Actigraphic, but not subjective, sleep measures are associated with cognitive impairment in memory clinic patients.

AIM: Sleep disturbances are prevalent in various dementia subtypes but rarely investigated in early clinical stages. Although memory clinics have become an established institution for the early diagnosis of dementia, sleep assessment is not part of their routine diagnostics. This study aimed to examine whether subjective and objective sleep variables are related to cognitive impairment in patients referred to a memory clinic. METHODS: On two consecutive days, patients underwent routine diagnostic procedures, including a neuropsychological examination (consortium to establish a registry for alzheimer's disease), and had their sleep quality evaluated by the Pittsburgh Sleep Quality Index and overnight hand-wrist actigraphy. RESULTS: Data of 31 patients (age, M ± SEM: 74.1 ± 1.5; 18 women, 13 men; Clinical Dementia Rating: 0-1) were analysed. One had been diagnosed with subjective cognitive impairment, 13 with mild cognitive impairment with or without depression, and 17 with dementia syndrome due to Alzheimer's and/or cerebrovascular disease. Compared to patients with subjective or mild cognitive impairment, dementia patients showed a significantly increased nocturnal acceleration magnitude; other differences in subjective and objective sleep measures were not significant. Comparing patients with subjectively poor (Pittsburgh Sleep Quality Index > 5: n = 9) and good sleep (Pittsburgh Sleep Quality Index ≤ 5: n = 22) yielded no differences in any neuropsychological and clinical variables. In contrast, patients with low actigraphically recorded sleep efficiency (<85%: n = 11) exhibited a significantly more impaired cognitive performance than those in the high sleep efficiency group (≥85%: n = 20). Correlation analyses demonstrated that actigraphically assessed disturbed sleep continuity accompanied by increased night-time motor activity was substantially associated with cognitive impairment. CONCLUSION: This study highlights that objectively assessed, but not self-reported, parameters of disturbed sleep are closely related to cognitive dysfunction in the early stages of dementia of different aetiologies. Possible diagnostic and treatment implications are discussed.

[Subjective memory impairments in early detection of dementia: Relation to acceptability of lumbar puncture in memory clinic patients]. / Subjektive Gedächtnisbeeinträchtigungen in der Früherkennung von Demenzen: Beziehung zur Akzeptanz der Lumbalpunktion bei Patienten einer Gedächtnissprechstunde.

BACKGROUND: In memory clinics, biomarker-based diagnostic tools for early detection and differential diagnosis of dementia are increasingly important, even if their acceptance by patients is relatively low. OBJECTIVE: The aim of study was to examine whether sociodemographic and clinical features of memory clinic patients are associated with acceptance of lumbar puncture (LP). Of particular interest was the patients' self-perception of memory decline (subjective memory impairment, SMI) accompanied by related concerns that might affect decision to consent to LP. METHODS: Consecutive patients were examined in a day-care hospital on two consecutive days in order to implement a diagnostic procedure based on the S3 guideline "Dementia" including offer of LP. We assessed demographic and clinical variables such as depression, anxiety, neurocognitive performance and dementia severity (Clinical Dementia Rating, CDR). Furthermore, patients were interviewed about perceived memory decline and were classified on this basis - independent of their neuropsychological results - into three groups: no SMI, SMI without concerns or SMI with concerns. RESULTS: Of 44 patients (73.8 ±â€Š8.3 years; 27 f/17 m; CDR < 1: n = 16, CDR = 1: n = 28), 29 had SMI with concerns. These patients tended to be younger and had a higher level of education than those who did not report SMI (n = 7) and those perceiving SMI without concerns (n = 8). Furthermore, patients without SMI more frequently had a dementia syndrome. Patients who agreed to lumbar puncture (n = 23) were - compared to patients refusing LP (n = 17; 4 patients had to be excluded because of medical contraindication for immediate LP) - more likely male, had significantly more frequent SMI with concerns and performed poorer on declarative memory tasks. Binary regression analysis yielded SMI with concerns, a more impaired memory performance and male sex as significant predictors for consenting to LP. CONCLUSIONS: The study provides evidence that patient characteristics such as subjective and objective memory impairment as well as sex may affect the likelihood to consent to a generally less accepted biomarker-based dementia diagnostic procedure such as LP.

Sleep Duration of Inpatients With a Depressive Disorder: Associations With Age, Subjective Sleep Quality, and Cognitive Complaints.

Sleep complaints and sleep disturbances are common in depression; however, the association of sleep duration and subjective sleep quality has been rarely investigated. Thus, subjective sleep quality and sleep duration were analyzed in depressed inpatients. Questionnaire data comprising clinical and sleep-related questions were sampled over a one-year period from adult inpatients with depressive syndromes. Sleep duration and items related to sleep quality were analyzed by means of group comparisons (sleep duration categories) and correlation analyses. Data of 154 patients (age 58.2±17.0 years, 63.6% women) were analyzed. Mean sleep duration was 7.2±2.1 h (16.9% of patients were below and 7.1% above age-specific recommendations), 25-40% of patients reported almost always daytime sleepiness, non-restorative sleep, attention deficits, or memory complaints with significant correlations between all variables (P<0.05). Sleep duration and sleep quality indicators showed significant curvilinear associations (quadratic contrast, P<0.05); i.e. extremely low and high sleep durations were associated with unfavorable sleep quality and subjective cognitive impairment. Non-recommended low or high sleep durations occur in a substantial proportion of patients with depression, and both were associated with poor sleep quality and subjectively impaired cognitive functions. Clinicians should be aware of these relationships. During hospitalization, a more individualized sleep-wake schedule should be applied.

Eveningness and poor sleep quality independently contribute to self-reported depression severity in psychiatric inpatients with affective disorder.

Background Chronotype and insomnia have been related to the development and to an unfavourable course of depression. However, the mutual relationship of both risk factors is as yet unclear, especially in acute, clinically manifest depressive disorders. Aims The present study was carried out to elucidate the separate direct and indirect influence of chronotype and poor sleep quality on depression severity in patients hospitalized for depression. Methods Depression severity (BDI-II), chronotype (Morningness-Eveningness Questionnaire), and subjective sleep quality (Pittsburgh Sleep Quality Index total score) were assessed concurrently in inpatients with a depressive syndrome and insomnia during routine treatment. Correlations, multiple regression and bootstrapping methods for testing mediation models were applied to assess the independent direct and indirect effects of chronotype and sleep quality on depression severity, after adjusting for effects of age and gender. Results Data from 57 consecutively admitted patients (88% with major depression) were analyzed (68% women, mean age 41 ± 13 years). Significant correlations between morningness-eveningness (p <0.05) or sleep quality (p <0.01) and depression severity were found; in a multiple regression model comprising chronotype, sleep quality, age and gender, only chronotype (p <0.05) and sleep disturbances (p <0.01) remained as independent significant concurrent predictors of depression severity (R(2) = 0.184, p <0.01). Two mediation models revealed no significant results. Conclusions Eveningness and poor subjective sleep quality were independently and directly associated with higher depression severity in inpatients with depressive syndromes. Chronotype and sleep quality should be taken into account not only in risk assessment and prevention but also in hospitalized patients to develop and improve treatment options.

Circadian preference and sleep quality in healthy controls and psychiatric inpatients with major depressive disorder - An actigraphy study incorporating morning and evening mood assessments.

Major depressive disorder (MDD) is frequently accompanied by sleep disturbance. Regarding diurnal preference (chronotype), sleep problems and low mood have been associated with evening orientation. Considering diurnal preference, we investigated subjective restorative value of sleep and actigraphy sleep parameters together with mood assessments twice a day, i.e. in the morning and evening, during weekdays and weekends in MDD psychiatric inpatients and healthy controls (HCs). The restorative value of sleep was higher during the weekend in HC, and bedtimes and risetimes were delayed during the weekend compared to weekdays in HC and MDD. Morning mood affected subjective sleep ratings in both groups, while association with symptom severity (BDI) in MDD remained insignificant. In HC, better evening mood was associated with later bedtimes. Regarding the chronotype in HC, evening orientation was associated with relatively low restorative value of sleep during weekdays, and morning orientation was associated with relatively higher actigraphy sleep efficiency during weekdays compared to weekend. In MDD, an association of evening orientation with later rise times could be observed, while no chronotype dependent effect emerged regarding the restorative value of sleep or sleep efficiency. Our results emphasize that research on sleep in MDD should incorporate weekdays as well as weekends, chronotype assessment, and measures of morning and evening mood, as these can be associated with ratings of the subjective restorative value of sleep (i.e. in our study, better morning mood was associated with higher restorative values), but also with behavioral sleep parameters (i.e. in our study, more positive evening mood was associated with later bedtimes). Potentially, the restorative value of sleep in MDD evening types can be improved by maintaining a regular sleep schedule, which needs to be investigated in an experimental design.

The effects of oral contraceptives on detection and pain thresholds as well as headache intensity during menstrual cycle in migraine.

BACKGROUND: Clinically, oral contraceptives (OC) can influence pain in both migraine headache and temporomandibular pain disorders. Estrogen as an ingredient of OC might be a responsible factor for these observations. We conducted the present study to test whether OC are able to alter the severity of headache attacks as well as the detection or pain thresholds over the course of the menstrual cycle in patients with migraine. METHODS: Thirteen healthy and regularly menstruating women and 26 migraineurs (13 using OC and 13 not using OC) were studied on the days 1, 4, 14, and 22 of their menstrual cycle. In all participants, saliva was collected first for determination of estrogen on each study day. Then, detection thresholds (warmth, cold, electrical current) and pain thresholds (cold, heat, pressure, electrical current) were assessed. Migraineurs were asked for headache attacks occurring in a period of 24 hours before testing and to estimate pain intensity on a verbal rating scale. RESULTS: On day 4 of the menstrual cycle, migraineurs using OC suffered significantly more from severe migraine attacks than migraineurs not taking OC. With respect to detection and pain thresholds, no effects of OC could be observed as concerning the differences between migraineurs with or without OC medication. On day 22, the severity of migraine headache was significantly related with the pain thresholds for pressure and electrical current, suggesting paradoxically more severe headache attacks in patients presenting with higher pain thresholds. Healthy volunteers disclosed higher salivary estrogen levels than migraineurs and migraineurs not using OC higher concentrations than migraineurs using OC throughout the menstrual cycle. CONCLUSIONS: In this study, the use of OC intensified migraine (however only at the end of menstruation) however had no influence on detection and pain thresholds in migraineurs. Possible reasons for this dissociation will be discussed.

The effects of recovery sleep on pain perception: A systematic review.

Experimental studies highlight profound effects of sleep disruptions on pain, showing that sleep deprivation (SD) leads to hyperalgesic pain changes. On the other hand, given that sleep helps normalizing bodily functions, a crucial role of restorative sleep in the overnight restoration of the pain system seems likely. Thus, a systematic review of experimental studies on effects of recovery sleep (RS; subsequently to SD) on pain was performed with the aim to check whether RS resets hyperalgesic pain changes occurring due to SD. Empirical animal and human studies including SD-paradigms, RS and pain assessments were searched in three databases (PubMed, Web of Science, PsycINFO) using a predefined algorithm. 29 studies were included in this review. Most results indicated a reset of enhanced pain sensitivity and vulnerability following RS, especially when total SD was implemented and pressure pain or painful symptoms (human studies) were assessed. Further research should focus on whether and how recovery is altered in chronic pain patients, as this yields implications for pain treatment by enhancing or stabilizing RS.

Influence of chronotype on daily mood fluctuations: pilot study in patients with depression.

Depression risk is associated with a late chronotype pattern often described as an 'evening chronotype'. Fluctuations in mood over consecutive days have not yet been measured according to chronotype in in-patients with depression. A total of 30 in-patients with depression and 32 healthy controls matched for gender and age completed a chronotype questionnaire and twice-daily ratings on mood for 10 consecutive days (registered in the German Clinical Trials Register: DRKS00010215). The in-patients had Saturdays and Sundays as hospital-leave days. The relationship between chronotype and daily mood was mediated by the weekday-weekend schedule with higher levels of negative affect in the evening-chronotype patient subgroup at weekends. Results are discussed with respect to a probably advantageous standardised clinical setting with early morning routines, especially for patients with evening chronotypes.

Evening preference and poor sleep independently affect attentional-executive functions in patients with depression.

Cognitive impairments are well documented in major depressive disorder (MDD), however, they cannot be fully explained by depressive symptom severity. We investigated how diurnal preference and sleep quality affect cognitive function in MDD. In 34 inpatients with current MDD and 29 healthy controls (HC), we obtained diurnal preference (Morningness-Eveningness Questionnaire, MEQ) and subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI). Further, current mood and neuropsychological performance (Trail Making Test, TMT, part A and B) were assessed in the evening and in the following morning. Patients with MDD performed worse than HC on the TMT-B (particularly requiring executive function), but not on the TMT-A (assessing foremost visuomotor processing speed). In general, participants with evening preference (MEQ-score median split) performed poorer on the TMT than participants with morning preference. Subgroup analyses within MDD confirmed the negative effect of evening preference on the TMT. In addition, patients with severely impaired sleep quality (PSQI > 10) performed cognitively worse than patients with normal to moderately impaired sleep quality (PSQI ≤ 10). The results were largely independent of current mood state. Our findings suggest that evening preference and severely impaired sleep quality independently contribute to cognitive impairment in MDD.

Effects of total sleep deprivation in major depression: overnight improvement of mood is accompanied by increased pain sensitivity and augmented pain complaints.

OBJECTIVE: Major depressive disorder (MDD) is associated with more pain complaints and an altered pain perception. Studies regarding the longitudinal relationship between depressive symptoms and pain processing have rarely been performed and have produced inconsistent results. To clarify how short-term alleviation of depressive mood is linked to changes in pain processing, the effect of sleep deprivation (SD) on pain and somatosensory thresholds, pain complaints, and mood was investigated in MDD patients. METHODS: Nineteen drug-free inpatients with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, diagnosis of MDD were investigated for 3 weeks. All patients received cognitive-behavioral therapy and were randomized to obtain either additional SD therapy (six nights of total SD, separated by recovery sleep) or no SD therapy (control group). Heat/cold pain thresholds, warmth/cold thresholds, measures of current pain complaints, and mood were assessed the evening before and the morning after SD as well as before and after a normal night sleep in the control group. Long-term changes of depressive symptomatology were assessed by weekly mood ratings. RESULTS: Both treatment groups improved markedly in mood over the 3-week treatment period. SD regularly induced a moderate but statistically nonsignificant overnight improvement of mood, which was abolished by recovery sleep. Compared with the control condition, SD significantly decreased heat pain thresholds and nearly significantly cold pain thresholds; SD significantly augmented pain complaints the next morning. No such effects were observed for somatosensory thresholds. CONCLUSIONS: SD induced differential short-term effects on mood and pain, with the patients being less depressed but more pain vulnerable.

Sleep deprivation and pain perception.

Chronically painful conditions are frequently associated with sleep disturbances, i.e. changes in sleep continuity and sleep architecture as well as increased sleepiness during daytime. A new hypothesis, which has attracted more and more attention, is that disturbances of sleep cause or modulate acute and chronic pain. Since it is well-known that pain disturbs sleep the relationship between the two has since recently been seen as reciprocal. To fathom the causal direction from sleep to pain we have reviewed experimental human and animal studies on the effects of sleep deprivation on pain processing. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can interfere with analgesic treatments involving opioidergic and serotoninergic mechanisms of action. The still existing inconsistency of the human data and the exclusive focus on REM sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity.

Subjective sleep quality and sleep duration of patients in a psychiatric hospital.

Sleep complaints and sleep disturbances are highly prevalent in patients with psychiatric disorders. During hospitalization the patients' condition may be even worse but little is known about the subjective sleep quality in psychiatric hospitals. Thus, we have investigated subjective sleep quality and mean sleep duration in patients with different psychiatric disorders at the end of hospitalization. For a period of one year, inpatients of a psychiatric hospital with diagnosis of substance use disorder (SUD), schizophrenia (SCZ), or anxiety/depressive disorders (AND) were routinely asked to fill in an easily comprehensible sleep quality questionnaire at the end of their hospitalization. Age, gender, subjective sleep quality, and sleep duration were analyzed; sleep duration was classified according to age-specific recommendations. Data of n=309 patients (age 52.1±17.9y, 56.1% women) were analyzed (n=63 SUD, n=50 SCZ, n=196 AND). Mean sleep duration was 7.0±2.0 h; 20.7% of patients had sleep durations below and 4.5% above age-specific recommendations. Non-restorative sleep during hospitalization was reported "almost always" in 38.2% (n=118), and "occasionally" in 30.1% (n=93). Subjective sleep quality was significantly associated with sleep duration (rs =-0.31, P<0.0005), but not with age, gender or diagnostic subgroup. The study showed that a great proportion of patients reported poor subjective sleep quality during hospitalization, regardless of age, gender and psychiatric diagnosis. As sleep quality was significantly associated with short sleep duration, a first step could be to take care to achieve recommended age-specific sleep durations in psychiatric hospitals.

Patterns of self-reported depressive symptoms in relation to morningness-eveningness in inpatients with a depressive disorder.

The stable and persisting preference for activities in the late evening (i.e. eveningness) is associated with a higher risk for depression, suicidality, and non-remission in major depression. The present study investigated symptom patterns in hospitalized patients with depressive syndromes in relation to morningness-eveningness (chronotypes). Depressive symptoms (Beck Depression Inventory [BDI-II]) and chronotype (German version of the Morningness-Eveningness Questionnaire [D-MEQ]) were assessed after admission and before discharge in inpatients with mainly major depression. Group differences of BDI-II single items and three BDI-II factors (cognitive, affective, somatic) between patients divided at the D-MEQ sample median into "morning preference" (MP) and "evening preference" (EP) were calculated. Data from 64 consecutively admitted patients (31MP/33EP) were analyzed. Both groups (MP/EP) were comparable regarding age, sex, diagnosis, length of stay, and subjective sleep quality, BDI-II scores were significantly higher in EP than in MP at admission. At admission and discharge, cognitive symptoms were significantly more pronounced in EP vs. MP; non-significant differences between EP and MP were found for affective and somatic symptoms. The results underline the importance of the trait-like chronotype for severity and symptomatology in patients with depressive disorders. The patients' chronotype should be taken into account in diagnostics and treatment of depressive disorders.

[MVT - A Multiprofessional Behavioural Therapy Program for Inpatient Treatment of Depression in Old Age]. / MVT - ein Multiprofessionelles VerhaltensTherapeutisches Programm zur stationären Behandlung von Depressionen im höheren Lebensalter.

OBJECTIVE: Depression in old age is common but patients are rarely treated in specialized units implementing a psychotherapeutic treatment approach. METHODS: A multiprofessional behavioral therapy program (MVT) for inpatient treatment of depressive elderlies was conceptualized, implemented and evaluated at a specialized unit of a hospital for psychiatry and psychotherapy. RESULTS: Preliminary analyses indicated that various behavioral group interventions were well accepted by patients. CONCLUSIONS: The implementation of a psychotherapeutic therapy program specifically designed for depressed elderly inpatients is feasible and could be more broadly applied to improve clinical practice for this patient group.

Chronotypes in patients with nonseasonal depressive disorder: Distribution, stability and association with clinical variables.

The individual's chronotype is regarded as rather stable trait with substantial heritability and normal distribution of the "morningness-eveningness" dimension in the general population. Eveningness has been related to the risk of developing affective, particularly depressive, disorders. However, age and other sociobiological factors may influence chronotypes. The present study investigated the distribution, stability, and clinical correlates of chronotype and morningness-eveningness in hospitalized patients with affective disorder. Chronotype was assessed with the morningness-eveningness questionnaire (MEQ) in 93 patients with nonseasonal depressive syndrome (85% major depression; 15% depressive adjustment disorder) after admission, and in 19 patients again before discharge. Distribution, stability and correlations of MEQ scores with clinical variables were calculated. Additionally, a literature analysis of chronotype distributions in samples of nondepressed persons and patients with nonseasonal depression was carried out. MEQ scores (mean 49 ± 11, range 23-75, higher scores indicate morningness) in 93 acutely depressed inpatients (age 41 ± 14 years, range 18-75 years; 63% women; hospitalization 48 ± 22 days; BDI-II 32 ± 11) were normally distributed (Shapiro-Wilk test; W = 0.993, p = 0.920) with 59.1% intermediate types, 19.4% evening types, and 21.5% morning types. MEQ change scores from admission to discharge were nonsignificant (-1.3 ± 5.0; paired t-test, t18 = -1.09; p = 0.29) despite significantly improved depression scores (-19.4 ± 7.6; paired t-test, t18 = 11.2, p < 0.001). Age (r = 0.24), and depression scores (r = -0.21) correlated significantly (p < 0.05) with MEQ scores; associations with sex and hospitalization duration were nonsignificant. The present study and literature findings revealed that the frequency of evening types is not clearly elevated in depression, but morning types are less frequent compared to healthy samples (p < 0.001). Morningness-eveningness scores were normally distributed and stable in depressive inpatients. In line with previous findings, but contrary to theoretical assumptions, evening types were not overrepresented in depressed patients. Additionally, relatively less morning types and more intermediate types were found in depressed patients. Future studies should focus on transitions from morning to intermediate types as a tentative risk or correlate of emerging depression.

Sleep deprivation affects thermal pain thresholds but not somatosensory thresholds in healthy volunteers.

OBJECTIVE: Sleep disturbances have been thought to augment pain. Sleep deprivation has been proven to produce hyperalgesic effects. It is still unclear whether these changes are truly specific to pain and not related to general changes in somatosensory functions. The aim of the present study was to evaluate the effect of total sleep deprivation on thermal pain thresholds (heat, cold) and pain complaints. Thermal detection thresholds (warmth, cold) were included as covariates to determine the contribution of somatosensory functions to changes in pain processing. METHODS: Twenty healthy volunteers were randomly assigned either to two nights of total sleep deprivation or to two nights of undisturbed night sleep. Sleep deprivation nights were separated by two days with normal night sleep. Heat and cold pain thresholds as well as warmth and cold detection thresholds were measured by use of a peltier thermode in the evening before and the morning after each deprivation or control night. Pain complaints were examined by use of a questionnaire in parallel. RESULTS: During treatment nights, sleep deprivation produced a significant overnight decrease in heat pain thresholds. Cold pain thresholds tended to decrease also during sleep deprivation, whereas the warmth and cold detection thresholds remained unaffected. Accordingly, no substantial contributions of the changes in thermal detection thresholds to the changes in thermal pain thresholds were determined by regression analyses. Pain complaints were not induced by sleep deprivation. CONCLUSIONS: The present findings suggest that sleep deprivation produces hyperalgesic changes that cannot be explained by nonspecific alterations in somatosensory functions.

The effect of sleep deprivation on pain.

Chronic pain syndromes are associated with alterations in sleep continuity and sleep architecture. One perspective of this relationship, which has not received much attention to date, is that disturbances of sleep affect pain. To fathom this direction of cause, experimental human and animal studies on the effects of sleep deprivation on pain processing were reviewed. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can counteract analgesic effects of pharmacological treatments involving opioidergic and serotoninergic mechanisms of action. The heterogeneity of the human data and the exclusive interest in rapid eye movement sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity. The significance of opioidergic and serotoninergic processes as mediating mechanisms of the hyperalgesic changes produced by sleep deprivation are discussed.

Comparison of polysomnographic variables and their relationship to cognitive impairment in patients with Alzheimer's disease and frontotemporal dementia.

Polysomnograhic (PSG) studies in Alzheimer's disease (AD) show REM sleep abnormalities, which may be indicative for the deterioration of cholinergic pathways and probably closely linked to declarative memory impairment. To clarify the specificity of the association between sleep and cognitive impairment in dementia, we compared AD patients with patients suffering from frontotemporal dementia (FTD) with regard to PSG and neuropsychological variables. 15 AD and 6 FTD patients underwent polysomonography and a neuropsychological battery (CERAD-NB). Group differences (age: AD > FTD; education level: AD < FTD) were considered as covariates. Polysomnography revealed a trend towards increased REM latency and reduced REM sleep in AD, as well as a decrease of stage 2 sleep, however, at least partly due to effects of age. Declarative memory was more impaired in AD than in FTD, but this difference disappeared when adjusted for covariates. While no relationship was found between REM sleep and CERAD-NB parameters, strong positive correlations between stage 2 sleep and declarative memory measures were observed, which were also detectable when analyzing both groups separately. Based on these results we conclude that REM sleep alterations may be specific for AD, distinguishable from other dementia diagnoses, whereas NonREM stage 2 sleep may be related to declarative memory formation in dementia independent of subtype.

Mid-term effects of serial sleep deprivation therapy implemented in cognitive-behavioral treatment on the neuroendocrine response to clomipramine in patients with major depression.

While data dealing with neurobiological effects of sleep deprivation (SD) are mainly restricted to the acute effects of a single night, only few studies have investigated mid-term effects after repeated SD. We therefore examined the clinical and hormonal characteristics of depressive patients before and after serial SD to determine potential sustained effects, focusing especially on serotoninergic functions. One tool to investigate serotoninergic dysfunction in depression is the use of serotoninergic agents to stimulate hormonal secretion, which is assumed to normalize during a clinically effective therapy. Eighteen drug-free inpatients with unipolar major depression received cognitive-behavioral treatment for three weeks and - according to a randomized control design - additional SD therapy (six nights of total SD within three weeks, separated by nights of recovery sleep) or no SD therapy (control group). Serotoninergic function was assessed by measuring cortisol and prolactin in response to intravenously administered clomipramine (12.5mg) before and after the treatment period. The post-treatment challenge test was performed three days after the last SD night. Apart from of a transient overnight improvement of mood induced by SD, both groups showed a comparable clinical course during the three-week treatment period. Compared to the control group, the SD-treated patients exhibited significantly decreased pre-stimulation cortisol levels and significantly increased cortisol responses to clomipramine, whereas no treatment effects were observed for prolactin. In conclusion, our findings suggest that the mid-term effects of serial SD therapy lead to a normalization of serotoninergic dysfunction, although an obvious impact on clinical symptoms was not detected.

Pain sensitivity in major depression and its relationship to central serotoninergic function as reflected by the neuroendocrine response to clomipramine.

Several studies reported a decreased pain sensitivity in patients with depression, but the underlying neurobiological mechanisms of this phenomenon are unclear. While there is extensive evidence that the serotoninergic system plays a key role in pain modulation, especially in pain inhibitory mechanisms via descending pathways, as well as in the pathophysiology of depression, no study so far has examined its potential relevance in mediating the alteration of pain processing. The present study addresses the question of whether indices of serotoninergic dysfunction, as investigated by a neuroendrocine challenge paradigm, are related to pain sensitivity. Nineteen drug-free inpatients with unipolar major depression underwent a neuroendocrine challenge test by measuring cortisol and prolactin in response to intravenously administered clomipramine (12.5mg). Heat/cold pain thresholds, warmth/cold detection thresholds, measures of current pain complaints and mood were assessed the day before and three day after challenge procedure. When patients were classified in subgroups based on a median split of their cortisol response values, the low-responsive group showed significantly elevated heat pain thresholds and nearly significantly elevated cold pain thresholds compared to the high-responsive group. No such group differences were found with regard to somatosensory thresholds, measures of pain complaints and mood. Subgrouping on the basis of prolactin responsiveness did not reveal significant differences in any parameter. In summary, a decreased pain sensitivity was demonstrated in patients characterized by a reduced neuroendocrine responsiveness to clomipramine, suggesting an involvement of serotoninergic dysfunction underlying altered pain perception in depression.