Marius Lahti

Cardiovascular morbidity, mortality and pharmacotherapy in patients with schizophrenia

BACKGROUND Patients with schizophrenia have excess cardiovascular morbidity and mortality. Previous studies suggest that this may be partly due to inadequate somatic treatment and care, such as non-optimal use of lipid-lowering and antihypertensive pharmacotherapy, but longitudinal studies on such aetiological pathways are scarce. METHOD We investigated the use of lipid-lowering and antihypertensive pharmacotherapy, and the risk of hospitalization for and death from coronary heart disease and stroke among patients with schizophrenia in a birth cohort of 12 939 subjects (Helsinki Birth Cohort Study). This cohort was followed for over 30 adult years by using national databases on cardio- and cerebrovascular hospitalizations and mortality and on reimbursement entitlements and use of drugs for treatment of hypertension, dyslipidaemia, coronary heart disease and diabetes. RESULTS Individuals with schizophrenia had a higher risk of hospitalization for coronary heart disease [hazard ratio (HR) 1.65, 95% confidence interval (CI) 1.03-2.57], and mortality from this disease was markedly higher (HR 2.92, 95% CI 1.70-5.00), particularly among women (p=0.001 for women, p=0.008 for men). Women with schizophrenia had also marginally increased stroke mortality (p=0.06). However, patients with schizophrenia used less lipid-lowering (odds ratio 0.47, 95% CI 0.27-0.80) and antihypertensive drug treatment (HR 0.37, 95% CI 0.22-0.61). CONCLUSIONS In this longitudinal study, coronary heart disease morbidity was increased and coronary heart disease mortality markedly increased in patients, especially in women with schizophrenia. These patients nevertheless received less antihypertensive and lipid-lowering treatment.

Risk of severe mental disorders in adults separated temporarily from their parents in childhood: The Helsinki birth cohort study

In a large, prospective epidemiological study we tested whether exposure to severe early life stress increases the risk of severe mental disorders in adulthood, and whether childhood socioeconomic background and sex modify these associations. Among the 12,747 participants of the Helsinki Birth Cohort Study, born 1934-1944, 1719 were recorded as separated temporarily from their parents in childhood. The separations took place during World War II when Finnish children were voluntarily evacuated unaccompanied by their parents to temporary foster care abroad (mean age at and length of separation 4.6 and 1.7 years, respectively). Severe mental disorders were identified from the Finnish Hospital Discharge and Causes of Death Registers between years 1969 and 2004. Compared to the non-separated, the separated had higher risks of mental, substance use and personality disorder (P-values ≤ 0.05). The risk of any mental and substance use disorder was, however, highest in the separated and lowest in the non-separated with an upper childhood socioeconomic background; individuals with a lower childhood socioeconomic background showed an intermediate risk regardless of their separation status (P-values for interactions ≤ 0.05). Temporary separation from parents poses a risk of severe mental disorders later in life. Children with an upper childhood socioeconomic background may be particularly sensitive to this type of early life stress, while for children with a lower childhood socioeconomic background it may not add to the risk already associated with lower socioeconomic position in childhood.

Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy

Accumulating research shows that prenatal exposure to maternal stress increases the risk for behavioral and mental health problems later in life. This review systematically analyzes the available human studies to identify harmful stressors, vulnerable periods during pregnancy, specificities in the outcome and biological correlates of the relation between maternal stress and offspring outcome. Effects of maternal stress on offspring neurodevelopment, cognitive development, negative affectivity, difficult temperament and psychiatric disorders are shown in numerous epidemiological and case-control studies. Offspring of both sexes are susceptible to prenatal stress but effects differ. There is not any specific vulnerable period of gestation; prenatal stress effects vary for different gestational ages possibly depending on the developmental stage of specific brain areas and circuits, stress system and immune system. Biological correlates in the prenatally stressed offspring are: aberrations in neurodevelopment, neurocognitive function, cerebral processing, functional and structural brain connectivity involving amygdalae and (pre)frontal cortex, changes in hypothalamo-pituitary-adrenal (HPA)-axis and autonomous nervous system.

Infant Growth after Preterm Birth and Neurocognitive Abilities in Young Adulthood

OBJECTIVES To examine whether faster growth from birth to term (40 postmenstrual weeks) and during the first year thereafter was associated with better neurocognitive abilities in adults born preterm with very low birth weight (VLBW; <1500 g). STUDY DESIGN Weight, length, and head circumference data of 103 VLBW participants of the Helsinki Study of Very Low Birth Weight Adults were collected from records. Measures at term and at 12 months of corrected age were interpolated. The participants underwent tests of general neurocognitive ability, executive functioning, attention, and visual memory at mean age of 25.0 years. RESULTS Faster growth from birth to term was associated with better general neurocognitive abilities, executive functioning, and visual memory in young adulthood. Effect sizes in SD units ranged from 0.23-0.43 per each SD faster growth in weight, length, or head circumference (95% CI 0.003-0.64; P values <.05). After controlling for neonatal complications, faster growth in head circumference remained more clearly associated with neurocognitive abilities than weight or length did. Growth during the first year after term was not consistently associated with neurocognitive abilities. CONCLUSIONS Within a VLBW group with high variability in early growth, faster growth from birth to term is associated with better neurocognitive abilities in young adulthood. Neurocognitive outcomes were predicted, in particular, by early postnatal head growth.

Early Life Origins Cognitive Decline: Findings in Elderly Men in the Helsinki Birth Cohort Study

Objectives To examine whether the adverse effects of slow prenatal and postnatal growth on cognitive function persist to old age and predict age related cognitive decline. Design and Setting A longitudinal birth cohort study of men born in Helsinki, Finland 1934-44. Participants Nine-hundred-thirty-one men of the Helsinki Birth Cohort Study, with detailed data on growth from birth to adulthood, aged 20.1 (SD = 1.4) at the first and 67.9 (SD = 2.5) years at the second cognitive testing. Main Outcome Measures The Finnish Defense Forces Basic Intellectual Ability Test assessed twice over nearly five decades apart. Results Lower weight, length and head circumference at birth were associated with lower cognitive ability at 67.9 years (1.04–1.55 points lower ability per each standard deviation [SD] unit decrease in body size, 95% Confidence Interval [95%CI]: 0.05 to 2.72) and with cognitive decline after 20.1 years (0.07–0.11 SD decline over time per each SD decrease in body size, 95%CI:0.00 to 0.19). Men who were born larger were more likely to perform better in the cognitive ability test over time (1.22–1.43 increase in odds to remain in the top relative to the lower two thirds in ability over time per each SD increase in body size, 95%CI:1.04 to 1.79) and were more resilient to cognitive decline after 20.1 years (0.69 to 0.76 decrease in odds to decline from than remain in the top third of ability over time per each SD increase in body size, 95%CI:0.49 to 0.99). Slower growth between birth and two years in weight, height and body mass index was associated with lower cognitive ability at 67.9 years, but not with cognitive decline. Conclusions Poorer lifetime cognitive ability is predicted by slower growth before and after birth. In predicting resilience to age related cognitive decline, the period before birth seems to be more critical.

Personality and Dietary Intake – Findings in the Helsinki Birth Cohort Study

Background Personality traits are associated with health outcomes including non-communicable diseases. This could be partly explained by lifestyle related factors including diet. The personality traits neuroticism, extraversion, openness, agreeableness, and conscientiousness are linked with resilience, meaning adaptability in challenging situations. Resilient people usually comply with favorable health behaviors. Objective Our objective was to explore the associations between food and nutrient intake, personality traits and resilience. Design A validated semi-quantitative food frequency questionnaire was used to measure diet and the NEO-personality inventory to assess personality in 1681 subjects. Linear regression analysis was used to explore diet-personality associations and cluster analysis to define resilient and non-resilient personality profiles. Results Adjusting for age, education and energy intake, and applying Bonferroni corrections, openness in men was associated with higher vegetable (14.9 g/d for 1 SD increase in the personality score, PBonf <0.01) and lower confectionery and chocolate (−2.8 g/d, PBonf <0.01) intakes. In women, neuroticism was associated with lower fish (−4.9 g/d, PBonf <0.001) and vegetable (−18.9 g/d, PBonf <0.01) and higher soft drink (19.9 g/d, PBonf <0.001) intakes. Extraversion, in women, associated with higher meat (5.9 g/d, PBonf <0.05) and vegetable (24.8 g/d, PBonf<0.001) intakes, openness with higher vegetable (23.4 g/d, PBonf <0.001) and fruit (29.5 g/d, PBonf <0.01) intakes. Agreeableness was associated with a lower soft drink (−16.2 g/d, PBonf <0.01) and conscientiousness with a higher fruit (32.9 g/d, PBonf<0.01) intake in women. Comparing resilient and non-resilient subjects, we found resilience in women to be associated with higher intakes of vegetables (52.0 g/d, P<0.001), fruits (58.3 g/d, P<0.01), fish (8.6 g/d, P<0.01) and dietary fiber (1.6 g/d, P<0.01). Conclusion Personality traits are associated with dietary intake and especially subjects with resilient personality profiles had healthier dietary intakes. These associations were stronger in women than in men.

Very Low Birth Weight, Infant Growth, and Autism-Spectrum Traits in Adulthood

OBJECTIVES: We examined whether adults born preterm at very low birth weight (VLBW; <1500 g) differ from term-born adults in autism-spectrum traits, and whether among VLBW adults, growth in infancy is associated with these traits. METHODS: A total of 110 VLBW and 104 term-born adults of the Helsinki Study of Very Low Birth Weight Adults completed the Autism-Spectrum Quotient yielding total, social interaction, and attention to detail sum scores. Growth in weight, length, and head circumference from birth to term and from term to 1 year of corrected age was determined as standardized residuals reflecting growth conditional on previous history. RESULTS: VLBW adults scored higher than term-born controls on social interaction sum score, indicating higher autism-spectrum traits. In contrast, they scored lower on attention to detail sum score, indicating lower autism-spectrum traits. Within the VLBW group, faster growth in weight, length, and head circumference from birth to term was associated with lower total and social interaction sum scores. In this group, growth from term to 1 year was not associated with autism-spectrum traits. CONCLUSIONS: Among those born preterm at VLBW, the risk for higher levels of autism-spectrum traits, particularly related to social interaction, may persist into adulthood. Faster growth from birth to term may ameliorate these effects, suggesting that targeted interventions could aid long-term neurodevelopment.

History of mental disorders and leukocyte telomere length in late adulthood: The Helsinki Birth Cohort Study (HBCS)

Shorter leukocyte telomere length (LTL) has been linked with mental disorders and with other manifestations of chronic non-communicable diseases. Mental disorders are associated with increased morbidity and premature mortality. It remains unclear if shorter LTL characterizes patients who have been diagnosed with mental disorders in the past, and who have survived till late adulthood. 1051 women and 905 men of the Helsinki Birth Cohort Study participated in this study. LTL was measured by using the real-time quantitative PCR method for subjects and patients at the mean age of 61.5 years. Patients with a mental disorder severe enough to warrant hospitalization (n = 116) were identified by their case records in the Finnish Hospital Discharge Register and the use of psychotropic medication by reimbursement entitlements or prescription fills (n = 665) data in the Finnish Social Insurance Register. Participants hospitalized for any mental or substance use disorders had longer LTL than non-hospitalized controls (p-values < 0.042). Moreover, only those any mental disorder patients who had psychotropic medication use had longer LTL than non-hospitalized controls (p = 0.02). Adjustment for a number of covariates did not attenuate the association. Our findings suggest that shorter LTL may not be an intrinsic feature of mental disorders. Future research is needed to elucidate if psychotropic medication is involved in leukocyte telomere length maintenance in subjects with mental disorders.

The history of sleep apnea is associated with shorter leukocyte telomere length: the Helsinki Birth Cohort Study.

OBJECTIVES Sleep apnea poses an elevated risk for chronic age-related diseases. Leukocyte telomere length (LTL), a biomarker and factor associated with accelerated cellular aging processes, may serve as a novel mechanism underlying these disease risks. We investigated if a history of clinician-diagnosed sleep apnea or primary snoring was associated with LTL in later adulthood. METHODS Data on sleep apnea, primary snoring and LTL, were available for 1948 participants from the Helsinki Birth Cohort Study. Patients with sleep apnea (n=44) and primary snoring (n=29) severe enough to be recorded as an inpatient diagnosis for hospitalization were identified by their case records through the Finnish Hospital Discharge Register. The LTL was measured by using the realtime quantitative polymerase chain reaction (PCR) method at a mean age of 61.5 years (standard deviation [SD], 2.9). RESULTS A history of sleep apnea was associated with shorter LTL (P=.010). Adjustment for a number of covariates did not alter the association. CONCLUSIONS Accelerated cellular aging reflected in shorter LTL in patients with a history of sleep apnea may partly explain their higher risk for age-related diseases. Future studies elucidating the impacts of long-term or successful treatment history of sleep apnea on the maintenance of LTL are warranted.

Prenatal origins of hospitalization for personality disorders: The Helsinki Birth Cohort Study

Although a suboptimal prenatal environment has been linked with schizophrenia and depression, possible associations with personality disorders remain unclear. The aim of this study was to examine the associations of body size at birth and length of gestation with hospitalization for personality disorders in a cohort study of 6506 men and 5857 women born in Helsinki, Finland, between 1934 and 1944. International Classification of Diseases (-8, -9, -10) diagnoses of personality disorders were extracted from the national Finnish Hospital Discharge Register since 1969. 102 men and 80 women had been hospitalized due to any personality disorder. 41 men and 30 women had dramatic personality disorders. Among men, head circumference showed an inverse J-shaped, nonlinear association with hospitalization for personality disorders. Men with a small head circumference were at increased risk. Also in men, a smaller head-to-length ratio linearly predicted personality disorders. Among women, a smaller placental area predicted increased risk of hospitalization for dramatic personality disorders. Vulnerability to personality disorders may be programmed during fetal life.