Additive effects of a family history of schizophrenia spectrum disorders and an environmental risk score for the outcome of patients with non-affective first-episode psychosis.

BACKGROUND: First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP). METHODS: We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach. RESULTS: A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval -16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery. CONCLUSIONS: Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.

Clinical illness course and family-related outcomes among parents with a first episode of schizophrenia spectrum disorder: a 20-year follow-up of the OPUS trial.

BACKGROUND: Studies investigating parenthood and how it affects long-term outcomes are lacking among individuals with schizophrenia spectrum disorders. This study aimed to examine the life of participants 20 years after their first diagnosis with a special focus on parenthood, clinical illness course, and family-related outcomes. METHODS: Among 578 individuals diagnosed with first-episode schizophrenia spectrum disorder between 1998 and 2000, a sample of 174 participants was reassessed at the 20-year follow-up. We compared symptom severity, remission, clinical recovery, and global functioning between 75 parents and 99 non-parents. Also, family functioning scored on the family assessment device, and the children's mental health was reported. We collected longitudinal data on psychiatric admission, supported housing, and work status via the Danish registers. RESULTS: Participants with offspring had significantly lower psychotic (mean (s.d.) of 0.89 (1.46) v. 1.37 (1.44), p = 0.031) negative (mean [s.d.] of 1.13 [1.16] v. 1.91 [1.07], p < 0.001) and disorganized symptom scores (mean [s.d.] of 0.46 [0.80] v. 0.85 [0.95], p = 0.005) and more were in remission (59.5% v. 22.4%, p < 0.001) and in clinical recovery (29.7% v. 11.1%, p = 0.002) compared to non-parents. When investigating global functioning over 20 years, individuals becoming parents after their first diagnosis scored higher than individuals becoming parents before their first diagnosis and non-parents. Regarding family-related outcomes, 28.6% reported unhealthy family functioning, and 10% of the children experienced daily life difficulties. CONCLUSIONS: Overall, parents have more favorable long-term outcomes than non-parents. Still, parents experience possible challenges regarding family functioning, and a minority of their children face difficulties in daily life.

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population.

Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is nonresponsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next-generation sequencing of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 48 putative affected and 180 putative carriers for TGDs were identified, with known or likely pathogenic variants in 79 genes. Despite screening for only 108 genetic disorders, this study showed a two-fold (2.09%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases is greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.

Borderline personality disorder vs. schizophrenia spectrum disorders in young people recruited within an "Early Intervention in Psychosis" service: clinical and outcome comparisons.

Borderline Personality Disorder (BPD) is under-recognized in First-Episode Psychosis (FEP) and its psychotic manifestations are difficult to differentiate from Schizophrenia Spectrum Disorders (SSD). The aim of this investigation was to compare clinical, sociodemographic, and outcome characteristics between FEP patients with BPD vs. FEP subjects with SSD both at baseline and across a 2-year follow-up period. Participants completed the Health of the Nation Outcome Scale (HoNOS), the Positive And Negative Syndrome Scale (PANSS), and the Global Assessment of Functioning (GAF) scale both at entry and every 12 months during the follow-up. A mixed-design ANOVA model was conducted to investigate the temporal stability of clinical scores within and between the two subgroups. Among 356 FEP participants, 49 had a BPD diagnosis. Compared to FEP/SSD (n = 307), FEP/BPD patients showed higher prevalence of employment, current substance use, and past attempted suicide. They had a lower equivalent dose of antipsychotic medication at entry and lower levels of negative symptoms. Finally, they had a higher 2-year drop-out rate and a significant improvement in psychopathological scores limited to the first year of treatment. BPD as categorical entity represents a FEP subgroup with specific clinical challenges. Appropriate treatment guidelines for this FEP subgroup are thus needed.

The Finnish Adoptive Family Study of Schizophrenia: differences in somatic diseases and conditions between adoptees with high or low genetic risk for schizophrenia spectrum disorders.

BACKGROUND AND AIMS: There is some evidence that offspring of patients with schizophrenia have higher somatic morbidity, which is thought to be partially due to genetic links between somatic disorders and schizophrenia. This study explored differences in somatic diseases and conditions of adoptees with high genetic risk (HR) or low genetic risk (LR) for schizophrenia spectrum disorders. MATERIAL AND METHODS: The study is part of the Finnish Adoptive Family Study of Schizophrenia. The adoptive research design used made it possible to examine how the somatic health of adoptees raised in similar adoptive families, is affected by their genetic susceptibility to schizophrenia. The study sample consisted of 373 adoptees, of whom 190 had HR and 183 had LR for schizophrenia spectrum disorders. Data on somatic morbidity were gathered from the hospital records and from the national registers of the Care Register of Health Care and the Social Insurance Institution. RESULTS: The only statistically significant difference found was in genitourinary diseases, the likelihood being twofold higher in HR adoptees compared to LR adoptees (16.8% vs. 8.2%; adj. OR = 2.13, 95% CI 1.06-4.25, p = .033). Adoptees who were female and aged over 40 had a higher prevalence of genitourinary illnesses than non-adoptees. CONCLUSION: The significant prevalence of genitourinary diseases in adoptees at risk for schizophrenia spectrum disorders suggests that some specific somatic diseases and schizophrenia may have a shared hereditary etiology. More research is required for specific somatic diseases in study populations that can differentiate between the effects of genetic and environmental factors.

Treatment Outcomes for Asian Americans Diagnosed with Schizophrenia Spectrum Disorder.

We implemented a pilot study to investigate symptoms and functional outcomes of Asian Americans treated in urban community mental health centers for a diagnosis of schizophrenia spectrum disorder. Furthermore, we investigated whether these outcomes differed between East and Southeast Asians. We collected quantitative data from 75 participants recruited using a nonprobability sampling strategy from six urban community mental health centers. We used the Positive and Negative Syndrome Scale (Kay et al. in Schizophrenia Bulletin 13(2):261-276, 1987) and the Strauss and Carpenter Outcome Scale (Strauss and Carpenter in Archives of General Psychiatry 27(6):739-746, 1972) to measure their symptoms and functional outcomes. To compare the outcomes between East and Southeast Asians, we used a multivariable logistic regression model, which adjusted for the estimated effects of age, sex assigned at birth, and age at onset of illness for each outcome examined. The data shows that the treatment outcomes for this group are poor. Only a small number of participants experienced symptomatic remission (30.67%), role restoration (34.67%), and clinical recovery (21.33%). The majority of those who did not experience clinical recovery had difficulties sustaining symptomatic remission and restoring role functioning (54.67%). However, more participants achieved social restoration (68.00%). The results did not vary by national origin groups and sex assigned at birth. However, the participant's age, the age at which the illness began, or both determined whether the treatment outcomes were favorable. Findings underscore the need for interventions that improve symptom control to increase the likelihood of other favorable outcomes.

Nurses' and patients' perceptions of physical health screening for patients with schizophrenia spectrum disorders: a qualitative study.

BACKGROUND: Despite worldwide concern about the poor physical health of patients with schizophrenia spectrum disorders (SSD), physical health screening rates are low. This study reports nurses' and patients' experiences of physical health screening among people with SSD using the Finnish Health Improvement Profile (HIP-F) and their ideas for implementation improvements. METHODS: A qualitative exploratory study design with five group interviews with nurses (n = 15) and individual interviews with patients with SSD (n = 8) who had experience using the HIP-F in psychiatric outpatient clinics. Inductive content analysis was conducted. RESULTS: Two main categories were identified. First, the characteristics of the HIP-F were divided into the subcategories of comprehensive nature, facilitating engagement, interpretation and rating of some items and duration of screening. Second, suggestions for the implementation of physical health screening consisted of two subcategories: improvements in screening and ideas for practice. Physical health screening was felt to increase the discussion and awareness of physical health and supported health promotion. The HIP-F was found to be a structured, comprehensive screening tool that included several items that were not otherwise assessed in clinical practice. The HIP-F was also considered to facilitate engagement by promoting collaboration in an interactive way. Despite this, most of the nurses found the HIP-F to be arduous and too time consuming, while patients found the HIP-F easy to use. Nurses found some items unclear and infeasible, while patients found all items feasible. Based on the nurses' experiences, screening should be clear and easy to interpret, and condensation and revision of the HIP-F tool were suggested. The patients did not think that any improvements to the HIP-F were needed for implementation in clinical settings. CONCLUSIONS: Patients with schizophrenia spectrum disorders are willing to participate in physical health screening. Physical health screening should be clear, easy to use and relatively quick. With this detailed knowledge of perceptions of screening, further research is needed to understand what factors affect the fidelity of implementing physical health screening in clinical mental health practice and to gain an overall understanding on how to improve such implementation.

Early Maladaptive Schemas and Depression in Caregivers of Individuals With Schizophrenia Spectrum and Bipolar Disorders.

OBJECTIVES: Early maladaptive schemas represent unhelpful frameworks of cognitions, emotions and subsequent behavioural responses and can be associated with depressive symptoms. Caregivers of individuals with serious mental illness (SMI) frequently report experiencing depressive symptoms. It is unclear whether depressive symptoms in caregivers are influenced by schemas. We aimed to compare activated schemas in caregivers of people with schizophrenia spectrum (SSD) and bipolar disorder (BD) diagnoses and to determine whether they were differentially related to depressive symptoms. DESIGN AND METHODS: Caregivers completed validated measures of depression and schemas. Independent samples t-tests and multivariate generalised linear models were used to assess differences in schemas and depressive symptoms between caregiver groups. Interrelationships between schema domains and caregiver depressive symptoms were delineated using correlational analyses and forward stepwise regressions. RESULTS: One hundred eight caregivers participated in the study (SSD n = 68, BD n = 40). No differences in depressive symptom severity or activated schemas were observed between caregiver groups. All schemas were significantly associated with depressive symptoms, and the Disconnection-Rejection schema domain explained the most variance in depressive symptoms in both caregiver groups. CONCLUSIONS: Schemas contribute to the severity of caregiver depression regardless of whether the person receiving care is diagnosed with SSD or BD. Schema therapeutic frameworks may be beneficial for use with caregivers to address schemas within the Disconnection-Rejection domain and alleviate depressive symptoms by reducing experiences of social isolation and alienation.

Cognitive function in early-phase schizophrenia-spectrum disorder: IQ subtypes, brain volume and immune markers.

BACKGROUND: Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation. METHOD: 161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α. RESULTS: Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls. CONCLUSIONS: The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

Use of multiple polygenic risk scores for distinguishing schizophrenia-spectrum disorder and affective psychosis categories in a first-episode sample; the EU-GEI study.

BACKGROUND: Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case-control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD). METHODS: Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons. RESULTS: In case-control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case-case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54-0.92] and PRS-D (OR = 1.31, 95% CI 1.06-1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23-3.74). CONCLUSIONS: Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.