Relapse Prevention Intervention after Suicidal Event (RISE): Feasibility study of a psychotherapeutic short-term program for inpatients after a recent suicide attempt

Recent research suggests that treating only mental disorders may not be sufficient to reduce the risk for future suicidal behavior in patients with a suicide attempt(s). It is therefore necessary to pay special therapeutic attention to past suicidal acts. Thus, the newly developed RISE (Relapse Prevention Intervention after Suicidal Event) program was built on the most effective components of existing psychotherapeutic and psychosocial interventions according to our current meta-analysis. The RISE program consists of five individual sessions designed for the acute psychiatric inpatient setting. The main goals of the treatment are to decrease future suicidal events and to improve patients' ability to cope with future suicidal crises. In the present study, feasibility and acceptance of the RISE program were investigated as well as its clinical effects on suicidal ideations, mental pain, self-efficacy and depressive symptoms. We recruited a sample of 27 inpatients of the Department of Psychiatry and Psychotherapy, University Hospital Jena, Germany. The final sample consisted of 20 patients hospitalized for a recent suicide attempt, including 60 percent of multiple attempters. The data collection included a structured interview and a comprehensive battery of questionnaires to evaluate the feasibility and acceptance of the RISE program as well as associated changes in clinical symptoms. A follow-up examination was carried out after 6 months. Considering the low dropout rate and the overall positive evaluation, the RISE program was highly accepted in a sample of severely impaired patients. The present study also demonstrated that the levels of suicidal ideations, mental pain, depressive symptoms, and hopelessness decreased significantly after RISE. Since all of these clinical parameters are associated with the risk of future suicidal behavior, a potential suicide-preventive effect of the intervention can be inferred from the present findings. The positive results of the follow-up assessment after 6 months point in the same direction. In addition, RISE treatment increased self-efficacy in patients, which is an important contributor for better coping with future suicidal crises. Thus, present study demonstrate that RISE is a suitable therapy program for the treatment of patients at high risk for suicidal behavior in an acute inpatient setting

Omega-6 to omega-3 polyunsaturated fatty acid ratio and subsequent mood disorders in young people with at-risk mental states: a 7-year longitudinal study

While cross-sectional studies suggest that patients with mood disorders have a higher ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) and lower levels of omega-3 PUFAs, it is unknown if a high n-6/3 ratio indicates vulnerability for depression. We tested this hypothesis in a 7-year follow-up study of young individuals with an ultra-high risk (UHR) phenotype. We conducted a secondary analysis of the Vienna omega-3 study, a longitudinal study of omega-3 PUFAs in individuals at UHR for psychosis (n = 69). Levels of n-6 and n-3 PUFAs were measured in the phosphatidylethanolamine fraction of erythrocyte membranes at intake into the study. Mood disorder diagnosis was ascertained with the Structured Clinical Interview for DSM-IV-TR and confirmed by review of medical records and interviews of caregivers. A higher n-6/3 PUFA ratio at baseline predicted mood disorders in UHR individuals over a 7-year (median) follow-up (odds ratio = 1.89, 95% CI = 1.075-3.338, P = 0.03). This association remained significant after adjustment for age, gender, smoking, severity of depressive symptoms at baseline and n-3 supplementation. Consistent results were obtained for individual PUFAs, including lower levels of eicosapentaenoic acid and docosahexaenoic acid. The predictive capacity of these findings was specific to mood disorders as no associations were found for any other psychiatric disorder. To our knowledge, our data provide the first prospective evidence that the n-6/3 PUFA ratio is associated with an increased risk for mood disorders in young people exhibiting an UHR phenotype. These findings may have important implications for treatment and risk stratification beyond clinical characteristics

ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and healthy subjects

Background Genetic variation in the gene encoding ZNF804A, a risk gene for schizophrenia, has been shown to affect brain functional endophenotypes of the disorder, while studies of white matter structure have been inconclusive. Method We analysed effects of ZNF804A single nucleotide polymorphism rs1344706 on grey and white matter using voxel-based morphometry (VBM) in high-resolution T1-weighted magnetic resonance imaging scans of 62 schizophrenia patients and 54 matched healthy controls. Results We found a significant (p<0.05, family-wise error corrected for multiple comparisons) interaction effect of diagnostic group x genotype for local grey matter in the left orbitofrontal and right and left lateral temporal cortices, where patients and controls showed diverging effects of genotype. Analysing the groups separately (at p<0.001, uncorrected), variation in rs1344706 showed effects on brain structure within the schizophrenia patients in several areas including the left and right inferior temporal, right supramarginal/superior temporal, right and left inferior frontal, left frontopolar, right and left dorsolateral/ventrolateral prefrontal cortices, and the right thalamus, as well as effects within the healthy controls in left lateral temporal, right anterior insula and left orbitofrontal cortical areas. We did not find effects of genotype of regional white matter in either of the two cohorts. Conclusions Our findings demonstrate effects of ZNF804A genetic variation on brain structure, with diverging regional effects in schizophrenia patients and healthy controls in frontal and temporal brain areas. These effects, however, might be dependent on the impact of other (genetic or non-genetic) disease factor

Report of the AACP Task Force on Patient-Centered Medical Homes and Accountable Care Organizations

A task force was convened by the American Association of Colleges of Pharmacy (AACP) to provide rationale for academic pharmacy engagement with organizations/institutions providing new models of team-based patient care designed to improve patient access, care quality, and affordable care. Descriptions of new care models, such as patient centered medical homes (PCMHs) and accountable care organizations (ACO), were included as well as descriptions of existing partnerships with academic pharmacy

Proteomic Biomarkers for the Prediction of Transition to Psychosis in Individuals at Clinical High Risk: A Multi-cohort Model Development Study

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan’s unimodality dip test). MEDLINE and EMBASE databases were searched from inception to September 2022 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia. 123 studies reporting on 8256 patients and 7532 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p &lt; 0.001; glutamine: CVR = 0.15, p = 0.003; Glx: CVR = 0.11, p = 0.002), dorsolateral prefrontal cortex (glutamine: CVR = 0.14, p = 0.05; Glx: CVR = 0.25, p &lt; 0.001) and thalamus (glutamate: CVR = 0.16, p = 0.008; Glx: CVR = 0.19, p = 0.008). Studies in younger, more symptomatic patients were associated with greater variability in the basal ganglia (BG glutamate with age: z = −0.03, p = 0.003, symptoms: z = 0.007, p = 0.02) and temporal lobe (glutamate with age: z = −0.03, p = 0.02), while studies with older, more symptomatic patients associated with greater variability in MFC (glutamate with age: z = 0.01, p = 0.02, glutamine with symptoms: z = 0.01, p = 0.02). For individual patient data, most studies showed a unimodal distribution of glutamatergic metabolites. Meta-analysis of mean differences found lower MFC glutamate (g = −0.15, p = 0.03), higher thalamic glutamine (g = 0.53, p &lt; 0.001) and higher BG Glx in patients relative to controls (g = 0.28, p &lt; 0.001). Proportion of males was negatively associated with MFC glutamate (z = −0.02, p &lt; 0.001) and frontal white matter Glx (z = −0.03, p = 0.02) in patients relative to controls. Patient PANSS total score was positively associated with glutamate SMD in BG (z = 0.01, p = 0.01) and temporal lobe (z = 0.05, p = 0.008). Further research into the mechanisms underlying greater glutamatergic metabolite variability in schizophrenia and their clinical consequences may inform the identification of patient subgroups for future treatment strategies

The association between migrant status and transition in an ultra-high risk for psychosis population

Purpose: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. Methods: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. Results: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147–756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62–1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70–1.51). Conclusions: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics

Identification of a biological signature for schizophrenia in serum

Biomarkers are now used in many areas of medicine but are still lacking for psychiatric conditions such as schizophrenia (SCZ). We have used a multiplex molecular profiling approach to measure serum concentrations of 181 proteins and small molecules in 250 first and recent onset SCZ, 35 major depressive disorder (MDD), 32 euthymic bipolar disorder (BPD), 45 Asperger syndrome and 280 control subjects. Preliminary analysis resulted in identification of a signature comprised of 34 analytes in a cohort of closely matched SCZ (n = 71) and control (n = 59) subjects. Partial least squares discriminant analysis using this signature gave a separation of 60-75% of SCZ subjects from controls across five independent cohorts. The same analysis also gave a separation of similar to 50% of MDD patients and 10-20% of BPD and Asperger syndrome subjects from controls. These results demonstrate for the first time that a biological signature for SCZ can be identified in blood serum. This study lays the groundwork for development of a diagnostic test that can be used as an aid for distinguishing SCZ subjects from healthy controls and from those affected by related psychiatric illnesses with overlapping symptoms. Molecular Psychiatry (2012) 17, 494-502; doi:10.1038/mp.2011.42; published online 12 April 201