An explorative single-arm clinical study to assess craving in patients with alcohol use disorder using Virtual Reality exposure (CRAVE)-study protocol.

BACKGROUND: Alcohol use disorder (AUD) belongs to the most burdensome clinical disorders worldwide. Current treatment approaches yield unsatisfactory long-term effects with relapse rates up to 85%. Craving for alcohol is a major predictor for relapse and can be intentionally induced via cue exposure in real life as well as in Virtual Reality (VR). The induction and habituation of craving via conditioned cues as well as extinction learning is used in Cue Exposure Therapy (CET), a long-known but rarely used strategy in Cognitive Behavioral Therapy (CBT) of AUD. VR scenarios with alcohol related cues offer several advantages over real life scenarios and are within the focus of current efforts to develop new treatment options. As a first step, we aim to analyze if the VR scenarios elicit a transient change in craving levels and if this is measurable via subjective and psychophysiological parameters. METHODS: A single-arm clinical study will be conducted including n = 60 patients with AUD. Data on severity of AUD and craving, comorbidities, demographics, side effects and the feeling of presence in VR will be assessed. Patients will use a head-mounted display (HMD) to immerse themselves into three different scenarios (neutral vs. two target situations: a living room and a bar) while heart rate, heart rate variability, pupillometry and electrodermal activity will be measured continuously. Subjective craving levels will be assessed before, during and after the VR session. DISCUSSION: Results of this study will yield insight into the induction of alcohol craving in VR cue exposure paradigms and its measurement via subjective and psychophysiological parameters. This might be an important step in the development of innovative therapeutic approaches in the treatment of patients with AUD. TRIAL REGISTRATION: This study was approved by the Charité-Universitätsmedizin Berlin Institutional Review Board (EA1/190/22, 23.05.2023). It was registered on ClinicalTrials.gov (NCT05861843).

Psychiatric presentations and admissions during the first wave of Covid-19 compared to 2019 in a psychiatric emergency department in Berlin, Germany: a retrospective chart review.

BACKGROUND: Most studies agree that the Covid-19 pandemic and the subsequent lockdown had a negative impact on mental health. On the other hand, international studies have shown that psychiatric emergency departments (pED) experienced a decrease in presentations and admissions. METHODS: Retrospective chart review of all pED presentations and admissions during the first wave of Covid-19 pandemic in Germany (Covid-19 period: 3/2/20 to 05/24/20) in a psychiatric hospital in Berlin compared to 1 year earlier (pre-Covid-19 period). Descriptive statistics and logistic regression were performed. RESULTS: We observed no statistical significant changes in overall pED presentations and overall hospital admissions during the Covid-19 period compared to the pre-Covid-19 period (813 vs. 894, - 9.1%, p = 0.064 and (363 vs. 437, - 16.9%, p = 0.080 respectively). In the subgroup analysis, less patients with depressive disorders (p = 0.035) and with personality disorders (p = 0.002) presented to the pED, a larger number of presentations with schizophrenia was observed (p = 0.020). In the Covid-19 period, less patients with substance use disorder and paranoid schizophrenia were admitted to the hospital via the pED than in the pre-Covid-19 period (p = 0.035 and p = 0.006, respectively). Bed capacity was reduced in the Covid-19 period by - 32.8% (p <  0.001). Presentations in police custody were 13.7% (p = 0.029) higher during the Covid-19 compared to pre-Covid-19 period, with higher rates in female presentations (p = 0.008) and suicide attempts (p = 0.012) and less hospital admissions (p = 0.048). Logistic regression analyses revealed that positive predictors for pED presentation during Covid-19 period were police custody (p <  0.001), being redirected from another hospital (p <  0.001), suicide attempt (p = 0.038), suicidal thoughts (p = 0.004), presentation with paranoid schizophrenia (p = 0.001) and bipolar and manic disorders (p = 0.004), negative predictors were hospital admission (p <  0.001), depressive disorders (p = 0.021) and personality disorders (p <  0.001). CONCLUSIONS: A larger number of presentations in police custody during the Covid-19 period may represent untreated medical needs. This was seen predominantly in female patients, suggesting this subgroup might have suffered particularly under lockdown measures. Patients with paranoid schizophrenia were the only subgroup, which increased in absolute numbers, also suggesting a particular lockdown effect. Reduced bed capacity due to infection curbing measures is suggestive to have played an important role in augmenting the threshold for hospital admissions.

[The application of virtual reality in the treatment of mental disorders]. / Die Anwendung der Virtuellen Realität in der Behandlung psychischer Störungen.

BACKGROUND: Virtual reality (VR) enables immersion in an interactive digital world with realistic experiences, that can be applied for controlled and personalized interventions. This review summarizes the current research on VR in the treatment of mental disorders. METHODS: Selective literature search in PubMed and Google Scholar. RESULTS: An increasing number of publications report the therapeutic application of VR for the treatment of mental disorders. Most VR applications are based on established therapy approaches, such as exposure therapy. According to meta-analytic data, virtual exposure therapy (VRET) for specific phobia and agoraphobia with panic disorder is as effective as traditional in vivo exposure therapy. VRET for the treatment of social phobia is significantly more effective than waitlist and placebo control groups with, however, currently inconsistent metanalytic results when compared to in vivo exposure therapy. VRET for the treatment of posttraumatic stress disorder (PTSD) is similar in effectiveness compared to active psychotherapy. For psychosis, positive results have been reported for the VR-based treatment of auditory verbal hallucinations. For patients with a substance use disorder, VR can induce craving, with still unverified diagnostic and therapeutic relevance. CONCLUSIONS: VRET can broaden the psychotherapy options for anxiety disorders. Encouraging results of VR-based treatments for psychosis and PTSD indicate the need for further research concerning its effectiveness and safety. In the field of substance use disorders, evaluation of clinical-orientated VR applications is needed.

Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

[Homelessness and mental illnesses]. / Wohnungslosigkeit und seelische Erkrankungen.

Homelessness is an expression of marked social exclusion phenomena and often particularly affects people with mental disorders. Mental disorders often precede the onset of homelessness but can also be a result of homelessness. Different forms of therapeutic and social support interventions have been evaluated in various countries, predominantly with an outreach treatment approach. These interventions were often combined with low threshold availability of housing programs. These showed positive effects on housing stability and reduction of psychiatric symptoms but not in reduction of substance use disorders. Peer support strategies and the use of digital media are possible options for future therapeutic strategies.

[Suicidal tendencies in adolescence : Dysfunctional familiar communication as risk factor]. / Suizidalität in der Adoleszenz : Dysfunktionale familiäre Kommunikation als Risikofaktor.

BACKGROUND: Suicide is one of the four most common causes of death in adolescence worldwide. Although it is well known that suicidal people often have insufficient communication strategies, the importance of family communication for adolescent suicidality has not yet been sufficiently explored. OBJECTIVE: The aim of this study was to provide a systematic review of family communication as a risk factor for adolescent suicidal tendencies and to develop treatment recommendations. METHODS: In this study a systematic literature search was conducted in PubMed, Embase, CENTRAL and PsychINFO. The methodological quality of the studies was evaluated and a summary prepared. RESULT: A total of 195 studies were extracted and screened for their suitability. Of these studies, 7 which examined a total of 13,107 adolescents aged 11-22 years were included in this review and critically evaluated. Of the studies evaluated six found a correlative relationship between dysfunctional parent-child communication and adolescent suicidality. Communication with the mother appears to be more essential. CONCLUSION: The results of this literature search indicate that functional communication with parents seems to be protective for suicidal adolescents. From this, recommendations can be derived for preventive measures in families with adolescents who are otherwise at increased risk of suicide. Longitudinal study designs are needed to conclusively answer the research question.

[Obsessive-Compulsive Symptoms in a Sample of Patients with Chronic Schizophrenia Under Clozapine Treatment]. / Zwangssymptome bei chronisch erkrankten Patienten mit einer Schizophrenie unter Clozapintherapie.

Background: There is a high prevalence of obsessive-compulsive symptoms (OCS) in patients with schizophrenia. Antipsychotic treatment, especially duration and type of substance, is suspected to increase or even cause OCS. Methods: We examined in a naturalistic cross-sectional study the severity of OCS (Obsessive-Compulsive Inventory - Revised) and the incidence of obsessive-compulsive disorder (OCD) according to ICD-10 criteria in 70 patients with schizophrenia. 26 patients were treated with clozapine and 44 patients were treated with another second-generation antipsychotic (SGA). After group matching, the two groups did not differ significantly in age, gender, duration of illness, treatment duration with the current antipsychotic substance and chlorpromazine-equivalent dosage. Results: Patients treated with Clozapine showed a significantly higher rate of OCD (χ2 = 7.304, p = 0.007) and a significantly higher severity of OCS (t = 2.216, p = 0.037) compared to patients treated with another SGA. For the whole sample, duration of treatment with the current antipsychotic medication correlated significantly (p = 0.033, r = 0.323) with the severity of OCS, controlled for duration of illness. However, there was no significant correlation between severity of OCS and duration of illness, controlled for duration of treatment with the current antipsychotic substance. Discussion: Our data suggest an interrelation between the development of OCS or OCD and antipsychotic treatment, especially clozapine. Thereby, duration of treatment is correlated with the severity of OCS, irrespective of the duration of illness.

[Maintenance treatment in opioid-dependent patients with migration background]. / Opioidsubstitution bei heroinabhängigen Patienten mit Migrationshintergrund.

BACKGROUND: No regional analyses regarding opioid-dependent patients in maintenance treatment with a migration background have so far been performed in German-speaking countries. OBJECTIVES: This study examined patients with and without a migration background regarding socioeconomic parameters, characteristics of dependency and attitude towards opiate maintenance treatment (OMT). MATERIAL AND METHODS: From May to October 2011 patients in OMT from all of the 20 psychiatry clinics and 110 physician practices in Berlin with a licence to provide OMT were included in this analysis. RESULTS: Out of the 986 participating patients, 956 gave information on migration background and of these, 204 (21.3 %) originated from a country other than Germany. Compared to patients without a migration background, their participation in a maintenance program was significantly shorter and they more often expressed a desire to end OMT and wanted a limited duration of OMT. CONCLUSION: The differences regarding duration of OMT and the wish to end OMT can reflect a stronger desire for abstinence and a different attitude towards maintenance treatment of patients with a migration background.