Jouko Miettunen

Obesity and depression: results from the longitudinal Northern Finland 1966 Birth Cohort Study

Objective:To examine the association between body size and depression in a longitudinal setting and to explore the connection between obesity and depression in young adults at the age of 31 years.Design:This study forms part of the longitudinal Northern Finland 1966 Birth Cohort Study (N=12 058). The follow-up studies were performed at 14 and 31 years. Data were collected by postal inquiry at 14 years and by postal inquiry and clinical examination at 31 years.Subjects:A total of 8451 subjects (4029 men and 4422 women) who gave a written informed consent and information on depression by three depression indicators at 31 years.Measurements:Body size at 14 (body mass index (BMI) and 31 (BMI and waist-to-hip ratio (WHR)) years and depression at 31 years by three different ways: depressive symptoms by the HSCL-25-depression questionnaire (HSCL-25), the use of antidepressants and self-reported physician-diagnosed depression.Results:Obesity at 14 years associated with depressive symptoms at 31 years; among male subjects using the cutoff point 2.01 in the HSCL-25 (adjusted odds ratio (OR) 1.97, 95% CI 1.06–3.68), among female subjects using the cutoff point 1.75 (adjusted OR 1.64, 95% CI 1.16–2.32). Female subjects who were obese both at baseline and follow-up had depressive symptoms relatively commonly (adjusted OR 1.40, 95% CI 1.06–1.85 at cutoff point 1.75); a similar association was not found among male subjects. The proportion of those who used antidepressants was 2.17-fold higher among female subjects who had gained weight compared to female subjects who had stayed normal-weighted (adjusted OR 2.17, 95% CI 1.28–3.68). In the cross-sectional analyses male subjects with abdominal obesity (WHR ⩾85th percentile) had a 1.76-fold risk of depressive symptoms using the cutoff 2.01 in the HSCL-25 (adjusted OR 1.76, 95% CI 1.08–2.88). Abdominally obese male subjects had a 2.07-fold risk for physician-diagnosed depression (adjusted OR 2.07, 95% CI 1.23–3.47) and the proportion of those who used antidepressants was 2.63-fold higher among obese male subjects than among male subjects without abdominal obesity (adjusted OR 2.63, 95% CI 1.33–5.21). Abdominal obesity did not associate with depression in female subjects.Conclusion:Obesity in adolescence may be associated with later depression in young adulthood, abdominal obesity among male subjects may be closely related to concomitant depression, and being overweight/obese both in adolescence and adulthood may be a risk for depression among female subjects.

A Systematic Review and Meta-Analysis of Recovery in Schizophrenia

OBJECTIVE Our primary aims were (a) to identify the proportion of individuals with schizophrenia and related psychoses who met recovery criteria based on both clinical and social domains and (b) to examine if recovery was associated with factors such as gender, economic index of sites, and selected design features of the study. We also examined if the proportions who met our definition of recovery had changed over time. METHOD A comprehensive search strategy was used to identify potential studies, and data were extracted for those that met inclusion criteria. The proportion who met our recovery criteria (improvements in both clinical and social domains and evidence that improvements in at least 1 of these 2 domains had persisted for at least 2 years) was extracted from each study. Meta-regression techniques were used to explore the association between the recovery proportions and the selected variables. RESULTS We identified 50 studies with data suitable for inclusion. The median proportion (25%-75% quantiles) who met our recovery criteria was 13.5% (8.1%-20.0%). Studies from sites in countries with poorer economic status had higher recovery proportions. However, there were no statistically significant differences when the estimates were stratified according to sex, midpoint of intake period, strictness of the diagnostic criteria, duration of follow-up, or other design features. CONCLUSIONS Based on the best available data, approximately, 1 in 7 individuals with schizophrenia met our criteria for recovery. Despite major changes in treatment options in recent decades, the proportion of recovered cases has not increased.

5-HTTLPR genotype and anxiety-related personality traits: a meta-analysis and new data.

We investigated the strength of evidence for association of the 5‐HTTLPR polymorphism and the personality trait of Harm Avoidance. We used new primary data from a large sample of adults drawn from the Finnish population. We also applied meta‐analytic techniques to synthesize existing published data. The large number of studies of the 5‐HTTLPR polymorphism allowed us to apply a formal test of publication bias, as well as formally investigate the impact of potential moderating factors such as measurement instrument. Univariate ANOVA of primary data (n = 3,872), with 5‐HTTLPR genotype as a between‐groups factor, indicated no evidence of association with Harm Avoidance (P = 0.99). Meta‐analysis indicated no evidence of significant association of 5‐HTTLPR with Harm Avoidance (d = 0.02, P = 0.37), or EPQ Neuroticism (d = 0.01, P = 0.71), although there was evidence of association with NEO Neuroticism (d = 0.18, P < 0.001). Our analyses indicate that the 5‐HTTLPR variant is not associated with Harm Avoidance. Together with our previous analyses of a large sample of participants with extreme Neuroticism scores (defined by the EPQ), we have data that excludes a meaningful genetic effect of the 5‐HTTLPR on two measures of anxiety‐related personality traits. There remains the possibility that the variant influences the NEO personality questionnaire measure of Neuroticism. However, a large, well‐powered primary study is required to test this hypothesis directly and adequately.

Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts

Objectives:We examine whether pregnancy weight (pre-pregnancy body mass index (BMI) and/or weight gain) is related to core symptoms of attention deficit hyperactivity disorder (ADHD) in school-age offspring.Design:Follow-up of prospective pregnancy cohorts from Sweden, Denmark and Finland within the Nordic Network on ADHD.Methods:Maternal pregnancy and delivery data were collected prospectively. Teachers rated inattention and hyperactivity symptoms in offspring. High scores were defined as at least one core symptom rated as ‘severe’ and two as ‘present’ (approximately 10% of children scored in this range). Logistic regression and latent class analyses were used to examine maternal pregnancy weight in relation to childrens ADHD core symptoms.Results:Teacher rated 12 556 school-aged children. Gestational weight gain outside of the Institute of Medicine guidelines was not related to ADHD symptoms (below recommendations: odds ratio (OR): 0.96; 95% confidence interval (CI): 0.81, 1.14; above recommendations: OR: 0.98; 95% CI: 0.82, 1.16). To examine various patterns of pre-pregnancy BMI and weight gain, we used latent class analysis and found significant associations between classes that included pre-pregnancy overweight or obesity and a high ADHD symptom score in offspring, ORs ranged between 1.37 (95% CI: 1.07, 1.75) and 1.89 (95% CI: 1.13, 3.15) adjusted for gestational age, birth weight, weight gain, pregnancy smoking, maternal age, maternal education, child gender, family structure and cohort country of origin. Children of women who were both overweight and gained a large amount of weight during gestation had a 2-fold risk of ADHD symptoms (OR: 2.10, 95% CI: 1.19, 3.72) compared to normal-weight women.Conclusions:We show for the first time that pre-pregnancy BMI is associated with ADHD symptoms in children. Our results are of public health significance if the associations are causal and will then add ADHD symptoms in offspring to the list of deleterious outcomes related to overweight and obesity in the prenatal period.

Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis

BACKGROUND Duration of untreated psychosis (DUP) is one of the few potentially modifiable predictors of outcomes of schizophrenia. Long DUP as a predictor of poor short-term outcome has been addressed in previous meta-analyses, but the long-term effects of DUP remain unclear. AIMS To analyse the associations between DUP and long-term outcomes of schizophrenia. METHOD A systematic literature search was performed using seven electronic databases and manual searches. Random effects weighted meta-analysis with correlation coefficients was used to pool the results. RESULTS We identified 3493 unique publications, from which 33 samples met our predefined selection criteria. Long DUP correlated statistically significantly with poor general symptomatic outcome, more severe positive and negative symptoms, lesser likelihood of remission and poor social functioning and global outcome (correlations 0.13-0.18). Long DUP was not associated with employment, quality of life or hospital treatment. CONCLUSIONS The small but mostly consistent correlation between long DUP and poor outcome indicates that early intervention in psychosis may have at least subtle positive effects on the long-term course of illness.

Co-occurrence of Metabolic Syndrome With Depression and Anxiety in Young Adults: The Northern Finland 1966 Birth Cohort Study

Objective: Only a few studies have dealt with the association of metabolic syndrome with depression and anxiety. We studied whether metabolic syndrome and its components are associated with depressive and anxiety symptoms in a young adult population cohort. Methods: This study forms part of the Northern Finland 1966 Birth Cohort Study. The study sample consists of 5,698 members of the cohort who participated in the field study in 1997 to 1998. Metabolic syndrome was defined according to the five criteria of the National Cholesterol Education Program. Depressive and anxiety symptoms were defined by the Hopkins Symptom Checklist-25 questionnaire. Results: Metabolic syndrome was not associated with depression or anxiety. The correlations between the components of the metabolic syndrome and psychological distress as continuous measures were low. High waist circumference (>102 cm in males and >88 cm in females) associated with depression (odds ratio, 1.30; 95% confidence interval, 1.05–1.61), but this association vanished when adjusted for gender, smoking, alcohol consumption, marital status, level of education, and physical activity. Conclusion: No clear association was found between the metabolic syndrome and psychological distress. ATP III = Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III); CI = confidence interval; HSCL-25 = Hopkins Symptom Checklist-25, OR = odds ratio; HDL = high-density lipoprotein.

Psychometric properties of the Finnish 20-item Toronto Alexithymia Scale

The aim of this study was to examine the factor structure and the validity of the Finnish version of the 20-item Toronto Alexithymia Scale (TAS-20). As part of the Northern Finland 1966 Birth Cohort Project, the TAS-20 was presented to a sample of 5034 31-year old persons. A confirmatory factor analysis showed that the three-factor model, earlier established with the original TAS-20, was in agreement with the Finnish version of the scale. Three criteria of goodness-of-fit met the standards for adequacy of fit. For the total scale, internal reliability (Cronbachs alpha) was 0.83 and for the three subscales (factors 1, 2, and 3) it was 0.81, 0.77, and 0.66, respectively. Two- and one-factor models for TAS-20 were also examined, but the other models did not perform as well as the three-factor model. The factor model also worked well with a sample of 516 students with a mean age of 24.8 years. In conclusion, the TAS-20 scale is useful in the Finnish version, too.

Reasons for the diagnostic discordance between clinicians and researchers in schizophrenia in the Northern Finland 1966 Birth Cohort

Abstract.Background: The diagnosis of schizophrenia by clinicians is not always accurate in terms of operational diagnostic criteria despite the fact that these diagnoses form the basis of case registers and routine statistics. This poses a challenge to psychiatric research. We studied the reasons for diagnostic discordance between clinicians and researchers. Methods: The Northern Finland 1966 Birth Cohort (n = 11,017) was followed from mid-gestation to the end of the 31st year. Psychiatric outcome was ascertained through linkage to the national hospital discharge register containing clinical diagnoses made by the attending physician. The hospital notes of all subjects admitted to hospital during the period 1982–1997 due to psychiatric disorder were reviewed and 475 research, operational DSM-III-R diagnoses were formulated. Results: Ninety-six cases met operational criteria for schizophrenia. Fifty-five (57 %) had concordant diagnoses: both the clinical and research diagnoses were schizophrenia. Forty-one (43 %) had discordant diagnoses: the clinical diagnosis was other than schizophrenia (mainly schizophreniform or other psychosis). Discordant cases were more likely to be older at onset, experience a shorter treatment duration, fewer treatment episodes, and to have a comorbid diagnosis mental retardation. Conclusions: Clinicians do not make the diagnosis of schizophrenia as often as the application of operational criteria would suggest they should. The discordance between clinical diagnosis and the research, operational diagnosis is especially likely in cases having late onset and few contacts to psychiatric hospital.

Meta-analysis of Paternal Age and Schizophrenia Risk in Male Versus Female Offspring

INTRODUCTION Advanced paternal age (APA) is a reported risk factor for schizophrenia in the offspring. We performed a meta-analysis of this association, considering the effect of gender and study design. METHODS We identified articles by searching Pub Med, PsychInfo, ISI, and EMBASE, and the reference lists of identified studies. Previously unpublished data from the Northern Finland 1966 Birth Cohort (NFBC 1966) study were also included. RESULTS There were 6 cohort studies and 6 case-control studies that met the inclusion criteria. In both study designs, there was a significant increase in risk of schizophrenia in the offspring of older fathers (≥30) compared to a reference paternal age of 25-29, with no gender differences. The relative risk (RR) in the oldest fathers (≥50) was 1.66 [95% confidence interval (95% CI): 1.46-1.89, P < 0.01]. A significant increase in risk was also found for younger fathers (<25) in males (RR = 1.08, 95% CI: 1.02-1.14, P = 0.01) but not females (RR = 1.04, 95% CI: 0.97-1.14, P = 0.28). The population attributable risk percentage (PAR%) was 10% for paternal age ≥30 and 5% for paternal age <25. DISCUSSION Both APA (≥30) and younger paternal age (<25) increase the risk of schizophrenia; younger paternal age may be associated with an increased risk in males but not females. This risk factor increases the risk of schizophrenia as much as any single candidate gene of risk. The mechanism of these associations is not known and may differ for older and younger fathers.

Fronto-cerebellar systems are associated with infant motor and adult executive functions in healthy adults but not in schizophrenia

Delineating longitudinal relationships between early developmental markers, adult cognitive function, and adult brain structure could clarify the pathogenesis of neurodevelopmental disorders such as schizophrenia. We aimed to identify brain structural correlates of infant motor development (IMD) and adult executive function in nonpsychotic adults and to test for abnormal associations between these measures in people with schizophrenia. Representative samples of nonpsychotic adults (n = 93) and people with schizophrenia (n = 49) were drawn from the Northern Finland 1966 general population birth cohort. IMD was prospectively assessed at age 1 year; executive function testing and MRI were completed at age 33–35 years. We found that earlier motor development in infancy was correlated with superior executive function in nonpsychotic subjects. Earlier motor development was also normally associated with increased gray matter density in adult premotor cortex, striatum, and cerebellum and increased white matter density in frontal and parietal lobes. Adult executive function was normally associated with increased gray matter density in a fronto-cerebellar system that partially overlapped, but was not identical to, the gray matter regions normally associated with IMD. People with schizophrenia had relatively delayed IMD and impaired adult executive function in adulthood. Furthermore, they demonstrated no normative associations between fronto-cerebellar structure, IMD, or executive function. We conclude that frontal cortico-cerebellar systems correlated with adult executive function are anatomically related to systems associated with normal infant motor development. Disruption of this anatomical system may underlie both the early developmental and adult cognitive abnormalities in schizophrenia.