Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial.

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.

Obstetric complications as risk factors for schizophrenia spectrum psychoses in offspring of mothers with psychotic disorder.

BACKGROUND: Obstetric complications have predicted future development of schizophrenia in previous studies, but they are also more common in mothers with schizophrenia. The aims of this study were to compare the occurrence of obstetric complications in children of mothers with schizophrenia spectrum psychoses and control children, and to investigate whether obstetric complications predicted children's psychiatric morbidity. METHOD: The Helsinki High-Risk (HR) Study monitors females born between 1916 and 1948 and treated for schizophrenia spectrum disorders in Helsinki psychiatric hospitals, their offspring born between 1941 and 1977, and controls. We examined information on obstetric complications and neonatal health of 271 HR and 242 control offspring. We compared the frequency of obstetric complications and neonatal health problems in the HR group vs controls and in HR children who later developed psychotic disorders vs healthy HR children. A Cox regression model was used to assess whether problems in pregnancy or delivery predicted psychiatric morbidity within the HR group. RESULTS: Few differences between HR and control offspring were found in obstetric complications. Within the HR group, infections (hazard rate ratio [HRR] 3.73, 95% CI 1.27-11.01), hypertension during pregnancy (HRR 4.10, 95% CI 1.15-14.58), and placental abnormalities (HRR 4.09, 95% CI 1.59-10.49) were associated with elevated risk of schizophrenia spectrum psychoses. CONCLUSIONS: Common medical problems during pregnancy were associated with increased risk of schizophrenia spectrum psychoses in offspring of mothers with schizophrenia spectrum psychoses. These results underline the role of the prenatal period in the development of schizophrenia and the importance of careful monitoring of pregnancies of mothers with psychotic disorder.

Childhood growth and future development of psychotic disorder among Helsinki high-risk children.

BACKGROUND: The Helsinki High-Risk (HR) Study is a follow-up study of offspring (born between 1960 and 1964) of all females treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975, and controls. AIM: To compare childhood growth among HR and control children, and to determine if any patterns in childhood growth predict later development of psychotic disorders within the HR group. METHODS: We accessed growth information from childhood health cards, which we obtained for 114 HR and 53 control offspring. The growth of HR children was compared with that of control children. Within the HR group, we investigated whether any association existed between childhood growth patterns and morbidity from psychotic disorders using logistic regression models. RESULTS: The HR girls were shorter than controls at birth (p=0.030), but this disparity vanished by age 7. In contrast, HR boys were only slightly shorter at birth than controls, but the height difference increased with age, being statistically significant at 10 years (p=0.020). Among HR children, the combination of being in the lowest tertile for ponderal index at birth but in the highest tertile for BMI at 7 years predicted later development of schizophrenia (OR 22.8, 95% CI 2.0, >100, p=0.040). CONCLUSIONS: Catch-up growth increases the risk of schizophrenia among offspring of mothers with psychotic disorder. Whether this is an independent risk factor or merely a reflection of some other risk factors needs further research.

Childhood predictors of future psychiatric morbidity in offspring of mothers with psychotic disorder: results from the Helsinki High-Risk Study.

BACKGROUND: The Helsinki High-Risk Study monitors women treated for schizophrenia-spectrum disorders in Helsinki mental hospitals before 1975, their offspring, and controls. AIMS: To compare the development of high-risk and control group children, and investigate which factors predicted future psychiatric disorders. METHOD: We examined information from childhood and school health record cards of 159 high-risk and 99 control group offspring. Logistic regression was used to assess whether developmental abnormalities predicted later mental disorders. RESULTS: Compared with controls, children in the high-risk group had more emotional symptoms before school age, attentional problems and social inhibition at school age, and neurological soft signs throughout. In this group pre-school social adjustment problems (OR=9.7, 95% CI 1.8-51.8) or severe neurological symptoms (Fisher's test, P=0.006) predicted future schizophrenia-spectrum disorder. Social adjustment problems and emotional symptoms during school age predicted future non-psychotic psychiatric disorders. CONCLUSIONS: Our study supports the validity of neurological, emotional, social and behavioural markers as vulnerability indicators of psychotic and other mental disorders, particularly among children genetically at high risk of psychosis.

Family structure and risk factors for schizophrenia: case-sibling study.

BACKGROUND: Several family structure-related factors, such as birth order, family size, parental age, and age differences to siblings, have been suggested as risk factors for schizophrenia. We examined how family-structure-related variables modified the risk of schizophrenia in Finnish families with at least one child with schizophrenia born from 1950 to 1976. METHODS: We used case-sibling design, a variant of the matched case-control design in the analysis. Patients hospitalized for schizophrenia between 1969 and 1996 were identified from the Finnish Hospital Discharge Register, and their families from the Population Register Center. Only families with at least two children (7914 sibships and 21059 individuals) were included in the analysis. Conditional logistic regression with sex, birth cohort, maternal schizophrenia status, and several family-related variables as explanatory variables was used in the case-sibling design. The effect of variables with the same value in each sibship was analyzed using ordinary logistic regression. RESULTS: Having a sibling who was less than five years older (OR 1.46, 95% CI 1.29-1.66), or being the firstborn (first born vs. second born 1.62, 1.87-1.4) predicted an elevated risk, but having siblings who were more than ten years older predicted a lower risk (0.66, 0.56-0.79). CONCLUSIONS: Several family-structure-related variables were identified as risk factors for schizophrenia. The underlying causative mechanisms are likely to be variable.

Cumulative incidence of mental disorders among offspring of mothers with psychotic disorder. Results from the Helsinki High-Risk Study.

BACKGROUND: The Helsinki High-Risk Study follows up all women born between 1916 and 1948 and treated for schizophrenia-spectrum disorders in psychiatric hospitals in Helsinki, their offspring born between 1960 and 1964, and controls. AIMS: To determine the cumulative incidence of adulthood Axis I disorders among offspring. METHOD: Using all hospital and out-patient treatment records we rediagnosed parents and offspring according to DSM-IV-TR criteria. Offspring were grouped by mother's diagnosis (schizophrenia n=104, schizoaffective disorder n=20, other schizophrenia-spectrum disorder n=30, and affective disorder n=25) and compared with a control group (n=176). The cumulative incidences of Axis I disorders among offspring were calculated. RESULTS: The cumulative incidences of any psychotic disorder were 13.5%, 10.0%, 10.0%, 4.0% and 1.1% among offspring of mothers with schizophrenia, schizo-affective disorder, other schizophrenia-spectrum disorders, affective disorders and controls, respectively. The corresponding figures for schizophrenia were 6.7%, 5.0%, 6.7%, 0% and 0.6%, and for any mental disorder 23.1%, 20.0%, 20.0%, 12.0% and 6.9%. CONCLUSIONS: Offspring of mothers with a psychotic disorder have heightened risk of developing a wide range of severe mental disorders.

Do maternal psychotic symptoms predict offspring's psychotic disorder? Findings from the Helsinki High-Risk Study.

The Helsinki High-Risk (HR) Study is a follow-up study of 179 offspring born to mothers with DSM-IV-TR diagnoses of schizophrenia, schizoaffective disorder, other schizophrenia spectrum disorders, and affective psychoses. Mothers comprised all female patients born between 1916 and 1948 who had been treated with hospital diagnoses of schizophrenia, schizophreniform, or schizoaffective psychoses in any mental hospital in the city of Helsinki up to 1974, and who had given birth in Helsinki between 1960 and 1964. In this report we conducted a principal factor analysis of maternal symptoms using 12 items of the Major Symptoms of Schizophrenia Scale (MSSS), the global ratings of anhedonia-asociality and avolition-apathy from the Scale for the Assessment of Negative Symptoms (SANS), and the global rating of bizarre behavior from the Scale for the Assessment of Positive symptoms (SAPS), and examined whether the factor scores predicted the offspring's morbidity from psychotic disorders. We found a four-factor solution (negative, positive, catatonic, and affective symptom factors). High maternal positive symptom factor score significantly predicted decreased morbidity from schizophrenia among offspring (P=0.0098). Our result suggests that maternal positive symptoms are less harmful to the child than other maternal psychotic symptoms, and supports the view that positive symptoms are non-specific symptoms of psychosis rather than core features of schizophrenia.

No association between season of birth of patients with schizophrenia and risk of schizophrenia among their siblings.

Previous studies on the relationship between the season of birth of patients with schizophrenia and the risk of schizophrenia among their siblings have yielded contradictory results. We investigated whether proband's month of birth affects siblings' risk of developing schizophrenia. We used the Finnish Hospital Discharge Register to identify all patients born in Finland from 1950 to 1976 who had been hospitalized because of schizophrenia at least once between 1969 and 1995. Their siblings were identified from the National Population Register, and data on siblings were linked to the Hospital Discharge Register to obtain information on any hospitalizations. We used logistic regression to investigate a sibling's probability of developing schizophrenia, defining the proband initially as the first sibling in calendar time to develop schizophrenia, then as the affected sibling with lowest onset age. Within-family dependence was taken into account by using robust standard error estimates. Neither models found any association between proband's month of birth and siblings' odds of developing schizophrenia. Our results support those previous studies that found no association between proband's month of birth and family history of schizophrenia, and suggest that the winter-spring excess of births among patients with schizophrenia is not caused by any genetic or environmental risk factor that operates independently of other risk factors.

Randomized trial of the efficacy of bright-light exposure and aerobic exercise on depressive symptoms and serum lipids.

BACKGROUND: Season-related subsyndromal depressive symptoms during winter are common among populations at high latitudes. Both physical exercise and exposure to bright light can relieve the fatigue and downturn of mood associated with the shortening length of day. Serum cholesterol level may be related to changes in mood, but the evidence is contradictory. Our objective was to compare the effect of aerobic exercise with or without bright-light exposure on health-related quality of life, mood, and serum lipids in a sample of relatively healthy adult subjects. METHOD: A randomized controlled trial was conducted with subjects allocated to group aerobics training in a gym with bright light (2500-4000 lux) (N = 40) or normal illumination (N = 42) or to relaxation/stretching sessions in bright light as a control group (N = 42) twice a week for a period of 8 weeks. Changes in mood were recorded using questionnaires at the beginning of the study, at weeks 4 and 8. and at follow-up 4 months after the study. A blood sample was drawn before and after the 8-week intervention to measure the concentrations of serum lipids. RESULTS: Ninety-eight subjects completed the 8-week study. Both exercise and bright light effectively relieved depressive symptoms. Bright light reduced atypical depressive symptoms more than exercise (p = .03), based on the atypical symptoms subscore of the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version Self-Rating Format. There were no significant differences between the study groups in the changes in serum lipid levels. CONCLUSION: Bright light administered twice a week, alone or combined with physical exercise, seems to be a useful intervention for relieving seasonal mood slumps.