Srinivasan S. Pillay

Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study

BACKGROUND Previous studies have shown that major depression is frequently accompanied by hypercortisolemia. There is some evidence suggesting that an increase in the glucocorticoid levels may make hippocampal cells more vulnerable to insults caused by hypoxia, hypoglycemia, or excitatory neurotransmitters. Using magnetic resonance imaging (MRI), the hippocampi of patients with major depression were measured and compared with values observed in control subjects. METHODS Thirty-eight patients with primary unipolar major depression were recruited. Twenty control subjects were matched for age, gender, and years of education. The hippocampal volume was measured from coronal MRI scans in all of the subjects. Patients were also grouped and compared as responders and nonresponders to treatment with fluoxetine of 20 mg/day, for 8 weeks. Hamilton Depression Rating Scale (HDRS) was used to determine the severity of depression. RESULTS No significant differences were observed between the hippocampal volumes of patients with major depression and control subjects; however, a significant correlation was observed between the left hippocampal volume of men and their HDRS baseline values. In addition, female responders had a statistically significant higher mean right hippocampal volume than nonresponders. CONCLUSIONS The results of our study indicate no reduction in the volume of the hippocampus in patients with major depression. Nonetheless, the results do suggest that the effects of disease severity, gender, and treatment response may influence hippocampal volume.

Basal ganglia choline levels in depression and response to fluoxetine treatment: an in vivo proton magnetic resonance spectroscopy study

We have investigated proton magnetic resonance spectra of the basal ganglia in 41 medication-free outpatients with major depression, prior to starting an 8-week standardized trial of open-label fluoxetine, and 22 matched comparison subjects. Upon completing the trial, depressed subjects were classified as treatment responders (n = 18) or nonresponders (n = 23), based on changes in the Hamilton Depression Rating Scale. Depressed subjects had a lower area ratio of the choline resonance to the creatine resonance (Cho/Cr) than comparison subjects. This statistically significant difference between the depressed subjects and comparison subjects was more pronounced in the treatment responders than in the nonresponders. There were no differences in the relative volumes of gray matter or white matter in the voxel used for proton spectroscopy in depressed subjects relative to comparison subjects. These results are consistent with an alteration in the metabolism of cytosolic choline compounds in the basal ganglia of depressed subjects and, in particular, those who are responsive to fluoxetine.

Is There a Relationship Between Clozapine and Obsessive-Compulsive Disorder?: A Retrospective Chart Review

The emergence of obsessive-compulsive symptoms during clozapine treatment has been reported in recent case studies, yet the incidence and significance of this finding is still unclear pending reliable data from a larger sample of patients. Hospital records of 142 randomly selected inpatients started on clozapine treatment at McLean Hospital before July 1, 1992, were reviewed retrospectively. Based on a limited retrospective chart review, there were no definitive cases of patients who developed obsessive-compulsive disorder (OCD) or whose OCD worsened as a result of clozapine treatment. Although some fluctuation of OCD symptoms may have occurred in two cases, it is unclear whether those symptoms were related to treatment with clozapine (or other psychotropic drugs) or to undulations in the natural history of OCD. No definitive relationship between OCD symptoms and clozapine treatment could be established in this limited study. Further clarification of this matter awaits outcome research using prospective methodologies.

Choline ingestion increases the resonance of choline-containing compounds in human brain: An in vivo proton magnetic resonance study

Choline is a crucial intermediate in several clinically relevant neurochemical processes. In this study, choline-containing compounds in human brain (principally phosphocholine, glycero-phosphocholine, and choline) were measured by 1H-magnetic resonance spectroscopy, before and after the ingestion of 50 mg/kg choline in four normal control subjects. Substantial and remarkably similar increases in the brain choline resonance occurred in each subject, with a nearly two-fold rise in the choline resonance observed 3 hr following choline ingestion (p = 0.008 versus baseline). One subject also received a dose of 200 mg/kg choline, and exhibited a proportionally larger increase in the brain choline resonance. The results are consistent with animal data reporting a rise in choline-containing compounds following choline administration. This is the first study to our knowledge where an oral nutrient has been shown to produce a detectable change in human brain composition in vivo. Studying choline transport and biotransformation in human brain may have relevance to several neuropsychiatric disorders, including affective disorders and dementia.

Basal ganglia volumetric studies in affective disorder : what did we learn in the last 15 years?

Summary.Until today, morphometric neuroimaging studies on affective disorders concentrate on the limbic system, especially the hippocampus, amygdala, and anterior cingulate. In most of the studies and reviews available today, the basal ganglia are of secondary interest. It seems that the basal ganglia are interest of neurologist, whereas the limbic system is reserved for psychiatric neuroimaging studies. We follow a different approach in this review, studying all available papers on MRI research of the basal ganglia in unipolar depression and bipolar disorder. We found a possibly larger neostriatum in bipolar and possibly smaller one in unipolar patients. None of the unipolar studies found any larger basal ganglion, and only one out of 12 bipolar studies found smaller basal ganglia. Both findings seemed to depend on age (tendency toward smaller volumes in unipolar and bipolar with older age), sex (men tending to pathology in both disorders) and bipolar patients show a possible influence of medication, which is not assessed so far in unipolar depression. We conclude that several methodological shortcomings in volumetric MRI research on the basal ganglia in affective disorders make it necessary to imply more research in this area. We suggest (a) better MRI methods (we do not have a single volumetric 3 Tesla study in this patient group); (b) studies of medication-naïve patients (thus ruling out the medication effect); (c) Studies that directly compare unipolar depressed and bipolar patients are needed to determine whether these apparent differences in morphometric abnormalities, as observed through the mediating comparison with healthy subjects, are real.

Cannabis and Motor Function: fMRI Changes Following 28 Days of Discontinuation

The authors hypothesized that supplementary motor cortex (SMA) and anterior cingulate cortex (ACC) activation in chronic cannabis users, studied 4 to 36 hours after their last episode of use, would disappear by Day 28 of abstinence during finger-tapping tests. Eleven cannabis users and 16 comparison subjects were scanned during right (RFT) and left (LFT) finger-tapping tasks on a GE 1.5 Tesla scanner retrofitted with a whole body echo planar coil. Image analyses were conducted in SPM99 using an ROI approach to define each Brodmann area (BA). Differences in cerebral activation were examined in the left and right primary motor cortex (BA4), SMA (BA6), and ACC (BA24 and BA32 separately). The authors found diminished activation for contralateral BA6 from Day 0 to Day 28. For LFT, the authors also found: ipsilaterally diminished BA6 activation on Day 7, but not Day 0 or Day 28; ipsilaterally diminished BA32 activation on Day 0, but not Day 7 or Day 28; contralaterally diminished BA 4 activation on Day 28, but not Day 0 or Day 7; and contralaterally diminished BA32 activation on Day 0 and Day 28, but not Day 7. For RFT, the authors found ipsilaterally diminished BA32 activation on Days 0 and 7 but not on Day 28; contralaterally diminished BA32 activation on Days 0, 7, and 28; and ipsilaterally diminished BA6 activation on Days 0, 7, and 28. These results suggest that residual diminished brain activation is still observed after discontinuing cannabis use in motor cortical circuits.

EEG Abnormalities Before Clozapine Therapy Predict a Good Clinical Response to Clozapine

The purpose of this study was to test the hypothesis that minor EEG abnormalities predict a favorable response to clozapine. Eighty-six psychotic clozapine-treated psychiatric inpatients with EEG records before starting clozapine were included in the study. When all diagnostic groups were combined, there were no significant differences in clinical outcome between patients with abnormal EEGs and patients with normal EEGs. However, female patients with abnormal EEGs had a significantly greater improvement in Global Assessment of Functioning (GAF) scores compared to female patients with normal EEGs. In addition, patients with major depressive episodes (bipolar, schizoaffective, unipolar) and abnormal EEGs had a significantly greater improvement in GAF scores compared to the same subgroup of patients with normal EEGs. The results suggest that EEG abnormalities before clozapine treatment many predict a favorable clinical response in specific groups of patients.

Psychiatric disorder in a South African general hospital: Prevalence in medical, surgical, and gynecological wards

The aim was to elicit the individual and comparative prevalence of psychiatric disorder in medical, surgical, and gynecological wards in a South African hospital comprising a predominantly Third World patient population. Results indicated that 21%, 95% confidence interval (16;26) of the total sample of 230 patients had a DSM-III-R psychiatric disorder. Fifty-six percent had a diagnosis of substance dependence and 33% were found to have depressive disorders. Comparative analysis between disciplines indicated that the highest prevalence was in surgical wards. There was a statistically significant difference between the sexes. The variables associated with the presence of a psychiatric disorder and implications for better recognition and treatment are discussed.

Psychotic Acts: The Question of Meaning

Mr. A. was a 19-year-old single white male who was recently hospitalized for a manic episode. An honor-roll sophomore in college, he was the youngest of three sons born to a middleclass family in the Midwest. As a child he had had a competitive relationship with his brothers, who were 3 and 5 years older than he was, but more recently they had grown closer. He was described by his mother as being extremely sensitive and often very preoccupied with justice and fairness. She also reported that he had always been sensitive to being touched and that when he had been hugged, even by relatives, he had experienced and expressed an awkwardness. Mr. A. had been raised by both parents and had always been close to them. He had been brought up Catholic. He stated that his mother was a “churchgoer” but that his parents had been inconsistent in attending church. Mr. A. himself had always delighted in avoiding church. Mr. A. had gone to a parochial school from grades one to six and had been confirmed. He described the school as useful in teaching him discipline, but he did not think that he had learned much else there. Subsequently, he had attended a school in the Midwest that was run by an Episcopalian minister but was culturally and socioeconomically diverse. He appreciated the sense of discipline that he believed he had gained in a high school with a reputation for producing students who would go on to achieve academic success. Mr. A. had started college at a Catholic institution, studying English and economics. Although he had found the school to be too conservative and lacking in diversity, he had been able to adjust to college life and had participated in the