Maiju Pankakoski

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 childrens 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.

An association between high birth weight and schizophrenia in a Finnish schizophrenia family study sample

Longitudinal cohort studies have implicated an association between both low and high birth weight and schizophrenia. It has been suggested that schizophrenia associated genes could augment an individuals susceptibility to adverse prenatal and perinatal environmental events. We investigated the association between birth weight and schizophrenia in a large Finnish schizophrenia family study sample. We utilized the birth weight data of 1051 offspring from 315 Finnish families with at least one offspring with a diagnosis of schizophrenia. We used a multivariate COX frailty model to analyze the effect of birth weight on the risk of developing schizophrenia within the families. Using information from the Medication Reimbursement Register and patient interviews, we further investigated the association of maternal type 2 diabetes and schizophrenia risk among offspring. High birth weight (>4000g) was associated with a 1.68-fold increase in schizophrenia susceptibility. Maternal diabetes at the time of data collection, a proxy for gestational diabetes, was associated with a 1.66-fold increase in the risk of developing schizophrenia among offspring. Our results corroborate recent findings showing an association between high birth weight and schizophrenia. Our results also point to a potential birth-weight independent association between maternal type 2 diabetes and schizophrenia among offspring.

Internet-based CBT intervention for gamblers in Finland: experiences from the field.

From September 2007 to May 2011 a total of 471 participants (325 males and 146 females) signed up for an 8-week Internet-based cognitive behavioral therapy offered for gamblers in Finland. Sixty-four percent of the participants were pathological gamblers (PGs) (NODS 5> points), 14% were problem gamblers (NODS 3-4 points) and 10% were at risk of gambling problems (NODS 1-2 points). Two hundred and twenty four participants completed the treatment and after the treatment period significant changes were found in the following variables: gambling related problems (NODS), gambling urge, impaired control of gambling, alcohol consumption (AUDIT-C), social consequences, gambling-related cognitive erroneous thoughts and depression (MARD-S). In this sample co-morbid alcohol consumption was stronger among males. The main finding of this study was that the onset age of gambling was associated with a greater amount of gambling-related cognitive erroneous thoughts.

A Randomised, Double-Blind, Placebo-Controlled Trial of As-Needed Naltrexone in the Treatment of Pathological Gambling.

Background/Aims: Effective treatment strategies are needed for the treatment of pathological gambling (PG). The efficacy of as-needed naltrexone was assessed in a single-centre, randomised, double-blind, placebo-controlled trial. Methods: The participants (n = 101) received either as-needed placebo or naltrexone (50 mg) and psychosocial support for 20 weeks. The primary outcome measure was the severity of PG assessed by the Yale-Brown Obsessive Compulsive Scale adapted for PG (PG-YBOCS). Secondary gambling-related outcome measures included thoughts/urges and behaviour subscales of PG-YBOCS as well as the highest daily expenditure and gambling frequency. In addition, RAND-36 scales of emotional well-being and social functioning were used as outcomes. The results were analysed using the intention-to-treat principle and linear random effects modelling. Results: No significant treatment group differences were found. In an exploratory analysis, emotional well-being increased in a subgroup of participants with AA genotype of opioid receptor, mu 1 (OPRM1) A118G polymorphism (p = 0.02). Conclusion: Overall, the as-needed naltrexone may not provide substantial additional benefit for PG patients receiving psychosocial support. Replication by larger scale studies is warranted to further evaluate naltrexone administration schedules for the treatment of PG and the role of OPRM1.

Confidence in the future, health-related behaviour and psychological distress: results from a web-based cross-sectional study of 101 257 Finns

Objectives To investigate the role of socioeconomic status and psychological stress to potential associations between confidence in the future and a wide range of health-related behaviours. Design Web-based cross-sectional study including an ‘Electronic Health Check’ at the Finnish Happiness-Flourishing Study website linked to a TV programme on happiness and depression. Setting The Finnish population with access to the internet. Participants 101 257 Finns aged 18 and above (21 365 men; 79 892 women). Participants who were under the age of 18 and who did not provide information about their gender were excluded. Primary outcome measures As planned, we assessed smoking, weekly alcohol consumption and binge drinking, daily intake of fruits and vegetables and regular exercise. Results Compared with participants with low confidence in the future, those with high confidence were less likely to be daily smokers (men OR 0.58, 95% CI 0.52 to 0.65; women 0.57, 95% CI 0.53 to 0.61) and binge drinkers (men 0.57; 0.52 to 0.63; women 0.54; 0.50 to 0.57). Participants with high confidence in the future were more likely to exercise regularly (men OR 2.82, 95% CI 2.55 to 3.13; women 2.57, 95% CI 2.44 to 2.71) and consume vegetables (men OR 2.48, 95% CI 2.25 to 2.74; women 2.13, 95% CI 2.03 to 2.24) and fruits (men OR 2.09, 95% CI 1.86 to 2.35; women 1.83, 95% CI 1.74 to 1.93) daily. Adjustment for current psychological distress and satisfaction for income attenuated the results. Conclusions Having confidence in the future is strongly associated with a healthy lifestyle, as assessed by a healthy diet, physical exercise and substance abuse. Health-related interventions may benefit from tailoring interventions according to the target populations level of confidence in the future as well as their level of psychological distress.

An interaction between NDE1 and high birth weight increases schizophrenia susceptibility

Pre- and perinatal environmental factors have been shown to increase schizophrenia risk particularly when combined with genetic liability. The investigation of specific gene environment interactions in the etiology of psychiatric disorders has gained momentum. We used multivariate GEE regression modeling to investigate the interaction between genes of the DISC1 pathway and birth weight, in relation to schizophrenia susceptibility in a Finnish schizophrenia family cohort. The study sample consisted of 457 subjects with both genotype and birth weight information. Gender and place of birth were adjusted for in the models. We found a significant interaction between birth weight and two NDE1 markers in relation to increased schizophrenia risk: a four SNP haplotype spanning NDE1 (b=1.26, SE=0.5, p=0.012) and one of its constituent SNPs rs4781678 (b=1.33, SE=0.51, p=0.010). Specifically, high birth weight (>4000g) was associated with increased schizophrenia risk among subjects homozygous for the previously identified risk alleles. The study was based on a family study sample with high genetic loading for schizophrenia and thus our findings cannot directly be generalized as representing the general population. Our results suggest that the functions mediated by NDE1 during the early stages of neurodevelopment are susceptible to the additional disruptive effects of pre- and perinatal environmental factors associated with high birth weight, augmenting schizophrenia susceptibility.

An association between both low and high birth weight and increased disorganized and negative symptom severity in schizophrenia and other psychoses

Longitudinal cohort studies have implicated an association between both low and high birth weight and increased schizophrenia risk. In this study, we investigated the effect of birth weight on the symptom severity of psychotic disorders including schizophrenia in a Finnish schizophrenia family study sample. We used a multivariate GEE (General Estimating Equation) regression model to investigate the association of birth weight and symptom severity in 282 subjects with a primary psychotic disorder, 178 of whom had a diagnosis of schizophrenia. The Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS) were used as a measure of symptom severity. Sex, place of birth and year of birth were adjusted for in the model. Both low and high birth weight were associated with more severe symptoms with respect to bizarre behaviour, affective flattening and attentional impairment. In addition, low birth weight was associated with more severe symptoms with respect to positive formal thought. Our findings suggest that both low and high birth weight can influence the symptom severity of psychotic disorders. Our results implicate an association between both low and high birth weight and disorganized and negative symptoms.

Sleep complaints in adolescent depression: one year naturalistic follow-up study

BackgroundSleep complaints are highly prevalent in adolescents suffering from major depressive disorder (MDD). The aims of this study were to describe the longitudinal course of sleep complaints, and to assess the association between sleep complaints and clinical outcome in a sample of adolescents with MDD during naturalistic follow-up.MethodsA sample of adolescent outpatients (n = 166; age 13-19 years, 17.5% boys) diagnosed with MDD was followed-up during one year in naturalistic settings. Sleep symptoms and psychiatric symptoms were assessed with interviews and self-report questionnaires.ResultsAll sleep complaints were less frequent at one-year follow-up compared to baseline. Baseline sleep complaints did not adversely affect clinical outcome at one-year follow-up: severity of the sleep complaints at baseline was associated with a steeper improvement of depressive and anxiety symptoms, suicidality/self-harm symptoms, and overall psychosocial functioning over time.ConclusionsOur results suggest that sleep disturbances at baseline do not necessarily lead to poorer clinical outcome during follow-up. Larger longitudinal studies combining both subjective and objective measures of sleep in depressed adolescents are needed to clarify the link between sleep and depression further.

The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484

Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the ‘DISC1 network’. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 × 10−8), located on a non-coding exon of NDE1. Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.

Together at school intervention programme. A pilot study on the feasibility and perceived benefits of a programme focusing on improving socio-emotional skills among schoolchildren in Finland

Abstract The aim of the Together at School Intervention Programme developed for the Finnish school system was to improve socio-emotional skills and prevent psychosocial problems among children (7−12 years). The aim of this pilot study was to evaluate the feasibility, safety and perceived benefits of the programme in order to justify its large-scale implementation for a randomized controlled study. Altogether, 23 classrooms from Grades 1–6 (N = 549, n = 451 children) in four schools participated in the study. Informants were teachers (n = 23), head masters (n = 4), children (n = 451) and their parents. Data were collected by questionnaires at three time points. The different tools assessed were considered to be beneficial for the children by 92−100% of the teachers, and pleasant to participate in by 73−89% of the children. During the follow-up, emotional symptoms reduced significantly among boys. Bullying behaviour was significantly reduced according to both teachers and children. The findings of this pilot study were encouraging.