Lower complement C1q levels in first-episode psychosis and in schizophrenia.

Recent evidence has implicated complement component (C) 4A in excessive elimination of synapses in schizophrenia. C4A is believed to contribute to physiological synapse removal through signaling within the C1q initiated classical activation axis of the complement system. So far, a potential involvement of C1q in the pathophysiology of schizophrenia remains unclear. In this study, we first utilized large-scale gene expression datasets (n = 586 patients with schizophrenia and n = 986 controls) to observe lower C1QA mRNA expression in prefrontal cortex tissue of individuals with schizophrenia (P = 4.8x10-05), while C1QA seeded co-expression networks displayed no enrichment for schizophrenia risk variants beyond C4A. We then used targeted liquid chromatography-mass spectrometry (LS-MS) to measure cerebrospinal fluid (CSF) levels of C1qA in 113 individuals with first-episode psychosis (FEP), among which 66 individuals was later diagnosed with schizophrenia, and 87 healthy controls. CSF concentrations of C1qA were lower in individuals diagnosed with FEP (P = 0.0001), also after removing subjects with a short-term prescription of an antipsychotic agent (P = 0.0005). We conclude that C1q mRNA and protein levels are lower in schizophrenia and that further experimental studies are needed to understand the functional implications.

A lowered threshold to partnerships: a mixed methods process evaluation of participants' experiences of a person-centred eHealth intervention.

BACKGROUND: In order to understand pathways of complex interventions, the Medical Research Council has suggested that process evaluations should be conducted alongside randomised controlled trials (RCTs). This paper presents a mixed methods process evaluation of a complex, person-centred eHealth intervention for persons on sick leave with common mental disorders. AIM: The aim of the study was to explore participants' experiences of a person-centred eHealth intervention and illuminate meaningful activities and processes. METHODS: Participants were recruited from the intervention arm of an RCT (n = 102). Questionnaires on perceived meaningfulness of the overall intervention and intervention activities were sent to participants on two occasions, after 3 and 6 months, and semi-structured interviews were conducted with a purposeful sample of 15 participants in the intervention group. Questionnaire data were analysed using descriptive statistics, and interview data were analysed using qualitative content analysis. The quantitative and qualitative data strands were integrated at interpretation. RESULTS: At both follow-ups, a majority of participants reported that the intervention was fully or partly meaningful and that the most meaningful activity was the phone calls with health care professionals working in the intervention. In the qualitative analysis, three categories describing participants' experiences of the intervention were formed: Acknowledgment in a disconcerting situation, Finding ways forward and Unmet expectations. A synthesis of quantitative and qualitative findings resulted in the overarching theme of meaningfulness as constituted by a lowered threshold to partnerships: support within reach, when needed. CONCLUSION: Experiences of meaningfulness of the intervention were constituted by a lowered threshold to forming care partnerships, in which support was within reach, when needed. If the content of the intervention was not in accordance with individuals' needs or expectations, access alone did not suffice to constitute meaningfulness. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03404583; 19/01/2018.

Increasing person-centeredness in psychosis inpatient care: care consumption before and after a person-centered care intervention.

BACKGROUND: Patients with psychotic disorders often need hospitalization with long stays. Person-centered care (PCC) has been shown to improve care quality and decrease the length of hospital stay in non-psychiatric settings. We carried out an educational intervention for inpatient staff, aiming to increase person-centeredness at a major Swedish psychosis clinic. The aim of this study was to test if the intervention could be associated with decreased length of hospital stay (LoS), involuntary stay (LoIS), and reduction in rapid readmissions. METHODS: Data from the clinic's administrative registry were compared for patients with a discharge diagnosis within the schizophrenia-spectrum treated during the one-year periods before and after the PCC intervention. RESULTS: Contrary to our hypotheses, a quantile regression estimated longer LoS post-intervention, median difference 10.4 d (CI 4.73-16.10). Neither age, sex nor diagnostic category were associated with LoS. Of all inpatient days, ∼80% were involuntary. While LoIS was numerically longer post-intervention, the difference did not reach significance in the final regression model (median difference 7.95 d, CI -1.40 to 17.31). Proportions with readmission within 2 weeks of discharge did not differ (7.7% vs 5.2%, n.s.). CONCLUSIONS: Increased length of inpatient care was observed after the PCPC intervention. This could reflect an increased focus on the unmet needs of persons with serious psychotic conditions, but it needs to be explored in future research using a more rigorous study design. TRIAL REGISTRATION: This study is part of a larger evaluation of Person-Centered Psychosis Care (PCPC), registered during data collection (after the study start, before analysis) at clinicaltrials.gov, identifier NCT03182283.

Cerebrospinal fluid concentration of complement component 4A is increased in first episode schizophrenia.

Postsynaptic density is reduced in schizophrenia, and risk variants increasing complement component 4A (C4A) gene expression are linked to excessive synapse elimination. In two independent cohorts, we show that cerebrospinal fluid (CSF) C4A concentration is elevated in patients with first-episode psychosis (FEP) who develop schizophrenia (FEP-SCZ: median 0.41 fmol/ul [CI = 0.34-0.45], FEP-non-SCZ: median 0.29 fmol/ul [CI = 0.22-0.35], healthy controls: median 0.28 [CI = 0.24-0.33]). We show that the CSF elevation of C4A in FEP-SCZ exceeds what can be expected from genetic risk variance in the C4 locus, and in patient-derived cellular models we identify a mechanism dependent on the disease-associated cytokines interleukin (IL)-1beta and IL-6 to selectively increase neuronal C4A mRNA expression. In patient-derived CSF, we confirm that IL-1beta correlates with C4A controlled for genetically predicted C4A RNA expression (r = 0.39; CI: 0.01-0.68). These results suggest a role of C4A in early schizophrenia pathophysiology.

The interactive work of narrative elicitation in person-centred care: Analysis of phone conversations between health care professionals and patients with common mental disorders.

INTRODUCTION: Narratives play a central part in person-centred care (PCC) as a communicative means of attending to patients' experiences. The present study sets out to explore what activities are performed and what challenges participants face in the interactive process of narrative elicitation, carried through in patient-professional communication in a remote intervention based on PCC. METHODS: Data were gathered from a randomized controlled trial (RCT) in a Swedish city where health care professionals (HCPs) conducted remote PCC for patients on sick leave due to common mental disorders. A sample of eleven audio-recorded phone conversations between HCPs and patients enroled in the RCT were collected and subjected to conversation analysis. RESULTS: Three interactive patterns in narrative elicitation were identified: Completed narrative sequences driven by the patient, question-driven narrative sequences guided by the HCP, and narrative sequences driven as a collaborative project between the patient and the HCP. In the question-driven narrative sequences, communication was problematic for both participants and they did not accomplish a narrative. In the other two patterns, narratives were accomplished but through various collaborative processes. CONCLUSION: This study provides insight into what challenges narrative elicitation may bring in the context of a remote PCC intervention and what interactive work patients and HCP need to engage in. Importantly, it also highlights tensions in the ethics of PCC and its operationalization, if the pursuit of a narrative is not properly balanced against the respect for patients' integrity and personal preferences. Our findings also show that narrative elicitation may represent an interactive process in PCC in which illness narratives are jointly produced, negotiated and transformed. PATIENT OR PUBLIC CONTRIBUTION: Stakeholders, including patient representatives, were involved in the design of the main study (the RCT). They have been involved in discussions on research questions and dissemination throughout the study period. They have not been involved in conducting the present study.

Striving for a more person-centered psychosis care: results of a hospital-based multi-professional educational intervention.

BACKGROUND: Reluctance on the part of mental health professionals constitutes an important barrier to patient participation in care. In order to stimulate person-centeredness in the inpatient care of persons with psychotic illness, we developed and tested an educational intervention for hospital staff (including psychiatrists) at all four wards at the Psychosis Clinic, Sahlgrenska University Hospital in Gothenburg, Sweden. The intervention was co-created by professionals, patients, and researchers using a participatory approach. In addition to lectures and workshops, staff created and implemented small projects to increase person-centeredness on their own wards. A primary focus was to establish a partnership between patient and staff by capturing and utilizing the patient's narrative to support active engagement in the care process. This included the development of a person-centered care plan. We hypothesized that the intervention would be associated with increased patient empowerment (primary outcome) and satisfaction with care (secondary outcome). METHODS: A before and after design was used to test group differences in patient empowerment (Empowerment Scale) and consumer satisfaction (UKU-ConSat Rating Scale). All patients receiving inpatient psychosis care during measuring periods were eligible if meeting inclusion criteria of schizophrenia spectrum disorder, age > 18, and ability to comprehend study information. Severe cognitive deficit and inadequate Swedish language skills were exclusion criteria. Data on possible confounding variables including overall health (EQ-5D), symptom burden (PANSS), and functional ability (GAF) were collected alongside outcome measures. RESULTS: ANCOVAs with overall health as a confounding variable showed no group differences regarding empowerment before (n = 50) versus after (n = 49) intervention, sample mean = 2.87/2.99, p = .142, eta2 = .02, CI = -.27-.04. Consumer satisfaction (n = 50/50) was higher in the post-implementation group (4.46 versus 11.71, p = .041 eta2 = .04, CI = -14.17- -.31). CONCLUSION: The hypothesis regarding the primary outcome, empowerment, was not supported. An increase in the secondary outcome, satisfaction, was observed, although the effect size was small, and results should be interpreted with caution. Findings from this staff educational intervention can inform the development of future studies aimed at improvement of inpatient care for persons with severe mental illness. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov June 9, 2017, identifier: NCT03182283.

Study protocol design and evaluation of a hospital-based multi-professional educational intervention: Person-Centred Psychosis Care (PCPC).

BACKGROUND: While patient involvement in mental health care is repeatedly stressed in policy documents, there are actually few studies that evaluate person-centred care interventions within psychiatric services. We present here the design and planned evaluation of an educational intervention for inpatient staff involved in the care of persons with schizophrenia and similar psychoses. METHODS/DESIGN: The care intervention will be assessed using a non-randomised trial with a before and after approach. The intervention involves an educational and experimental learning phase for hospital staff, followed by an implementation phase. The intervention is multi-professional; psychiatrists, psychiatric nurses, psychiatric carers, social workers, occupational therapists, and a medical secretary will be engaged in a participatory approach where they practice how to create a partnership and explore recovery-related goals together with patients. Patient-related outcomes include empowerment and satisfaction with care. Ward-level outcomes include daily ward burden, length of inpatient stay, and number of days with involuntary care. In addition, qualitative methods will be applied to capture patient, next-of-kin, and staff perspectives. DISCUSSION: The care intervention is expected to contribute to the improvement of inpatient care for persons with severe and complex mental health issues. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov June 9, 2017, identifier: NCT03182283 .

Attachment styles and symptoms in individuals with psychosis.

BACKGROUND: The capacity to manage affects is rooted in early interactions with caregivers, which in adulthood are internalized as different attachment styles. Few studies have explored associations between all four attachment styles and symptoms. AIM: Our aim was to investigate the relations between the four attachment styles and psychological distress in a group of people with psychosis. METHOD: In a cross-sectional study, associations between self-reported attachment style and symptoms in a psychosis group were explored. Attachment styles were measured with the Relationship Questionnaire (RQ) and symptoms were assessed with the revised version of the Symptom Checklist (SCL-90R) RESULTS: The analyses showed a significant positive association between preoccupied attachment and the severity of symptoms. Furthermore, the analyses indicated significant positive associations between preoccupied attachment and the subscales measuring depression, anxiety, interpersonal sensitivity, paranoia and psychoticism. We also found significant positive associations between fearful attachment and both interpersonal sensitivity and psychoticism. CONCLUSION: The associations between attachment styles and symptoms found here are consistent with those of previous studies. It could be important for clinicians to identify patients' attachment styles. Such knowledge would help mental health professionals to understand better the patients' capacity to handle distress and help professionals to address interventions aiming to target each patient's specific needs.