Treatment of bipolar depression: clinical practice vs. adherence to guidelines-data from a Bavarian drug surveillance project.

Objectives: Pharmacotherapy of bipolar depression (BPD) is confronted with major clinical challenges, like limited evidence-based treatment options, regular cases of treatment resistance, and risk of treatment-emergent affective switches. Medical guidelines can support practitioners to make decisions based on current scientific evidence. The objective of this study is to evaluate to what extent recommendations of the 2019 German S3 guidelines "Diagnosis and Treatment of Bipolar Disorders" are reflected in clinical practice in inpatient treatment. Methods: We conducted a descriptive analysis of prescription numbers in 2,627 patients with BPD in a naturalistic inpatient setting analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig) from the years 2014-2022. Results: Of the patients, 38% were not administered any drug explicitly recommended for treatment of BPD, that is, quetiapine, lamotrigine, carbamazepine, or olanzapine. Only 6% of the patients received monotherapy with one of those drugs. Of the patients, 34% were administered ≥4 psychotropic drugs simultaneously. Patients received 912 different therapy regimens of mono or combination therapy with mood stabilizers (MS), atypical antipsychotics (AAP), and antidepressants. Of the patients, 72% received an antidepressant and 6% without concomitant prescription of an AAP or MS. Prescription rates of venlafaxine (21% to 14%) and tricyclic antidepressants (9% to 6%) decreased significantly from the first (2014-2016) to the last (2020-2022) observed time period. Of the patients, 60% received an MS. Prescription rate of valproate (22% to 14%) decreased significantly, while lithium prescription increased significantly (29% to 35%). Of the patients, 71% were administered an AAP. Quetiapine was the most prescribed drug overall (43%). Only two patients were administered a combination of olanzapine and fluoxetine. Conclusion: Our results demonstrate a substantial gap between guideline recommendations and current clinical practice. The remarkable heterogeneity in treatment regimens, with no discernible dominant treatment approach, is in part a reflection of the complexity of bipolar disorder but also substantiates the need of comprehensive recommendations regarding combination therapies. Increase in lithium prescription is an encouraging development due to its unique efficacy in maintenance treatment. To improve the quality of clinical practice guideline implementation, more randomized controlled trials should be conducted in the future to prospectively investigate different implementation strategies.

The Clinical Impact of Real-Time fMRI Neurofeedback on Emotion Regulation: A Systematic Review.

Emotion dysregulation has long been considered a key symptom in multiple psychiatric disorders. Difficulties in emotion regulation have been associated with neural dysregulation in fronto-limbic circuits. Real-time fMRI-based neurofeedback (rt-fMRI-NFB) has become increasingly popular as a potential treatment for emotional dysregulation in psychiatric disorders, as it is able to directly target the impaired neural circuits. However, the clinical impact of these rt-fMRI-NFB protocols in psychiatric populations is still largely unknown. Here we provide a comprehensive overview of primary studies from 2010 to 2023 that used rt-fMRI-NFB to target emotion regulation. We assessed 41 out of 4001 original studies for methodological quality and risk of bias and synthesised concerning the frequency of significant rt-fMRI-NFB-related effects on the neural and behaviour level. Successful modulation of brain activity was reported in between 25 and 50 percent of study samples, while neural effects in clinical samples were more diverse than in healthy samples. Interestingly, the frequency of rt-fMRI-NFB-related behavioural improvement was over 75 percent in clinical samples, while healthy samples showed behavioural improvements between 0 and 25 percent. Concerning clinical subsamples, rt-fMRI-NFB-related behavioural improvement was observed in up to 100 percent of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) samples. Substance use samples showed behavioural benefits ranging between 50 and 75 percent. Neural effects appeared to be less frequent than behavioural improvements: most neural outcomes ranged between 25 and 50 percent for MDD and substance use and between 0 and 25 percent for PTSD. Using multiple individualised regions of interest (ROIs) for rt-fMRI-NFB training resulted in more frequent behavioural benefits than rt-fMRI-NFB solely based on the amygdala or the prefrontal cortex. While a significant improvement in behavioural outcomes was reported in most clinical studies, the study protocols were heterogeneous, which limits the current evaluation of rt-fMRI-NFB as a putative treatment for emotional dysregulation.

What Chemsex does to the brain - neural correlates (ERP) regarding decision making, impulsivity and hypersexuality.

Chemsex describes the use of specific substances (methamphetamine, GHB/GBL, mephedrone, ketamine) which initiate or enhance sexual experiences and is mainly prevalent among men who have sex with men. Many Chemsex users experience somatic complications (for example sexually transmitted diseases) and sometimes adverse sociological, psychological, and neurological symptoms, such as depression, impulse control disorders or hypersexuality. Changes in impulsivity and deficits in executive functions have demonstrated to be associated with addiction and impulse control disorders as well as frontal brain dysfunction and behavioral control deficits. This study aims to explore the effects of neurophysiological correlates of inhibition and decision making in Chemsex users with an EEG paradigm using event-related potentials (N2, P3). 15 Chemsex users and 14 matched control subjects, all of them men who have sex with man, participated in an auditory Go/NoGo/Voluntary Selection EEG paradigm. In addition, clinical data (e.g. regarding depression), demographic information as well as measures of well-being and sexual behavior were collected. The results demonstrated that clinical symptoms, hypersexuality, and sexual risk behavior were more pronounced in Chemsex users compared to non-users. P3 amplitudes did not differ significantly between groups. However, the Chemsex users showed decreased electrophysiological N2 responses in fronto-central brain regions during decision-making, indicating compromised executive function and inhibitory control. The observed impairments may lead to increased risk behavior regarding drug abuse and hypersexuality. Understanding the neurobiological mechanisms can contribute to targeted interventions in order to mitigate the negative consequences of engaging in Chemsex and improve general well-being.

Corrigendum: Estimating the prevalence of alcohol-related disorders and treatment utilization in Bremen 2016/2017 through routine data linkage.

[This corrects the article DOI: 10.3389/fpsyt.2023.1002526.].

[Discharged, but where to? The Current Situation of Long Stay Patients in German Psychiatric Clinics]. / Entlassen, aber wohin? Zur aktuellen Situation der "Langlieger" in deutschen psychiatrischen Kliniken.

OBJECTIVE: The study analyses the number, characteristics and reasons for a length of stay of patients in German psychiatric clinics in excess of 6 months. METHODS: The study was implemented in the form of a nationwide online survey, which was addressed to chief physicians of psychiatric clinics. RESULTS: In the sample, 174 patients in 80 psychiatric clinics were identified who could not be discharged because no suitable follow-up services were available in the region. The majority of patients are male, often have an F2 diagnosis and exhibit aggressive behaviour during their hospital stay. CONCLUSION: To avoid inappropriate health care and prevent prolonged stays for a subgroup of mentally ill people, individual complex services should be implemented in community psychiatry.

Clustering care pathways of people with alcohol dependence using a data linkage of routine data in Bremen, Germany.

BACKGROUND: Although many individuals with alcohol dependence (AD) are recognized in the German healthcare system, only a few utilize addiction-specific treatment services. Those who enter treatment are not well characterized regarding their prospective pathways through the highly fragmented German healthcare system. This paper aims to (1) identify typical care pathways of patients with AD and their adherence to treatment guidelines and (2) explore the characteristics of these patients using routine data from different healthcare sectors. METHODS: We linked routinely collected register data of individuals with a documented alcohol-related diagnosis in the federal state of Bremen, Germany, in 2016/2017 and their addiction-specific health care: two statutory health insurance funds (outpatient pharmacotherapy for relapse prevention and inpatient episodes due to AD with and without qualified withdrawal treatment (QWT)), the German Pension Insurance (rehabilitation treatment) and a group of communal hospitals (outpatient addiction care). Individual care pathways of five different daily states of utilized addiction-specific treatment following an index inpatient admission due to AD were analyzed using state sequence analysis and cluster analysis. The follow-up time was 307 days (10 months). Individuals of the clustered pathways were compared concerning current treatment recommendations (1: QWT followed by postacute treatment; 2: time between QWT and rehabilitation). Patients' characteristics not considered during the cluster analysis (sex, age, nationality, comorbidity, and outpatient addiction care) were then compared using a multinomial logistic regression. RESULTS: The analysis of 518 individual sequences resulted in the identification of four pathway clusters differing in their utilization of acute and postacute treatment. Most did not utilize subsequent addiction-specific treatment after their index inpatient episode (n = 276) or had several inpatient episodes or QWT without postacute treatment (n = 205). Two small clusters contained pathways either starting rehabilitation (n = 26) or pharmacotherapy after the index episode (n = 11). Overall, only 9.3% utilized postacute treatment as recommended. CONCLUSIONS: A concern besides the generally low utilization of addiction-specific treatment is the implementation of postacute treatments for individuals after QWT.

Implications of Switching from Conventional to Electronic Cigarettes on Quality of Life and Smoking Behaviour: Results from the EQualLife Trial.

INTRODUCTION: Electronic cigarettes and "vaping" have become popular since their appearance in Europe and the USA in approximately 2006. They are often perceived as having fewer health risks than conventional cigarettes, which makes them of interest as a support tool in smoking cessation. However, its efficacy regarding cessation or reduction of smoking under real-life conditions remains controversial. Our objective was to clarify this question in an observational study of smoking habits after initiating vaping without targeted intervention, as compared to a validated cessation programme. METHODS: From October 2015 to April 2018, 80 subjects (60 in the e-cigarette group and 20 in the supervised smoking cessation group) were included in two trial visits, one at the start of the trial and the second after 3 months, plus 4 questionnaire surveys: at the start of the trial and after a 1, 2, and 3 month period. The questionnaire included a nicotine use inventory, a modified Fagerström test for nicotine dependence, and the WHO-QOL-BREF survey. RESULTS: E-cigarettes were effective, leading to a significant (p < 0.03) reduction (p < 0.03) in tobacco consumption and nicotine dependence, with an abstinence rate of 43% after 3 months. Compared to participants in the smoking cessation programme, their use was not associated with an improvement in quality of life during the quitting attempt, and there were no significant differences in clinical symptoms between groups. The reduction in nicotine dependence was more pronounced (p < 0.012) for the smoking cessation programme, with higher abstinence rates (p = 0.011 after 12 weeks) and lower (p < 0.003) remaining tobacco consumption compared to electronic cigarettes. DISCUSSION/CONCLUSIONS: The use of electronic cigarettes reduced nicotine dependence and tobacco consumption, but a supervised smoking cessation programme was superior in terms of achieved cessation in both regards. Electronic cigarettes did not improve the quality of life. Since e-cigarettes could be associated with long-term health risks, their usefulness in smoking cessation remains questionable, and a professionally guided and validated smoking cessation programme still appears to be superior and preferable, in terms of achieved cessation. Although this trial is limited regarding the number of participants and follow-up time, it highlights the need for additional, large clinical trials evaluating the efficacy of e-cigarettes for smoking cessation in comparison to a professionally guided smoking cessation programme.

Signature of Altered Retinal Microstructures and Electrophysiology in Schizophrenia Spectrum Disorders Is Associated With Disease Severity and Polygenic Risk.

BACKGROUND: Optical coherence tomography and electroretinography studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSDs). However, it remains unclear which specific retinal layers are affected; how the retina, brain, and clinical symptomatology are connected; and how alterations of the visual system are related to genetic disease risk. METHODS: Optical coherence tomography, electroretinography, and brain magnetic resonance imaging were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSDs and 130 healthy control individuals. The sparse partial least squares algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with individual polygenic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisons were performed for each individual optical coherence tomography and electroretinography parameter. RESULTS: The sparse partial least squares analysis yielded a phenotype-eye-brain signature of SSDs in which greater disease severity, longer duration of illness, and impaired cognition were associated with electrophysiological alterations and microstructural thinning of most retinal layers. Higher individual loading onto this disease-relevant signature of the visual system was significantly associated with elevated polygenic risk for schizophrenia. In case-control comparisons, patients with SSDs had lower macular thickness, thinner retinal nerve fiber and inner plexiform layers, less negative a-wave amplitude, and lower b-wave amplitude. CONCLUSIONS: This study demonstrates multimodal microstructural and electrophysiological retinal alterations in individuals with SSDs that are associated with disease severity and individual polygenic burden.

P300 parameters in major depressive disorder: A systematic review and meta-analysis.

OBJECTIVES: Event-related potential measures have been extensively studied in mental disorders. Among them, P300 amplitude and latency reflect impaired cognitive abilities in major depressive disorder (MDD). The present systematic review and meta-analysis was conducted to investigate whether patients with MDD differ from healthy controls (HCs) with respect to P300 amplitude and latency. METHODS: PubMed and Web of Science databases were searched from inception to 15 January 2023 for case-control studies comparing P300 amplitude and latency in patients with MDD and HCs. The primary outcome was the standard mean difference. A total of 13 articles on P300 amplitude and latency were included in the meta-analysis. RESULTS: Random effect models indicated that MDD patients had decreased P300 amplitude, but similar latency compared to healthy controls. According to regression analysis, the effect size increased with the severity of depression and decreased with the proportion of women in the MDD samples. Funnel plot asymmetry was not significant for publication bias. CONCLUSIONS: Decreased P300 amplitude may be a candidate diagnostic biomarker for MDD. However, prospective studies testing P300 amplitude as a monitoring biomarker for MDD are needed.

[Video-Assisted Psychotherapy For Refugees: A Pilot Study]. / Videogestützte Psychotherapie für Geflüchtete: Eine Pilotstudie.

OBJECTIVE: Global conflicts and humanitarian crises led to an increase in forced migration to Germany in recent years. To improve the mental health care system for refugees and asylum seekers in Germany perspectively, we aim to examine the feasibility of implementing the culturally sensitive group psychotherapy Empowerment for refugees with affective disorders in a video-assisted setting. METHODS: Empowerment is a culturally sensitive, interpreter-assisted intervention for the treatment of depressive and stress-related symptoms in refugees. Four male refugees from Afghanistan participated in a pilot study. The intervention included 16 modules delivered via video over a 12-week period. RESULTS: The internet connection was frequently unstable and led to organizational challenges. The therapy was feasible in terms of linguistic and interactional aspects. DISCUSSION: The stability of the internet connection represents the major criterion for a successful implementation of the therapy. Implications for future studies are discussed. CONCLUSION: Regarding the potential opportunities to improve the mental health care provision to refugees and asylum seekers in the future, the video-assisted therapy concept could be investigated in a randomized controlled trial.

Short-term effectiveness of the national German quitline for smoking cessation: results of a randomized controlled trial.

BACKGROUND: The objective of the present study was to examine the short-term effectiveness of the national German quitline for smoking cessation. METHODS: A parallel-group, two-arm, superiority, randomized controlled trial with data collection at baseline and post-intervention (three months from baseline) was conducted. Individuals were randomized to either the intervention group, receiving up to six telephone counselling calls, or the control group, receiving an active control intervention (self-help brochure). The primary outcome was the seven-day point prevalence abstinence at post-assessment. Secondary outcomes included changes in smoking-related cognitions and coping strategies from pre- to post-assessment, the perceived effectiveness of intervention components, and the satisfaction with the intervention. RESULTS: A total of n = 905 adult daily smokers were assigned to either the intervention group (n = 477) or the control group (n = 428). Intention-to-treat analyses demonstrated that individuals allocated to the telephone counselling condition were more likely to achieve seven-day point prevalence abstinence at post-assessment compared to those allocated to the self-help brochure condition (41.1% vs. 23.1%; OR = 2.3, 95% CI [1.7, 3.1]). Participants who received the allocated intervention in both study groups displayed significant improvements in smoking-related cognitions and coping strategies with the intervention group showing greater enhancements than the control group. This pattern was also found regarding the perceived effectiveness of intervention components and the satisfaction with the intervention. CONCLUSION: The present study provides first empirical evidence on the short-term effectiveness of the national German quitline for smoking cessation, highlighting its potential as an effective public health intervention to reduce the burden of disease associated with smoking. TRIAL REGISTRATION: This study is registered in the German Clinical Trials Register (DRKS00025343). Date of registration: 2021/06/07.

Neuronal correlates of intensification and acceptance of symptoms during exposure therapy in patients with obsessive-compulsive disorder.

Introduction: Cognitive behaviour therapy with exposure and response prevention is efficient in treating patients with obsessive-compulsive disorder (OCD). Nevertheless, it would be helpful for many patients to complement the therapeutic treatment with acceptance strategies to further increase the therapeutic benefit. The aim of the present study was to examine neurobiological responses to acceptance and intensification strategies during symptom provocation alongside the psychotherapeutic process. Method: A total of 23 patients diagnosed with OCD (subtype: washing/contamination fear) was instructed to utilise either an acceptance strategy (ACS) or an intensification strategy (INS) to cope with their emotional and cognitive reactions to personalised symptom-triggering and neutral pictures. Fourteen patients participated twice: at the beginning [T1] and at the end [T2] of an inpatient multimodal treatment including cognitive behaviour therapy with response prevention to assess functional variations. Results: For the contrast of T1 and T2, ACS showed increased brain activity in the left inferior frontal gyrus (IFG), left caudate body, and posterior cingulate gyrus (PCC). They also showed decreased activity in the left anterior insula. INS showed decreased activation in right lingual gyrus and right caudate body. At T2, ACS showed increased activation compared to INS in the left cerebrum: IFG, caudate nucleus, middle and superior temporal gyrus, and PCC/cuneus. For the comparison of T1 and T2, the ACS revealed increased brain activity in the left IFG, left caudate body, and right inferior parietal lobe. It showed decreased activity in the left anterior insula. The INS revealed decreased activity in right lingual gyrus and right caudate body.The psychometric questionnaires suggested that patients were able to reduce obsession, compulsion, and depression symptoms. Furthermore, patients rated the ACS as more useful for themselves compared with the INS. Conclusion: The increased left IFG activity using ACS (T1 vs. T2) could be interpreted as a better inhibitory top-down process, while the increased PCC response might be due to a better reappraisal strategy after therapy. ACS seems to mobilise neuronal activations under therapy, especially in the left hemisphere. Both strategies showed reductions in emotional networks as a neuronal correlate of therapy success. Overall, ACS may be more efficient than INS, as rated by the patients and as in accordance with neurobiological findings.

Understanding the Pathophysiology of Mental Diseases and Early Diagnosis Thanks to Electrophysiological Tools: Some Insights and Empirical Facts.

Objective. Neurophysiological tools remain indispensable instruments in the assessment of psychiatric disorders. These techniques are widely available, inexpensive and well tolerated, providing access to the assessment of brain functional alterations. In the clinical psychiatric context, electrophysiological techniques are required to provide important information on brain function. While there is an immediate benefit in the clinical application of these techniques in the daily routine (emergency assessments, exclusion of organic brain alterations), these tools are also useful in monitoring the progress of psychiatric disorders or the effects of therapy. There is increasing evidence and convincing literature to confirm that electroencephalography and related techniques can contribute to the diagnostic workup, to the identification of subgroups of disease categories, to the assessment of long-term causes and to facilitate response predictions. Methods and Results. In this report we focus on 3 different novel developments of the use of neurophysiological techniques in 3 highly prevalent psychiatric disorders: (1) the value of EEG recordings and machine learning analyses (deep learning) in order to improve the diagnosis of dementia subtypes; (2) the use of mismatch negativity in the early diagnosis of schizophrenia; and (3) the monitoring of addiction and the prevention of relapse using cognitive event-related potentials. Empirical evidence was presented. Conclusion. Such information emphasized the important role of neurophysiological tools in the identification of useful biological markers leading to a more efficient care management. The potential of the implementation of machine learning approaches together with the conduction of large cross-sectional and longitudinal studies was also discussed.

[Inpatient Treatment of Mentally Ill Prisoners in General Psychiatric Departments and Hospitals]. / Status der stationären Behandlung psychisch erkrankter Strafgefangener in allgemeinpsychiatrischen Abteilungen und Kliniken.

BACKGROUND: Inpatient psychiatric treatment of prisoners is organized differently in Germany, depending on the structural conditions of the federal state and prison. There are very few findings on the different possibilities of treatment and the view of the hospitals on this issue. OBJECTIVES: Our aim was to gain an up-to-date picture of inpatient treatment of prisoners in general psychiatric departments and hospitals and the challenges these institutions face. METHODS: We conducted an anonymous online survey of the frequency, extent, and challenges of inpatient treatment of prisoners. Approximately 460 chief physicians of German general psychiatric departments and hospitals were invited to participate in this survey. In addition to descriptive statistics, we calculated group differences by type of hospital and by subjective responsibility for inpatient care of prisoners. RESULTS: A total of 74 chief physicians surveyed participated; 51.4% of the surveyed hospitals provided psychiatric inpatient treatment to prisoners in 2020. Group differences between the different types of hospitals were found only for the presence of anticipated anxiety among regular inpatients. Various differences were found between responsible and non-responsible hospitals, especially with regard to organizational aspects. DISCUSSION: For the treatment of mentally ill prisoners, various organizational challenges as well as fears of hospital staff and fellow patients were mentioned by the participants. The type of hospital appears to play a subordinate role here, whereas the responsibility of the hospital for the inpatient treatment of mentally ill prisoners might be more decisive for anticipated concerns and barriers.

REM parameters in drug-free major depressive disorder: A systematic review and meta-analysis.

Previous studies revealed that rapid eye movement (REM) parameters, such as REM latency (RL) and REM density (RD) could be used as electrophysiological markers of depression. Yet these finding should be re-tested in a comorbid-free and drug-free sample. The present systematic review and meta-analysis was conducted to investigate whether drug-free and comorbid-free patients with unipolar depression differentiate from controls with respect to the RL and RD. The PubMed and Web of Science databases were screened from inception to 23 January 2023 for case-control studies comparing RL and RD of patients with unipolar depression and controls. The primary outcome was the standard mean difference. The data were fitted with a random-effects model. Meta-regressions were conducted to investigate patient characteristics and effect size. Publication bias assessment was checked by Egger's Regression and funnel plot asymmetry. Among 43 articles accepted as eligible, 46 RL and 22 RD measurements were included in the meta-analysis. The results indicated shortened RL and increased RD in the patient group than controls. Neither Egger's regression nor funnel plot asymmetry were significant for publication bias. In conclusion, our results tested within drug-free and comorbid-free samples are in line with the literature.

The influence of marathon running on resting-state EEG activity: a longitudinal observational study.

Physical activity (PA) has positive effects on various health aspects and neuronal functions, including neuronal plasticity. Exceeding a certain exercise frequency and duration has been associated with negative effects. Our study investigated the effects of excessive PA with a marathon run (MA) and regular PA (training and recovery phases) on electrocortical activity, as measured by electroencephalography (EEG). Thirty healthy marathon runners (26 male, 45 ± 9 yrs) were enrolled in the study. Four resting-state 32 channel EEG recordings were conducted: 12-8 weeks before MA (T-1), 14-4 days prior to MA (T0), 1-6 days after (T2), and 13-15 weeks after MA (T3). Power spectrum analyses were conducted using standardized Low-Resolution Electromagnetic Tomography (sLORETA) and included the following frequency bands: delta (1.5-6 Hz), theta (6.5-8.0 Hz), alpha1 (8.5-10 Hz), alpha2 (10.5-12.0 Hz), beta1 (12.5-18.0 Hz), beta2 (18.5-21.0 Hz), beta3 (21.5-30.0 Hz), and total power (1.5-30 Hz). Statistical nonparametric mapping showed reduced power both in the alpha-2 (log-F ratio = - 0.705, threshold log-F ratio = ± 0.685, p < 0.05) and in the delta frequency band (log-F ratio = -0.699, threshold log-F ratio = ± 0.685, p < 0.05) in frontal cortical areas after MA (T2 vs. T0). These effects diminished at long-term follow-up (T3). The results can be interpreted as correlates for subacute neuroplasticity induced by strenuous and prolonged PA. Although previous studies reported an increase in alpha frequency during and directly postexercise, the adverse observation a few days after exercise cessation suggests counterregulatory mechanisms, whose complex origin can be suspected in subcortical circuits, changes in neurotransmitter systems and modulation of affectivity.

Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission.

PURPOSE: Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA). METHODS: FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level. RESULTS: Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912). CONCLUSION: Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.

[COVID-19 vaccination for people with severe mental diseases : Results of the COVID Ψ outpatient survey and recommendations for psychiatry]. / COVID-19-Impfung für Menschen mit schweren psychischen Erkrankungen : Ergebnisse des COVID-Ψ-Ambulant-Surveys und Empfehlungen für die Psychiatrie.

BACKGROUND: Severe mental illnesses are risk factors for SARS-CoV-2-related morbidity and mortality. Vaccination is an effective protection; therefore, high vaccination rates should be a major priority for people with mental illnesses. OBJECTIVES: (1) Identification of at-risk groups for non-vaccination and structures and interventions needed for widespread vaccination among people with mental illnesses from the perspective of outpatient psychiatrists and neurologists, (2) discussion of the results in the context of the international literature and (3) recommendations derived from them. MATERIAL AND METHODS: Qualitative content analysis of COVID-19 vaccination-related questions from the COVID Ψ online survey of n = 85 psychiatrists and neurologists in Germany. RESULTS: In the survey, people with schizophrenia, severe lack of drive, low socioeconomic status and homelessness were seen as risk groups for non-vaccination. Increased and targeted information, education, addressing and motivation and easily accessible vaccination offers by general practitioners, psychiatrists, and neurologists as well as complementary institutions were considered as important interventions. DISCUSSION: COVID-19 vaccinations as well as information, motivation and access support should be systematically offered by as many institutions of the psychiatric, psychotherapeutic and complementary care systems in Germany as possible.

The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research.

Introduction: Treatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking. Furthermore, the development of drugs to treat SMIs such as schizophrenia is limited by the use of operationalized symptom-based clusters for diagnosis. Methods: In line with the Research Domain Criteria initiative, the Clinical Deep Phenotyping (CDP) study is using a multimodal approach to reveal the neurobiological underpinnings of clinically relevant schizophrenia subgroups by performing broad transdiagnostic clinical characterization with standardized neurocognitive assessments, multimodal neuroimaging, electrophysiological assessments, retinal investigations, and omics-based analyzes of blood and cerebrospinal fluid. Moreover, to bridge the translational gap in biological psychiatry the study includes in vitro investigations on human-induced pluripotent stem cells, which are available from a subset of participants. Results: Here, we report on the feasibility of this multimodal approach, which has been successfully initiated in the first participants in the CDP cohort; to date, the cohort comprises over 194 individuals with SMI and 187 age and gender matched healthy controls. In addition, we describe the applied research modalities and study objectives. Discussion: The identification of cross-diagnostic and diagnosis-specific biotype-informed subgroups of patients and the translational dissection of those subgroups may help to pave the way toward precision medicine with artificial intelligence-supported tailored interventions and treatment. This aim is particularly important in psychiatry, a field where innovation is urgently needed because specific symptom domains, such as negative symptoms and cognitive dysfunction, and treatment-resistant symptoms in general are still difficult to treat.

The relationship between blood-brain barrier dysfunction and neurocognitive impairments in first-episode psychosis: findings from a retrospective chart analysis.

BACKGROUND: Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood-brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated. AIMS: To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention. METHOD: We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest. RESULTS: Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments. CONCLUSIONS: The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed.