This page contains a Flash digital edition of a book.
Substance use disorder in adult Tourette syndrome

and behavioral impulsivity likely resulting from dysfunction of the orbitofrontal circuit 57,58 while comorbid ADHDmay relate to dysfunction of the dorsolateral prefrontal and anterior cingulate (AC) circuits.59,60 Insights of this nature concerning the shared pathobiologic bases for primary symptoms and associated psychiatric disorders in TS have implications both for diagnostic classification and for treatment.55

Similar observations have prompted discussion regarding

the true nature of, and basis for, the ‘‘comorbidities’’ accompanying substance abuse. Thus, appreciation of overlap of the biological substrates and of the neurophysiology of addictive process on the one hand and psychiatric symptoms associated with addiction on the other has suggested that specific mood, anxiety, and impulse-control dimensions should be incorporated into the nosology of addiction.16

Of relevance to this discussion is the recognition that certain components of TS-related frontalsubcortical circuitry are shared by the drug reward circuit. Principal elements of the latter circuit are the A10 dopaminergic cell group of the ventral tegmental area, the mesocorticolimbic dopamine system, and the limbic structures of the basal forebrain, namely, OF cortex, AC cortex, and ventral striatum, particu- larly shell of the nucleus accumbens.61 Some of these brain regions, including the limbic region and prefrontal and OF cortices, are also involved in the regulation of mood and aggressive behavior.6264 Moreover, just as frontal lobe abnormalities have been identified in TS,5,56,6572 panic disorder appears to be characterized by deficits in the prefrontal inhibitory control over a hyperactive limbic cir- cuit.73,74 Thus, frontalsubcortical circuit dysfunction, in- cluding disordered limbic circuitry, is common to substance abuse, TS, TS-related mood lability (rage reactions), and panic disorder. This is likely to underlie the interrelationships that we and others have noted between these disorders and has implications for a more unifying conceptualization of psychiatric comorbidities not only in TS but also in other neuropsychiatric disorders.

Although dysfunction of parallel but interconnected frontal subcortical circuits and their modulating neurotrans- mitter systems (especially mesolimbic dopamine) may under- lie the complex behavioral manifestations and comorbidities of TS, including associated SUD, there is also an opportunity for one linked condition and/or its treatment to interact with another. Importantly in this regard, our findings support other data that suggest that SUD in TS may both drive and be driven by tics, as exemplified by the recognized aggravation of tics by cocaine, on the one hand,17 and their potential amelioration by cannabis, benzodiazepines, or alcohol, on the other.1820 Several of the substances abused by our patients have the potential to ameliorate tics or anxiety and likely became preferred drugs of abuse for this reason. However, the development of cocaine abuse in four of our patients indicates the potential for development of a particu- larly self-destructive pattern of drug abuse in some TS patients. Although severe SIB was only exhibited by three of our patients, we were not able to exclude the possibility that 13

severe SIB in TS might, in some cases, lower the threshold for cocaine dependence and polysubstance abuse.

Limitations of this study include its retrospective nature,

possible referral bias, lack of utilization of a more widely accepted standardized interview for SUD such as the Addiction Severity Index,75 the relatively small number of study patients, and the limited use of formal psychiatric rating instruments, especially for assessment of mood disorders. However, our results support previous data concerning the frequency of SUD in TS and offer consistent evidence that mood and impulse dysregulation in the form of panic disorder and rage attacks may be useful markers for potentially serious SUD risk in TS. Corroboration of these results in a larger patient population would strengthen the utility of such predictors in clinical practice.

Based on our findings, it is recommended that adult TS patients be routinely screened for SUD, with heightened vigilance in the case of patients with history of affective and behavioral instability, especially panic disorder or rage attacks. Of the common drugs of abuse, benzodiazepines in particular may have substantial efficacy for tics and anxiety in TS but have significant abuse potential and require close monitoring. Considering the relative frequency of narcotic abuse in our series, caution should also be used in the choice of analgesic therapy in TS patients, especially those with chronic pain. Equally, it should be recognized that satisfac- tion of emergent drug craving, which has been compared to tic-related sensory-motor craving-and-relief cycles,14 will typically supercede the need for control of sensory urges and tics, such that even severely affected TS patients may become dependent upon drugs such as cocaine, with potentially disastrous consequences for their tic disorder. Our experience underscores the importance of considering possible cocaine abuse in all poorly controlled adults with TS.

Disclosure: The author declares no conflict of interest.

REFERENCES 1. Coffey B, Park K. Behavioral and emotional aspects of Tourette syndrome. Neurol Clin. 1997;15(2):277289.

2. Robertson M, Orth M. Behavioral and affective disorders in Tourette syndrome. Adv Neurol. 2006;99:3960.

3. Mink J. Neurobiology of basal ganglia circuits in Tourette syndrome: faulty inhibition of unwanted motor patterns? Adv Neurol. 2001;85:113 122.

4. Mink J. Neurobiology of basal ganglia and Tourette syndrome: basal ganglia circuits and thalamocortical outputs. Advances in Neurology. 2006;99:8998.

5. Ziemann U, Paulus W, Rothenberger A. Decreased motor inhibition in Tourette’s disorder: evidence from transcranial magnetic stimulation. Am J Psychiatry. 1997;154(9):12771284.

6. Stern E, Blair C, Peterson B. Inhibitory deficits in Tourette’s syndrome. Dev Psychobiol. 2008;50(1):918.

7. Jankovic J, Kwak C, Frankoff R. Tourette’s syndrome and the law. J Neuropsychiatry Clin Neurosci. 2006;18:8695.

8. Kurlan R, Daragjati C, Como P, et al. Non-obscene complex socially inappropriate behavior in Tourette’s syndrome. J Neuropschiatry Clin Neurosci. 1996;8:311317.

9. Comings D. Genetic factors in substance abuse based on studies of Tourette syndrome and ADHD probands and relatives. I. Drug abuse. Drug Alcohol Depend. 1994;35:116.

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

Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89