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Mind & Brain, the Journal of Psychiatry


Table 2. Comparison of Comorbidities in Subjects With and Without a History of Substance Use Disorder


Comorbid Disorder Childhood ADHD


Adult ADHD OCD


Obsessional worrying/anxiety disorder NOS


Generalized anxiety disorder Panic disorder* Social phobia


Depressive disorder$ Bipolar disorder Rage attacks SIB


Severe SIB SUD SUD


8 (53.3%) 15 (29.4%) 5 (33.3%) 10 (19.6%) 9 (60.0%) 31 (60.8%) 4 (26.7%) 5 (8.2%)


4 (26.7%) 7 (11.5%) 5 (33.3%) 3 (4.9%) 1 (6.7%) 3 (4.9%) 4 (26.7%) 18 (35.3%) 3 (20.0%) 5 (9.8%) 4 (26.7%) 0 (0.0%) 3 (20.0%) 4 (7.8%) 2 (13.3%) 1 (2.0%)


p


0.09 0.30 0.96 0.19


0.25 0.01 1.00 0.95 0.37


0.0019 0.18 0.13


SUD, substance use disorder; ADHD, attention deficit-hyperactivity dis-


order; OCD, obsessive-compulsive disorder; SIB, self-injurious behaviors. *Agoraphobia accompanied panic disorder in two subjects, one with and one without SUD. The former patient also exhibited other specific phobias


(acrophobia, claustrophobia). $Depressive disorder included major depression (n12) and dysthymia (n10).


prevalence of life-time drug abuse and dependence to be 7.7% and 2.6%,28 respectively, comparable figures in our TS population being 13.6% and 6.0%, respectively. In contrast, the prevalence of life-time alcohol abuse and dependence in the National Epidemiologic Survey was 17.8% and 12.5%, respectively,28 compared with 10.6% and 0%, respectively, in our series. Considering the limited duration of follow-up for many of our study patients, our figures may be an under- estimate. Thus, these data suggest that SUD in adult TS involves primarily nonalcoholic substances, with such sub- stance abuse/dependence being approximately twice as com- mon as in the general population.


Consistent with the findings of Comings’ earlier studies,9, 10


tic severity was not an independent predictor of SUD risk in our population. However, in three of our patients, cocaine/ polysubstance abuse was associated with severe tics and severe SIB. This supports previous correlations of severe (but not mild) TS-related SIB with impulse dysregulation and risk- taking behavior.29


Nonmedical prescription drug use disorders are known to


be highly comorbid with other Axis I and II disorders. In particular, BD may share common genetic determinants with SUD30 and is a well-recognized risk factor for SUD in the general population.31 Although the association of SUD with BD fell short of statistical significance in our study, the phenomenon of rage attacks (also referred to in children or adults as episodic dyscontrol syndrome or intermittent explosive disorder32), a condition that is well characterized in TS,24,33,34 was observed only in subjects with SUD. Considering the conditions together, emotional instability


M&B 2011; 2:(1). July 2011 12


in the form of either rage attacks or BD was a strong unique predictor of SUD in the logistic regression analysis.


Some investigators have described an increased prevalence


of panic disorder and specific phobias in TS patients when compared with normal controls 1 and, in our series, SUD was also more common in TS subjects with panic disorder. This is consistent with associations noted for SUD in the general population, where symptoms related to the domains not only of impulse control but also of mood disorders, including anxiety, may precede drug abuse and represent a specific risk factor for addiction.16


Although ADHD is a predictor for SUD in the general population35,36 and appears to co-segregate with SUD in amanner suggestive of variable expressivity of a common risk factor,37 we found a nonsignificant trend only for increased frequency of childhood ADHD in subjects with SUD. This is consistent with findings of a previous study, which showed discipline problems but not ADHD to be a significant predictor of SUD in TS.9 Our SUD patients were also not more likely to exhibit residual adult ADHD, which was characterized primarily by attentional and executive dysfunc- tion and not by persisting neurobehavioral disinhibition.23 The latter construct has been linked with early age at onset of SUD 38 and, as originally defined in the pediatric population, includes affective dysregulation. In our adult population, such symptomatology was displayed predominantly by subjects with BD and rage attacks. OCD severity was also not a predictor of SUD in our series. This contrasts with the earlier findings of Comings 9,10 but is consistent with the currently accepted categorical separation of obsessive-compulsive spectrum disorders from drug addiction and impulse control disorders (the latter recognized by some as behavioral addictions).3945


Although the strength of our conclusions is limited by the


small size of the study population, these findings suggest that SUD in TS is primarily linked with disorders of affect and impulse control. The basis for this association may be shared neurobiological substrates for TS, habit formation, drug addiction, and certain affect and impulse control disorders, which involves dysfunction of corticostriato thalamocortical (frontalsubcortical) circuitry and the neu- rotransmitter systems modulating these circuits, particularly dopamine, serotonin, gamma-amino-butyric acid, and opioid pathways.40,41,4650


Aconvergence of data, including findings from structural and functional imaging studies, implicates abnormalities in tha- lamo-striatal, limbic, and cortical components of frontalsub- cortical circuitry in TS, with dysregulation of their component neurotransmitter systems.5154 It has been proposed that TS might reasonably be viewed as part of a spectrum of impulse control disorders, rooted in frontalsubcortical circuit dys- function, and that differences in the behavioral profile of TS patients might be related to the specific frontalsubcortical circuit affected.4,55 Thus, simple motor and vocal tics and sensory urges may reflect involvement of the motor circuit,56 more complex behaviors including compulsions or obsessions


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