Discussing the concept of substance-induced psychosis (SIP).

Substance-induced psychosis (SIP) is characterized by both substance use and a psychotic state, and it is assumed that the first causes the latter. In ICD-10 the diagnosis is categorized as and grouped together with substance use disorders, and to a large extent also treated as such in the health care system. Though criticism of the diagnostic construct of SIP dates back several decades, numerous large and high-quality studies have been published during the past 5-10 years that substantiate and amplify this critique. The way we understand SIP and even how we name it is of major importance for treatment and it has judicial consequences. It has been demonstrated that substance use alone is not sufficient to cause psychosis, and that other risk factors besides substance use are at play. These are risk factors that are also known to be associated with schizophrenia spectrum disorders. Furthermore, register-based studies from several different countries find that a large proportion, around one in four, of those who are initially diagnosed with an SIP over time are subsequently diagnosed with a schizophrenia spectrum disorder. This scoping review discusses the construct validity of SIP considering recent evidence. We challenge the immanent causal assumption in SIP, and advocate that the condition shares many features with the schizophrenia spectrum disorders. In conclusion, we argue that SIP just as well could be considered a first-episode psychotic disorder in patients with substance use.

Problematic diagnosis of substance-induced disorders in ICD-11.

The ICD-11 was introduced in January 2022. In chapter 6, "Mental, behavioral and neurodevelopmental disorders" we find the section "Disorders due to substance use and addictive behaviors" (section 6C4). Changes from the ICD-10 in this section include broadening the categories of harmful use and dependence, including more types of substances, and the addition of more behavioral addictions (gaming disorder). These changes have been discussed and debated [1].

People who die by suicide without having attended hospital-based psychiatric care: Who are the ones that do not seek help?

BACKGROUND: Little is known regarding those who die by suicide without having received help. The aim of this study was to compare those who died by suicide without having attended psychiatric care with controls (a) with a psychiatric diagnosis and (b) from the general population. METHODS: Cases were all individuals 15+ who lived in Denmark during 2010-2021 and had died by suicide without having attended hospital-based psychiatric care. Cases were matched to controls from the two comparison-groups using a 1:10 ratio and compared using age-and sex-adjusted logistic regression analyses. Geographical variations in psychiatric care utilization were examined. RESULTS: Among 7119 individuals who died by suicide, 3474 (48.8 %) had not attended psychiatric care. Compared to controls with a psychiatric diagnosis, cases were more likely to be male (OR, 3.9, 95 % CI, 3.6-4.2), older (80+ years: OR, 10.7, 95 % CI, 9.2-12.5), have lost a close relative (OR, 1.8, 95 % CI, 1.3-2.6) or recently retired (OR, 1.4, 95 % CI, 1.0-1.1.8). Compared to controls from the general population, cases were associated with male sex (OR, 4.6, 95 % CI, 4.2-5.0), living alone (OR, 2.3, 95 % CI, 2.2-2.5), unemployment (OR, 2.1, 95 % CI, 1.8-2.5), and having lost a close relative (OR, 5.0, 95 % CI, 3.5-7.2) or divorced (OR, 3.6, 95 % CI, 2.7-4.9). LIMITATIONS: Characteristics and preceding events were limited to available register data. CONCLUSIONS: About half of all who died by suicide had not attended psychiatric care. Being older, male, or exposed to recent stressors were some of the major markers when compared to controls.

Long-term quality of life and social disconnection 20 years after a first episode psychosis, results from the 20-year follow-up of the OPUS trial.

OBJECTIVE: Schizophrenia disorders severely impact social and occupational function and reduce quality of life, furthermore patients often suffer from social withdrawal and isolation. The aim of this study was to investigate long-term quality of life and social disconnection and determine 10-year changes in quality of life and social disconnection later in life in association with changes in symptom severity, cognition, and global function. METHODS: We used assessments of quality of life and assessor rated social disconnection from the 10- and 20-year follow-up of the OPUS trial to examined 10-year changes in self-rated quality of life and social disconnection in the later stage of illness following a first episode psychosis. Self-rated social disconnection was only assessed in the 174 participants of the 20-year follow-up. RESULTS: Twenty years after a first episode psychosis only half of the participants reported having face-to-face contact with someone in their network more than once a week, while 90 % reported often or always being able to get emotional support when needed. Quality of life ratings were lower in our study population compared to the general population. On average physical and environmental quality of life worsened from the 10- to the 20-year follow-up while psychological and social quality of life remained stable. All quality-of-life domains were associated with negative symptoms (physical QoL: b = -6.6, p < 0.001, psychological QoL: b = -8, p < 0.001, social QoL: b = -5.7, p < 0.001 and environmental QoL: b = -6.5, p < 0.001) and global function (physical QoL: b = -0. 47, p < 0.001, psychological QoL: b = 0.52, p < 0.001, social QoL: b = 0.31, p < 0.001 and environmental QoL: b = 0.49, p < 0.001). CONCLUSION: Social disconnection seems to persist over time. Social disconnection and quality of life were associated with negative symptoms and poor functioning, therefore interventions aimed at improving global and social function might likely also improve quality of life.

The use of composite endpoints in cardiovascular outcome trials for diabetes: A review of 22 randomized clinical trials published since 2008.

AIM: To describe the use of composite endpoints (CEs) in cardiovascular outcome trials (CVOTs) of type 2 diabetes and to evaluate the significance of the individual outcomes included within these CEs from the perspectives of both patients and clinicians. Secondary objectives were to estimate the gradient of treatment effects and events across outcomes. MATERIALS AND METHODS: Eligible studies were randomized controlled trials assessing CV outcomes for patients with diabetes from 2008 and onwards. Trials were identified by searching the reports from the CVOT Summit of the Diabetes & CV Disease EASD (European Association for the Study of Diabetes) Study Group. The individual outcomes comprising the CE were compared for differences in importance for patients and clinicians, proportion of events, and effect size. RESULTS: We included 22 trials randomizing a mean of 8098 patients to an active intervention or a comparator group for an average of 33 months (standard deviation 16). All primary outcomes were CEs, and from a patient perspective there was no gradient of importance across outcomes in 22 of 22 (100%) CEs, while the gradient was small in 22 of 22 (100%) from a clinician perspective. The gradient of effect was moderate to large in 9 of 18 (50%) reporting studies, while assessment of events was available in 15 of 22 studies (68%), finding that three of 15 (20%) had a gradient of effect of more than 5% points between included outcomes. In 10 of 22 (45%) trial reports, the results were not clearly presented as based on a CE. CONCLUSIONS: To avoid misinterpretation, clinicians and regulatory authorities should be careful when interpreting the results of trials, of which the main outcomes are CEs.

Interventions targeting patients with co-occuring severe mental illness and substance use (dual diagnosis) in general practice settings - a scoping review of the literature.

BACKGROUND: People with dual diagnosis die prematurely compared to the general population, and general practice might serve as a setting in the healthcare system to mend this gap in health inequity. However, little is known about which interventions that have been tested in this setting. AIM: To scope the literature on interventions targeting patients with dual diagnosis in a general practice setting, the outcomes used, and the findings. DESIGN AND SETTING: A scoping review of patients with dual diagnosis in general practice. METHODS: From a predeveloped search string, we used PubMed (Medline), PsychInfo, and Embase to identify scientific articles on interventions. Studies were excluded if they did not evaluate an intervention, if patients were under 18 years of age, and if not published in English. Duplicates were removed and all articles were initially screened by title and abstract and subsequent fulltext were read by two authors. Conflicts were discussed within the author group. A summative synthesis of the findings was performed to present the results. RESULTS: Seven articles were included in the analysis. Most studies investigated integrated care models between behavioural treatment and primary care, and a single study investigated the delivery of Cognitive Behavioral treatment (CBT). Outcomes were changes in mental illness scores and substance or alcohol use, treatment utilization, and implementation of the intervention in question. No studies revealed significant outcomes for patients with dual diagnosis. CONCLUSION: Few intervention studies targeting patients with dual diagnosis exist in general practice. This calls for further investigation of the possibilities of implementing interventions targeting this patient group in general practice.

Traumatic brain injury and long-term associations with work, divorce and academic achievement.

OBJECTIVE: Traumatic brain injuries (TBI), irrespective of severity, may have long-term social implications. This study explores the relationships between TBI severity and outcomes related to work stability, divorce, and academic achievement. METHODS: Using a Danish nationwide sample of persons with and without TBI, we employed case-control and longitudinal cohort designs. The case-control design utilized individuals aged 18 to 60 years and examined work stability. Each case, employed at time of TBI, was compared with 10 matched controls. The cohort design utilized individuals alive from 1980 to 2016 with and without TBI and assessed the likelihood of 1) divorce and 2) higher-level education. TBI exposures included concussion, skull fractures, or confirmed TBI. RESULTS: TBI cases exhibited higher odds ratios (OR) for work instability at all follow-ups compared to controls. Increased TBI severity was associated with a higher risk of work instability at 2-year follow-up (concussion: OR = 1.83; skull fracture: OR = 2.22; confirmed TBI: OR = 4.55), and with a higher risk of not working at 10-year follow-up (confirmed TBI: OR = 2.82; concussion: OR = 1.63). The divorce incidence rate ratio (IRR) was elevated in individuals with TBI (males: IRR = 1.52; females: IRR = 1.48) compared to those without TBI. Individuals with childhood TBI had reduced chances of attaining high school degree or higher (males: IRR = 0.79; females: IRR = 0.85) compared to those without TBI. CONCLUSION: TBI is associated with an increased long-term risk of social consequences, including work instability, divorce, and diminished chances of higher education, even in cases with concussion.

Inflammatory markers, somatic complaints, use of medication and health care in 11-year-old children at familial high risk of schizophrenia or bipolar disorder compared with population-based controls. The Danish High Risk and Resilience Study - via 11.

PURPOSE: Patients with schizophrenia or bipolar disorder are at increased risk of somatic illnesses and have more somatic complaints compared with the general population. Schizophrenia and bipolar disorder are highly heritable. Already during childhood, children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BD) are at increased risk of psychiatric disorders and cognitive and social impairments. Knowledge about physical conditions is sparse. MATERIALS AND METHODS: Through blood tests (n = 293), interviews, and questionnaires, we assessed inflammatory markers, somatic complaints, medication - and health care use in 11-year-old children at FHR-SZ, FHR-BD, and population-based controls (PBC). RESULTS: Children at FHR-SZ had higher concentrations of leucocytes (mean 6.41, SD 0.73) compared with PBC (mean 5.78, SD 0.27, p = 0.005) and of neutrophilocytes (FHR-SZ: mean 3.11, SD 1.32, PBC: mean 2.70, SD 0.96, p = 0.024). Compared with PBC (26.6%), more children at FHR-SZ (40.5%, p = 0.007) reported somatic complaints. So did caregivers and teachers to children at FHR-BD. Somatic complaints, higher concentrations of leucocytes, and neutrophilocytes were associated with lower levels of physical activity. Children at FHR-BD with psychiatric disorders reported more somatic complaints compared with those without. CONCLUSION: Children at FHR-SZ had higher concentrations of leucocytes and neutrophilocytes than PBC. Children at FHR-SZ or FHR-BP displayed more somatic complaints than controls. Our study highlights rarely explored disadvantage of being born to parents with schizophrenia or bipolar disorder. To enhance understanding of how physical conditions in childhood may interplay with later transition to mental disorders in children at FHR-SZ and FHR-BD, further research is needed.

Schema therapy versus treatment as usual for outpatients with difficult-to-treat depression: study protocol for a parallel group randomized clinical trial (DEPRE-ST).

BACKGROUND: About one third of patients with depression are in a condition that can be termed as "difficult-to-treat". Some evidence suggests that difficult-to-treat depression is associated with a higher frequency of childhood trauma and comorbid personality disorders or accentuated features. However, the condition is understudied, and the effects of psychotherapy for difficult-to-treat depression are currently uncertain. The aim of this trial is to investigate the beneficial and harmful effects of 30 sessions of individual schema therapy versus treatment as usual for difficult-to-treat depression in the Danish secondary, public mental health sector. METHODS: In this randomized, multi-centre, parallel-group, superiority clinical trial, 129 outpatients with difficult-to-treat depression will be randomized (1:1) to 30 sessions of individual schema therapy or treatment as usual; in this context mainly group-based, short-term cognitive behaviour or psychodynamic therapy. The primary outcome is the change from baseline in depressive symptoms 12 months after randomization, measured on the observer-rated 6-item Hamilton Rating Scale for Depression. The secondary outcomes are health-related quality of life assessed with the European Quality of Life 5 Dimensions 5 Level Version, functional impairment assessed with the Work and Social Adjustment Scale, psychological wellbeing assessed with the WHO-5 Well-being Index, and negative effects of treatment assessed with the Negative Effects Questionnaire. Exploratory outcomes are improvement on patient self-defined outcomes, personal recovery, anxiety symptoms, anger reactions, metacognitive beliefs about anger, and perseverative negative thinking. Outcomes will be assessed at 6, 12, and 24 months after randomization; the 12-month time-point being the primary time-point of interest. Outcome assessors performing the depression-rating, data managers, statisticians, the data safety and monitoring committee, and conclusion makers for the outcome article will be blinded to treatment allocation and results. To assess cost-effectiveness of the intervention, a health economic analysis will be performed. DISCUSSION: This trial will provide evidence on the beneficial and harmful effects, as well as the cost-effectiveness of schema therapy versus treatment as usual for outpatients with difficult-to-treat depression. The results can potentially improve treatment for a large and understudied patient group. TRIAL REGISTRATION: ClinicalTrials.gov NCT05833087. Registered on 15th April 2023 (approved without prompts for revision on 27th April 2023).

Use of antipsychotic medication, benzodiazepines, and psychiatric hospitalization in cannabis-related versus cannabis-unrelated schizophrenia - a nationwide, register-based cohort study.

BACKGROUND: Evidence suggests that cannabis may be a causal factor for development of schizophrenia. We aimed to investigate whether use of antipsychotic medication, benzodiazepines, and psychiatric service use differs among patients with schizophrenia depending on whether psychosis was precipitated by a diagnosis of cannabis use disorder (CUD). METHODS: We utilized the nationwide Danish registries to identify all individuals with an incident diagnosis of schizophrenia from 1995 to 2016. We also collected information on whether first CUD diagnosis preceded schizophrenia and thus defined a group of potentially cannabis-related schizophrenia. We compared the cannabis-related schizophrenia group both with all non-cannabis-related patients with schizophrenia and with non-cannabis-related patients with schizophrenia that were propensity-score matched to cases using a range of potentially confounding variables. RESULTS: We included 35 714 people with incident schizophrenia, including 4116 (11.5%) that were cannabis-related. In the unmatched-comparison analyses, there were no clear differences over time in use of antipsychotics and benzodiazepines related to whether the diagnosis of schizophrenia was cannabis-related. After propensity-score matching, use of antipsychotics and benzodiazepines was significantly lower among cannabis-related cases of schizophrenia. In the unmatched comparison, the cannabis-related group had significantly more days admitted than the non-cannabis-related group. This was markedly attenuated after propensity-score matching. CONCLUSIONS: Our findings indicate the importance of considering cannabis-related cases of schizophrenia as a potentially distinct disorder in terms of prognosis. It is unclear, however, if these differences are due to different biological types of schizophrenia being compared or if they rather indicate behavioral differences such as reduced adherence and treatment-seeking.

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.

20-year neurocognitive development following a schizophrenia spectrum disorder and associations with symptom severity and functional outcomes.

BACKGROUND: Cognitive deficits are a core feature of schizophrenia and are closely associated with poor functional outcomes. It remains unclear if cognitive deficits progress over time or remain stable. Determining patients at increased risk of progressive worsening might help targeted neurocognitive remediation approaches. METHODS: This 20-year follow-up study examined neurocognitive outcomes of 156 participants from the OPUS I trial. Neurocognition was assessed using the brief assessment of cognition in schizophrenia at the 10- and 20-year follow-up, allowing us to examine changes in neurocognition over ten years. RESULTS: We found that 30.5% of patients had a declining course of neurocognition, 49.2% had a stable course of neurocognition and 20.3% experienced improvements in neurocognition. Good cognitive functioning at the 20-year follow-up was significantly associated with higher levels of social functioning (B 6.86, CI 4.71-9.02, p < 0.001) while increasing experiential negative symptoms were significantly correlated to cognitive worsening (PC-0.231, p = 0.029). Younger age at inclusion (B: 0.23 per 10-years, CI 0.00-0.045, p = 0.047) and low level of education (below ten years) (mean difference: -0.346, CI -0.616 to -0.076, p = 0.012) predicted declining neurocognition. CONCLUSION: Our findings support the notion of different schizophrenia subtypes with varying trajectories. Neurocognitive impairment at the 20-year follow-up was associated with other poor outcomes, highlighting the importance of treatments aimed at improving neurocognition in patients with schizophrenia spectrum disorders.

Exploring the relationship between attributional style measured in virtual reality and bullying among children at familial high risk of schizophrenia or bipolar disorder compared with controls.

BACKGROUND: Children of parents with severe mental illness report bullying more often compared with controls. We hypothesized that deviations in attributional styles may explain the increased prevalence of bullying experiences. We aimed to assess real-time responses to standardized ambiguous social situations, bullying experiences by children, their primary caregivers, and teachers, and to investigate potential associations between attributional styles and bullying. METHOD: The study included 465 children aged 11-12, born to parents with schizophrenia, N =179, bipolar disorder, N = 105, or population-based controls, N = 181. Attributional style was evaluated using virtual reality environments depicting ambiguous social everyday situations. We created a tailored assessment since no suitable assessments were found. Bullying was assessed through self-reports and reports from primary caregivers and teachers. RESULTS: We observed no group differences in the attributional style of the children. Reports from children, primary caregivers, and teachers revealed that compared with controls, children born to parents with schizophrenia were more likely to perceive bullying victimization, with high consistency among reports. No associations were found between bullying reports and attributional style. CONCLUSIONS: Children of parents with schizophrenia consistently experienced more bullying, as reported by the children themselves, primary caregivers, and teachers. No differences in attributional style were found, indicating that attributional style did not explain the increased prevalence of bullying reports. While it cannot be ruled out that our virtual environments were insufficient to trigger a sense of social exclusion, the results suggest that the observed differences in reported bullying are genuine and not a result of the child's attributional style.

The bidirectional association between psychiatric disorders and sheltered homelessness.

BACKGROUND: Psychiatric disorders and homelessness are related, but temporal associations are unclear. We aimed to explore the overlap between hospital-based psychiatric disorders and sheltered homelessness. METHODS: This population-based cohort study was conducted using the Danish registers e.g., the Danish Homeless Register and the Danish National Patient Register. The study cohort included all individuals aged 15 years or older, living in Denmark at least one day during 2002-2021 (born 1984-2006). First psychiatric diagnosis was used to define psychiatric disorder and first homeless shelter contact to define homelessness. Adjusted incidence rate ratios (IRRs) and cumulative incidences were estimated. RESULTS: Among 1 530 325 individuals accounting for 16 787 562 person-years at risk aged 15-38 years, 11 433 (0.8%) had at least one homeless shelter contact. Among 1 406 410 individuals accounting for 14 131 060 person-years at risk, 210 730 had at least one psychiatric disorder. People with any psychiatric disorder had increased risk of sheltered homelessness relative to individuals with no psychiatric disorder [IRR 9.2, 95% confidence interval (CI) 8.8-9.6]. Ten years after first psychiatric disorder, 3.0% (95% CI 2.9-3.1) had at least one homeless shelter contact. Individuals experiencing homelessness had increased risk of any psychiatric disorder compared to individuals with no homeless shelter contact (IRR 7.0, 95% CI 6.7-7.4). Ten years after first homeless shelter contact, 47.1% (45.3-48.0) had received a hospital-based psychiatric diagnosis. CONCLUSION: Strong bidirectional associations between psychiatric disorders and homelessness were identified. Health and social care professionals should be aware of and address these high risks of accumulated psychiatric and social problems.

Predictors of transfer and prognosis after transfer from child and adolescent mental health services to adult mental health services-a Danish nationwide prospective register-based cohort study.

Onset of mental health disorder peaks during adolescence making continuity of care during this period of life crucial both to ensure a smooth treatment course and high quality of mental health services for adolescents. We aimed to examine which clinical and sociodemographic features predict transfer from child and adolescent mental health services to adult mental health services and if transfer is associated with prognosis. A Danish register study including all 16-17-year-olds with an outpatient contact in child and adolescent mental health services, who were discharged in the period of 1/1/06-10/05/15. Out of 27,170 Danish adolescents, 16% transferred to adult mental health services. Transfer was predicted by schizophrenia (OR 6.16; 95% CI 5.51-6.90) and personality disorders (OR 2.08; 95% CI 1.84-2.34), while hyperkinetic (OR 0.54; 95% CI 0.49-0.59) and pervasive developmental disorders (OR 0.42; 95% CI 0.31-0.58) decreased likelihood of transfer. Transfer was also substantially predicted by inpatient admission (OR 3.37; 95% CI 3.14-3.61) and psychiatric medication (OR 2.07; 95% CI 1.92-2.23). Transfer was associated with higher rates of inpatient admission to adult mental health services (IRR 5.83; 95% CI 4.37-7.77), more psychiatric emergency contacts (IRR 12.0; 95% CI 10.7-13.4), more convictions (IRR 1.40; 95% CI 1.23-1.59) and suicide attempts (IRR 5.70; 95% CI 4.72-6.90). Policy-makers and clinicians should push for improvements and open a discussion of how to ensure continuity of care for adolescents with psychiatric disorders.

Association of maternal and paternal personality disorders with risk of mental disorders in children: A nationwide, register-based cohort study of 1,406,965 children.

BACKGROUND: Knowledge of the association between parental personality disorders and mental disorders in children is limited. To examine the association between parental personality disorders and the risk of mental disorders in offspring. METHODS: We linked Danish health registers to create a cohort of children born from January 1, 1995, to December 31, 2016. Children were followed until their 18th birthday, diagnosis set, emigration, death, or December 31, 2016. Parental personality disorders according to the International Classification of Diseases (ICD) Eighth or 10th Revision. Poisson regression analyses were used to estimate the incidence risk ratio (IRR) and cumulative incidence of ICD 10th mental disorders in offspring (age 0-17). RESULTS: The study cohort included 1,406,965 children. For girls, maternal or paternal personality disorder (MPD/PPD) was associated with mental disorders: MPD girls (IRR, 2.74; 95% CI, 2.59-2.89) and PPD girls (IRR, 2.10; 95% CI, 1.94-2.27). Likewise, the risk was increased for both MPD boys (IRR, 2.44; 95% CI, 2.33-2.56) and PPD boys (IRR, 2.04; 95% CI, 1.91-2.18). For girls and boys combined, exposure to two parents with a personality disorder was associated with the highest risk (IRR, 3.69; 95% CI, 3.15-4.33). At age 18, the cumulative incidence of any mental disorder in children of one or two parents with a personality disorder was 34.1% (95% CI, 33.0-35.1), which was twice the cumulative incidence of mental disorders in nonexposed children (15.2% [95% CI, 15.1-15.3]). CONCLUSION: Children of parents with a personality disorder were at a 2 to 3.5 times higher risk of mental disorders compared with nonexposed offspring. Possible mechanisms of transmission of mental disorders from parent to child involve genetic, environmental, and gene-environment pathways. More research into these mechanisms and research into preventive interventions is warranted.

Multi-morbid patients with co-existing mental and physical illness.

This review investigates the mortality gap that exists between people with or people without mental illness. Poor physical health is the leading cause of excess mortality among people with mental illness. Mental disorders increase the risk of developing a broad range of physical diseases and the risk of death caused by somatic diseases is increased. Also, mental disorder is associated with less optimal treatment in the somatic healthcare system, which is also evident within a broad spectrum of somatic diseases. The role of structural factors such as the design of the healthcare system and stigma are developing.

Pubertal timing, sex hormone levels, and associations between early life adversity and accelerated development amongst 11-year-old children of parents with schizophrenia or bipolar disorder and controls: The Danish high risk and Resilience study via 11.

Background: Children of parents with severe mental illness have several known risk factors for altered pubertal timing. Pubertal timing is important for children's physical and emotional development. We aimed to examine pubertal timing and associations between pubertal timing, early life adversity and child problem behavior including psychiatric diagnoses among children of parents with schizophrenia or bipolar disorder and controls. Methods: Self-reported Tanner stage (mean age 11.9, range 10.87-12.67), sex hormone levels, home environment, placement out of home, and problem behavior including psychiatric diagnoses of children at familial high-risk (FHR) of schizophrenia (FHR-SZ), bipolar disorder (FHR-BP) and population-based controls (PBC) were assessed. Results: A total of 465 children participated in the study (Tanner assessment N = 417, sex hormones N = 293). Assessed with self-reported Tanner, no difference in pubertal timing was found between groups (p = 0.09). Hormone levels did not differ between groups except for inhibin B (mean (SD) = 55.86 (29.13) pg/mL for FHR-SZ girls vs 84.98 (47.98) pg/mL) for PBC girls (p < 0.001)) and for follicle stimulating hormone (FSH) (mean (SD) = 5.82 (1.45) U/L for FHR-BP girls vs 4.54 (1.68) U/L for PBC girls (p < 0.001)). FHR children who were placed out of home (17 children, 3.8% of participants) had higher Tanner stages than those living at home (p < 0.001). Timing was not associated with level of problem behavior or psychiatric diagnoses. Conclusions: FHR children did not differ from controls in pubertal timing. Early life adversity assessed as placement out of home may be associated with accelerated pubertal timing among children of parents with schizophrenia or bipolar disorder.

20-year trajectories of positive and negative symptoms after the first psychotic episode in patients with schizophrenia spectrum disorder: results from the OPUS study.

This study aimed to identify the 20-year trajectories of positive and negative symptoms after the first psychotic episode in a sample of patients with an ICD-10 diagnosis of schizophrenia spectrum disorder, and to investigate the baseline characteristics and long-term outcomes associated with these trajectories. A total of 373 participants in the OPUS trial were included in the study. Symptoms were assessed at baseline and after 1, 2, 5, 10 and 20 years using the Scales for the Assessment of Positive and Negative Symptoms. We used latent class growth mixture modelling to identify trajectories, and multinominal regression analyses to investigate predictors of membership to identified trajectories. Five trajectories of positive symptoms were identified: early continuous remission (50.9% of the sample), stable improvement (18.0%), intermittent symptoms (10.2%), relapse with moderate symptoms (11.9%), and continuous severe symptoms (9.1%). Substance use disorder (odds ratio, OR: 2.83, 95% CI: 1.09-7.38, p=0.033), longer duration of untreated psychosis (OR: 1.02, 95% CI: 1.00-1.03, p=0.007) and higher level of negative symptoms (OR: 1.60, 95% CI: 1.07-2.39, p=0.021) were predictors of the relapse with moderate symptoms trajectory, while only longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00-1.02, p=0.030) predicted membership to the continuous severe symptoms trajectory. Two trajectories of negative symptoms were identified: symptom remission (51.0%) and continuous symptoms (49.0%). Predictors of the continuous symptoms trajectory were male sex (OR: 3.03, 95% CI: 1.48-6.02, p=0.002) and longer duration of untreated psychosis (OR: 1.01, 95% CI: 1.00-1.02, p=0.034). Trajectories displaying continuous positive and negative symptoms were linked to lower neurocognition, as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) (z-score: -0.78, CI: -1.39 to -0.17, for continuous positive symptoms; z-score: -0.33, CI: -0.53 to -0.13, for continuous negative symptoms). The same trajectories were also linked to higher use of antipsychotic medication at 20-year follow-up (continuous positive symptoms: 78%; continuous negative symptoms: 67%). These findings suggest that the majority of patients with first-episode schizophrenia spectrum disorder have a trajectory with early stable remission of positive symptoms. Long duration of untreated psychosis and comorbid substance abuse are modifiable predictors of poor trajectories for positive symptoms in these patients. In about half of patients, negative symptoms do not improve over time. These symptoms, in addition to being associated with poor social and neurocognitive functioning, may prevent patients from seeking help.

Development of social functioning in preadolescent children at familial high-risk of schizophrenia or bipolar disorder - a 4-year follow-up study from age 7 to 11.

Social functioning is a major indicator of psychosis risk and evidence is lacking regarding social functioning development during preadolescence in children at familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP). We aimed to investigate development of social functioning from age 7 to 11 in children at FHR-SZ or FHR-BP compared with population-based controls. At 4-year follow-up, 179 children at FHR-SZ (mean age 12.0 y, SD 0.3), 105 children at FHR-BP (mean age 11.9 y, SD 0.2), and 181 controls (mean age 11.9 y, SD 0.2) participated. We used the Vineland-II to measure social functioning. Development of social functioning was non-significantly different across groups on the Socialization Composite score as well as the subscales Interpersonal Relations, Play and Leisure, and Coping Skills. At 4-year follow-up, children at FHR-SZ demonstrated impaired social functioning, whereas children at FHR-BP displayed social functioning comparable to controls except from impaired coping skills. From age 7 to 11, the maturational pace of social functioning in children at FHR-SZ and FHR-BP is parallel to that of controls. Children at FHR-SZ show stable social functioning deficits, whereas children at FHR-BP show normal social functioning except from emergence of discretely impaired coping skills at age 11.