Visual memory and alcohol use in a middle-aged birth cohort.

Light and moderate alcohol use has been reported to be associated with both impaired and enhanced cognition. The purpose of this study was to explore whether there was a linear relationship between visual memory and alcohol consumption in males and females in a large middle-aged birth cohort population in cross-sectional and longitudinal settings. Data were collected from 5585 participants completing 31-year (1997-1998) and 46-year (2012-2014) follow-ups including Paired Associate Learning (PAL) test at 46-years follow-up. The participants were originally from 12,231 study population of the Northern Finland Birth Cohort 1966 (NFBC1966). The PAL test was conducted to assess visual memory. Reported alcohol use was measured as total daily use of alcohol, beer, wine, and spirits converted into grams and as frequency and amount of use of beer, wine, and spirits. The total daily alcohol use was not associated with reduced visual memory. The frequency of use of beer and wine in males was associated with better visual memory in cross-sectional and longitudinal settings. Using six or more servings of spirits was associated with worse visual memory in males in cross-sectional and longitudinal settings. Using six or more servings of spirits was associated with worse visual memory in males in cross-sectional and longitudinal setting. The study suggested a lack of a linear association between drinking and visual memory in the middle-aged population.

Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.

Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards). Using a hierarchical model, ranking the psychotic diagnoses according to clinical severity, we show that high schizophrenia PGS (SZ-PGS) was associated with progression from lower ranked psychotic disorders to schizophrenia (OR = 1.32 [1.23-1.43], p = 1.26e-12). This development manifested already at psychotic illness onset as a higher psychiatric hospitalization burden, the proxy for disease-course severity. In schizophrenia (n = 5 479), both a high SZ-PGS and a low educational attainment PGS (EA-PGS) were associated with increased psychiatric hospitalization burden (p = 1.00e-04 and p = 4.53e-10). The SZ-PGS and the EA-PGS associated with distinct patterns of hospital usage. In individuals with high SZ-PGS, the increased hospitalization burden was composed of longer individual hospital stays, while low EA-PGS associated with shorter but more frequent hospital visits. The negative effect of a low EA-PGS was found to be partly mediated via substance use disorder, a major risk factor for hospitalizations. In conclusion, we show that high SZ-PGS and low EA-PGS both impacted psychotic disease-course development negatively but resulted in different disease-course trajectories.

Maternal Thyroid Function During Pregnancy and Offspring White Matter Microstructure in Early Adulthood: A Prospective Birth Cohort Study.

Background: The fetus is fully dependent on maternal thyroid hormones until mid-gestation and suboptimal maternal thyroid function has been associated with alterations in the neurodevelopment of the offspring. We used maternal free thyroxine (fT4) and thyrotropin (TSH) levels in early gestation to study the association of maternal thyroid function during early pregnancy and offspring brain white matter (WM) integrity in early adulthood. Methods: Our study population consisted of a total of 292 mother-child pairs. Maternal fT4 and TSH were used as predictors and offspring multimodal imaging measures of fractional anisotropy, mean diffusivity, and magnetization transfer ratio (FA, MD, and MTR) as dependent variables. First, as Global analysis, all analyzed 14 WM tracts were studied simultaneously using linear-mixed effect models. Second, if a global effect was detected, a post hoc Tract-wise analysis was carried out using linear models individually in each WM tract. Study population was stratified by sex. Results: We found a positive association between maternal fT4 and offspring Global FA in males when adjusted for all maternal and offspring covariates (n = 114; ß = 0.154; confidence interval = 0.045-0.263; p = 0.006). The finding was observed to be driven by multiple WM tracts, of which three projection fiber tracts and the forceps minor survived correcting for multiple comparisons in Tract-wise analysis. Conclusions: Maternal thyroid function in early pregnancy was observed to be associated with WM microstructure in male offspring in early adulthood. Our results suggest that maternal fT4 levels in early pregnancy may modulate axonal characteristics, with a long-term effect on offspring WM development.

Emotional neglect and parents' adverse childhood events.

INTRODUCTION: Emotional neglect means that the child's emotional and developmental needs are not fulfilled by the parents or other caregivers. Adverse childhood events (ACEs) are a risk factor for mental health problems and impaired parenting skills. The objective here was to examine whether parents' ACEs increase the child's risk of experiencing emotional neglect. METHODS: The participants in the present study were members of the Northern Finland Birth Cohort 1986 (NFBC1986). Emotional neglect experiences were measured in 190 members of this cohort by means of the Trauma and Distress Scale (TADS), and ACEs in both parents were measured with a specific questionnaire. A linear regression model was used to examine the association between parents' ACEs and the children's emotional neglect scores. RESULTS: The children's mean emotional neglect score was 8.11 on a scale from 5 to 25. There was no significant difference between males (mean 8.01) and females (mean 8.19). Only father's ACEs were associated with child's emotional neglect score. In the linear regression model, the children's emotional neglect scores increased by 0.3 points for father's ACE. CONCLUSIONS: Our findings suggest that father's ACEs may increase the child's risk of experiencing emotional neglect. It seems that childhood adversities are transferred from parents to children, but larger samples would be needed to confirm these findings.

Cohort profile: SUPER-Finland - the Finnish study for hereditary mechanisms of psychotic disorders.

PURPOSE: SUPER-Finland is a large Finnish collection of psychosis cases. This cohort also represents the Finnish contribution to the Stanley Global Neuropsychiatric Genetics Initiative, which seeks to diversify genetic sample collection to include Asian, Latin American and African populations in addition to known population isolates, such as Finland. PARTICIPANTS: 10 474 individuals aged 18 years or older were recruited throughout the country. The subjects have been genotyped with a genome-wide genotyping chip and exome sequenced. A subset of 897 individuals selected from known population sub-isolates were selected for whole-genome sequencing. Recruitment was done between November 2015 and December 2018. FINDINGS TO DATE: 5757 (55.2%) had a diagnosis of schizophrenia, 944 (9.1%) schizoaffective disorder, 1612 (15.5%) type I or type II bipolar disorder, 532 (5.1 %) psychotic depression, 1047 (10.0%) other psychosis and for 530 (5.1%) self-reported psychosis at recruitment could not be confirmed from register data. Mean duration of schizophrenia was 22.0 years at the time of the recruitment. By the end of the year 2018, 204 of the recruited individuals had died. The most common cause of death was cardiovascular disease (n=61) followed by neoplasms (n=40). Ten subjects had psychiatric morbidity as the primary cause of death. FUTURE PLANS: Compare the effects of common variants, rare variants and copy number variations (CNVs) on severity of psychotic illness. In addition, we aim to track longitudinal course of illness based on nation-wide register data to estimate how phenotypic and genetic differences alter it.

Association between participation in the Northern Finland Birth Cohort 1966 study and use of psychiatric care services.

AIMS: In most population-based epidemiological follow-up studies the aim is not to intervene in the life of the participants. Although the idea is not to intervene, being a member of the longitudinal follow-up study and studies conducted during follow-up may affect the target population. A population-based study including mental health enquiries might reduce the unmet need for psychiatric treatment by motivating people to seek treatment for their psychiatric ill-health. We examined the use of psychiatric care services in the population born in the year 1966 in Northern Finland, of whom 96.3% are participants in the prospective Northern Finland Birth Cohort 1966 (NFBC1966). METHODS: As a study cohort we used people born in 1966 in Northern Finland (n = 11 447). The comparison cohort included all the people born in the years 1965 and 1967 in the same geographical area (n = 23 339). The follow-up period was from age 10 to 50 years. The outcome measure was the use of psychiatric care services, which was analysed using Cox Proportional Hazard regression and Zero-Truncated Negative Binomial Regression. RESULTS: People born in 1966 in Northern Finland did not differ from those born in 1965 and 1967 in terms of the outcome measure. CONCLUSIONS: We found no association between participation in an epidemiological follow-up study and the use of psychiatric care services. The NFBC1966 may be regarded as a representative at the population level in terms of psychiatric outcomes despite the personal follow-up of the birth cohort. The associations of participation in epidemiological follow-up studies have previously been under-examined, and the results need to be replicated.

The interplay between inflammatory cytokines and cardiometabolic disease: bi-directional mendelian randomisation study.

Objective: To leverage large scale genetic association data to investigate the interplay between circulating cytokines and cardiometabolic traits, and thus identifying potential therapeutic targets. Design: Bi-directional Mendelian randomisation study. Setting: Genome-wide association studies from three Finnish cohorts (Northern Finland Birth Cohort 1966, Young Finns Study, or FINRISK study), and genetic association summary statistics pooled from observational studies for expression quantitative trait loci and cardiometabolic traits. Participants: Data for 47 circulating cytokines in 13 365 individuals from genome-wide association studies, summary statistic data for up to 21 735 individuals on circulating cytokines, summary statistic gene expression data across 49 tissues in 838 individuals, and summary statistic data for up to 1 320 016 individuals on cardiometabolic traits. Interventions: Relations between circulating cytokines and cardiovascular, anthropometric, lipid, or glycaemic traits (coronary artery disease, stroke, type 2 diabetes mellitus, body mass index, waist circumference, waist to hip ratio, systolic blood pressure, glycated haemoglobin, high density lipoprotein cholesterol, low density lipoprotein cholesterol, total cholesterol, triglycerides, C reactive protein, glucose, fasting insulin, and lifetime smoking). Main outcome methods: Genetic instrumental variables that are biologically plausible for the circulating cytokines were generated. The effects of cardiometabolic risk factors on concentrations of circulating cytokines, circulating cytokines on other circulating cytokines, and circulating cytokines on cardiometabolic outcomes were investigated. Results: Genetic evidence (mendelian randomisation P<0.0011) suggests that higher body mass index, waist circumference, smoking, higher concentrations of lipids, and systolic blood pressure increase circulating concentrations of several inflammatory cytokines and C reactive protein. Evidence for causal relations (mendelian randomisation P<0.0011) were noted between circulating cytokines, including a key role of vascular endothelial growth factor on influencing the concentrations of 10 other cytokines. Both mendelian randomisation (P<0.05) and colocalisation (posterior probability >0.5) suggested that coronary artery disease risk is increased by higher concentrations of circulating tumour necrosis factor related apoptosis-inducing ligand (TRAIL), interleukin-1 receptor antagonist (IL1RA), and macrophage colony-stimulating factor (MCSF). Conclusion: This study offers insight into inflammatory mediators of cardiometabolic risk factors, cytokine signalling cascades, and effects of circulating cytokines on different cardiometabolic outcomes.

Depression mediates the relationship between alexithymia and obesity in the Northern Finland Birth Cohort 1966 (NFBC1966).

BACKGROUND: The fact that a complex relationship exists between alexithymia and body mass index (BMI) is well established, but the underlying mechanisms remain poorly understood. Here, we explore the relationship between alexithymia and depressive symptoms in relation to adiposity measures, including the direct and indirect effect of alexithymia and depressive symptoms on obesity over a 15-year time-period, in the Northern Finland Birth Cohort 1966 (NFBC1966). METHODS: The study included individuals from the Northern Finland Birth Cohort 1966 (NFBC1966) who had available data for adiposity measures (body mass index and waist-to-hip ratio), alexithymia (measured by the 20-Item Toronto Alexithymia Scale: TAS-20), depressive symptoms (measured by the 13-item depression subscale of Hopkins Symptom Checklist: HSCL-13) at age of 31 years (n = 4773) and 46 years (n = 4431). Pearson's (r) correlation, and multiple linear regression were used to investigate the relationships between alexithymia, depressive symptoms, and adiposity measures. The potential mediating role of depressive symptoms was examined via Hayes' procedure (PROCESS). RESULTS: Positive correlations were confirmed between adiposity measures (BMI and WHR) and the TAS-20 score (and its subscale), but not between obesity and HSCL-13 score. The strongest correlation was between the DIF (difficulty identifying feelings) subscale of the TAS-20 and HSCL-13 at both time points (31 y: r(3013) = 0.41, p < 0.01, 46 y: r(3013) = 0.43, p < 0.01). Depressive symptoms completely (z = 2.55 (±0.00003), p = 0.01) and partly (z = 2.16 (±0.0001), p = 0.03) mediated the alexithymia-obesity relationship over the 15-year time-period. LIMITATIONS: Other psychological and environmental factors such as interoception, dietary intake and physical activities may also play a role as a potential mediating factor in alexithymia-obesity relationship. CONCLUSIONS: Our findings provide additional insights of theoretical framework of depressive symptoms mediation effect in the relationship between alexithymia and obesity. Alexithymia and depression should, therefore, be considered in the design of future clinical obesity research.

Association between participation in the Northern Finland Birth Cohorts and cardiometabolic disorders.

BACKGROUND: We studied the association between participation in the longitudinal follow-up study and cardiometabolic disorders in two longitudinal studies which started prospectively in the antenatal period: the Northern Finland Cohort 1966 (NFBC1966) and the Northern Finland Birth Cohort 1986 (NFBC1986). Both birth cohorts have been followed up since birth with multiple follow-ups including questionnaires, and clinical examinations. METHODS: The NFBC studies were compared to comparison cohorts of individuals who were born in the same area as the study cohorts, but in different years. The data for the comparison cohort were obtained from registers. The cumulative incidence rates of hospital-treated cardiometabolic disorders were calculated for study and comparison cohorts covering the age of 7-50 years in NFBC1966 and the age of 0-29 years in NFBC1986. Cardiometabolic-related causes of death were analysed in NFBC1966 and the comparison cohort from the age of 0-50 years. The analysed cardiometabolic disorders were diabetes mellitus, coronary artery disease, hyperlipidaemia, obesity, hypertension, and cerebrovascular disorders. The risk ratio (RR) with 95% confidence intervals (CI) was calculated by sex. RESULTS: In NFBC1966, no differences in cumulative incidences of cardiometabolic disorders or cardiometabolic-related deaths compared to the comparison cohort were found. Male members of NFBC1986 had decreased risk of obesity (RR: 0.45, 95% CI: 0.27-0.75) and any cardiometabolic disorders (RR: 0.75, 95% CI: 0.59-0.95) compared to the comparison cohort. CONCLUSIONS: The results suggest that participation in the NFBC1986 may have a weak positive health effect among men. Agreement to follow-up studies focusing on diet, substance use, and physical activity, may slightly decrease the incident risk of cardiometabolic disorders in the study population.KEY MESSAGESEven mild interventions, such as follow-up studies in the prospective follow-up studies, might affect participants' behaviour and consequently the incidence of cardiometabolic disordersThe fact that follow-up itself might affect the study population in terms of risk factors, has to be taken into account when estimating the representativeness of the followed population.

Insulin resistance and lipid levels in the middle-aged offspring of parents with severe mental illness.

BACKGROUND: Type 2 diabetes and dyslipidemias co-occur frequently with severe mental illnesses (SMI). However, less is known about serum insulin and lipid levels and prevalence of Insulin Resistance (IR) in offspring with familial risk for SMI. METHOD: The Northern Finland Birth Cohort 1966 consists of 12,068 mothers, 11,068 fathers, and 12,231 children from the two northernmost provinces in Finland. At age 46 they participated in clinical examination including measurements of glucose, lipids, and IR and answered a questionnaire including information about their nutrition and physical activity. The information on parental SMI was obtained from the Hospital Discharge Register. Parents with SMI were those who had been treated in hospital for any psychiatric disorder during 1969-1982 (ICD-8 codes 290-315). The final study group included 334 (7.3 %) offspring who had a parent with SMI and 4249 (92.7 %) offspring in the comparison group. RESULTS: We did not find increased risk for disturbances in lipid levels, insulin levels, or IR levels between the study group (offspring of either parent with SMI) compared with the comparison group. All offspring, especially female offspring of either parent with SMI, had an increased risk for higher glucose levels and waist circumference. The results remained the same after excluding offspring with SMI. CONCLUSION: Our findings suggest that offspring of parents with SMI, especially female offspring, have partly increased risk for disturbances in cardiometabolic risk factors. Disturbances in glucose metabolism may have an effect via familial risk of severe mental illness.

Parental suicide attempts and offspring mental health problems in childhood and adolescence.

BACKGROUND: The relationship between parental suicide attempts and offspring suicide risk has been established. However, the impact of parental suicide attempts on mental health problems in offspring as youth remains unexplored. This study examined the prospective association between parental suicide attempts and offspring internalizing, externalizing, and attention/hyperactivity problems in childhood and adolescence. We also examined how offspring mental health problems in childhood mediated the association between parental suicide attempts and offspring mental health problems in adolescence. METHODS: A subsample of 6,381 (48.4% female) cohort members with complete data on mental health problems in childhood and adolescence was extracted from the Northern Finland Birth Cohort 1986 Study. Offspring mental health problems were assessed via teacher's Rutter B2 scale during the childhood assessment (child's age of 8) and the Youth Self-Report scale (child's age of 15/16). Information about first parental suicide attempts was collected using ICD codes from hospital discharge records. RESULTS: Lifetime parental suicide attempts during the study period (N = 95) were associated with offspring internalizing, externalizing, and attention/hyperactivity problems in adolescence. Parental suicide attempts before the childhood assessment (N = 55) were associated with offspring behavioral problems in childhood [B (95% CI) = .64 (0.08-1.28)]. In the mediation models, parental suicide attempts before the childhood assessment had a significant indirect effect on offspring externalizing [B (95% CI) = .03 (0.01-0.05)] and attention/hyperactivity problems [B (95% CI) = .02 (0.01-0.04)] in adolescence via offspring behavioral problems in childhood. CONCLUSIONS: Our findings highlight the importance of assessing and monitoring mental health problems in offspring whose parents have been hospitalized for attempting suicide. Among children with behavioral problems, clinicians should inquire about parental history of suicide attempts, as children with familial vulnerability to suicide may develop externalizing and attention/hyperactivity problems in adolescence.

Specific adolescent prodromal symptoms associated with onset of psychosis in the Northern Finland Birth Cohort 1986.

BACKGROUND: Several psychological symptoms in adolescence associate with later development of psychosis. However, it is unclear which symptoms specifically predict psychotic disorders rather than psychiatric disorders in general. We conducted a prospective study comparing how specific adolescent psychotic-like symptoms, predicted psychotic and non-psychotic hospital-treated psychiatric disorders in the population-based Northern Finland Birth Cohort 1986 (NFBC1986). METHODS: At age 15-16 years, 6632 members of the NFBC1986 completed the PROD-screen questionnaire. New hospital-treated mental disorders of the NFBC1986 participants were detected between age 17 and 30 years from the Finnish Care Register for Health Care. Multiple covariates were used in the analysis. RESULTS: During the follow-up, 1.1% of the participants developed a psychotic and 3.2% a non-psychotic psychiatric disorder. Three symptoms were specifically associated with onset of psychosis compared to non-psychotic psychiatric disorders: 'Difficulty in controlling one's speech, behaviour or facial expression while communicating' (adjusted OR 4.00; 95% CI 1.66-9.92), 'Difficulties in understanding written text or heard speech' (OR 2.25; 1.12-4.51), and 'Difficulty or uncertainty in making contact with other people' (OR 2.20; 1.03-4.67). Of these, the first one remained statistically significant after Bonferroni correction for multiple comparisons. CONCLUSION: To our knowledge, this is the first general-population-based prospective study exploring psychiatric symptoms predicting the onset of hospital-treated first-episode psychosis in comparison to non-psychotic disorders. We found three symptoms related with difficulties in social interaction which predicted onset of psychosis. This is a novel finding and should be replicated.

Body mass index in the middle-aged offspring of parents with severe mental illness.

BACKGROUND: People with severe mental illness (SMI) have an elevated risk of obesity but the causes and mechanisms are unclear. We explored the familial association between parental SMI and body mass index (BMI) in middle-aged offspring. Our objective was to determine if the offspring of either parent with SMI have an increased risk for obesity. METHODS: The Northern Finland Birth Cohort 1966 is a cohort study of offspring with expected date of birth in 1966. The data include originally 12 068 mothers and 12 231 children from the provinces of Lapland and Oulu in Finland. The final study sample included 5050 middle-aged offspring. Parental SMI was used as exposure in the study. BMI measured at the age of 46 years was used as a primary outcome. RESULTS: Risk for obesity was elevated in the offspring of mothers with SMI [overweight: adjusted odds ratio (OR) 1.93 (1.29-2.90), obese class I: 1.97 (1.20-3.25), obese classes II-III: 2.98 (1.67-5.33)]. For the offspring of either parent with SMI, statistically significant results were found in obese class I and obese classes II-III [overweight: adjusted OR 1.21 (0.94-1.54), obese class I: 1.52 (1.03-1.08), obese classes II-III: 1.53 (1.01-2.32)]. CONCLUSIONS: We found an elevated risk of obesity in the middle-aged offspring of either parent with SMI, especially in the offspring of mothers with SMI. Thus, there might be a common familial pathway leading to the co-occurrence of obesity and SMI.

Parental suicide attempts and offspring's risk of attempting or dying by suicide: does the timing of a parental suicide attempt matter?

BACKGROUND: Studies on the transmission of suicide risk have focused on parental history of suicide attempts (SAs), overlooking when the attempt happened. This study examined how the offspring's risk of attempting or dying by suicide varied by the timing of a first parental SA and the sex of the parent who attempted suicide. METHODS: Participants were 59 469 members of the 1987 Finnish Birth Cohort. The Finnish Hospital Discharge and Cause of Death Registers were the sources for parental and offspring SAs and offspring suicide. Timing of parental SA was coded as before (pre-pregnancy and pregnancy) and after the child's birth [infant/toddler years (0-2 years), childhood (3-11 years), adolescence (12-17 years), and young adulthood (18-26 years)]. RESULTS: In the multivariate models, having a parent who attempted suicide increased the offspring's risk of attempting suicide (odds ratio (OR) = 1.77, 95% confidence interval (CI) 1.39-2.25), but not of dying by suicide. Compared to unexposed offspring, those exposed after child's birth were at higher risk of attempting suicide (OR = 1.90, 95% CI 1.46-2.47), specifically when the parent attempted during offspring's childhood, adolescence, and young adulthood. A first maternal SA increased offspring's risk of attempting suicide regardless of the timing. CONCLUSIONS: The impact of a parental SA on offspring's risk of attempting suicide differed depending on the timing and sex of the parent who attempted suicide, suggesting that the transmission of suicide risk may occur through genetic as well as environmental factors. Our findings call for an intergenerational approach in suicide risk assessment.

Potential for prediction of psychosis and bipolar disorder in Child and Adolescent Mental Health Services: a longitudinal register study of all people born in Finland in 1987.

Current strategies to predict psychosis identify only a small proportion of individuals at risk. Additional strategies are needed to increase capacity for pre-diction and prevention of serious mental illness, ideally during childhood and adolescence. One possible approach would be to investigate systems in which psychosis risk factors are concentrated during childhood. One notable such system is represented by Child and Adolescent Mental Health Services (CAMHS). Although psychotic disorders are uncommon in CAMHS, many risk factors for psychosis are highly prevalent in young people who enter this system. We hypothesized, therefore, that youth attending CAMHS would be a high-risk group for psychosis if followed into adulthood and, furthermore, that CAMHS systems would capture a substantial proportion of future psychosis cases. We constructed a total population cohort study of all Finns born in 1987 (N=55,875), linking together extensive register data on health care contacts from birth through age 28 years. We identified all individuals diagnosed with a psychotic or bipolar disorder by age 28 (N=1,785). The risk of psychosis/bipolar disorder by age 28 years was 1.8% for individuals who had not attended CAMHS during childhood or adolescence, whereas it was 12.8% for those with a history of any outpatient CAMHS contact (odds ratio, OR=7.9, 95% CI: 7.2-8.7). Furthermore, the risk of psychosis/bipolar disorder by age 28 years was 2.3% for individuals without a history of inpatient CAMHS admission, whereas it was 24.0% for those with a history of inpatient CAMHS admission (OR=13.3, 95% CI: 11.9-14.9), and 36.5% for those with a history of inpatient CAMHS admission in adolescence (age 13-17 years) (OR=24.2, 95% CI: 21.2-27.6). Individuals who attended CAMHS but received no mental disorder diagnosis had an equally high risk of subsequently developing a psychosis/bipolar disorder as individuals who did receive a diagnosis (OR=0.9, 99.5% CI: 0.7-1.1). Compared to other CAMHS attendees, individuals who developed psychosis or bipolar disorder were more likely to have had an initial CAMHS diagnosis of depressive or other mood disorder (OR=2.3, 99.5% CI: 1.6-3.0) and disruptive behaviour disorder (OR=1.7, 99.5% CI: 1.2-2.5). Of all psychosis/bipolar diagnoses by age 28 years, 50.2% occurred in individuals who had, at some point in childhood or adolescence, attended CAMHS, indicating that CAMHS represent not only a high-risk but also a high-capacity system for prediction of psychosis/bipolar disorder. These findings suggest an enormous, untapped potential for large-scale psychosis/bipolar disorder prediction and prevention research within existing specialist CAMHS.

Trajectories of adolescent psychotic-like experiences and early cannabis exposure: Results from a Finnish Birth Cohort Study.

BACKGROUND: Longitudinal studies examining the effect of cannabis exposure (CE) on the prognosis of adolescents with psychotic-like experiences (PLEs) are scarce. We examined trajectories of mental health in adolescents with PLEs and cannabis exposure. METHODS: The Northern Finland Birth Cohort 1986 (n = 6552) with linkage to nationwide register data was used. Information on lifetime cannabis exposure was collected when participants were aged 15/16. Register-based outcome data on diagnoses made in clinical practice were obtained until age 33. Logistic regression was used to study the association of PLE/CE patterns and subsequent psychiatric disorders. The group with neither PLEs nor CE was utilized as the reference group. Parental psychiatric disorders, family structure, sex, frequent alcohol intoxications, daily smoking and illicit substance use other than cannabis were adjusted for. RESULTS: In all, 6552 subjects (49.2 % males) were included in analysis. PLEs with cannabis exposure were associated with any psychiatric disorder (OR = 2.59; 95 % CI 1.82-3.68), psychotic disorders (OR = 3.86; 95 % CI 1.83-8.11), mood disorders (OR 4.07; 95 % CI 2.74-6.04), depressive disorders (OR = 4.35; 95 % CI 2.93-6.48), anxiety disorders (OR = 2.06; 95 % CI 1.34-3.17) and substance use disorders (OR = 2.26; 95 % CI 1.13-4.50) compared to reference group. Effect sizes were greater for group with both PLEs and cannabis use than for group with PLEs only. CONCLUSIONS: Early-onset cannabis use is an adverse prognostic marker for adolescents with PLEs after extensive confounder control including other substance use.

Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder.

We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.

Association of participation in the Northern Finland Birth Cohort 1986 with mental disorders and suicidal behaviour.

OBJECTIVES: In prospective follow-up studies, participants are normally contacted during the follow-up period. Even though the idea is not to intervene, the studies conducted during follow-up may affect the target population. Our hypotheses were that participation in the prospective Northern Finland Birth Cohort 1986 study (NFBC 1986) increased the use of mental health services and reduced suicidal behaviour due to participation in follow-up studies. METHODS: The NFBC 1986 study covered people with an expected date of birth between July 1985 and June 1986 in northern Finland (n=9,396). The participants of the NFBC 1986 were followed since the antenatal period with follow-ups including clinical examinations. The comparison cohort comprised people born in the same area in 1987 (n=8,959), who were not contacted. Registry data on psychiatric treatment, suicide attempts, and suicides were available. Crude risk ratios (RRs) and adjusted (for marital status and education) Mantel-Haenszel RRs were reported. RESULTS: No increase in mental disorders were found in NFBC 1986 compared to comparison cohort. In the crude RR analysis of female participants, a lower risk for suicide attempts was found (RR, 0.67; 95% confidence interval, 0.49 to 0.92; p=0.011). CONCLUSIONS: The results did not support our first hypothesis regarding the increased use of mental health services in the NFBC 1986 cohort. However, our second hypothesis gained some support as female participants of the NFBC 1986 had a lower risk of suicide attempts, although it was not due to a higher number of participants receiving psychiatric treatment.

Optic Nerve Parameters and Cognitive Function in the Northern Finland Birth Cohort Eye Study.

PURPOSE: The optic nerve head (ONH) is a part of the brain that can be easily studied through the transparent medium of the eye. We explored the relationship between the properties of the optic nerve head, the retinal nerve fiber layer (RNFL) and cognitive function. METHODS: Participants of the Northern Finland Birth Cohort (NFBC) 1966 underwent an ophthalmic and cognitive assessment after randomization at age 46. The ophthalmological parameters obtained were the disc area and the neuroretinal rim volume of the ONH and the average RNFL thickness. The surrogates used for cognitive function were the paired associates learning test (PAL), level of education, grade point average (GPA) and Humphrey 24-2 perimetric test time (HFA). We did exploratory research between the ophthalmological parameters and the surrogates for cognition and the correlations between the surrogates for cognition. RESULTS: We found that a larger disc area was associated with a higher level of education, faster accomplishment of the HFA (R = -0.065) but a lower GPA (R = -0.084). An increase in neuroretinal rim volume was associated with fewer errors in the PAL test (R = -0.056), higher level of education, higher GPA (R = 0.072) and faster accomplishment of the HFA (R = -0.047). A thicker RNFL was associated with faster accomplishment of the HFA (R = -0.047). CONCLUSION: We were able to find statistically significant associations between the parameters of the optic nerve head, the RNFL and cognition in the NFBC Eye study. However, the correlations were negligible at best and of limited predictive value.