Brain structural correlates of depressive comorbidity in obsessive–compulsive disorder
Introduction
The prevalence of depressive symptoms in patients with obsessive–compulsive disorder (OCD) has been estimated in one to two thirds of all cases (Pigott et al., 1994) and, consequently, major depressive disorder (MDD) is often considered to be the major psychiatric comorbidity in OCD (Rasmussen and Eisen, 1992). Although such a high-rate of comorbidity in OCD has been linked to known clinical factors such as greater age, the severity and chronicity of OC symptoms or poor treatment response and outcome (Perugi et al., 1997), very little is currently known as to the underlying pathophysiological mechanisms of depressive episodes suffered by OCD patients.
From a neurobiological perspective, one obvious question regarding the depressive comorbidity of OCD patients is whether it may share similar pathophysiological features to that implicated in MDD alone (Saxena et al., 2001). Although existing data are limited, early work using positron emission tomography (PET) suggested that there might be certain pathophysiological correlates common to unipolar depression, bipolar depression and OCD patients with comorbid MDD (Baxter et al., 1989). Specifically, Baxter and colleagues reported a generalized reduction in the resting-state metabolism of the dorsolateral prefrontal cortex. More recently, this group has reported a pattern of reduced metabolic activity in the left hippocampal region common to MDD patients and patients with concurrent OCD and MDD, but not OCD patients alone (Saxena et al., 2001). Thus, such findings suggest that there may be some common pathophysiological alterations associated with depressive susceptibility in these subgroups, irrespective of patients’ primary clinical diagnoses.
In a recent magnetic resonance imaging (MRI) study carried out by our group, we characterized a pattern of brain structural alterations in a large series of OCD patients involving significant reductions of gray matter volume in the medial frontal gyrus (MdFG), the medial orbitofrontal cortex (mOFC) and the left insulo-opercular region, together with relative volume increases in the ventral striatum and anterior cerebellum (Pujol et al., 2004). In this particular study, no relationship was found between brain alterations in OCD patients and the severity of depressive symptomatology at the time of scanning, assessed by total Hamilton Depression Rating Scale score (HAM-D) (Hamilton, 1960), although we did not specifically study the association between patients’ history of lifetime depression and brain volumetric measurements.
Current epidemiological and clinical evidence suggests that OCD and MDD appear to co-occur in three major comorbidity patterns: (i) where OCD occurs first; (ii) where there is a concurrent onset of both OC and MDD symptoms; and (iii) where depression precedes the onset of OC symptoms (Demal et al., 1993). Thus, it is possible that our previous assessment of OCD patients’ depressive symptom severity using HAM-D scores may have failed to represent the actual incidence of MDD comorbidity. Therefore, in the current study, we conducted a region-of-interest (ROI) analysis to test the extent to which lifetime history of MDD may contribute to the previously described structural alterations in OCD (Pujol et al., 2004). We also extended our assessment by performing exploratory voxelwise analyses to investigate a possible association of MDD comorbidity with alterations in other brain areas and networks outside these regions.
Section snippets
Subjects
Seventy-two patients with OCD (32 women; mean ± SD age of 29.8 ± 10.5 years; range 18–60 years) and 72 control subjects (32 women, 30.1 ± 10.2 years, range 18–57 years), corresponding to the sample previously described (Pujol et al., 2004), were assessed in this study. Patients and control subjects were equivalent in the demographic variables of age, sex, and handedness (11 left-handed subjects per group) assessed by the Edinburgh Handedness Inventory (Oldfield, 1971; see Table 1).
The OCD group
Results
Table 1 presents the demographic and clinical characteristics of all three subjects groups. The three groups differed significantly in age, but did not differ in their gender ratio or handedness. OCD patients with lifetime MDD were older than patients with OCD alone. These patients also showed greater depressive symptom at the time of scanning (HAM-D scores) and had a longer illness duration. There were no significant differences between the two patient groups on total YBOCS score, presence of
Discussion
Our primary finding was that OCD patients with a lifetime history of MDD showed a more pronounced volume reduction in the mOFC. Interestingly, gray matter volume of the OFC showed an abnormal pattern of correlations with other relevant brain areas, involving the MdFG, insula and parahippocampal–amygdala complex in OCD patients with lifetime MDD, and the rostral anterior cingulate cortex in patients with OCD alone.
Dysfunction of the mOFC has been hypothesized in a range of neurological and
Acknowledgments
This study was supported in part by the Fondo de Investigación Sanitaria (Grants No.00/0226 and PI020102), the Fundació La Marató TV3, the Direcció General de Recerca de la Generalitat de Catalunya (Grants No. 1999SGR-328 and 2000XT-43) and by the Spanish Ministry of Health, Instituto de Salud Carlos III, Red de Enfermedades Mentales (REM-TAP Network). Dr. Harrison is supported by a NHMRC Training Award (I.D. 400420).
We thank Gerald Fannon, PhD, for revising the manuscript.
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