Gut Microbiome Composition and Its Association with Sleep in Major Psychiatric Disorders.

INTRODUCTION: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality. METHODS: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera. RESULTS: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8). CONCLUSION: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.

Novel approaches for the assessment of relative body weight and body fat in diagnosis and treatment of anorexia nervosa: A cross-sectional study.

BACKGROUND & AIMS: Anorexia nervosa (AN) is a severe psychosomatic disease that seriously affects nutritional status. Therapeutic approaches primarily aim for rapid weight restoration by high caloric diets and activity restriction. This often promotes abdominal body fat gain, which potentially negatively influences the patient's compliance and increases the risk of relapse. This study focused on the evaluation of body weight and subcutaneous adipose tissue (SAT) in AN patients by novel approaches. METHODS: The SAT of AN patients (n = 18, body mass index (BMI) 15.3 ± 1.3 kg/m2) was determined by a highly accurate and reliable ultrasound method. The sum of SAT thicknesses of eight sites (DINCL) was calculated. Individual metabolic profiles were analyzed. The mass index (MI), which considers body proportions, was used in addition to BMI. Additional to the standard laboratory diagnostics, dermal carotenoids measured by resonance Raman spectroscopy, leptin, and oxidative stress indicators were determined. RESULTS: The mean MI was 15.7 ± 1.4 kg/m2. The DINCL considerably differed between individuals with the same BMI. Half of the patients (Group 1) had low DINCL: 1.3-28.4 mm, and Group 2 showed values up to 58.2 mm (corresponding to approximately 6 kg SAT mass). The two group means differed by more than 300% (P < 0.001). Accordingly, leptin levels significantly differed (P < 0.001). Mean SAT thicknesses were significantly higher in Group 2 at all eight sites. The groups also significantly differed in two oxidative stress parameters: total antioxidative capacity, malondialdehyde-modified low density lipoprotein immunoglobulin M (MDA-LDL IgM), and in the carotenoid level. CONCLUSION: Half of the patients had sufficiently high fat mass, despite very low BMI. Consequently, their muscle (and other organ) masses must have been extremely low. Diagnostic criteria and treatment protocols for AN should consider each patient's body composition. In addition to dietary treatments, muscle training at low energy turnover rates may be essential for avoiding unnecessary body fat gain, better treatment results, and long-term recovery.

[Strangulation as scenic behavior. A case report of a pseudosuicide in the course of a NREM-parasomnia]. / Strangulation als szenische Handlung. Ein Fallbericht über einen Pseudosuizidversuch im Verlauf einer NREM-Parasomnie.

It is generally accepted, that sleepwalkers show complex behaviors leading to non-intended consequences. It is not unusual that these persons are thereby injured. However, sporadically a bizarre endangering of themselves or others is reported also, which ranges from homicide of the life partner to accidental (pseudo-)suicide.In this article, we report on a 28year-old man who unexpectedly attempted to hang himself by a whip at night. We discuss the reasons, why this bizarre act should actually be taken as a scenic behavior in the course of a NREM-parasomnia, and the difficulty to proof this claim.

Baseline plasma epinephrine levels predict Wisconsin Card Sorting Test scores in healthy volunteers.

The present study was undertaken to further explore the potential neuropsychological information associated with baseline plasma levels of catecholamines and dopamine D3 receptor (DRD3) mRNA expression in peripheral blood lymphocytes (PBL). Baseline plasma norepinephrine and epinephrine levels and PBL DRD3 mRNA expression were compared with performance in the Wisconsin Card Sorting Test (WCST) in n=79 healthy volunteers (mean+/-S.D. age: 24.1+/-3.2 years, 34 males). After correction for multiple testing, we found that baseline plasma epinephrine levels predicted WCST total number of errors (Spearman's rho=-0.36, p<0.05), number of perseverative responses (Spearman's rho=-0.36, p<0.05) and percent conceptual level responses (Spearman's rho=0.37, p<0.05). Plasma norepinephrine levels and PBL DRD3 mRNA expression did not predict WCST scores, but PBL DRD3 mRNA expression correlated negatively with plasma epinephrine levels (Spearman's rho=-0.45, p<0.001). Further studies should be undertaken to explore possible neurophysiological links between plasma epinephrine levels and the neurobiology underlying cognitive performance.

[35S]GTPgammaS binding at the human dopamine D4 receptor variants hD4.2, hD4.4 and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine.

Aim of the present study was to investigate possible differences between the human dopamine D4 receptor 48 bp polymorphism variants hD4.2, hD.4. and hD4.7 in agonist stimulated [35S]GTPgammaS binding, to investigate dopamine D4 receptor sodium sensitivity and to further characterize norepinephrine and epinephrine agonism at this receptor. G-protein activation at the receptor variants hD4.2, hD4.4 and hD4.7 expressed in CHO-K1 cells, following stimulation by dopamine, norepinephrine and epinephrine, was investigated using the [35S]GTPgammaS assay at experimental conditions of 10 and 100 mM sodium, respectively. Dopamine displayed a 2 fold higher potency of stimulating [35S]GTPgammaS binding at the hD4.2, compared to the hD4.4 and hD4.7 at 10 mM sodium. A significant difference in sodium sensitivity of basal [35S]GTPgammaS binding was found, with the hD4.7 being 1.7 fold more sensitive than the hD4.4 and 2.5 fold more sensitive than the hD4.2. Norepinephrine and epinephrine both produced concentration-dependent increases in [35S]GTPgammaS binding at all three receptor variants, and epinephrine showed only 2 fold less potency than dopamine. The present results are in certain line with previous reports of functional 2-3 fold differences between the dopamine D4 receptor variants. Agonism of norepinephrine and epinephrine at the dopamine D4 receptor may indicate an important way of cross-reactivity among the different monoamine neurotransmitter systems.

[A systemic view on psychosis]. / Psychosen aus systemischer Sicht.

The experience of time changes during life. In the youth time changes slowly from the longitudinal point of view, looking cross on life very fast. In older ages regularly it is the opposite matter, although there are throughout all ages significant intra- and interindividually differences. Experience of time is highly sensitive towards changes of one's self-experience, which can be well observed in psychiatric disorders. In case of psychosis identity of time and experienced synchronism (as certainty to be in the time with others) will be destroyed. There is a kind of breaking up time, a compression of time, where there is no before nor after. In depressed people time experience is similar to elder people, accordingly manic patients feel something like children in this sense. Dissociation of time has got a key role for understanding psychosis from the systemic point of view. Synchrone dissociation is distinguished from diachrone dissociation. In the first case conflicts will be "solved" through excessive simultaneity, undercutting the minimal time interval. The possibilities of differences are made impossible. Secondly the maximum of the time interval is exceeded; therefore the integration of opposite aspects is impossible. Equally no conflict will be possible. Both kinds of dissociation lead to "pseudo-harmony" of interrelational systems, despite of potency for conflicts. In family systems with schizophrenic members synchrone dissociation is typical, whereas diachrone dissociation is common in those with affective disorders. Both of them will be found in communicative systems with patients suffering from schizoaffective disorders. In between occur fierce arguments, when "protection" of dissociation is not granted.

Test-retest reliability of a lifetime drug use questionnaire.

By adopting the investigational principle of the Lifetime Drinking History (LDH) interview, we developed a Lifetime Drug Use (LDU) Questionnaire to assess the amount and frequency of lifetime drug consumption. The Pearson Correlation Coefficients for test-retest reliability, investigated in a sample of N=47 residents of a drug rehabilitation center and averaged over the investigated seven drug categories, were r=.95 for the abstinence-corrected total duration of regular use, r=.89 for the mean number of consumption days per month of regular use, r=.89 for the mean daily amount, r=.83 for the variability in consumption days per month of regular use, and r=.75 for month variability in daily amount. Applicability and further research needs are discussed.

Dopamine receptor D3 mRNA expression in human lymphocytes is negatively correlated with the personality trait of persistence.

It has been proposed that neurotransmitter receptor expression in peripheral immune cells reflects expression of these receptors in the brain. To test this "peripheral marker hypothesis", we compared mRNA expression of the dopamine receptors D3 (DRD3) and D4 (DRD4) in peripheral blood lymphocytes (PBL) to personality traits assessed with the Temperament and Character Inventory (TCI) in 50 healthy and unmedicated Caucasian individuals. A shared variance of at least 17% (p=0.016) between DRD3 mRNA expression in PBL and the personality trait of persistence was found. As personality traits have been generally assumed polygenic with a single gene accounting for rarely more than 1-2% of observed variance in a trait, this result lends further support to the peripheral marker hypothesis for DRD3 mRNA expression in PBL. It may also suggest a significant role for the DRD3 in the neurobiology of persistence and point to an interesting link between personality and functioning of the immune system.

Reduced dopamine D4 receptor mRNA expression in lymphocytes of long-term abstinent alcohol and heroin addicts.

AIM: It has been repeatedly suggested that dopamine receptor expression in peripheral blood lymphocytes reflects, to some extent, brain status. The aim of the present study was to investigate dopamine receptor expression in peripheral blood lymphocytes of long-term abstinent alcohol and heroin addicts against the background of the hypothesis, that a persisting dysfunction of the dopaminergic system contributes a biological cause to the chronic character of addiction. DESIGN: Dopamine D3 and D4 receptor mRNA expression in peripheral blood lymphocytes was measured by real-time polymerase chain reaction (PCR) in 19 alcohol addicts, abstinent for 6.2 +/- 4.7 months (mean +/- SD), and 20 heroin addicts, abstinent for 6.7 +/- 3.7 months (mean +/- SD), and compared to a control group of 29 age- and sex-matched individuals with no life-time history of substance abuse. FINDINGS: One-way anova showed significant differences in D4 mRNA expression between the groups (P = 0.005): both groups of addicts showed an approximately 50% reduction in D4 receptor mRNA expression in peripheral blood lymphocytes (PBL) compared to controls. No differences were found for D3 mRNA expression between the groups. CONCLUSION: The results of the present study indicate a withdrawal-persisting dopaminergic imbalance in abstinent addicts as measured by a suggested peripheral marker.

Reduced dopamine D3 receptor expression in blood lymphocytes of smokers is negatively correlated with daily number of smoked cigarettes: a peripheral correlate of dopaminergic alterations in smokers.

The mesolimbic dopaminergic system is known to mediate rewarding effects of nicotine administration, and dysfunctions of this system may underlie failure to stop cigarette smoking. Expression of dopamine receptors in peripheral blood lymphocytes (PBLs) has been indicated as a peripheral correlate of brain status. Dopamine receptor D(3) (DRD3) and D(4) (DRD4) mRNA expression in PBLs was measured by real-time polymerase chain reaction in smokers (n=26) and former smokers (n=14), compared with nonsmoking control subjects (n=35). A significant (p=.032, Bonferroni corrected) 30% reduction of DRD3 mRNA expression in PBLs was found in smokers but not former smokers in comparison with controls. DRD3 mRNA expression in PBLs in smokers but not former smokers was negatively correlated with daily number of cigarettes consumed (Pearson correlation coefficient r=-.54, p=.005). These data suggest a selective inhibiting effect of smoking on DRD3 mRNA expression and, with the known involvement of DRD3 in reward mediation, indicates a vicious-cycle explanation for the motivation for continued smoking.