CLINICAL CORRELATIONS BETWEEN ADHD IN ADULT AGE, DRUG USE, ALCOHOL AND ANTISOCIAL BEHAVIOR

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1 REVIEW ARTICLES CLINICAL CORRELATIONS BETWEEN ADHD IN ADULT AGE, DRUG USE, ALCOHOL AND ANTISOCIAL BEHAVIOR 1 Ionela Cristina Nicolae Abstract: Attention deficit hyperactivity disorder is the most common psychiatric disorder in patients aged 6-17 years, with prevalence estimates ranging from 2-16%, or in other word,with at least one patient in every classroom. Prevalence estimates range from 1% to 5% in adults. Its economic impact is substantial, affecting society and the individual's family. A diagnosis of attention deficit hyperactivity disorder is currently based on a ''classic triad'' of signs: inattention and/or hyperactivity with impulsivity. Adult substance users are known to have above average rates of Attention deficit Hyperactivity Disorder (ADHD). It is highly prevalent in populations with substance use disorders and alcohol and associated with more severe course of the syndrome. Studies of ADHD and recidivism generally indicate that it is associated with greater risk of psychopathy, repeated antisocial behavior, and recidivism. Attention deficit/hyperactivity disorder (ADHD) is quiet frequent, yet difficult to recognize in the adult patient. The important functional impairment and the high prevalence of comorbid disorders within this group of patients lead to the necessity for a careful diagnosis and treatment. Key words: attention deficit, impulsivity, hiperactivity, genetic variants, tobacco Rezumat: Deficitul de atenþie cu tulburare de hiperactivitate este cel mai frecvent tip de tulburare psihicã la pacienþii în vârstã de 6-17 ani, cu estimãri prevalente variind între 2-16%, sau cu alte cuvinte, cel puþin un pacient în fiecare salã de clasã. La adulþi prevalenþa este între 1-5 %. Impactul economic al acestui fapt este substanþial, afectând atât societatea cât ºi familia individului. Un diagnostic al deficitului de atenþie cu tulburãri de hiperactivitate se bazeazã în prezent pe un grup ''clasic'' de simptome având drept caracteristici: lipsa de concentrare ºi / sau hiperactivitate cu impulsivitate. Utilizatorii de substanþe ºi alcool adulþi sunt cunoscuþi a fi afectaþi superior ratelor medii de ADHD. Este foarte rãspândit în aceste grupuri de pacienþi ºi sunt asociate de manifestãri mult mai severe ale sindromului. Studiile legate de ADHD ºi recidivism indicã faptul cã ADHD se asociazã cu un risc crescut de psihopatie, comportament antisocial repetat ºi recidivism. Tulburarea hiperactivitate/deficit de atenþie (ADHD) este frecventã dar dificil de recunoscut la pacientul adult. Necesitatea diagnosticãrii ºi tratamentului acestei afecþiuni îºi gãseºte motivul în gradul important de deteriorare funcþionalã ºi frecvenþa mare a situaþiilor comorbide existente la aceºti pacienþi. Cuvinte cheie: deficit de aten?ie, impulsivitate, hiperactivitate, variante genetice, fumat Attention deficit hyperactivity disorder (ADHD) is the most common cognitive, emotional and behavioral disorder in children (1, 2). The DSM-IV recognizes three subtypes of ADHD: a predominantly inattentive subtype (mainly characterized by difficulty to sustain attention, forgetfulness and distractibility), a predominantly hyperactive impulsive subtype (mainly characterized by fidgeting, excessive talking, restlessness and/or difficulty waiting one's turn and frequent interruption of others) and a combined inattentive hyperactive subtype (2). Whereas early findings suggested that ADHD symptoms tend to disappear in adulthood (3), there is increasing evidence suggesting that some symptoms or even a full syndrome could persist into adulthood in a substantial proportion of cases (4, 1). The persistence of ADHD is associated with a high social impairment (1) and risk to develop other psychiatric disorders (5, 6), such as alcohol and drug abuse (7), antisocial behavior (8), anxiety, depression (9) and bipolar disorder (10). Despite the paucity of formal genetics evidence, there is consensus that adult and childhood forms may share common genetic background (11). In particular, a great variety of studies focused on the genetic, environmental and psychological concomitants of childhood ADHD. These studies have mainly focused on dopamine pathway genes, such as the dopamine transporter (SLC6A3) and the dopamine receptors D4 and D5 (DRD4 and DRD5) (12), although the noradrenergic and serotoninergic neurotransmitter pathways have been consistently studied as well. In an early meta-analysis, Faraone et al. (2005) reported seven candidate genes associated to ADHD, including SLC6A3, DRD4 and DRD5, dopamine beta hydroxylase (DBH), serotonin transporter (SLC6A4), serotonin receptor 1B (HTR1B) and synaptosomal-associated protein 25 (SNAP 25). Conversely, the involvement of other genes, such as the serotonin receptor 2A (HTR2A) and the nicotinic receptor CHRNA7, was not replicated (13). Further studies confirmed a significant role of DRD4 (14), DRD5 (15) and SLC6A3 (15) in the aetiology of childhood ADHD. Note however that some of these genetic variants could be fairly specific for the predominantly inattentive and combined clinical subtypes (16) and that following meta-analysis found only limited evidence about the 1 Resident Psychiatry, Clinical Hospital of Psychiatry Prof. Dr. Alexandru Obregia, Bucharest; dr.cristinanicolae@gmail.com 100

2 Romanian Journal of Psychiatry, vol. XII, No.3, 2010 involvement of SLC6A3 in ADHD (17, 18). More recently, a comprehensive meta-analysis confirmed the role of SLC6A3, DRD4, DRD5, SLC6A4, HTR1B, and SNAP25 in ADHD (19). However, a significant heterogeneity was observed for SLC6A3, DRD4, DRD5, DBH, ADRA2A, SLC6A4, TPH2, MAOA, and SNAP25, suggesting that future studies should explore potential moderators of these associations (19). Interestingly, DRD4 showed a significant association with ADHD not only in children but also in adults (11). Recent studies further supported the involvement of SLC6A4 (20) and SLC6A3 (21). Additionally, the gene coding for brain derived neurotrophic factor (BDNF) has been associated to childhood ADHD (22) and adult ADHD (23) as well, even though the latter finding was not confirmed by a following meta-analysis (24). Studies focusing on the environmental factors associated to childhood ADHD suggested that the aggregate of many adversity factors (i.e., severe parental discord, low social class, paternal criminality, maternal mental disorder, and foster care placement), rather than the presence of any single factor, could lead to psychopathology. The importance of adverse family-environment variables as risk factors for childhood ADHD has been particularly emphasized. In addition, consistent evidence suggests that birth complications and prenatal exposure to smoking and alcohol could be related to childhood ADHD (25) and that environmental factors could play a role in adult ADHD severity as well (20). In addition to genetics and environmental influences, a great number of studies showed significant differences in personality traits between subjects diagnosed with adult ADHD and healthy controls. Adult ADHD patients have been found to have more likely pessimistic thoughts, to be self-centred, introverted, withdrawn, passive, unconventional and rebellious (26), to have a combination of pathological personality traits such as narcissistic, antisocial and aggressive-sadistic (27) and to have higher levels of neuroticism, lower levels of extraversion, openness to experience and conscientiousness, as measured by the Revised NEO Personality Inventory (NEO-PI-R) (28). Further, adult subjects with ADHD were found to have higher levels of harm avoidance and novelty seeking in comparison to healthy controls as measured by the Temperament and Character Inventory (TCI) (29) or by the earlier Tridimensional Personality Questionnaire (TPQ) in several independent studies (28, 30, 31, 32). Despite the increasing evidence about genetic, environmental and psychological determinants of persistent ADHD in adulthood, less attention has been given to the effect of the interaction of these variables on the severity of such disorder. In a previous study (20), it has been observed a significant reciprocal association between stressful life events, SLC6A4 variants and adult ADHD severity. The aim of recent studies ha been to evaluate the impact of (1) adverse events, (2) personality traits, (3) other genetic variants chosen on the basis of previous findings and (4) their potential reciprocal interconnections (whether some genes were significantly associated to ADHD severity) on adult ADHD severity in the same sample of Canadian adult ADHD patients. Previous studies suggested a possible influence of genetic variants in the SLC6A3, DBH, DRD4, DRD5, HTR2A, CHRNA7, BDNF as well as two further polymorphisms in the protein kinase G1 (PRKG1) and TAAR9, selected on the basis of of such variants on ADHD (33). All these genes are involved in signalling pathways which are supposed to be altered in ADHD. A major problem of diagnosis of ADHD with adult patients is the frequency of psychiatric comorbidity, with predominance in the affective sphere (depression, bipolar disorder, dysthymia, anxiety) and substance use (abuse, dependence). ADHD COMORBIDITY WITH SUBSTANCE USE DISORDER (SUD) AND ALCOHOL ABUSE Substance abuse is one of the most important comorbidities in case of adults with ADHD. It begins in adolescence and young adulthood is associated with a worse long-term prognosis, often associating it with an increased risk of delinquency, school failure, family problems and unwanted pregnancies and the risk of association with other addictions to substances, dangerous and recurrent (34). Wilens (1995) showed that 15-25% of adults with alcohol dependence and drug co-abuse are suffering from ADHD. Levin in 2009 showed that 10% of cocaine addicts meet the criteria for ADHD. Substance abuse in patients with ADHD, installs earlier than in subjects without ADHD (34), have more severe dependence and greater difficulties in dispensing with these behaviors. It seems that 17-45% of adults with ADHD are dependent on alcohol, and 9-30% are addicted to drugs of abuse (34). It was hypothesized that early use of stimulant medication for ADHD in childhood increases the risk of substance dependence (including cocaine) with adults, but clinical data obtained so far are contradictory. Adult substance users are known to have above average rates of Attention Deficit Hyperactivity Disorder (ADHD), but the psychometric properties of self-report measures of ADHD symptoms for adult substance users are unknown. Subjects adults with a DSM-IV substance abuse disorder were administered the Conners Adult ADHD Rating Scales (CAARS) upon enrolling in outpatient treatment. A factor structure similar to that reported for other populations was obtained and internal consistency reliabilities for the subscales and the overall index were high. Compared with CAARS norms, substance users scored significantly above average on all subscales as well as on the overall index. The CAARS may prove useful for measuring ADHD symptomatology among substance users, but additional reliability and validity evidence is needed. The CAARS should not be used by itself to diagnose individuals for ADHD. Attention deficit hyperactivity disorder (ADHD) is highly prevalent in populations with substance use disorders and associated with more severe course of the syndrome. Methylphenidate (MPH) constitutes first line treatment for ADHD both in children and in adults. There have been several case reports and open label clinical trials of MPH for the treatment of patients with SUD and comorbid ADHD suggesting that treatment with MPH may lead to a reduction in drug use as well as in the ADHD symptoms. However, the collective finding from these trials 101

3 Ionela Cristina Nicolae: Clinical Correlations Between Adhd In Adult Age, Drug Use, Alcohol And Antisocial Behavior suggeststhat the use of central stimulant medication in substance dependent populations does not lead to an increase in craving or drug use. There are two important aspects of comorbidity situations: - untreated ADHD is a risk factor for SUD. There is evidence that ADHD may reduce age of onset for substance use (34), and number of smoked cigarettes increases with the number of symptoms and hyperactivity lack of attention / self-reported impulsivity for people who have smoked for a long time. - in case of comorbidity ADHD treatment with SUD is complicated by the potential addictive stimulant drug. Risks appear to be lower for patients who maintained abstinence for a period before administering stimulant. Current recommendations are for first-line treatment of both disorders co-modal (non-stimulating or stimulating medication prolonged-release or transdermal administration for ADHD and individual and group therapy for SUD). ADHD AND TABACCO USE Studies of adolescents and young adults have found higher levels of various smoking behaviors among persons with the diagnosis or symptoms of ADHD in comparison with non-affected individuals, i.e., higher lifetime prevalence, (35), greater amount smoked, and earlier age of smoking onset. On the other hand there is much evidence that nicotine improves attentiveness and performance deficits among persons with ADHD (37, 38). This way nicotine could be looked upon like selfmedicating. Pre-clinical data showing that dopamine, a neurotransmitter relevant to attentional processes (39) and impulse control (40) is released upon smoking (41) is consistent with the self-medication hypothesis. Divergent relationships of the symptom subtypes with nicotine or smoking outcomes have been observed. Among studies that examined nicotine effects on both symptoms in the same study, most found that nicotine exerted positive effects on attention, but neither positive or adverse effects on hyperactivity and impulsivity. ADHD AND ANTISOCIAL AND CRIMINAL BEHAVIOUR An important element of assessment of ADHD is the social implications of legal issues. Several longitudinal studies have shown that ADHD is associated with an increased rate of crime in adolescence and adulthood. It has been shown that individuals with ADHD have a higher risk of committing both minor offenses such as violation of traffic and speeding and crimes leading to prison. Illegal actions most commonly associated with ADHD have been robbery, concealed weapon, and illegal possession of drugs, also the rate of arrests of these individuals was higher than the control population (34). Crime risk in adulthood is significantly greater for children with behavioral disorders; if they are absent this risk is insignificant. The UMASS study, conducted in , showed that adults with ADHD showed a probability of about 3 times more likely to sell drugs compared with control subjects (21% vs. 6%). The Milwaukee study, initiated in 1977, the most recent assessment conducted in , adults with ADHD found a 3 times higher probability to initiate physical fights (30% vs. 9%), destroy others' property (31% vs. 8%) and break and enter (20% vs. 7%) (34). A similar study conducted in New York showed that diagnosis of ADHD was a risk factor for later criminality in adulthood, but this relationship was mediated solely by the development of antisocial personality disorder - so these subjects presented a higher rate of arrests (39% vs. 20%) of convictions (28% vs. 11%) and imprisonment (9% vs. 1%) than subjects in the control group. SIt has been shown that individuals with ADHD have a higher risk of committing both minor offenses such as violation of traffic and speeding and crimes leading to prison. Illegal actions most commonly associated with ADHD have been robbery, concealed weapon, and illegal possession of drugs, also the rate of arrests of these individuals was higher than the control population (34). These data support the hypothesis that ADHD should be a predisposing factor for antisocial personality disorder and legal issues. Another important social factor in patients with ADHD is the risk they pose to themselves and others the higher probability of accidents, the core symptoms of this condition interfering with driving skills. It is known that adolescents and adults with ADHD have a higher risk of being involved in collisions with other vehicles than the general population (34). Risk of accidents in these patients is increased and impulsivity, for them to commit more violations of traffic laws (speeding, failure of traffic lights). Compared to those not suffering from ADHD, they have a higher probability of receiving fines for speeding, to see their driving license suspended, to be involved in accidents, including those resulting in casualties, its passengers declared that they drive dangerously - disorderly, they brake inadequately and have slow response times (34). Predisposition to accidents of such patients is obvious when it comes to workplace accidents, probably because of their tendency to impulsive, hyperactive behavior. They are more likely than subjects without ADHD health problems resulting from these accidents, such as fractures, craniocerebral trauma, open wounds, bruises, and loss of teeth or accidental poisoning. There is a 2004 study estimated the incidence and costs Swensen AR accidents among patients with ADHD, so subjects with ADHD were more likely than subjects in the control group to present at least one accident, this risk increases with advance old - 28% vs. 18% of children vs. 32%. 23% of adolescents and 38% vs. 18% in adults. ADHD is associated with many other issues at work with adults, such as low job performance, lower occupational status, less stable employment, a higher rate of unemployment and a greater number of absences from service compared to adults who do not have ADHD (34). Patients with ADHD have a 3-fold higher probability of being dismissed compared to people who do not have ADHD and they change jobs on average 2-3 times in 10 years (33). All this can have significant economic implications. Researches published in the literature over the past years have shown that psychopathy, ADHD 102

4 Romanian Journal of Psychiatry, vol. XII, No.3, 2010 and brain dysfunction are all associated with persistent antisocial behavior (42). Compared to non-psychopaths subjects, psychopaths were identified as having ADHD at a 5-6 times higher rate. Studies of ADHD and recidivism generally indicate that it is associated with greater risk of psychopathy, repeated antisocial behavior, and recidivism (43-45). ADHD related more to general recidivism than to sexual offense recidivism. The impulsiveness of the ADHD individual may be a factor that leads them to engage in a variety of criminal acts, not thinking through the consequences of their behavior, whereas specific deviant sexual needs may primarily drive sex offense recidivism(46). DISCUSSIONS The reasons behind the fact that the history of this diagnosis (ADHD) is so recent (compared to other disorders, like affective disorders which have been known since antiquity) are, at least partially, due to the fact that ADHD symptoms can sometimes be generally attributed to the human behavior. It is less likely to find persons that have never been impulsive, inattentive or have never had difficulties with organizing specific tasks. What brings the need of diagnosis and treatment of ADHD is the presence of these symptoms for a long enough time and significant deterioration in social, family or professional functioning. That this disorder may persist in adulthood was recognized only in 1987 with the advent of DSM-III-R. Today it has been proved that this pathology without appropriate treatment can have a prolonged development, resulting in functionality under the expected parameters for the intelligence level of the concerned person. 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