Pirjo Mäki

Association of cannabis use with prodromal symptoms of psychosis in adolescence

Recent interest has focused on the association between cannabis use and risk of psychosis. In the largest unselected, population-based study on this topic to date, we examined cannabis use and prodromal symptoms of psychosis at age 15-16 years among 6330 adolescents. Those who had tried cannabis (n=352; 5.6% of the total sample) were more likely to present three or more prodromal symptoms even after controlling for confounders including previous behavioural symptoms (OR=2.23; 95% CI 1.70-2.94). A dose-response effect was seen. We conclude that cannabis use is associated with prodromal symptoms of psychosis in adolescence.

Longitudinal associations between childhood and adulthood externalizing and internalizing psychopathology and adolescent substance use.

BACKGROUND Emotional and behavioral problems are commonly associated with substance use in adolescence but it is unclear whether substance use precedes or follows mental health problems. The aim was to investigate longitudinal associations between externalizing and internalizing psychopathology and substance use in a prospective population study design. METHOD The sample was the Northern Finland Birth Cohort 1986 Study (NFBC 1986; n = 6349; 3103 males). Externalizing and internalizing mental health problems were assessed at age 8 years (Rutter scales), substance use and externalizing and internalizing problems [Youth Self-Report (YSR)] at age 15-16 years, and hospital diagnoses for internalizing disorders (age 25) and criminal offences (age 20) from nationwide registers in adulthood. RESULTS Externalizing problems at age 8 were associated with later substance use. After adjustment for sociodemographic factors, parental alcohol use and psychiatric disorders, and earlier externalizing and internalizing problems, substance use predicted criminality, especially among males, with the highest odds ratio (OR) for cannabis use [adjusted OR 6.2, 95% confidence interval (CI) 3.1-12.7]. Early internalizing problems were not a risk for later substance use. Female adolescent cannabis (OR 3.2, 95% CI 1.4-7.3) and alcohol (OR 2.1, 95% CI 1.1-4.2) use predicted internalizing disorders in adulthood. CONCLUSIONS Externalizing problems precede adolescent substance use in both genders, whereas, among boys, substance use also precedes criminal offences. Internalizing problems may follow substance use in females. These associations were robust even when taking into account previous mental health problems.

Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication.

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.

Impact of temperament on depression and anxiety symptoms and depressive disorder in a population-based birth cohort

BACKGROUND The aim of this study was to characterize at the population level how innate features of temperament relate to experience of depressive mood and anxiety, and whether these symptoms have separable temperamental backgrounds. METHODS The study subjects were 4773 members of the population-based Northern Finland Birth Cohort 1966, a culturally and genetically homogeneous study sample. Temperament was measured at age 31 using the temperament items of the Temperament and Character Inventory and a separate Pessimism score. Depressive mood was assessed based on a previous diagnosis of depressive disorder or symptoms of depression according to the Hopkins Symptom Check List - 25. Anxiety was assessed analogously. RESULTS High levels of Harm avoidance and Pessimism were related to both depressive mood (effect sizes; d=0.84 and d=1.25, respectively) and depressive disorder (d=0.68 and d=0.68, respectively). Of the dimensions of Harm avoidance, Anticipatory worry and Fatigability had the strongest effects. Symptoms of depression and anxiety showed very similar underlying temperament patterns. LIMITATIONS Although Harm avoidance and Pessimism appear to be important endophenotype candidates for depression and anxiety, their potential usefulness as endophenotypes, and whether they meet all the suggested criteria for endophenotypes will remain to be confirmed in future studies. CONCLUSIONS Personality characteristics of Pessimism and Harm avoidance, in particular its dimensions Anticipatory worry and Fatigability, are strongly related to symptoms of depression and anxiety as well as to depressive disorder in this population. These temperamental features may be used as dimensional susceptibility factors in etiological studies of depression, which may aid in the development of improved clinical practice.

Serum C-reactive protein in adolescence and risk of schizophrenia in adulthood: A prospective birth cohort study

Highlights • This is one of the first longitudinal studies of serum CRP & subsequent schizophrenia.• Elevated serum CRP in adolescence is associated with risk of adult schizophrenia.• The CRP-schizophrenia association is consistent with a dose-response relationship.

Interaction of early environment, gender and genes of monoamine neurotransmission in the aetiology of depression in a large population-based Finnish birth cohort

Objectives Depression is a worldwide leading cause of morbidity and disability. Genetic studies have recently begun to elucidate its molecular aetiology. The authors investigated candidate genes of monoamine neurotransmission and early environmental risk factors for depressiveness in the genetically isolated population-based Northern Finland Birth Cohort 1966 (12 058 live births). Design The authors ascertained and subdivided the study sample (n=5225) based on measures of early development and of social environment, and examined candidate genes of monoamine neurotransmission, many of which have shown prior evidence of a gene–environment interaction for affective disorders, namely SLC6A4, TPH2, COMT, MAOA and the dopamine receptor genes DRD1–DRD5. Results and conclusion The authors observed no major genetic effects of the analysed variants on depressiveness. However, when measures of early development and of social environment were considered, some evidence of interaction was observed. Allelic variants of COMT interacted with high early developmental risk (p=0.005 for rs2239393 and p=0.02 for rs4680) so that the association with depression was detected only in individuals at high developmental risk group (p=0.0046 and β=0.056 for rs5993883–rs2239393–rs4680 risk haplotype CGG including Val158), particularly in males (p=0.0053 and β=0.083 for the haplotype CGG). Rs4274224 from DRD2 interacted with gender (p=0.017) showing a significant association with depressiveness in males (p=0.0006 and β=0.0023; p=0.00005 and β=0.069 for rs4648318–rs4274224 haplotype GG). The results support the role of genes of monoamine neurotransmission in the aetiology of depression conditional on environmental risk and sex, but not direct major effects of monoaminergic genes in this unselected population.

Young people at risk for psychosis: case finding and sample characteristics of the Oulu Brain and Mind Study

Aim: Set within the general population‐based Northern Finland Birth Cohort 1986, the Oulu Brain and Mind Study aims to explore the causes and pathogenesis of psychotic illness by following young people at risk for psychosis due to having a first‐degree relative with psychotic illness or due to having experienced psychotic‐like symptoms themselves. We report the study methods and explore the relationship between these definitions of high risk for psychosis and operational criteria for a prodromal psychosis syndrome based on interview.

Parental separation at birth and depression in adulthood: a long-term follow-up of the Finnish Christmas Seal Home Children

BACKGROUND Early separation of a child from the mother has been considered a risk factor for later depression. We investigated the association between very early separation and depression in adulthood in a unique dataset. METHOD The index cohort consisted of 3020 subjects born in 1945-1965 in Finland, isolated from their family due to tuberculosis in the family and placed in special nurseries, immediately after birth, for an average time of 7 months. Those subjects alive at 1 January, 1971 were identified. For every index subject two reference subjects were chosen, the matching criteria being sex, year of birth and place of birth. Data on depression were obtained from the Finnish Hospital Discharge Register by the end of year 1998. RESULTS In males, 4.2% of the index subjects and 2.6% (Adjusted Rate Ratio RR 1.7, 95% CI 1.3-2.3) of the reference subjects had been treated in hospital due to a depressive episode. In females the respective figures were 3.9% for index subjects and 3.6% (RR 1.1, 95% CI 0.8-1.5) for reference subjects. CONCLUSIONS The index subjects had an elevated risk for hospital treated depression in adulthood. One explanation may be that the very early temporal separation from the mother at birth may have unfavourable effects on later psychological development. On the other hand, separation from the parents at birth was not found to be strongly associated with severe adulthood depression.

Temporary parental separation at birth and substance use disorder in adulthood

BackgroundAdversities in the early mother-infant relation pose a hypothetical risk for addiction. We studied the association between very early separation and later development of substance use disorder.MethodA follow-up study was performed of subjects temporarily isolated from their family immediately after birth to adequate nursing homes in order to protect them against morbidity and mortality for tuberculosis. The average separation time was 7 months. The index cohort consisted of 3,020 subjects born in 1945–1965. For every index subject, two reference subjects were matched for sex, year of birth and place of birth. We were able to obtain the SES of the family of origin as recorded in 1971 from Statistics Finland. Finnish Hospital Discharge Register was used to identify subjects with substance use disorder arising from childhood to middle age, between January 1,1971 and December 31, 1998.ResultsThe 28-year cumulative incidence of alcohol use disorders was 4.2% in the index cohort and 3.1% in the reference cohort (rate ratio, RR 1.4, 95% CI 1.1–1.8). The incidences of hospital-treated drug abuse or dependence were 0.6% and 0.2% (RR 2.5, 95% CI 1.2–5.1), respectively. The differences in socioeconomic status of the family of origin did not explain the differences found.ConclusionsSubstance use disorders were more prevalent among subjects temporarily separated at birth from their mothers because of tuberculosis in the family than in the reference cohort. While risks experienced during pregnancy, delivery and childhood are alternative explanations, this result suggests that very early temporal separation from the mother at birth may have had unfavourable but modest effects on later psychological development, including vulnerability to addiction.

Maternal separation at birth and schizophrenia—a long-term follow-up of the Finnish Christmas Seal Home Children

OBJECTIVE Problems in the early mother-infant relation pose a hypothetical risk factor of schizophrenia. We studied the association between very early separation and later development of schizophrenia or other psychoses in a unique data set. METHOD The index cohort consisted of 3020 subjects born in 1945-1965 in Finland who were temporarily isolated from their family immediately after birth to adequate nursing homes due to tuberculosis in the family. The average separation time was 7 months. For every index subject, two reference subjects were matched for sex, year of birth and place of birth. The Finnish Hospital Discharge Register was used to identify subjects with schizophrenia and other psychoses arising from childhood to middle age, between January 1, 1971 and December 31, 1998. RESULTS The 28-year cumulative incidence of schizophrenia was 1.6% both in the index cohort and in the reference cohort (rate ratio 1.01, 95% CI 0.75-1.37). The incidences of other psychotic disorders were 1.5% and 1.3% (RR 1.11, 95% CI 0.79-1.58), respectively. CONCLUSION Separation at birth was not found to be associated with either schizophrenia or other psychotic illness. Temporary placement to adequate nursing homes in the first year of life is unlikely to increase the risk for schizophrenia or other psychoses.