Assessing physical activity in people with mental illness: 23-country reliability and validity of the simple physical activity questionnaire (SIMPAQ).

BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.

Adjuvant Rosa Damascena has a Small Effect on SSRI-induced Sexual Dysfunction in Female Patients Suffering from MDD.

BACKGROUND: Treating major depressive disorders (MDD) with selective serotonin-reuptake inhibitors (SSRIs) may impact negatively on sexual function. On the other hand, a satisfying sexual life is associated with overall life satisfaction. Therefore, managing this negative side effect of SSRIs may have an important role in the treatment of MDD. In a former study, adjuvant Rosa damascena oil improved sexual dysfunction in male patients suffering from both MDD and SSRI-induced sexual dysfunction (SSRI-I SD). The aim of the present study was to test whether the same pattern of results would be observed among female patients suffering from both SSRI-I SD and MDD. METHOD: In a double-blind, randomized and placebo-controlled clinical trial, a total of 50 female patients (mean age: 34 years) treated with an SSRI and suffering from MDD and SSRI-I SD were randomly assigned either to the verum (Rosa damascena oil) or to the placebo condition. Patients completed self-ratings of depression and sexual function at baseline, 4 weeks later, and at the end of the study 8 weeks after its start. RESULTS: Sexual desire, sexual orgasms, and sexual satisfaction increased over time. Patients in the verum group reported decreased pain. Overall sexual score increased in the verum as compared to the placebo condition. CONCLUSIONS: Whereas in male patients suffering from both MDD and SSRI-I SD adjuvant Rosa damascena oil improved sexual function, data on female patients are less robust and suggest only modest effects on female sexual function.

Serum levels of sodium valproate in patients suffering from bipolar disorders: comparing acute and maintenance phases of mania.

OBJECTIVES: Bipolar disorders (BD) are characterized by episodes of mania and depression. There is evidence that states of psychiatric disorders impact on neurotransmitters, endocrine system and membrane transport and, therefore, it is possible that specific phases of BD differentially influence the pharmacokinetics of some drugs. The aim of the present study was to investigate the drug-disease interaction between sodium valproate, one of the major drugs used in the treatment of bipolar disorder, and acute versus maintenance states of manic episodes. METHOD: 37 patients (mean age ± SD = 37.54 ± 11.27 years; 23 males, 14 females) suffering from bipolar disorder completed the study. Blood samples were taken during both acute and maintenance states. RESULTS: Neither the trough concentration (p = 0.567) nor the internal clearances (p = 0.729) of sodium valproate in the acute phase of mania differed statistically or descriptively from those in the maintenance phase. Marginally significant phase by gender interactions were observed. CONCLUSION: No significant effect of the acute phase of mania was observed in bipolar patients and no relationship could be found between drug pharmacokinetics and disease phase. This may be explained by specific pharmacokinetic features of the drug such as low extraction ratio values. However, phase by gender interactions indicate possible gender-related issues.

Microsleep during partial sleep deprivation in depression.

BACKGROUND: Sleep deprivation (SD) exerts a beneficial effect on mood and sleep in about 60% of depressed patients usually followed by a relapse into depression after the recovery night. Short phases of sleepiness, especially naps in the early morning, may be responsible for this phenomenon. METHODS: To evaluate the effect of short, even ultrashort phases of sleep-microsleep (MS) during partial sleep deprivation (PSD) on mood, cognitive psychomotor performance (CPP), and sleep, an electroencephalograph (EEG) was continuously recorded over 60 hours in 12 patients with major depression. Subjective mood was assessed by a visual analogue scale and CPP by a letter cancellation test. RESULTS: The results illustrate that in depressed patients during PSD the amount of MS is increased, predominantly in the early morning, which was subjectively unrecognized and not observed by nursing staff. Patients with a low cumulative amount of MS during PSD improved significantly in mood, CPP, and sleep pattern compared to the patients with a high amount of MS who showed only slight changes. CONCLUSION: Therefore, accumulated MS may influence the SD-induced positive effects in depressed patients.

Hypothalamic-pituitary-adrenal system function in patients with Alzheimer's disease.

The neuropathologic hallmarks of Alzheimer's disease (AD) are very prominent in the hippocampus, a brain site which is pivotal for the regulation of the hypothalamic-pituitary-adrenal (HPA) system. Thus, the combined dexamethasone-suppression/CRH-stimulation-test outcome in patients with AD was compared to that of healthy elderly controls to assess--with a more refined neuroendocrine challenge procedure--HPA function in AD. Cortisol secretion after dexamethasone (DEX) pretreatment and before CRH was increased in Alzheimer's patients and 21% of this group were DST-nonsuppressors. None of the healthy control subjects escaped DEX-induced suppression of cortisol. However, after additional CRH administration, AD patients released significantly less cortisol and ACTH than the control subjects. No correlations were found between any of the endocrine parameters and degree of severity of dementia. It is concluded that the DST part of the DEX/CRH test better reflects glucocorticoid feedback disturbances, probably at a suprapituitary level. The CRH part of the DEX/CRH-test outcome might indicate the loss of endogenous CRH-Arginine-Vasopressin (AVP) synergism of the HPA system of these patients.

Clinical differentiation between lethal catatonia and neuroleptic malignant syndrome.

Lethal catatonia, a syndrome described several decades before the advent of neuroleptic drugs, has been regarded by many investigators as clinically similar to, and perhaps indistinguishable from, neuroleptic malignant syndrome. However, published case reports of the two syndromes indicate differences in mode of onset, signs and symptoms, and outcome. Lethal catatonia often begins with extreme psychotic excitement, which, if persistent, can lead to fever, exhaustion, and death. Neuroleptic malignant syndrome begins with severe extrapyramidally induced muscle rigidity. Because lethal catatonia often requires neuroleptic treatment and neuroleptic malignant syndrome necessitates immediate cessation of neuroleptics, their early clinical differentiation is important.

Neuroendocrine effects of a 20-mg citalopram infusion in healthy males. A placebo-controlled evaluation of citalopram as 5-HT function probe.

Pharmacokinetic measurements, neuroendocrine responses, and side effects profiles of intravenous infusions of 20 mg citalopram over 30 minutes during the early afternoon have been studied. Eight healthy male volunteers were enrolled in a placebo- (saline) controlled, single-blind, cross-over protocol. Plasma concentrations of the parent compound showed a double exponential decay. Demethyl and didemethyl metabolites were not detectable, but low concentrations of the propionic acid derivative of citalopram were found. Determination of the citalopram enantiomers yielded a balanced S(+)/R(-) ratio of 0.9 to 1.2. The endocrine response to the drug was characterized by significant increases in plasma prolactin and cortisol. Except for one subject, who developed pronounced side effects, human growth hormone showed a surge following saline that was inhibited following citalopram. Rectal temperature and heart rate were not affected and tolerability was favorable. Because of citalopram's extremely high selectivity for the presynaptic 5-hydroxytryptamine nerve terminals, the present data suggest that it might be a promising tool for the investigation of serotonergic function in the human brain in vivo.

Effects of the novel acetylcholinesterase inhibitor SDZ ENA 713 on sleep in man.

A novel brain-selective acetylcholinesterase inhibitor, SDZ ENA 713, is under development for the treatment of dementia of the Alzheimer type. To determine the threshold dose for central activity, single doses of the compound were administered to 20 young male volunteers in a double-blind cross-over design and the effects on the sleep electroencephalography studied. The first group of eight volunteers received in random order: placebo, 0.5 mg; and 1 mg SDZ ENA 713. The second group of 12 volunteers received: placebo, 1.3 mg; and 2 mg SDZ ENA 713. Sleep quality was not affected by the study medication, which was well tolerated by all subjects. A statistically significant increase in rapid-eye movement sleep density was observed after doses of 1 mg, 1.3 mg, and 2 mg. Rapid-eye movement latency and slow-wave sleep were not altered. The results demonstrate that SDZ ENA 713 is centrally active in man at well-tolerated doses.

Effect of zopiclone and temazepam on sleep EEG parameters, psychomotor and memory functions in healthy elderly volunteers.

RATIONALE: The increased prevalence of sleep disturbance in old age is accompanied by a higher prescription rate of hypnotics, predominantly benzodiazepines in the elderly. In young volunteers zopiclone exerts a beneficial effect on sleep continuity without suppression of SWS and REM sleep; psychomotor performance and vigilance seemed to be less impaired than under classical benzoediazepines. OBJECTIVE: The present study investigates the effects of zopiclone on sleep EEG and cognitive performance in comparison to temazepam and placebo in the elderly population. METHODS: Single oral doses of zopiclone (7.5 mg), temazepam (20 mg) and placebo were administered in a randomized double-blind, completely counterbalanced cross-over design to 12 healthy elderly men and women (65.9 +/- 3.6 years, range 60-70 years). On each of the 3 study nights a sleep EEG was registered from 10 p.m. to 6.30 a.m. and cognitive performance tests were applied at 8 p.m., 2 a.m. (when subjects were awake for 30 min), 7 a.m. and 9 a.m. RESULTS: After zopiclone treatment, sleep continuity had significantly improved and sleep stage 4 was increased compared to temazepam and placebo. In addition, both active substances significantly reduced REM density. Neither active compound substantially altered psychomotor and memory performance. CONCLUSIONS: Zopiclone and temazepam can be considered as effective hypnotics in elderly subjects when administered in that dosage. The superiority of zopiclone on sleep architecture may be related to a more specific action of zopiclone at the GABA-A benzodiazepine receptor complex. The suppression of REM density by both compounds and their subtle effects on cognition may reflect a GABAergic mediated reduction of cholinergic neuro-transmission.

Effects of flumazenil on recovery sleep and hormonal secretion after sleep deprivation in male controls.

The effects of flumazenil, a benzodiazepine antagonist, on the sleep electroencephalogram (EEG) and neuroendocrine secretion in early morning recovery sleep (0500-0800 hours) following sleep deprivation (SD; 2300-0500 hours) were studied in seven healthy men. SD induced an increase in slow wave sleep (SWS), a decrease in sleep onset latency (SOL), an enhancement of EEG delta and theta power in non-rapid-eye-movement sleep, an increase in plasma human growth hormone (GH) concentration, and a decrease in plasma cortisol levels in recovery sleep (0500-0800 hours). Plasma GH, but neither plasma cortisol nor adrenocorticotrophic hormone (ACTH) concentration was attenuated during SD as compared to sleep (2300-0445 hours). The administration of flumazenil (3 x 1 mg intravenously) during recovery sleep resulted in an inhibition in SWS, an increase in stage 2 sleep, a selective reduction in delta and theta power, and a tendency to prolongation of SOL. Plasma GH concentration was decreased but plasma cortisol and ACTH remained unaffected. Since the SD-induced changes in sleep EEG and plasma GH secretion were antagonized by flumazenil, it is suggested that electrophysiological and hormonal effects of SD are mediated at least in part through GABAergic mechanisms.

Human plasma DSIP decreases at the initiation of sleep at different circadian times.

Nocturnal plasma delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) was determined serially in seven healthy male subjects. Time courses during nocturnal sleep (2300-0800 h), nocturnal sleep deprivation (2300-0500 h), and morning recovery sleep (0500-0800 h) after sleep deprivation were compared. A significant decrease in plasma DSIP-LI was found at the transition from wakefulness to sleep in both evening sleep (2300 h) and morning recovery sleep (0500 h). Time courses were accompanied by physiological changes in sleep electroencephalographic slow-wave activity, and in plasma concentrations of cortisol and human growth hormone. No sleep stage specificity was found. It is concluded that DSIP is influenced by the initiation of sleep.

Differential mood response to natural and synthetic corticosteroids after bilateral adrenalectomy: a case report.

A 48-year-old woman who had had a bilateral adrenalectomy for Cushing's syndrome developed severe psychotic symptoms that were unresponsive to psychotropic drugs as long as she was taking prednisone (PRED) as replacement therapy. However, after she was switched to a regimen of cortisol (CORT) and fludrocortone (FLUD) the psychopathology disappeared. Mechanisms related to the differences in the interaction of natural (e.g. CORT) and synthetic (e.g. PRED) corticosteroids with the central glucocorticoid and mineralocorticoid receptors may explain the different effects upon psychopathology.

Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment--neurobiological and psychometric assessment of course.

The present study was designed to investigate the clinical efficacy of trimipramine with adjunct sleep deprivation (SD) or bright light (BL) and to evaluate psychometric and neurobiological variables that might be of predictive value for treatment response. We used (1) the combined dexamethasone-corticotropin releasing hormone test (DEX-CRH test) to characterize alterations of the hypothalamic-pituitary-adrenal (HPA) system; (2) polysomnography to evaluate sleep disturbances; and (3) a standardized test battery to assess cognitive psychomotor functions after study initiation and after 5 weeks of treatment. The overall response rate (> or = 50% decrease in score on Hamilton Rating Scale for Depression [HRS]) was 55% (N = 42). The response rate in the group with trimipramine monotherapy (N = 14) was 79%, whereas in the groups with adjunct SD (N = 14) and BL (N = 14), respectively, it was only 43%. All three groups showed significant improvement at the end of the third week of treatment. Neither of the adjunct treatments hastened the onset of antidepressant action as measured by HRS. A significantly higher proportion of nonresponders than responders (p < .05) had HPA dysregulation, disturbed rapid eye movement (REM) sleep (REM latency, REM% first third of night) and decreased non-REM sleep (% stage 2). The non-responders showed significantly more corticotropin (ACTH) secretion after CRH stimulation in the DEX-CRH test than the responders and a less rapid normalization of the neuroendocrine dysregulation (cortisol secretion) (p < .01). In addition, REM latency was significantly shorter in the BL group than in the monotherapy group and estimated duration of illness significantly longer in the SD group than in the monotherapy group. REM latency, percentage of REM sleep during the first third of the total sleep period, percentage of non-REM sleep stage 2 and ACTH release after a DEX-CRH challenge predicted response across all three treatment groups. The neurobiological symptoms were unevenly distributed, among the three groups, thus creating heterogeneity in these measures. This heterogeneity may have contributed to the different treatment response rates as defined by psychopathology (HRS). In contrast, the neuropsychological tests and some of the sleep-EEG investigations revealed different response patterns for different groups: The onset of improvement in simple cognitive functions and in sleep continuity was earlier in the adjunct treatment groups. This study underlines the need for a multidimensional approach including use of neurobiological and neuropsychological measures to identify the therapeutic profiles of different treatment strategies and predictors of outcome.

Effect of sleep deprivation on neuroendocrine response to a serotonergic probe in healthy male subjects.

Neuroendocrine responses to stimulation with a selective serotonin reuptake inhibitor (citalopram) were measured to investigate the effects of all-night sleep deprivation on serotonergic function in healthy male subjects (n = 7). We studied citalopram-stimulated prolactin and cortisol plasma concentrations in a placebo-controlled cross-over protocol following sleep and sleep deprivation. Citalopram infusion (20 mg i.v. at 14:20-14:50 h) after a night of undisturbed sleep prompted robust increases in both plasma prolactin and cortisol concentrations. Following a night of sleep deprivation, by contrast, the citalopram-induced prolactin response was blunted, but the cortisol response was not significantly altered. This differential response pattern relates to the distinct pathways through which serotonin may activate the corticotrophic and the lactotrophic systems. While an unchanged cortisol response does not indicate (but also does not refute the possibility of) an altered serotonergic responsivity following sleep deprivation, the suppressed prolactin response could reflect a downregulation of 5-HT1A or 2 receptors. An alternative, not mutually exclusive, explanation points to the possibility that sleep deprivation activates the tubuloinfundibular dopaminergic system, the final inhibitory pathway of prolactin regulation.

Serial partial sleep deprivation as adjuvant treatment of depressive insomnia.

1. Sleep disturbance is a prominent symptom of major depression. Despite specific treatment with antidepressants, there is a substantial number of patients who improve in depressed mood but remain sleep disturbed. 2. Polysomnographic sleep (PSG) data and self reported sleep measures were assessed at baseline and after one week in 18 patients (35-65 years) randomly assigned to treatment with either trimipramine alone 200 mg/d (group 1) or trimipramine (200 mg/d) and additional serial partial sleep deprivation in the second half of the night (3x/week) (group 2). 3. In group 1 no marked changes between baseline and after treatment were found. 4. In group 2 the PSG data showed a significant increase of slow wave sleep and a compensatory decrease in stage 1. Sleep continuity improved in terms of numbers of awakenings, sleep onset latency and total sleep time. These changes were in parallel with the subjective estimation of sleep in group 2. 5. There was no significant difference in the Hamilton rating scale scores neither at baseline nor after treatment. 6. These observed effects on sleep following additional serial PSD therapy seem to occur independent from the antidepressive effect.

Increased trimipramine plasma levels during fluvoxamine comedication.

A depressive patient, a non-responder to trimipramine (TRI), was comedicated first with citalopram (CIT) and then with fluvoxamine (FLUV). Both the TRI-CIT and TRI-FLUV combination treatments led to a worsening of the depressive state and to the appearance of panic attacks. The addition of FLUV to TRI resulted in a twofold increase of the plasma levels of TRI and to a slight increase of its N-demethylated and 2-hydroxylated metabolites. These results suggest that the interaction between FLUV and TRI occurred at the level of cytochrome P-450IID6 and cytochrome P-450meph in this patient, phenotyped as an extensive metabolizer of both dextromethorphan and mephenytoin. The adverse effects were possibly due to (a) a pharmacokinetic interaction between CIT and FLUV with TRI and/or (b) alterations in serotonergic and/or dopaminergic neurotransmission.

Repeated administration of the combined dexamethasone-human corticotropin releasing hormone stimulation test during treatment of depression.

Human corticotropin releasing hormone (h-CRH) was administered to 14 patients with major depression, after premedication with an overnight dose of 1.5 mg dexamethasone. Cortisol response, expressed as area under the time course curve (AUC), was significantly higher in the 14 patients than in a group of 13 age-matched control subjects (9.4 +/- 7.6 ng x min x 1,000/ml vs. 3.1 +/- 3.6 ng x min x 1,000/ml). Corresponding AUC values for plasma adrenocorticotropic hormone (ACTH) were also significantly higher in patients than in control subjects (4.9 +/- 1.4 pg x min x 1,000/ml vs. 2.6 +/- 0.9 pg x min x 1,000/ml). After patients were treated with trimipramine (200 mg/day) for 6 weeks, the combined dexamethasone/h-CRH test was repeated. At that time, depression scores were significantly improved and the patients' cortisol response pattern became indistinguishable from that of controls. While plasma cortisol output normalized during treatment with trimipramine, ACTH release remained exaggerated. The combined dexamethasone/h-CRH challenge test may be of particular value in the detection of state-dependent changes of pituitary-adrenocortical neuroregulation.

Sleep in depression and sleep deprivation: a brief conceptual review.

Risk factors for somnipathies are psychological stress or psychiatric illness. More severe sleep difficulties have been found to be clearly related to psychiatric illness such as depression and phobias, as well as to addiction. Somnipathies can objectively be identified by means of polygraphy. Overall, polysomnographic measures in patients with affective disorders differ most frequently and significantly from those in normal control subjects. Persistent sleep disturbances are associated with significant risk of both relapse and recurrence in mood disorders and an increased risk of suicide. In addition to changes in sleep architecture, patients with major depression show profoundly altered patterns of nocturnal hormone secretion, possibly through mechanisms that link regulation of sleep with neuroendocrine activity. Basic and clinical approaches of sleep research established neurobiological models into the underlying pathophysiology associated with psychiatric disorders.

Suicidal tendencies: detection and evaluation.

Initially we differentiate a simple psychosocial crisis from a psychiatric crisis; the former is usually a non-pathological phenomenon, which may result in a pathological development. As one critical assumption, we consider suicidal potential. After discussing the phenomena of suicide and attempted suicide, the problem of suicide and family is emphasized in regard to biological-genetic and psychosocial aspects. Finally, we refer to prophylactic-therapeutic interventions for psychosocial crisis and manifest suicidal tendency.