An EEG sleep study of a bipolar (manic-depressive) patient with a nocturnal switch process.

Fifty-eight all-night polygraphic sleep recordings were obtained on an unmedicated female bioplar (manic-depressive) patient who switched into and out of mania eight times. While depressed she was hypersomniac and exhibited elevated Rapid Eye Movement (REM) sleep time and short REM latency. On four nights, she apparently switched into mania while asleep. The last recorded sleep stage in each case was REM sleep.     

The switch process in manic-depressive illness

Research data collected on 75 Bipolar I patients, hospitalized at the NIMH between 1963 and 1975, were reviewed to identify “switches” into and out of mania. There were 27 “slow” switches (i.e. occurring over a period of 2–6 days) in 14 patients and 89 “rapid” switches (i.e. occurring in 24 hours or less) in 35 patients. No patient showed both “rapid” and “slow” switches during his hospitalization. Among the 89 rapid switches, 52 switches were into mania and 37 were out of mania. Rapid switches into and out of mania occurred significantly more often in the morning (7 a.m. to 3 p.m.) than at night (11 p.m. to 7 a.m.) or in the evening (3 p.m. to 11 p.m.). Estimated average sleep time on the night prior to switch into mania showed a significant drop as compared to sleep time on the second, third and fourth nights prior to switch. Patients who switched into mania at night were rated as significantly more manic during the 4 days following the switch than patients who switched in the morning or evening. Patients who switched into mania at night and evening were rated as sleeping significantly less during the 4 days following the switch than patients who switched in the morning.     

Serendipity in biological psychiatry--a myth?

It is often stated that major biological treatments in psychiatry were discovered by accident or serendipity. Tracing the history of the concept of serendipity, we find that serendipity has been subjected to greatly divergent interpretations. According to the current usage, it is a discovery in which chance was a necessary and/or sufficient condition. With this definition, none of the discoveries of major biological treatments in psychiatry can be labeled serendipitous. The necessary factors common to these discoveries were creative minds that were variably influenced by the zeitgeist and that were persistent in their search for answers. Another important prerequisite was the availability of crucial basic knowledge of many related sciences. We conclude that chance cannot substitute for long-term research and that the latter is the most likely way to lead to valuable discoveries.     

Nocturnal catecholamines and immune function in insomniacs,depressed patients,and control subjects

Insomnia predicts cardiovascular and non-cardiovascular disease mortality. This study evaluated EEG sleep, nocturnal sympathetic activity, and daytime measures of immune function in subjects with primary insomnia (n = 17) and patients with current major depression (n = 14) as compared to controls (n = 31). Insomniacs showed disordered sleep continuity along with nocturnal increases of average levels of circulating norepinephrine and decreases of natural killer cell responses, whereas depressed patients showed declines of natural killer cell activity, but no differences of EEG sleep or nocturnal catecholamines as compared to controls. Impairments of sleep efficiency correlated with nocturnal elevations of norepinephrine in the insomniacs but not in the depressives or controls. These data indicate that insomnia is associated with nocturnal sympathetic arousal and declines of natural immunity, and further support the role of sleep in the regulation of sympathetic nervous and immune system functioning.     

Low-dose nitro-L-arginine administration in baboon (Papio hamadryas) pregnancy

1. The purpose of the present study was to examine the effect of nitric oxide (NO) inhibition on mean arterial pressure (MAP), endothelin (ET) and the renin-aldosterone system in pregnancy in the non-human primate (baboon). 2. Twenty pregnant baboons (Papio hamadryas) were examined prospectively after the administration of an oral NO inhibitor in different phases of pregnancy. Haemodynamic responses to NO inhibition, evidence of pre-eclampsia and the renin-aldosterone system were examined under anaesthesia. 3. Oral NL-nitro-L-arginine (NOLA; 5 or 10 mg/kg) was given for 1 week in early (6-8 weeks gestation), middle (14-16 weeks gestation) and late (22-24 weeks gestation) pregnancy and while non-pregnant. Mean arterial pressure, heart rate, haematology, biochemistry, ET, plasma renin activity (PRA) and aldosterone were measured. Foetal effects of NOLA were also examined by ultrasound and neonatal measurements. 4. Nitric oxide inhibition led to an increase in MAP in non-pregnant animals (9 mmHg) and in middle and later pregnancy (6 and 7 mmHg, respectively). Mean arterial pressure in early pregnancy was not affected. A reduction in PRA occurred after NO inhibition in all stages of pregnancy. Significant proteinuria occurred only in late pregnancy. 5. Nitric oxide is involved in the maintenance of lower blood pressure in late pregnancy and inhibition leads to an increase in blood pressure and proteinuria in the baboon. Nitric oxide insufficiency may contribute to the clinical manifestations of human pre-eclampsia. Nitric oxide was not involved in the normal vasodilation of early primate pregnancy.     

Acute experimental cerebral ischemia: MR enhancement using Gd-DTPA

The effects of a paramagnetic contrast agent, gadolinium-DTPA (Gd-DTPA), on magnetic resonance (MR) imaging of acute cerebral ischemia was investigated in a feline model of middle cerebral artery occlusion. Imaging was performed both before and after administration of an intravenous dose of 0.2 mmol/kg of Gd-DTPA. The animals were then sacrificed for pathologic correlation. No changes in intensity or relaxation times were noted before or after Gd-DTPA administration in two animals with 2 hours of occlusion. Infarcts were noted before and after contrast enhancement in all six cats with ischemia of greater than 16-hours duration. Gd-DTPA caused significant increase in intensity of infarct but not in that of normal cerebral tissue. Rapid enhancement was visible in infarcts of 16-24 hours, but such enhancement was slower in infarcts of 72-168 hours, presumably owing to slowed inflow caused by increased vasogenic edema in the latter group. Contrast enhancement of acute cerebral ischemic lesions with Gd-DTPA offers no improvement in sensitivity of MR imaging, although the conspicuity of the lesion may be improved. Additionally, contrast media may provide potential temporal and pathophysiological data for better characterization of cerebral ischemia.