N-acetyl-l-aspartate values of hippocampus are reduced in patients with hypochondriasis ()
1. INTRODUCTION
Hypochondriasis, a somatoform disorder according to Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), preoccupation with fears of having, or the idea that one has, a serious disease based on the person’s misinterpretation of bodily symptoms despite repetitive medical evaluation and reassurance. In the etiology of hypochondriasis, psychosocial factors particularly psychodynamic explanations have been always leaded until last years. However, even though they are limited, investigations have been started to account for neurobiological basis of hypochondriasis. In this context, our research team also carried out some neuroradiological studies in hypochondriasis. One of them, we volumetrically evaluated the orbito-frontal cortex (OFC), anterior cingulate, caudate nucleus, and thalamus volumes in hypochondriac patients and determined that hypochondriac patients had significantly smaller mean left and right OFC, and greater left but not right thalamus volumes compared with healthy controls, without any differences on caudate and anterior cingulate volumes. So, in that investigation, we suggested that abnormalities in the OFC and thalamus might play an important role in the pathophysiology of hypochondriasis. In another structural study, we examined possible alterations in the pituitary anatomy in patients with hypochondriasis by means of quantitative MRI which was the first MRI investigation of pituitary of the patients with hypochondriasis [1]. We detected significantly smaller pituitary volumes of the group of hypochondriac patients compared with the those of o healthy controls concluded that this could be the keystone to a better understanding of the neurobiological basis of hypochondriasis. Magnetic resonance spectroscopy (MRS), increasing trend in psychoneuroradiology, is a safe and non-invasive technique for the in vivo study of brain chemistry and metabolism, which investigate basic brain metabolites such as N-acetyl-l-aspartate (NAA; a marker of neuronal viability), combined glutamate and glutamine, choline (CHO; a marker of cell membrane turnover), myo-inositol, and creatine (CRE; a marker of cellular energy). We previosly reported structurally hippocampal and amygdalar abnormalities OCD [2]. On the other hand, in a MRS investigation of hippocampus of OCD patients, we showed that OCD patients had a significant diagnostic effect for NAA/CHO, with a near-significant diagnostic effect for NAA/CRE and.concluded that these data might suggest a neuronal degeneration. Given that on the one side considerable similarities between hypochondriasis and OCD by means of sharing a number of features, including intrusive thoughts and repeated checking [3], on the other side similar structural neuroimaging data that found hypochondriac patients to have significantly smaller mean left and right OFC, and greater left thalamus volumes compared to those of healthy controls, we considered to investigate the hippocampal neurochemicals in hypochondriac patients.
2. METHODS
2.1. Subjects and Clinical Evaluation
Fifteen patients recruited from the psychiatric in or outpatient’s clinic, at the Firat University School of Medicine Department of Psychiatry in Elazig, and eighteen healthy controls who were all right handed, and had a mean age of 28.1 ± 3.4 and 30.6 ± 4.2 years, respectively, were the subjects of this study. Normal volunteers were recruited from the hospital staff. Diagnoses were made by using the Structured Clinical Interview for DSM-IV (SCID) [4]. Ratings of obsessive and compulsive symptoms, and depressive signs were ascertained using the Yale-Brown Obsession Compulsion Scale (Y-BOCS) and Hamilton Depression Rating Scale (HDRS), respectively. This study was carried out under guidelines of Helsinki Declaration. Written informed consent was obtained from all subjects. The exclusion criteria consisting of the presence of any current comorbid psychiatric disorder, current severe medical problems, problems that prevent suffering from MRI investigation, presence of any neurological disease, any worry about willingness to participate in the study procedures, expressed by providing written informed consent after complete description of the study, or alcohol/substance abuse within the 6 months preceding the study. Of the patients, one had lifetime history of major depressive disorder, and one had simple phobia. On the other hand, some criteria were administered to the healthy control subjects. For inclusion in the study, healthy subjects had to meet the following inclusion criteria: Not having DSM-IV Axis I disorders in self or in a first-degree relative, as determined by the SCID non-patient version, no current or previous history of medical problems, neurologic or psychiatric disorders, no previous history of severe mental retardation, alcoholism and drug dependence or abuse in the last 6 months, and willingness to participate in the study procedures, expressed by providing written informed consent after complete description of the study. If the patients and healthy control subjects fulfilled the inclusion criteria, they were asked to participate in the study.
2.2. Procedure
Briefly, MRI and 1H-MRSI scans were acquired using a GE Signa Excite 1.5 T whole body scanner (GE Medical Systems, Milwaukee, Wisconsin), with the following values (repetition time [TR] = 2000 ms, echo time [TE] = 15.6 ms, field of view [FOV] = 240 mm, flip angle = 200, bandwidth = 20.8, slice thickness = 2.4 mm, echo spacing = 15.6 ms, 8 echoes, resolution = 0.9375 × 0.9375 × 2.4 mm).
We investigated following neurochemical markers; NAA, CRE, and CHO. For all voxels, NAA, CHO, and CRE peaks were determined automatically. Position of hippocampal voxels and sample magnetic resonance spectrum are presented in Figure 1.
In addition to 1H-MRSI scans, hippocampus of the patients and healthy controls were structurally measured. In the tracings of the hippocampus, it was benefited from standard anatomic atlases [5-7] and from Caetano et al. [8] and Brambilla et al. [9]. As described earlier [2], for the tracing of hippocampus, the process was started on the coronal slice at the point that the superior colliculus
Figure 1. A sample spectrum, representing of the hippocampal region.
completely connected with the thalamus and finished one slice before the mammilary bodies appeared. The lateral border was accepted as the inferior horn of the lateral ventricle. As the superior border of the hippocampus, the corona radiata and ambient cistern were accepted. The inferior border was selected as the white matter.
2.3. Statistical Analysis
The statistical analyses were performed using SPSS version 13.0 (SPSS, Chicago, IL). Independent t test was used to assess differences in the volumes of hippocampus, whole brain, metabolite values, and some demographical data. Correlation analyses between volume measurements and clinical and demographic variables were carried out by means of Pearson’s correlation coefficients. For the camparisons of each metabolite ratio, NAA/CRE, NAA/ CHO, and CHO/CRE, independent t test was used. The criterion of significance level was set at p < 0.05.
3. RESULTS
Figure 2 displays the hippocampal neurochemical ratios of 1H MRS for the hypochondriac patients and healthy controls. On the other hand, no difference was found in regard to age (31.00 ± 5.13 for patients and 29.20 ± 5.99 for controls; t = 0.88, p > 0.05), gender (nine females and six males for patients and eight females and seven males for controls; p > 0.05), HDRS scores (9.47 ± 3.76 for patients and 7.20 ± 2.27 for controls; t = 1.99, p > 0.05) or whole brain volumes (1348.11 ± 51.23 for patients and 1358.59 ± 36.53 for controls; t = –0.65, p > 0.05).