Hanefi Yildirim

Volumetric MRI study of key brain regions implicated in obsessive-compulsive disorder

Neuroanatomic abnormalities have been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). To date, no study has measured the orbito-frontal cortex (OFC), anterior cingulate, caudate nucleus, and thalamus concurrently in first-episode patients. Thus, we performed a volumetric MRI study in patients who were treatment-naive and healthy controls focusing on the in vivo neuroanatomy of the whole brain, total gray and white matter volume, thalamus, caudate nucleus, anterior cingulate cortex, and OFC concurrently. The volumes of thalamus, caudate nucleus, anterior cingulate cortex, and OFC were measured in 12 OCD patients who were treatment-naive and 12 healthy control subjects. Anterior cingulate and OFC volumes included both white and gray matters. Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5 T. The patients had increased white matter volume than healthy controls. The patient group had significantly smaller left and right OFC volumes and significantly greater left and right thalamus volumes compared with healthy controls. Anterior cingulate exhibited a near-significant difference between the patients and healthy controls on left side. Significant correlations were found between Y-BOCS scores and left OFC, and right OFC, and between Y-BOCS and left thalamus volumes in the patient group. In conclusion, our findings suggest that abnormalities in these areas may play an important role in the pathophysiology of OCD.

Corpus callosum areas in first-episode patients with bipolar disorder

BACKGROUND Morphological changes in the corpus callosum (CC) have been described in bipolar disorder, but with inconsistencies among the reports. We investigated the CC areas by magnetic resonance imaging (MRI) in 12 first-episode patients with bipolar disorder and 12 controls. METHOD Twelve medication-naive patients with bipolar I disorder (six males, six females; aged 28 x 2+/-6 x 5 years) with manic or mixed episodes and 12 age- and gender-matched healthy controls (six males, six females; aged 26 x 8+/-7 x 6 years) were recruited to the study. MRI scans was obtained using a 1.5-T GE Signa Excite high-speed scanner. Anatomical measurements were conducted on a computer workstation with the software Scion Image Beta-3b for Windows. Statistical analysis was performed using an analysis of covariance (ANCOVA), the t test, chi2 and partial correlation analyses. RESULTS Bipolar patients had significantly smaller areas of total CC, anterior body posterior body and isthmus compared with healthy control subjects by ANCOVA, with age, gender and intracranial volume (ICV) as covariates. There was a negative correlation between total CC, posterior body and isthmus areas and Young Mania Rating Scale (YMRS) scores. CONCLUSION The findings suggest that CC morphology may be associated with the pathophysiology of bipolar disorder.

Hippocampus and amygdalar volumes in patients with refractory obsessive–compulsive disorder

Functional and structural neuroimaging studies have implicated the hippocampus-amygdala complex in the pathophysiology of obsessive-compulsive disorder (OCD), although no consensus has been established. These brain regions have not been investigated in refractory OCD patients. Volumes of the hippocampus, and amygdala were measured by magnetic resonance imaging (MRI) in a sample of 14 refractory OCD patients and 14 healthy comparison subjects. The mean left and right hippocampal and amygdala volumes of the patients were smaller than those of the healthy controls. OCD severity was not correlated with amygdala volumes but was related to the left hippocampus. Duration of illness was correlated with both hippocampus and left amygdala. Our findings suggest that hippocampus and amygdalar abnormalities can be considered in refractoriness to OCD.

Hippocampal 1H MRS in patients with bipolar disorder taking valproate versus valproate plus quetiapine.

BACKGROUND No study to date has examined the effects of mood stabilizer alone and the combination of mood stabilizer and atypical antipsychotic, quetiapine, on hippocampal neurochemical markers of bipolar disordered patients concurrently. We therefore undertook a proton magnetic resonance spectroscopy (1H MRS) study of drug-free patients with bipolar disorder (drug-free group), patients undergoing valproate treatment (valproate group), patients administered valproate+quetiapine (valprote+quetiapine group) and healthy controls, focusing on the in vivo neuroanatomy of the hippocampus. METHOD Thirty patients from the Firat University School of Medicine Department of Psychiatry and 10 healthy controls gave written informed consent to participate in the study. The patients and controls underwent proton magnetic resonance spectroscopic imaging (1H MRSI), and measures of N-acetylaspartate (NAA), choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in hippocampal regions were obtained. RESULTS The drug-free patients had significantly lower NAA/CRE and NAA/CHO ratios compared with the valproate and valproate+quetiapine groups and the healthy controls. The lower NAA/CRE and NAA/CHO ratios remained statistically significant even after covarying for age or whole brain volume compared with the valproate and valproate+quetiapine groups and healthy controls. In post hoc comparisons, a significant difference was found between the valproate+quetiapine group and the valproate group only with regard to NAA/CHO. CONCLUSION Our findings suggest that valproate has a neuroprotective effect. In post hoc comparisons, a significant difference was found between the valproate+quetiapine and the valproate group with regard to NAA/CHO, indicating that the addition of quetiapine further increases the level of NAA and provides an additional neuroprotective effect.

Hippocampal 1H MRS in first-episode bipolar I patients

Based on earlier structural and functional neuroimaging studies, we specifically wanted to assess N-acetylaspartate (NAA), choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) levels in brain hippocampus previously demonstrated to be involved in the pathophysiology of bipolar disorder which have not been evaluated in first-episode patients. Twelve patients meeting DSM-IV criteria for bipolar disorder who consecutively applied to our department and 12 healthy controls were studied. The patients and controls underwent proton magnetic resonance spectroscopy ((1)H MRS), and measures of NAA, CHO, and CRE in hippocampal regions were obtained. ANOVA revealed in the hippocampus a significant effect of diagnosis for NAA/CRE and for NAA/CHO but not for CHO/CRE. Post hoc analysis showed that patients had a significant bilateral reduction of NAA/CRE and of NAA/CHO. No significant correlation was found between hippocampus volume and ratio measures. Correlation analyses exhibited significant correlation between NAA values and the YMRS for both side of the hippocampus, but not any other clinical variables (age, age at onset, and duration of illness). In summary, hippocampal neuronal abnormalities seem to be present at the onset of bipolar I disorder. These data suggest that neuronal abnormalities in hippocampus may be associated with the severity of bipolar I disorder. As these data were obtained in patients in their first-episode (all the patients were manic), they cannot be explained by chronicity of illness or pharmacological treatment.

Brain morphology of patients with body dysmorphic disorder.

BACKGROUND There has been dearth of investigations concerning morphometric magnetic resonance imaging (MRI) study of regional brain volumes in body dysmorphic disorder (BDD). So we performed a volumetric MRI study in patients with BDD focusing on the in vivo neuroanatomy of thalamus, caudate nucleus, anterior cingulate cortex, and orbito-frontal cortex (OFC) concurrently. METHODS The whole brain, total gray and white matter volume, thalamus, caudate nucleus, anterior cingulate cortex, and OFC volumes were blindly measured in 12 unmedicated male BDD patients not having any comorbidity and 12 male control subjects matched for age, and gender. RESULTS The mean OFC and anterior cingulate volumes were significantly smaller than those of healthy controls. The mean white matter volume was larger than that of controls. There was a trend toward increased thalamic volume in patients compared with that of control subjects. Length of illness was inversely correlated with OFC volumes in the patient group both on the left and right sides. CONCLUSIONS These findings may be interpreted as further evidence for the inclusion of BDD among a group of obsessive-compulsive spectrum disorders. Future research is necessary to confirm these preliminary findings, to extend them, and to clarify their significance with respect to the etiology and pathophysiology of BDD.

Hippocampus and amygdalar volumes in patients with somatization disorder.

In regard to somatization disorder which covers an important section of our patient population, there is no systematic structural magnetic resonance imaging (MRI) study in the literature. Therefore, we aimed to use structural MRI to evaluate the hippocampus amygdalar complex which is associated with both stress and regulation of emotion that are main basis clinical presentation of somatization disorder in the patients with somatization disorder. Totally 40 subjects (20 patients with somatization disorder and 20 healthy controls) were enrolled. Intracranial volume (ICV), whole brain volume, gray and white matter volumes, and hippocampus and amygdalar volumes of the subjects were measured. In regard to unadjusted mean volumes of measured structures, the patients had significantly smaller mean volumes of the left and right amygdala. However, two groups did not differ significantly in terms of whole brain, total gray and white matter or hippocampus volumes. The repeated measures ANCOVA predicting left and right amygdala volumes demonstrated a significant main effect of diagnostic group. In conclusion, the findings of the present study revealed that the patients with somatization disorder had significantly smaller mean volumes of the left and right amygdala without any differences in regard to whole brain, total gray and white matter or hippocampus volumes. On the basis of the current findings, it seems reasonable to evaluate that abnormalities in connectivity and/or metabolism dimensions and to examine the effects of drugs or psychotherapeutic approaches could be especially informative.

Neurochemistry of the hippocampus in patients with obsessive–compulsive disorder

Aim:  To date, despite possible neuroanatomical importance, no magnetic resonance spectroscopy (MRS) study on hippocampus has been performed in obsessive–compulsive disorder (OCD). The purpose of the present study was therefore to compare hippocampal chemicals in patients with OCD with those in healthy subjects with no psychopathology.

Smaller pituitary volume in adult patients with obsessive-compulsive disorder

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).

Serotonin transporter gene polymorphism implicates reduced orbito-frontal cortex in obsessive–compulsive disorder

Although a number of magnetic resonance imaging (MRI) and genetic studies have been performed on obsessive-compulsive disorder (OCD), only limited studies in which genetic and neuroanatomical variables are evaluated concurrently have been performed. Therefore, the aim of our present study is (to understand) better understanding how genetic variation in the promoter region of the 5-HTT gene (5-HTTLPR) is associated with key brain structures in OCD, orbito-frontal cortex (OFC), thalamus and anterior cingulate. 5-HTT genotypes (SS, SL, LL) were determined for 40 patients with OCD and the same number of healthy controls. MRI-derived volumes of the OFC, thalamus, and anterior cingulate were determined by reliable tracing techniques. Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5T, and were done blindly. In comparison with controls, OCD patients demonstrated volumes reduction in OFC, increased volumes of thalamus and total white matter volumes, but no difference in total brain volume, total gray matter volumes and anterior cingulate volumes. No significant difference was observed in allelic frequencies between the patients and controls. The stronger effects of 5-HTT polymorphism on brain morphology in OCD than those in controls were determined in the both OFC and thalamus. On the other hand, for the OCD patients, ANCOVA revealed a significant main effect of genotype for both the OFC and thalamus and a significant genotype-by-side interaction for the OFC, demonstrating that the short variants had a smaller right OFC than the long variants. In conclusion, we found a significant genotype-diagnosis interaction effects on key brain structures, with a stronger effects of 5-HTT polymorphism in OFC and thalamus of OCD patients, whereas no morphological changes related to the polymorphism were found in normal individuals.