[Show abstract][Hide abstract]ABSTRACT: Background:
Distinguishing between symptoms of schizotypal (SPD) and borderline personality disorders (BPD) is often difficult due to their partial overlap and frequent co-occurrence. We investigated correlations in self-reported symptoms of SPD and BPD in questionnaires at the levels of both total scores and individual items, examining overlapping dimensions.
Two questionnaires, the McLean Screening Instrument (MSI) for BPD and the Schizotypal Personality Questionnaire Brief (SPQ-B) for SPD, were filled in by patients with mood disorders (n=282) from specialized psychiatric care in a study of the Helsinki University Psychiatric Consortium. Correlation coefficients between total scores and individual items of the MSI and SPQ-B were estimated. Multivariate regression analysis (MRA) was conducted to examine the relationships between SPQ-B and MSI.
The Spearman's correlation between total scores of the MSI and SPQ-B was strong (rho=0.616, P<0.005). Items of MSI reflecting disrupted relatedness and affective dysregulation correlated moderately (rφ varied between 0.2 and 0.4, P<0.005) with items of SPQ. Items of MSI reflecting behavioural dysregulation correlated only weakly with items of SPQ. In MRA, depressive symptoms, sex and MSI were significant predictors of SPQ-B score, whereas symptoms of anxiety, age and SPQ-B were significant predictors of MSI score.
Items reflecting cognitive-perceptual distortions and affective symptoms of BPD appear to overlap with disorganized and cognitive-perceptual symptoms of SPD. Symptoms of depression may aggravate self-reported features of SPQ-B, and symptoms of anxiety features of MSI. Symptoms of behavioural dysregulation of BPD and interpersonal deficits of SPQ appear to be non-overlapping.
Full-text available · Article · Mar 2016 · European Psychiatry
[Show abstract][Hide abstract]ABSTRACT: Converging evidence suggests that infections and alterations in the immune system may contribute to the development of psychotic disorders. Psychotic disorders, particularly schizophrenia, are viewed as neurodevelopmental diseases, in which the illness is the end state of an abnormal neurodevelopmental process that has already started during prenatal development and continued in adolescence. It is believed that the illness is caused by a combination of genetic predisposition and environmental insults. Infections and other inflammation-provoking exposures are among the most widely studied environmental risk factors. People with first-episode psychosis and with chronic psychotic disorders seem to have both proinflammatory activation of the innate immune system and an activation of T cells of the adaptive immune system. These alterations are mostly marked during an acute psychotic episode. In patients with chronic psychotic disorders, systemic inflammation is associated with metabolic comorbidities, such as obesity, type 2 diabetes, and dyslipidemia. In this chapter, the evidence linking innate immune responses to the developmental process leading to psychotic disorders has been reviewed.
[Show abstract][Hide abstract]ABSTRACT: People with schizophrenia have 2- to 5-fold higher risk of type 2 diabetes than the general population. The traditional risk factors for type 2 diabetes, especially obesity, poor diet, and sedentary lifestyle, are common in people with schizophrenia already early in the course of illness. People with schizophrenia also often have low socioeconomic status and income, which affects their possibilities to make healthy lifestyle choices. Antipsychotic medications increase the risk of type 2 diabetes both directly by affecting insulin sensitivity and indirectly by causing weight gain. Lifestyle modification interventions for prevention of diabetes should be an integral part of treatment of patients with schizophrenia. In the treatment of type 2 diabetes in patients with schizophrenia, communication and collaboration between medical care and psychiatric treatment providers are essential.
Full-text available · Article · Feb 2016 · Current Diabetes Reports
[Show abstract][Hide abstract]ABSTRACT: Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.
[Show abstract][Hide abstract]ABSTRACT: Aspects to be taken into consideration in the total care of women of reproductive age and affected with schizophrenia include possible contraception, pharmacological therapy during pregnancy and need for support in parenthood. Compared with other pregnant women, those affected with schizophrenia are older, are more frequently smokers during pregnancy and more often neglect health monitoring during pregnancy. Schizophrenia predisposes for preterm delivery, miscarriage and lower Apgar score of the infant. In regard to parenthood, the effects of the illness itself or the prescribed medication on the interactive mother-child relationship may emerge as problematic issues.
[Show abstract][Hide abstract]ABSTRACT: Objective:
We performed a whole-genome expression study to clarify the nature of the biological processes mediating between inherited genetic variations and cognitive dysfunction in schizophrenia.
Gene expression was assayed from peripheral blood mononuclear cells using Illumina Human WG6 v3.0 chips in twins discordant for schizophrenia or bipolar disorder and control twins. After quality control, expression levels of 18,559 genes were screened for association with the California Verbal Learning Test (CVLT) performance, and any memory-related probes were then evaluated for variation by diagnostic status in the discovery sample (N = 190), and in an independent replication sample (N = 73). Heritability of gene expression using the twin design was also assessed.
After Bonferroni correction (p < 2.69 × 10-6), CVLT performance was significantly related to expression levels for 76 genes, 43 of which were differentially expressed in schizophrenia patients, with comparable effect sizes in the same direction in the replication sample. For 41 of these 43 transcripts, expression levels were heritable. Nearly all identified genes contain common or de novo mutations associated with schizophrenia in prior studies.
Genes increasing risk for schizophrenia appear to do so in part via effects on signaling cascades influencing memory. The genes implicated in these processes are enriched for those related to RNA processing and DNA replication and include genes influencing G-protein coupled signal transduction, cytokine signaling, and oligodendrocyte function. (PsycINFO Database Record
[Show abstract][Hide abstract]ABSTRACT: Aims:
Research demonstrates that migrants are more vulnerable to poor mental health than general populations, but population-based studies with distinct migrant groups are scarce. We aim to (1) assess the prevalence of mental health symptoms in Russian, Somali and Kurdish origin migrants in Finland; (2) compare the prevalence of mental health symptoms in these migrant groups to the Finnish population; (3) determine which socio-demographic factors are associated with mental health symptoms.
We used data from the Finnish Migrant Health and Wellbeing Study and Health 2011 Survey. Depressive and anxiety symptoms were measured using the Hopkins Symptom Checklist-25 (HSCL-25), and 1.75 was used as cut-off for clinically significant symptoms. Somatization was measured using the Symptom Checklist-90 (SCL-90) somatization scale. The age-adjusted prevalence of mental health symptoms in the studied groups was calculated by gender using predicted margins. Logistic regression analysis was used to determine which socio-demographic factors are associated with mental health symptoms in the studied population groups.
The prevalence of depressive and anxiety symptoms was higher in Russian women (24%) and Kurdish men (23%) and women (49%) than in the Finnish population (9-10%). These differences were statistically significant (p <.001). Socioeconomic disadvantage (e.g. unemployment and poor economic situation) and migration-related factors (e.g. poor language proficiency and short time since migration) significantly increased the odds for depressive and anxiety symptoms.
Mental health symptoms are highly prevalent particularly in Kurdish migrants in Finland. Holistic interventions and co-operation between integration and mental health services are acutely needed.
Article · Dec 2015 · Scandinavian Journal of Public Health
[Show abstract][Hide abstract]ABSTRACT: Genome-wide association studies (GWAS) of schizophrenia have yielded more than 100 common susceptibility variants, and strongly support a substantial polygenic contribution of a large number of small allelic effects. It has been hypothesized that familial schizophrenia is largely a consequence of inherited rather than environmental factors. We investigated the extent to which familiality of schizophrenia is associated with enrichment for common risk variants detectable in a large GWAS. We analyzed single nucleotide polymorphism (SNP) data for cases reporting a family history of psychotic illness (N=978), cases reporting no such family history (N=4,503), and unscreened controls (N=8,285) from the Psychiatric Genomics Consortium (PGC1) study of schizophrenia. We used a multinomial logistic regression approach with model-fitting to detect allelic effects specific to either family history subgroup. We also considered a polygenic model, in which we tested whether family history positive subjects carried more schizophrenia risk alleles than family history negative subjects, on average. Several individual SNPs attained suggestive but not genome-wide significant association with either family history subgroup. Comparison of genome-wide polygenic risk scores based on GWAS summary statistics indicated a significant enrichment for SNP effects among family history positive compared to family history negative cases (Nagelkerke's R2=0.0021; P=0.00331; P-value threshold <0.4). Estimates of variability in disease liability attributable to the aggregate effect of genome-wide SNPs were significantly greater for family history positive compared to family history negative cases (0.32 and 0.22, respectively; P=0.031). We found suggestive evidence of allelic effects detectable in large GWAS of schizophrenia that might be specific to particular family history subgroups. However, consideration of a polygenic risk score indicated a significant enrichment among family history positive cases for common allelic effects. Familial illness might, therefore, represent a more heritable form of schizophrenia, as suggested by previous epidemiological studies.
Full-text available · Article · Dec 2015 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
[Show abstract][Hide abstract]ABSTRACT: Background:
Research has demonstrated a bidirectional relationship between physical function and depression, but studies on their association in migrant populations are scarce. We examined the association between mental health symptoms and mobility limitation in Russian, Somali and Kurdish migrants in Finland.
We used data from the Finnish Migrant Health and Wellbeing Study (Maamu). The participants comprised 1357 persons of Russian, Somali or Kurdish origin aged 18-64 years. Mobility limitation included self-reported difficulties in walking 500 m or stair climbing. Depressive and anxiety symptoms were measured using the Hopkins Symptom Checklist-25 (HSCL-25) and symptoms of somatization using the somatization subscale of the Symptom Checklist-90 Revised (SCL-90-R). A comparison group of the general Finnish population was selected from the Health 2011 study.
Anxiety symptoms were positively associated with mobility limitation in women (Russians odds ratio [OR] 2.98; 95% confidence interval [CI] 1.28-6.94, Somalis OR 6.41; 95% CI 2.02-20.29 and Kurds OR 2.67; 95% CI 1.41-5.04), after adjustment for socio-demographic factors, obesity and chronic diseases. Also somatization increased the odds for mobility limitation in women (Russians OR 4.29; 95% CI 1.76-10.44, Somalis OR 18.83; 95% CI 6.15-57.61 and Kurds OR 3.53; 95% CI 1.91-6.52). Depressive symptoms were associated with mobility limitation in Russian and Kurdish women (Russians OR 3.03; 95% CI 1.27-7.19 and Kurds OR 2.64; 95% CI 1.39-4.99). Anxiety symptoms and somatization were associated with mobility limitation in Kurdish men when adjusted for socio-demographic factors, but not after adjusting for obesity and chronic diseases. Finnish women had similar associations as the migrant women, but Finnish men and Kurdish men showed varying associations.
Mental health symptoms are significantly associated with mobility limitation both in the studied migrant populations and in the general Finnish population. The joint nature of mental health symptoms and mobility limitation should be recognized by health professionals, also when working with migrants. This association should be addressed when developing health services and health promotion.
Full-text available · Article · Dec 2015 · BMC Public Health
[Show abstract][Hide abstract]ABSTRACT: Under-treated depression may be especially harmful in early adulthood. The aims of this study are to describe treatments received for depressive disorders, to define factors associated with treatment adequacy and dropouts from treatment in a Finnish general population sample of young adults.
A nationally representative two-stage cluster sample of 1894 Finns aged 19 to 34 years was sent a questionnaire containing several mental health screens. All screen positives and a random sample of screen negatives were invited to participate in a mental health assessment including a SCID interview. Case records from mental health treatments for the same sample were obtained for the final diagnostic assessment. Based on all available information, receiving antidepressant pharmacotherapy for at least two months with at least four visits with any type of physician or at least eight sessions of psychotherapy within 12 months or at least four days of hospitalization were regarded as minimally adequate treatment. Treatment dropout was rated if the treatment strategy was assessed to be adequate according to the case records but the patient discontinued the visits.
Of participants with depressive disorders (n = 142), 40.9% received minimally adequate treatment. In multiple logistic regression models, substance use disorder and female gender were associated with at least one visit with a physician, while having major depressive disorder was associated with visits with a physician at least 4 times a year. Women had higher odds of having received any psychotherapy and psychotherapy lasting for at least 8 sessions in a year. Low education and a history of suicide attempt were associated with increased odds of treatment dropout. None of the factors explained the final outcome of minimally adequate treatment.
Treatment adequacy in the present study was better than previously seen, but more efforts are needed to provide adequate treatment for young adults, especially those with low education and suicidality.
Full-text available · Article · Dec 2015 · BMC Psychiatry
[Show abstract][Hide abstract]ABSTRACT: Background:
Depressive disorders are among the most pressing public health challenges worldwide. Yet, not enough is known about their long-term outcomes. This study examines the course and predictors of different outcomes of depressive disorders in an eleven-year follow-up of a general population sample.
In a nationally representative sample of Finns aged 30 and over (BRIF8901), major depressive disorder (MDD) and dysthymia were diagnosed with the Composite International Diagnostic Interview (M-CIDI) in 2000. The participants were followed up in 2011 (n=5733). Outcome measures were diagnostic status, mortality, depressive symptoms and health-related quality of life. Multiple imputation (MI) was used to account for nonresponse.
At follow-up, 33.8% of persons with baseline MDD and 42.6% with baseline dysthymia received a diagnosis of depressive, anxiety or alcohol use disorder. Baseline severity of disorder, measured by the Beck Depression Inventory, predicted both persistence of depressive disorder and increased mortality risk. In addition, being never-married, separated or widowed predicted persistence of depressive disorders, whereas somatic and psychiatric comorbidity, childhood adversities and lower social capital did not. Those who received no psychiatric diagnosis at follow-up still had residual symptoms and lower quality of life.
We only had one follow-up point at eleven years, and did not collect information on the subjects' health during the follow-up period.
Depressive disorders in the general population are associated with multiple negative outcomes. Severity of index episode is the strongest predictor of negative outcomes. More emphasis should be placed on addressing the long-term consequences of depression.
Article · Nov 2015 · Journal of Affective Disorders
[Show abstract][Hide abstract]ABSTRACT: First-episode psychosis (FEP) is associated with weight gain during the first year of treatment, and risk of abdominal obesity is particularly increased. To identify early risk markers of weight gain and abdominal obesity, we investigated baseline metabolic differences in 60 FEP patients and 27 controls, and longitudinal changes during the first year of treatment in patients. Compared to controls at baseline, patients had higher low-density lipoprotein, triglyceride and apolipoprotein B levels, and lower levels of high-density lipoprotein and apolipoprotein A-I but no difference in body mass index or waist circumference. At 12-month follow-up, 60.6% of patients were overweight or obese and 58.8% had abdominal obesity. No significant increase during follow-up was seen in markers of glucose and lipid metabolism or blood pressure, but increase in C-reactive protein between baseline and 12-month follow-up was statistically significant. Weight increase was predicted by baseline insulin resistance and olanzapine use, while increase in waist circumference was predicted by baseline insulin resistance only. In conclusion, insulin resistance may be an early marker of increased vulnerability to weight gain and abdominal obesity in young adults with FEP. Olanzapine should be avoided as a first-line treatment in FEP due to the substantial weight increase it causes. In addition, the increase in the prevalence of overweight and abdominal obesity was accompanied by the emergence of low-grade systemic inflammation.
Full-text available · Article · Nov 2015 · Schizophrenia Research
[Show abstract][Hide abstract]ABSTRACT: Aim:
We explored whether cognitive performance, and verbal learning in particular, predicts psychosis or psychiatric hospitalizations among unselected first-admission adolescent patients in general psychiatric care.
Up to 152 adolescents aged 15-18 were interviewed with the SIPS, tested with a cognitive test battery in the beginning of their psychiatric treatment, and followed for a maximum of 9 years (median 4.5 years).
The composite factors of processing speed, verbal performance and visuospatial performance did not predict psychosis (n = 7) or all-cause psychiatric hospitalizations (n = 26) beyond psychosis risk symptoms. However, those who developed psychosis performed worse on California Verbal Learning Test (CVLT) compared to other adolescents. Lower scores of CVLT immediate recall predicted psychosis (P = .003, HR = 1.13 per CVLT point decrease). However, when general verbal ability was adjusted for, CVLT did not reach significance.
Impaired verbal list learning may predict psychosis also among adolescent psychiatric patients not preselected for psychosis risk suspicion.
Article · Oct 2015 · Early Intervention in Psychiatry
[Show abstract][Hide abstract]ABSTRACT: Background:
Conduct problems during adolescence are associated with an elevated mortality risk. This study investigated the mortality rate, causes of death, and changes over time in a Finnish residential school (RS) population.
All adolescents (N = 885, M/F = 594/291, age mean 15.2 years at baseline) residing in the RS system in 1991, 1996, 2001, and 2006 and matched controls were included in a register-based study with a follow-up time of up to 22 years.
The all-cause mortality rate for people with an RS background was 6.7 % compared to 1.0 % in the controls (Hazard Ratio HR = 6.95, 95 % 4.66-10.37, p < 0.001). 8.1 % of the RS boys had died compared to 2.2 % of the girls (HR = 2.2, p = 0.02). The HR for substance-related death was 24.31 (95 % CI 9.3-65.53, P < 0.001), for suicide 7.23 (95 % CI 3.24-16.11, P < 0.001) and for other external causes 5.45 (95 % CI 2.41-12.36, P < 0.001) compared to controls. Mortality peaked among RS boys at approximately 25 years, whereas for girls it peaked after 30 years.
Adolescents with severe disruptive behavior problems have a seven-fold risk for premature adult-age death compared to matched controls. The most common causes for death were avoidable, substance-related followed by suicide. Effective treatment of mental and substance use related problems during and after the placement is needed to reduce mortality.
Full-text available · Article · Sep 2015 · Child and Adolescent Psychiatry and Mental Health
[Show abstract][Hide abstract]ABSTRACT: The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.