- Top of page
Aims: Another structure in the obsessive–compulsive disorder (OCD) circuit may be the pituitary gland because of the fact that limbic–hypothalamic–pituitary–adrenal (LHPA) axis abnormality has been reported in patients with OCD. There has been only one prior study, however, concerning pituitary volumetry, in which the sample was a pediatric group. The purpose of the present study was therefore to investigate this in an adult OCD patient group using magnetic resonance imaging (MRI).
Methods: Pituitary volume was measured in 23 OCD patients and the same number of healthy control subjects. Volumetric measurements were made on T1-weighted coronal MRI, with 2.40-mm-thick slices, at 1.5 T, and were done blindly.
Results: A statistically significantly smaller pituitary volume was found in OCD patients compared to healthy controls (age and intracranial volume as covariates). With regard to gender and diagnosis, there was a significant difference in pituitary gland volume (F = 4.18, P < 0.05). In addition, post-hoc analysis indicated near-significant difference in men with OCD as compared with women with OCD (P = 0.07) and significant difference between control men and control women (F = 10.96, P < 0.001).
Conclusions: Taking into consideration that the prior study found decreases in pituitary volume in pediatric patients with OCD as compared with healthy control subjects, future large MRI studies should investigate pituitary size longitudinally, with a careful characterization of hypothalamo-pituitary-adrenal (HPA) function in conjunction with anatomic MRI evaluation.
OBSESSIVE–COMPULSIVE DISORDER (OCD) is a chronic and often disabling anxiety disorder and is characterized by intrusive unwanted thoughts, ideas, or images that are distressing (obsessions) and urges to perform ritualistic behaviors or mental acts (compulsions) to reduce this distress. Data from the Epidemiological Catchment Area survey and other epidemiological studies showed that the lifetime prevalence of OCD was between 2% and 3% in the general population.1
Structural and functional imaging studies suggest a model for the pathophysiology of OCD that includes volumetric abnormalities and hyperactivity in the fronto-subcortical neuronal pathway of the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC) and the caudate nucleus, sometimes called the ‘OCD circuit’.2 The findings regarding key brain regions from structural imaging studies have been inconsistent, with reports of increases in caudate nucleus,3 decreases in caudate nucleus, OFC and amygdala,4,5 or no differences in ACC, caudate nucleus and thalamus volumes.6–8 Recently Kang et al. measured the volumes of the OFC, ACC, thalamus, and caudate nucleus, which are the main components of the frontal subcortical circuitry in patients with OCD and in normal subjects.9 Other candidate structures, however, have been described. One of these structures may be the pituitary gland because of the fact that limbic–hypothalamic–pituitary–adrenal (LHPA) axis abnormality has been reported in patients with OCD.10–12 An increased activity of the HPA axis in OCD has been reported both indirectly (corticotropin-releasing hormone [CRH] levels in cerebrospinal fluid [CSF] were significantly higher in patients with OCD than in healthy controls10) and directly (Kluge et al. examined the blood of patients and controls every 20 min between 23.00 h and 7.00 h during sleep using a long catheter for later adrenocorticotropic hormone (ACTH) and cortisol analysis13). There has been only one study evaluating pituitary volumes in OCD patients.14 In that study the authors found that pituitary volume was significantly smaller in pediatric patients with OCD as compared with healthy control subjects (11% smaller). No study regarding pituitary volumes has been done in adult OCD patients, however. With this in mind, we therefore evaluated pituitary volume in adult patients with OCD and healthy controls and to determine whether smaller pituitary volume in patients with OCD might also be an epiphenomenon of the underlying psychopathology of the illness, as suggested by MacMaster et al.14
- Top of page
There were no significant differences between the groups on comparisons for age (mean age ± SD: patients, 29.8 ± 4.4 years; controls, 32.2 ± 5.7 years), education, gender (exactly same number men and women in each group) and ICV (patients, 1422.9 ± 111.4 mm3; controls, 1440.4 ± 123.6; P < 0.05). In the patient group, mean Y-BOCS score was 16.8 ± 3.1 (Table 1).
Table 1. Subject details
|Item||Patient group (n = 23)||Control group (n = 23)||P|
|Age (years)||26.9 ± 5.1||28.7 ± 3.7||>0.05|
|Education|| || ||>0.05|
| High school||13||16|| |
| Elementary school||5||3|| |
| First school||5||4|| |
|Length of illness (years)||4.6 ± 3.4||–|| |
|Total Y-BOCS score||16.8 ± 3.1||–|| |
|Gray matter volume (cm3)||761.5 ± 67.3||779.3 ± 78.8||>0.05|
|White matter volume (cm3)||459.7 ± 31.7||475.6 ± 48.8||>0.05|
|Pituitary volume (cm3)||0.691 ± 0.062||0.846 ± 0.073||<0.001|
| Male||0.673 ± 0.059||0.773 ± 0.081||<0.01|
| Female||0.719 ± 0.077||0.959 ± 0.089||<0.001|
Table 1 lists the unadjusted mean volumes of measured structures for OCD patients and healthy controls. We found significantly smaller pituitary volume in the whole group of OCD patients compared to healthy controls (age and ICV as covariates). With regard to gender and diagnosis, there was a significant difference in pituitary gland volume (F = 4.18, d.f. = 1, 42; P < 0.05). Post-hoc analysis indicated near-significant difference in men with OCD as compared with women with OCD (P = 0.07), and significant difference between control men and control women (F = 10.96, d.f. = 1, 24; P < 0.001).
We found a significant negative correlation between smaller pituitary volume and both duration of illness (r = −0.47, P < 0.05) and onset age (r = −0.44, P < 0.05) in the patient group. There was no correlation, however, between pituitary volume and severity of illness, as determined on Y-BOCS score (r = 0.17, P > 0.05).
- Top of page
The present study found statistically significantly smaller pituitary volume in patients with OCD compared to healthy controls and a significant negative correlation between smaller pituitary volume and both duration of illness and onset age. In addition, post-hoc analysis demonstrated that both men with OCD and control men had smaller pituitary volume compared to women with OCD and control women, respectively. The pituitary gland is a central part of the neuroendocrine system. Increased activity of the HPA axis in OCD is indicated by the finding that CRH levels in CSF were significantly higher in patients with OCD than in healthy controls.11 In contrast, Chappelli et al. found similar CRH levels in both groups.23 A non-suppression of cortisol secretion in the dexamethasone suppression test (DST) in patients with OCD also points to HPA hyperactivity.11,24 In the pathophysiology of OCD, abnormalities in the HPA axis have been reported due to cortisol non-suppression in the DST in patients with OCD,11,24 and due to the finding that CRH levels in CSF were found to be significantly higher in patients with OCD than in healthy controls,2 but these results were not confirmed in other studies.25–27 There was only one prior study on OCD patients with DST non-suppression13 and it found decreases in pituitary volume in patients with OCD as compared with healthy control subjects (11% smaller), as well as an association between decrease in pituitary volume and increased compulsive but not obsessive symptom severity. The present volumetric findings are in accordance with those of MacMaster et al.14 They speculated that this abnormality might be an early marker of the illness that might be related to the developmental pathophysiology of OCD and concluded that their findings were not consistent with a progressive process in OCD because they did not find any correlation between illness duration and age of onset of OCD. In the present study, however, we also found a significant association between smaller pituitary volumes and both the duration of illness and onset age in the patient group. Therefore, although the present study was also a cross-sectional one, as was the MacMaster et al. study, the aforementioned association suggests that this difference might be a degenerative and progressive process. Meanwhile although all patients did not take OCD medication for at least 2 weeks prior to the study, they took a variety of medications for their OCD including serotonin re-uptake inhibitors, lithium, antipsychotic drugs and so on. It is worth noting that these agents might have affected pituitary volume. For example, it has been demonstrated that antipsychotics may interact with the HPA axis by decreasing cortisol levels28,29 and that changes in endocrine function can affect pituitary morphology.30,31
Several points need to be considered when interpreting these results. First, the present sample, relatively small, may limit the generalizability of our findings, and replication of the results using larger samples is necessary. Second, the present study did not involve a longitudinal follow up. Third, because the sample size was small, it was not possible to determine whether there was an interaction between symptom dimensions and volumes. Finally, the use of 2.4-mm-thick slices should be acknowledged as a limitation.
In conclusion, the present study found significant smaller pituitary volume in adult OCD patients compared to healthy controls. Taking into consideration that a prior study found decreases in pituitary volume in pediatric patients with OCD as compared with healthy control subjects,14 future large MRI studies should investigate pituitary size longitudinally with a careful characterization of HPA function in conjunction with anatomical MRI evaluation.