Attention-deficit hyperactivity disorder (ADHD) symptoms include inattention, motor hyperactivity and impulsiveness. Roughly half of the adults who report ADHD symptoms also report a co-existing substance-abuse disorder. New findings published in the October issue of Alcoholism: Clinical & Experimental Research have identified a distinct phenotype or "profile" of individuals with co-existing ADHD and alcoholism. Although prior studies have suggested a genetic commonality of ADHD and alcoholism, the study found no significant contribution of two specific candidate genes, the promoter polymorphism of the serotonin transporter gene (5-HTT) and the 5-HT2c receptor Cys23Ser polymorphism.
"Our results indicate that individuals with persisting ADHD symptoms in adulthood seem to be at high risk of developing an alcohol-use disorder," said Monika Johann, medical doctor and research associate at the University of Regensburg and first author of the study. "Moreover, there is evidence for a highly increased severity of alcohol dependence in subjects with ADHD."
Researchers examined 314 adult alcoholics (262 males, 52 females) as well as 220 unrelated healthy control subjects, all of German descent. Each participant was assessed for psychiatric disorders, such as substance-use disorders (including alcoholism), ADHD, and antisocial personality disorder (APD). Patients with a history of major psychiatric disorders, including depression and schizophrenia, and those with addictions to drugs other than alcohol and nicotine, were excluded from the investigation. Genotyping was performed without knowledge of diagnostic status, with a focus on the 5-HTT promoter and the 5-HT2c Cys23Ser polymorphism.
"Prior neuroendocrine challenge studies with a drug called fenfluramine in subjects with ADHD or alcoholism revealed similar differences in the serotonergic neurotransmission when compared to normal subjects," explained Johann. "The usual response to fenfluramine administration is a measurable increase in the circulating prolactin. This usual increase is blunted in subjects with ADHD or alcoholism. The main structures responsible for the fenfluramine-induced prolactin release are the 5-HTT and the 5-HT2c receptors. Therefore, both seemed plausible as overlapping sources of genetic liability of ADHD and alcoholism."
Neither of them, however, appear to be genetic risk factors in the sample examined. "Our data demonstrate that the 5-HTT promoter and the 5-HT2c Cys23Ser polymorphism do not contribute to the putative common genetic predisposition for ADHD and alcohol dependence," said Johann. "However, several other candidate genes have yet to be investigated."
Nonetheless, the findings do indicate a distinct phenotype, a way to measure an observable trait or behavior. Adult alcoholics with ADHD had a significantly higher daily and record intake of alcohol per month, an earlier age of onset of alcohol dependence, a higher frequency of thoughts about suicide, a greater number of court proceedings, and a greater occurrence of APD.
Thus, despite the lack of support for a common genetic predisposition, "the data show once again that to have ADHD means to be at high risk for developing alcohol dependence," said Ema Loncarek, a medical doctor and clinician at the psychiatric clinic of the University of Regensburg. Loncarek works on a ward for illegal drug addiction, providing detoxification and therapy.
"Dr. Johann’s findings of a phenotype are very close to what we see in drug addicts with ADHD, and what has been described before by other authors. We see on a regular basis that drug addicts with ADHD are difficult to handle. They start to abuse drugs earlier than other people, change earlier to "hard" drugs, take longer to start treatment, and take longer to successfully finish therapy."
Johann described in more detail the phenotypic variations she and her colleagues found. "Within this group of alcoholics, subjects with ADHD in adulthood are five to 10 times more frequent than in the normal population," she said. "Compared to alcoholics without ADHD, alcoholics with ADHD in adulthood were at least four years younger at onset of alcoholism, drank about 50 grams pure alcohol more per day during the previous month, had a nearly twofold higher rate of first-degree positive family history of alcoholism, had a nearly three times higher frequency of antisocial personality disorder, had a nearly seven times higher frequency of court proceedings, and had a more than two times higher frequency of suicidal thoughts."
Both Johann and Loncarek spoke of a need for the development and evaluation of specialized treatment programs that address "phenotypical specifics" as well as co-existing disorders such as alcoholism and ADHD. While pharmacological remedies, they noted, have been extensively evaluated for the treatment of ADHD in childhood, little attention has been given to substance-abusing individuals with ADHD in adulthood."
"ADHD seems to be highly underestimated in adulthood," said Johann, "yet seems to be an important risk factor for the development of alcohol dependence."
Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.
Articles were written based on the following published research:
Johann,M., Bobbe. G., Putzhammer, A., Wodarz, N. (October 2003). Comorbidity of alcohol dependence with attention-deficit hyperactivity disorder: differences in phenotype with increased severity of the substance disorder, but not in genotype (serotonin transporter and 5-hydroxytryptamine-2c receptor). Alcoholism: Clinical & Experimental Research, 27(10), 1527 – 1535.
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