR, Johnson J, Reichert E, Pauls D, Biederman J. · Clinical and Research Program in Pediatric Psychopharmacology, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02318, USA. · J Child Adolesc Psychopharmacol. · Pubmed #18759647 No free full text.

Abstract: OBJECTIVE: To examine whether adverse perinatal experiences of children are associated with obsessive compulsive disorder (OCD) in youth. METHODS: Subjects were 130 children and adolescents with OCD recruited from a family genetic study of pediatric OCD and 49 matched controls from a contemporaneous family case-control study of attention-deficit/hyperactivity disorder (ADHD). Subjects were comprehensively assessed in multiple domains of function. A systematic history of pregnancy, delivery, and infancy complications was obtained. RESULTS: Compared to normal controls, children with OCD had mothers with significantly higher rates of illness during pregnancy requiring medical care (chi(2) +/- 8.61, p +/- 0.003) and more birth difficulties (induced labor, forceps delivery, nuchal cord, or prolonged labor) (chi(2) +/- 7.51, p +/- 0.006). Among the OCD-affected children, we found several significant associations between adverse perinatal experiences and earlier age at onset, increased OCD severity, and increased risk for comorbid ADHD, chronic tic disorder, anxiety disorder, and major depressive disorder. CONCLUSION: Although exploratory, our analyses found that children with OCD had higher rates of several adverse perinatal experiences compared with controls. Among OCD-affected children, comorbid psychopathology was predicted by specific perinatal risk factors. Prospective studies of perinatal adverse events that minimize potential recall bias and type I errors are needed.

Antshel KM, Faraone SV, Maglione K, Doyle A, Fried R, Seidman L, Biederman J. · Department of Psychiatry and Behavioral Sciences, State University of New York-Upstate Medical University, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #18520956 No free full text.

Abstract: OBJECTIVE: The diagnosis of attention-deficit/hyperactivity disorder (ADHD) in high-IQ youths remains controversial. METHOD: To further explore the diagnostic validity of ADHD in this population, we studied two cohorts of high-IQ youths, both with and without ADHD, across a 4.5-year period. RESULTS: Compared to those without ADHD, high-IQ youths with ADHD had significantly higher rates of mood, anxiety, and disruptive behavior disorders at follow-up. In addition, ADHD status was a significant predictor for higher impairments across most social, academic, and family functional domains. Associations between baseline and follow-up IQ scores did not differ between groups. Syndromal persistence rates of ADHD were similar between high-IQ and average-IQ youths with ADHD. CONCLUSIONS: These results provide further support for the predictive validity of ADHD in high-IQ youths.

Petty CR, Monuteaux MC, Mick E, Hughes S, Small J, Faraone SV, Biederman J. · Massachusetts General Hospital, Boston, MA 02114, USA. · J Psychiatr Res. · Pubmed #18455189 No free full text.

Abstract: BACKGROUND: Family risk analysis can provide an improved understanding of the association between attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), attending to the comorbidity with conduct disorder (CD). METHODS: We compared rates of psychiatric disorders in relatives of 78 control probands without ODD and CD (Control, N=265), relatives of 10 control probands with ODD and without CD (ODD, N=37), relatives of 19 ADHD probands without ODD and CD (ADHD, N=71), relatives of 38 ADHD probands with ODD and without CD (ADHD+ODD, N=130), and relatives of 50 ADHD probands with ODD and CD (ADHD+ODD+CD, N=170). RESULTS: Rates of ADHD were significantly higher in all three ADHD groups compared to the Control group, while rates of ODD were significantly higher in all three ODD groups compared to the Control group. Evidence for co-segregation was found in the ADHD+ODD group. Rates of mood disorders, anxiety disorders, and addictions in the relatives were significantly elevated only in the ADHD+ODD+CD group. CONCLUSIONS: ADHD and ODD are familial disorders, and ADHD plus ODD outside the context of CD may mark a familial subtype of ADHD. ODD and CD confer different familial risks, providing further support for the hypothesis that ODD and CD are separate disorders.

Hirshfeld-Becker DR, Masek B, Henin A, Blakely LR, Rettew DC, Dufton L, Segool N, Biederman J. · Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA. · Harv Rev Psychiatry. · Pubmed #18415883 No free full text.

Abstract: Despite evidence that preschool and early elementary school-age children can present with anxiety disorders that may put them at risk for later psychopathology and dysfunction, the cognitive-behavioral protocols available for treating anxiety in children have been tested almost exclusively in older children. However, there could be benefits to treating children earlier, before anxiety disorders begin to impair their social and academic development. This report discusses the adaptations necessary in providing cognitive-behavioral therapy to young anxious children and describes a manualized, cognitive-behavioral intervention, with child and parent components, that was piloted openly in nine families with children aged 4 to 7 years - each of whom had multiple risk factors for developing anxiety disorders, and most of whom had already presented with anxiety disorders. Eight of the nine children were judged "much" or "very much improved" at postintervention on number of anxiety diagnoses, number of DSM-IV anxiety symptoms, and ability to cope with feared situations. Cases are presented to illustrate the way that cognitive-behavioral therapy can be conducted with youngsters in this age range. Whereas randomized, controlled trials are needed to confirm the efficacy of this manualized treatment, our experience suggests that cognitive-behavioral protocols for anxiety can be adapted and successfully implemented with young children.

Hirshfeld-Becker DR, Micco J, Henin A, Bloomfield A, Biederman J, Rosenbaum J. · Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA. · Depress Anxiety. · Pubmed #18412062 No free full text.

Abstract: Over the past 25 years, our understanding of the risks conferred by "behavioral inhibition to the unfamiliar" (BI) has grown tremendously, yet many questions remain. BI represents the persistent tendency to show extreme reticence, fearfulness, or avoidance in novel situations or with unfamiliar people. Prospective studies of high-risk offspring, selected community children, and unselected epidemiologic samples converge to suggest that BI confers specific risk for social anxiety disorder in early and middle childhood and adolescence. Later outcomes are less clear, with some studies suggesting associations with depression or panic disorder. Studies that find broad associations between BI and anxiety proneness in general may be limited by the absence of information about parental psychopathology (an important potential confound associated with both BI and anxiety disorders in offspring). A critical area for further inquiry is the degree to which BI confers risk for social anxiety disorder in the absence of family history of anxiety disorders. Additionally, although progress has been made in identifying risk factors, protective factors, and treatments that may influence the course of BI and associated anxiety, more work is needed. Also, several exciting inroads have been made into the genetic and neurobiologic underpinnings of BI, and future studies promise greater elucidation of these areas. For now, the clinical take-home message is that preschool-age children presenting with extreme and persistent BI are at elevated risk for social anxiety disorder and possibly for other future disorders; preliminary evidence suggests that these children may be helped by early cognitive-behavioral intervention.

Hirshfeld-Becker DR, Petty C, Micco JA, Henin A, Park J, Beilin A, Rosenbaum JF, Biederman J. · Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, United States. · J Affect Disord. · Pubmed #18378320 No free full text.

Abstract: OBJECTIVE: Although the offspring of parents with major depressive disorder (MDD) are at increased risk to develop disruptive behavior disorders (DBD) in addition to MDD, it remains unclear whether this heightened risk is due to MDD or to comorbid DBD in the parents. METHOD: In a secondary analysis of longitudinal data from offspring at risk for MDD and panic disorder and comparison children, we stratified 169 children of parents who had been treated for MDD based upon presence (n=50) or absence (n=119) of parental history of DBD (ADHD, oppositional disorder, and conduct disorder) and contrasted them with children of parents with DBD but without MDD (n=19) and children whose parents had neither MDD nor DBD (n=106). The children had been assessed in middle childhood using structured diagnostic interviews. RESULTS: Offspring of parents with MDD + DBD had significantly higher rates of MDD, DBD in general, and ADHD in particular, compared with offspring of parents with MDD alone. Offspring of parents with MDD + DBD also had higher rates of mania than controls. Both parental MDD and DBD conferred independent risk for MDD and DBD in the offspring. However, only parental DBD conferred independent risk for conduct disorder and ADHD and only parental MDD conferred independent risk for oppositional defiant disorder. CONCLUSION: Elevated rates of DBD in the offspring of parents with MDD appear to be due in part to the presence of DBD in the parents. Further studies of samples not selected on the basis of parental panic disorder are needed to confirm these results.

Wilens TE, Biederman J, Adamson JJ, Henin A, Sgambati S, Gignac M, Sawtelle R, Santry A, Monuteaux MC. · Massachusetts General Hospital, Pediatric Psychopharmacology Unit, Boston, MA 02114, USA. · Drug Alcohol Depend. · Pubmed #18343050 links to  free full text

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.