Antisocial and borderline personality disorders in the offspring of antenatally depressed mothers - a follow-up until mid-adulthood in the Northern Finland 1966 birth cohort.

Background: Maternal depression is common during pregnancy, affecting 10-15% of mothers. In previous reports, the offspring of antenatally depressed mothers have had an elevated risk for antisocial, criminal and violent behaviour in adolescence, and for borderline personality features in childhood, but long-term outcomes are unknown.Aims: To study whether the adult offspring of antenatally depressed mothers have an elevated risk for antisocial (ASPD) or borderline personality disorder (BPD) when followed until mid-adulthood.Methods: In the general population-based Northern Finland 1966 Birth Cohort, mothers of 12,058 children were asked during mid-gestation if they felt depressed. Of the mothers, 14% reported being depressed. The offspring were followed for 49 years. The diagnoses of in- and outpatient-treated ASPD and BPD in the offspring were detected using the Finnish Care Register for Healthcare. Maternal antenatal smoking, newborn´s low birthweight or short gestational age, father's social class, and family type at birth were considered as confounding variables. Logistic regression analyses on the potential confounders were performed. Maternal postnatal depression and paternal ASPD information was not available.Results: In the male offspring of antenatally depressed mothers, the risk for ASPD was elevated (adjusted odds ratio 5.6; 95% confidence interval 1.8-17.8), but not in female offspring. The risk for BPD was not elevated in the offspring of antenatally depressed mothers in this study.Conclusions: The sons of antenatally depressed mothers had an increased risk for ASPD. Prevention and treatment of antenatal depression might present an opportunity to decrease the risk of antisocial personality in the offspring.

Severe mood disorders and schizophrenia in the adult offspring of antenatally depressed mothers in the Northern Finland 1966 Birth Cohort: Relationship to parental severe mental disorder.

BACKGROUND: Maternal antenatal depression may alter offspring neurodevelopment, but long follow-up studies are lacking. We studied the risks for mood disorders and schizophrenia in adult offspring of antenatally depressed mothers, taking account parental severe mental disorders. METHODS: In the general population-based Northern Finland 1966 Birth Cohort with 12,058 children, 13.9% of the mothers reported themselves depressed at mid-gestation. The offspring were followed 43 years. Severe mood disorders and schizophrenia in the offspring and severe mental disorders in the parents were detected using the Care Register for Healthcare. Maternal smoking during pregnancy, perinatal complications, fathers´ social class, family type at birth, and grand multiparity were considered as confounding variables. RESULTS: The offspring of antenatally depressed mothers had an elevated risk for depression (adjusted OR 1.5; 95% CI 1.03-2.2), compared to cohort members without maternal antenatal depressed mood. The offspring with maternal antenatal depressed mood and parental severe mental disorder had markedly elevated risks for depression (3.3; 1.8-6.2), and schizophrenia (3.9; 2.0-7.5), compared to the offspring without one or both of these risk factors. LIMITATIONS: Maternal antenatal depressed mood was determined by one question and did not necessarily signify a clinical condition. Data on maternal postnatal mood was not available. CONCLUSION: The offspring with maternal antenatal depressed mood and parental severe mental disorder had high risk for depression and schizophrenia. Early interventions in parental severe mental disorder might present an opportunity for decreasing the risk for mood disorders and schizophrenia in the offspring.

The family-oriented open dialogue approach in the treatment of first-episode psychosis: Nineteen-year outcomes.

Open Dialogue (OD) is a family-oriented early intervention approach which has demonstrated good outcomes in the treatment of first-episode psychosis (FEP). Nevertheless, more evidence is needed. In this register-based cohort study the long-term outcomes of OD were evaluated through a comparison with a control group over a period of approximately 19 years. We examined the mortality, the need for psychiatric treatment, and the granting of disability allowances. Data were obtained from Finnish national registers regarding all OD patients whose treatment for FEP commenced within the time of the original interventions (total N = 108). The control group consisted of all Finnish FEP patients who had a follow-up of 19-20 years and who were guided to other Finnish specialized mental healthcare facilities (N = 1763). No difference between the samples was found regarding the annual incidence of FEP, the diagnosis, and suicide rates. Over the entire follow-up, the figures for durations of hospital treatment, disability allowances, and the need for neuroleptics remained significantly lower with OD group. Findings indicated that many positive outcomes of OD are sustained over a long time period. Due to the observational nature of the study, randomized trials are still needed to provide more information on effectiveness of approach.

Adolescent inhalant use and psychosis risk - a prospective longitudinal study.

BACKGROUND: Cross-sectional studies have suggested inhalant use is associated with psychosis. This association was examined in a longitudinal study accounting for other substance use and potential confounders. METHODS: We used a prospective sample (N = 6542) from the Northern Finland Birth Cohort 1986. Self-report questionnaires on substance use and psychotic experiences were completed when the cohort members were 15-16 years old. Inhalant use was categorized into four groups (never, once, 2-4 times, 5 times or more). Subsequent psychosis diagnoses (ICD-10) until age 30 years were obtained from national registers. Cox regression analysis was used to examine the association between adolescent inhalant use and risk of psychosis. RESULTS: During the observation period 124 individuals were diagnosed with incident psychosis. Overall, there were 225 (3.4%) subjects with any inhalant use, 18 (8.0%) of whom were diagnosed with psychosis during the follow up. Of non-inhalant users (n = 6317) 106 (1.7%) were diagnosed with psychosis. Compared to non-users, those using inhalants had increased risk of incident psychosis with most frequent inhalant use associated with the greatest risk (unadjusted HR = 9.46; 3.86-23.20). After adjusting for baseline psychotic experiences, other substance use, comorbid mental disorder and parental substance abuse, the increased risk of psychosis persisted (HR = 3.06; 1.05-8.95). Furthermore, a dose-response effect between inhalant use and risk of psychosis was identified (OR = 2.34; 1.83-2.99). CONCLUSIONS: Inhalant use in adolescence was independently associated with incident psychosis. The adverse health outcomes associated with adolescent inhalant use provide compelling reasons for implementation of policies to reduce the use of volatile substances in adolescents.

Cognition, psychosis risk and metabolic measures in two adolescent birth cohorts.

BACKGROUND: Psychoses, especially schizophrenia, are often preceded by cognitive deficits and psychosis risk states. Altered metabolic profiles have been found in schizophrenia. However, the associations between metabolic profiles and poorer cognitive performance and psychosis risk in the population remain to be determined. METHODS: Detailed molecular profiles were measured for up to 8976 individuals from two general population-based prospective birth cohorts: the Northern Finland Birth Cohort 1986 (NFBC 1986) and the Avon Longitudinal Study of Parents and Children (ALSPAC). A high-throughput nuclear magnetic resonance spectroscopy platform was used to quantify 70 metabolic measures at age 15-16 years in the NFBC 1986 and at ages 15 and 17 years in ALSPAC. Psychosis risk was assessed using the PROD-screen questionnaire at age 15-16 years in the NFBC 1986 or the psychotic-like symptoms assessment at age 17 years in ALSPAC. Cognitive measures included academic performance at age 16 years in both cohorts and general intelligence and executive function in ALSPAC. Logistic regression measured cross-sectional and longitudinal associations between metabolic measures and psychosis risk and cognitive performance, controlling for important covariates. RESULTS: Seven metabolic measures, primarily fatty acid (FA) measures, showed cross-sectional associations with general cognitive performance, four across both cohorts (low density lipoprotein diameter, monounsaturated FA ratio, omega-3 ratio and docosahexaenoic acid ratio), even after controlling for important mental and physical health covariates. Psychosis risk showed minimal metabolic associations. CONCLUSIONS: FA ratios may be important in marking risk for cognitive deficits in adolescence. Further research is needed to clarify whether these biomarkers could be causal and thereby possible targets for intervention.

Adolescent cannabis use, baseline prodromal symptoms and the risk of psychosis.

BACKGROUND: The association between cannabis use and the risk of psychosis has been studied extensively but the temporal order still remains controversial. Aims To examine the association between cannabis use in adolescence and the risk of psychosis after adjustment for prodromal symptoms and other potential confounders. METHOD: The sample (n = 6534) was composed of the prospective general population-based Northern Finland Birth Cohort of 1986. Information on prodromal symptoms of psychosis and cannabis use was collected using questionnaires at age 15-16 years. Participants were followed up for ICD-10 psychotic disorders until age 30 years using nationwide registers. RESULTS: The risk of psychosis was elevated in individuals who had tried cannabis five times or more (hazard ratio, (HR) = 6.5, 95% CI 3.0-13.9). The association remained statistically significant even when adjusted for prodromal symptoms, other substance use and parental psychosis (HR = 3.0, 95% CI 1.1-8.0). CONCLUSIONS: Adolescent cannabis use is associated with increased risk of psychosis even after adjustment for baseline prodromal symptoms, parental psychosis and other substance use. Declaration of interest None.

Early adversity and brain response to faces in young adulthood.

Early stressors play a key role in shaping interindividual differences in vulnerability to various psychopathologies, which according to the diathesis-stress model might relate to the elevated glucocorticoid secretion and impaired responsiveness to stress. Furthermore, previous studies have shown that individuals exposed to early adversity have deficits in emotion processing from faces. This study aims to explore whether early adversities associate with brain response to faces and whether this association might associate with the regional variations in mRNA expression of the glucocorticoid receptor gene (NR3C1). A total of 104 individuals drawn from the Northern Finland Brith Cohort 1986 participated in a face-task functional magnetic resonance imaging (fMRI) study. A large independent dataset (IMAGEN, N = 1739) was utilized for reducing fMRI data-analytical space in the NFBC 1986 dataset. Early adversities were associated with deviant brain response to fearful faces (MANCOVA, P = 0.006) and with weaker performance in fearful facial expression recognition (P = 0.01). Glucocorticoid receptor gene expression (data from the Allen Human Brain Atlas) correlated with the degree of associations between early adversities and brain response to fearful faces (R2 = 0.25, P = 0.01) across different brain regions. Our results suggest that early adversities contribute to brain response to faces and that this association is mediated in part by the glucocorticoid system. Hum Brain Mapp 38:4470-4478, 2017. © 2017 Wiley Periodicals, Inc.

Association of stress and depression with chronic facial pain: A case-control study based on the Northern Finland 1966 Birth Cohort.

OBJECTIVE: The aim was to study the association between stress level and chronic facial pain, while controlling for the effect of depression on this association, during a three-year follow-up in a general population-based birth cohort. METHODS: In the general population-based Northern Finland 1966 Birth Cohort, information about stress level, depression and facial pain were collected using questionnaires at the age of 31 years. Stress level was measured using the Work Ability Index. Depression was assessed using the 13-item depression subscale in the Hopkins Symptom Checklist-25. Three years later, a subsample of 52 subjects (42 women) with chronic facial pain and 52 pain-free controls (42 women) was formed. RESULTS: Of the subjects having high stress level at baseline, 73.3% had chronic facial pain, and 26.7% were pain-free three years later. The univariate logistic regression analysis showed that high stress level at 31 years increased the risk for chronic facial pain (crude OR 6.1, 95%, CI 1.3-28.7) three years later. When including depression in a multivariate model, depression associated statistically significantly with chronic facial pain (adjusted OR 2.5, 95%, CI 1.0-5.8), whereas stress level did not (adjusted OR 2.3, 95%, CI 0.6-8.4). CONCLUSION: High stress level is connected with increased risk for chronic facial pain. This association seems to mediate through depression.

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

OBJECTIVE: Meta-analyses of cross-sectional studies confirm an increase in circulating inflammatory markers during acute psychosis. Longitudinal studies are scarce but are needed to understand whether elevated inflammatory markers are a cause or consequence of illness. We report a longitudinal study of serum C-reactive protein (CRP) in adolescence and subsequent risk of schizophrenia and related psychoses in adulthood in the Northern Finland Birth Cohort 1986. METHOD: Serum high-sensitivity CRP was measured at age 15/16 years in 6362 participants. ICD-10 diagnoses of schizophrenia and related psychoses were obtained from centralised hospital inpatient and outpatient registers up to age 27 years. Logistic regression calculated odds ratios (ORs) for psychotic outcomes associated with baseline CRP levels analysed as both continuous and categorical variables using American Heart Association criteria. Age, sex, body mass index, maternal education, smoking, and alcohol use were included as potential confounders. RESULTS: By age 27years, 88 cases of non-affective psychosis (1.38%), of which 22 were schizophrenia (0.35%), were identified. Adolescent CRP was associated with subsequent schizophrenia. The adjusted OR for schizophrenia by age 27yearsfor each standard deviation (SD) increase in CRP levels at age 15/16yearswas 1.25 (95% CI, 1.07-1.46), which was consistent with a linear, dose-response relationship (P-value for quadratic term 0.23). Using CRP as a categorical variable, those with high (>3mg/L) compared with low (<1mg/L) CRP levels at baseline were more likely to develop schizophrenia; adjusted OR 4.25 (95% CI, 1.30-13.93). There was some indication that higher CRP was associated with earlier onset of schizophrenia (rs=-0.40; P=0.07). CONCLUSIONS: A longitudinal association between adolescent CRP levels and adult schizophrenia diagnosis indicates a potentially important role of inflammation in the pathogenesis of the illness, although the findings, based on a small number of cases, need to be interpreted with caution and require replication in other samples.

Smoking in pregnancy, adolescent mental health and cognitive performance in young adult offspring: results from a matched sample within a Finnish cohort.

BACKGROUND: The association between prenatal exposure to maternal cigarette smoking (PEMCS) and adult cognition is debated, including if there are differences according to sex. We aimed to determine if there are associations between PEMCS and cognition in early adulthood in men and women and examine if observed associations were mediated by adolescent mental health factors that are associated with cognition, namely psychotic-like experiences (PLEs), inattention and hyperactivity, and other externalizing behaviors. METHODS: Participants were 471 individuals drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986) followed up from pregnancy and birth to early adulthood; individuals with PEMCS were matched with those without PEMCS by socioeconomic and demographic factors. Cognitive performance in adulthood was assessed with a range of tests and their association with PEMCS was measured by sex using hierarchical linear regression, unadjusted and then controlling for potential confounders, mediators and moderators, including adolescent mental health factors. RESULTS: There were no associations between PEMCS and cognitive scores in females. In males, there were associations with vocabulary (beta = -0.444, 95% CI: -0.783, -0.104) and matrix reasoning (beta = -0.379, 95% CI: -0.711, -0.047). CONCLUSIONS: While associations between PEMCS and cognition were limited, observed findings with measures of general intelligence in males contribute to suggestions of differences in response to PEMCS by sex. Furthermore, observed associations may be partly mediated by earlier inattention and hyperactivity. Findings add support to efforts aimed to eliminate smoking in pregnancy.

Body mass index and brain white matter structure in young adults at risk for psychosis - The Oulu Brain and Mind Study.

Antipsychotic medications and psychotic illness related factors may affect both weight and brain structure in people with psychosis. Genetically high-risk individuals offer an opportunity to study the relationship between body mass index (BMI) and brain structure free from these potential confounds. We examined the effect of BMI on white matter (WM) microstructure in subjects with familial risk for psychosis (FR). We used diffusion tensor imaging and tract-based spatial statistics to explore the effect of BMI on whole brain FA in 42 (13 males) participants with FR and 46 (16 males) control participants aged 20-25 years drawn from general population-based Northern Finland Birth Cohort 1986. We also measured axial, radial and mean diffusivities. Most of the participants were normal weight rather than obese. In the FR group, decrease in fractional anisotropy and increase in radial diffusivity were associated with an increase in BMI in several brain areas. In controls the opposite pattern was seen in participants with higher BMI. There was a statistically significant interaction between group and BMI on FA and radial and mean diffusivities. Our results suggest that the effect of BMI on WM differs between individuals with FR for psychosis and controls.

Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.

Cerebellar activity in young people with familial risk for psychosis--The Oulu Brain and Mind Study.

OBJECTIVE: The cerebellum plays a critical role in cognition and behavior. Altered function of the cerebellum has been related to schizophrenia and psychosis but it is not known how this applies to spontaneous resting state activity in young people with familial risk for psychosis. METHODS: We conducted resting-state functional MRI (R-fMRI) in 72 (29 male) young adults with a history of psychosis in one or both parents (FR) but without their own psychosis, and 72 (29 male) similarly healthy control subjects without parental psychosis. Both groups in the Oulu Brain and Mind Study were drawn from the Northern Finland Birth Cohort 1986. Participants were 20-25 years old. Parental psychosis was established using the Care Register for Health Care. R-fMRI data pre-processing was conducted using independent component analysis with 30 and 70 components. A dual regression technique was used to detect between-group differences in the cerebellum with p<0.05 threshold corrected for multiple comparisons. RESULTS: FR participants demonstrated statistically significantly increased activity compared to control subjects in the anterior lobe of the right cerebellum in the analysis with 70 components. The volume of the increased activity was 73 mm(3). There was no difference between the groups in the analysis with 30 components. CONCLUSION: The finding suggests that increased activity of the anterior lobe of the right cerebellum may be associated with increased vulnerability to psychosis. The finding is novel, and needs replication to be confirmed.

Association Between Clinical Signs of Temporomandibular Disorders and Psychological Distress Among an Adult Finnish Population.

AIMS: To evaluate the association between signs of temporomandibular disorders (TMD) and psychological distress in a general population-based sample of Finnish adults. METHODS: The Health 2000 Survey was conducted in 2000-2001 by the National Institute for Health and Welfare in Finland. Of the sample of adults aged 30 or over (n=8,028), 79% participated in a clinical oral health examination, which included examination of TMD signs. The participants (n=6,155) also completed questionnaires, including the 12-item General Health Questionnaire (GHQ-12), which measured psychological distress. Associations between TMD signs and psychological distress measured by the GHQ-12 were examined in both genders. Statistical measures included chi-square tests, t tests, and logistic regression analyses. RESULTS: The prevalence of the TMD signs (limited opening, clicking, crepitation, temporomandibular joint [TMJ] palpation pain, and muscle palpation pain) was 11.2%, 17.6%, 10.5%, 5.1%, and 18.9% in women, and 6.1%, 12.9%, 5.3%, 2.4%, and 7.2% in men, respectively. High GHQ-12 scores, measured as continuous variables and in quartiles by distress level, were significantly associated with masticatory muscle pain on palpation in both genders (P<.05) and with TMJ pain on palpation in women (P<.05). Additionally, high GHQ-12 scores as continuous were associated with TMJ crepitation in men (P<.05). The logistic regression analyses showed that higher GHQ-12 scores were associated significantly with masticatory muscle pain on palpation both in women (odds ratio [OR]=2.18; 95% confidence interval [CI]=1.6-2.9) and men (OR=2.03; 95% CI=1.3-3.1). CONCLUSION: TMD signs and psychological distress appear to be associated. However, due to the limitations of the study, the findings can be regarded as preliminary.

White matter structure in young adults with familial risk for psychosis - The Oulu Brain and Mind Study.

According to the disconnectivity model, disruptions in neural connectivity play an essential role in the pathology of schizophrenia. The aim of this study was to determine whether these abnormalities are present in young adults with familial risk (FR) for psychosis in the general population based sample. We used diffusion tensor imaging (DTI) and tract-based spatial statistics to compare whole-brain fractional anisotropy, mean diffusivity, and axial and radial diffusion in 47 (17 males) FR subjects to 51 controls (17 males). All the participants were aged between 20 and 25 years and were members of the Northern Finland Birth Cohort 1986 (Oulu Brain and Mind Study). Region of interest analyses were conducted for 12 tracts. Separately, we analysed whole-brain FA for the subgroup with FR for schizophrenia (n=13) compared with 13 gender-matched controls. Contrary to our expectations there were no differences in any of the DTI measures between FR and control groups. This suggests that white matter abnormalities may not be a genetic feature for risk of psychosis and preceding the onset of a psychotic disorder. Our findings do not support the theory of disconnectivity as a primary sign of psychosis in young adults with FR for the illness.

Longitudinal regional brain volume loss in schizophrenia: Relationship to antipsychotic medication and change in social function.

BACKGROUND: Progressive brain volume loss in schizophrenia has been reported in previous studies but its cause and regional distribution remains unclear. We investigated progressive regional brain reductions in schizophrenia and correlations with potential mediators. METHOD: Participants were drawn from the Northern Finland Birth Cohort 1966. A total of 33 schizophrenia individuals and 71 controls were MRI scanned at baseline (mean age=34.7, SD=0.77) and at follow-up (mean age=43.4, SD=0.44). Regional brain change differences and associations with clinical mediators were examined using FSL voxelwise SIENA. RESULTS: Schizophrenia cases exhibited greater progressive brain reductions than controls, mainly in the frontal and temporal lobes. The degree of periventricular brain volume reductions were predicted by antipsychotic medication exposure at the fourth ventricular edge and by the number of days in hospital between the scans (a proxy measure of relapse duration) at the thalamic ventricular border. Decline in social and occupational functioning was associated with right supramarginal gyrus reduction. CONCLUSION: Our findings are consistent with the possibility that antipsychotic medication exposure and time spent in relapse partially explain progressive brain reductions in schizophrenia. However, residual confounding could also account for the findings and caution must be applied before drawing causal inferences from associations demonstrated in observational studies of modest size. Less progressive brain volume loss in schizophrenia may indicate better preserved social and occupational functions.

Association between Dopamine Receptor D2 (DRD2) Variations rs6277 and rs1800497 and Cognitive Performance According to Risk Type for Psychosis: A Nested Case Control Study in a Finnish Population Sample.

BACKGROUND: There is limited research regarding the association between genes and cognitive intermediate phenotypes in those at risk for psychotic disorders. METHODS: We measured the association between established psychosis risk variants in dopamine D2 receptor (DRD2) and cognitive performance in individuals at age 23 years and explored if associations between cognition and these variants differed according to the presence of familial or clinical risk for psychosis. The subjects of the Oulu Brain and Mind Study were drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986). Using linear regression, we compared the associations between cognitive performance and two candidate DRD2 polymorphisms (rs6277 and rs1800497) between subjects having familial (n=61) and clinical (n=45) risk for psychosis and a random sample of participating NFBC 1986 controls (n=74). Cognitive performance was evaluated using a comprehensive battery of tests at follow-up. RESULTS: Principal components factor analysis supported a three-factor model for cognitive measures. The minor allele of rs6277 was associated with poorer performance on a verbal factor (p=0.003) but this did not significantly interact with familial or clinical risk for psychosis. The minor allele of rs1800497 was associated with poorer performance on a psychomotor factor (p=0.038), though only in those at familial risk for psychotic disorders (interaction p=0.049). CONCLUSION: The effect of two DRD2 SNPs on cognitive performance may differ according to risk type for psychosis, suggesting that cognitive intermediate phenotypes differ according to the type (familial or clinical) risk for psychosis.

Functional mapping of dynamic happy and fearful facial expressions in young adults with familial risk for psychosis - Oulu Brain and Mind Study.

BACKGROUND: Social interaction requires mirroring to other people's mental state. Psychotic disorders have been connected to social interaction and emotion recognition impairment. We compared the brain activity between young adults with familial risk for psychosis (FR) and matched controls during visual exposure to emotional facial expression. We also investigated the role of the amygdala, the key region for social interaction and emotion recognition. METHODS: 51 FR and 52 control subjects were drawn from the Northern Finland 1986 Birth Cohort (Oulu Brain and Mind Study). None of the included participants had developed psychosis. The FR group was defined as having a parent with psychotic disorder according to the Finnish Hospital Discharge Register. Participants underwent functional MRI (fMRI) using visual presentation of dynamic happy and fearful facial expressions. FMRI data were processed to produce maps of activation for happy and fearful facial expression, which were then compared between groups. Two spherical regions of interest (ROIs) in the amygdala were set to extract BOLD responses during happy and fearful facial expression. BOLD responses were then compared with subjects' emotion recognition, which was assessed after fMRI. Psychophysiological interaction (PPI) for the left and right amygdala during happy and fearful facial expression was conducted using the amygdala as seed regions. RESULTS: FR subjects had increased activity in the left premotor cortex and reduced deactivation of medial prefrontal cortex structures during happy facial expression. There were no between-group differences during fearful facial expression. The FR group also showed a statistically significant linear correlation between mean amygdala BOLD response and facial expression recognition. PPI showed that there was a significant negative interaction between the amygdala and the dorsolateral prefrontal cortex (dlPFC) and superior temporal gyrus in FR subjects. CONCLUSIONS: Increased activations by positive valence in FR were in brain regions crucial to emotion recognition and social interaction. Increased activation of the premotor cortex may serve as a compensatory mechanism as FR subjects may have to exert more effort on processing the stimuli, as has been found earlier in schizophrenia. Failure to deactivate PFC structures may imply error in the default mode network. Abnormal PFC function in FR was also suggested by PPI, as the dlPFC showed decreased functional connectivity with the amygdala in the FR group. This may indicate that in FR subjects the amygdala have to take a greater role in emotion recognition and social functioning. This inference was supported by our discovery of statistically significant correlations between the amygdala BOLD response and emotion recognition in the FR group but not in controls.

Central executive network in young people with familial risk for psychosis--the Oulu Brain and Mind Study.

OBJECTIVE: The central executive network controls and manages high-level cognitive functions. Abnormal activation in the central executive network has been related to psychosis and schizophrenia but it is not established how this applies to people with familial risk for psychosis (FR). METHODS: We conducted a resting-state functional MRI (R-fMRI) in 72 (29 males) young adults with a history of psychosis in one or both parents (FR) but without psychosis themselves, and 72 (29 males) similarly healthy control subjects without parental psychosis. Both groups in the Oulu Brain and Mind Study were drawn from the Northern Finland Birth Cohort 1986. Participants were 20-25years old. Parental psychosis was established using the Care Register for Health Care. R-fMRI data pre-processing was conducted using independent component analysis with 30 and 70 components. A dual regression technique was used to detect between-group differences in the central executive network with p<0.05 threshold corrected for multiple comparisons. RESULTS: FR participants demonstrated statistically significantly lower activity compared to control subjects in the right inferior frontal gyrus, a key area of central executive network corresponding to Brodmann areas 44 and 45, known as Broca's area. The volume of the lower activation area with 30 components was 896mm(3) and with 70 components was 1151mm(3). CONCLUSION: The activity of the central executive network differed in the right inferior frontal gyrus between FR and control groups. This suggests that abnormality of the right inferior frontal gyrus may be a central part of vulnerability for psychosis.