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.

The Impact of Cardiovascular Rehabilitation on Psychophysiological Stress, Personality and Tryptophan Metabolism: A Randomized Pilot Feasibility Study.

Multicomponent cardiac rehabilitation (CR) is a secondary prevention strategy for cardiac patients to tackle stress and psychosocial wellbeing. However, there is a lack of data on its psychoneuroimmunological effects and of biomarkers to determine individual risk and to develop treatment strategies. We conducted a pilot randomized controlled trial (RCT) to investigate the feasibility of deriving psychophysiological stress markers in patients with cardiovascular diseases. Thirty individuals with cardiovascular disease (mean age 58.8 years; 23.3% female) were enrolled and randomized into three treatment groups: standard rehabilitation, yoga, or transcendental meditation (TM). Depression, anxiety, sleep, stress perception, personality functioning, hair cortisol, serum tryptophan, kynurenine and neopterin concentrations were estimated at baseline and after a four-week intervention. Hair cortisol levels decreased significantly after rehabilitation in all groups (F = 15.98, p < 0.001). In addition, personality functioning improved in all patients over time. Participants with impairments in personality functioning showed a positive correlation with baseline neopterin that did not remain significant after Bonferroni correction. Concentrations of serum tryptophan and its metabolite kynurenine did not change significantly. This pilot RCT provides preliminary evidence of multicomponent CR leading to stabilization of hair cortisol levels and improved psychophysiological wellbeing and personality functioning. Impairments in personality functioning were correlated with neopterin levels, which may impact the symptomatology and outcome.

PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression-A Randomized Controlled Trial.

Gut microbiota are suspected to affect brain functions and behavior as well as lowering inflammation status. Therefore, an effect on depression has already been suggested by recent research. The aim of this randomized double-blind controlled trial was to evaluate the effect of probiotic treatment in depressed individuals. Within inpatient care, 82 currently depressed individuals were randomly assigned to either receive a multistrain probiotic plus biotin treatment or biotin plus placebo for 28 days. Clinical symptoms as well as gut microbiome were analyzed at the begin of the study, after one and after four weeks. After 16S rRNA analysis, microbiome samples were bioinformatically explored using QIIME, SPSS, R and Piphillin. Both groups improved significantly regarding psychiatric symptoms. Ruminococcus gauvreauii and Coprococcus 3 were more abundant and ß-diversity was higher in the probiotics group after 28 days. KEGG-analysis showed elevated inflammation-regulatory and metabolic pathways in the intervention group. The elevated abundance of potentially beneficial bacteria after probiotic treatment allows speculations on the functionality of probiotic treatment in depressed individuals. Furthermore, the finding of upregulated vitamin B6 and B7 synthesis underlines the connection between the quality of diet, gut microbiota and mental health through the regulation of metabolic functions, anti-inflammatory and anti-apoptotic properties. Concluding, four-week probiotic plus biotin supplementation, in inpatient individuals with a major depressive disorder diagnosis, showed an overall beneficial effect of clinical treatment. However, probiotic intervention compared to placebo only differed in microbial diversity profile, not in clinical outcome measures.

Differences in psychological and somatic symptom cluster score profiles between subjects with Idiopathic environmental intolerance, major depression and schizophrenia.

Idiopathic Environmental Intolerance (IEI) has been associated with psychogenic factors and an increased number of comorbid psychiatric disorders such as depression and anxiety disorder. The purpose of the current study was to examine a possible overlap of psychological and somatic symptoms between subjects with IEI and patients with major depression and schizophrenia as well as to specify characteristic differences. The different symptom clusters included symptoms of chemical intolerance, neurotoxicity and psychological distress as well as measurements of mental health such as anxiety, depression, somatoform symptoms, and schizophrenia-specific disturbances in cognitive domains. IEI patients reported higher overall levels in physical symptoms such as chemical intolerance, neurotoxicity and somatic symptoms not attributable to an organic cause. Schizophrenia patients showed higher overall levels in self-experienced disturbances in several schizophrenia-specific cognitive domains, whereas general psychological distress, anxiety and depression were rated highest by patients with major depression. Importantly, the groups markedly differed in the shapes of profiles of various symptom clusters. Our results provide evidence that IEI patients can be distinguished on the phenomenological level from patients with major depression or schizophrenia, and that distinct domains of psychological and somatic symptoms are particularly problematic in specific diagnostic groups.

Visual height intolerance and acrophobia: distressing partners for life.

The course of illness, the degree of social impairment, and the rate of help-seeking behavior was evaluated in a sample of individuals with visual height intolerance (vHI) and acrophobia. On the basis of a previously described epidemiological sample representative of the German general population, 574 individuals with vHI were identified, 128 fulfilled the DSM-5 diagnostic criteria of acrophobia. The illness of the majority of all susceptible individuals with vHI ran a year-long chronic course. Two thirds were in the category "persistent/worse", whereas only one third was in the category "improved/remitted". Subjects with acrophobia showed significantly more traumatic triggers of onset, more signs of generalization to other height stimuli, higher rates of increasing intensity of symptom load, higher grades of social impairment, and greater overall negative impact on the quality of life than those with pure vHI. An unfavorable course of illness in pure vHI was predicted by major depression, agoraphobia, social phobia, posttraumatic stress, initial traumatic trigger, and female sex; an unfavorable course in acrophobia was predicted by major depression, chronic fatigue, panic attacks, initial traumatic trigger, social phobia, other specific phobic fears, and female sex. Help-seeking behavior was astonishingly low in the overall sample of individuals with vHI. The consequences of therapeutic interventions if complied with at all were quite modest. In adults pure vHI and even more so acrophobia are by no means only transitionally distressing states. In contrast to their occurrence in children they are more often persisting and disabling conditions. Both the utilization of and adequacy of treatment of these illnesses pose major challenges within primary and secondary neurological and psychiatric medical care.

Auditory top-down control and affective theory of mind in schizophrenia with and without hallucinations.

Social cognitive impairments may represent a core feature of schizophrenia and above all are a strong predictor of positive psychotic symptoms. Previous studies could show that reduced inhibitory top-down control contributes to deficits in theory of mind abilities and is involved in the genesis of hallucinations. The current study aimed to investigate the relationship between auditory inhibition, affective theory of mind and the experience of hallucinations in patients with schizophrenia. In the present study, 20 in-patients with schizophrenia and 20 healthy controls completed a social cognition task (the Reading the Mind in the Eyes Test) and an inhibitory top-down Dichotic Listening Test. Schizophrenia patients with greater severity of hallucinations showed impaired affective theory of mind as well as impaired inhibitory top-down control. More dysfunctional top-down inhibition was associated with poorer affective theory of mind performance, and seemed to mediate the association between impairment to affective theory of mind and severity of hallucinations. The findings support the idea of impaired theory of mind as a trait marker of schizophrenia. In addition, dysfunctional top-down inhibition may give rise to hallucinations and may further impair affective theory of mind skills in schizophrenia.

Visual height intolerance and acrophobia: clinical characteristics and comorbidity patterns.

The purpose of this study was to estimate the general population lifetime and point prevalence of visual height intolerance and acrophobia, to define their clinical characteristics, and to determine their anxious and depressive comorbidities. A case-control study was conducted within a German population-based cross-sectional telephone survey. A representative sample of 2,012 individuals aged 14 and above was selected. Defined neurological conditions (migraine, Menière's disease, motion sickness), symptom pattern, age of first manifestation, precipitating height stimuli, course of illness, psychosocial impairment, and comorbidity patterns (anxiety conditions, depressive disorders according to DSM-IV-TR) for vHI and acrophobia were assessed. The lifetime prevalence of vHI was 28.5% (women 32.4%, men 24.5%). Initial attacks occurred predominantly (36%) in the second decade. A rapid generalization to other height stimuli and a chronic course of illness with at least moderate impairment were observed. A total of 22.5% of individuals with vHI experienced the intensity of panic attacks. The lifetime prevalence of acrophobia was 6.4% (women 8.6%, men 4.1%), and point prevalence was 2.0% (women 2.8%; men 1.1%). VHI and even more acrophobia were associated with high rates of comorbid anxious and depressive conditions. Migraine was both a significant predictor of later acrophobia and a significant consequence of previous acrophobia. VHI affects nearly a third of the general population; in more than 20% of these persons, vHI occasionally develops into panic attacks and in 6.4%, it escalates to acrophobia. Symptoms and degree of social impairment form a continuum of mild to seriously distressing conditions in susceptible subjects.

Clinical course of illness in women with early onset puerperal psychosis: a 12-year follow-up study.

OBJECTIVE: To complete a follow-up analysis at a mean of 12 years after patients had presented with an early onset puerperal psychotic index episode. METHOD: A retrospective design was used. Patients with puerperal psychosis and onset within 4 weeks after childbirth who had been referred to the Psychiatric Department of the Ludwig Maximilian University of Munich, Munich, Germany, between 1975 and 1995 (maximum: 24 years, minimum: 7 years) were followed up after a mean of 12 years post index episode. Ninety patients were included in the study. Before the index episode, 35 of the patients had previous nonpuerperal psychoses, while 55 patients presented their index episode as the first manifestation of a psychotic illness. Diagnostic evaluation at follow-up was performed by the Structured Clinical Interview for DSM-IV Axis I Disorders according to DSM-IV-TR. Differential rates of risk of psychotic relapse were calculated. Data on some gynecologic variables (postpartum blues, premenstrual tension, psychiatric symptoms triggered perimenstrually, mood symptoms while taking oral contraceptives) were collected. Clinical and psychosocial outcomes were measured by the Global Assessment Scale and Disability Assessment Scale. RESULTS: Patients who presented with major depression and bipolar affective disorder with psychotic features at the initial index episode showed overall diagnostic stability. Many patients with initial brief psychosis (cycloid psychosis) shifted to a clear bipolar affective disorder. The general risk of a psychotic relapse was high (previous psychosis = 0.77 vs first psychotic manifestation = 0.56; not significant). The risk after further pregnancies was 0.57 versus 0.48, respectively (not significant), and the risk regarding at least 1 other psychotic nonindex episode was 0.71 versus 0.44, respectively (P = .015). Gynecologic variables did not significantly discriminate between the groups. In some patients, a possible link to a hormonal susceptibility was discussed. Patients who remained without any further psychotic relapse (n = 24) had a favorable outcome. CONCLUSIONS: Puerperal psychosis of an early onset seemed to be of a prevailing affective nature. Brief psychosis (cycloid psychosis) during a puerperal index episode showed a strong link to bipolar affective disorder in the further course of illness. Outcome was excellent in patients without a further psychotic relapse.

Clinical effects of electroconvulsive therapy in severe depression and concomitant changes in cerebral glucose metabolism--an exploratory study.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective mode of treatment--especially for severe depression and for depression refractory to pharmacotherapy, nevertheless the mode of action of ECT is far from being fully understood. This study assessed the effects of a series of ECT in depressive subjects on cerebral glucose metabolism measured by FDG-PET scans pre- and post-therapy in thus far the largest group of 12 patients. METHODS: Our analysis included careful repeated evaluation of clinical changes in mood and behaviour by standardised questionnaires, which allowed testing for a potential correlation between clinical and cerebral metabolic changes. PET scanning was done within a predefined time window and we used predefined ROIs with counts normalized to the pons activity. RESULTS: We observed few changes in cerebral glucose metabolism over time. There was a marginal increase in the left temporal and a trend for a decrease in left frontobasal areas subsequent to treatment in our sample. FDG uptake patterns remained remarkably stable in all the other predefined ROIs pre- and post-treatment. There were no significant correlations between changes in relative metabolic rates and changes in depression scores and parameters derived from neurocognitive testing. CONCLUSIONS: Our study thus cannot support the view that FDG-PET can assess the functional brain changes that are likely to occur subsequent to ECT in such a scenario, but this may be related to limited sensitivity given the sample size. Future studies thus might wish to challenge this notion in larger patient samples to clarify this issue.

Sexual behavior, body image, and partnership in chronic illness: a comparison of Huntington's disease and multiple sclerosis.

Huntington's disease (HD) and multiple sclerosis (MS) are both chronic progressive illnesses posing a serious challenge to affected patients and families. Sexual dysfunction in HD as well as in MS is a very common problem, although it is unclear whether the dysfunction is caused by the chronic illness itself or by the sociopsychiatric burden related to the illness. Twenty-nine patients with HD and 27 patients with MS each participated in a semistructured interview and several standardized questionnaires concerning partnership, sexual function, and body image. The results display significant differences in both patient groups, displaying higher sexual desire and activity in HD patients, but MS patients also reported fewer sexual problems compared to the norming values. Conversely, the MS patients' relationships seemed to be stable despite subjectively perceived lower initiative on sexual activities. The results are discussed under the possible influences of the underlying organic changes and the psychosocial consequences of chronic progressive disorders.

Sinusoidal smooth pursuit eye tracking at different stimulus frequencies: position error and velocity error before catch-up saccades in schizophrenia and in major depressive disorder.

OBJECTIVE: The aim of the present study was to ascertain the extent of impairment of position error and velocity error processing in eye tracking dysfunction in schizophrenic and depressive patients. METHOD: A total of 21 schizophrenic and 19 unipolar depressive patients and 21 healthy controls were subjected to an eye tracking test with electro-oculography using horizontal sinusoidal stimuli with frequencies of 0.2-0.7 Hz. Position error and velocity error were measured over a saccade-free range of 200 ms before catch-up saccades at 50 ms intervals. RESULTS: For position error, the schizophrenia patients displayed increased values particularly compared to controls, more rarely compared to depressive patients, depending on the stimulus frequency used. The increase in stimulus frequency did not lead to an increase in position error in any group of subjects over a prolonged period. For velocity error, in contrast, the study groups differed only in a few, isolated pre-saccadic intervals. The increase in stimulus frequency, however, led to an increase in velocity error in the schizophrenia patients over the entire 200 ms interval. The depressive patients did not differ notably from the controls, neither in terms of position error nor velocity error. CONCLUSIONS: Eye tracking dysfunction in schizophrenia can be described as follows with regard to position error and velocity error: On the one hand, there is an increased position error tolerance largely independent of stimulus frequency, possibly due to an impairment of processing localization information. On the other hand, velocity processing is more severely impaired by an increase in stimulus frequency.