Cohort profile: SUPER-Finland - the Finnish study for hereditary mechanisms of psychotic disorders.

PURPOSE: SUPER-Finland is a large Finnish collection of psychosis cases. This cohort also represents the Finnish contribution to the Stanley Global Neuropsychiatric Genetics Initiative, which seeks to diversify genetic sample collection to include Asian, Latin American and African populations in addition to known population isolates, such as Finland. PARTICIPANTS: 10 474 individuals aged 18 years or older were recruited throughout the country. The subjects have been genotyped with a genome-wide genotyping chip and exome sequenced. A subset of 897 individuals selected from known population sub-isolates were selected for whole-genome sequencing. Recruitment was done between November 2015 and December 2018. FINDINGS TO DATE: 5757 (55.2%) had a diagnosis of schizophrenia, 944 (9.1%) schizoaffective disorder, 1612 (15.5%) type I or type II bipolar disorder, 532 (5.1 %) psychotic depression, 1047 (10.0%) other psychosis and for 530 (5.1%) self-reported psychosis at recruitment could not be confirmed from register data. Mean duration of schizophrenia was 22.0 years at the time of the recruitment. By the end of the year 2018, 204 of the recruited individuals had died. The most common cause of death was cardiovascular disease (n=61) followed by neoplasms (n=40). Ten subjects had psychiatric morbidity as the primary cause of death. FUTURE PLANS: Compare the effects of common variants, rare variants and copy number variations (CNVs) on severity of psychotic illness. In addition, we aim to track longitudinal course of illness based on nation-wide register data to estimate how phenotypic and genetic differences alter it.

Functional Characterization of Six SLCO1B1 (OATP1B1) Variants Observed in Finnish Individuals with a Psychotic Disorder.

Variants in the SLCO1B1 (solute carrier organic anion transporter family member 1B1) gene encoding the OATP1B1 (organic anion transporting polypeptide 1B1) protein are associated with altered transporter function that can predispose patients to adverse drug effects with statin treatment. We explored the effect of six rare SLCO1B1 single nucleotide variants (SNVs) occurring in Finnish individuals with a psychotic disorder on expression and functionality of the OATP1B1 protein. The SUPER-Finland study has performed exome sequencing on 9381 individuals with at least one psychotic episode during their lifetime. SLCO1B1 SNVs were annotated with PHRED-scaled combined annotation-dependent (CADD) scores and the Ensembl variant effect predictor. In vitro functionality studies were conducted for the SNVs with a PHRED-scaled CADD score of >10 and predicted to be missense. To estimate possible changes in transport activity caused by the variants, transport of 2',7'-dichlorofluorescein (DCF) in OATP1B1-expressing HEK293 cells was measured. According to the findings, additional tests with rosuvastatin and estrone sulfate were conducted. The amount of OATP1B1 in crude membrane fractions was quantified using a liquid chromatography tandem mass spectrometry-based quantitative targeted absolute proteomics analysis. Six rare missense variants of SLCO1B1 were identified in the study population, located in transmembrane helix 3: c.317T>C (p.106I>T), intracellular loop 2: c.629G>T (p.210G>V), c.633A>G (p.211I>M), c.639T>A (p.213N>L), transmembrane helix 6: 820A>G (p.274I>V), and the C-terminal end: 2005A>C (p.669N>H). Of these variants, SLCO1B1 c.629G>T (p.210G>V) resulted in the loss of in vitro function, abolishing the uptake of DCF, estrone sulfate, and rosuvastatin and reducing the membrane protein expression to 31% of reference OATP1B1. Of the six rare missense variants, SLCO1B1 c.629G>T (p.210G>V) causes a loss of function of OATP1B1 transport in vitro and severely decreases membrane protein abundance. Carriers of SLCO1B1 c.629G>T might be susceptible to altered pharmacokinetics of OATP1B1 substrate drugs and might have increased likelihood of adverse drug effects such as statin-associated musculoskeletal symptoms.

Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder.

We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.

Maternal schizophrenia and out-of-home placements of offspring: A national follow-up study among Finnish women born 1965-1980 and their children.

Schizophrenia may affect a mother's ability to parent. We investigated out-of-home placements among children with a biological mother having schizophrenia, and their relation to maternal characteristics and adverse perinatal health outcomes of the offspring. For each Finnish woman born between 1 JAN 1965 - 31 DEC 1980 and diagnosed with schizophrenia before 31 DEC 2013 (n = 5214), five matched controls were randomly selected from the Finnish Central Population Register. Children born to these women were identified and followed till 31 DEC 2013. The Child Welfare Register, the Medical Birth Register and the Register of Congenital Malformations were used to gather information. Altogether 35.1% of children with an affected mother and 3.2% of control children were placed out of home during the follow-up. The incidence rate ratio (IRR) of out-of-home placement among children with an affected mother was 12.6 (95% confidence interval (CI) 10.80-13.46) when children with a non-affected mother served as a reference. Single motherhood (IRR 2.2, 95% Cl 1.88-2.60) and maternal smoking (IRR 1.9, 95% Cl 1.68-2.16), but not an adverse perinatal outcome of the offspring, increased the risk of out-of-home placement. To conclude, maternal schizophrenia is a strong risk factor for placement of children in out-of-home care.

The Relationship Between Smoking and Suicidal Behavior in Psychiatric Patients with Major Depressive Disorder.

Smoking is frequently associated with suicidal behavior, but also with confounding other risk factors. We investigated whether smoking independently predicts suicidal ideation, attempts (SAs), or modifies risk of SAs during major depressive episodes (MDEs). In the Vantaa Depression Study (VDS), a 5-year prospective study of psychiatric patients (N = 269) with major depressive disorder (MDD), we investigated the association of suicidal ideation and smoking, and smoking as an independent risk factor for SAs in 2-level analyses of risk during MDEs. Smoking was not significantly associated with suicidal ideation, nor SAs after controlling for confounding factors, and no evidence of a significant effect during MDEs was found. Smoking was neither significantly associated with suicidal ideation, nor predicted suicide attempts.

Obstetric and perinatal health outcomes related to schizophrenia: A national register-based follow-up study among Finnish women born between 1965 and 1980 and their offspring.

BACKGROUND: This national register-based study assesses obstetric and perinatal health outcomes in women with schizophrenia and their offspring. METHODS: Using the Care Register for Health Care, we identified Finnish women who were born in 1965- 1980 and diagnosed with schizophrenia. For each case, five age- and place-of-birth- matched controls were obtained from the Central Population Register of Finland. They were followed from the day when the disorder was diagnosed in specialized health-care (the index day) until 31.12.2013. Information related to births was obtained from the Medical Birth Register and the Register of Congenital Malformations. We focused on singleton pregnancies that led to a delivery after the index day. We restricted the analysis of deliveries in controls to those that occurred after the index day of the case. Maternal age, marital status, smoking status, sex of the newborn, and parity were used as covariates in adjusted models. RESULTS: We identified 1162 singleton births among women with schizophrenia and 4683 among controls. Schizophrenic women had a 1.4-fold increased risk of induction of labor, delivery by cesarean section, and delivery by elective cesarean section. Regarding offspring, the risk of premature birth and the risk of low Apgar score at 1 min (<7) were 1.6-fold, of resuscitation 2.5-fold, and of neonatal monitoring 2.1-fold higher. CONCLUSIONS: Schizophrenia associates with some specific delivery methods, but delivery complications are rare and their prevalence does not differ from that observed among community women. Maternal schizophrenia associates with some negative perinatal health outcomes of the offspring.

Alcohol use and smoking in burn patients at the Helsinki Burn Center.

OBJECTIVE: We investigated alcohol use and smoking at time of burn and their relationships with severity of burn and presence of mental disorders. METHODS: Consecutive acute burn patients (N=107) admitted to the Helsinki Burn Center were assessed with the structured clinical interview for mental disorders (SCID) at baseline and after 6 months. Information regarding being under the influence of alcohol and having smoking-related activity at burn as well as about hazardous drinking (Alcohol Use Disorders Identification Test) and heavy smoking before the burn was recorded. RESULTS: Around half (52%) of the acute burn patients were under the influence of alcohol and 19% had been both drinking and smoking at the time of the burn. Patients under the influence at the time of burn had significantly higher prevalence of lifetime mental disorders compared to those patients who were not under the influence of alcohol (73.2% vs. 45.1%, p=0.003), especially alcohol dependence (55.4% vs. 13.7%, p<0.001) and anxiety disorders (28.6% vs. 9.8%, p=0.015). Patients who had both alcohol use and smoking at burn had even more often at least one mental disorder (95.0% vs. 51.7%, p<0.001), in specific alcohol dependence (90.0% vs. 23.0%, p<0.001), or psychotic disorder (25.0% vs. 6.9%, p=0.016). The main characteristics of the burns themselves did not differ significantly between these groups. CONCLUSION: Half of the burn patients were under the influence of alcohol at the time of the burn in this study. In almost all patients where alcohol and smoking contributed to the burn a diagnosable alcohol use disorder was present. Interventions for those with alcohol use disorders and the associated risk behaviors are important for the prevention of burns.

Psychoactive substance use in specialized psychiatric care patients.

Objective Life expectancy of psychiatric patients is markedly shorter compared to the general population, likely partly due to smoking or misuse of other substances. We investigated prevalence and correlates of substance use among psychiatric patients. Methods Within the Helsinki University Psychiatric Consortium Study, data were collected on substance use (alcohol, smoking, and illicit drugs) among patients with schizophrenia or schizoaffective disorder (n = 113), bipolar (n = 99), or depressive disorder (n = 188). Clinical diagnoses of substance use were recorded, and information on smoking, hazardous alcohol use, or misuse of other substances was obtained using questionnaires. Results One-fourth (27.7%) of the patients had clinical diagnoses of substance use disorders. In addition, in the Alcohol Use Disorders Identification Test, 43.1% had hazardous alcohol use and 38.4% were daily smokers. All substance use was more common in men than in women. Bipolar patients had the highest prevalence of alcohol use disorders and hazardous use, whereas those with schizophrenia or schizoaffective disorder were more often daily smokers. In regression analyses, self-reported alcohol consumption was associated with symptoms of anxiety and borderline personality disorder and low conscientiousness. No associations emerged for smoking. Conclusions The vast majority of psychiatric care patients have a diagnosed substance use disorder, hazardous alcohol use, or smoke daily, males more often than females. Bipolar patients have the highest rates of alcohol misuse, schizophrenia or schizoaffective disorder patients of smoking. Alcohol use may associate with symptoms of anxiety, borderline personality disorder, and low conscientiousness. Preventive and treatment efforts specifically targeted at harmful substance use among psychiatric patients are necessary.

Depression and smoking: a 5-year prospective study of patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) and smoking are major public health problems and epidemiologically strongly associated. However, the relationship between smoking and depression and whether this is influenced by common confounding factors remain unclear, in part due to limited longitudinal data on covariation. METHODS: In the Vantaa Depression Study, psychiatric out- and inpatients with DSM-IV MDD and aged 20-59 years at were followed from baseline to 6 months, 18 months, and 5 years. We investigated course of depression, smoking, and comorbid alcohol-use disorders among the 214 patients (79.6% of 269) participating at least three time points; differences between smoking versus nonsmoking patients, and covariation of MDD, smoking, and alcohol-use disorders. RESULTS: Overall, 31.3% of the patients smoked regularly, 41.1% intermittently, and 27.6% never. Smokers were younger, had more alcohol-use disorders and Cluster B and C personality disorder symptoms, a higher frequency of lifetime suicide attempts, higher neuroticism, smaller social networks, and lower perceived social support than never smokers. Smoking and depression had limited longitudinal covariation. Depression, smoking, and alcohol-use disorders all exhibited strong autoregressive tendencies. CONCLUSIONS: Among adult psychiatric MDD patients, smoking is strongly associated with substance-use and personality disorders, which may confound research on the impact of smoking. Rather than depression or smoking covarying or predicting each other, depression, smoking, and alcohol-use disorders each have strong autoregressive tendencies. These findings are more consistent with common factors causing their association than either of the conditions strongly predisposing to the other.

Living alone and antidepressant medication use: a prospective study in a working-age population.

BACKGROUND: An increasing proportion of the population lives in one-person households. The authors examined whether living alone predicts the use of antidepressant medication and whether socioeconomic, psychosocial, or behavioral factors explain this association. METHODS: The participants were a nationally representative sample of working-age Finns from the Health 2000 Study, totaling 1695 men and 1776 women with a mean age of 44.6 years. In the baseline survey in 2000, living arrangements (living alone vs. not) and potential explanatory factors, including psychosocial factors (social support, work climate, hostility), sociodemographic factors (occupational grade, education, income, unemployment, urbanicity, rental living, housing conditions), and health behaviors (smoking, alcohol use, physical activity, obesity), were measured. Antidepressant medication use was followed up from 2000 to 2008 through linkage to national prescription registers. RESULTS: Participants living alone had a 1.81-fold (CI = 1.46-2.23) higher purchase rate of antidepressants during the follow-up period than those who did not live alone. Adjustment for sociodemographic factors attenuated this association by 21% (adjusted OR = 1.64, CI = 1.32-2.05). The corresponding attenuation was 12% after adjustment for psychosocial factors (adjusted OR = 1.71, CI = 1.38-2.11) and 9% after adjustment for health behaviors (adjusted OR = 1.74, CI = 1.41-2.14). Gender-stratified analyses showed that in women the greatest attenuation was related to sociodemographic factors and in men to psychosocial factors. CONCLUSIONS: These data suggest that people living alone may be at increased risk of developing mental health problems. The public health value is in recognizing that people who live alone are more likely to have material and psychosocial problems that may contribute to excess mental health problems in this population group.

Screening of psychiatric outpatients for borderline personality disorder with the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD).

BACKGROUND: Detecting patients with borderline personality disorder (BPD) is important, and feasible screening instruments are needed. AIMS: To investigate our Finnish translation of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) as a screen for BPD among psychiatric outpatients, its psychometric and screening properties, and feasibility in improving the recognition of BPD. METHODS: We screened 302 consecutive psychiatric outpatients at the Department of Psychiatry at the Helsinki University Central Hospital in Finland for BPD using the Finnish MSI-BPD. Of the patients, 69 (23%) were assigned to a random sample that was stratified according to the number of screens returned to the outpatient clinics, and further stratified into the three strata, high scores deliberately enriched, according to the MSI-BPD scores. Finally, a stratified random sample of 45 patients was interviewed with the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) by the interviewers blind to the patients' MSI-BPD scores. RESULTS: One third (29%) of 302 screened patients had a positive MSI-BPD. The internal consistency of the MSI-BPD was good (Cronbach's alpha = 0.77). Of the 45 patients interviewed with the SCID-II, 11 (24%) were found to have BPD, five (46%) of whom a previously clinical diagnosis. In a ROC analysis, the optimal cut-off score was 7. CONCLUSIONS: The translated MSI-BPD was found to be a feasible screen for BPD in Finnish psychiatric outpatient care. Further studies investigating the clinical utility of MSI-BPD in larger clinical samples are warranted.

Treatment of major depressive disorder in the Finnish general population.

BACKGROUND: Few general population studies of the treatment of major depressive disorder (MDD) have included the whole spectrum of treatments. We estimated the rates of different treatments and the effect of individual and disorder characteristics plus provider type on treatment received. METHODS: In the Health 2000 Study, a representative sample (n=6,005) from the adult Finnish population (> or =30 years) were interviewed (CIDI) in 2000-2001 for the presence of DSM-IV mental disorders during the past 12 months. Logistic regression models were used to examine factors influencing the type of treatment: either pharmacotherapies (antidepressants, anxiolytics, sedatives/hypnotics, antipsychotics) or psychological treatment. RESULTS: Of the individuals with MDD (n=288), currently 24% used antidepressants, 11% anxiolytics, 16% sedatives/hypnotics, 5% antipsychotics, and 17% reported having received psychological treatment. Overall, 31% received antidepressants or psychological treatment or both; 18% received minimally adequate treatment. Of those 33% (n=94) using health care services for mental reasons, 76% received antidepressants or psychological treatment or both; 54% received minimal adequate treatment. In logistic regression models, the use of antidepressants was associated with female sex, being single, severe MDD, perceived disability, and comorbid dysthymic disorder; psychological treatment with being divorced, perceived disability, and comorbid anxiety disorder. CONCLUSIONS: Due to the low use of health services for mental reasons, only one-third of subjects with MDD use antidepressants, and less than one-fifth receives psychological treatment. The treatments provided are determined mostly by clinical factors such as severity and comorbidity, in part by sex and marital status, but not education or income.

Adequacy of, attitudes toward, and adherence to treatments by suicidal and nonsuicidal depressed patients.

We examined differences in treatments received, and attitudes and adherence to them between suicidal and nonsuicidal patients with major depressive disorder (MDD). Psychiatric MDD patients with no suicidal behavior (N = 92), suicidal ideation (N = 92), or attempts (N = 34) were compared during 6 months of follow-up in the Vantaa Depression Study (VDS). Patients with suicidal behavior received antidepressants or adequate antidepressant treatment significantly more often, had more frequent appointments with psychiatrists, more psychotherapeutic support, and more favorable attitudes toward antidepressant treatment than nonsuicidal patients. However, after adjusting for the confounding severity of depression, the significance of these differences was lost. Adherence to treatment was similar in the patient groups. Overall, among psychiatric patients with MDD, those known to be suicidal have higher suicide risk and should receive more intensive treatment. However, suicidal behavior per se does not seem to markedly influence treatments provided nor should it be associated with negative attitudes or poor adherence to treatments.

Adequacy of treatment received by diagnosed and undiagnosed patients with bipolar I and II disorders.

OBJECTIVE: To investigate the adequacy of pharmacotherapy received by psychiatric inpatients and outpatients with a research diagnosis of bipolar I or II disorder, including patients both with and without a clinical diagnosis of bipolar disorder. METHOD: In the Jorvi Bipolar Study (JoBS), 1630 psychiatric inpatients and outpatients in 3 Finnish cities were systematically screened between January 1, 2002, and February 28, 2003, for bipolar I and II disorders using the Mood Disorder Questionnaire. By using SCID-I and -II interviews, 191 patients were diagnosed with bipolar disorder (90 bipolar I and 101 bipolar II). Information was collected on clinical history, diagnosis, and treatment. The adequacy of treatment received was evaluated. RESULTS: Of the 162 patients with previous bipolar disorder episodes, only 34 (20.9%) of all and 30 (55.5%) of those with a clinical diagnosis of bipolar disorder were using a mood stabilizer at onset of the index episode. Only 81 (42.4%) of all 191 patients and 76 (65.0%) of those diagnosed with bipolar disorder received adequate treatment for the acute index phase. The factor most strongly independently associated with adequate treatment was clinical diagnosis of bipolar disorder (OR = 25.34). In addition, rapid cycling (OR = 2.45), polyphasic index episode (OR = 2.41), or depressive index phase (OR = 3.36) independently predicted inadequate treatment. Outpatients received adequate treatment markedly less often than inpatients. CONCLUSIONS: Clinical diagnosis of bipolar disorder is by far the most important prerequisite for adequate treatment. Problems in treatment are associated mostly with outpatient settings, where adequacy of treatment of bipolar depression is a major concern. Lack of attention to the longitudinal course of illness is another major problem area.

Lifetime prevalence of psychotic and bipolar I disorders in a general population.

CONTEXT: Recent general population surveys of psychotic disorders have found low lifetime prevalences. However, this may be owing to methodological problems. Few studies have reported the prevalences of all specific psychotic disorders. OBJECTIVE: To provide reliable estimates of the lifetime prevalences of specific psychotic disorders. DESIGN: General population survey. SETTING AND PARTICIPANTS: A nationally representative sample of 8028 persons 30 years or older was screened for psychotic and bipolar I disorders using the Composite International Diagnostic Interview, self-reported diagnoses, medical examination, and national registers. Those selected by the screens were then re-interviewed with the Structured Clinical Interview for DSM-IV. Best-estimate DSM-IV diagnoses were formed by combining the interview and case note data. Register diagnoses were used to estimate the effect of the nonresponders. MAIN OUTCOME MEASURES: Diagnosis of any psychotic or bipolar I disorder according to the DSM-IV criteria. RESULTS: The lifetime prevalence of all psychotic disorders was 3.06% and rose to 3.48% when register diagnoses of the nonresponder group were included. Lifetime prevalences were as follows: 0.87% for schizophrenia, 0.32% for schizoaffective disorder, 0.07% for schizophreniform disorder, 0.18% for delusional disorder, 0.24% for bipolar I disorder, 0.35% for major depressive disorder with psychotic features, 0.42% for substance-induced psychotic disorders, and 0.21% for psychotic disorders due to a general medical condition. The National Hospital Discharge Register was the most reliable of the screens (kappa = 0.80). Case notes supplementing the interviews were essential for specific diagnoses of psychotic disorders. CONCLUSIONS: Multiple sources of information are essential for accurate estimation of lifetime prevalences of psychotic disorders. The use of comprehensive methods reveals that their lifetime prevalence exceeds 3%.

The association between burnout and physical illness in the general population--results from the Finnish Health 2000 Study.

OBJECTIVE: The association between burnout and physical diseases has been studied very little. The purpose of this study was to examine the relationship between burnout and physical illness in a representative nationwide population health study. METHODS: As a part of the "Health 2000 Study" in Finland, 3368 employees aged 30-64 years were studied. Burnout was assessed with the Maslach Burnout Inventory-General Survey. Physical diseases were diagnosed in a comprehensive health examination by research physicians. RESULTS: Physical illness was more common among subjects with burnout than others (64% vs. 54%, P<.0001), and the prevalence of diseases increased with the severity of burnout (P<.0001). Burnout was an important correlate of cardiovascular diseases among men (OR=1.35; 95% CI, 1.13-1.61) and musculoskeletal disorders among women (OR=1.22, 95% CI, 1.07-1.38) when adjusted for age, marital status, education, socioeconomic status, physical strenuousness of work, smoking, physical activity, alcohol consumption, body mass index, and depressive symptoms. The prevalence of musculoskeletal disorders and cardiovascular diseases increased with the severity of all three dimensions of burnout, that is, exhaustion (P<.0001 and P<.001, respectively), cynicism (P=.0001 and P<.001, respectively), and lack of professional efficacy (P<.01 and P<.0001, respectively). CONCLUSIONS: Burnout is associated with musculoskeletal diseases among women and with cardiovascular diseases among men. These associations are not explained by sociodemographic factors, health behavior, or depression. Physical illnesses are associated with all three dimensions of burnout and not only with the exhaustion dimension. In the future, the causal relationships between burnout and physical diseases need to be investigated in prospective studies.

Breakdown of long-range temporal correlations in theta oscillations in patients with major depressive disorder.

Neuroimaging has revealed robust large-scale patterns of high neuronal activity in the human brain in the classical eyes-closed wakeful rest condition, pointing to the presence of a baseline of sustained endogenous processing in the absence of stimulus-driven neuronal activity. This baseline state has been shown to differ in major depressive disorder. More recently, several studies have documented that despite having a complex temporal structure, baseline oscillatory activity is characterized by persistent autocorrelations for tens of seconds that are highly replicable within and across subjects. The functional significance of these long-range temporal correlations has remained unknown. We recorded neuromagnetic activity in patients with a major depressive disorder and in healthy control subjects during eyes-closed wakeful rest and quantified the long-range temporal correlations in the amplitude fluctuations of different frequency bands. We found that temporal correlations in the theta-frequency band (3-7 Hz) were almost absent in the 5-100 s time range in the patients but prominent in the control subjects. The magnitude of temporal correlations over the left temporocentral region predicted the severity of depression in the patients. These data indicate that long-range temporal correlations in theta oscillations are a salient characteristic of the healthy human brain and may have diagnostic potential in psychiatric disorders. We propose a link between the abnormal temporal structure of theta oscillations in the depressive patients and the systems-level impairments of limbic-cortical networks that have been identified in recent anatomical and functional studies of patients with major depressive disorder.

Gluten-free diet may alleviate depressive and behavioural symptoms in adolescents with coeliac disease: a prospective follow-up case-series study.

BACKGROUND: Coeliac disease in adolescents has been associated with an increased prevalence of depressive and disruptive behavioural disorders, particularly in the phase before diet treatment. We studied the possible effects of a gluten-free diet on psychiatric symptoms, on hormonal status (prolactin, thyroidal function) and on large neutral amino acid serum concentrations in adolescents with coeliac disease commencing a gluten-free diet. METHODS: Nine adolescents with celiac disease, aged 12 to 16 years, were assessed using the semi-structured K-SADS-Present and Lifetime Diagnostic interview and several symptom scales. Seven of them were followed at 1 to 2, 3, and 6 months on a gluten-free diet. RESULTS: Adolescent coeliac disease patients with depression had significantly lower pre-diet tryptophan/ competing amino-acid (CAA) ratios and free tryptophan concentrations, and significantly higher biopsy morning prolactin levels compared to those without depression. A significant decrease in psychiatric symptoms was found at 3 months on a gluten-free diet compared to patients' baseline condition, coinciding with significantly decreased coeliac disease activity and prolactin levels and with a significant increase in serum concentrations of CAAs. CONCLUSION: Although our results of the amino acid analysis and prolactin levels in adolescents are only preliminary, they give support to previous findings on patients with coeliac disease, suggesting that serotonergic dysfunction due to impaired availability of tryptophan may play a role in vulnerability to depressive and behavioural disorders also among adolescents with untreated coeliac disease.

The clinical characteristics of DSM-IV bipolar I and II disorders: baseline findings from the Jorvi Bipolar Study (JoBS).

OBJECTIVE: To obtain a comprehensive view of the clinical epidemiology of bipolar I and II disorder in secondary-level psychiatric settings. METHODS: In the Jorvi Bipolar Study (JoBS), 1630 non-schizophrenic psychiatric in- and outpatients in three Finnish cities were screened for bipolar I and II disorders with the Mood Disorder Questionnaire. Diagnoses were made using semistructured SCID-I and -II interviews. Information collected included clinical history, current episode, symptom status, and other characteristics. RESULTS: A total of 191 patients with bipolar disorder (90 bipolar I and 101 bipolar II) were included in the JoBS. The majority of bipolar II (50.5%) and many bipolar I (25.6%) patients were previously undiagnosed; the remainder had a median 7.8 years delay from first episode to diagnosis. Despite several lifetime episodes, 26 and 58% of bipolar I and II patients, respectively, had never been hospitalized. A polyphasic episode was current in 51.3%, rapid cycling in 32.5%, and psychotic symptoms in 16.2% of patients. Mixed episodes occurred in 16.7% of bipolar I, and depressive mixed states in 25.7% of bipolar II patients. CONCLUSION: Even in psychiatric settings, bipolar disorders usually go undetected, or recognized only after a long delay. A significant proportion of not only bipolar II, but also bipolar I patients are never hospitalized. Polyphasic episodes and rapid cycling are prevalent in both types. Depressive mixed states are at least as common among bipolar II patients as mixed episodes among bipolar I.