David Gyllenberg

Childhood Bullying Behavior and Later Psychiatric Hospital and Psychopharmacologic Treatment Findings From the Finnish 1981 Birth Cohort Study

CONTEXT No prospective population-based study examining predictive associations between childhood bullying behavior and long-term mental health outcomes in both males and females exists. OBJECTIVE To study predictive associations between bullying and victimization in childhood and later psychiatric hospital and psychopharmacologic treatment. DESIGN Nationwide birth cohort study from age 8 to 24 years. PARTICIPANTS Five thousand thirty-eight Finnish children born in 1981 with complete information about bullying and victimization at age 8 years from parents, teachers, and self-reports. MAIN OUTCOME MEASURES National register-based lifetime information about psychiatric hospital treatments and psychopharmacologic medication prescriptions. RESULTS When controlled for psychopathology score, frequent victim status at age 8 years among females independently predicted psychiatric hospital treatment and use of antipsychotic, antidepressant, and anxiolytic drugs. Among males, frequent bully-victim and bully-only statuses predicted use of antidepressant and anxiolytic drugs. Frequent bully-victim status among males also predicted psychiatric hospital treatment and use of antipsychotics. However, when the analysis was controlled with total psychopathology score at age 8 years, frequent bully, victim, or bully-victim status did not predict any psychiatric outcomes among males. CONCLUSIONS Boys and girls who display frequent bullying behavior should be evaluated for possible psychiatric problems, as bullying behaviors in concert with psychiatric symptoms are early markers of risk of psychiatric outcome. Among females, frequent childhood victimization predicts later psychiatric problems irrespective of psychiatric problems at baseline.

Childhood Predictors of Completed and Severe Suicide Attempts: Findings From the Finnish 1981 Birth Cohort Study

CONTEXT To our knowledge, no prospective, population-based study in existence examines predictive associations between early or middle childhood psychopathologic disorders and later completed suicides. OBJECTIVE To study predictive associations between childhood psychopathologic disorders at the age of 8 years and later completed suicides and severe suicide attempts. DESIGN Birth cohort study of individuals 8 to 24 years old. SETTING Finland. PARTICIPANTS The sample includes 5302 Finnish people born in 1981 who were examined at the age of 8 years to gather information about psychopathologic conditions, school performance, and family demographics from parents, teachers, and children. MAIN OUTCOME MEASURES National register-based lifetime information about completed suicides and suicide attempts that prompted hospital admission. RESULTS Of all 24 deaths among males between 8 and 24 years of age, 13 were suicides, whereas of 16 deaths among females, only 2 were suicides. Fifty-four males and females (1%) had either completed suicide or made a serious suicide attempt, defined as a suicide attempt that prompted hospital admission. Of 27 males with completed or serious suicide attempts, 78% screened positive on parent or teacher Rutter scales at the age of 8 years, whereas of 27 females only 11% screened positive. Among males, completed or serious suicide attempt outcome was predicted at the age of 8 years by living in a nonintact family; psychological problems as reported by the primary teacher; or conduct, hyperkinetic, and emotional problems. However, self-reports of depressive symptoms at the age of 8 years did not predict suicide outcome. No predictive associations between the study variables measured at the age of 8 years and suicide outcome were found among females. Male suicide outcome was predicted most strongly by comorbid conduct and internalizing problems. CONCLUSIONS Most males who completed suicide and/or made serious suicide attempts in adolescence or early adulthood had psychiatric problems by the age of 8 years, indicating a trajectory that persists throughout their lives. However, female severe suicidality is not predicted by psychopathologic disorders at the age of 8 years. The results give additional support to the importance of early detection and treatment of psychiatric problems in males.

Pregnancy Complications Following Prenatal Exposure to SSRIs or Maternal Psychiatric Disorders: Results From Population-Based National Register Data

OBJECTIVE Using national register data, the authors examined the relationship between prenatal selective serotonin reuptake inhibitor (SSRI) treatment and pregnancy complications, accounting for psychiatric diagnoses related to SSRI use. METHOD This was a population-based prospective birth cohort study using national register data. The sampling frame included 845,345 offspring, representing all singleton live births in Finland between 1996 and 2010. Pregnancies were classified as exposed to SSRIs (N=15,729), unexposed to SSRIs but with psychiatric diagnoses (N=9,652), and unexposed to medications and psychiatric diagnoses (N=31,394). Pregnancy outcomes in SSRI users were compared with those in the unexposed groups. RESULTS Offspring of mothers who received SSRI prescriptions during pregnancy had a lower risk for late preterm birth (odds ratio=0.84, 95% CI=0.74-0.96), for very preterm birth (odds ratio=0.52, 95% CI=0.37-0.74), and for cesarean section (odds ratio=0.70, 95% CI=0.66-0.75) compared with offspring of mothers unexposed to medications but with psychiatric disorders. In contrast, in SSRI-treated mothers, the risk was higher for offspring neonatal complications, including low Apgar score (odds ratio=1.68, 95% CI=1.34-2.12) and monitoring in a neonatal care unit (odds ratio=1.24, 95% CI=1.14-1.35). Compared with offspring of unexposed mothers, offspring of SSRI-treated mothers and mothers unexposed to medications but with psychiatric disorders were both at increased risk of many adverse pregnancy outcomes, including cesarean section and need for monitoring in a neonatal care unit. CONCLUSIONS In a large national birth cohort, treatment of maternal psychiatric disorders with SSRIs during pregnancy was related to a lower risk of preterm birth and cesarean section but a higher risk of neonatal maladaptation. The findings provide novel evidence for a protective role of SSRIs on some deleterious reproductive outcomes, possibly by reducing maternal depressive symptoms. The divergent findings suggest that clinical decisions on SSRI use during pregnancy should be individualized, taking into account the mothers psychiatric and reproductive history.

Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort

BACKGROUND Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early gestation to mid-gestation is associated with schizophrenia in offspring. METHODS The investigation is based on the Finnish Prenatal Study of Schizophrenia, a nested case-control study that included archived maternal sera from virtually all pregnancies since 1983 (N = >1 million). We identified all offspring in the cohort with a diagnosis of schizophrenia based on the national inpatient and outpatient register and matched them on sex, date of birth, and residence in Finland at time of onset of the case to comparison subjects (1:1) from the cohort. Maternal sera of 1010 case-control pairs were assessed for free thyroxine, and sera of 948 case-control pairs were assessed for thyroid-stimulating hormone. RESULTS Maternal hypothyroxinemia (free thyroxine ≤10th percentile, normal thyroid-stimulating hormone) was associated with an increased odds of schizophrenia (odds ratio = 1.75, 95% confidence interval = 1.22-2.50, p = .002). When adjusted for maternal psychiatric history, province of birth, and maternal smoking during pregnancy, the association remained significant (odds ratio = 1.70, 95% confidence interval = 1.13-2.55, p = .010). CONCLUSIONS In a large, national birth cohort, prospectively documented hypothyroxinemia during early gestation to mid-gestation was associated with increased odds of schizophrenia in offspring. This information can inform translational studies of maternal hypothyroxinemia examining molecular and cellular deviations relevant to schizophrenia.

Association of Selective Serotonin Reuptake Inhibitor Exposure During Pregnancy With Speech, Scholastic, and Motor Disorders in Offspring

Importance Speech/language, scholastic, and motor disorders are common in children. It is unknown whether exposure to selective serotonin reuptake inhibitors (SSRIs) during pregnancy influences susceptibility to these disorders. Objective To examine whether SSRI exposure during pregnancy is associated with speech/language, scholastic, and motor disorders in offspring up to early adolescence. Design, Setting, and Participants This prospective birth cohort study examined national population-based register data in Finland from 1996 to 2010. The sampling frame includes 845 345 pregnant women and their singleton offspring with data on maternal use of antidepressants and depression-related psychiatric disorders during pregnancy. Exposures There were 3 groups of offspring: 15 596 were in the SSRI-exposed group, ie, had mothers diagnosed as having depression-related psychiatric disorders with a history of purchasing SSRIs during pregnancy; 9537 were in the unmedicated group, ie, had mothers diagnosed as having depression-related psychiatric disorders without a history of purchasing SSRIs during pregnancy; and 31 207 were in the unexposed group, ie, had mothers without a psychiatric diagnosis or a history of purchasing SSRIs. Main Outcomes and Measures Cumulative incidence of speech/language, scholastic, or motor disorders (829, 187, and 285 instances, respectively) from birth to 14 years. All hypotheses tested were formulated before data collection. Results Of the 56 340 infants included in the final cohort, 28 684 (50.9%) were male and 48 782 (86.6%) were 9 years or younger. The mean (SD) ages of children at diagnosis were 4.43 (1.67), 3.55 (2.67), and 7.73 (2.38) for speech/language, scholastic, and motor disorders, respectively. Offspring of mothers who purchased SSRIs at least twice during pregnancy had a significant 37% increased risk of speech/language disorders compared with offspring in the unmedicated group. The cumulative hazard of speech/language disorders was 0.0087 in the SSRI-exposed group vs 0.0061 in the unmedicated group (hazard ratio, 1.37; 95% CI, 1.11-1.70; P = .004). There was a significantly increased risk of these disorders in offspring in the SSRI-exposed and unmedicated groups compared with offspring in the unexposed group. For scholastic and motor disorders, there were no differences between offspring in the SSRI-exposed group and in the unmedicated group. Conclusions and Relevance Exposure to SSRIs during pregnancy was associated with an increased risk of speech/language disorders. This finding may have implications for understanding associations between SSRIs and child development.

Parental age and the risk of attention-deficit/hyperactivity disorder: a nationwide, population-based cohort study.

OBJECTIVE An increasing number of studies has shown an association between parental age and psychiatric disorders. However, there are inconsistent results regarding whether age at parenthood is associated with attention-deficit/hyperactivity disorder (ADHD). The aim of this study is to examine whether low or advanced parental age is associated with ADHD. METHOD In this nested case-control study, we identified 10,409 individuals with ADHD born in Finland during 1991 to 2005 and diagnosed with ADHD between 1995 and 2011, along with 39,125 controls matched on sex, date, and place of birth, from nationwide population-based registers. Conditional logistic regression was used to examine the association between parental age and ADHD in offspring, adjusting for potential confounding due to parental psychiatric history, maternal socioeconomic status, marital status, maternal smoking during pregnancy, number of previous births, and birth weight for gestational age. RESULTS Fathers younger than 20 years had a 1.5-fold (odds ratio [OR] = 1.55, 95% CI = 1.11-2.18, p = .01) increased risk of having offspring with ADHD as compared to fathers aged 25 to 29 years. Mothers of the same age group had a 1.4-fold (OR = 1.41, 95% CI = 1.15-1.72, p =.0009) increased risk. Advanced maternal age was inversely associated with ADHD (OR = 0.79, 95% CI = 0.64-0.97, p = .02). CONCLUSION ADHD was associated with young fathers or mothers at the time of birth. Health professionals working with young parents should be aware of the increased risk of ADHD in offspring. This will improve early detection; however, for the development of preventive measures and appropriate interventions, more information on the developmental pathways is needed.

Childhood Predictors of Use and Costs of Antidepressant Medication by Age 24 Years: Findings from the Finnish Nationwide 1981 Birth Cohort Study.

OBJECTIVE Prior studies on antidepressant use in late adolescence and young adulthood have been cross-sectional, and prospective associations with childhood psychiatric problems have not been examined. The objective was to study the association between childhood problems and lifetime prevalence and costs of antidepressant medication by age 24 years. METHOD A total of 5,547 subjects from a nation-wide birth cohort were linked to the National Prescription Register. Information about parent- and teacher-reported conduct, hyperkinetic and emotional symptoms, and self-reported depressive symptoms was gathered at age 8 years. The main outcome measure was national register-based lifetime information about purchases of antidepressants between ages 8 and 24 years. In addition, antidepressant costs were analyzed using a Heckman maximum likelihood model. RESULTS In all, 8.8% of males and 13.8% of females had used antidepressants between age 13 and 24 years. Among males, conduct problems independently predicted later antidepressant use. In both genders, self-reported depressive symptoms and living in other than a family with two biological parent at age 8 years independently predicted later antidepressant use. Significant gender interactions were found for conduct and hyperkinetic problems, indicating that more males who had these problems at age 8 have used antidepressants compared with females with the same problems. CONCLUSIONS Childhood psychopathology predicts use of antidepressants, but the type of childhood psychopathology predicting antidepressant use is different among males and females.

Infant and childhood neurodevelopmental outcomes following prenatal exposure to selective serotonin reuptake inhibitors: overview and design of a Finnish Register-Based Study (FinESSI)

BackgroundExperimental animal studies and one population-based study have suggested an increased risk for adverse neurodevelopmental outcome after prenatal exposure to SSRIs. We describe the methods and design of a population-based study examining the association between prenatal SSRI exposure and neurodevelopment until age 14.Methods and designThis is a cohort study of national registers in Finland: the Medical Birth Register, the Register of Congenital Malformations, the Hospital Discharge Register including inpatient and outpatient data, the Drug Reimbursement Register, and the Population Register. The total study population includes 845,345 women and their live-born, singleton offspring aged 14 or younger and born during Jan 1st 1996-Dec 31st 2010. We will compare the prevalence of psychiatric and neurodevelopmental outcomes in offspring exposed prenatally to SSRIs to offspring exposed to prenatal depression and unexposed to SSRIs. Associations between exposure and outcome are assessed by statistical methods including specific modeling to account for correlated outcomes within families and differences in duration of follow-up between the exposure groups. Descriptive results. Of all pregnant women with pregnancy ending in delivery (n = 859,359), 1.9% used SSRIs. The prevalence of diagnosed depression and depression-related psychiatric disorders within one year before or during pregnancy was 1.7%. The cumulative incidence of registered psychiatric or neurodevelopmental disorders was 6.9% in 2010 among all offspring born during the study period (age range 0–14 years).DiscussionThe study has the potential for significant public health importance in providing information on prenatal exposure to SSRIs and long-term neurodevelopment.

Specialized Service Use for Psychiatric and Neurodevelopmental Disorders by Age 14 in Finland

OBJECTIVE Most studies on the diagnostic patterns of usage of specialized services for childhood psychiatric and neurodevelopmental disorders have been cross-sectional, and the aim of this study was to provide longitudinal data. METHODS The Medical Birth Register and the Finnish Hospital Discharge Register were used to study the use of inpatient or public outpatient specialized services for psychiatric and neurodevelopmental disorders between birth and age 14 in 2010 (cumulative incidence) and in year 2010 at age 14 (one-year prevalence) among Finnish children born in 1996 (N=58,538 singleton live births). RESULTS The cumulative incidence of specialized service use for any psychiatric or neurodevelopmental disorders between birth and age 14 was 12.9%, and the one-year prevalence in 2010 at 14 years was 4.2%. The cumulative incidence by age 14 was 5.5% for learning and coordination disorders, 2.2% for anxiety disorders, 2.0% for hyperkinetic disorders, 1.7% for conduct disorders, 1.4% for depression, 1.0% for autism spectrum disorders, and .7% for stress and adjustment disorders. Learning and coordination, hyperkinetic, and autism spectrum disorders were more prevalent among boys, were often diagnosed before school age, and had 9%-51% lifetime comorbidity with each other. Depressive, anxiety, and stress and adjustment disorders had similar distributions between the sexes, were often diagnosed in early adolescence, and showed 8%-31% lifetime comorbidity with each other. CONCLUSIONS Every eighth Finnish child had visited specialized services for psychiatric or neurodevelopmental disorders sometime between birth and age 14. Learning and coordination disorders were diagnosed more than twice as often as anxiety, hyperkinetic, and conduct disorders.