[Show abstract][Hide abstract] ABSTRACT: AimWe investigated the associations between clinical high-risk for psychosis (CHR), psychotic-like symptoms and suicidality among adolescent psychiatric patients.Methods
The sample consisted of 54 CHR and 107 non-CHR psychiatric patients aged 15–18 in Helsinki, Finland, who were assessed at the beginning of their psychiatric treatment with the Structured Interview for Prodromal Syndromes (SIPS). Current suicidality was measured with the Beck Depression Inventory (item 9), while lifetime suicidality was evaluated from all available data, including patient files. The participants were followed for 2.8–8.9 years via the national hospital discharge register, with the follow-up outcome being intentional self-harm. Data on suicides were also gathered from the Causes of Death statistics.ResultsOnly 30.5% of the adolescents had no suicidal ideation at the beginning of their treatment. CHR risk state and SIPS-assessed delusions, suspiciousness, and hallucinations were associated with higher current suicidality. Of the 154 adolescents with register follow-up, there were five (3.2%) with intentional self-harm resulting in hospital treatment, all female. CHR status was not associated with self-harm. Current suicidality, familial risk of psychosis, and SIPS decreased expression of emotions were associated with self-harm during follow-up. In a Cox regression analysis model among girls, only decreased expression of emotions remained a significant predictor of intentional self-harm. Baseline suicidality measures were not associated with transitions to psychosis.ConclusionsCHR status was associated with higher current suicidality but did not predict follow-up intentional self-harm in treatment-seeking adolescents. Decreased expression of emotions may indicate higher risk of intentional self-harm in adolescent treatment-seeking girls.
Early Intervention in Psychiatry 02/2015; DOI:10.1111/eip.12218 · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Approximately five percent of the Finnish population are Swedish-speaking and have higher socioeconomic position and longer life expectancy than the Finnish-speaking majority. Previous studies have not investigated whether Swedish-speaking Finns have lower risk of schizophrenia spectrum disorders (SSD) than Finnish-speaking Finns. We investigated this in a representative sample of 47 445 Finns born in 1972-1984. Hazard ratios of SSD between language groups were assessed with conditional proportional hazards regression. Sex, parental ages at birth, paternal employment around conception, parental psychosis and place and residence in the capital area were used as other explanatory variables. The prevalence of SSD was 0.7% in the Swedish-speaking minority and 1.5% in the Finnish-speaking majority. In the adjusted regression model, belonging to the Swedish-speaking minority was associated with lower risk of SSD (hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.24-0.69). In a subset analysis by gender, the protective effect was evident among Swedish-speaking males (HR 0.32, 95% CI 0.15-0.68) but marginal in females (HR 0.75, 95% CI 0.41-1.37). Parental psychosis and place of birth in the capital area were associated with higher risk of SSD, whereas paternal employment at the time of conception was associated with lower risk of SSD. Our results support the role of social factors in the etiology of schizophrenia. Belonging to a minority with high socioeconomic status and social capital may be protective against schizophrenia, especially for males.
Schizophrenia Research 09/2014; 159(2-3). DOI:10.1016/j.schres.2014.09.014 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hearing impairment is associated with psychotic symptoms, but has not been systematically studied in people with psychotic disorder. We used a population-based sample of 6654 persons aged 30 + to compare hearing, as measured by audiometry, in persons with schizophrenia, other non-affective psychosis and affective psychosis in the general population. The prevalence of hearing impairment did not differ in persons with psychotic disorder compared with the general population. Participants with schizophrenia and affective psychotic disorder had significantly more difficulties to hear in a noisy environment than the general population. Our results suggest that psychotic disorders are associated with minor hearing difficulties but not hearing impairment.
Schizophrenia Research 09/2014; 159(2-3). DOI:10.1016/j.schres.2014.08.016 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lähtökohdat
Tutkimuksessa selvitettiin koulutusryhmien välisten terveys- ja hyvinvointierojen kehitystä
30–74-vuotiailla suomalaisilla vuodesta 2000 vuoteen 2011.
Tutkimuksessa verrattiin kahta poikkileikkaustilannetta käyttämällä koko aikuisväestöä edustavia
toistomittaukseen perustuvia Terveys 2000 ja Terveys 2011 -aineistoja. Tutkimukseen osallistujat
valittiin kaksiasteisella koko aikuisväestöä edustavalla ositetulla ryväsotanta-asetelmalla.
30–74-vuotiaita osallistujia oli 6 107 vuonna 2000 ja 5 164 vuonna 2011. Koulutusryhmät määriteltiin
Tilastokeskuksen tutkintorekisterin tietojen perusteella. Terveyden, toimintakyvyn, elintapojen ja
elinolojen osoittimina olivat koettu terveys, pitkäaikaissairastavuus, lääkärinhoidon tarpeen
psyykkinen kuormittuneisuus, suoriutuminen puolen kilometrin kävelystä, opittujen
sanojen lukumäärä CERAD-tehtäväsarjan muistitestissä, työkykypistemäärä, tupakointi, kasvisten ja
juuresten käyttö, toimeentulon riittävyys ja työttömyys. Mallivakioinnin avulla laskettiin esiintyvyysluvut
tai keskiarvot ja näiden 95 %:n luottamusvälit. Koulutusryhmien välisiä eroja testattiin logistisen
tai lineaarisen regressiomallin avulla.
Koulutusryhmien väliset terveys- ja hyvinvointierot olivat huomattavat useimpien osoittimien
mukaan. Ylimmässä koulutusryhmässä tilanne oli paras ja alimmassa koulutusryhmässä huonoin.
Miesten ja naisten pitkäaikaissairastavuuden koulutusryhmittäiset erot kaventuivat. Miehillä myös
koetun terveyden ja naisilla oppimiskyvyn koulutusryhmittäiset erot kaventuivat. Kasvisten käytön,
kävelyvaikeuksien, työkyvyn, riittämättömän toimeentulon ja työttömyyden yleisyyden koulutusryhmien
väliset jyrkät erot säilyivät ennallaan. Tupakoinnin koulutusryhmittäiset erot kasvoivat
naisilla, kun enintään perusasteen koulutuksen suorittaneiden tupakointi yleistyi ja korkea-asteen
koulutuksen suorittaneiden tupakointi väheni.
Väestön terveys ja hyvinvointi pääosin kohenivat vuodesta 2000 vuoteen 2011. Kuitenkin useimmilla
terveyden ja hyvinvoinnin ulottuvuuksilla koulutusryhmien väliset erot säilyivät suurina.
havainto oli tupakoinnin koulutusryhmittäisten erojen kasvu naisten keskuudessa.
Suomen lääkärilehti. Finlands läkartidning 09/2014; 69(36):2185-2192.
[Show abstract][Hide abstract] ABSTRACT: Objective
Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder.
Patients (N = 2342) treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010 were compared with general population controls (N = 9368) matched for age, sex, and place of residence. Data of 30 autoimmune diseases from the Hospital Discharge Register from 1969 to 2010 were analyzed using conditional and Poisson regression models.
Of patients, 8.9% vs. 5.4% of control individuals had been diagnosed with one or more autoimmune disease (OR 1.7, 95% CI 1.5–2.0, P<0.001). The increase in endocrinological diseases (OR 2.4, 95% CI 1.8–3.2, P<0.001) was explained by type 1 diabetes, whereas Crohn's disease contributed most to the risk of gastroenterological diseases (OR 1.8, 95% CI 1.4–2.5, P<0.001). Higher prevalence of autoimmune diseases among patients with eating disorders was not exclusively due to endocrinological and gastroenterological diseases; when the two categories were excluded, the increase in prevalence was seen in the patients both before the onset of the eating disorder treatment (OR 1.5, 95% CI 1.1–2.1, P = 0.02) and at the end of the follow-up (OR 1.4, 95% CI 1.1–1.8, P = 0.01).
We observed an association between eating disorders and several autoimmune diseases with different genetic backgrounds. Our findings support the link between immune-mediated mechanisms and development of eating disorders. Future studies are needed to further explore the risk of autoimmune diseases and immunological mechanisms in individuals with eating disorders and their family members.
PLoS ONE 08/2014; 9(8):e104845. DOI:10.1371/journal.pone.0104845 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
[Show abstract][Hide abstract] ABSTRACT: The Prodromal Questionnaire (PQ) identifies psychiatric help-seekers in need of clinical interviews to diagnose psychosis risk. However, some providers use the PQ alone to identify risk. Therefore, we tested its predictive utility among 731 adolescent psychiatric help-seekers, with a 3-9-year register-based follow-up. Nine latent factors corresponded well with postulated subscales. Depersonalization predicted later hospitalization with a psychosis diagnosis (HR 1.6 per SD increase), and Role Functioning predicted any psychiatric hospitalization (HR 1.3). Published cut-off scores were poor predictors of psychosis; endorsement rates were very high for most symptoms. Therefore, we do not recommend using the PQ without second-stage clinical interviews.
Schizophrenia Research 07/2014; 158(1-3). DOI:10.1016/j.schres.2014.06.031 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. OBJECTIVES To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. DESIGN, SETTING, AND PARTICIPANTS Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). MAIN OUTCOMES AND MEASURES Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. RESULTS Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. CONCLUSIONS AND RELEVANCE These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.
[Show abstract][Hide abstract] ABSTRACT: Objective
The aim of this study is to explore the prevalence of hospital-treated suicide attempts in a large clinical population of eating disorder patients.
Follow-up study of adults (N = 2462, 95% women, age 18–62 years) admitted to the Eating Disorder Clinic of Helsinki University Central Hospital in the period 1995–2010. For each patient four controls were selected and matched for age, sex and place of residence. The end-point events were modeled using Cox’s proportional hazard model, taking matching into account.
We identified 156 patients with eating disorder (6.3%) and 139 controls (1.4%) who had required hospital treatment for attempted suicide. Of them, 66 (42.3%) and 37 (26.6%) had more than one attempt. The rate ratio (RR) for suicide attempt in patients with eating disorder was 4.70 (95% CI 1.41–15.74). In anorexia nervosa RR was 8.01 (95% CI 5.40–11.87) and in bulimia nervosa 5.08 (95% CI 3.46–7.42). In eating disorder patients with a history of suicide attempt, the risk of death from any cause was 12.8%, suicide being the main cause in 45% of the deaths.
Suicide attempts and repeated attempts are common among patients with eating disorders. Suicidal ideation should be routinely assessed from patients with eating disorders.
General hospital psychiatry 05/2014; 36(3). DOI:10.1016/j.genhosppsych.2014.01.002 · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study pregnancy, obstetric, and perinatal health outcomes and complications in women with lifetime eating disorders.
Female patients (n=2 257) treated at the Eating Disorder Clinic of Helsinki University Central Hospital during 1995-2010 were compared with unexposed women retrieved from the population (n=9028). Register-based information on pregnancy, obstetric, and perinatal health outcomes and complications were acquired for all singleton births during the follow up time among women with broad anorexia nervosa (AN, n=302 births), broad bulimia nervosa (BN, n=724), binge eating disorder (BED, n=52), and unexposed women (n=6319).
Women with AN and BN gave birth to babies with lower birth weight compared to unexposed women, while the opposite was observed in BED. Maternal AN was related to anemia, slow fetal growth, premature contractions, short duration of the first stage of labor, very premature birth, small for gestational age, low birth weight, and perinatal death. Increased odds of premature contractions, resuscitation of the neonate, and very low Apgar score at 1 min were observed in mothers with BN. BED was positively associated with maternal hypertension, long duration of the first and second stage of labor, and birth of large for gestational age infants.
Eating disorders appear to be associated with several adverse perinatal outcomes, particularly in offspring. We recommend close monitoring of pregnant women with either past or current eating disorder. Attention should be paid to children born to these mothers.
American journal of obstetrics and gynecology 04/2014; 211(4). DOI:10.1016/j.ajog.2014.03.067 · 4.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Current psychosis risk criteria have often been studied on a pre-selected population at specialized clinics. We investigated whether the Structured Interview for Prodromal Syndromes (SIPS) is a useful tool for psychosis risk screening among adolescents in general psychiatric care.
161 adolescents aged 15–18 with first admission to adolescent psychiatric services in Helsinki were interviewed with the SIPS to ascertain Clinical High-Risk (CHR) state. The participants were followed via the national hospital discharge register, patient files, and follow-up interviews. DSM-IV Axis I diagnoses were made at baseline and 12 months. Register follow-up spanned 2.8–8.9 years, and hospital care for a primary psychotic disorder and any psychiatric disorder were used as outcomes.
CHR criteria were met by 54 (33.5%) of the adolescents. Three conversions of psychosis as defined by SIPS emerged during follow-up, two of whom belonged to the CHR group. The positive predictive value of the CHR status was weak (1.9%) but its negative predictive value was 98.0%. Using the DSM-IV definition of psychosis, there were five conversions, three of which were in the CHR group. In regression analyses, hospital admissions for primary psychotic disorder were predicted by positive symptom intensity in the baseline SIPS. In addition, CHR status and SIPS positive and general symptoms predicted hospitalization for psychiatric disorder.
Psychosis incidence was low in our unselected sample of adolescent psychiatric patients. CHR status failed to predict SIPS or DSM-IV psychoses significantly at 12 months. However, in a longer follow-up, CHR did predict psychiatric hospitalization.
Schizophrenia Research 04/2014; 158(1-3). DOI:10.1016/j.schres.2014.06.028 · 3.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Genome-wide association studies (GWAS) have identified several loci associated with schizophrenia and/or bipolar disorder. We performed a GWAS of psychosis as a broad syndrome rather than within specific diagnostic categories.
1239 cases with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder; 857 of their unaffected relatives, and 2739 healthy controls were genotyped with the Affymetrix 6.0 single nucleotide polymorphism (SNP) array. Analyses of 695,193 SNPs were conducted using UNPHASED, which combines information across families and unrelated individuals. We attempted to replicate signals found in 23 genomic regions using existing data on nonoverlapping samples from the Psychiatric GWAS Consortium and Schizophrenia-GENE-plus cohorts (10,352 schizophrenia patients and 24,474 controls).
No individual SNP showed compelling evidence for association with psychosis in our data. However, we observed a trend for association with same risk alleles at loci previously associated with schizophrenia (one-sided p = .003). A polygenic score analysis found that the Psychiatric GWAS Consortium's panel of SNPs associated with schizophrenia significantly predicted disease status in our sample (p = 5 × 10(-14)) and explained approximately 2% of the phenotypic variance.
Although narrowly defined phenotypes have their advantages, we believe new loci may also be discovered through meta-analysis across broad phenotypes. The novel statistical methodology we introduced to model effect size heterogeneity between studies should help future GWAS that combine association evidence from related phenotypes. Applying these approaches, we highlight three loci that warrant further investigation. We found that SNPs conveying risk for schizophrenia are also predictive of disease status in our data.
[Show abstract][Hide abstract] ABSTRACT: Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).Molecular Psychiatry advance online publication, 20 November 2012; doi:10.1038/mp.2012.157.