Progress in Neuro-Psychopharmacology and Biological Psychiatry
Volumetric differences in the pituitary between drug-naïve and medicated male patients with obsessive–compulsive disorder
Introduction
Obsessive–compulsive disorder (OCD) is characterized by recurrent and persistent thoughts, impulses, images, and/or repetitive behaviors. Obsessions cause marked anxiety or distress, and OCD is a stress-responsive disorder with increased symptoms during stressful events (Findley et al., 2003, Zohar et al., 1991). Cromer et al. (2007) reported that traumatic life events were associated with severity of OCD. In addition, the hypothalamic-pituitary-adrenal (HPA) axis is an important regulatory system of the physiological stress response (Sapolsky et al., 2000), and the pituitary gland is a central component of the HPA axis. The hypothalamus releases a corticotrophin releasing hormone (CRH) to induce secretion of an adreno-corticotropin hormone (ACTH) from the anterior pituitary; in turn, ACTH stimulates the adrenal gland to release cortisol. The control and release of hormones is governed by hypothalamic releasing factors and feedback loops (Wilson et al., 1998).
In patients with OCD, elevated cortisol levels in plasma (Catapano et al., 1992, Kluge et al., 2007, Monteleone et al., 1994), increased urinary free cortisol levels (Gehris et al., 1990), and higher CRH levels in cerebrospinal fluid (Altemus et al., 1992), indicating increased activity in the HPA axis have been reported. Patients with OCD can also exhibit non-suppression of cortisol during suppression tests, suggesting increased activity in the HPA axis (Catapano et al., 1990, Cottraux et al., 1984). Bailly et al. (1994) interpreted the blunted ACTH secretion after CRH administration to indicate possible desensitized pituitary due to permanently elevated CRH levels in patients with OCD. Although results are inconsistent (Chappell et al., 1996, Weizman et al., 1990), dysregulation of the HPA axis has been reported in patients with OCD.
Few magnetic resonance imaging (MRI) studies have examined pituitary morphology in patients with OCD. One study of 31 pediatric drug-naïve patients with OCD (MacMaster et al., 2006a) found that these patients had a significantly smaller (11%) pituitary volume compared to control subjects. Smaller pituitary volume has also been reported in patients with eating disorder, which is classified as obsessive–compulsive spectrum disorders (Doraiswamy et al., 1991). However, to our knowledge, no studies have examined pituitary volume in adult patients with OCD.
Studies have consistently shown that females tend to have larger pituitary volume than males at all ages, including pubertal age (Elster et al., 1990, MacMaster et al., 2007b, Suzuki et al., 1990). MacMaster et al. (2006a) reported that pediatric male patients with OCD and control boys had significantly smaller pituitary volumes than pediatric female patients with OCD (31% smaller) and control girls (21% smaller). Another study found that in both genders, pituitary volume was the largest during puberty; this hyperplasia has been suggested to reflect the physical hypersecretion of pituitary hormones at puberty (Elster et al., 1990). Pituitary volume tends to decrease with increasing age after adolescence, but increases during pregnancy and the early postpartum period (Dinc et al., 1998).
Other studies have found that medication can influence pituitary volume. Typical antipsychotic medications increased pituitary volume in patients with first-onset psychotic episode (Pariante et al., 2005). MacMaster et al. (2007b) reported significantly increased pituitary volume in patients with schizophrenia after they were treated with antipsychotic medication (12% increase).
Considering these influences of gender and medication, we measured the pituitary volume of male patients with OCD, divided into drug-naïve and medicated groups, by using MRI. We hypothesized that drug-naïve patients with OCD would have a smaller pituitary volume compared to control subjects and medicated patients with OCD would have a larger pituitary volume compared to drug-naïve patients.
Section snippets
Subjects
We recruited 62 male patients from the OCD clinic at Seoul National University Hospital and divided them into medicated (N = 50) and drug-naïve (N = 12) groups. Patients' diagnoses were based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) (American Psychiatric Association, 1994) for OCD using the Structured Clinical Interview for DSM-IV (SCID-I) (First et al., 1996). Durations of illness for medicated patients and drug-naïve patients were 7.3 ± 6.2 years and
Results
Overall, we found no significant difference in pituitary volume between male control subjects (543.0 ± 113.7 mm3) and male patients with OCD (both medicated and drug-naïve patient groups; 556.0 ±126.4 mm3, P = 0.70). However, pituitary volume differed significantly between drug-naïve and medicated patients with OCD and control subjects; post hoc analysis using age and ICV as covariates revealed that pituitary volume was significantly smaller in drug-naïve male patients with OCD (465.0 ± 55.8 mm3)
Discussion
To our knowledge, this is the first study using MRI to identify differences in pituitary volume between drug-naïve and medicated adult male patients with OCD. Our findings suggest that reduced pituitary volume may be related to dysregulation of the HPA axis in adult drug-naïve patients with OCD, and that increased pituitary volume in medicated patients may reflect the effect of drugs on the pituitary.
A previous study found that activation of the HPA axis in psychiatric patients, as manifested
Conclusions
Our results suggest that dysregulation of the HPA axis might be influenced in patients with OCD and decreased pituitary volume might represent a biological marker not only in pediatric but also in adult drug-naïve patients with OCD, although longitudinal follow-up studies in drug-naïve patients with OCD will be helpful to determine long-term changes in pituitary volume. In addition, increased pituitary volume in medicated patients with OCD may reflect the effect of pharmacotherapy on the
Acknowledgment
This research was supported by a grant (M10644020003-08N4402-00310) from the Cognitive Neuroscience Program of the Korean Ministry of Science and Technology of the Republic of Korea.
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2016, Neurotoxicology and TeratologyCitation Excerpt :For example, smaller pituitary volumes have been noted in patients with obsessive-compulsive disorder (Atmaca et al., 2009; Jung et al., 2009), but larger volumes have been found in patients with first episode psychosis (Pariante et al., 2004; Büschlen et al., 2011). Furthermore, medications can impact pituitary structure (Jung et al., 2009; MacMaster et al., 2007a, Pariante et al., 2005). Caregivers reported that 73% of the alcohol-exposed subjects were using medication (e.g., psychostimulants, antidepressants, antipsychotics, anticonvulsants, or asthma/allergy treatments), supplementation (e.g., melatonin, GABA), or hormonal treatments (e.g., growth hormone, letrozole) versus only 15% of the control subjects (psychostimulants or asthma/allergy treatments).
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2013, Psychiatry ResearchCitation Excerpt :Pituitary volumes were significantly smaller in patients with OCD than in healthy controls (MacMaster et al., 2006; Atmaca et al., 2009). OCD patients who have never been treated with medications have smaller pituitary glands relative to the pituitary glands of people who are on medication or individuals without OCD (Jung et al., 2009). Medication may increase the size of the pituitary in people with OCD, and the increase in size may improve regulation of the body's stress response.
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2011, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Given these associations, it is reasonable to expect similar pituitary volume alterations in patients with PD but no study to date has evaluated the pituitary volumes in these patients. Our findings are also consistent with other previous studies showing reduced pituitary volumes in patients with obsessive–compulsive spectrum disorders, which are classified as an anxiety disorder (Atmaca et al., 2009, 2010; Doraiswamy et al., 1991; Jung et al., 2009; MacMaster et al., 2006a). Finally, it is possible that common pathological mechanisms associated with stress response mechanisms lead to shrinkage of the pituitary gland.
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2009, Journal of Psychiatry and NeuroscienceCitation Excerpt :However, unlike volumetric measures, categorical measures of gross morphology have been shown to be robust to minor differences between scanners,19 and there were no significant differences between the 2 scanners in the paracingulate sulcus classifications. In our previous study using the same 2 scanners, we also observed no differences in the pituitary volume of controls between MRI scanners.58 Our study was restricted to 1 specific brain region, and we did not calculate cerebral fissurization.