Human circadian rhythms in continuous darkness: entrainment by social cues.

Three groups of two subjects each were kept in underground chambers, first for 4 days in an artificial light-dark cycle, and thereafter for 4 days in complete darkness. They lived on a rigorous time schedule. Physiological as well as psychological functions were measured at 3-hour intervals. There were no differences in the results between the two sections of the experiment. Social cues are sufficient to entrain human circadian rhythms, and absence of light has no immediate effect on the functions measured.

Controllability of an aversive stimulus in depressed patients and health controls: a study using slow brain potentials.

Slow brain potentials (CNV and PINV) were recorded from 18 patients with primary depression and 18 health controls under three experimental conditions. A short tone (S1) indicated the occurrence of an aversive tone stimulus (S2) which could not be terminated by a motor reaction in Condition 1 (C1) but was terminated in C2. In C3 the reaction time (RT) had to be faster than the shortest mean RT from C1 and C2 in order to stop the aversive stimulus. For both groups the RT decreased from C1 to C2 to C3 and the CNV increased from C2 to C3. CNV and RT did not differ between the groups in either condition. In C1 and C3 (uncontrollability and restricted control over the aversive stimulus) patients developed a marked PINV which was not observed in the control group. In view of other investigations which found a PINV in normal subjects in situations of sudden, unexpected uncontrollability, the present results demonstrate that depressed patients are more sensitive to levels and variation of uncontrollability than healthy subjects. A possible relationship to Seligman's concept of helplessness is discussed.

Single-dose kinetics of the neuroleptic drug perazine in psychotic patients.

Eight male and two female unmedicated psychotic patients received 100 mg perazine orally and seven blood samples were taken within 25 h. Plasma levels of perazine and its demethylated metabolite were analyzed by HPLC with electrochemical detection. They exhibited large interindividual variations, with maximal concentrations as well as AUC values of perazine differing more than 10-fold. From the decay of plasma levels during the last 12-18 h half-lives were estimated to be between 7.5 and 10 h; they did not correlate with AUC. There was a significant positive correlation between AUC and age. Desmethylperazine was consistently present at lower concentrations than the parent drug during the first 12 h.

Therapeutic sleep deprivation in depressives, restricted to the two nocturnal hours between 3:00 and 5:00.

1. In 33 patients with a depressive syndrome the effects of partial SD restricted to the 2 hours between 3:00 and 5:00 in the morning was compared to that of no SD (= undisturbed sleep, n = 17) and total SD (n = 16) in a balanced crossover design. 2. Partial SD had a moderate antidepressant effect which is, however, clearly inferior to that of total SD. 3. Reasons for the scarceness of the effect may be an inappropriate timing of this 2-hr SD period (which seems improbable), too short a duration of SD, or the resumption of sleep at 5 o'clock. 4. "Intermediate" SD in the form it was used here represents no therapeutic advantage as we had expected. Its moderate effects lend support to the hypothesis that sleep disturbance is a sign of (mostly insufficient) restorative or self-healing efforts of the depressive organism.

The timing of partial sleep deprivation in depression.

In 26 major depressed and 4 schizoaffective inpatients (according to the RDC) early and late partial sleep deprivation (PSD) were carried out. For most of the patients (N = 25) this was done in a balanced crossover design. Residual sleep, starting at 21:00 or 2:00 respectively, was recorded polygraphically. Total sleep time was held constant between the 2 conditions (168 +/- 46 min in early sleep, 173 +/- 28 min in late sleep). Mood ratings with 5 different measures on the 2 days following each PSD revealed significant therapeutic effects from both procedures with only minor differences between them. Thus, sleep reduction as such and not the time at which it takes place (first or second half of the night) appears to be the therapeutic agent in PSD.

The recruitment process for a multicenter study on the long-term prophylactic treatment of affective disorders.

The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders. Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons. Further, a number of patients equal to that eventually allocated to the trial refused to participate for personal, idiosyncratic reasons. In spite of this, the patients in the trial were very similar to those not participating with respect to relevant variables such as age, sex, number of and intervals between previous episodes or severity of the present episode.

Lithium versus carbamazepine in the maintenance treatment of bipolar disorders--a randomised study.

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; lithium serum level: 0.63 +/- 0.12 mmol/l, carbamazepine dose: 621 +/- 186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (P = 0.041) and/or adverse effects (P = 0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years; P = 0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P = 0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.

Comparative efficacy of lithium and amitriptyline in the maintenance treatment of recurrent unipolar depression: a randomised study.

The present study, including 81 depressive patients, compares the prophylactic efficacy of lithium and amitriptyline in recurrent unipolar depression over a treatment period of 2.5 years in a randomised multicentre design. Hospitalisation, re-emergence of depressive or subdepressive recurrences, unwanted side-effects and need of concomitant psychotropic medication were considered to indicate treatment failures. Average dosage for amitriptyline was 98 +/- 37 mg/day, average lithium blood level was 0.59 +/- 0.12 mmol/l. Survival analyses demonstrated a significant superiority of lithium (P = 0.015) regarding the outcome criteria 'recurrences and/or subclinical recurrences' and non-significantly better results of lithium compared to amitriptyline concerning 'recurrence' (P = 0.059) or 'recurrence and/or concomitant medication' (P = 0.066).

The relationship between P3-latency and reaction time in depression.

A random series of frequencies and infrequent clicks was presented to 13 primary depressives and 13 healthy controls matched for age and gender. Subjects were instructed to press a button as fast as possible in response to the infrequent clicks. P3 amplitudes and latencies as well as correlations between P3 latency and reaction time were calculated on a single trial basis using Woody's adaptive filter. While reaction times were significantly longer in patients, neither P3 latencies nor P3 amplitudes differed between the groups. Thus, delayed reaction time of depressives seems to be a consequence of impaired selection, activation, or execution of the motor response rather than of delayed stimulus evaluation. The correlation between P3 latency and reaction time was significantly smaller in patients then in controls.

Plasma levels, psychophysiological variables, and clinical response to amitriptyline.

Hamilton depression scale ratings and physiological measurements were made for 37 patients with primary depression before treatment with amitriptyline (150 mg/day) and again after 2 and 4 weeks of treatment; plasma drug levels were determined weekly. Improvement was maximal at mean amitriptyline + nortriptyline concentrations of 125-200 ng/ml (14 patients), while at lower levels the outcome was significantly poorer (12 patients). Highly variable results were seen in 11 patients with levels between 200 and 301 ng/ml, with lesser improvement occurring in those patients who exhibited poor habituation of the skin resistance response before treatment. Other psychophysiological variables showed significant changes during treatment, but no correlation with clinical results or drug levels.

Postoperative psychosis in homocystinuria.

Young homocystinuria patients suffering from lens dislocation frequently have to undergo eye surgery. We describe a 16-year-old girl with mild mental retardation who became psychotic-delirant immediately after the last of three lentectomia operations performed under general thiopental anaesthesia. Because methionine, homocysteine, its oxidation product homocysteate and cysteine are potent glutamate agonists, the disturbance of the sulphur containing amino acid (SCAA) metabolism in homocystinuria patients may alter the function of cerebral glutamatergic transmission. The chronic and acute neurological and psychiatric symptoms of homocystinuria patients offer a clue to studies of the neurotoxic but also antipsychotic potency of glutamate agonists like the SCAAs in humans.

[Chronobiology of depression]. / Chronobiologie der Depression.

Depressive signs and symptoms can change on a daily, monthly and annual scale (diurnal variation of mood, premenstrual dysphoric disorder, seasonal affective disorders). This can be understood as a coupling of psychopathology to pre-existing rhythmic processes (association hypothesis). Also early morning awakening, short REM-sleep-latencies and the antidepressive effects of sleep deprivation and of phase advance therapy bear no evidence of a particular chronopathology in depression. Correspondingly, most studies in depressives have not shown an abnormal phasing of circadian rhythms.

Psychophysiological aspects of depressive syndromes.

Compared to 30 healthy controls, 59 drug free patients with primary major depression exhibited significantly higher rates of heart beat, respiration, and eye blinking; longer simple and associative reaction times; fewer spontaneous fluctuations of skin resistance, a lower salivation rate, a faster habituation rate of skin resistance orienting response, and a smaller CNV area in the EEG. Skin resistance level, speech pause time, N1P2 amplitudes of acoustically evoked potentials and the postimperative negative variation (PINV) in the EEG did not differ between groups. All deviations are nosologically unspecific; they can be regarded as signs of overarousal, as deficits, or as the result of protective inhibition. In all subjects the investigation was repeated twice, while the patients were treated with either amitriptyline or oxaprotiline, repetition of measurement influenced several variables, but most patient/control differences remained unaffected--irrespective of the drug applied.

Lithium suppresses hibernation in the Turkish hamster.

Daily uptake of lithium salt (LiCl) in the drinking water at a rate of over 100 micrograms/g b.wt (or 2.4 mEq/kg) reduced or suppressed natural torpidity (hibernation) in the Turkish hamster (Mesocricetus brandti). The data indicate a direct influence of lithium on clock-related functions controlling the hibernation process rather than indirect effects by preventing gonadal regression and thereby also hibernation.

Recurring short delirium with postpartum onset in two sisters.

We report on a 30-year-old woman who twice developed a short postpartum psychosis with organic signs, but without obvious organic cause. Extensive investigations only yielded a state of moderate hypercoagulability. Her sister had developed similar signs and symptoms during her second puerperium and died 5 days after her delivery. We discuss the combination of various precipitating factors for postpartum psychosis, the possible impact of the findings on its cause and its classification.

[Measurement of body temperature in the auditory canal or in the rectum: first experience with a device for continuous registration of body temperature of psychiatric patients (author's transl)]. / Die Temperaturmessung im Gehörgang und im Rektum" Erste Erfahrungen mit einem Gerät zur fortlaufenden Temperaturregistrierung bei psychiatrischen Patienten

A method for continuous measurement of body temperature over a 24-h period is presented. the temperature is measured by an active sensor placed in the external auditory canal or in the rectum, and stored on a magnetic tape in a portable cassette recorder weighing 400 g. Rectal temperature is less sensitive to environmental influence and easier to record than ear temperature. With this method possible disturbances of the diurnal temperature rhythm in psychiatric patients can be registered.

Evoked potentials, expectancy wave, and skin resistance in depressed patients and healthy controls.

Averaged evoked potentials, expectancy waves and number and amplitude of skin resistance responses to auditory stimuli are found to be significantly smaller in a group of 18 patients with primary depression than in 27 healthy controls. AEP amplitude attenuation is shown not to be an averaging artifact, due to varying response latencies. There are no simple relations between electrocortical and electrodermal parameters, but patients display more significant correlations between these two sets of variable than controls. Amplitude attenuations are interpreted as hyporesponsivity resulting from depressive inhibition. The narrower coupling of variables in the depressed group is viewed as a limitation in physiological plasticity.

[Changes in slow evoked potentials in depressed patients treated with amitriptyline and oxaprotiline]. / La modification des potentiels évoqués lents chez les déprimés sous amitriptyline et oxaprotiline.

Using a simple S1S2-R paradigm, acoustically evoked potentials, CNV, and PINV were recorded in 59 patients with major depressive disorder before and during a 4 week double blind pharmacological treatment with either amitriptyline (AT) or oxaprotiline (OT). In parallel, 30 healthy subjects were investigated 3 times, in identical intervals of 2 weeks. In the depressed state patients exhibited significantly smaller CNVs than the controls. In the AT-group clinical improvement and drug plasma levels of nortriptyline (NT, the principal metabolite of AT and an active antidepressant by itself) were positively related to increases in CNV-area; in the OT-group the reverse was true: increase in CNV-area was related to smaller OT plasma levels and less favourable outcome. The control group displayed a steady decline in CNV area during the 3 test sessions. N1P2 amplitude and PINV were not significantly different between groups and exhibited only minor variations during treatment.