| Abstract|| |
Background: Early onset (EO) alcohol dependence (AD) has been found to represent a subtype of alcoholism with a distinct profile and prognosis compared to late onset (LO) alcohol dependence. Externalizing disorders, especially attention deficit hyperactivity disorder (ADHD) that may continue as attention deficit hyperactivity disorder, residual type (ADD, RT) in adulthood, may increase susceptibility to early-onset AD.
Aims: To examine the relationship between ADHD and ADD, RT symptoms and age at onset of AD in a sample of Indian male patients. 70 male subjects with AD presenting to the De-Addiction Services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, were studied. The study had a retrospective design.
Materials and Methods: Patients were examined for evidence of past ADHD in childhood and current ADD, RT using structured instruments. Chi-square tests and odds ratios were used to express the relative risk of association of ADHD with early- and late-onset AD.
Results: Significantly more EO alcoholics (19/30, 63.3%) had a history of ADHD in childhood compared to LO alcoholics (7/28, 25%, P < 0.05) ADD, RT was also over-represented in EO probands.
Conclusions: The results of this study are consistent with previous research that shows a high incidence of ADHD in early-onset alcoholics. This may have important management implications.
Keywords: ADHD, alcohol dependence, early-onset
|How to cite this article:|
Singeri SR, Rajkumar RP, Muralidharan K, Chandrashekar CR, Benegal V. The association between attention-deficit/hyperactivity disorder and early-onset alcohol dependence: A retrospective study. Indian J Psychiatry 2008;50:262-5
|How to cite this URL:|
Singeri SR, Rajkumar RP, Muralidharan K, Chandrashekar CR, Benegal V. The association between attention-deficit/hyperactivity disorder and early-onset alcohol dependence: A retrospective study. Indian J Psychiatry [serial online] 2008 [cited 2020 Oct 29];50:262-5. Available from: https://www.indianjpsychiatry.org/text.asp?2008/50/4/262/44748
| Introduction|| |
Early onset (EO) of alcohol dependence (AD) represents a discrete form of alcoholism , which is significantly associated with greater severity of alcohol-related problems, family history, childhood behavioral problems, craving, hostility, antisocial traits, mood disturbance, and poor social functioning compared to subjects with late onset (LO) alcohol dependence. ,, EO alcoholics and their first degree relatives may also be differentiated from families of LO alcoholics using a variety of putative risk markers. , EO alcoholism perhaps represents a more severe and heritable subtype,  which is associated with externalizing disorders such as attention deficit hyperactivity disorder (ADHD) and conduct disorder (CD). ,,,, An analysis of data from the Collaborative Study of the Genetics of Alcoholism (COGA) found that the mean age of onset of AD in those with comorbid disruptive behavior disorders was 14 ± 1.9 years. 
ADHD is one of the most studied disruptive behavior disorders in childhood. It usually first manifests by the age of 7 and is more common in boys (M : F = 2-3:1). Outcome studies of children with ADHD have showed that the disorder can persist into adolescence in 50-80% of cases. ,,, Although overactivity mellows down into subjective restlessness, attentional problems and impulsivity continue, leading on to problems at school or work, peer relationships and low self-esteem.
Various studies have examined the co-occurrence of ADHD and substance use disorder in adolescents and adults. ADHD has been robustly associated with nicotine use disorder in mid-adolescence,  as well as with alcohol and other substance use disorders in late adolescence and early adulthood. , Biederman et al .  reported a prevalence of substance dependence in 21% of adults who had ADHD in childhood compared to 12% in controls. Subsequent studies also found high rates of comorbidity between ADHD and substance abuse, ranging from 24 to 47%. ,,, A follow-up study  of children with ADHD found alcohol dependence in 16.6% of patients with mild attentional difficulties and 33.3% in those with severe attentional difficulties. The same authors followed up this cohort for 25 years, however, and found that this association was largely mediated by conduct symptoms.  The association between attentional impairment and substance use was corroborated by Tapert et al .  Impulsivity, which is another key feature of ADHD, has been associated with AD.  Milin et al .  reported a high prevalence of ADHD and ADD, residual type (RT) symptoms in patients with substance use disorder. Finally, the age of onset of AD in patients with ADHD has been found to be earlier. ,
| Materials and Methods|| |
70 male subjects aged 16-60 years, admitted for alcohol related problems to the De-addiction Centre at the National Institute of Mental Health and Neurosciences, India, who met ICD-10 Diagnostic Criteria For Research  for Alcohol Dependence Syndrome were recruited for the study. Only those subjects whose parents (preferably mothers) reported adequate knowledge of patient's childhood, and were available for interview, were chosen. Diagnosis of AD was made clinically by obtaining information from as many informants as available. In order to minimize recall bias, the ages of onset of craving, tolerance, and withdrawal were obtained and the average of the three was taken to indicate the age of onset of dependence. The diagnosis was confirmed in each case by two independent clinicians (SK and VB). Subjects with co-morbid neuro-psychiatric illness or dependence on any other substance except nicotine were excluded.
The patients who satisfied the criteria for AD were assessed and divided into Early Onset (EO, those who had developed dependence before the age of 25 years) and Late Onset (LO - developed dependence after 25 years) groups. To minimize the potential overlap between these groups, subjects who had developed dependence after the age of 30 yrs were purposively selected. The severity of AD was rated using the Short Alcohol Dependence Data (SADD) questionnaire. 
Two or more first degree relatives who lived in close contiguity to the subject - preferably the subjects' mother and/or older siblings - who by reason of the extended or joint family systems commonly found in India, were likely to be most informative - were then interviewed to collect information on family history of AD, childhood symptoms of ADHD and current ADD, RT. If the mother or older sibling was not available, information was collected from at least three first-degree relatives. Family history of AD was collected using the Family Interview for Genetic Studies FIGS  and retrospective history of ADHD was gathered using the Parent Rating Scale for ADHD (PRS). The PRS is a modification of Conner's abbreviated teachers' rating scale, with 10 items each scored between 0 and 10. A score of 12 or more places the person above the 95 th percentile of childhood hyperactivity. The PRS has been used by earlier researchers ,, to retrospectively assess childhood ADHD. The presence of ADD, RT during adult life was assessed using the Wender-Utah criteria for diagnosis of ADD, RT,  based on information derived from the proband, his spouse and one other first-degree relative. Where a spouse was not available, another first-degree relative was interviewed. This checklist, based on a modified version of the DSM III-R criteria for ADD, RT, assesses the presence of both attentional deficits and hyperactivity and at least two other signs and symptoms such as affective lability, hot temper, and sensitivity to stress. The symptoms must occur in the absence of schizophrenia, schizoaffective disorder, primary affective disorder, schizotypal or borderline personality disorder. Data on family history, ADHD and ADD, RT were collected by an independent clinician (SK), blind to the age-at-onset status of the patient.
| Results|| |
70 subjects with AD were recruited. Of these, 37 had an EO of dependence and 33 had a LO. Of these, the records of seven subjects in the EO group and five in the LO group had to be discarded as there was insufficient data on both childhood ADHD and adult ADD, RT symptoms.
The EO subjects had a significantly lower age at onset of AD than the LO subjects (22.08 ± 3.38 years vs. 36.73 ± 6.35 years; t =12.36, P <0.001). The two groups did not differ significantly on other demographic or clinical variables such as education, income, religion, marital status, residential status, and severity of alcoholism scores on the SADD.
[Table 1] shows the prevalence of ADHD and ADD, RT in the two groups. A significantly larger number of EO alcoholics had a positive history of ADHD in childhood compared to LO alcoholics (c2 = 4.3758; P < 0.05) and there was similar over-representation of ADD, RT in EO probands (c2 = 8.9318; P < 0.01).
The odds ratio of a subject with ADHD and/or ADD, RT developing EO alcoholism was 5.8. This was in contrast to the odds ratio of 0.17 obtained for subjects with ADHD and/or ADD, RT developing LO alcoholism [Table 2].
| Discussion|| |
A significantly higher number of the EO subjects had a history of ADHD and/or ADD, RT compared to the LO subjects. The results of this study are consistent with previous research that show a high incidence of childhood ADHD and ADD, RT in substance abusers. ,,,,,
The odds ratio of subjects with ADHD and/or ADD, RT developing EO dependence was nearly 6:1 compared to those without comorbid ADHD. This supports the evidence that the presence of externalizing symptoms, especially ADHD, is an important risk factor for AD at an early age, and is in line with previous studies in this patient population. , This association did not hold true for patients with LO of AD, further supporting the notion that it is the EO type of alcoholism, and not AD as a whole, that is specifically associated with childhood externalizing disorders. 
The prevalence of ADHD in our sample was higher than in previous studies. However, most previous studies ,, have examined the comorbidity between AD in general and ADHD, and a study which examined families with a dense pedigree  found a prevalence of 47%. This study on the other hand contrasted EO subjects with LO, which may account for the higher rates of ADHD found in our sample.
70.8% of all subjects (17 of 24) in our study who had evidence of ADHD in childhood also had ADD, RT as adults. This data lends support to the finding that ADHD symptoms persist from childhood into adulthood in over 50% of cases. ,,
Several studies have shed light on the mechanisms underlying the association between disruptive behavior disorders and ADHD. Kuperman et al .  found that disruptive behavior disorders precede the onset of substance dependence, and therefore represent a proximal step in the trajectory from childhood psychopathology to AD, a finding that was corroborated in a later retrospective study.  Various mechanisms have been proposed to explain this association, including attentional deficit, , impulsivity  and serotonergic dysfunction, , while others are still being elucidated.
The findings of this study must be interpreted in the context of several methodological limitations. Firstly, the retrospective assessment of ADHD relies heavily on the observation of informants, which may be coloured by recall and confounding biases, especially when delineating ADD, RT from alcohol-related behaviors. Secondly, the study sample was selected from a tertiary care center, and may have included severely ill patients, accounting for the high rates of comorbid ADHD. Other comorbidities, especially externalizing disorders, were not assessed, and the clinical profile of the two subgroups, apart from severity of dependence, was not compared, making it difficult to draw conclusions about the impact of comorbid ADHD. Thirdly, we do not have information on all those subjects who were screened and excluded from the study, or their socio-demographic or clinical variables. These people were excluded from the study at screening itself because neither parent was available to provide information. Finally, the study was cross-sectional in origin, so that course and outcome could not be commented upon.
Nevertheless, these results strongly suggest a need for greater evaluation of ADHD in populations of adults with AD, especially those with an EO of AD, and more intensive management of this high-risk group in view of their poorer prognosis. Since treatment of ADHD in adolescents, including stimulants, is known to reduce substance use, including alcohol use, , assessment of comorbid ADD, RT in adults has important therapeutic implications.
| References|| |
|1.||Cloninger CR, Bohman M, Sigvardsson S. Inheritance of alcohol abuse: Cross-fostering analysis of adopted men. Arch Gen Psychiatry 1981;38:861-8. |
|2.||Johnson BA, Cloninger CR, Roache JD, Bordnick PS, Ruiz P. Age of onset as a discriminator between alcoholic subtypes in a treatment-seeking outpatient population. Am J Addict 2000;9:17-27. [PUBMED] |
|3.||Watson CG, Hancock M, Gearhart LP, Malovrh P, Mendez C, Raden M. A comparison of the symptoms associated with early and late onset alcohol dependence. J Nerv Ment Dis 1997;185:507-9. [PUBMED] [FULLTEXT]|
|4.||Brown J, Babor TF, Litt MD, Kranzler HR. The type A / type B distinction. Subtyping alcoholics according to indicators of vulnerability and severity. Ann N Y Acad Sci 1994;28:23-33. |
|5.||Van Der Stelt O. ESBRA-Nordmann 1998 Award Lecture: Visual P3 as a potential vulnerability marker of alcoholism: Evidence from the Amsterdam study of children of alcoholics. European Society for Biomedical Research on Alcoholism. Alcohol Alcohol 1999;34:267-82. |
|6.||Benegal V, Jain S, Subbukrishna DK, Channabasavanna SM. P300 amplitudes vary inversely with continuum of risk in first degree male relatives of alcoholics. Psychiatr Genet 1995;5:149-56. [PUBMED] |
|7.||Kono Y, Yoneda H, Sakai T, Nonomura Y, Inayama Y, Koh J, et al . Association between early-onset alcoholism and the dopamine D2 receptor gene. Am J Med Genet 1997;74:179-82. [PUBMED] [FULLTEXT]|
|8.||Johnson BA, Roache JD, Javors MA, DiClemente CC, Prihoda TJ, Bordnick PS, et al . Ondansetron for reduction of drinking among biologically predisposed alcoholic patients. JAMA 2000;284:963-71. [PUBMED] [FULLTEXT]|
|9.||Button TM, Rhee SH, Hewitt JK, Young SE, Corley RP, Stallings MC. The role of conduct disorder in explaining the comorbidity between alcohol and illicit drug dependence in adolescence. Drug Alcohol Depend 2007;87:46-53. [PUBMED] [FULLTEXT]|
|10.||Schubiner H, Tzelepis A, Milberger S, Lockhart N, Kruger M, Kelley BJ, et al . Prevalence of attention-deficit/hyperactivity disorder and conduct disorder among substance users. J Clin Psychiatry 2000;61:244-51. [PUBMED] |
|11.||Schulz KP, McKay KE, Newcorn JH, Sharma V, Gabriel S, Halperin JM. Serotonin function and risk for alcoholism in boys with attention-deficit hyperactivity disorder. Neuropsychopharmacol 1998;18:10-7. |
|12.||Kuperman S, Schlosser SS, Kramer JR, Bucholz K, Hesselbrock V, Reich T, et al . Developmental sequence from disruptive behavior diagnosis to adolescent alcohol dependence. Am J Psychiatry 2001;158:2022-6. [PUBMED] [FULLTEXT]|
|13.||Gittelman R, Manuzza S, Shenker S, Bonagura N. Hyperactive boys almost grown up: I. Psychiatric status. Arch Gen Psychiatry 1988;42:937-47. |
|14.||Weiss G. Hyperactivity: Overview and new directions. Psychiatr Clin North Am 1985;8:737-53. [PUBMED] |
|15.||Barkley RA, Fischer M, Edelbrock CS, Smallish CL. The adolescent outcome of hyperactive children diagnosed by research criteria, I: An 8-year prospective follow-up study. J Am Acad Child Adolesc Psychiatry 1990;29:546-57. |
|16.||Barkley RA, Fischer M, Smallish L, Fletcher K. The persistence of attention-deficit / hyperactivity disorder into young adulthood as a function of reporting source and definition of disorder. J Abnorm Psychol 2002;111:279-89. [PUBMED] [FULLTEXT]|
|17.||Milberger S, Biederman J, Faraone S, Wilens T, Chu MP. Associations between ADHD and psychoactive substance use disorders: Findings from a longitudinal study of high-risk siblings of ADHD children. Am J Addict 1997;6:318-29. |
|18.||Biederman J. Impact of comorbidity in adults with attention-deficit/hyperactivity disorder. J Clin Psychiatry 2004;65:3-7. |
|19.||Biederman J, Monuteaux MC, Mick E, Spencer T, Wilens TE, Silva JM, et al . Young adult outcome of attention deficit hyperactivity disorder: A controlled 10-year follow-up study. Psychol Med 2006;36:167-79. [PUBMED] [FULLTEXT]|
|20.||Biederman J, Faraone SV, Keenan K, Benjamin J, Krifcher B, Moore C, et al . Further evidence for family genetic risk factors in attention deficit disorder: Pattern of co-morbidity in probands and relatives in psychiatrically and pediatrically referred samples. Arch Gen Psychiatry 1992;49:728-38. [PUBMED] |
|21.||Palacio JD, Castellanos FX, Pineda DA, Lopera F, Arcos-Burgos M, Quiroz YT, et al . Attention-deficit/hyperactivity disorder and comorbidities in 18 Paisa Colombian multigenerational families. J Am Acad Child Adolesc Psychiatry 2004;43:1506-15. [PUBMED] [FULLTEXT]|
|22.||Biederman J, Faraone SV, Spencer T, Wilens T, Norman D, Lapey KA, et al . Pattern of psychiatric co-morbidity, cognition and psychosocial functioning in adults with attention deficit hyperactivity disorder. Am J Psychiatry 1993;150:1792-98. [PUBMED] [FULLTEXT]|
|23.||McGough JJ, Smalley SL, McCracken JT, Yang M, Del'Homme M, Lynn DE, et al . Psychiatric comorbidity in adult attention deficit hyperactivity disorder: Findings from multiplex families. Am J Psychiatry 2005;162:1621-7. [PUBMED] [FULLTEXT]|
|24.||Fergusson DM, Lynskey MT, Horwood LJ. Attentional difficulties in middle childhood and psychosocial outcomes in young adulthood. J Child Psychol Psychiatry 1997;38:633-44. [PUBMED] |
|25.||Fergusson DM, Horwood LJ, Ridder EM. Conduct and attentional problems in childhood and adolescence and later substance use, abuse and dependence: results of a 25-year longitudinal study. Drug Alcohol Depend 2007;88:S14-26. [PUBMED] [FULLTEXT]|
|26.||Tapert S, Baratta MV, Abrantes AM, Brown SA. Attention dysfunction predicts substance involvement in community youth. J Am Acad Child Adolesc Psychiatry 2002;41:680-6. |
|27.||Finn PR, Bobova L, Wehner E, Fargo S, Rickert ME. Alcohol expectancies, conduct disorder and early-onset alcoholism: Negative alcohol expectancies are associated with less drinking in non-impulsive versus impulsive subjects. Addiction 2005;100:953-62. |
|28.||Milin R, Loh E, Chow J, Wilson A. Assessment of symptoms of attention-deficit hyperactivity disorder in adults with substance use disorders. Psychiatr Serv 1997;48:1378-95. [PUBMED] [FULLTEXT]|
|29.||Wilens TE, Biederman J, Mick E, Faraone SV, Spencer T. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. J Nerv Ment Dis 1997;185:475-82. [PUBMED] [FULLTEXT]|
|30.||Kim JW, Park CS, Hwang JW, Shin MS, Hong KE, Cho SC, et al . Clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder. Alcohol Alcohol 2006;41:407-11. [PUBMED] [FULLTEXT]|
|31.||World Health Organization. International Classification of Diseases. 10th revision (ICD-10). Classification of Mental and Behavioural Disorders. Diagnostic Criteria for Research. Geneva: WHO; 1993. |
|32.||Davidson R, Raistrick D. The validity of the Short Alcohol Dependence Data (SADD) Questionnaire: A short self-report questionnaire for the assessment of alcohol dependence. Br J Addict 1986;81:217-22. [PUBMED] |
|33.||Maxwell ME. Family interview for genetic studies: Manual for FIGS. Clinical Neurogenetics Branch, Intramural Research Programme, Bethesda, Maryland: NIMH; 1992. |
|34.||Wender PH, Reimherr WF, Wood DR. Attention deficit disorder (Minimal brain dysfunction) in adults: A replication study of diagnosis and drug treatment. Arch Gen Psychiatry 1981;38:449-56. |
|35.||Wender PH, Wood DR, Reinherr PW. Pharmacological treatment of attention deficit disorder, residual type (ADD, RT, "Minimal brain dysfunction") in adults. Psychopharmacol Bull 1985;21:222-31. |
|36.||Ward MF, Mender PH, Reimherr FW. The Wender Utah Rating Scale: An aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder. Am J Psychiatry 1993;150:885-90. |
|37.||Tarter RE, McBride H, Buonpane N, Schneider DU. Differentiation of alcoholics. Arch Gen Psychiatry 1977;34:761-8. [PUBMED] |
|38.||Mannuzza S, Klein RG, Bessler A, Malloy P, LaPadula M. Adult outcome of hyperactive boys: Educational achievement, occupational rank and psychiatric status. Arch Gen Psychiatry 1993;50:565-76. [PUBMED] |
|39.||Myers MG, Stewart DG, Brown SA. Progression from conduct disorder to antisocial personality disorder following treatment for adolescent substance abuse. Am J Psychiatry 1998;155:479-85. [PUBMED] [FULLTEXT]|
|40.||Ercan ES, Koscunol H, Varan A, Toksoz K. Childhood attention deficit / hyperactivity disorder and alcohol dependence: A 1-year follow-up. Alcohol Alcohol 2003;38:352-6. |
|41.||Hahesy AL, Wilens TE, Biederman J, Van Patten SL, Spencer T. Temporal association between childhood psychopathology and substance use disorders: Findings from a sample of adults with opioid or alcohol dependency. Psychiatry Res 2002;109:245-53. [PUBMED] [FULLTEXT]|
|42.||Wilens TE, Faraone SV, Biederman J, Gunawardene S. Does stimulant therapy of attention-deficit / hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics 2003;111:179-85. |
|43.||Wilens TE. Does medicating ADHD increase or decrease the risk for later substance use? Rev Bras Psiquiatr 2003;25:127-8. [PUBMED] [FULLTEXT]|
Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore-560 029
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2]