Lifestyle modification as intervention for seasonal affective disorder: A systematic review.

Bright light therapy (BLT) and pharmacological therapies currently represent the first line treatments for patients with seasonal affective disorder (SAD). Lifestyle modifications offer a diverse field of additional intervention options. Since it is unclear, if lifestyle modifications are effective in SAD patients, this systematic review aims to synthesize the current evidence on their effectiveness and safety. We systematically searched for randomized controlled trials (RCTs) assessing lifestyle modifications (nutrition, exercise, staying outdoors, sleep, social aspects, mindfulness methods) in SAD patients. We defined the primary outcome as the post-therapeutic extent of depressive symptoms, measured by validated psychiatric symptom scales. Due to the insufficient number of studies and the high heterogeneity of the interventions we were not able to calculate a meta-analysis. We identified 6 studies from the following areas of lifestyle modification: diet, exercise, staying outdoors, sleep and music therapy. All studies showed improvements of depression scores in the intervention as well as in the control groups. The risk of bias was rated as high for all studies and the certainty of evidence was rated as very low. The results point towards the possible effectiveness of the interventions examined, but due to the small number of studies found, too small sample sizes and methodological limitations, we cannot draw a valid conclusion about the effectiveness of lifestyle-modifying measures in SAD patients. Larger, high-quality RCTs are needed to make evidence-based recommendations and thus to expand the range of therapeutic options for SAD.

The history of circadian rhythm research in Austria.

In view of the recent revival of interest in circadian biology and circadian epidemiology at the Medical University of Vienna, it seems appropriate to highlight the rich and pioneering history of circadian research in Austria. Among the forefathers of circadian research in Vienna are Otto Marburg (1874-1948), who discovered important elements of the pineal gland physiology, Robert Hofstätter (1883-1970), who used pineal gland extract in obstetrics/gynecology, and Paul Engel (1907-1997), who discovered that the pineal gland was controlled by light. More recently, Vera Lapin (1920-2007) showed that surgical removal of the pineal gland increased tumor growth, while Franz Waldhauser (*1946) investigated melatonin in conjunction with night work. Michael Kundi (*1950) and his team conducted among the first studies demonstrating differences in rhythms of night workers and early evidence for health impairments among them. Furthermore, Vienna-born Erhard Haus (1926-2013) pioneered the discovery of the role and importance of melatonin in relation to numerous diseases. This rich pioneering contribution of scientists in Vienna or with roots in Vienna is continued today by a new generation of chronobiologists, epidemiologists and clinicians in Vienna whose new insights contribute to the rapidly developing field of circadian rhythms research. Current topics and contributions relate to the impact of circadian rhythm disruption on health, and the application of chronotherapeutic approaches in clinical and preventive settings.

Development of an Arduino-based, open-control interface for hardware in the loop applications.

This article presents a flexible control interface based on low-cost hardware solutions for electric drives which classically come either with a proprietary hardware solution or a high-cost interface solution. The interface presented can be used to connect a standard PC with an electric drive to enable testing simulation and control applications. The control interface is developed based on the open-source Python scripting language and Arduino's open-source and accessible hardware. The new interface communicates with the test stand through its I/O terminals via developed electronic amplifiers and creates a solid base for further development towards more extensive hardware in the loop simulations.

Impact of genetic variants within serotonin turnover enzymes on human cerebral monoamine oxidase A in vivo.

Variants within the monoamine oxidase A (MAO-A, MAOA) and tryptophan hydroxylase 2 (TPH2) genes, the main enzymes in cerebral serotonin (5-HT) turnover, affect risk for depression. Depressed cohorts show increased cerebral MAO-A in positron emission tomography (PET) studies. TPH2 polymorphisms might also influence brain MAO-A because availability of substrates (i.e. monoamine concentrations) were shown to affect MAO-A levels. We assessed the effect of MAOA (rs1137070, rs2064070, rs6323) and TPH2 (rs1386494, rs4570625) variants associated with risk for depression and related clinical phenomena on global MAO-A distribution volume (VT) using [11C]harmine PET in 51 participants (21 individuals with seasonal affective disorder (SAD) and 30 healthy individuals (HI)). Statistical analyses comprised general linear models with global MAO-A VT as dependent variable, genotype as independent variable and age, sex, group (individuals with SAD, HI) and season as covariates. rs1386494 genotype significantly affected global MAO-A VT after correction for age, group and sex (p < 0.05, corr.), with CC homozygotes showing 26% higher MAO-A levels. The role of rs1386494 on TPH2 function or expression is poorly understood. Our results suggest rs1386494 might have an effect on either, assuming that TPH2 and MAO-A levels are linked by their common product/substrate, 5-HT. Alternatively, rs1386494 might influence MAO-A levels via another mechanism, such as co-inheritance of other genetic variants. Our results provide insight into how genetic variants within serotonin turnover translate to the cerebral serotonin system. Clinicaltrials.gov Identifier: NCT02582398. EUDAMED Number: CIV-AT-13-01-009583.

Effect of MAOA DNA Methylation on Human in Vivo Protein Expression Measured by [11C]harmine Positron Emission Tomography.

BACKGROUND: Epigenetic modifications like DNA methylation are understood as an intermediary between environmental factors and neurobiology. Cerebral monoamine oxidase A (MAO-A) levels are altered in depression, as are DNA methylation levels within the MAOA gene, particularly in the promoter/exon I/intron I region. An effect of MAOA methylation on peripheral protein expression was shown, but the extent to which methylation affects brain MAO-A levels is not fully understood. METHODS: Here, the influence of MAOA promoter/exon I/intron I region DNA methylation on global MAO-A distribution volume (VT), an index of MAO-A density, was assessed via [11C]harmine positron emission tomography in 22 patients (14 females) suffering from seasonal affective disorder and 30 healthy controls (17 females). RESULTS: No significant influence of MAOA DNA methylation on global MAO-A VT was found, despite correction for health status, sex, season, and MAOA variable number of tandem repeat genotype. However, season affected average methylation in women, with higher levels in spring and summer (Puncorr = .03). We thus did not find evidence for an effect of MAOA DNA methylation on brain MAO-A VT. CONCLUSIONS: In contrast to a previous study demonstrating an effect of methylation of a MAOA promoter region located further 5' on brain MAO-A, MAOA methylation of the region assessed here appears to affect brain protein levels to a limited extent at most. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system. CLINICALTRIALS.GOV IDENTIFIER: NCT02582398 (https://clinicaltrials.gov/ct2/show/NCT02582398).

Prescriptions of psychopharmacologic drugs in Austria in 2019 and 2020 - Implications of the COVID-19 pandemic.

BACKGROUND: Measures to reduce the spread of the SARS-CoV-2 virus have an impact on the mental health of the general population. Drug prescription rates can be used as a surrogate marker to estimate help seeking and health parameters of a population. The aim of this study was to compare psychopharmacologic drug prescriptions in Austria from the start of the pandemic in 2020 over time and with the previous year and to investigate the impact of the COVID-19 lockdowns in 2020. METHODS: Data from the three largest public health insurances in Austria, covering over 98% of the general population, were analyzed. A total of 1,365,294 patients with a prescription of a psychopharmacologic drug in the months March to December in 2019 and 2020 were selected. RESULTS: There was no significant change in prescribed defined daily doses (DDDs) during the lockdowns. However, there was a stockpiling effect before and at the beginning of lockdown 1. The number of new patients initiating psychopharmacologic treatment was significantly reduced during lockdown 1 but not during lockdown 2. CONCLUSIONS: The first COVID-19 lockdown in 2020 functioned as a barrier for new psychiatric patients seeking help, whereas the patients with ongoing treatments did not have significant problems. These results have to be taken into account for future planning, but follow-up studies are needed, as our results could be indicative of a change in the effect of the protective measures on the utilization of the healthcare system over time.

Biodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[11C]Me-NB1.

BACKGROUND: The NMDA receptor (NMDAR) plays a key role in the central nervous system, e.g., for synaptic transmission. While synaptic NMDARs are thought to have protective characteristics, activation of extrasynaptic NMDARs might trigger excitotoxic processes linked to neuropsychiatric disorders. Since extrasynaptic NMDARs are typically GluN2B-enriched, the subunit is an interesting target for drug development and treatment monitoring. Recently, the novel GluN2B-specific PET radioligand (R)-[11C]Me-NB1 was investigated in rodents and for the first time successfully translated to humans. To assess whether (R)-[11C]Me-NB1 is a valuable radioligand for (repeated) clinical applications, we evaluated its safety, biodistribution and dosimetry. METHODS: Four healthy subjects (two females, two males) underwent one whole-body PET/MR measurement lasting for more than 120 min. The GluN2B-specific radioligand (R)-[11C]Me-NB1 was administered simultaneously with the PET start. Subjects were measured in nine passes and six bed positions from head to mid-thigh. Regions of interest was anatomically defined for the brain, thyroid, lungs, heart wall, spleen, stomach contents, pancreas, liver, kidneys, bone marrow and urinary bladder contents, using both PET and MR images. Time-integrated activity coefficients were estimated to calculate organ equivalent dose coefficients and the effective dose coefficient. Additionally, standardized uptake values (SUV) were computed to visualize the biodistribution. RESULTS: Administration of the radioligand was safe without adverse events. The organs with the highest uptake were the urinary bladder, spleen and pancreas. Organ equivalent dose coefficients were higher in female in almost all organs, except for the urinary bladder of male. The effective dose coefficient was 6.0 µSv/MBq. CONCLUSION: The GluN2B-specific radioligand (R)-[11C]Me-NB1 was well-tolerated without reported side effects. Effective dose was estimated to 1.8 mSv when using 300 MBq of presented radioligand. The critical organ was the urinary bladder. Due to the low effective dose coefficient of this radioligand, longitudinal studies for drug development and treatment monitoring of neuropsychiatric disorders including neurodegenerative diseases are possible. Trial registration Registered on 11th of June 2019 at https://www.basg.gv.at (EudraCT: 2018-002933-39).

Syngas fermentation and microbial electrosynthesis integration as a single process unit.

Industrially relevant syngas (15 % CO, 15% H2, 20% N2 in 50% CO2) fermentation and microbial electrosynthesis were integrated as a single process unit in open and closed-circuit modes. This study examined the impact of electrochemical reducing power from -50 to -400 mV on the acetic acid synthesis and CO inhibition on fermentation. -150 mV vs. Ag/AgCl (3.0 NaCl) was identified as the lowest benchmark potential for improved acetic acid synthesis rate (0.263 mmol L-1h-1), which is 15-fold higher than the open circuit mode's rate. No significant inhibition by CO in the fermentation was observed, while 60% of the gas was consumed. Anodic potential above 2.0 V substantially lowered the product formation. Superseding the fermentation medium with fresh inoculum through a fed-batch operation helped lower the anodic potential.

Serotonergic modulation of effective connectivity in an associative relearning network during task and rest.

An essential core function of one's cognitive flexibility is the use of acquired knowledge and skills to adapt to ongoing environmental changes. Animal models have highlighted the influence serotonin has on neuroplasticity. These effects have been predominantly demonstrated during emotional relearning which is theorized as a possible model for depression. However, translation of these mechanisms is in its infancy. To this end, we assessed changes in effective connectivity at rest and during associative learning as a proxy of neuroplastic changes in healthy volunteers. 76 participants underwent 6 weeks of emotional or non-emotional (re)learning (face-matching or Chinese character-German noun matching). During relearning participants either self-administered 10 mg/day of the selective serotonin reuptake inhibitor (SSRI) escitalopram or placebo in a double-blind design. Associative learning tasks, resting-state and structural images were recorded before and after both learning phases (day 1, 21 and 42). Escitalopram intake modulated relearning changes in a network encompassing the right insula, anterior cingulate cortex and right angular gyrus. Here, the process of relearning during SSRI intake showed a greater decrease in effective connectivity from the right insula to both the anterior cingulate cortex and right angular gyrus, with increases in the opposite direction when compared to placebo. In contrast, intrinsic connections and those at resting-state were only marginally affected by escitalopram. Further investigation of gray matter volume changes in these functionally active regions revealed no significant SSRI-induced structural changes. These findings indicate that the right insula plays a central role in the process of relearning and SSRIs further potentiate this effect. In sum, we demonstrated that SSRIs amplify learning-induced effective connections rather than affecting the intrinsic task connectivity or that of resting-state.

Impact of electrochemical reducing power on homoacetogenesis.

Homoacetogenesis was performed in a microbial electrosynthesis single-chamber reactor at open and closed circuits modes. The aim is to investigate how an applied reducing power affects acetic acid synthesis and H2 gas-liquid mass transfer. At a cathode voltage of -175 mV vs. Ag/AgCl (3.0 NaCl), the acetic acid synthesis rate ramped up to 0.225 mmol L-1h-1 due to additional electrons and protons liberation from carbon-free sources such as water and ammonium via anodic oxidation. The study sets a new lowest benchmark that acetic acid can be bioelectrochemical synthesized at - 175 mV. The applied reducing power did not increase the H2 gas-liquid mass transfer because the direct electron transfer from cathode to microorganisms reduced the demand for H2 in the fermentation medium. Microbial analysis shows a high presence of Veillonellaceae spore-forming clostridia, which are identified as homoacetogens.

Urological adverse drug reactions of psychotropic medication in psychiatric inpatients - A drug surveillance report from German-speaking countries.

Urological adverse drug reactions (UADR) are common during treatment with psychotropic medication. The aim of this study was to provide a systematic description of the differential profile of UADR of psychotropic drugs in a large naturalistic population. Data stems from psychiatric hospitals collected by AMSP (Arzneimittelsicherheit in der Psychiatrie), a continuous multi-center pharmacovigilance program in Austria, Germany, and Switzerland. 171 cases of severe UADR (0.037%) among a total population of 462 661 inpatients treated with psychotropic drugs in 99 psychiatric hospitals between 1993 and 2016 were examined. Urinary retention (129 cases, 0.028%) was the most common UADR followed by incontinence (23 cases, 0.005%) and nocturnal enuresis (16 cases, 0.003%). Risk of UADR was higher in patients with mania than in other diagnostic groups. Promethazine and haloperidol were the antipsychotics with the highest rate of UADR. Tricyclic antidepressants had a higher and selective serotonin reuptake inhibitors a lower risk for UADR than the respective other antidepressants. Amitriptyline and clomipramine were the most common causes of urinary retention and clozapine of urinary incontinence. This research improves our knowledge of the urological risk profiles of psychotropic drugs in inpatients and highlights compounds associated with higher or lower risk.

Translating the immediate effects of S-Ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial.

Antidepressant doses of ketamine rapidly facilitate synaptic plasticity and modify neuronal function within prefrontal and hippocampal circuits. However, most studies have demonstrated these effects in animal models and translational studies in humans are scarce. A recent animal study showed that ketamine restored dendritic spines in the hippocampal CA1 region within 1 h of administration. To translate these results to humans, this randomized, double-blind, placebo-controlled, crossover magnetic resonance imaging (MRI) study assessed ketamine's rapid neuroplastic effects on hippocampal subfield measurements in healthy volunteers. S-Ketamine vs. placebo data were analyzed, and data were also grouped by brain-derived neurotrophic factor (BDNF) genotype. Linear mixed models showed that overall hippocampal subfield volumes were significantly larger (p = 0.009) post ketamine than post placebo (LS means difference=0.008, standard error=0.003). Post-hoc tests did not attribute effects to specific subfields (all p > 0.05). Trend-wise volumetric increases were observed within the left hippocampal CA1 region (p = 0.076), and trend-wise volumetric reductions were obtained in the right hippocampal-amygdaloid transition region (HATA) (p = 0.067). Neither genotype nor a genotype-drug interaction significantly affected the results (all p > 0.7). The study provides evidence that ketamine has short-term effects on hippocampal subfield volumes in humans. The results translate previous findings from animal models of depression showing that ketamine has pro-neuroplastic effects on hippocampal structures and underscore the importance of the hippocampus as a key region in ketamine's mechanism of action.

Case Report: Bupropion Reduces the [123I]FP-CIT Binding to Striatal Dopamine Transporter.

The diagnosis of parkinsonian syndromes in patients with severe depression may be challenging due to overlapping clinical phenomena, especially regarding psychomotor and affective symptoms. [123I]FP-CIT-SPECT is a useful method to detect degenerative parkinsonian disorders. However, some drugs may influence the tracer binding and thus alter the result. We present a case of 56-year-old female inpatient with difficult-to-treat late-onset depression. Since the current major depressive episode (MDE) was accompanied by psychotic features including delusions and hallucinations as well as hypokinesia, stooped posture and hypomimia, underlying degenerative parkinsonism was suspected. The pathologic [123I]FP-CIT-SPECT scan under ongoing antidepressant therapy with bupropion 300 mg/die (serum level of bupropion 43 ng/ml and hydroxybupropion 2,332 ng/ml) showed reduced [123I]FP-CIT binding throughout the striatum. The scan normalized upon a wash-out phase of four half-time periods (serum level of bupropion was 0.4 ng/ml and for hydroxybupropion 80.5 ng/ml). Our report should serve as a cautionary note for use of [123I]FP-CIT in depressed patients, particularly in those treated with drugs interfering with the dopamine transporter. Furthermore, our case argues for a need of consultation of a movement disorder specialist prior to dopamine transporter imaging.

Second-generation antidepressants for treatment of seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent depressive episodes that is often treated with second-generation antidepressants (SGAs), light therapy, or psychotherapy. OBJECTIVES: To assess the efficacy and safety of second-generation antidepressants (SGAs) for the treatment of seasonal affective disorder (SAD) in adults in comparison with placebo, light therapy, other SGAs, or psychotherapy. SEARCH METHODS: This is an update of an earlier review first published in 2011. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1) in the Cochrane Library (all years), Ovid MEDLINE, Embase, and PsycINFO (2011 to January 2020), together with the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all available years), for reports of randomised controlled trials (RCTs). We hand searched the reference lists of all included studies and other systematic reviews. We searched ClinicalTrials.gov for unpublished/ongoing trials. We ran a separate update search for reports of adverse events in the Ovid databases.  SELECTION CRITERIA: For efficacy we included RCTs of SGAs compared with other SGAs, placebo, light therapy, or psychotherapy in adult participants with SAD. For adverse events we also included non-randomised studies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications against the inclusion criteria. Data extraction and 'Risk of bias' assessment were conducted individually. We pooled data for meta-analysis where the participant groups were similar, and the studies assessed the same treatments with the same comparator and had similar definitions of outcome measures over a similar duration of treatment. MAIN RESULTS: In this update we identified no new RCT on the effectiveness of SGAs in SAD patients. We included 2 additional single-arm observational studies that reported on adverse events of SGAs.  For efficacy we included three RCTs of between five and eight weeks' duration with a total of 204 participants. For adverse events we included two RCTs and five observational (non-randomised) studies of five to eight weeks' duration with a total of 249 participants. All participants met the DSM (Diagnostic and Statistical Manual of Mental Disorders) criteria for SAD. The average age ranged from 34 to 42 years, and the majority of participants were female (66% to 100%). Results from one trial with 68 participants showed that fluoxetine (20/36) was numerically superior to placebo (11/32) in achieving clinical response; however, the confidence interval (CI) included both a potential benefit as well as no benefit of fluoxetine (risk ratio (RR) 1.62, 95% CI 0.92 to 2.83, very low-certainty evidence). The number of adverse events was similar in both groups (very low-certainty evidence). Two trials involving a total of 136 participants compared fluoxetine versus light therapy. Meta-analysis showed fluoxetine and light therapy to be approximately equal in treating seasonal depression: RR of response 0.98 (95% CI 0.77 to 1.24, low-certainty evidence), RR of remission 0.81 (95% CI 0.39 to 1.71, very low-certainty evidence). The number of adverse events was similar in both groups (low-certainty evidence). We did not identify any eligible study comparing SGA with another SGA or with psychotherapy. Two RCTs and five non-randomised studies reported adverse event data on a total of 249 participants who received bupropion, fluoxetine, escitalopram, duloxetine, nefazodone, reboxetine, light therapy, or placebo. We were only able to obtain crude rates of adverse events, therefore caution is advised regarding interpretation of this information. Between 0% and 100% of participants who received an SGA suffered an adverse event, and between 0% and 25% of participants withdrew from the study due to adverse events. AUTHORS' CONCLUSIONS: Evidence for the effectiveness of SGAs is limited to one small trial of fluoxetine compared with placebo showing a non-significant effect in favour of fluoxetine, and two small trials comparing fluoxetine against light therapy suggesting equivalence between the two interventions. The lack of available evidence precluded us from drawing any overall conclusions on the use of SGAs for SAD. Further, larger RCTs are required to expand and strengthen the evidence base on this topic, and should also include comparisons with psychotherapy and other SGAs. Data on adverse events were sparse, and a comparative analysis was not possible. The data we obtained on adverse events is therefore not robust, and our confidence in the data is limited. Overall, up to 25% of participants treated with SGAs for SAD withdrew from the study early due to adverse events.

Cardiovascular Adverse Reactions During Antipsychotic Treatment: Results of AMSP, A Drug Surveillance Program Between 1993 and 2013.

BACKGROUND: Cardiovascular diseases are still the leading cause of global mortality. Some antipsychotic agents can show severe cardiovascular side effects and are also associated with metabolic syndrome. METHODS: This observational study was based on data of AMSP (Arzneimittelsicherheit in der Psychiatrie), a multicenter drug surveillance program in Austria, Germany and Switzerland, that recorded severe drug reactions in psychiatric inpatients. RESULTS: A total of 404 009 inpatients were monitored between 1993 and 2013, whereas 291 510 were treated with antipsychotics either in combination or alone. There were 376 cases of severe cardiovascular adverse reactions reported in the given timespan, yielding a relative frequency of 0.13%. The study revealed that incidence rates of cardiovascular adverse reactions were highest during treatment with ziprasidone (0.35%), prothipendyl (0.32%), and clozapine (0.23%). The lowest rate of cardiovascular symptoms occurred during treatment with promethazine (0.03%) as well as with aripiprazole (0.06%). The most common clinical symptoms were orthostatic collapse and severe hypotonia, sinustachycardia, QTc prolongation, myocarditis, and different forms of arrhythmia. The dosage at the timepoint when severe cardiovascular events occurred was not higher in any of the given antipsychotics than in everyday clinical practice and was in average therapeutic ranges. In terms of subclasses of antipsychotics, no significant statistical difference was seen in the overall frequencies of adverse reactions cases, when first-generation high potency, first-generation low potency, and second-generation antipsychotics were compared. Thirty percent of adverse events among second-generation antipsychotics were induced by clozapine. CONCLUSIONS: Our findings on cardiovascular adverse reactions contribute to a better understanding of cardiovascular risk profiles of antipsychotic agents in inpatients.

The Efficacy of Light Therapy in the Treatment of Seasonal Affective Disorder: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Bright light therapy (BLT) has been used as a treatment for seasonal affective disorder (SAD) for over 30 years. This meta-analysis was aimed to assess the efficacy of BLT in the treatment of SAD in adults. METHOD: We performed a systematic literature search including randomized, single- or double-blind clinical trials investigating BLT (≥1,000 lx, light box or light visor) against dim light (≤400 lx) or sham/low-density negative ion generators as placebo. Only first-period data were used from crossover trials. The primary outcome was the post-treatment depression score measured by validated scales, and the secondary outcome was the rate of response to treatment. RESULTS: A total of 19 studies finally met our predefined inclusion criteria. BLT was superior over placebo with a standardized mean difference of -0.37 (95% CI: -0.63 to -0.12) for depression ratings (18 studies, 610 patients) and a risk ratio of 1.42 (95% CI: 1.08-1.85) for response to active treatment (16 studies, 559 patients). We found no evidence for a publication bias, but moderate heterogeneity of the studies and a moderate-to-high risk of bias. CONCLUSIONS: BLT can be regarded as an effective treatment for SAD, but the available evidence stems from methodologically heterogeneous studies with small-to-medium sample sizes, necessitating larger high-quality clinical trials.

Alcohol consumption in Austrian physicians.

BACKGROUND: Alcohol is one of the leading exogenous causes for adverse health consequences in Europe. The aim of the present study was to examine the pattern of alcohol consumption in Austrian physicians. METHODS: A telephone survey was conducted in 400 office-based physicians in Austria. Our questionnaire included the four questions of the CAGE questionnaire and questions to assess alcohol consumption on the previous day. RESULTS: 131 participants (32.8%) completed the interview. 3.8% of the subjects had a CAGE score of 2 or higher indicating a problem with alcohol, but this rate was not statistically different from numbers reported for the general population (4.1%). 46.6% of our subjects had drunken alcohol on the previous day. Compared to the general population, the rate of having drunk alcohol yesterday was higher in both gender of our sample, but the amount of alcohol drunk was significantly lower. Doctors in rural areas had drunken alcohol more frequently and in greater quantities on the previous day than those in urban areas. There was a positive correlation between age and the amount of drinking on the previous day, and between age and CAGE scores. Furthermore, subjects who had consumed alcohol yesterday obtained higher scores on the CAGE. CONCLUSIONS: Our findings indicate that the rate of Austrian physicians with problematic alcohol consumption is similar to the general population. Physicians in rural areas and older doctors might be of higher risk for alcohol abuse.

Association between dynamic resting-state functional connectivity and ketamine plasma levels in visual processing networks.

Numerous studies demonstrate ketamine's influence on resting-state functional connectivity (rsFC). Seed-based and static rsFC estimation methods may oversimplify FC. These limitations can be addressed with whole-brain, dynamic rsFC estimation methods. We assessed data from 27 healthy subjects who underwent two 3 T resting-state fMRI scans, once under subanesthetic, intravenous esketamine and once under placebo, in a randomized, cross-over manner. We aimed to isolate only highly robust effects of esketamine on dynamic rsFC by using eight complementary methodologies derived from two dynamic rsFC estimation methods, two functionally defined atlases and two statistical measures. All combinations revealed a negative influence of esketamine on dynamic rsFC within the left visual network and inter-hemispherically between visual networks (p < 0.05, corrected), hereby suggesting that esketamine's influence on dynamic rsFC is highly stable in visual processing networks. Our findings may be reflective of ketamine's role as a model for psychosis, a disorder associated with alterations to visual processing and impaired inter-hemispheric connectivity. Ketamine is a highly effective antidepressant and studies have shown changes to sensory processing in depression. Dynamic rsFC in sensory processing networks might be a promising target for future investigations of ketamine's antidepressant properties. Mechanistically, sensitivity of visual networks for esketamine's effects may result from their high expression of NMDA-receptors.