Jeffrey A. Coffman

A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia

Two previous postmortem studies reported an increased thickness of the corpus callosum in schizophrenic patients compared to psychiatric controls. We report an in vivo study of the corpus callosum in schizophrenic patients (n = 38) and healthy controls (n = 41) using magnetic resonance (MR) brain imaging. A significant increase in mean callosal thickness was found in the middle and anterior, but not the posterior, parts of the callosal body. However, when the patients and controls were compared by gender and handedness, schizophrenic men were found not to differ from control men in callosal thickness, regardless of handedness, whereas schizophrenic women were found to have a highly significant increase in callosal middle and anterior thickness compared to control women. The data suggest that increased callosal thickness in schizophrenia is gender related, a factor that is not considered by postmortem studies. The implications of increased callosal dimensions in female schizophrenics are discussed.

Cognitive impairment and cerebral structure by MRI in bipolar disorder

The distinction between bipolar disorder and schizophrenia customarily follows examination of the clinical symptomatology and course of illness. The presence of cognitive impairment has been held to be uncommon in bipolar disorder and more likely in schizophrenia. This study explored neuropsychological function in 30 ambulatory outpatients with a DSM-III-R diagnosis of bipolar affective disorder (all of whom had been psychotic during manic episodes), comparing their performance with that of controls. These bipolar patients proved to have significant levels of diffusely represented cognitive impairment when compared with controls. Further, the degree of impairment was significantly correlated with reduction in midsagittal areas of brain structures measured on magnetic resonance imaging scans. The implications of these findings in relation to bipolar disorder are discussed.

Neuropsychological deficit in schizophrenic subtypes: Paranoid, nonparanoid, and schizoaffective subgroups

Schizophrenic patients were carefully diagnosed and screened for a history of neurological disorders. Diagnosis and subtyping was based on DSM-III-R criteria, using the Structured Clinical Interview for DSM-III-R, which was administered by trained interviewers and confirmed by a research psychiatrist. The schizophrenic patients were compared with an age-matched control group on an extensive battery of neuropsychological measures. The undifferentiated/disorganized schizophrenic patients were consistently the most impaired on a broad range of tasks. When the effect of symptom severity and drug level were statistically controlled (analysis of covariance), however, the magnitude and number of differences were substantially reduced. The perseverative error score from the Wisconsin Card Sort Test showed the greatest difference between the groups. However, the strongest and most consistent effects were observed in relation to symptom ratings. These data indicate the importance of controlling for medication and symptom severity, and suggest that current diagnostic classifications may not be the most useful factors for studies of the cognitive correlates of schizophrenia.

Esmolol reduces autonomic hypersensitivity and length of seizures induced by electroconvulsive therapy

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting, β1-adrenergic receptor blocking drug, to control the sinus tachycardia and increase in arterial blood pressures induced by electroconvulsive therapy (ECT). Each of 20 patients, ASA physical status I-III, participated in a double-blind, randomized study involving four match-pair trials (placebo versus esmolol) during ECT. Each patient acted as his or her own control (total number of ECT procedures, 160). We administered a 4-min infusion of either placebo or esmolol at the rate of 500 μg · kg−1 · min−1. We then induced anesthesia with methohexital and succinylcholine. After administration of electrical stimulation for ECT, the rate of infusion decreased to 300 μg · kg−1 · min−1 for three additional minutes and was then discontinued. Statistically significant reductions in mean heart rate from minute 2 until minute 15 and in maximum heart rate (the mean of each patients maximum heart rate after seizure changed from 152 ± 23 to 115 ± 24 beats/min) occurred in patients given esmolol. During and immediately after infusion, arterial blood pressure also decreased. Finally, the length of seizures decreased, as manifested clinically from 48 ± 18 to 39 ± 14 s and on electroencephalogram from 86 ± 41 to 67 ± 28 s. We conclude that esmolol effectively controls the hyperdynamic response to ECT and reduces the length of seizures. The significance of the latter to the overall effectiveness of ECT is not known.

Perinatal complications and genetic loading in schizophrenia: Preliminary findings

History of perinatal complications (PCs) and first degree family history (FH) of psychiatric illness were examined in groups of schizophrenic/schizoaffective (n = 21) and bipolar (n = 10) patients. PCs were significantly more frequent in the schizophrenic and schizoaffective patients than in bipolar patients. An inverse relationship was found between PCs and FH status, with FH-positive patients having significantly fewer PCs than the FH-negative group. This relationship persisted when the bipolar patients were excluded. Findings emphasize the etiological importance of genetics and perinatal events in the psychoses, and support the validity of a familial/sporadic distinction.

Cholinergic hypothesis of depression: a reappraisal.

Evidence for the cholinergic hypothesis of depression is reviewed, arguments directed against this hypothesis are set forth, and the strengths and weaknesses of these criticisms are discussed. The authors conclude that the cholinergic hypothesis is tenable but suggest new areas of study.

Midsagittal cerebral anatomy by magnetic resonance imaging: The importance of slice position and thickness

Several recent studies of psychiatric patients have relied upon magnetic resonance imaging (MRI) to demonstrate features of cerebral anatomy in the midsagittal plane. Methodologies have varied somewhat in relation to thickness and position of planes of view. Due to concerns over the effects of slice thickness and position on measurements, the authors used a multislice thin plane method to assess these effects in 143 individuals (34 controls, 58 schizophrenics, and 51 with bipolar or schizoaffective disorder). Substantial variance in area measurements attributable to slice position emerged, especially in ventricular, cerebral and cerebellar area. Of greater importance would be the demonstrated interaction of position with diagnosis and sex in measures of several regions. The implications of these findings for MRI studies are discussed.

Defining the dose range for esmolol used in electroconvulsive therapy hemodynamic attenuation.

We evaluated the clinical effectiveness of esmolol, an ultra-short-acting, β-adrenergic receptor blocking drug, to control the sinus tachycardia and increase in arterial blood pressure induced by electroconvulsive therapy (ECT). Each of 20 patients, ASA physical status IIII, participated in a double-blind, randomized Latin-Square study involving two matched-pair trials (placebo versus esmolol given as a 500-μg/kg bolus followed by either 300 μg-kg-1-min-1 [high dose], 200 μg-kg_1-min_1 [medium dose], or 100 μg-kg_1-min_1 [low dose] infusion of esmolol) during ECT. Each patient acted as his or her own control (total number of ECT procedures were 160). We administered a 1-min bolus of placebo (normal saline) or esmolol at the rate of 500 μg-kg_1-min_1 followed by either high-, medium-, or low-dose esmolol or placebo for an additional 3 min. We then induced anesthesia with methohexital (1 mg/kg) and succinylcholine (0.5 mg/kg) IV. Ninety seconds after the administration of succinylcholine, the electrical stimulus was applied to induce seizure. The infusion of placebo or esmolol was discontinued 3 min after the electrical stimulus. Significant decreases were found in mean heart rate from minute 3 until minute 7 and in the maximum heart rate. The mean of each patients maximum heart rate after seizure changed from 147 ± 18 bpm in placebo patients to 112 ± 20 bpm in high-dose esmolol patients; to 121 ± 23 bpm in medium-dose esmolol patients; and to 124 ± 20 bpm in low-dose esmolol patients. Mean arterial blood pressure was significantly lower in the high-dose esmolol patients (100 ± 18 mm Hg) compared with the same patients given placebo (122 ± 25 mm Hg). Finally, the side effect of clinically determined length of seizures decreased in the high- (36 ± 14 s) and medium-dose (34 ± 14 s) esmolol patients as compared with placebo (42 ± 11 s) patients. Low-dose esmolol did not significantly reduce the clinically determined length of seizure (38 ± 11 s). We conclude that the 100-μg-kg-1-min-1 infusion following a 500-μg/kg bolus of esmolol effectively controls the hyperdynamic response to ECT.

Brain density patterns in schizophrenia and mania.

Regional brain density as measured by X-ray computed tomography was assessed in young schizophrenic (mean age 29.8 years) and manic (mean age 32.7 years) males in order to determine whether this parameter would distinguish between these groups of patients. Our findings reveal similar patterns of interhemispheric density differences in the two groups but significantly greater overall density among manics for the uppermost brain sections studied (16-24 mm above the slice intercepting the body of the lateral ventricles). Clinical implications of these findings are discussed.

Relationships between brain density, cortical atrophy and ventriculomegaly in schizophrenia and mania.

ABSTRACT– A number of parameters assessed by computed tomography have been shown to differentiate between populations of psychiatric patients and normal controls. Changes in these parameters have been felt to result from atrophic processes. We hypothesized that changes in one parameter ought to result in related changes in another if they result from the same process. We tested this hypothesis by comparing CT scan results of density measurement with area and linear measurements of ventricular size and radiological assessments of cortical and cerebellar atrophy. Our results indicate that few statistically significant relationships appear to be present, the only such relationship being found between increased third ventricular size and cerebellar atrophy. We conclude that regional changes in brain density are not necessarily correlated with local changes in CSF volume, which suggests the involvement of disparate processes in their causation.