Intergenerational transmission of psychiatric disorders: the 1987 Finnish Birth Cohort study.

The causes of mental disorders are multifactorial including genetic and environmental exposures, parental psychopathology being the greatest risk factor for their offspring. We set out to quantify the risk of parental psychiatric morbidity with the incidence of mental disorders among their offspring before the age of 22 years and study the sex- and age-specific associations. The present study utilises the 1987 Finnish Birth Cohort (FBC) data, which is a register-based follow-up of all 60,069 children born in Finland 1987 and followed-up until 2008. Data on psychiatric morbidity are based on inpatient care episodes of parents and both inpatient and outpatient visits of offspring and were collected from the Finnish Hospital Discharge Register which covers all Finnish citizens accessing specialized care. Altogether 7.6% of the cohort members had a parent or both parents treated at psychiatric inpatient care during the follow-up. Parental psychiatric morbidity increased the offspring's risk for psychiatric diagnoses two to threefold versus those children without parental psychiatric hospitalization, mother's morbidity comprising a greater risk than that of father's. The risk was prominent for both sexes of the offspring throughout childhood and adolescence. Psychiatric disorders possess significant intergenerational continuum. It is essential to target preventive efforts on the high-risk population that comprises families with a parent or both having mental disorders. It also implies developing appropriate social and health care interventions to support the whole family.

Determinants of underage induced abortion--the 1987 Finnish Birth Cohort study.

INTRODUCTION: Although underage pregnancies often end in induced abortion, data on girls who undergo termination of pregnancy are lacking. Our aim was to identify determinants of underage induced abortion and compare them with those of childbirth. MATERIAL AND METHODS: All girls born in 1987 in Finland surviving the perinatal period (n = 29 041) were included in the study and divided into three study groups: Girls undergoing induced abortion (n = 1041, 3.6%) or childbirth (n = 395, 1.4%) at <18 years of age and girls with no underage pregnancies (n = 27 605, 95.0%). RESULTS: Shared risk factors of underage induced abortion and childbirth included early onset behavioral and emotional disorders [adjusted OR 1.9 (1.4-2.5) and 2.7 (95% CI 1.8-3.9)], a history of foster care [1.5 [1.1-1.9] and 3.0 [2.3-4.1)], and socioeconomic factors, including living in a family receiving income support [1.8 (1.5-2.1) and 3.4 (2.7-4.4)], respectively. Specific risk factors of underage induced abortion were psychoactive substance use disorders [2.2 (1.3-3.5)], having a mother who smoked during pregnancy [1.5 (1.3-1.8)] or had undergone induced abortion [1.8 (1.5-2.2)]. Coping with a chronic physical illness [0.7 (0.5-0.9)], and perinatal problems [0.6 (0.4-0.7)] were inversely associated with underage induced abortion. CONCLUSIONS: The traditionally acknowledged determinants of underage childbirth played a less prominent role in induced abortion. Novel risk factors of underage induced abortion were found, including severe substance abuse and adverse maternal reproductive history, and should be addressed at all levels offering youth healthcare and social welfare services.

Mental disorder diagnoses of offspring affected by parental cancer before early adulthood: the 1987 Finnish Birth Cohort study.

OBJECTIVE: The purpose of this study is to investigate psychiatric diagnoses given to children affected by parental cancer in psychiatric and somatic specialized health care settings. METHODS: The 1987 Finnish Birth Cohort data (n = 59 476) were followed up through national registers from birth of cohort members up to the end of 2008. The health-related data of cohort members and their parents were obtained from the Care Register of Health Care provided by the National Institute of Health and Wellbeing. RESULTS: By the age of 21 years 7711 of the cohort members had used specialized psychiatric outpatient care and, of them, 549 (7.1%) were affected by parental cancer. Of affected offspring a mental disorder diagnosis was made in 424 (77.2%), while 125 (22.8%) children had not been given any specific mental disorder diagnosis. In females the likelihood for a mental disorder diagnosis assessed in outpatient care was significantly increased by up to 1.2 fold in cases of parental cancer. In males with a father having cancer, psychological development disorders were significantly increased whether assessed in outpatient (OR 1.5) or inpatient (OR1.9) settings. CONCLUSIONS: The prevalence of psychiatric diagnoses in children with parental cancer does not seem to differ from those of children with parents without cancer. However, evidence was found that children affected by parental cancer are at increased risk for some specific psychiatric disorders. Quarter of affected offspring who were referred to specialized psychiatric outpatient care only received diagnoses related to use of health care services or crises or received no psychiatric diagnosis at all. Copyright © 2016 John Wiley & Sons, Ltd.

Parents' traumatic brain injury increases their children's risk for use of psychiatric care: the 1987 Finnish Birth Cohort study.

OBJECTIVE: Traumatic brain injury (TBI) of a parent causes significant changes in their family life and parent-children relationships. However, the number of children affected by parental TBI and the long-term consequences for these children remain unknown. We estimated the prevalence of children affected by parental TBI and investigated whether these children had greater use of psychiatric services than their peers. METHODS: This a retrospective population-based register study. All 60,069 children born in Finland in 1987 were followed up through national health and social registers from 1987 to 2008. RESULTS: During the 21-year follow-up, 1532 (2.6%) children had a parent with TBI. Overall, 22.5% of those having a parent with TBI were treated in specialized psychiatric care. Use of psychiatric care was significantly increased among those cohort members with a parent with mild [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.37-2.38] or severe (OR 1.49, 95% CI 1.12-1.98) TBI compared to their peers. CONCLUSIONS: Parental TBI is associated with increased use of specialized psychiatric services by children. Adult health care services must have appropriate systems in place to address the psychosocial needs and support the welfare and development of children of patients with TBI.

Allele-specific N-glycosylation delays human surfactant protein B secretion in vitro and associates with decreased protein levels in vivo.

BACKGROUND: Surfactant protein B (SP-B) is essential for normal lung function, and decreased concentrations of SP-B have a deleterious effect on pulmonary outcome. SP-B levels may correlate with variations in the encoding gene (SFTPB). SFTPB single-nucleotide polymorphism Ile131Thr affects proSP-B N-glycosylation in humans and the glycosylated Thr variant associates with pulmonary diseases. METHODS: We analyzed SP-B levels in amniotic fluid samples for associations with SFTPB polymorphisms and generated cell lines expressing either proSP-B/131Ile or proSP-B/131Thr for examining the effect of glycosylation on proSP-B secretion kinetics. To determine any transcription preference between Ile131Thr allelic variants, we used heterozygous human lungs for allelic expression imbalance assays. RESULTS: Protein levels correlated with Ile131Thr genotype and the lowest SP-B levels were observed in Thr/Thr homozygotes. Our results suggest that Ile131Thr variation-dependent N-glycosylation associates with decreased levels of SP-B, which is secreted from fetal lung to amniotic fluid. Glycosylated proSP-B/131Thr was secreted from transfected cells at a lower rate than nonglycosylated proSP-B/131Ile. Expression levels of the mRNA variants were equal. Secretion of the glycosylated variant was thus delayed in vitro by a posttranscriptional mechanism. CONCLUSION: These data support the hypothesis that proSP-B glycosylation due to Ile131Thr variation may have a causal role in genetic susceptibility to acute respiratory distress.

Social determinants of mental health: a Finnish nationwide follow-up study on mental disorders.

BACKGROUND: Most mental disorders start in childhood and adolescence. Risk factors are prenatal and perinatal, genetic as well as environmental and family related. Research evidence is, however, insufficient to explain the life-course development of mental disorders. This study aims to provide evidence on factors affecting mental health in childhood and adolescence. DATA AND METHODS: The 1987 Finnish Birth Cohort covers all children born in Finland in 1987 (N=59 476) who were followed up until the age of 21 years. The study covers detailed health, social welfare and sociodemographic data of the cohort members and their parents from Finnish registers. RESULTS: Altogether, 7578 (12.7%) cohort members had had a diagnosed mental disorder. Several prenatal, perinatal and family-related risk factors for mental disorders were found, with sex differences. The main risk factors for mental disorders were having a young mother (OR 1.30 (1.16 to 1.47)), parents' divorce (OR 1.33 (1.26 to 1.41)), death of a parent (OR 1.27 (1.16 to 1.38)), parents' short education (OR 1.23(1.09 to 1.38)), childhood family receiving social assistance (OR 1.61 (1.52 to 1.71)) or having a parent treated at specialised psychiatric care (OR 1.47 (1.39 to 1.55)). Perinatal problem (OR 1.11 (1.01 to 1.22)) and prenatal smoking (OR 1.09 (1.02 to 1.16)) were risk factors for mental disorders, even after controlling for background factors. Elevated risk was seen if the cohort member had only basic education (OR 3.37 (3.14 to 3.62)) or had received social assistance (OR 2.45 (2.30 to 2.60)). CONCLUSIONS: Mental disorders had many social risk factors which are interlinked. Although family difficulties increased the risk for mental disorders, they were clearly determined by the cohort member's low education and financial hardship. This study provides evidence for comprehensive preventative and supporting efforts. Families with social adversities and with parental mental health problems should be supported to secure children's development.

Socioeconomic and regional aspects in the use of specialized psychiatric care--a Finnish nationwide follow-up study.

BACKGROUND: Mental health problems in childhood and adolescence are an important public health concern. The general aim of Finnish health policy is to offer equal services for all inhabitants according to need, irrespective of socio-economic background or place of residence. Here, we assess equity in access to psychiatric care in a long-term nationwide follow-up study from birth to early adulthood. METHODS: All 60 069 children born in Finland in 1987 were followed up through health registers from 1987 to 2008. The cohort members' use of specialized psychiatric outpatient and inpatient care was assessed and linked to their socio-economic status and residential area. RESULTS: Altogether, 14.4% of the cohort members had received specialized psychiatric care during the follow-up. Females used significantly more specialized psychiatric outpatient care than males. In addition, the use of specialized psychiatric care was more common among young people with a poor socio-economic background and those living in urban areas. CONCLUSIONS: A notable number of the young adults born in Finland in 1987 used specialized psychiatric care during their childhood and adolescence. Use was clearly defined by sex and residential area, as well as by parental socio-economic status and education. The data indicate that equity in access to mental health services should be highlighted in health policies, as contemporary outpatient mental health care has not been equally available for people living within and outside urban areas.

Material deprivation or minimal education? Social class and crime in an egalitarian welfare state.

Research on social class and crime is dominated by perspectives that assume socioeconomic disadvantage to exert causal influence on offending. As an alternative approach, the present study examined hypotheses derived from a social selection perspective which treats intergenerational continuity in antisocial propensity as the primary source of socioeconomic differences in criminal activity. Under this theory, individual characteristics of the parents influence their personal socioeconomic attainment as well as the behavioral traits they pass on to their children. Consistent with both of these perspectives, longitudinal data tracking Finnish males born in 1987 (n=21,513) showed strong negative associations between family socioeconomic status (SES) and offspring rates of criminal offending. In critical support for the selection perspective: (1) these association were linear rather than discrete, (2) parents' educational attainment accounted for most of the association between the occupational measure of family SES and crime, and (3) measures of offspring criminal propensity mediated a substantial share of these effects. Adolescent educational marginalization emerged as the key factor linking childhood socioeconomic status to the risk of criminal offending in emerging adulthood. We discuss the implications of this finding for social influence and social selection models of explanation.

Surfactant protein D modulates levels of IL-10 and TNF-α in intrauterine compartments during lipopolysaccharide-induced preterm birth.

Prematurity is the main cause of perinatal mortality and morbidity, and preterm birth is often associated with intrauterine inflammation. Surfactant protein D (SP-D) functions in lung homeostasis and has multiple roles in innate immunity. It is present in amniotic fluid and in gestational tissues. We propose that SP-D may regulate intrauterine inflammatory responses related to preterm labor. Our aim was to investigate the role of SP-D in lipopolysaccharide-induced preterm birth in mice that overexpress rat SP-D (rSP-D) under the human SP-C promoter. SP-D protein in amniotic fluid and in gestational tissues was detected by western analysis. TNF-α, IL-10, and IL-6 concentrations in serum and amniotic fluid and mRNA levels in gestational tissues were quantified using cytometric bead array and ribonuclease protection assay, respectively. Increased levels of SP-D protein were detected in the amniotic fluid and gestational tissues of rSP-D mice. Lipopolysaccharide given at 17 days post-coitum to rSP-D dams led to preterm birth of live-born offspring within 18 h. Preterm birth of live-born pups was induced with a lower dose of lipopolysaccharide compared to wild-type mice. In rSP-D mice, the lipopolysaccharide-induced levels of TNF-α and IL-10 in amniotic fluid and fetal serum and the expression of IL-10 in placenta and fetal membranes were significantly different from wild-type mice. We conclude that SP-D in fetal and gestational tissues modulates the levels of intrauterine inflammatory mediators involved in preterm birth and may contribute to inflammatory processes related to spontaneous preterm labor.

The prevalence of children affected by parental cancer and their use of specialized psychiatric services: the 1987 Finnish Birth Cohort study.

The studies reporting population-based estimates of the proportion of children with a parent suffering from cancer are very few. These children have been shown to suffer from psychological symptoms, but it is not known whether their use of psychiatric services is increased. Our study examined the prevalence of children affected by parental cancer at national level and whether these children use specialized psychiatric services more than their peers. The study is a retrospective population-based registry study. All 60,069 children born in Finland in 1987 were followed up with various health and social registers from 1987 to 2008. The associations of parental cancer treatments with children's psychiatric service use were analyzed with logistic regressions. During the 21-year follow-up 3,909 (6.6%) of the children had a parent suffering from cancer. The children of the cancer patients used more specialized psychiatric care than their peers and the service use depended on parent's gender, as well as cohort members' gender and the age at occurrence. The combination of parental cancer and psychiatric disorder, whether the ill parent or spouse, increased the children's psychiatric service use even more. Children affected by parental cancer comprise a substantial part of the population in society using increased level of psychiatric services. Parental cancer is clearly an illness which has to be taken into account in planning child- and parenting-focused prevention and promotion actions in adult health care. "Parent's cancer is like a tsunami which rolls over the whole family. If it struck a thousand families at the same time the whole healthcare system would be mobilized. But when it strikes one family at a time you are left alone with your children" (quote from a father during a family intervention). Weaver et al.1 have reported that 14% of all cancer survivors in the USA have minor dependent children, representing a population of about 1.58 million survivors and 2.85 million children. A significant part of working age population is thus struggling with concerns related to serious illness, parenting and the wellbeing of children.

Surfactant protein A modulates the lipopolysaccharide-induced inflammatory response related to preterm birth.

Surfactant protein A (SP-A) functions in homeostasis of lung surfactant and in innate immunity. SP-A is secreted by the fetal lung into amniotic fluid. Additionally it has been detected in gestational tissues. We propose that SP-A influences intrauterine inflammation that is commonly associated with preterm birth, the main underlying cause of neonatal mortality and morbidity. We used our previously established mouse model of LPS-induced preterm birth of live-born pups to investigate the role of SP-A in preterm birth. Mice overexpressing rat SP-A (rSP-A) under the control of human SP-C promoter were used. Cytokine concentrations in maternal and fetal serum and in amniotic fluid and mRNA levels of several inflammatory mediators in lungs and in intrauterine tissues were quantified using Cytometric Bead Array and RNase Protection Assay, respectively. Higher levels of SP-A mRNA were observed in fetal lungs and intrauterine tissues of rSP-A mice compared with wild-type. Using Western blot we detected excess of SP-A protein in fetal lung and in amniotic fluid of rSP-A animals. Despite some differences in the basal levels of TNF-α and IL-10 between rSP-A and wild-type animals, there were no differences in the duration of pregnancy. However, the levels of TNF-α, IL-10 and some other inflammatory mediators in intrauterine tissues and in amniotic fluid differed significantly between the mouse lines after maternal LPS given at 17dpc. We conclude that SP-A modulates the levels of intrauterine inflammatory mediators involved in preterm birth and may contribute to inflammatory processes related to spontaneous preterm labor.

Genetic association of SP-C with duration of preterm premature rupture of fetal membranes and expression in gestational tissues.

BACKGROUND: Surfactant protein (SP) C has been shown to be expressed also outside pulmonary alveoli. Certain SP-C gene (SFTPC) polymorphisms associate with lung diseases and very preterm birth. AIMS: We investigated the association of SFTPC single nucleotide polymorphism (SNP) rs4715 with factors affecting spontaneous preterm birth and characterized the SP-C expression in human and mouse gestational tissues. METHODS: The SFTPC SNP rs4715 polymorphism was genotyped in a homogeneous northern European population of mothers and infants in spontaneous preterm birth and term controls. The expression and protein of SP-C in gestational tissues was analyzed. RESULTS: SFTPC SNP rs4715 did not associate with spontaneous preterm birth. However, fetuses with short interval (<72 hours) between preterm premature rupture of fetal membranes (PPROM) and preterm birth had significant over-representation of the minor allele A, whereas in fetuses with prolonged PPROM (>or=72 hours) the frequency was decreased. Maternal SFTPC did not associate with the duration of PPROM. SP-C mRNA and proprotein were detected in fetal membranes, placenta, and pregnant uterus. CONCLUSION: SFTPC SNP rs4715 associates with the duration of PPROM, and SP-C is expressed in gestational tissues. We propose that fetal SFTPC moderates the inflammatory activation within the fetal extra-embryonic compartment.

Blood cytokines during the perinatal period in very preterm infants: relationship of inflammatory response and bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the influence of chorioamnionitis (CA) on plasma cytokines and the cytokine-associated risk of bronchopulmonary dysplasia (BPD) during the perinatal period. STUDY DESIGN: Eleven cytokines from 128 very low gestational age infants were analyzed from cord blood and from plasma at ages 1 day and 7 days after birth. The diagnosis of CA was based on histology of the placenta, fetal membranes, and umbilical cord. Neonatal risk factors were recorded. RESULTS: In the 48 infants born with CA, high concentrations of inflammatory cytokines in cord blood decreased during the first postnatal day. Inflammatory cytokines in cord blood was associated with the severity of CA. At 1 day after birth, the concentration of interleukin (IL)-8 predicted the risk of BPD. For the 75 infants born without CA, cytokine concentrations increased after birth. For the 128 infants born with or without CA, at 1 day after birth, the concentrations of IL-8, granulocyte colony-stimulating factor, and anti-inflammatory IL-10 were associated with the risk of BPD, after adjustment for the duration of gestation and severity of respiratory distress during the first day. CONCLUSIONS: In infants exposed to CA, insufficient inhibition of high fetal inflammatory cytokine response shortly after birth may increase the risk of BPD.

Maternal endotoxin-induced preterm birth in mice: fetal responses in toll-like receptors, collectins, and cytokines.

Major cause of prematurity is spontaneous preterm birth (PTB) associated with intrauterine inflammation. Our aim was to establish a model of endotoxin Lipopolysaccharide-induced PTB of live-born pups and to study early immune activation in fetal and maternal compartments. Expression of several proteins that bind microbes (Toll-like receptors TLR4, TLR2; surfactant proteins SP-A, SP-D) was analyzed. At 16 or 17 d of gestation, C57BL/6 dams received a single dose of intraperitoneal LPS, leading to PTB within 17 h. Cytokine levels increased in maternal serum, followed by a modest increase in fetal serum and in amniotic fluid. In uterus, placenta, and fetal membranes, LPS mostly increased the expressions of TLR, SPs, and cytokines. The number of TLR2-positive macrophages increased in labyrinthine placenta. In fetal lung, intestine, liver, and brain there were modest changes in cytokine expressions. In fetal lung, SP and TLR mRNAs decreased and TLR2-positive macrophages redistributed around vessels. LPS-induced fetal deaths associated with early age (16 d gestation) rather than with proinflammatory activation. Here we propose that maternal LPS response leads to PTB and acute decrease of immune proteins in epithelial lining of fetal lung. Instead, acceleration of lung maturity has been previously observed in intraamniotic inflammation.

Expression of toll-like receptor 4 and endotoxin responsiveness in mice during perinatal period.

Endotoxin [lipopolysaccharide (LPS)] from Gram-negative bacteria is found in amniotic fluid in intrauterine infections that associate with the risk for spontaneous premature birth, bronchopulmonary dysplasia (BPD), and respiratory distress syndrome. Toll-like receptor 4 (TLR4) is the signaling receptor for LPS. The aim was to investigate the primary inflammatory response in mice shortly after administration of LPS to the dam (14 and 17 d of pregnancy), to the newborn, or into the amniotic fluid. The expression levels of TLR4, IL-1, tumor necrosis factor-alpha, IL-6, IL-10, macrophage inflammatory protein-2, and IL-1 receptor 1 were studied with ribonuclease protection assay. In addition, TLR4 protein was analyzed with Western blotting. The fetal membranes expressed TLR4 mRNA and protein and showed an acute cytokine response to LPS when LPS was administrated into the amniotic fluid. There was distinct ontogeny in the responsiveness of fetal lung to LPS: on fetal day 14 (term 20 d), both the expression of TLR4 and the acute cytokine response were undetectable 5 h after LPS; they became detectable by fetal day 17. TLR4 and the cytokine response further increased after birth. In maternal lung, the TLR4 expression was strongest and up-regulated in parallel with the induction of the cytokines. We propose that TLR4 controls the magnitude of the LPS-induced cytokine response during the perinatal period.

Transcription factors NF-kappaB and C/EBPdelta and IL-1-induced expression of surfactant protein A in lung explants during the perinatal period.

Interleukin-1 (IL-1) increases the expression of surfactant protein A (SP-A) in rabbit, lamb and human fetal lung. The upregulation disappears towards term. Among the transcription factors, IL-1 activates nuclear factor kappaB (NF-kappaB) and CCAAT/enhancer-binding protein delta (C/EBPdelta). NF-kappaB presumably has a role in IL-1-induced upregulation of SP-A. Also, C/EBPdelta may regulate SP-A expression. The aim was to study the role of these transcription factors in the induced effect of IL-1 on SP-A expression. Explants from fetal and neonatal rabbit lung were cultured in vitro followed by studies using immunohistochemistry, electrophoretic mobility shift assay and Northern analysis. We found gestation-dependent changes in IL-1-induced immunoreactivities of NF-kappaB and C/EBPdelta in the nuclei of alveolar cells. This increase in nuclear transcription factors correlated with IL-1-induced SP-A expression levels. As studied in the explants from fetal and newborn lung, the SP-A mRNA expression additionally associated with C/EBPdelta mRNA and with the binding of nuclear extracts from the lung explants to the C/EBP consensus probe. On the basis of the present and previous studies, we propose that NF-kappaB and C/EBPdelta have potential mediator roles in IL-1-induced upregulation of SP-A in immature lung.

Eustachian tube surfactant is different from alveolar surfactant: determination of phospholipid composition of porcine eustachian tube lavage fluid.

Phosphatidylcholine (PC) is the main phospholipid in lung surfactant and, more specifically, dipalmitoyl PC (PC16:0/16:0) is the major surface-active component. Several studies have tentatively shown that eustachian tube lavage fluid (ETLF) contains surface-active material. The aim of the present study was to determine, using electrospray ionization mass spectrometry, whether the phospholipid molecular species composition of ETLF is similar to that of lung surfactant. PC was the main component of both ETLF and bronchoalveolar lavage fluid (BALF). The concentration of phosphatidylethanolamine was higher and phosphatidylglycerol was undetectable in ETLF compared with BALF. The molecular species composition of PC in ETLF was notably different from that of BALF, palmitoyloleoyl PC being the major component. Importantly, given its predominance in BALF PC, the concentration of PC16:0/16:0 was low in ETLF. As expected on the basis of this molecular species composition of PC, ETLF did not generate low surface tension values under dynamic compression in a pulsating bubble surfactometer. We conclude that the surfactant in ET is different from lung surfactant, and that low surface tension is not a major determinant of ETLF function.