European Archives of Psychiatry and Clinical Neuroscience最新文献

As a wide group of medicines, the effectiveness and safety of 'medical cannabis' products is likely to vary in relation to product-specific dimensions such as potency, dosage, route of administration, and cannabinoid composition. Systematic reviews can perform a crucial role in analysing and synthesising the outcomes of medical cannabis interventions found in empirical research. We analysed 23 contemporary systematic reviews on the effectiveness and safety of medical cannabis to discern the extent to which this body of work aimed to capture, and ultimately captured, the differing outcomes of medical cannabis products by product-specific dimensions of treatment. We further highlighted the methodological reasons given by authors for an inability to describe this granular level of information. We found that a minority of systematic reviews explicitly aimed to perform a subgroup analysis to determine differences in treatment outcomes by product-specific dimensions of medical cannabis, with even fewer subsequently doing so. Authors' stated reasons for this concerned either overly large or overly small levels of variation in the characteristics, compositions, and administrations of medical cannabis products used, rendering subgroup analyses methodologically inappropriate or inapplicable. Furthering systematic reviews' abilities to capture granular information on medical cannabis treatment outcomes in relation to product-specific dimensions of treatments will require further standardisation of treatments in empirical studies.

Cardiac autonomic dysfunction (CADF), mainly characterized by increased heart rate, decreased heart rate variability, and loss of vagal modulation, has been extensively described in patients with schizophrenia (SCZ) and their healthy first-degree relatives. As such, it represents an apparent physiological link that contributes to the increased cardiovascular mortality in these patients. Common genetic variation is a putative underlying mechanism, along with lifestyle factors and antipsychotic medications. However, the extent to which CADF is associated with genetic factors for SCZ is unknown. A sample of 83 drug-naive SCZ patients and 96 healthy controls, all of European origin, underwent a 30-minute autonomic assessment under resting conditions. We incorporated parameters from several domains into our model, including time and frequency domains (mean heart rate, low/high frequency ratio) and compression entropy, each of which provides different insights into the dynamics of cardiac autonomic function. These parameters were used as outcome variables in linear regression models with polygenic risk scores (PRS) for SCZ as predictors and age, sex, BMI, smoking status, principal components of ancestry and diagnosis as covariates. Of the three CADF parameters, SCZ PRS was significantly associated with mean heart rate in the combined case/control sample. However, this association was was no longer significant after including diagnosis as a covariate (p = 0.29). In contrast, diagnostic status is statistically significant for all three CADF parameters, accounting for a significantly greater proportion of the variance in mean heart rate compared to SCZ PRS (approximately 16% vs. 4%). Despite evidence for a common genetic basis of CADF and SCZ, we were unable to provide further support for an association between the polygenic burden of SCZ and cardiac autonomic function beyond the diagnostic state. This suggests that there are other important characteristics associated with SCZ that lead to CADF that are not captured by SCZ PRS.

This study aimed to examine longitudinal changes in motor dexterity (MD) performance in first episode of psychosis (FEP), focusing on diagnosis-specific trajectories. Participants were recruited from the project PAFIP in Spain (134 FEP, 84 HC). MD was assessed using the Grooved Pegboard Test at baseline and at 10-year follow-up. Clinical and premorbid data were collected for the patients. FEP participants were classified as having schizophrenia (SCZ) or other psychosis (OP) and compared with a group of healthy controls (HC). MD correlated significantly with age and intelligence in all participants. MD in SCZ patients was additionally correlated with premorbid adjustment and negative symptoms, whereas in the OP group the association was with antipsychotic dose. SCZ patients showed a slight decline in MD at follow-up, whereas the OP and HC groups remained stable. There may be different long-term trajectories of MD across diagnoses in FEP patients. Early developmental factors such as premorbid adaptation and cognitive function, together with age-related changes, may influence a mild decline in MD specifically in schizophrenia.

Individuals with persistent depressive disorder (PDD) are at increased risk for suicidality. Suicidality may be precipitated by loneliness. However, their temporal interplay in PDD has not been studied. We conducted a feasibility study using ecological momentary assessment (EMA) to measure short-term courses of suicidality and loneliness in 20 inpatients with PDD and current suicidality. EMA adherence of 13 completers was 81.3%. Suicidal ideations and loneliness varied with one standard deviation over three to six hours. This pilot study confirmed the feasibility of EMA in PDD and provided new insights in dynamics of suicidality and loneliness informing future study designs.

Recent empirical findings suggest that negative symptoms are not limited to schizophrenia (SCZ) but also present in major depressive disorder (MDD) and bipolar disorder (BD) patients. Although SCZ patients generally showed a latent structure comprising the motivation and pleasure (MAP) and expression (EXP) factors, it remains unclear whether the same latent structure exists in MDD and BD patients. We administered the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS) to 179 MDD patients and 152 BD patients. Confirmatory Factor Analysis (CFA) was conducted to examine the one-factor model, the two-factor model of the MAP and the EXP domain, the five-factor model of anhedonia, avolition, asociality, alogia, and blunted affect, and the hierarchical model comprising the first-order five-factor, and the second-order two-factor (MAP and EXP factors). We further examined the correlations between demographics and the negative symptom dimensions found in the best factor model. The CFA showed that, when the CAINS and the BNSS were combined together, the two-factor model of MAP and EXP provided the best model fit than other competing models, in the MDD alone sample, BD alone sample, and the combined clinical sample. The two-factor model of the MAP and EXP appears to be a stable, transdiagnostic latent structure of negative symptoms across BD and MDD. Clarifying negative symptoms in MDD and BD can facilitate future research on the underlying neural mechanisms of the MAP and EXP dimensions.

Diffusion imaging studies in Attention-deficit/hyperactivity disorder (ADHD) have revealed alterations in anatomical brain connections, such as the fronto-parietal connection known as superior longitudinal fasciculus (SLF). Studies in neurotypical adults have shown that the three SLF branches (SLF I, II, III) support distinct brain functions, such as attention and inhibition; and that their pattern of lateralization is associated with attention performance. However, most studies in ADHD have investigated the SLF as a single bundle and in children; thus, the potential contribution of the lateralization of the SLF branches to adult ADHD pathophysiology remains to be elucidated. We used diffusion-weighted spherical deconvolution tractography to dissect the SLF branches in 60 adults with ADHD (including 26 responders and 34 non-responders to methylphenidate, MPH) and 20 controls. Volume and hindrance modulated orientational anisotropy (HMOA), which respectively reflect white matter macro- and microstructure, were extracted to calculate the corresponding lateralization indices. We tested whether neurotypical controls differed from adults with ADHD, and from treatment response groups in sensitivity analyses; and investigated associations with clinico-neuropsychological profiles. All the three SLF branches were lateralized in adults with ADHD, but not in controls. The lateralization of the SLF I HMOA was associated with performance at the line bisection, not that of the SLF II volume as previously reported in controls. Further, an increased left-lateralization of the SLF I HMOA was associated with higher hyperactivity levels in the ADHD group. Thus, an altered asymmetry of the SLF, perhaps especially of the dorsal branch, may contribute to adult ADHD pathophysiology.

This systematic review aims to elucidate the nexus between ketamine's psychoactive properties and its efficacy in treating a broad spectrum of psychiatric disorders. We searched three databases and used citation tracking to include 29 studies. Predominantly, mood disorders, including bipolar disorder (BD) and major depressive disorder (MDD) (MDD + BD: + n = 25 studies), a large part of them involve treatment-resistant patients (n = 14 studies), substance use disorder (SUD, n = 3 studies), and social anxiety disorder (SAD, n = 1 study). From all included studies (n = 29), 15 (51.72%) of them identified a positive relation between ketamine-induced altered states of consciousness and clinical outcomes, while 13 studies (44.83%) showed no linkage between them, and one study (3.45%) delineated a negative association. Focusing solely on intravenous (IV) ketamine infusions (n = 25), 14 studies (56%) reported a positive modulation of ketamine's psychoactive effects and therapeutic benefits, whereas 10 studies (40%) confirmed no relationship, and one study (4%) showed a negative association. The single study (33.34%) involving subcutaneous ketamine and all three studies (66.6%) intranasal administration did not demonstrate a significant interaction between ketamine's psychoactive effects and therapeutic response. All three SUD studies reported a positive correlation between ketamine's psychoactive effects and therapeutic response. In contrast, the single SAD study did not find a relationship between these parameters. For studies involving mood disorders (n = 25), 12 studies (48%) reported a positive relationship between psychoactive effects and therapeutic response. Others 12 studies (48%) identified a null relationship, and one study (4%) found a significant negative association. Although we have found a larger association than previous studies between ketamine's psychoactive properties and its efficacy in treating a broad spectrum of psychiatric disorders, its topic remains indeterminate, mainly due to the high heterogeneity.

The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) demonstrated excellent results in its original study, with a sensitivity of 97% and a specificity of 100% (Ritvo et al. in J Autism Dev Disord 41:1076-1089, 2011). As a result, it was included in the National Institute for Health and Care Excellence (NICE) guidelines (Recommendations | Autism spectrum disorder in adults: diagnosis and management | Guidance | NICE, 2022). The questionnaire includes 80 questions across four subcategories (language, social relatedness, circumscribed interests, sensory motor). So far, the subcategory sensory motor has not been addressed in most available instruments, despite being part of the diagnostic criteria specified in DSM-5 (Falkai et al., in Diagnostisches Und Statistisches Manual Psychischer Störungen DSM-5. Hogrefe, 2015) and ICD-11 (ICD-11 for Mortality and Morbidity Statistics, 2022). In our validation study, we tested a translated German version of the questionnaire in 299 individuals (110 persons with ASD according to ICD-10 F84.0, F84.5, 64 persons with an primary mental disorders (PMD), 125 persons with no disorders). To enhance the practical use of the instrument in clinical everyday practice, the questionnaire was completed by the participants without the presence of a clinician-unlike the original study. Psychiatric diagnoses were established following the highest standards, and psychometric properties were calculated using established protocols. The German version of the RADS-R yielded very good results, with a high sensitivity of 92.5% and a high specificity of 93.6%. The area under the curve (AUC = 0.976), indicates a high quality and discriminatory power of RADS-R. Furthermore, the ROC curve analysis showed that the optimal threshold to distinguish between the ASD and non-ASD groups in the German version of the RAADS-R is a score of 81. In comparison to the RADS-R, the co-administered instruments Social Responsiveness Scale (SRS), Autism Spectrum Quotient (AQ), and Empathy Quotient (EQ) each showed slightly better specificity but worse sensitivity in this sample.The study included individuals already diagnosed with ASD according to ICD-10 (F84.0, F84.5), with or without an primary mental disorders, preventing us from identifying the influence of comorbidities on the RADS-R results. In addition, a self-report questionnaire has generally only limited objectivity and may allow for false representation of the symptoms. The RADS-R compares well with other questionnaires and can provide valuable additional information. It could turn out to be a helpful diagnostic tool for patients in Germany. We propose naming the German version RADS-R (Ritvo Autism Diagnostic Scale - rRevised) to reflect the change in terminology.

We present a narrative review of clinical trials investigating the anxiolytic and antidepressant effects of silexan, an active substance derived from lavender oil and summarize nonclinical findings from pharmacological studies supporting its therapeutic use. Six studies investigated the efficacy of the lavender oil in patients with subthreshold and generalized anxiety disorders as well as in mixed anxiety and depressive disorder (MADD). Furthermore, we present data indicating that silexan may influence sleep quality as well as anxiety or depressive disorders in individuals with post-COVID-19. Silexan taken orally at a daily dose of 80 mg for 10 weeks was significantly superior to placebo in reducing psychic and somatic symptoms of anxiety and was as effective as 0.5 mg/d lorazepam and 20 mg/d paroxetine. In patients with mild or moderate major depression, silexan was superior to placebo and comparably effective to 50 mg/d sertraline. Significant antidepressant effects were also observed in MADD and depression co-morbid with anxiety. The herbal product had a beneficial effect on activities of daily living and health-related quality of life. Adverse events associated with silexan in clinical trials were limited to eructation and mild, transient gastrointestinal complaints. The herbal product was not associated with drug interactions, sedation, sleep disturbance, dependence and abuse potential, sexual dysfunction, weight gain or withdrawal symptoms. Silexan was therefore safe and effective in subthreshold and syndromal anxiety disorders and in major depression.

Reward system dysfunction is implicated in the pathogenesis of major psychiatric disorders. We conducted a genome-wide association study (GWAS) to identify genes that influence activation strength of brain regions within the extended reward system in humans. A homogeneous sample of 214 participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All subjects performed the 'desire-reason dilemma' (DRD) paradigm allowing systematic investigation of systems-level mechanisms of reward processing in humans. As a main finding, we identified the single nucleotide variant rs113408797 in the DnaJ Heat Shock Protein Family Member C13 gene [DNAJC13], alias Receptor-Mediated Endocytosis 8 [RME-8], that was associated with the activation strength of the ventral tegmental area (VTA; p = 2.50E-07) and the nucleus accumbens (NAcc; p = 5.31E-05) in response to conditioned reward stimuli. Moreover, haplotype analysis assessing the information across the entire DNAJC13 locus demonstrated an impact of a five-marker haplotype on VTA activation (p = 3.21E-07), which further corroborates a link between this gene and reward processing. The present findings provide first direct empirical evidence that genetic variation of DNAJC13 influences neural responses within the extended reward system to conditioned stimuli. Further studies are required to investigate the role of this gene in the pathogenesis and pathophysiology of neuropsychiatric disorders.