Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders.

BACKGROUND: Endothelial inflammation may be involved in the pathogenesis of schizophrenia, and cellular adhesion molecules (CAMs) on endothelial cells may facilitate leukocyte binding and transendothelial migration of cells and inflammatory factors. The aim of the present study was to assess levels of soluble cellular adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD) in patients with schizophrenia compared to healthy controls. METHODS: The study population consists of 138 patients with schizophrenia-spectrum disorder, of whom 54 were drug-naïve, compared to 317 general population controls. The potential confounders age, gender, smoking and body mass index (BMI) were adjusted for in linear regression models. RESULTS: The total patient group showed significantly higher levels of ICAM-1 (p < 0.001) and VCAM-1 (p < 0.001) compared to controls. Previously medicated patients showed higher ICAM-1 levels compared to drug-naïve patients (p = 0.042) and controls (p < 0.001), and elevated VCAM-1 levels compared to controls (p < 0.001). Drug-naive patients had elevated levels of VCAM-1 (p = 0.031) compared to controls. CONCLUSIONS: In our study, patients with schizophrenia - including the drug-naïve - have higher levels of soluble CAMs compared to healthy controls. These findings suggest activation of the endothelial system as in inflammation.

Association between cytokines and suicidality in patients with psychosis: A multicentre longitudinal analysis.

Suicide is a common cause of death in all phases of schizophrenia spectrum disorder, particularly in the youngest patients. Clinical measures have demonstrated limited value in suicide prediction, spurring the search for potential biomarkers. The causes of suicidal behaviour are complex, but the immune system seems to be involved as it reflects or even causes mental suffering. We aimed to identify cytokines with associations to suicidality in a sample of patients with symptoms of active psychosis. Patients with schizophrenia spectrum disorder (N = 144) participating in a semi-randomized antipsychotic drug trial (the BeSt InTro study) were assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) at eight visits across 12 months. The Clinical Global Impression for Severity of Suicidality scale (CGI-SS) was used for assessing suicidality. Serum concentrations of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-4, IL-6, and IL-10 were measured using immunoassays. A logistic regression model was used to investigate the association between cytokine levels and suicidality. To enhance clinical significance, the CGI-SS scores were dichotomized into two groups before analyses: low (=1) and high (≥2) risk for suicidality. Both uni- and multi-variate analyses revealed an inverse correlation between IL-2 and IL-10 serum levels and suicidality, where lower cytokine concentrations of IL-2 and IL-10 were associated with higher suicidality scores. The results were consistent when adjusted for depression and substance use. These results indicate that inflammatory processes are linked to the risk of suicidality in patients with schizophrenia spectrum disorders.

Implementing Clinical Guidelines for the Treatment of Psychosis: The Frontline Leaders' Point of View. A Qualitative Study.

Background: Despite the large amount of leadership and implementation theories and recommendations, healthcare services continue to struggle with efficiently incorporating new knowledge. The questioning of conventional leadership approaches in healthcare organizations prompted us to investigate how frontline leaders comprehend their own implementation intentions and actions, and how these intentions and actions may impact the implementation of clinical guidelines in mental healthcare in Norway. Methods: Employing a theory-driven qualitative design, we conducted nine semi-structured interviews with frontline leaders who had recently led implementation of clinical guidelines for the treatment of psychosis in mental health. We employed Systematic Text Condensation, informed by Normalization Process Theory, to structure and analyze the data and used fidelity scales to measure the degree of implementation and distinguish between leaders' levels of success in implementation. Results: Frontline leaders in units that achieved high success in implementation described their intentions and actions differently, from those with less success. The former group's actions aligned more closely with the constructs of the Normalization Process Theory compared to the latter group when describing their actions. Frontline leaders leading units with a high degree of implementation success describe relation-orientation, trust, and providing adaptive space for staff members to take initiative. In contrast, those leading units with less implementation success describe more control and guidance of co-operators and place more emphasize on information and knowledge. Conclusion: Differences in how frontline leaders describe their actions and intentions to achieve clinical guideline implementation suggest that the leadership approach of these frontline leaders is an important factor to consider when planning and conducting implementation. To better understand the implementation process, it is important to pay attention to how frontline leaders customize their leadership approaches to the dynamics of complex organizations, and how they interact with their team and superiors.

We need to talk: a qualitative inquiry into pathways to care for young men at ultra-high risk for psychosis.

Introduction: It is known from the literature that men are slower to seek help and staying engaged in mental health care compared to women. Seeing that in psychosis, men more often than women have insidious onsets but also a more malign illness course, it is important to find ways to improve timely help-seeking. The aim of this study was to explore barriers and facilitators for help-seeking in young male persons struggling with early signs of psychosis. Methods: Qualitative interviews with nine young men who suffer from a first episode of psychosis or psychosis risk symptoms. Results: Male stereotypical ideals, significant others, and knowledge of symptoms and where to get help as well characteristics of symptom trajectories appeared to be important determinants of help-seeking behavior. Discussion: Interviews indicated that help-seeking in the participants was delayed first, because of reluctancy to disclose distress and second, because significant others were unable to accurately recognize symptoms. Information, awareness, and easy access to care remain important in early detection and intervention in psychosis and psychosis risk. However, more emphasis should be placed on de-stigmatizing mental health problems in men and aiming information specifically at them.

Exploring key determinants of health among individuals with serious mental Illness: qualitative insights from a first episode psychosis cohort, 20 years postdiagnosis.

BACKGROUND: Individuals with serious mental illness (SMI) are more likely to experience functional decline, low well-being, comorbidities, shorter lifespan, and diminished quality of life than the general population. This qualitative study explores determinants of health that individuals with SMI perceive as important to their health, well-being, and ability to live a meaningful life. METHOD: We conducted interviews with 13 individuals with early detected first episode psychosis as part of a 20-year follow-up study of a larger cohort. Interview data were analyzed using qualitative content analysis. RESULTS: Analysis identified two themes comprising eight categories representing determinants of health. The first theme reflected management of mental and physical health. Categories in this theme were: access to mental healthcare adapted to individual needs, strategies during deterioration, use of psychotropic medication, maintenance of physical health and lifestyle. The second theme reflected social health determinants in coping with mental illness and comprised three categories: family and friends, engaging in meaningful hobbies and activities, and the influence of employment on mental health. CONCLUSIONS: Individuals with SMI outlined mental, physical, and social determinants of health that were important for their health, well-being, and ability to live a meaningful life. In future clinical practice, coordinated care addressing the complexity of health determinants will be important.

Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised study.

OBJECTIVES: Drug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use. METHODS: The BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20-29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score. RESULTS: At baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients. CONCLUSION: The current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.

Association between early suicidal trajectories in first-episode psychosis and 10-year follow-up: TIPS registry-linked study.

BACKGROUND: Although the risk of suicidality is high in first-episode psychosis, patterns and individual variability in suicidal thoughts and behaviours over time are under-researched. We aimed to identify early trajectories of suicidality over a 2-year follow-up, assess their baseline predictors, and explore associations between those trajectories and later suicidality. METHODS: This longitudinal follow-up study was a part of the Early Treatment and Intervention in Psychosis (TIPS)study. Participants, linked to Norwegian and Danish death registries, were recruited from four catchment areas (665 000 inhabitants) in Norway and Denmark (both inpatient and outpatient). We included participants aged 15-65 years, with an intelligence quotient of more than 70, willing to give informed consent, and with a first episode of active psychotic symptoms. Individuals with comorbid neurological or endocrinal disorders, or those with contraindications to antipsychotics, were excluded. Growth mixture modelling was used to identify trajectories of suicidal thoughts and behaviours over the first 2 years. Multinomial logistic regression was applied to examine the baseline predictors of those trajectories and their associations with suicidality at 10-year follow-up. FINDINGS: A total of 301 participants were recruited from Jan 1, 1997, to Dec 31, 2000. Of the 299 with completed suicidality data at baseline, 271 participated in 1-year follow-up, 250 in 2-year follow-up, 201 in 5-year follow-up, and 186 at 10-year follow-up. At baseline, 176 (58%) were male, 125 (42%) were female. The mean age was 27·80 years (SD 9·64; range 15-63). 280 (93%) participants were of Scandinavian origin. Four trajectories over 2 years were identified: stable non-suicidal (217 [72%]), stable suicidal ideation (45 [15%]), decreasing suicidal thoughts and behaviours (21 [7%]), and worsening suicidal thoughts and behaviours (18 [6%]). A longer duration of untreated psychosis (odds ratio [OR] 1·24, 95% CI 1·02-1·50, p=0·033), poorer premorbid childhood social adjustment (1·33, 1·01-1·73, p=0·039), more severe depression (1·10, 1·02-1·20, p=0·016), and substance use (2·33, 1·21-4·46, p=0·011) at baseline predicted a stable suicidal ideation trajectory. Individuals in the stable suicidal ideation trajectory tended to have suicidal thoughts and behaviours at 10-year follow-up (3·12, 1·33-7·25, p=0·008). Individuals with a worsening suicidal trajectory were at a higher risk of death by suicide between 2 and 10 years (7·58, 1·53-37·62, p=0·013). INTERPRETATION: Distinct suicidal trajectories in first-episode psychosis were associated with specific predictors at baseline and distinct patterns of suicidality over time. Our findings call for early and targeted interventions for at-risk individuals with persistent suicidal ideation or deteriorating patterns of suicidal thoughts and behaviours, or both. FUNDING: Health West, Norway; the Norwegian National Research Council; the Norwegian Department of Health and Social Affairs; the National Council for Mental Health and Health and Rehabilitation; the Theodore and Vada Stanley Foundation; the Regional Health Research Foundation for Eastern Region, Denmark; Roskilde County, Helsefonden, Lundbeck Pharma; Eli Lilly; Janssen-Cilag Pharmaceuticals, Denmark; a National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award and The National Institute of Mental Health grant; a National Alliance for Research on Schizophrenia & Depression Young Investigator Award from The Brain & Behavior Research Foundation; Health South East; Health West; and the Regional Centre for Clinical Research in Psychosis.

Childhood trauma, antipsychotic medication, and symptom remission in first-episode psychosis.

BACKGROUND: To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics. METHODS: FEP (N = 191) were recruited from in- and outpatient services 1997-2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15-65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale. RESULTS: CIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms. CONCLUSION: Results indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.

Antidepressive Effectiveness of Amisulpride, Aripiprazole, and Olanzapine in Patients With Schizophrenia Spectrum Disorders: A Secondary Outcome Analysis of a Pragmatic, Randomized Trial (BeSt InTro).

BACKGROUND: Depressive symptoms are frequent in schizophrenia and associated with a poorer outcome. Currently, the optimal treatment for depressive symptoms in schizophrenia remains undetermined. Amisulpride, aripiprazole, and olanzapine all have antidepressive pharmacodynamic properties, ranging from serotonergic affinities to limbic dopaminergic selectivity. Consequently, in a 12-month pragmatic, randomized clinical trial, we aimed to investigate differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as a secondary outcome, measured by change in the Calgary Depression Scale for Schizophrenia sum score in patients within the schizophrenia spectrum. METHODS: Psychotic patients within the schizophrenia spectrum were included, and effectiveness was analyzed with latent growth curve modeling. RESULTS: Of the 144 patients, 51 (35%) were women, the mean age was 31.7 (SD 12.7), and 39% were antipsychotic naive. At inclusion, 68 (47%) participants had a Calgary Depression Scale for Schizophrenia sum score >6, indicating severe depressive symptoms. Across the 12-month follow-up, there was a depressive symptom reduction in all medication groups, but no statistically significant differences between the study drugs. Separate analyses of the subcohort with elevated depressive symptoms at inclusion also failed to find differences in depressive symptom reduction between study drugs. The reduction in depressive symptoms mainly occurred within 6 weeks after randomization. CONCLUSIONS: There was a reduction in depressive symptoms under treatment with amisulpride, aripiprazole, and olanzapine in acutely psychotic patients with schizophrenia spectrum disorder, but no differences between the drugs.

Lower circulating neuron-specific enolase concentrations in adults and adolescents with severe mental illness.

BACKGROUND: Both neurodegenerative and neurodevelopmental abnormalities have been suggested to be part of the etiopathology of severe mental illness (SMI). Neuron-specific enolase (NSE), mainly located in the neuronal cytoplasm, may indicate the process as it is upregulated after neuronal injury while a switch from non-neuronal enolase to NSE occurs during neuronal maturation. METHODS: We included 1132 adult patients with SMI [schizophrenia (SZ) or bipolar spectrum disorders], 903 adult healthy controls (HC), 32 adolescent patients with SMI and 67 adolescent HC. Plasma NSE concentrations were measured by enzyme immunoassay. For 842 adults and 85 adolescents, we used total grey matter volume (TGMV) based on T1-weighted magnetic resonance images processed in FreeSurfer v6.0. We explored NSE case-control differences in adults and adolescents separately. To investigate whether putative case-control differences in NSE were TGMV-dependent we controlled for TGMV. RESULTS: We found significantly lower NSE concentrations in both adult (p < 0.001) and adolescent patients with SMI (p = 0.007) compared to HC. The results remained significant after controlling for TGMV. Among adults, both patients with SZ spectrum (p < 0.001) and bipolar spectrum disorders (p = 0.005) had lower NSE than HC. In both patient subgroups, lower NSE levels were associated with increased symptom severity. Among adults (p < 0.001) and adolescents (p = 0.040), females had lower NSE concentrations than males. CONCLUSION: We found lower NSE concentrations in adult and adolescent patients with SMI compared to HC. The results suggest the lack of progressive neuronal injury, and may reflect abnormal neuronal maturation. This provides further support of a neurodevelopmental rather than a neurodegenerative mechanism in SMI.

Systemic Cell Adhesion Molecules in Severe Mental Illness: Potential Role of Intercellular CAM-1 in Linking Peripheral and Neuroinflammation.

BACKGROUND: Cell adhesion molecules (CAMs) orchestrate leukocyte trafficking and could link peripheral and neuroinflammation in patients with severe mental illness (SMI), by promoting inflammatory and immune-mediated responses and mediating signals across blood-brain barrier. We hypothesized that CAMs would be dysregulated in SMI and evaluated plasma levels of different vascular and neural CAMs. Dysregulated CAMs in plasma were further evaluated in vivo in leukocytes and brain tissue and in vitro in induced pluripotent stem cells. METHODS: We compared plasma soluble levels of different vascular (VCAM-1, ICAM-1, P-SEL) and neural (JAM-A, NCAD) CAMs in circulating leukocytes in a large SMI sample of schizophrenia (SCZ) spectrum disorder (n = 895) and affective disorder (n = 737) and healthy control participants (n = 1070) controlling for age, sex, body mass index, C-reactive protein, and freezer storage time. We also evaluated messenger RNA expression of ICAM1 and related genes encoding ICAM-1 receptors in leukocytes using microarray (n = 842) and in available RNA sequencing data from the CommonMind Consortium (CMC) in postmortem samples from the dorsolateral prefrontal cortex (n = 474). The regulation of soluble ICAM-1 in induced pluripotent stem cell-derived neurons and astrocytes was assessed in patients with SCZ and healthy control participants (n = 8 of each). RESULTS: Our major findings were 1) increased soluble ICAM-1 in patients with SMI compared with healthy control participants; 2) increased ITGB2 messenger RNA, encoding the beta chain of the ICAM-1 receptor, in circulating leukocytes from patients with SMI and increased prefrontal cortex messenger RNA expression of ICAM1 in SCZ; and 3) enhanced soluble ICAM-1 release in induced pluripotent stem cell-derived neurons from patients with SCZ. CONCLUSIONS: Our results support a systemic and cerebral dysregulation of soluble ICAM-1 expression in SMI and especially in patients with SCZ.

Perspectives on Coordinating Health Services for Individuals with Serious Mental Illness - A Qualitative Study.

Purpose: Individuals with serious mental illness (SMI) might require coordinated health services to meet their healthcare needs. The overall aim of this study was to describe the perspectives of professionals (registered nurses, medical doctors, social educators, and social workers) on care coordination and measures to ensure proper and coordinated follow-up of the healthcare needs of individuals with SMI. More specifically, we investigated which measures are taken by employees in municipal health and care services to prevent the deterioration of health conditions and which measures are taken in cases where deterioration occurs despite preventive efforts. Method: The study comprised individual qualitative interviews with professionals employed in municipal health and care services in two Norwegian municipalities. The interview material was analyzed using systematic text condensation. Results: Three categories and seven subcategories were created in the data analysis: 1) Maintain a stable and meaningful home life, including ensuring proper housing and access to services and assistance in receiving healthcare; 2) Measures to prevent deterioration of the health condition, including close monitoring of symptoms, emergency psychiatric care plans and emergency room calls and visits; and 3) Inpatient care to stabilize acute and severe symptoms, including municipal inpatient care, returning home after inpatient care and a need for shared responsibility for treatment and care. Conclusion: Professionals employed in municipal health and care services coordinate health services to ensure proper and coordinated follow-up of the healthcare needs of individuals with SMI by ensuring housing services and access to the required healthcare. Measures taken when deterioration occurs include monitoring symptoms, use of emergency psychiatric care plans, emergency room contacts, or inpatient care.

Psychiatric patients' attitudes towards being hospitalized: a national multicentre study in Norway.

BACKGROUND: The aim of the study was to explore patients' attitudes towards voluntary and involuntary hospitalization in Norway, and predictors for involuntary patients who wanted admission. METHODS: A multi-centre study of consecutively admitted patients to emergency psychiatric wards over a 3 months period in 2005-06. Data included demographics, admission status (voluntary / involuntary), symptom levels, and whether the patients expressed a wish to be admitted regardless of judicial status. To analyse predictors of wanting admission (binary variable), a generalized linear mixed modelling was conducted, using random intercepts for the site, and fixed effects for all variables, with logit link-function. RESULTS: The sample comprised of 3.051 patients of witch 1.232 (40.4%) were being involuntary hospitalised. As expected 96.5% of the voluntary admitted patients wanted admission, while as many as 29.7% of the involuntary patients stated that they wanted the same. The involuntary patients wanting admission were less likely to be transported by police, had less aggression, hallucinations and delusions, more depressed mood, less use of drugs, less suicidality before admission, better social functioning and were less often referred by general practitioners compared with involuntary patients who did not want admission. In a multivariate analysis, predictors for involuntary hospitalization and wanting admission were, not being transported by police, less aggression and less use of drugs. CONCLUSIONS: Almost a third of the involuntary admitted patients stated that they actually wanted to be hospitalized. It thus seems to be important to thoroughly address patients' preferences, both before and after admission, regarding whether they wish to be hospitalized or not.

Associations between symptom and neurocognitive dimensions in clinical high risk for psychosis.

Introduction: Clinical high risk for psychosis (CHR) is associated with mild cognitive impairments. Symptoms are clustered into positive, negative and disorganization symptoms. The association between specific symptom dimensions and cognitive functions remains unclear. The aim of this study was to investigate the associations between cognitive functions and positive, negative, and disorganization symptoms. Method: 53 CHR subjects fulfilling criteria for attenuated psychotic syndrome in the Structural Interview for Prodromal Syndromes (SIPS) were assessed for cognitive function. Five cognitive domain z-scores were defined by contrasting with observed scores of a group of healthy controls (n = 40). Principal Components Analyses were performed to construct general cognitive composite scores; one using all subtests and one using the cognitive domains. Associations between cognitive functions and symptoms are presented as Spearman's rank correlations and partial Spearman's rank correlations adjusted for age and gender. Results: Positive symptoms were negatively associated with executive functions and verbal memory, and disorganization symptoms with poorer verbal fluency. Negative symptoms were associated with better executive functioning. There were no significant associations between the general cognitive composites and any of the symptom domains, except for a trend for positive symptoms. Conclusion: In line with previous research, data indicated associations between positive symptoms and poorer executive functioning. Negative symptoms may not be related to executive functions in CHR the same way as in psychosis. Our results could indicate that attenuated positive symptoms are more related to cognitive deficits in CHR than positive symptoms in schizophrenia and FEP.

Can systematic implementation support improve programme fidelity by improving care providers' perceptions of implementation factors? A cluster randomized trial.

BACKGROUND: Investigations of implementation factors (e.g., collegial support and sense of coherence) are recommended to better understand and address inadequate implementation outcomes. Little is known about the relationship between implementation factors and outcomes, especially in later phases of an implementation effort. The aims of this study were to assess the association between implementation success (measured by programme fidelity) and care providers' perceptions of implementation factors during an implementation process and to investigate whether these perceptions are affected by systematic implementation support. METHODS: Using a cluster-randomized design, mental health clinics were drawn to receive implementation support for one (intervention) and not for another (control) of four evidence-based practices. Programme fidelity and care providers' perceptions (Implementation Process Assessment Tool questionnaire) were scored for both intervention and control groups at baseline, 6-, 12- and 18-months. Associations and group differences were tested by means of descriptive statistics (mean, standard deviation and confidence interval) and linear mixed effect analysis. RESULTS: Including 33 mental health centres or wards, we found care providers' perceptions of a set of implementation factors to be associated with fidelity but not at baseline. After 18 months of implementation effort, fidelity and care providers' perceptions were strongly correlated (B (95% CI) = .7 (.2, 1.1), p = .004). Care providers perceived implementation factors more positively when implementation support was provided than when it was not (t (140) = 2.22, p = .028). CONCLUSIONS: Implementation support can facilitate positive perceptions among care providers, which is associated with higher programme fidelity. To improve implementation success, we should pay more attention to how care providers constantly perceive implementation factors during all phases of the implementation effort. Further research is needed to investigate the validity of our findings in other settings and to improve our understanding of ongoing decision-making among care providers, i.e., the mechanisms of sustaining the high fidelity of recommended practices. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03271242 (registration date: 05.09.2017).

Frontline leadership for implementing clinical guidelines in Norwegian mental health services: a qualitative study.

PURPOSE: The purpose of this study was to explore and interpret how frontline leaders define, experience and rationalise their approaches to the successful implementation of clinical guidelines in mental health care. DESIGN/METHODOLOGY/APPROACH: Employing an interpretative phenomenological design, the authors conducted and analysed individual interviews of frontline leaders at 14 psychiatric clinics involved in a national study of implementing evidence-based clinical guidelines in mental health. FINDINGS: The authors found a broad spectrum of attitudes and attributes, as well as a wide repertoire of strategies for frontline implementation leadership. Three main approaches were revealed, comprising "Curious and welcoming", "Integrity and setting standards" and "Caring and collegial". RESEARCH LIMITATIONS/IMPLICATIONS: The study present what experienced frontline leaders emphasise to enable implementation of guidelines, not empirical pieces of evidences for what they in fact do or if these actions lead to implementation. The generalisability to other settings is unknown. Another sample profile, context or organisational level may have impacted the result. The concreteness of the frontline leaders' considerations, approaches and actions gives important knowledge about frontline leaders leadership across traditional leadership theories. ORIGINALITY/VALUE: Existing leadership theories describe different leadership styles, while this study reveals the need for a wide range of approaches to balance the many needs and demands. The complexity of leadership approaches this study found is in line with implementation theories; thus, the present study incorporates implementation science into the leadership literature.

Reduced Expression of Emotion: A Red Flag Signalling Conversion to Psychosis in Clinical High Risk for Psychosis (CHR-P) Populations.

Objective: In this hypothesis-testing study, which is based on findings from a previous atheoretical machine-learning study, we test the predictive power of baseline "reduced expression of emotion" for psychosis.Method: Study participants (N = 96, mean age 16.55 years) were recruited from the Prevention of Psychosis Study in Rogaland, Norway. The Structured Interview for Prodromal Syndromes (SIPS) was conducted 13 times over two years. Reduced expression of emotion was added to positive symptoms at baseline (P1-P5) as a predictor of psychosis onset over a two-year period using logistic regression.Results: Participants with a score above zero on expression of emotion had over eight times the odds of conversion (OR = 8.69, p < .001). Data indicated a significant dose-response association. A model including reduced expression of emotion at baseline together with the positive symptoms of the SIPS rendered the latter statistically insignificant.Conclusions: The study findings confirm findings from the previous machine-learning study, indicating that observing reduced expression of emotion may serve two purposes: first, it may add predictive value to psychosis conversion, and second, it is readily observable. This may facilitate detection of those most at risk within the clinical high risk of psychosis population, as well as those at clinical high risk. A next step could be including this symptom within current high-risk criteria. Future research should consolidate these findings.

Association between C-reactive protein levels and antipsychotic treatment during 12 months follow-up period after acute psychosis.

BACKGROUND: A potential role of inflammatory pathways in the pathology of schizophrenia has been suggested for at least a subgroup of patients. Elevated levels of the inflammatory marker C-reactive protein (CRP) have been observed, with associations to pathogenesis and symptoms. The current evidence regarding effects of antipsychotics on CRP levels is ambiguous. OBJECTIVES: To examine and compare the influence on CRP levels of three pharmacologically diverse new generation antipsychotics during a one-year follow-up in schizophrenia spectrum disorder. METHODS: In a multicenter, pragmatic and rater-blinded randomized trial, the effects of amisulpride, aripiprazole and olanzapine were compared in 128 patients with schizophrenia spectrum disorder. All had positive symptoms of psychosis at study entry. Clinical and laboratory assessments including the measurement of CRP levels were conducted at baseline, and 1, 3, 6, 12, 26, 39, and 52 weeks thereafter. RESULTS: For all antipsychotic drugs analysed together, there was an increase in CRP levels during the one-year follow-up. Aripiprazole, as opposed to amisulpride and olanzapine, was associated with a reduced CRP level after one week, after which the CRP level caught up with the other drugs. Compared to those previously exposed to antipsychotic drugs, antipsychotic-naïve patients had lower CRP levels at all follow-up time points, but with the same temporal patterns of change. CONCLUSION: Treatment with amisulpride, aripiprazole and olanzapine showed different effects on CRP levels in patients with schizophrenia spectrum disorders, modified by previous antipsychotics exposure status. This finding suggests that antipsychotic drugs may vary with respect to their influence on pro-inflammatory pathways. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT01446328; URL: http://www. CLINICALTRIALS: gov/.

Exploring specific predictors of psychosis onset over a 2-year period: A decision-tree model.

AIM: The fluctuating symptoms of clinical high risk for psychosis hamper conversion prediction models. Exploring specific symptoms using machine-learning has proven fruitful in accommodating this challenge. The aim of this study is to explore specific predictors and generate atheoretical hypotheses of onset using a close-monitoring, machine-learning approach. METHODS: Study participants, N = 96, mean age 16.55 years, male to female ratio 46:54%, were recruited from the Prevention of Psychosis Study in Rogaland, Norway. Participants were assessed using the Structured Interview for Psychosis Risk Syndromes (SIPS) at 13 separate assessment time points across 2 years, yielding 247 specific scores. A machine-learning decision-tree analysis (i) examined potential SIPS predictors of psychosis conversion and (ii) hierarchically ranked predictors of psychosis conversion. RESULTS: Four out of 247 specific SIPS symptom scores were significant: (i) reduced expression of emotion at baseline, (ii) experience of emotions and self at 5 months, (iii) perceptual abnormalities/hallucinations at 3 months and (iv) ideational richness at 6 months. No SIPS symptom scores obtained after 6 months of follow-up predicted psychosis. CONCLUSIONS: Study findings suggest that early negative symptoms, particularly those observable by peers and arguably a risk factor for social exclusion, were predictive of psychosis. Self-expression and social behaviour might prove relevant entry points for early intervention in psychosis and psychosis risk. Testing study results in larger samples and at other sites is warranted.