Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries.

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.

Omega-3 fatty acids during adolescence prevent schizophrenia-related behavioural deficits: Neurophysiological evidences from the prenatal viral infection with PolyI:C.

The likely involvement of inflammation and oxidative stress (IOS) in mental disease has led to advocate anti-oxidant and anti-inflammatory drugs as therapeutic strategies in the treatment of schizophrenia. Since omega-3 fatty acids (ω-3) show anti-inflammatory/neuroprotective properties, we aim to evaluate whether ω-3 treatment during adolescence in the maternal immune stimulation (MIS) animal model of schizophrenia could prevent the brain and behavioural deficits described in adulthood. At gestational day 15, PolyI:C (4 mg/kg) or saline (VH) were injected to pregnant Wistar rats. Male offspring received ω-3 (800 mg/kg) or saline (Sal) daily from postnatal day (PND) 35-49, defining 4 groups: MIS-ω-3; MIS-Sal; VH-ω-3 and VH-Sal. At PND70, rats were submitted to prepulse inhibition test (PPI). FDG-PET and T2-weighted MRI brain studies were performed in adulthood and analyzed by means of SPM12. IOS markers were measured in selected brain areas. MIS-offspring showed a PPI deficit compared with VH-offspring and ω-3 treatment prevented this deficit. Also, ω-3 reduced the brain metabolism in the deep mesencephalic area and prevented the volumetric abnormalities in the hippocampus but not in the ventricles in MIS-offspring. Besides, ω-3 reduced the expression of iNOS and Keap1 and increased the activity/concentration of HO1, NQO1 and GPX. Our study demonstrates that administration of ω-3 during adolescence prevents PPI behavioural deficits and hippocampal volumetric abnormalities, and partially counteracts IOS deficits via iNOS and Nrf2-ARE pathways in the MIS model. This study highlights the need for novel strategies based on anti-inflammatory/anti-oxidant compounds to alter the disease course in high-risk populations at early stages.

Placebo response in pharmacological and dietary supplement trials of autism spectrum disorder (ASD): systematic review and meta-regression analysis.

BACKGROUND: Placebo response in autism spectrum disorder (ASD) might dilute drug-placebo differences and hinder drug development. Therefore, this meta-analysis investigated placebo response in core symptoms. METHODS: We searched ClinicalTrials.gov , CENTRAL, EMBASE, MEDLINE, PsycINFO, WHO-ICTRP (up to July 8, 2018), and PubMed (up to July 4, 2019) for randomized pharmacological and dietary supplement placebo-controlled trials (RCTs) with a minimum of seven days of treatment. Single-group meta-analyses were conducted using a random-effects model. Standardized mean changes (SMC) of core symptoms in placebo arms were the primary outcomes and placebo positive response rates were a secondary outcome. Predictors of placebo response were investigated with meta-regression analyses. The protocol was registered with PROSPERO ID CRD42019125317 . RESULTS: Eighty-six RCTs with 2360 participants on placebo were included in our analysis (87% in children/adolescents). The majority of trials were small, single-center with a duration of 8-12 weeks and published after 2009. Placebo response in social-communication difficulties was SMC = - 0.32, 95% CI [- 0.39, - 0.25], in repetitive behaviors - 0.23[- 0.32, - 0.15] and in scales measuring overall core symptoms - 0.36 [- 0.46, - 0.26]. Overall, 19%, 95% CI [16-22%] of participants were at least much improved with placebo. Caregiver (vs. clinician) ratings, lower risk of bias, flexible-dosing, larger sample sizes and number of sites, less recent publication year, baseline levels of irritability, and the use of a threshold of core symptoms at inclusion were associated with larger placebo response in at least a core symptom domain. LIMITATIONS: About 40% of the trials had an apparent focus on core symptoms. Investigation of the differential impact of predictors on placebo and drug response was impeded by the use of diverse experimental interventions with essentially different mechanisms of action. An individual-participant-data meta-analysis could allow for a more fine-grained analysis and provide more informative answers. CONCLUSIONS: Placebo response in ASD was substantial and predicted by design- and participant-related factors, which could inform the design of future trials in order to improve the detection of efficacy in core symptoms. Potential solutions could be the minimization and careful selection of study sites as well as rigorous participant enrollment and the use of measurements of change not solely dependent on caregivers.

Dietary Interventions for Autism Spectrum Disorder: A Meta-analysis.

CONTEXT: Dietary interventions such as restrictive diets or supplements are common treatments for young people with autism spectrum disorder (ASD). Evidence for the efficacy of these interventions is still controversial. OBJECTIVE: To assess the efficacy of specific dietary interventions on symptoms, functions, and clinical domains in subjects with ASD by using a meta-analytic approach. DATA SOURCES: Ovid Medline, PsycINFO, Embase databases. STUDY SELECTION: We selected placebo-controlled, double-blind, randomized clinical trials assessing the efficacy of dietary interventions in ASD published from database inception through September 2017. DATA EXTRACTION: Outcome variables were subsumed under 4 clinical domains and 17 symptoms and/or functions groups. Hedges' adjusted g values were used as estimates of the effect size of each dietary intervention relative to placebo. RESULTS: In this meta-analysis, we examined 27 double-blind, randomized clinical trials, including 1028 patients with ASD: 542 in the intervention arms and 486 in the placebo arms. Participant-weighted average age was 7.1 years. Participant-weighted average intervention duration was 10.6 weeks. Dietary supplementation (including omega-3, vitamin supplementation, and/or other supplementation), omega-3 supplementation, and vitamin supplementation were more efficacious than the placebo at improving several symptoms, functions, and clinical domains. Effect sizes were small (mean Hedges' g for significant analyses was 0.31), with low statistical heterogeneity and low risk of publication bias. LIMITATIONS: Methodologic heterogeneity among the studies in terms of the intervention, clinical measures and outcomes, and sample characteristics. CONCLUSIONS: This meta-analysis does not support nonspecific dietary interventions as treatment of ASD but suggests a potential role for some specific dietary interventions in the management of some symptoms, functions, and clinical domains in patients with ASD.

Neuropsychological correlates of P50 sensory gating in patients with schizophrenia.

Impaired inhibition of P50 cerebral evoked response is one of the best validated endophenotypes in schizophrenia. There are controversial data on the relationship between P50 evoked potential deficit and measures of cognitive function in schizophrenia. A comprehensive clinical and neurocognitive assessment plus an evaluation of P50 sensory gating was performed in 160 schizophrenia patients and 64 controls. Neurocognitive scores from each cognitive domain were converted to demographically-adjusted T-scores (age, gender, and years of education) for all study participants. The relationship between P50 and neurocognitive variables was assessed via parametric and nonparametric correlations and categorical strategies: we compared neuropsychological test scores in patients and controls in the lowest P50 quartile vs. the highest. Controls had better performance than schizophrenia patients in all cognitive domains. Schizophrenia patients had significantly higher P50 ratios than controls, and no significant correlation was found between P50 gating measures and neuropsychological test scores in schizophrenia patients or healthy controls. Moreover, no differences in neurocognitive performance were found between subjects in the lowest P50 ratio quartile vs. the highest in healthy controls or patients with schizophrenia. We concluded that there is no evidence of an association between P50 ratio and cognitive measures in schizophrenia patients, and this seems to be also the case in healthy controls.

Regional specificity of thalamic volume deficits in male adolescents with early-onset psychosis.

BACKGROUND: Thalamic volume deficits are associated with psychosis but it is unclear whether the volume reduction is uniformly distributed or whether it is more severe in particular thalamic regions. AIMS: To quantify whole and regional thalamic volume in males with early-onset psychosis and healthy male controls. METHOD: Brain scans were obtained for 80 adolescents: 46 individuals with early-onset psychosis with a duration of positive symptoms less than 6 months and 34 healthy controls. All participants were younger than 19 years. Total thalamic volumes were assessed using FreeSurfer and FSL-FIRST, group comparisons of regional thalamic volumes were studied with a surface-based approach. RESULTS: Total thalamic volume was smaller in participants with early-onset psychosis relative to controls. Regional thalamic volume reduction was most significant in the right anterior mediodorsal area and pulvinar. CONCLUSIONS: In males with minimally treated early-onset psychosis, thalamic volume deficits may be most pronounced in the anterior mediodorsal and posterior pulvinar regions, adding strength to findings from post-mortem studies in adults with psychosis.

Cannabis and first-episode psychosis: different long-term outcomes depending on continued or discontinued use.

OBJECTIVE: To examine the influence of cannabis use on long-term outcome in patients with a first psychotic episode, comparing patients who have never used cannabis with (a) those who used cannabis before the first episode but stopped using it during follow-up and (b) those who used cannabis both before the first episode and during follow-up. METHODS: Patients were studied following their first admission for psychosis. They were interviewed at years 1, 3, and 5. At follow-up after 8 years, functional outcome and alcohol and drug abuse were recorded. Patients were classified according to cannabis use: 25 had cannabis use before their first psychotic episode and continuous use during follow-up (CU), 27 had cannabis use before their first episode but stopped its use during follow-up (CUS), and 40 never used cannabis (NU). RESULTS: The 3 groups did not differ significantly in symptoms or functional outcome at baseline or during short-term follow-up. The CUS group exhibited better long-term functional outcome compared with the other 2 groups and had fewer negative symptoms than the CU group, after adjusting for potential confounders. For the CUS group, the effect size was 1.26 (95% confidence interval [CI]=0.65 to 1.86) for functional outcome and -0.72 (95% CI=-1.27 to -0.14) for negative symptoms. All patients experienced improvements in positive symptoms during long-term follow-up. CONCLUSION: Cannabis has a deleterious effect, but stopping use after the first psychotic episode contributes to a clear improvement in outcome. The positive effects of stopping cannabis use can be seen more clearly in the long term.

Antipsychotic effects on auditory sensory gating in schizophrenia patients.

P50 sensory gating deficit has repeatedly been demonstrated in schizophrenia. Studies have produced inconsistent findings with respect to normalization of P50 gating in patients with schizophrenia receiving treatment with different antipsychotics. The current study was designed to determine whether there is a difference in P50 gating in schizophrenia patients treated with first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), including clozapine. P50 evoked potential recordings were obtained from 160 patients with schizophrenia and 77 healthy comparison subjects. Forty-three patients were being treated with clozapine, sixty-eight were taking SGAs (33 risperidone, 21 olanzapine, 11 aripiprazole, and 3 combinations of SGAs) and 49 were being treated with FGAs. Schizophrenia patients exhibited significantly higher P50 ratios than healthy subjects. When patients treated with different antipsychotics were compared, there were no differences in any of the neurophysiological findings. Second-generation antipsychotics were not related to more normal sensory gating in this population of patients with chronic schizophrenia.

Brain morphology and neurological soft signs in adolescents with first-episode psychosis.

BACKGROUND: Adolescents with first-episode psychosis have increased severity of neurological soft signs when compared with controls, but it is unclear whether increased severity of neurological soft signs is an expression of specific structural brain deficits. AIMS: To examine whether increased severity of neurological soft signs was associated with decreased brain volumes in adolescents with first-episode psychosis. METHOD: Brain scans were obtained for 70 adolescents (less than 18 years of age) with first-episode psychosis (duration of positive symptoms less than 6 months). Volumes were assessed using voxel-based morphometry and through segmentation of anatomical structures. RESULTS: Increased severity of sensory integration neurological soft signs correlated with smaller right and left thalamus volume, whereas increased severity of sequencing of complex motor acts neurological soft signs correlated with smaller right caudate volume. CONCLUSIONS: Neurological soft signs may be an easy-to-assess marker of region-specific structural brain deficits in adolescents with first-episode psychosis.

Olanzapine effects on auditory sensory gating in schizophrenia.

OBJECTIVE: New-generation antipsychotics have been proposed to normalize the P50 sensory gating index in patients with schizophrenia. In the context of a double-blind comparison of olanzapine and haloperidol, the authors examined the effect of olanzapine on P50 suppression. METHOD: P50 measurements were obtained at baseline while patients were being treated with fluphenazine and after 12 weeks of double-blind treatment with either olanzapine (N=12) or haloperidol (N=12). RESULTS: There were no treatment group differences in P50 amplitude, latency, or sensory gating ratio. CONCLUSIONS: These results suggest that there is not a significant differential effect of olanzapine and haloperidol on the P50 sensory gating index in schizophrenia.