A recent article by Zito et al 1 raised concerns as to the apparent excessive use of psychotropics in preschoolers. Using data from large datasets, these researchers documented two trends: (1) that 1% of preschoolers in the United States were receiving psychotropics and (2) that there has been a substantial rise in the use of psychotropics over the last decade. 1 They appropriately comment on the scarcity of data on the safety and efficacy of psychotropics in preschoolers and view these trends as disturbing. Yet, the absence of scientific data on the use of psychotropics in preschoolers should not necessarily be viewed as inappropriate.
In fact, the use of psychotropics in preschoolers needs to be evaluated in context with the mental health problems afflicting this age group. 2,3 Despite the scarcity of systematic observations, converging evidence suggests that pediatric psychiatric disorders frequently emerge in the preschool years. For example, previous work has documented that attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), and opposition defiant disorder (ODD), as well as mood and anxiety disorders, frequently begin in the preschool years. 4–10 The literature also suggests that preschoolers tend to have high rates of psychiatric comorbidity and substantial morbidity related to their psychopathology. 6,9,11,12 Given that up to 15% of school-aged children have been reported to manifest psychopathology, 13,14 it is expected that a sizable number of preschoolers may have significant psychopathology 15 likely to benefit from psychopharmacological intervention.
This issue is of particular relevance considering that preschoolers are increasingly enrolled in school settings. Those youth with severe psychopathology may manifest dangerous behaviors and severe moodiness that could lead to expulsion from day care and early education placements. Thus, it is not at all surprising that a small fraction (i.e., 1%) of our preschoolers end up being medicated despite inadequate scientific data to support their efficacy and safety. 1
Unfortunately, preschoolers have often been excluded from clinical trials and epidemiological and clinical studies. 2 As highlighted in recent hearings for the U.S. Surgeon General’s Report on Children’s Mental Health, 16 this state of affairs has led to a worrisome state of diagnostic and therapeutic nihilism toward preschoolers, depriving the clinical community of appropriate tools to address the severe mental health problems of this age group and to offer these youth safe and effective treatments. The delay in diagnosis and treatment of these youth may result in developmental deviance begetting further perturbed development, 7,17,18 kindling of further psychopathology, 19 disturbances in family functioning, 7,20 and the sequela of untreated mental health problems.
A first step to begin to deal with this issue is to evaluate the magnitude and the severity of the “preschool problem” in the mental health clinical setting. To this end, we systematically evaluated the prevalence and clinical characteristics of clinically referred preschoolers. Based on the available literature, we hypothesized that preschoolers will be commonly referred for treatment and will have high rates of identifiable psychiatric disorders with high rates of psychiatric comorbidity and dysfunction worthy of intervention.
This was a systematic review of the clinical characteristics of all children ≤ 6 years of age referred for routine clinical care in a pediatric psychiatry clinic at a major medical academic center from 1991 to 1999. This clinic sample was unselected in that preschoolers were referred for a psychiatric evaluation but not for evaluation of any specific disorder. All cases underwent a comprehensive, standardized assessment battery as part of the diagnostic procedures implemented at our center. We had institutional review board approval to review, analyze, and report on these findings.
Diagnostic information relied on the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiologic Version (KSADS-E) 21 administered to the parents by highly trained and supervised raters. Interviewers were blind to the referral status and chief complaint of the preschooler. Diagnoses were made according to DSM-III-R criteria. For every diagnosis, information was gathered regarding the ages at onset and offset of full syndromic criteria. As in our previous work, we used the presence of two or more anxiety disorders to indicate the presence of a clinically meaningful anxiety syndrome. 22 Rates reported reflect lifetime prevalence of disorders.
All diagnoses were reviewed by a team of highly experienced, board-certified psychiatrists and psychologists. 23 Diagnoses were considered positive only if a consensus was achieved that criteria were met to a degree that would be considered clinically meaningful. By “clinically meaningful” we mean that the data collected from the structured interview indicated that the diagnosis should be a clinical concern because of the nature of the symptoms, the associated impairment, and the coherence of the clinical picture. A key point is that these diagnoses were made as part of the clinical assessment procedures for our clinic; they were not simply research diagnoses computed by counting symptoms endorsed and applying an algorithm. We consider these diagnoses “clinically meaningful” because they are routinely used in planning the treatment of children in our clinic.
We computed kappa coefficients of agreement by having three experienced, board-certified child and adult psychiatrists and psychologists diagnose subjects from audiotaped interviews made by the assessment staff. Based on 173 interviews, the kappas were attention deficit hyperactivity disorder (ADHD) (.99), bipolar disorder (.94), and depression (.86). We also assessed the 1-year, test-retest reliability of the lifetime diagnoses generated by our interviewers. As Faraone et al 24 reported in detail, the 1-year test-retest kappas were .95 for ADHD, .66 for major depression, and .71 for bipolar disorder. These interrater and test-retest kappas were all within the range described as substantial to almost perfect by Landis and Koch. 25
Social functioning was evaluated using the Social Adjustment Inventory for Children and Adolescents (SAICA) 26 assessing the past year’s functioning. We administered the SAICA at the same time as the psychiatric interview. The SAICA individual and global items are rated on a 4-point scale with higher numbers corresponding to worse functioning. A total score is then calculated as the arithmetic mean of all global rating scores. To assess family functioning we used the Moos Family Environment Scale (FES). 27,28 Parents reported on 27 true/false questions about the cohesion, expression, and conflict among their family members. On the cohesion (1–68) and expression (15–73) subscales, lower scores reflect worse functioning, whereas on the conflict subscale (32–81), higher scores represent worse functioning. Family data were available for 93 preschoolers.
Socioeconomic status was determined by the Hollingshead Four Factor Index. 29 Overall functioning was determined using the global assessment of functioning (GAF) scale from the DSM-III-R 30 capturing lifetime and current (past 30 d) functioning. Data are expressed as means ± SD unless otherwise stated.
Demographic and Clinical Characteristics
From the pool of 1658 consecutive referrals on which structured psychiatric data were available, we identified 200 (12%) children ≤ 6 years of age (preschoolers). The mean age of the sample was 5.2 ± 0.9 years with a median age of 5 years (Table 1). The majority of preschoolers were male and came from middle-class families.
Table 2 depicts the rates and ages of onset of psychiatric disorders in clinically referred preschoolers. Ninety-three percent of referred preschoolers were found to manifest at least one major psychopathological condition by a structured psychiatric interview. The most common disorders were attention deficit hyperactivity disorder (ADHD; 86%), followed by other disruptive behavioral (61%), mood (43%), and anxiety disorders (28%).
ADHD had the earliest onset followed closely by mood and other disruptive behavioral disorders. On average, preschoolers’ psychiatric disorders had an onset of 2.2 ± 1.3 years before their age at evaluation.
Comorbid psychopathology was common in our referred preschoolers (Fig. 1). Only 25% of preschoolers had one major psychiatric disorder (ADHD, conduct/opposition, mood, anxiety), whereas 68% had two or more disorders. Preschoolers had a mean of 2.2 ± 1.2 psychiatric disorders each at evaluation.
The global assessment of functioning (GAF) scores placed these children solidly in the moderate severity range of dysfunction associated with their psychopathology. 30 Similarly, the Social Adjustment Inventory for Children and Adolescents (SAICA) overall score of 17 ± 5 indicated that preschoolers had mild to moderate social dysfunction. 26 Family functioning assessment indicated normal functioning in cohesion (52 ± 18), expressiveness (50 ± 12), and conflict (52 ± 13) domains in these families 27,28 (Table 3).
Our results show that preschoolers are commonly referred for psychiatric evaluation and frequently manifest substantial psychopathology and morbidity. Preschoolers were affected by a mean of two major psychiatric disorders with attention deficit hyperactivity disorder (ADHD) and opposition defiant disorder (ODD) being the most common disorders identified. The onset of the psychopathology proceeded the age at referral by over 2 years. These data support the notion of the existence of diagnosable psychopathology and associated social and global dysfunction in a high number of referred preschoolers of such severity as to likely require intervention including psychotherapy, psychopharmacology, or the combination.
The current findings are consistent with an emerging literature documenting high levels of psychopathology in preschool-aged youth. 4,6–9,12,31–34 Our results mirror those in other clinically referred groups indicating high rates of ADHD and disruptive, mood, and anxiety disorders in these youth 31,33,35 —similar to their older school-aged peers.
In addition, our current findings, using structured psychiatric interviews that generated categorical diagnoses, broaden the extant literature by highlighting the high rates of psychiatric comorbidity in preschoolers. In fact, our youth typically had at least two disorders per child with functional impairment associated with these disorders. Our findings are consistent with recently reported data indicating the coexistence of internalizing disorders in 45% of preschoolers (mean age of 3 yr) diagnosed with an externalizing disorder by the Child Behavior Checklist (CBCL). 12 Our results are also consistent with those of a longitudinal pediatric-based study in that one third of preschoolers with abnormal disruptive symptomatology subsequently developed an emotional disorder by the age of 6 years. 36 Taken together, these findings provide an important diagnostic foundation in evaluating the use of psychotherapies and psychopharmacology in this age group. 2
Consistent with previous findings, we found that mood (depression and bipolar disorder), disruptive, and anxiety disorders also had very early onsets—identical to previous reports. 4,8–10,31,36,37 This is not surprising as symptoms of ADHD, 4,12 anxiety, 36 depression, 31,36,38 and bipolar disorder 5,11,39–41 have been reported to have very early onset in subgroups of children and adolescents.
Although the etiology and course of early onset highly comorbid psychiatric disorders in these clinically referred preschoolers remains to be evaluated in a comprehensive review of the literature, Campbell reported that approximately half of psychiatric problems in very young children persists into later childhood. 7 More recently, using serial CBCL in youth ascertained from pediatricians’ offices, Lavigne et al 36 have shown the stability of psychopathology in preschoolers, particularly when diagnosed after the age of 4 years. This group also reported that 50% of youth diagnosed in preschool years continued to manifest psychiatric disorders 4 years later. These aggregate data add to the growing notion of the stability and chronicity of psychiatric disorders originating in preschool years. 7,36
Very early onset psychopathology has been linked to high rates of familiality, as well as chronicity and a more pernicious course. 10,42,43 For example, early onset mood disorders are typically characterized by high rates of familiality, impairment, and comorbidity. 38,42,44–46 Moreover, data on preschoolers with ADHD 2,47 or bipolar disorders 46,48,49 suggest that this group responds less well to pharmacological intervention and have more adverse events compared with older youth with similar psychiatric disorders.
Our findings of low levels of family disruption are similar to findings from a recent report, 34 and in our data this suggests that family dysfunction may not have been directly related to the preschoolers’ emotional and behavioral problems. Our preschoolers were, however, dysfunctional socially. Considering that marked social dysfunction has been shown to be a strong predictor of later behavioral difficulties and substance abuse, 50,51 the identification and treatment of these preschoolers is of high clinical importance.
The current data also support the notion that even if children present to a psychiatric clinic as preschoolers, the condition for which they seek evaluation and treatment is typically chronic, with a mean of 2 years onset before evaluation. In some cases, more than half of the youth’s life has been burdened with emotional or behavioral problems by the time of presentation. Considering that the disorders identified in our preschoolers can be targeted with psychotherapy 52 and psychotropics, 53 our findings support the need to evaluate various interventions in this subgroup of youth. Moreover, early identification and treatment of less severe psychopathology when it emerges may reduce the development of a more severe disorder with their associated morbidity and impairment. For example, a growing literature suggests that preschool disruptive disorders identifiable by the first grade predicts later substance abuse, 54–56 and that treatment may reduce the risk for substance abuse. 57 It remains to be seen if aggressive intervention of subacute mental health difficulties will moderate the development of more pronounced and chronic psychopathology, which in turn may attenuate the compromised developmental trajectory in these youth.
Our findings should be evaluated in light of their methodological limitations. Although extensive acceptable reliability data for the Kiddie Schedule for Affective Disorders and Schizophrenia-Epidemiologic Version (KSADS-E) has been documented, 58 less is known about the validity of the various modules in preschoolers. However, structured diagnostic interview techniques can minimize informant and clinician bias and may represent an improvement over the standard clinical assessment. 59 Moreover, in our series, structured interview data were reviewed by an experienced, board-certified child and adolescent psychiatrist or psychologist before final diagnostic assignment, enhancing the credibility of the findings. In this study, all structured interviews were done with a parent, usually the mother, about the child. Although young children are not always good reporters of their lifetime psychopathology, future studies would benefit from direct interview of the child in addition to the parent. Reliability data on the global assessment of functioning (GAF) scale were not available in this age group.
As most of our subjects were male and from middle-class families, additional work with females and preschoolers from other social strata are needed to determine whether our results would generalize to females and other socioeconomic groups. Because we studied children referred to a pediatric psychiatry clinic, our findings may not generalize to other psychiatric sampling frames, pediatric clinics, or to community samples. It is possible that our clinic is known for the management of difficult and comorbid cases, and this may explain the high rate of psychiatric comorbidity seen in our sample of referred children. It may be that nonreferred preschoolers may manifest less severe psychopathology and comorbid states, as well as a more limited course of the disorder. Clearly, more work is needed to further address this issue with large and diagnostically representative samples of general pediatric and psychiatric referrals, as well as epidemiological samples.
The growing concerns of psychopathology and appropriate treatment in preschoolers necessitates substantial research effort. Follow-up of our clinically referred preschoolers evaluating the stability of their diagnoses, medication response, and side effects, as well as long-term outcome, are necessary. Given the clinical bias in our current report, carefully conducted epidemiological studies on very young children, presumably with less severe psychopathology, with longitudinal follow-up are necessary. Such studies should evaluate symptomatic, syndromic, and functional status over time. Treatment studies of preschoolers with psychopathology need to be undertaken including the role and efficacy of specific types of psychotherapy (e.g., cognitive, structural, family, and individual) in this age group. Moreover, the short- and long- term effectiveness of psychotherapy, pharmacotherapy, and the combination in improving outcome in these preschoolers in multiple domains is warranted.
Despite these considerations, the results of our study suggest that preschoolers are commonly referred and have high rates of psychopathology with psychiatric comorbidity and functional impairment. The current data add to the existing literature by highlighting the serious nature of the psychopathology and impairment found in preschoolers referred for evaluation and treatment. The seriousness of the disorders identified in preschoolers should be balanced against the concerns about the increasing prevalence of psychotropic use in this age group.
1. Zito JM, Safer DJ, dosReis S, Gardner JF, Boles M, Lynch F: Trends in the prescribing of psychotropic medications to preschoolers. JAMA 283:1025–1030, 2000
2. Greenhill LL: The use of psychotropic medication in preschoolers: Indications, safety, and efficacy. Can J Psychiatry 43:576–581, 1998
3. Shaywitz SE, Shaywitz BA: Increased medication use in attention-deficit hyperactivity disorder: Regressive or appropriate? JAMA 260:2270–2272, 1988
4. Lavigne JV, Gibbons RD, Christoffel KK, et al: Prevalence rates and correlates of psychiatric disorders among preschool children. J Am Acad Child Adolesc Psychiatry 35:204–214, 1996
5. Weller RA, Weller EB, Tucker SG, Fristad MA: Mania in prepubertal children: Has it been underdiagnosed? J Affect Disord 11:151–154, 1986
6. Johnson MA: Prevalence of psychopathology in preschool-age children. J Child Adolesc Psychiatr Nurs, in press, 2002
7. Campbell SB: Behavior problems in preschool children: A review of recent research. J Child Psychol Psychiatry 36:113–149, 1995
8. Keenan K, Shaw DS, Walsh B, Delliquadri E, Giovannelli J: DSM-III-R disorders in preschool children from low-income families. J Am Acad Child Adolesc Psychiatry 36:620–627, 1997
9. Hooks MY, Mayes LC, Volkmar FR: Psychiatric disorders among preschool children. J Am Acad Child Adolesc Psychiatry 27:623–627, 1988
10. Moffitt TE: Juvenile delinquency and attention deficit disorder boys’ developmental trajectories from age 3 to 15. Child Dev 61:893–910, 1990
11. Wozniak J, Biederman J, Kiely K, et al: Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry 34:867–876, 1995
12. Thomas JM, Guskin KA: Disruptive behavior in young children: What does it mean? J Am Acad Child Adoles Psychiatry 40:44–51, 2001
13. Costello J, Angold A, Burns B, Erkanli A, Stangl D, Tweed D: The Great Smoky Mountains study of youth. Functional impairment and serious emotional disturbance. Arch Gen Psychiatry 53:1137–1143, 1996
14. Bird HR, Gould MS, Staghezza BM: Patterns of psychiatric comorbidity in a community sample of children aged 9 through 16 years. J Am Acad Child Adolesc Psychiatry 32:361–368, 1993
15. Anderson JC, Williams S, McGee R, Silva PA: DSM III disorders in preadolescent children. Arch Gen Psychiatry 44:69–76, 1987
16. Psychopharmacology for young children: Clinical needs and research opportunities. Presented at the National Institute of Mental Health and the Food and Drug Administration, Washington, DC, October 2–3, 2000
17. Tarter RE, Laird SB, Kabene M, Bukstein O, Kaminer Y: Drug abuse severity in adolescents is associated with magnitude of deviation in temperament traits. Brit J Addict 85:1501–1504, 1990
18. Brook JS, Tseng L, Cohen P: Toddler adjustment: Impact of parents’ drug use, personality, and parent-child relations. J Genet Psychol 157:281–295, 1996
19. Post RM: Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 149:999–1010, 1992
20. Barkley RA, Karlsson J, Pollard S, Murphy JV: Developmental changes in the mother-child interactions of hyperactive boys: Effects of two dose levels of Ritalin. J Child Psychol Psychiatry 26:705–715, 1985
21. Orvaschel H: Psychiatric interviews suitable for use in research with children and adolescents. Psychopharmacol Bull 21:737–748, 1985
22. Biederman J, Rosenbaum JF, Hirshfeld DR, et al: Psychiatric correlates of behavioral inhibition in young children of parents with and without psychiatric disorders. Arch Gen Psychiatry 47:21–26, 1990
23. Leckman JF, Sholomskas D, Thompson D, Belanger A, Weissman MM: Best estimate of lifetime psychiatric diagnosis: A methodological study. Arch Gen Psychiatry 39:879–883, 1982
24. Faraone S, Biederman J, Milberger S: How reliable are maternal reports of their children’s psychopathology? One year recall of psychiatric diagnoses of ADHD children. J Am Acad Child Adolesc Psychiatry 34:1001–1008, 1995
25. Landis JR, Koch GG: The measurement of observer agreement for categorical data. Biometrics 33:159–174, 1977
26. John K, Gammon D, Prusoff BA, Warner V: The social adjustment inventory for children and adolescents (SAICA): Testing of a new semistructured interview. J Am Acad Child Adolesc Psychiatry 26:898–911, 1987
27. Moos RH, Moos BS: A typology of family environments. Fam Process 15:357–372, 1976
28. Moos RH, Moos BS: Manual for the Family Environment Scale. Palo Alto, CA, Consulting Psychologists Press, 1974
29. Hollingshead AB: Four Factor Index of Social Status. New Haven, CT, Yale University Press, 1975
30. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders III R, 3rd ed rev. Washington, DC, American Psychiatric Association Press, 1987
31. Kashani JH, Carlson GA: Seriously depressed preschoolers. Am J Psychiatry 144:348–350, 1987
32. Halfon N, Newacheck PW: Prevalence and impact of parent-reported disabling mental health conditions among US children. J Am Acad Child Adolesc Psychiatry 38:600–609; discussion 610–613, 1999
33. Ulloa RE, Birmaher B, Axelson D, et al: Psychosis in a pediatric mood and anxiety disorders clinic: Phenomenology and correlates. J Am Acad Child Adolesc Psychiatry 39:337–345, 2000
34. Mesman J, Koot HM: Early preschool predictors of preadolescent internalizing and externalizing DSM IV diagnoses. J Am Acad Child Adolesc Psychiatry 40:1029–1036, 2001
35. Kashani JH, Allan WD, Beck NC, Bledsoe Y, Reid JC: Dysthymic disorder in clinically referred preschool children. J Am Acad Child Adolesc Psychiatry 36:1426–1433, 1997
36. Lavigne J, Arend R, Rosenbaum D, Binns H, Christoffel K, Gibbons R: Psychiatric disorders with onset in the preschool years. I. Stability of diagnoses. J Am Acad Child Adolesc Psychiatry 37:1246–1254, 1998
37. Geller B, Zimerman B, Williams M, et al: Diagnostic characteristics of 93 cases of a prepubertal and early adolescent bipolar disorder phenotype by gender, puberty and comorbid attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol 10:157–164, 2000
38. Birmaher B, Ryan ND, Williamson DE, et al: Childhood and adolescent depression: A review of the past 10 years. Part I. J Am Acad Child Adolesc Psychiatry 35:1427–1439, 1996
39. Wozniak J, Biederman J, Kiely K, Ablon JS, Faraone S: Prepubertal mania revisited. Presented at the Scientific Proceedings of the American Academy of Child and Adolescent Psychiatry, San Antonio, TX, 1993
40. Geller B, Sun K, Zimerman B, Luby J, Frazier J, Williams M: Complex and rapid-cycling in bipolar children and adolescents: A preliminary study. J Affect Disord 38:1–10, 1995
41. Hagino OR, Weller EB, Weller RA, Washing D, Fristad MA, Kontras SB: Untoward effects of lithium treatment in children aged four through six years. J Am Acad Child Adolesc Psychiatry 34:1584–1590, 1995
42. Wozniak J, Biederman J, Mundy E, Mennin D, Faraone SV: A pilot family study of childhood-onset mania. J Am Acad Child Adolesc Psychiatry 34:1577–1583, 1995
43. Weller E, Weller RA: Mood Disorders in Children, in Weiner JM (ed): Textbook of Child and Adolescent Psychiatry. Washington, DC, American Psychiatric Press, Inc., 1991, pp 240–247
44. Faraone SV, Biederman J, Wozniak J, Mundy E, Mennin D, O’Donnell D: Is comorbidity with ADHD a marker for juvenile-onset mania? J Am Acad Child Adolesc Psychiatry 36:1046–1055, 1997
45. Biederman J, Faraone SV, Keenan K, Benjamin J, Krifcher B: Further evidence for family-genetic risk factors in attention deficit disorder: Patterns of comorbidity in probands and relatives in psychiatrically and pediatrically referred samples. Arch Gen Psychiatry 49:728–738, 1992
46. Strober M, Morrell W, Burroughs J, Lampert C, Danforth H, Freeman R: A family study of bipolar I disorder in adolescence: Early onset of symptoms linked to increased familial loading and lithium resistance. J Affect Disord 15:255–268, 1988
47. Wilens T, Spencer T: The stimulants revisited, in Stubbe C (ed): Child and Adolescent Psychiatric Clinics of North America, 3rd ed, vol 9. Philadelphia, PA, Saunders, 573–603, 2000
48. Hagino OR, Weller EB, Weller RA, Fristad MA: Comparison of lithium dosage methods for preschool and early school-age children. J Am Acad Child Adolesc Psychiatry 37:60–65, 1998
49. Biederman J, Mick E, Bostic J, et al: The naturalistic course of pharmacologic treatment of children with manic like symptoms: A systematic chart review. J Clin Psychiatry 59:628–637, 1998
50. Greene R, Biederman J, Faraone S, Sienna M, Garcia-Jetton J: Adolescent outcome of boys with attention-deficit/hyperactivity disorder and social disability: Results from a 4-year longitudinal follow-up study. J Consult Clin Psychol 65:758–767, 1997
51. Ollendick T, Weist M, Borden M, Greene R: Sociometric status and academic, behavioral, and psychological adjustment: A five year longitudinal study. J Consult Clin Psychol 60:80–87, 1992
52. Sonuga-Barke E, Daley D, Thompson M, Laver-Bradbury C, Weeks A: Parent-based therapies for preschool ADHD: A randomized, controlled trial with a community sample. J Am Acad Child Adolesc Psychiatry 40:402–408, 2001
53. Wilens T: Straight Talk About Psychiatric Medications for Kids. New York, NY, Guilford Press, 1999
54. Lecca PJ, Watts TD: Preschoolers and Substance Abuse: Strategies for Prevention and Intervention. New York, NY, The Haworth Press, 1993
55. Kellam SG, Ensminger ME, Simon MB: Mental health in first grade and teenage drug, alcohol, and cigarette use. Drug Alcohol Depend 5:273–304, 1980
56. Brook JS, Whiteman M, Cohen P, Shapiro J, Balka E: Longitudinally predicting late adolescent and young adult drug use: Childhood and adolescent precursors. J Am Acad Child Adolesc Psychiatry 34:1230–1238, 1995
57. Biederman J, Wilens T, Mick E, Spencer T, Faraone S: Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics 104:e20, 1999
58. Chambers W, Puig-Antich J, Hirsch M, et al: The assessment of affective disorders in children and adolescents by semistructured interview. Arch Gen Psychiatry 42:696–702, 1985
59. Robins L: How recognizing “comorbidities” in psychopathology may lead to an improved research nosology. Clin Psychol Sci Pract 1:93–195, 1994