Renee M. Dupont

Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep (primarily stages 2 and 3) showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than waking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.

Subcortical signal hyperintensities in bipolar patients detected by MRI

Psychiatry Research. 21,357-358 Elsevier Letter Subcortical Signal Hyperintensities in Bipolar Patients Detected by MRI To the Editors: Some recent reports have shown increased ventricle-brain ratios (Nasrallah et al., 1984; Pearlson et al., 1984) and altered attenuation values (Coffmanand Nasrallah, 1984; Schle- gal and Kretzschmar, 1987) in the computed tomographic (CT) scans of bipolar patients compared with controls. Using magnetic resonance imaging (MRI), we have exam- ined 15 bipolar patients and 8 controls for the presence of ventricular enlargement and par- enchymal abnormalities. All patients and controls were screened with the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (Endi- cott and Spitzer, 1978), history, and labora- tory and physical examinations. Participants with a history of a neurological disorder, birth trauma, developmental delay, uncon- trolled hypertension, or significant alcohol or drug abuse were excluded. Controls were free of personal and family history of psychi- atric disorder. All screening was completed before the MRI. Ventricular rank and pres- ence of parenchymal abnormalities were evaluated by experienced observers without knowledge of group membership of the images (T.J. and J.R.H., respectively). Sub- cortical white matter abnormalities were defined by an increased signal on mixed T,/ T, and T, weighted images (TR-2,00Oms, TE-25, 70 ms) obtained in axial and coronal planes. Regions of increased signal found normally directly anterior to the frontal horn or posterior to the occipital horn ofthe lateral ventricle were excluded. Fifteen bipolar patients met Research Diagnostic Criteria (Spitzer et al., 1978) for the disorder. However, one patient was excluded from analysis due to the presence of a previously undiagnosed arachnoid cyst dis- placing the left temporal lobe. The remaining @ 1987 Ekvier bipolar patients were 13 males and 1 female. Seven patients were on lithium alone, two were on lithium plus a tricyclic anti- depressant, one was on lithium, benztropine, and fluphenazine HCl, one was on carba- mazepine, and three were unmedicated. One bipolar male had recentlycompletedacourse of electroconvulsive therapy (ECT). Eight males served as controls. The average age of the patients was 38 + 8 years, and that of the controls was 41 f 9 years (NS difference). Eight of the 14 bipolars and none of the controls exhibited white matter abnormali- ties @ 0.90). To our knowledge, this is the first study demonstrating focal parenchymal abnor- malities in bipolar patients using MRI. Further studies are underway to evaluate the relationship of these lesions to performance on tests of cognitive functioning. Scientific Publishers Ireland Ltd.

Preliminary evidence of an association between increased REM density and poor antidepressant response to partial sleep deprivation.

BACKGROUND One night of total sleep deprivation or of late-night partial sleep deprivation (PSD) produces a temporary remission in approximately 40-60% of patients with major depressive disorder; however, little is known about polysomnography (PSG) characteristics of responders to these types of sleep deprivation (SD). METHODS Twenty-three unmedicated unipolar patients (17-item Hamilton Depression Rating Scale (HDRS17) >16) and 14 normal controls underwent 1 night of late-night PSD (awake after 3 a.m.) Subjects underwent baseline PSG and received the HDRS17 at standard times before and after PSD. Clinical response was defined as a reduction of >30% in the modified HDRS17 (omitting sleep and weight loss items) following PSD. RESULTS The 12 responders and 11 nonresponders did not differ from each other significantly on baseline HDRS17 or PSG variables. The only PSG variable correlating with percent decrease in modified HDRS17 was baseline REM density (Pearsons r=-0.52, n=23, P=0.01.) In other words, the lower the baseline REM density, the more robust the antidepressant response was. LIMITATIONS Subject numbers are relatively small. CONCLUSIONS Increased REM density, which reflects the number of rapid eye movements per epoch of REM sleep, may be a physiological marker for severity or poor prognosis in a variety of psychiatric disorders, including relapse in recovering alcoholics, suicidality in schizophrenia, and poor response to PSD or interpersonal psychotherapy in depression.

Reduction in cortical IMP-SPET tracer uptake with recent cigarette consumption in a young group of healthy males

Functional brain imaging techniques are being used increasingly to infer disturbances in brain function in various neuropsychiatric disorders, but the specificity of such findings is not always clear. We retrospectively examined the effects of one possible confound - cigarette smoking - on cortical uptake of iodine-123 iodo-amphetamine (IMP) using single-photon emission tomographic imaging in a young (mean age=35 years) healthy group of male controls divided according to their smoking history. Subjects who had never smoked (n=17), or those with a history of smoking but no recent smoking (n=8), had equivalent and significantly higher mean cortical uptake of IMP than subjects with a history of smoking and who were current smokers (n=8). There were no differences in the cortical distribution of IMP. Our results indicate that cigarette smoking has an acute effect on global cerebral blood flow. This potential confound must be considered before abnormalities in cortical tracer uptake are attributed to some neuropsychiatric disorder of interest.

Single photon emission computed tomography with iodoamphetamine-123 and neuropsychological studies in long-term abstinent alcoholics

Ten long-term abstinent alcoholics (mean abstinence = 7.7 years) were compared with 13 recently detoxified substance-dependent inpatients (mean abstinence = 25 days) and 8 nonalcoholic control subjects on global end regional measures of cortical cerebral blood flow (CBF), and on neuropsychological measures. CBF was assessed using 123iodoamphetamine (IMP) single photon emission computed tomography (SPECT) under conditions of behavioral challenge (Ravens Progressive Matrices). CBF and neuropsychological test performance were worse in the recently detoxified inpatients. Of greater interest, there was a dissociation in the long-term abstinent group, which, while neuropsychologically indistinguishable from controls, showed significantly decreased mean cortical IMP uptake. We conclude that there may be persistent physiologic abnormalities in long-term abstinent alcoholics who have achieved full behavioral recovery. Smoking on the day of SPECT scanning was also identified to be a significant confound to understanding CBF changes in alcoholism.

Regional cerebral blood flow in cocaine- versus methamphetamine-dependent patients with a history of alcoholism

Although abuse of cocaine or methamphetamine usually takes place in the context of heavy drinking, there is little information on the effects of such substance use comorbidity on brain perfusion. We explored similarities and differences in the effects of these two drugs in combination with alcohol on brain function using SPECT. Global and regional cerebral blood flow (CBF) were examined in 7 abstinent cocaine-dependent alcoholics (CDA; mean age = 39.2 yr, S.D. = 9.2 yr), 7 abstinent methamphetamine-dependent alcoholics (MDA; mean age = 36.8 yr, S.D. = 5.0 yr), and 7 non-alcoholic/non-stimulant abusing controls (NAC; mean age = 37.3 yr, S.D. = 9.6 yr). MDA had significantly lower global CBF than CDA who, in turn, were significantly lower than NAC. In addition, CDA had abnormal perfusion in the superior posterior frontal region compared to NAC; while MDA did not display specific regional deficits. Therefore, it appears that cocaine alters the relationship between global and regional CBF in alcoholics, while methamphetamine does not.

Is there a relationship between delta sleep at night and afternoon cerebral blood flow, assessed by HMPAO-SPECT in depressed patients and normal control subjects? Preliminary data.

We wished to explore the relationships between waking HMPAO uptake and visually scored polysomnography. We hypothesized that HMPAO activity would correlate positively with slow wave sleep measures the same night. Eight unmedicated unipolar patients with current DSM-IV major depression (17-item Hamilton Depression Rating Scale score 21.5+/-2.9) and seven control subjects received polysomnography on 2 consecutive nights. On the afternoon following the adaptation night, subjects received cerebral SPECT, with 15 mCi Tc-99m-HMPAO injected while subjects performed the Continuous Performance Task. Patients and control subjects did not significantly differ on demographic, polysomnographic, and SPECT variables. Slow wave sleep measures correlated positively (Spearmans) with global and regional tracer activity for depressed (n = 8), control (n = 7) and combined groups (n = 15); in other words, the greater the global or regional afternoon HMPAO uptake, the greater the slow wave sleep measures were the same night. In addition, the greater the waking afternoon global or regional HMPAO activity, the faster subjects fell asleep and the less Stage 2% they had. In patients, global and regional HMPAO activity correlated positively with REM density. Positive correlations between waking tracer activity and subsequent slow wave measures are consistent with previous hypotheses linking slow wave sleep with brain energy conservation and restoration. Further study is needed to determine whether these functional relationships differ in depression.

Preliminary report : cerebral blood flow abnormalities in older schizophrenic patients

We compared global and regional cerebral blood flow in 11 schizophrenic patients and 11 normal comparison subjects, all over the age of 45 years. The schizophrenic patients had lower global cortical uptake than the control subjects. Among the individual regions of interest, the schizophrenic patients had significant decrements in the left posterior frontal region and in the bilateral inferior temporal regions. The uptake did not correlate with age of onset or duration of schizophrenia, current daily neuroleptic dose, severity of psychopathology, or global cognitive impairment.

Neuroendocrine effects of intravenous ovine corticotropin-releasing factor in affective disorder patients and normal controls

A wide variety of neuroendocrine abnormalities have been reported in affective disorder patients. Probably the most extensively studied have been hypothalamic-pituitary-adrenal activation and dexamethasone resistance. The recent sequencing and availability of corticotropin-releasing factor allows direct testing of pituitary responsivity to this neuropeptide in affective disorder patients. Thus, we report the effects of intravenously administered ovine corticotropin-releasing factor (0.03 I*g/kg) on plasma concentrations of adrenocorticotrophic hormone (ACTH) and cortisol in depressed patients and ageand sex-matched normal controls.