Katri Räikkönen

Depressive Symptoms and Stressful Life Events Predict Metabolic Syndrome Among Middle-Aged Women: A comparison of World Health Organization, Adult Treatment Panel III, and International Diabetes Foundation definitions

OBJECTIVE—We evaluated whether psychosocial factors that are related to cardiovascular disease and type 2 diabetes predict prospectively the risk for the metabolic syndrome using the different clinical criteria available for defining the syndrome. RESEARCH DESIGN AND METHODS—Women were enrolled in a population-based prospective cohort study called the Healthy Women Study and were followed for an average of 15 years after baseline. Metabolic syndrome was defined via the World Health Organization, the National Cholesterol Education Program Adult Treatment Panel III, and the International Diabetes Foundation clinical criteria. RESULTS—Among women who did not have the metabolic syndrome at the baseline, the risk for the metabolic syndrome defined in multiple ways varied from 1.21- to 2.12-fold ([95% CI 1.00–4.25], P < 0.05) for more severe depressive symptoms or very stressful life event(s). These associations were largely the same, regardless of the clinical criteria used to define the metabolic syndrome. Those who at the baseline reported feeling frequently and intensely angry, tense, or stressed also had an increased risk for developing the metabolic syndrome at least by one definition (relative risk 1.19–1.66 [1.00–2.39]). CONCLUSIONS—These are the first data to demonstrate that psychosocial factors predict the risk for developing the metabolic syndrome by multiple definitions. Psychosocial factors may play a causal role in the chain of events leading to the metabolic syndrome.

Effects of Optimism, Pessimism, and Trait Anxiety on Ambulatory Blood Pressure and Mood During Everyday Life

This study tested whether disposition^ measures of optimism, pessimism, and anxiety affected ambulatory blood pressure (BP) and mood and whether any cardiovascular effects of dispositions were moderated by mood. Pessimistic and anxious adults had higher BP levels and felt more negative and less positive than did optimists or low anxious adults throughout the monitoring. The few times that optimists did feel negative were associated with levels of BP as high as those observed among pessimists or anxious individuals, regardless of their mood. To the extent that trait anxiety measures neuroticism, these findings suggest that neuroticism is directly related to health indicators rather than simply to illness behavior. Furthermore, the results suggest that pessimism has broad physiological and psychological consequences.

Meta-analysis of genome-wide association studies for personality

Personality can be thought of as a set of characteristics that influence peoples thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17 375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ∼2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P=2.8 × 10−8 and 3.1 × 10−8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P=4.9 × 10−8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

Short Sleep Duration and Behavioral Symptoms of Attention-Deficit/Hyperactivity Disorder in Healthy 7- to 8-Year-Old Children

OBJECTIVE. It has been hypothesized that sleep deprivation may manifest in children as behavioral symptoms rather than as tiredness, but only a few studies have investigated this hypothesis. The objective of our study was to evaluate whether short sleep is associated with behavioral symptoms of attention-deficit/hyperactivity disorder in 7- to 8-year-old children. METHODS. We performed a cross-sectional study of children born in 1998 in Helsinki, Finland. The participants included 280 (146 girls, 134 boys) children with a mean age of 8.1 years (SD: 0.3; range: 7.4–8.8). Sleep quality was measured by using actigraphs. The Sleep Disturbance Scale for Children and the Attention-Deficit/Hyperactivity Disorder Rating Scale IV were administered to parents. RESULTS. Children whose average sleep duration as measured by actigraphs was short (<10th percentile, ie, <7.7 hours) and had a higher hyperactivity/impulsivity score (9.7 vs 7.8 or 7.5) and a higher attention-deficit/hyperactivity disorder total score (17.3 vs 14.5 or 13.1) but a similar inattention score (7.6 vs 6.7 or 5.6) compared with children sleeping 7.7 to 9.4 hours or >9.4 hours. In multivariate statistical models, short sleep duration remained a statistically significant predictor of hyperactivity/impulsivity, and sleeping difficulties were associated with hyperactivity/impulsivity, inattention, and the total score. There were no significant interactions between short sleep and sleeping difficulties. CONCLUSIONS. Childrens short sleep duration and sleeping difficulties increase the risk for behavioral symptoms of attention-deficit/hyperactivity disorder.

Very Low Birth Weight and Behavioral Symptoms of Attention Deficit Hyperactivity Disorder in Young Adulthood: The Helsinki Study of Very-Low-Birth-Weight Adults

OBJECTIVE Children with very low birth weight (<1500 g) are at increased risk for attention deficit hyperactivity disorder (ADHD). Whether this increased risk continues into adulthood is unknown. The authors assessed behavioral symptoms of ADHD in a well-characterized cohort of very-low-birth-weight young adults who were either small for gestational age (less than two standard deviations below the Finnish mean) or appropriate for gestational age (within two standard deviations of the mean). METHOD A total of 162 very-low-birth-weight subjects (small for gestational age: N=52; appropriate for gestational age: N=110) and 172 term comparison subjects 18 to 27 years of age completed the Adult Problem Questionnaire, which yielded six exploratory factor analysis-derived subscales. Participants were also asked about substance use. RESULTS Very-low-birth-weight adults in the small for gestational age subgroup scored higher on the executive dysfunctioning and emotional instability subscales of the Adult Problem Questionnaire than did those in the appropriate for gestational age subgroup and the comparison group. The appropriate for gestational age and comparison groups had similar scores on these subscales. On the alcohol use subscale of the Adult Problem Questionnaire, both the appropriate and small for gestational age subgroups scored lower than comparison subjects and also reported fewer risk-taking behaviors (alcohol, smoking, and use of recreational drugs) than did comparison subjects. CONCLUSIONS Rather than very low birth weight per se, intrauterine growth retardation, as reflected by small for gestational age status in the very-low-birth-weight subjects, confers a risk for behavioral and emotional adversity related to ADHD in young adulthood.

Depression in Young Adults With Very Low Birth Weight: The Helsinki Study of Very Low-Birth-Weight Adults

CONTEXT Little is known about the mental health outcomes of very low-birth-weight (VLBW) (< 1500 g) infants in young adulthood. OBJECTIVE To test whether young adults aged 18 to 27 years with VLBW differ from term control subjects in depressive symptoms, current use of antidepressant medication, and the rate of depression diagnosed by a physician. DESIGN Retrospective longitudinal study. SETTING Academic research. PARTICIPANTS A total of 162 VLBW young adults (response rate, 65.1%) and 172 term control subjects (response rate, 54.8%) born between February 22, 1978, and November 8, 1985, in Helsinki, Finland. MAIN OUTCOME MEASURES Antidepressant use, history of physician-diagnosed depression, Beck Depression Inventory score, and Center for Epidemiologic Studies Depression Scale score. RESULTS The VLBW participants reported 20.1% (95% confidence interval [CI], -40.8% to -5.1%) lower CES-D scores than the controls (P =.02). However, this finding was confined to 110 VLBW participants who were born appropriate for gestational age (birth weight > or = -2 SDs according to Finnish birth weight charts), whose Center for Epidemiologic Studies Depression Scale scores were 29.1% (95% CI, -53.7% to -8.4%) lower than those of the controls (P =.004). Furthermore, VLBW participants born appropriate for gestational age were 4.8 (95% CI, 1.3-10.0) times less likely to report a depression diagnosis than controls (P =.02). In contrast, 52 VLBW participants born small for gestational age (birth weight < -2 SDs according to Finnish birth weight charts) reported 36.2% (95% CI, 1.1%-83.5%) higher Beck Depression Inventory scores (P =.04), were 4.0 (95% CI, 1.1-14.3) times more likely to use antidepressants (P =.03), and were 2.5 (95% CI, 1.0-6.3) times more likely to report a depression diagnosis (P =.04) compared with controls. CONCLUSIONS This is the first study (to our knowledge) to show that intrauterine growth pattern may modify associations between VLBW and depression. Intrauterine growth retardation rather than VLBW per se may pose a risk of depression in young adulthood.

Optimistic attitudes protect against progression of carotid atherosclerosis in healthy middle-aged women.

Objective: Optimistic people report a higher quality of life, engage in more active coping and adopt more health-promoting behaviors than people low in optimism, ie, pessimism. We evaluated whether pessimists are more likely to show progression in carotid disease than optimists. Methods: A total of 209 middle-aged healthy premenopausal women enrolled in an epidemiological study of cardiovascular risk factors and had carotid scans 10.4 years and 13.5 years later when they were at least 5 years postmenopausal. Women completed the Life Orientation Test (LOT), a measure of pessimistic and optimistic attitudes, at study entry and at the time of the first carotid scan. Analyses evaluated the association of LOT scores and change in carotid intima medial thickness (IMT) across 3 years. Results: Multiple linear regression analyses showed that the higher the pessimism scores at study entry, the greater the increase in mean IMT (&bgr; = 0.17, p < .007). A comparison of those in the lowest quartile of LOT scores (most optimistic) with those in the other three quartiles showed that the most optimistic group had less progression than the remaining more pessimistic women (mean percent increase = 1.3 and 6.0 for mean IMT, F = 15.4, p < .001). Women who were chronically optimistic at study entry and at the first carotid scan (bottom quartiles at both times) had less progression in mean IMT than did those who were chronically pessimistic (top quartiles at both times). Conclusions: Optimistic women are less likely to show progression of carotid disease in mid-life than are pessimists. LOT = Life Orientation Test; IMT = intima medial thickness; HWS = Healthy Women Study; DBP = diastolic blood pressure; SBP = systolic blood pressure; HDL-C = high-density lipoprotein cholesterol; BMI = body mass index; HT = hormone therapy; ANCOVA = analyses of covariance.

Prenatal and postnatal growth and cognitive abilities at 56 months of age: A longitudinal study of infants born at term

OBJECTIVE. The aim of the study was to investigate whether weight, length, BMI (kilograms per meter squared), and head circumference at birth and their postnatal growth are associated with cognitive abilities at 56 months of age among infants born at term. PATIENTS AND METHODS. Our sample was composed of 1056 Finnish children born at term, (37 to 41 weeks) free of any major impairments. Weight, length, and head circumference were measured at birth and at 5, 20, and 56 months of age, and BMI was calculated. We assessed cognitive abilities by conducting tests of general reasoning, visual-motor integration, verbal competence, and language comprehension at 56 months of age. RESULTS. Firstly, for every 1 SD lower in weight or BMI at birth, general reasoning and/or visual-motor integration was >1.20 points lower, and for every 1 SD lower in length or head circumference at birth, abilities across all of the cognitive domains were >1.31 points lower. Second, for every 1 SD slower gain in weight or BMI from birth to 5 months, general reasoning and visual-motor integration decreased by >0.97 points; for every 1 SD slower gain in length from 5 to 20 months and from 20 to 56 months, respectively, visual-motor integration, and verbal competence and language comprehension decreased by >1.03 points; and for every 1 SD slower increase in head circumference from birth to 5 months and from 5 to 20 months, respectively, visual-motor integration and language comprehension decreased by >1.17 points. Third, tests for nonlinear relationships revealed that, in some cases, large body size and faster growth were also associated with lower scores in cognitive tests. CONCLUSIONS. Our findings suggest that, even within the range of children born at term, prenatal and postnatal growth in body size are associated with individual differences in cognitive abilities.

A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

A Genome-Wide Association Study of Depressive Symptoms

BACKGROUND Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms. METHODS In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies. RESULTS The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10(-3)). This 5q21 region reached genome-wide significance (p = 4.78×10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258). CONCLUSIONS The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.