Obsessive Compulsive Disorder

Adult OCD has been summarized in Chapter 13 of this volume. Herein we will address the childhood variant as an expression of vulnerability genes for TS and relevant brain imaging findings for this condition.

All forms of OCD are characterized by recurrent, distressing, and intrusive thoughts, images, or urges to action, together with their repetitive behavioral counterparts. Usually, performance of the compulsion brings some degree of relief from the urge to action and from the anxiety associated with the imagined consequences of failing to perform the compulsion.

Several large factor analytic studies have confirmed the presence of at least four main components to OCD symptoms: (1) aggressive, sexual, religious, and somatic obsessions, and checking compulsions; (2) symmetry and ordering; (3) cleanliness and washing; and (4) hoarding (Baer, 1994; Leckman et al., 1997). The age of onset of OCD in the general community is probably bimodal, with one mode of onset at 10 to 12 years of age and the other in early adulthood (Rasmussen and Tsuang, 1986; Berg et al., 1989; Valleni-Basile et al., 1996; Geller et al., 1998). The childhood-onset form of OCD most commonly occurs in the context of a personal history of a tic disorder, and it occurs even more commonly in the context of a personal or family history of tic disorder (this is the so-called tic-related form of OCD). The adult-onset form of OCD, in contrast, is much less likely to occur in the context of a personal or family history of tics, while the early onset form appears to be more strongly familial (Pauls et al., 1995).

The symptoms of the tic-related form of OCD are significantly more likely to be those of the first or third of the factor-based groupings listed previously, whereas the non-tic-related form is more likely to involve symmetry and ordering (Leckman et al., 1997). When present together, the severities of OCD and tic symptoms have been shown to covary with one another, suggesting an underlying common modulator of severity over the short term (Lin et al., in press). In contrast to tics, childhood-onset OCD symptoms over the long term tend more often to persist into late adolescence and adulthood, and they are usually more functionally debilitating than are tics alone (Swedo et al., 1989a; Leonard et al., 1990).

Genetics. Segregation analyses suggest the presence of genes of major effect, although the mode of transmission is likely to be complex (Alsobrook et al., 2002). Linkage and association studies of childhood-onset OCD have been initiated, but few findings have been reported thus far. Candidate genes related to the serotonin system have received the greatest attention, with few significant findings reported. The strongest evidence for linkage in a preliminary study of 7 families with childhood-onset

OCD was on chromosome 9 (9p, LOD = 1.97), with weaker evidence for linkage on 19q (Hanna et al., 2002). In addition, an analysis of 77 sib-pairs with TS suggested significant joint effects of specific loci on 4q and 5q for developing the obsessive-compulsive symptom of hoarding (Zhang et al., 2002).

Neurochemistry. Virtually no studies of norepinephrine or dopaminergic systems have been reported in children with OCD. Data relevant to serotonin systems derives from the efficacy of serotonergic medications in the treatment of children with OCD (March et al., 1998; Liebowitz et al., 2002). Studies of glutamate and glutamine have been more extensive. An MRS study has reported elevated GLX (combined glutamate and glutamine) concentrations in the caudate nuclei of treatment-naive children who have OCD but no tics, and these caudate GLX concentrations normalized after a 12-week course of antiobsessional treatment with paroxetine (Rosenberg et al., 2000b) but not behavioral therapy (Benazon et al., 2002). Changes in GLX concentrations in the caudate correlated positively with changes in OCD symptom severity during paroxetine treatment, suggesting that elevated pretreatment GLX concentrations in the caudate may predict treatment response to serotonergic medications.

Cerebrospinal fluid studies of children have suggested that arginine vasopressin may be inversely associated with the severity of OCD symptoms (Swedo et al., 1992a). A subsequent study of adults (many with childhood-onset illness) failed to find group differences in vasopressin but did report elevated CSF levels of a related peptide, oxytocin, in individuals with OCD (Leckman et al., 1994). Yet another study failed to find group differences in oxytocin in the CSF associated with a diagnosis of OCD (Altemus et al., 1994). Finally, intranasal administration of oxytocin in adults with OCD in a placebo-controlled crossover study did not affect OCD symptoms (Epperson et al., 1996). Clearly, disturbances in these neuropeptide systems have not proved to be reproducible, leaving unclear the role of these compounds in the etiology of OCD.

Neurobiological Substrate. Structural and functional imaging studies implicate orbitofrontal portions of CSTC circuits in the pathophysiology of OCD. Hyperme-tabolism and elevated blood flow in prefrontal cortices are probably the most consistent findings in subjects with OCD. Furthermore, the severity of OCD symptoms correlates positively with resting prefrontal and orbitofrontal metabolism in adults (Swedo et al., 1992b). In response to successful antiobsessional therapies, hypermetabolism normalizes (Rubin et al., 1995), and the improvement in symptoms correlates with the decrement in blood flow or metabolism in most (Hoehn-Saric et al., 1991; Swedo et al., 1992b) but not all studies (Baxter et al., 1992; Schwartz et al., 1996). Conversely, symptom provocation increases blood flow in orbitofrontal regions (Rauch et al., 1994; Breiter et al., 1996). Despite these functional abnormalities in orbitofrontal cortices, prefrontal volumes seem to be normal in subjects with OCD (Robinson et al., 1995), although increased volumes of the anterior cingulate cortex have been reported in children (Rosenberg and Keshavan, 1998).

In the basal ganglia, the most consistent functional abnormalities reported in OCD have been elevated metabolism and blood flow in the right caudate nucleus both at rest (Baxter et al., 1988) and during symptom provocation (Rauch et al., 1994; Breiter et al., 1996). Caudate nucleus hypermetabolism appears to normalize in response to successful antiobsessional treatment (Baxter et al., 1992; Schwartz et al., 1996). Volumetric findings in the caudate nucleus are inconsistent, but the largest and most rigorous studies report volume reductions bilaterally (Luxenberg et al., 1988; Robinson et al., 1995), and they correlate inversely with the severity of OCD symptoms. In adults performing an attentional task, factor-based scores for OCD symptoms associated with tics (described previously) correlated only with blood flow to the striatum (Rauch et al., 1998), whereas non-tic-related OCD symptoms correlated significantly with flow in a variety of prefrontal regions, most strongly in the prefrontal cortex. Tic-related symptoms, in other words, were associated with basal ganglia functioning, whereas non-tic-related symptoms were associated with prefrontal functioning.

Increased volumes of the thalamus, another key structure in CSTC circuitry, have been reported at pretreatment baseline in OCD children (Gilbert et al., 2000). These volumes normalized after 12 weeks of treatment with paroxetine but not behavioral therapy (Rosenberg et al., 2000a). Abnormal levels of N-acetylaspartate (NAA, a measure of neuronal viability) (Birken and Oldendorf, 1989) were localized to the medial portion of the thalamus in these same children (Fitzgerald et al., 2000).

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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