Tourette’s and comorbid syndromes: Obsessive compulsive and attention deficit hyperactivity disorder. a common etiology?
Introduction
TOURETTE’S SYNDROME (TS) is a disorder of childhood onset characterized by simple and/or complex motor and vocal tics. Tics are usually defined as repetitive, stereotyped movements or vocalizations that are “involuntary” (Singer & Walkup, 1991), although more recent clinical observation suggests that some of the repetitive behaviors in TS are voluntary in nature (Miguel et al., 1997). At onset, which is predominantly before 10 years of age, the TS patient typically exhibits one or two simple motor tics, such as eye blinking or neck movements. These symptoms progress over time and usually become more severe and complex (Bornstein, King, & Carroll, 1983). More complex tics include touching objects, squatting, twirling while walking, retracing steps, and hopping. Vocalizations include inarticulate sounds, such as barking, coughing, and grunting, as well as the more complex palilalia (repetition of one’s own words/phrases), echolalia (the repetition of another’s words or phrases), and coprolalia (uttering of obscenities).
A diagnosis of TS occurs in approximately 1 in 1,500 children (Cohen, Riddle, & Leckman, 1992). Familial studies suggest that TS is an autosomal dominant disorder with incomplete penetrance and variable expressivity affecting males 3 times more commonly than females. The latter are more likely to exhibit obsessive-compulsive (OC) behaviors, with or without tics (Eapen, Pauls, & Robertson, 1993). Behaviors such as hyperactivity, impulsivity, and distractibility are also commonly associated with TS (American Psychiatric Association, 1994), which has led to speculations regarding possible genetic links between TS and ADHD.
Obsessive-Compulsive Disorder (OCD) is characterized by the presence of obsessions and/or compulsions that the patient perceives to be excessive at some time during the disorder. Prevalence of OCD in the general population has been estimated at around 1 to 2%, according to epidemiological studies Rasmussen & Eisen 1994, Whitaker et al. 1990, and this may be an underestimation due to a general reluctance for patients to admit to obsessions and compulsions during general screening techniques (Rasmussen & Eisen, 1992). OCD may occur in childhood, however, it more commonly begins to manifest in late adolescence or early adulthood Angst 1994, Leonard et al. 1992.
Obsessions are defined as recurrent and persistent thoughts, impulses, or images that are perceived as intrusive and inappropriate, and that may cause anxiety (American Psychiatric Association, 1994). Common obsessive thoughts include fears of harm/injury to self or loved ones and fears of contamination by dirt or germs Leonard et al. 1992, Singer & Walkup 1991. Compulsions are repetitive and seemingly purposeful behaviors that are usually, but not always, performed in response to an obsession, in a stereotyped fashion or in accordance with certain rules Flament 1994, Rapoport et al. 1995. Typical compulsions include excessive cleaning (e.g., repeated handwashing, showering), checking rituals, reordering or arranging habits, repeating rituals, and counting Leonard et al. 1992, Singer & Walkup 1991. The OCD patient often feels driven to perform these behaviors to neutralize distress associated with the obsessions or prevent a certain stressful situation.
Attention deficit hyperactivity disorder (ADHD) is a complex syndrome whose etiology remains largely unknown. Its primary symptoms include impulsivity, distractibility, and hyperactivity, with additional symptoms including emotional lability and short attention span (Ratey, Middledorp-Crispijn, & Leveroni, 1995). Increasing evidence suggests that problems of failing to inhibit impulsive actions and difficulty in focusing and sustaining attention may be due to a disturbance in frontal lobe function Castellanos et al. 1996, Heilman et al. 1991, Lou et al. 1989, Zametkin et al. 1990, and the most recent theories of ADHD have been developed with this in mind (Barkley, 1997). Frontal lobe involvement is supported by clinical observations of executive-function deficits, such as increased spontaneity, the inability to operate in favor of a remote or abstract reward, a decreased capacity to self-monitor behavior, a decreased ability to respond to stimuli or follow commands, and difficulty maintaining sustained attention Gualtieri 1995, Ratey et al. 1995. For a diagnosis of ADHD, the onset of the disorder is usually before the age of 7 years, though between 30 and 60% of child ADHD sufferers continue to exhibit clinical symptoms in adulthood (Ratey et al., 1995).
Section snippets
Clinical comparison of ts, ocd, and adhd
TS and OCD have many common clinical features. TS follows a similar progression to OCD in that both patients usually suffer initially from only simple motor tics/obsessions and compulsions followed by more complex tics and vocalizations or more severely disturbing obsessions and compulsions as the disorder progresses (Como, 1995). TS typically has an onset before the age of 10, while OCD usually develops prior to the age of 15. In both disorders, repetitive behaviors are considered by some to
Frontal and Striatal Neuroimaging Studies
An underlying assumption in the functional imaging literature is that regional cerebral blood flow (rCBF) directly reflects cerebral metabolism, and, therefore, function, in a particular region of the brain (Velakoulis & Pantelis, 1996). Cerebral blood flow correlates highly with cerebral metabolism (Baron et al., 1982), and most of the reviewed functional imaging literature has assumed that this is also the case for TS, OCD, and ADHD (see Table 1).
Volumetric magnetic resonance imaging (MRI)
Neural stimulation studies and psychosurgery
In addition to the neuroimaging literature, other research that provides a wealth of evidence regarding possible pathological substrates for each disorder, are neural stimulation and lesioning studies. For example, electrical stimulation of the anterior cingulate cortex in humans leads to execution of complex, tic-like coordinated movement patterns that are difficult to inhibit (Talairach et al., 1973). Typical responses include touching, leaning, stretching, and rubbing, which are often
Neurochemical abnormalities
A biochemical abnormality at specific locations within the BGTC circuit(s) could conceivably produce symptoms of TS (Singer & Walkup, 1991). Neurotransmitter systems, such as the cholinergic, serotonergic, dopaminergic, and noradrenegic systems, form extrinsic connections with BGTC circuits, and can thus regulate activity within these parallel segregated circuits (Leckman et al., 1997).
Most commonly implicated in TS are the catecholamines, which include the dopaminergic, serotonergic and
Neuropathological considerations and comorbidity
It is apparent when reviewing the wealth of recent neuroimaging, lesion, and neurochemical literature that TS, OCD, and ADHD may result from aberrant functioning of specific BGTC pathways, whose neuroanatomic organization is thought to involve a series of parallel circuits, each encompassing relatively discrete nonoverlapping parts of the striatum, globus pallidus, substantia nigra, thalamus, and cortex (Alexander, DeLong, & Strick, 1986). Within each of these circuits, information is
Genetics and comorbidity
TS has recently been described as a complex neuropsychiatric spectrum disorder, intimately associated with OCD, as well as with other behavioral disorders Cohen et al. 1992, Comings 1995, Eapen et al. 1993. The majority of familial studies suggest that the mode of transmission of TS is autosomal dominant with incomplete penetrance Curtis et al. 1992, Eapen et al. 1993. Studies of large kindreds of TS may provide insight into the characteristics of a genetically “pure” form of the disorder.
Concluding remarks
The similarity of the primary symptoms of TS and OCD is striking; OCD is sometimes considered as the cognitive counterpart to the motor disorder TS, with, respectively, involuntary cognitions as opposed to sensory phenomena preceding the repetitive behaviors. Notably all three conditions may be considered disorders of disinhibition: TS and OCD are associated with failures to inhibit voluntary and involuntary repetitive behaviors; ADHD a failure to inhibit socially unacceptable behavior, verbal
References (102)
- et al.
The genetic susceptibility to Gilles de la Tourette syndrome in a large multiple affected British kindredLinkage analysis excludes a role for the genes coding for dopamine D1, D2, D3, D4, D5 receptors, dopamine beta hydroxylase, tyrosinase, and tyrosine hydroxylase
Biological Psychiatry
(1995) - et al.
Pharmacotherapy of Tourette’s syndrome and associated disorders
Pediatric Psychopharmacology
(1992) - et al.
Elevated frontal cerebral blood flow in Gilles de la Tourette’s syndromea 99 Tcm-HMPAO SPECT study
Psychiatry Research
(1992) - et al.
Regional 133Xenon cerebral blood flow and 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment
Biological Psychiatry
(1995) - et al.
Site and size of lesion and psychosurgical outcome in obsessive-compulsive disorderA magnetic resonance imaging study
Biological Psychiatry
(1996) - et al.
Increased right caudate nucleus size in obsessive-compulsive disorderdetection with magnetic resonance imaging
Psychiatry Research: Neuroimaging
(1992) - et al.
Attention deficit hyperactivity disorder and the frontal lobe syndrome
Brain and Cognition
(1992) - et al.
The cingulate gyrus and human behavior
Electroencephalography and Clinical Neurophysiology
(1973) - et al.
Behavioral laterality in individuals with Gilles de la Tourette’s syndrome and basal ganglia alterationsA preliminary report
Biological Psychiatry
(1995) - et al.
Basal ganglia-thalamocortical circuitsParallel substrates for motor, oculomotor, “prefrontal” and “limbic” functions
Parallel organization of functionally segregated circuits linking basal ganglia and cortex
Annual Review of Neuroscience
The epidemiology of obsessive compulsive disorder
Cingulotomy for intractable obsessive-compulsive disorder. Prospective long-term follow-up of 18 patients
Archives of General Psychiatry
Cingulotomy in a case of concomitant obsessive-compulsive disorder and Tourette’s syndrome
Archives of General Psychiatry
Behavioral inhibition, sustained attention, and executive functionsConstructing a unified theory of ADHD
Psychological Bulletin
Frontal lobe functions in attention deficit disorder with and without hyperactivityA review and research report
Journal of Abnormal Child Psychology
Non invasive measurement of blood flow, oxygen consumption and glucose utilization in the same brain regions in man by positron emission tomography
Journal of Nuclear Medicine
Local cerebral glucose metabolic rates in obsessive-compulsive disorderA comparison with rates in unipolar depression and in normal controls
Archives of General Psychiatry
Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder
Archives of General Psychiatry
Obsessive-compulsive disorder associated with brain lesionsclinical phenomenology, cognitive function, and anatomic correlates
Neurology
Changes in metabolism of cerebral glucose after stereotactic leukotomy for refractory obsessive-compulsive disorderA case report
Journal of Neurology, Neurosurgery and Psychiatry
Neuropsychological abnormalities in Gilles de la Tourette’s syndrome
Journal of Nervous and Mental Disease
The functional neuroanatomy of Tourette’s syndromean FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls
Neuropsychopharmacology
Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder
Archives of General Psychiatry
Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder
Archives of General Psychiatry
Gilles de la Tourette syndromestudies with the Fluorine-18–labelled fluorodeoxyglucose positron emission tomographic method
Annals of Neurology
Structural and functional studies of Gilles de la Tourette syndrome
Revue Neurologique
Tourette’s syndromeA behavioral spectrum disorder
Obsessive-compulsive disorder in Tourette’s syndrome
Autosomal dominant gene transmission in a large kindred with Gilles de la Tourette Syndrome
British Journal of Psychiatry
Neurological examination
The response of ADD children to reinforcementtheoretical and clinical implications
Evidence for autosomal dominant transmission in Tourette’s syndrome
British Journal of Psychiatry
Gilles de la Tourette syndrome and attention deficit hyperactivity disorderNo evidence for a genetic relationship
Neuropsychiatry, Neuropsychology, and Behavioral Neurology
The metabolic anatomy of Tourette’s syndrome
Neurology
Recent findings in childhood onset obsessive compulsive disorder
Obsessions in obsessive-compulsive disorder with and without Gilles de la Tourette’s syndrome
American Journal of Psychiatry
Quantitative morphology of the corpus callosum in attention deficit hyperactivity disorder
American Journal of Psychiatry
Comparative effects of methylphenidate and thioridazine in hyperkinetic children I. Clinical results
Archives of General Psychiatry
Normative data on Revised Conners Parent and Teacher Rating Scales
Journal of Abnormal Child Psychology
The psychology of fear and stress
Tourette syndrome and obsessive-compulsive disorder
The contribution of the frontal lobes to a theory of psychopathology
Brain perfusion patterns with Tc-99mHMPAO/SPECT in patients with Gilles de la Tourette’s syndrome [Abstract]
European Journal of Nuclear Medicine
A possible pathophysiologic substrate of attention deficit hyperactivity disorder
Journal of Child Neurology
Outcome after the psychosurgical operation of stereotactic subcaudate tractotomy
Journal of Neuropsychiatry
Cerebral morphometric abnormalities in Tourette’s syndromeA quantitative MRI study of monozygotic twins
Neurology
Attention deficit hyperactivity disorder and asymmetry of the caudate nucleus
Journal of Child Neurology
Functional organisation of the dopamine system in normal and abnormal behaviour
Advances in Neurology
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