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Background: Major depressive episodes (MDEs) of major depressive (MDD) or bipolar disorders (BD) are frequently complicated by features of borderline personality disorder (BPD). Mixed features are a hallmark of BD and affective lability of BPD, and both may markedly influence illness course. However, direct comparisons of outcome of depression in MDD, BD, and BPD are scarce.Methods: In a cohort study based on stratified sampling, we diagnosed psychiatric MDE patients with SCID-I/P and SCID-II interviews and examined mixed symptoms using the Mix-MDE scale and borderline symptoms using the Borderline Personality Disorder Severity Index. During a six-month prospective follow-up, the MDE patients with MDD (n = 39), BD (n = 33), or BPD (n = 23) completed biweekly online assessments. Using life chart methodology, we divided the follow-up period into qualitatively different mood state periods. We investigated durations of mood episodes, times to first full symptomatic remission, and their predictors.Results: Remission rates were similar in MDD, MDE/BD, and MDE/BPD patients. MDE/BD patients experienced more numerous and shorter distinct mood state periods during follow-up than the others. MDE/BD was associated with shorter (HR = 2.44, 95 % CI = 1.27-4.67) and dimensionally assessed BPD severity with longer time to first remission (HR = 0.95, 95 % CI = 0.91-1.00). Limitations: Moderate sample size and follow-up duration.Conclusions: Course of illness over six months differs between the three depressive groups. Bipolar depressive patients have the most alternating course and the shortest time to first period of remission. Dimensionally assessed severity of BPD may predict longer time to remission from depression.

BACKGROUND: Adverse pregnancy outcomes (APO) contribute to higher risk of maternal cerebrovascular disease, but longitudinal data that include APO and stroke timing are lacking. We hypothesized that APO are associated with younger age at first stroke, with a stronger relationship in those with >1 pregnancy with APO. METHODS: We analyzed longitudinal Finnish nationwide health registry data from the FinnGen Study. We included women who gave birth after 1969 when the hospital discharge registry was established. We defined APO as a pregnancy affected by gestational hypertension, preeclampsia, eclampsia, preterm birth, small for gestational age infant, or placental abruption. We defined stroke as first hospital admission for ischemic stroke or nontraumatic intracerebral or subarachnoid hemorrhage, excluding stroke during pregnancy or within 1 year postpartum. We used Kaplan-Meier survival curves and multivariable-adjusted Cox and generalized linear models to assess the relationship between APO and future stroke. RESULTS: We included 144 306 women with a total of 316 789 births in the analysis sample, of whom 17.9% had at least 1 pregnancy with an APO and 2.9% experienced an APO in ≥2 pregnancies. Women with APO had more comorbidities including obesity, hypertension, heart disease, and migraine. Median age at first stroke was 58.3 years in those with no APO, 54.8 years in those with 1 APO, and 51.6 years in those with recurrent APO. In models adjusted for sociodemographic characteristics and stroke risk factors, risk of stroke was greater in women with 1 APO (adjusted hazard ratio, 1.3 [95% CI, 1.2–1.4]) and recurrent APO (adjusted hazard ratio, 1.4 [95% CI, 1.2–1.7]) compared with those with no APO. Women with recurrent APO had more than twice the stroke risk before age 45 (adjusted odds ratio, 2.1 [95% CI, 1.5–3.1]) compared with those without APO. CONCLUSIONS: Women who experience APO have earlier onset of cerebrovascular disease, with the earliest onset in those with more than 1 affected pregnancy.

Knowledge of the effectiveness and limits of the suitability of brief interventions in suicide prevention is greatly needed. We investigated subgroup differences and predictors for suicide re-attempts within a clinical trial population recruited for a brief intervention to prevent re-attempts.Consenting adult patients receiving treatment for a suicide attempt in Helsinki City general hospital emergency rooms in 2016-2017 (Re-attempts were predicted by participants' younger age (OR 0.965 [0.933-0.998]), previous suicide attempts (OR 2.437 [1.106-5.370]), psychiatric hospitalization in the year preceding baseline (OR 3.256 [1.422-7.458]), and clinical diagnosis of a personality disorder (OR 4.244 [1.923-9.370]), especially borderline personality disorder (OR 5.922 [2.558-13.709]).Within a population of suicide attempters consenting to a brief intervention trial, the risk of re-attempt was strongly predicted by subjects' young age, history of previous attempts, psychiatric hospitalizations, and personality disorder, particularly borderline personality disorder. The composition of treated populations with regard to these characteristics may strongly influence the observed success of brief interventions. Their potential as moderators of treatment effectiveness and as indicators of the utility of brief interventions warrants further investigation.HIGHLIGHTSDuring the 2-year follow-up, 32% of trial participants reattempted suicide.Rates of reattempts varied and were strongly predicted by clinical subgroup.Subgroup composition may strongly influence brief interventions' observed outcome.

Introduction: An increase in brain white matter hyperintensities (WMHs) and a decrease in white matter fractional anisotrophy (FA) have been detected in bipolar I (BPI), II (BPII), and major depressive disorder (MDD) patients. Their relationship, and differences in diagnostic groups are obscure. Longitudinal studies are rare. Objective: After 5-year follow-up, we evaluated WMHs in BPI, BPII, and MDD patients as compared with controls, and studied the effects of clinical variables. We also explored the associations of clinical variables with cross-sectional whole brain FA. Methods: Eight BPI, 8 BPII, 6 MDD patients, and 19 controls participated in magnetic resonance imaging at baseline and follow-up. Diffusion weighted imaging was included at follow-up. WMHs were rated by the Coffey scale, and a tract-based spatial statistics method was used for diffusion data. The general linear model, ANOVA, Fisher’s exact, Wilcoxon sign, and Kruskal-Wallis tests were used for statistical analyses. Results: Periventricular WMHs were increased in BPI patients (p = 0.047) and associated with the duration of disorder and lifetime occurrence of substance use disorder (p = 0.018). FA decrease was found in the corpus callosum of BPI patients (p < 0.01). MDD patients showed FA decrease in the right cerebellar middle peduncle (RCMP) (p < 0.01). In BPI patients, the duration of disorder associated with FA increase in RCMP (p < 0.05). No FA decrease was detected in patients with WMHs as compared with those without. Conclusions: Preceding illness burden associated modestly with WMHs, and FA increase in RCMP in BPI patients. MDD patients had FA decrease in RCMP. No association with FA decrease and WMHs was found.

Despite accumulation of clinical research on risk factors for suicidal process, understanding of the mechanisms and pathways underlying the emergence of suicidal thoughts and their progression to acts is insufficient. The suicidal process has been conceptualized in multiple psychological theories that have aimed to shed light on the interplay of contributing factors. One of the central concepts included in both the cubic model of suicide and the three-step theory of suicide is psychological pain (mental pain or psychache). Over the two last decades, interest in psychological pain has increased considerably, particularly since the discovery of the complex link between the pain processing system and the neurobiology of suicide, and the putative antisuicidal effect of buprenorphine. Growing evidence supports the association between experiencing psychological pain and suicidal ideation and acts in both clinical and non-clinical samples. However, many questions related to the concept of psychological pain and its role in prediction of suicidal behavior remain to be answered in future research. In this narrative review, we have outlined the history of the concept, the definition of psychological pain, and the tools developed for its measurement, summarized the empirical research on psychological pain in relation to suicidal behavior, and suggested future directions for clinical research on psychological pain and suicidal behavior.

Background Bipolar disorder (BD) is one of the leading causes of disability worldwide. However, the prevalence and predictors of long-term work disability among patients with type I and II BD have scarcely been studied. We investigated the clinical predictors of long-term work disability among patients with BD. Methods The Jorvi Bipolar Study (JoBS) is a naturalistic prospective cohort study (n = 191) of adult psychiatric in- and out-patients with DSM-IV type I and II BD in three Finnish cities. Within JoBS we examined the prevalence and predictors of disability pension being granted during a six-year follow-up of the 152 patients in the labor force at baseline and collected information on granted pensions from national registers. We determined the predictors of disability pension using logistic regression models. Results Over the 6 years, 44% of the patients belonging to the labor force at baseline were granted a disability pension. Older age; type I BD; comorbidity with generalized anxiety disorder, post-traumatic stress disorder or avoidant personality disorder; and duration of time with depressive or mixed symptoms predicted disability pensions. Including disability pensions granted before baseline increased their total prevalence to 55.5%. The observed predictors were similar. Conclusion This regionally representative long-term prospective study found that about half of patients with type I or II bipolar disorder suffer from persistent work disability that leads to disability pension. In addition to the severity of the clinical course and type I bipolar disorder, the longitudinal accumulation of time depressed, psychiatric comorbidity, and older age predicted pensioning.

PurposeSUPER-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.Participants10 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 date5757 (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 plansCompare 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.

To examine seasonal patterns of hospital admissions due to mood and psychotic disorders and to investigate whether the admission rates show variation according to the seasonal daylength (photoperiods).A retrospective nationwide register-based cohort of all psychiatric admissions (N=978,079) during 1987-2017 in Finland was utilized. The smoothed time-series of adjusted ratio of observed and expected (O/E) daily counts were estimated to examine seasonal variation. The mean O/E with 95% confidence intervals (CI) was used to study the admission rates by photoperiods. The calendar days were classified into the 71-day photoperiods based on the daylength (long/summer, short/winter, equal/spring, equal/fall) and the pace of change in daylength (slowly/rapidly increasing/decreasing daylength).Manic episodes peaked in summer during the long (mean O/E=1.10, 95% CI=1.06-1.13) and slowly decreasing (1.09, 1.06-1.13) photoperiods and had a nadir in winter during the slowly increasing (0.93, 0.89-0.98) photoperiod. Admissions for unipolar depressive (UPD) episodes peaked in autumn and in spring at the end of the rapidly decreasing (1.03, 1.02-1.04) and increasing (1.03, 1.01-1.04) photoperiod, and dropped in summer during the long and slowly decreasing (0.95, 0.94-0.96) photoperiods. Bipolar depressive (BPD) and mixed episodes signaled excess admissions in autumn and in spring. Admissions for schizophrenia were higher than expected from summer to early-autumn, during the long and slowly decreasing photoperiods (1.02, 1.02-1.03), and lower than expected in other seasons, especially in mid-spring during the rapidly increasing photoperiod (0.98, 0.98-0.99).The study indicates the seasonality and photoperiodicity of mental disorders, especially for manic episodes. The seasonal pattern is similar between schizophrenia and manic episodes, and between UPD, BPD, and mixed episodes.

ASSIP (Attempted Suicide Short Intervention Program) is a brief psychotherapeutic intervention found remarkably effective in reducing rate of suicide attempt repetition in the pivotal study in Bern, Switzerland. We compared effectiveness of the ASSIP to usual crisis counselling (CC) in a randomized trial (ISRCTN13464512).Adult patients receiving somatic treatment for a suicide attempt at the Helsinki City general hospital emergency rooms in 2016-2017 were requested to participate. Psychotic or likely nonadherent substance abusing or dependent patients were excluded. Consenting, eligible patients (Of patients randomized, two thirds initiated either ASSIP (We found no evidence for a difference in effectiveness of the two active interventions in preventing the repetition of suicide attempts.

Objective To examine temporal patterns and predictors for diagnostic conversion from unipolar depression (UD) to bipolar disorder (BD), schizophrenia, and schizoaffective disorder (SAD). Methods A prospective nationwide register-based cohort (n = 43 495) of all first psychiatric hospitalizations due to UD during 1996-2011 was followed up to 15 years. We used cumulative incidence function (CIF) analyses and the Fine-Gray subdistribution model to define the cumulative incidence of the conversions and subdistribution hazard ratios (SHRs) for predictors. Results The overall 15-year cumulative incidence of conversion was 11.1% (95% CI 10.7-11.6): 7.4% (95% CI 7.0-7.8) for BD, 2.5% (95% CI 2.3-2.7) for schizophrenia, and 1.3% (95% CI 1.1-1.4) for SAD. The highest crude incidence rate emerged during the first year. Psychotic depression predicted higher conversion risk to BD (SHR = 2.0, 95% CI 1.5-2.7), schizophrenia (SHR = 5.3, 95% CI 3.3-8.7), and SAD (SHR = 10.6, 95% CI 4.0-28.4) than mild depression. Female sex, greater overall disturbance, and comorbid personality disorder predicted conversion to BD, whereas young age and male sex to psychotic disorders. Conclusions Among patients with first hospitalization due to UD, approximately one in nine converts to another major psychiatric disorder during 15 years, with the highest risk occurring within the first year. Patients with psychotic depression are particularly vulnerable for conversion to other major psychiatric disorders. Conversion to psychotic disorders occurs earlier than to BD. Males are at higher risk for progression to psychotic disorders, whereas females, patients with recurrent depressive episodes, severe disturbance of overall functioning, and personality disorder are at higher risk for converting to BD.

We have previously reported a replicable association between variants at the PDE4D gene and familial schizophrenia in a Finnish cohort. In order to identify the potential functional mutations underlying these previous findings, we sequenced 1.5 Mb of the PDE4D genomic locus in 20 families (consisting of 96 individuals and 79 independent chromosomes), followed by two stages of genotyping across 6668 individuals from multiple Finnish cohorts for major mental illnesses. We identified 4570 SNPs across the PDE4D gene, with 380 associated to schizophrenia (p ≤ 0.05). Importantly, two of these variants, rs35278 and rs165940, are located at transcription factor-binding sites, and displayed replicable association in the two-stage enlargement of the familial schizophrenia cohort (combined statistics for rs35278 p = 0.0012; OR = 1.18, 95% CI: 1.06–1.32; and rs165940 p = 0.0016; OR = 1.27, 95% CI: 1.13–1.41). Further analysis using additional cohorts and endophenotypes revealed that rs165940 principally associates within the psychosis (p = 0.025, OR = 1.18, 95% CI: 1.07–1.30) and cognitive domains of major mental illnesses (g-score p = 0.044, β = –0.033). Specifically, the cognitive domains represented verbal learning and memory (p = 0.0091, β = –0.044) and verbal working memory (p = 0.0062, β = −0.036). Moreover, expression data from the GTEx database demonstrated that rs165940 significantly correlates with the mRNA expression levels of PDE4D in the cerebellum (p-value = 0.04; m-value = 0.9), demonstrating a potential functional consequence for this variant. Thus, rs165940 represents the most likely functional variant for major mental illness at the PDE4D locus in the Finnish population, increasing risk broadly to psychotic disorders.

To assess psychosocial and somatic risk factors related to pregnancy, and pregnancy-related complications or disorders in women with schizophrenia compared to population controls. In this register-based cohort study, we identified all Finnish women who were born in 1965–1980 and diagnosed with schizophrenia in psychiatric care before 31 December 2013. For each case, five age- and place-of-birth matched controls were randomly selected. They were followed from the day when the disorder was diagnosed in specialized health care till the end of 2013. The mean follow-up time was 14.0 + 6.91 vs. 14.3 + 6.89 years. Altogether, 1162 singleton pregnancies were found among affected women and 4683 among controls. Affected women were significantly older and more often single; their body mass index before pregnancy was significantly higher, and they smoked significantly more often both in the beginning of pregnancy and after the first trimester than controls. They showed a significantly higher odds for pathologic oral glucose tolerance test (odds ratio (OR) 1.66, 95% confidence interval (95% CI) 1.27–2.17), initiation of insulin treatment (OR 1.84, 95% CI 1.15–2.93), fast fetal growth (OR 1.62, 95% CI 1.03–2.52), premature contractions (OR 2.42, 95% CI 1.31–4.49), hypertension (OR 1.81, 95% CI 1.01–3.27), and pregnancy-related hospitalizations (OR 1.97, 95% CI 1.66–2.33). Suspected damage to the fetus from alcohol/drugs was significantly more common among affected women than controls. Women with schizophrenia have higher prevalence of psychosocial and somatic risk factors related to pregnancy, as well as pregnancy-related complications and disorders than non-affected women.

PurposeWe constructed a CYP2D6 copy-number imputation panel by combining copy-number information to GWAS chip data. In addition, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland.MethodsWe combined GWAS chip and CYP2D6 copy-number variation (CNV) data from the Breast Cancer Pain Genetics study (BrePainGen) to construct an imputation panel (N=902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9,262 non-related individuals passing genotype data quality control procedures. The panel performance was evaluated by genotyping the CNV from a subset (N=297) of SUPER-Finland participants.ResultsCYP2D6 CNV was imputed correctly in 272 (92%) individuals. Sensitivity and specificity for detecting a duplication were 0.986 and 0.946, respectively. Sensitivity and specificity for detecting a deletion using imputation were 0.886 and 0.966, respectively. Based on imputation, the frequency of a CYP2D6 duplication and deletion in the whole SUPER-Finland sample with 9,262 non-related individuals passing quality control were 8.5% and 2.7%, respectively. We confirm the higher frequency of CYP2D6 ultrarapid metabolizers in Finland compared with non-Finnish Europeans. Additionally, we confirm a 21-fold enrichment of the UGT1A1 decreased function variant rs4148323 (also known as 211G>A, G71R or UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland.ConclusionOur results demonstrate that imputation of CYP2D6 CNV is possible. The methodology is not accurate enough to be used in clinical decision making, but it enables studying CYP2D6 in large biobanks with genome-wide data. In addition, it allows for researchers to recontact patients with certain pharmacogenetic variations through biobanks. We show that bottle-necked populations may have pharmacogenetically important variants with allele frequencies very different from the main ancestral group. Future studies should assess whether these differences are large enough to cause clinically significant changes in trial results across different ancestral groups.

Mental disorders are a major global cause of morbidity and mortality. The surge in adoption of smartphones and other wearable devices has made it possible to use the data generated by them for clinical purposes. In particular, in psychiatry, detailed and high-resolution information on patient’s state, mood, and behavior can significantly improve the assessment, diagnosis and the treatment of patients. However, there is long path to turn the raw data created by these sensors, to information and insights that can be applied in clinical practice.Here, we introduce the MoMo-Mood Pilot: a study created to investigate the feasibility of using smartphones and wearables as data collection tools from subjects suffering from major depressive disorder. We collect data from 14 patients and 22 controls in two phases (active and passive). We demonstrate the feasibility of monitoring patients with several devices over short periods and passively monitoring them over long periods of time with minimal disruption in their daily activities. We identify and describe a series of challenges in this process.The MoMo-Mood pilot study is an encouraging step in the process of determining the effectiveness of using wearables for quantifying the behavior and the state of psychiatric patients with high temporal resolution, which can lead to their potential adoption in clinical practice.

Background and objectives Schema group therapy is a potentially cost-effective treatment for borderline personality disorder (BPD). We piloted the feasibility and effectiveness of a 20-session schema group therapy without individual therapy among psychiatric BPD outpatients in a randomized pilot study registered as a clinical trial (ISRCTN76381242). Methods Altogether 42 psychiatric outpatients diagnosed with BPD were randomized 2:1 to a 20-session weekly schema group therapy plus treatment as usual (TAU) (n = 28) vs. a control group with TAU alone (n = 14). The primary outcome was decline of BPD symptoms in the short Borderline Symptom List (BSL-23) score. Secondary outcomes were decline in symptoms of anxiety, depression, alcohol use, and improvement in functioning and schema modes. Two external experts evaluated validity of the intervention based on videotaped sessions. Results Overall, 23 schema group therapy patients (82%) and 12 controls (86%) completed their treatment. Treatment validity good or very good. However, no significant differences emerged in the primary outcome mean BSL-23 decline (6.95 [SE 5.91] in group schema therapy vs. 12.55 [4.85] in TAU) or in any of the secondary outcome measures. Limitations Despite randomization, the TAU subgroup had non-significantly higher baseline scores in most measures. Small sample size predisposing to type II errors; reliance on self-reported outcomes. Conclusions Schema group therapy was feasible for psychiatric outpatients with BPD. However, in this small pilot study we did not find it more effective than TAU. Effectiveness of this short intervention remains open.

Bipolar symptoms and borderline personality features occur in both unipolar and bipolar major depressive episodes (MDEs). We investigated their prevalence, severity, co-occurrence and overlap.We interviewed 124 psychiatric outpatients with MDE using the Structured Clinical Interview for DSM-IV-TR Axis I and II Disorders, the Borderline Personality Disorder Severity Index (BPDSI-IV), and about past (hypo)manic episodes, and stratified them according to the principal diagnosis into subcohorts of major depressive disorder (MDD, n = 50), bipolar disorder (BD, n = 43), and borderline personality disorder (BPD, n = 31). We quantified (hypo)manic symptoms using a novel semi-structured interview (MIXed symptoms during MDE, MIX-MDE) with good psychometric qualities.The subcohorts did not differ in MDE severity. They differed significantly in some (hypo)manic symptoms being present on most days in 24% of MDD, 30% of BD, and 42% of BPD subcohort, but only 5% of the BD subcohort fulfilled the DSM-5 mixed features. The mean MIX-MDE scores were 5.7 (SD 4.0), 12.0 (8.2) and 10.5 (7.5), and BPDSI-IV scores 15.6 (7.0), 17.2 (6.2) and 26.9 (8.7), respectively (both p0.001). (Hypo)manic days and unspecific symptoms of distractibility and irritability inflated the correlation of observed (hypo)manic symptoms and borderline features.Moderate sample size, limited age variation (18-50 years); no previous validation of MIX-MDE.Presence of some mixed and borderline features is common in MDEs, with overlap and diagnosis-specific differences. Unspecific symptoms of irritability and distractibility and the aggravating impact of hypomania on perceived BPD features blur the differential diagnosis.

Objective The cognitive theory of suicide postulates that hopelessness is an essential precondition for suicidal ideation in patients with depressive disorder . However, the explanatory power and predictive value of hopelessness for suicidal ideation remain uncertain. Methods From 1997 to 2007, patients with depressive disorder who were cohorts from the Vantaa Depression Studies (n = 406) completed the Scale for Suicide Ideation (SSI), Beck Hopelessness Scale (BHS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Perceived Social Support Scale-Revised (PSSS-R), and Eysenck Personality Inventory-Q (EPI-Q) at baseline, 6 and 18 months, and 5 years. We conducted a mixed-effects generalized linear regression and clustered receiver-operating characteristics analysis to test how well BDI and BHS predict severe suicidal ideation within and between patients. Results BHS predicted clinically significant suicidal ideation (odds ratio [OR] = 2.8), explaining 13.1% of between-patient and and 3.5% of within-patient variance of SSI. Adjusting for the fixed effect of BDI removed a substantial part of the effect of BHS on SSI (adjusted OR = 1.38, P = .018). BAI moderated the effect of BHS on SSI, whereas EPI-Q and PSSS-R did not. BDI detected suicidal ideation more accurately (area under the receiver-operating characteristics curve [AUC] = 0.846) than BHS (AUC = 0.754). Conclusions In patients with depressive disorder, hopelessness explains suicidal ideation, but largely because it covaries with depressive symptoms. The role of hopelessness as a central determinant of suicidal ideation in depression may have been overestimated. Symptoms of anxiety moderate the association between hopelessness and suicidal ideation. Severity of depressive symptoms may predict suicidal ideation more accurately than hopelessness.

Through copy number variations, the 16p13.11 locus has been consistently linked to mental disorders. This locus contains the NDE1 gene, which also encodes microRNA-484. Both of them have been highlighted to play a role in the etiology of mental illness. A 4-SNP haplotype spanning this locus has been shown to associate with schizophrenia in Finnish females. Here we set out to identify any functional variations implicated by this haplotype. We used a sequencing and genotyping study design to identify variations of interest in a Finnish familial cohort ascertained for schizophrenia. We identified 295 variants through sequencing, none of which were located directly within microRNA-484. Two variants were observed to associate with schizophrenia in a sex-dependent manner (females only) in the whole schizophrenia familial cohort (rs2242549 P = .00044; OR = 1.20, 95% CI 1.03–1.40; rs881803 P = .00021; OR = 1.20, 95% CI 1.02–1.40). Both variants were followed up in additional psychiatric cohorts, with neuropsychological traits, and gene expression data, in order to further examine their role. Gene expression data from the familial schizophrenia cohort demonstrated a significant association between rs881803 and 1504 probes (FDR q < 0.05). These were significantly enriched for genes that are predicted miR-484 targets (n = 54; P = .000193), and with probes differentially expressed between the sexes (n = 48; P = .000187). While both SNPs are eQTLs for NDE1, rs881803 is located in a predicted transcription factor binding site. Based on its location and association pattern, we conclude that rs881803 is the prime functional candidate under this locus, affecting the roles of both NDE1 and miR-484 in psychiatric disorders.

Poor adherence to psychiatric treatment is a common clinical problem, leading to unfavourable treatment outcome and increased healthcare costs.The aim of this study was to investigate the self-reported adherence and attitudes to outpatient visits and pharmacotherapy in specialized care psychiatric patients.Within the Helsinki University Psychiatric Consortium (HUPC) pilot study, in- and outpatients with schizophrenia or schizoaffective disorder (SSA, n = 113), bipolar disorder (BD, n = 99), or depressive disorder (DD, n = 188) were surveyed about their adherence and attitudes towards outpatient visits and pharmacotherapy. Correlates of self-reported adherence to outpatient and drug treatment were investigated using regression analysis.The majority (78.5%) of patients reported having attended outpatient visits regularly or only partly irregularly. Most patients (79.2%) also reported regular use of pharmacotherapy. Self-reported non-adherence to preceding outpatient visits was consistently and significantly more common among inpatients than outpatients across all diagnostic groups (p .001). Across all groups, hospital setting was the strongest independent correlate of poor adherence to outpatient visits (SSA β = -2.418, BD β = -3.417, DD β = -2.766; p .001 in all). Another independent correlate of non-adherence was substance use disorder (SSA β = -1.555, p = .001; BD β = -1.535, p = .006; DD β = -2.258, p .000). No other socio-demographic or clinical factor was significantly associated with poor adherence in multivariate regression models.Irrespective of diagnosis, self-reported adherence to outpatient care among patients with schizophrenia or schizoaffective disorder, bipolar disorder, and depression is associated strongly with two factors: hospital setting and substance use disorders. Thus, detection of adherence problems among former inpatients and recognition and treatment of substance misuse are important to ensure proper outpatient care.

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.

Background:Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders.Methods:Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n = 287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts.Results:The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P = 0.002) and independent of current depressive symptoms.Conclusions:The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation.

Objectives Few long-term studies on bipolar disorder (BD) have investigated the incidence and risk factors of suicide attempts (SAs) specifically related to illness phases. We examined the incidence of SAs during different phases of BD in a long-term prospective cohort of bipolar I (BD-I) and bipolar II (BD-II) patients, and risk factors specifically for SAs during major depressive episodes (MDEs). Methods In the Jorvi Bipolar Study (JoBS), 191 BD-I and BD-II patients were followed using life-chart methodology. Prospective information on SAs of 177 patients (92.7%) during different illness phases was available up to 5 years. The incidence of SAs and their predictors were investigated using logistic and Poisson regression models. Analyses of risk factors for SAs occurring during MDEs were conducted using two-level random-intercept logistic regression models. Results During the 5 years of follow-up, 90 SAs per 718 patient-years occurred. The incidence was highest, over 120-fold higher than in euthymia, during mixed states (765/1000 person-years; 95% confidence interval [CI] 461−1269 person-years), and also very high in MDEs, almost 60-fold higher than in euthymia (354/1000 person-years; 95% CI 277−451 person-years). For risk of SAs during MDEs, the duration of MDEs, severity of depression, and cluster C personality disorders were significant predictors. Conclusions We confirmed in this long-term study that the highest incidences of SAs occur in mixed and major depressive illness phases. The variations in incidence rates between euthymia and illness phases were remarkably large, suggesting that the question “when” rather than “who” may be more relevant for suicide risk in BD. However, risk during MDEs is likely also influenced by personality factors.

Background Comorbid alcohol use disorder (AUD) is common among patients with major depressive disorder (MDD), and often complicates presentation and treatment. However, there is a scarcity of clinical studies investigating the characteristics and outcome of psychiatric MDD patients with AUD. Methods In the Vantaa Depression Study (VDS), a five-year prospective study of psychiatric out- and inpatients (N = 269) with MDD, we investigated the clinical features of MDD, comorbid Axis I and II disorders, psychosocial factors, and long-term outcome of patients with or without AUD. Results Depressed patients with comorbid AUD at baseline (n = 66/269, 24.5%) were more often male (OR=3.57, [95% CI 1.72 – 7.41], p = 0.001), had more suicidal ideation (OR=1.06 [1.02 – 1.11], p = 0.008), comorbid panic disorders (OR=3.44 [1.47 – 8.06], p = 0.004), symptoms of any personality disorder (OR=1.04 [1.00 – 1.08], p = 0.038), and more often smoked daily (OR=2.79 [1.32 – 5.88], p = 0.007) than those without. At five years, 13.9% (25/180) still had AUD. More specifically, alcohol abuse was associated with suicide attempts, and dependence with suicidal ideation, and Cluster B personality disorder. Patients with AUD spent more time depressed and had more suicide attempts during follow-up. Limitations We did not investigate other substance use disorders. The AUD diagnoses were based on DSM-IV criteria. Conclusions Psychiatric MDD patients with comorbid alcohol use disorders have characteristics consistent with the epidemiology of AUDs in the general population. They are more often males and smoke, and have more comorbid mental disorders and suicidal behavior. Prospectively they spend more time depressed, thus having worse outcomes than patients without AUDs.

BackgroundDepressive disorders are known to impair health-related quality of life (HRQoL) both in the short and long term. However, the determinants of long-term HRQoL outcomes in primary care patients with depressive disorders remain unclear.MethodsIn a primary care cohort study of patients with depressive disorders, 82% of 137 patients were prospectively followed up for five years. Psychiatric disorders were diagnosed with SCID-I/P and SCID-II interviews; clinical, psychosocial and socio-economic factors were investigated by rating scales and questionnaires plus medical and psychiatric records. HRQoL was measured with the generic 15D instrument at baseline and five years, and compared with an age-standardized general population sample (n = 3707) at five years.ResultsDepression affected the 15D total score and almost all dimensions at both time points. At the end of follow-up, HRQoL of patients in major depressive episode (MDE) was particularly low, and the association between severity of depression (Beck Depression Inventory [BDI]) and HRQoL was very strong (r = −0.804). The most significant predictors for change in HRQoL were changes in BDI and Beck Anxiety Inventory (BAI) scores. The mean 15D score of depressive primary care patients at five years was much worse than in the age-standardized general population, reaching normal range only among patients who were in clinical remission and had virtually no symptoms.ConclusionsAmong depressive primary care patients, presence of current depressive symptoms markedly reduces HRQoL, with symptoms of concurrent anxiety also having a marked impact. For HRQoL to normalize, current depressive and anxiety symptoms must be virtually absent.

OBJECTIVE Personality features may indicate risk for both mood disorders and suicidal acts. How dimensions of temperament and character predispose to suicide attempts remains unclear. METHOD Patients (n = 597) from 3 prospective cohort studies (Vantaa Depression Study [VDS], Jorvi Bipolar Study [JoBS], and Vantaa Primary Care Depression Study [PC-VDS]) were interviewed at baseline, at 18 months, and, in VDS and PC-VDS, at 5 years (1997-2003). Personality was measured with the Temperament and Character Inventory-Revised (TCI-R), and follow-up time spent in major depressive episodes (MDEs) as well as lifetime (total) and prospectively ascertained suicide attempts during the follow-up were documented. RESULTS Overall, 219 patients had 718 lifetime suicide attempts; 88 patients had 242 suicide attempts during the prospective follow-up. The numbers of both the total and prospective suicide attempts were associated with low self-directedness (β = -0.266, P = .004, and β = -0.294, P < .001, respectively) and high self-transcendence (β = 0.287, P = .002, and β = 0.233, P = .002, respectively). Total suicide attempts were linked to high novelty seeking (β = 0.195, P = .05). Prospective, but not total, suicide attempts were associated with high harm avoidance (β = 0.322, P < .001, and β = 0.184, P = .062, respectively) and low reward dependence (β = -0.274, P < .001, and β = -0.134, P = .196, respectively), cooperativeness (β = -0.181, P = .005, and β = -0.096, P = .326, respectively), and novelty seeking (β = -0.137, P = .047). No association remained significant when only prospective suicide attempts during MDEs were included. After adjustment was made for total time spent in MDEs, only high persistence predicted suicide attempts (β = 0.190, P < .05). Formal mediation analyses of harm avoidance and self-directedness on prospectively ascertained suicide attempts indicated significant mediated effect through time at risk in MDEs, but no significant direct effect. CONCLUSIONS Among mood disorder patients, suicide attempt risk is associated with temperament and character dimensions. However, their influence on predisposition to suicide attempts is likely to be mainly indirect, mediated by more time spent in depressive episodes.

BackgroundDistinguishing 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.MethodsTwo 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.ResultsThe 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.ConclusionsItems 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.

Background Schizophrenia patients have been found to have long lasting, clinical state independent impairments in intellectual abilities as well as in specific cognitive domains of which visual learning and memory are central to our current study. The main aim of this study was to investigate the sociodemographic and lifestyle factors associated with good visual learning and memory in patients with schizophrenia in a sample of patients. Methods The basic population for this study consists of Finnish SUPER study on genetic mechanisms of psychotic disorders (SUPER), part of the Stanley Global Neuropsychiatric Genomics Initiative. The Northern Finland Birth Cohort 1966 (NFBC 1966) functioned as a reference group to define good cognitive performance. The Finnish SUPER study on genetic mechanisms of psychotic disorders is a part of the international Stanley Global Neuropsychiatric Genomics Initiative. The objective of the study is to understand the genetic and biological background of psychotic disorders. The participants of the present study were patients with clinical diagnosis of schizophrenia who were born between 1950–1979 (N=1,907). The reference group of members of the NFBC 1966 consisted 5,506 individuals aged 46–47 years. Paired Associates Learning (PAL) was used both in SUPER and NFBC 1966 studies. PAL test measures visual memory and new learning. We used the primary outcome variable of ‘total errors adjusted’ (TEA) which assesses learning over repeated attempts. Lower than the mean score of TEA of NFBC 1966 was used as cut-off for good performance in PAL test. SUPER participants with good performance in the PAL test were compared to other SUPER participants. Participants in SUPER study were interviewed and filled in a questionnaire about general mental wellbeing, subjective health and lifestyle factor. The association of following sociodemographic and lifestyle factors were investigated: education, age, marital status, self-rated memory, psychotropic medication use, alcohol consumption and cigarette smoking. Results Of the SUPER participants, 129 (6,9 %) performed at least on the level on which 50% of the participants of the NFBC 1966 performed. Of SUPER participant males 5,9 % and of the females 8,1 % performed on this level. Performing above the NFBC 1966 50% level in the PAL test was associated with higher educational level and higher use of alcohol in males, and with higher educational level and being married in females. Discussion In previous studies age, education, duration of illness, severity of symptoms have been found to count for some of the overall impairments found in schizophrenia. We found a subgroup of schizophrenia patients with good visual learning and memory and sociodemographic and lifestyle factors that were associated with good performance. In our study education and marital status in women and alcohol use in men was associated with better performance in PAL test.

We have previously reported a replicable association between variants at thePDE4Dgene and familial schizophrenia in a Finnish cohort. In order to identify the potential functional mutations alluded to by these previous findings, we sequenced the 1.5Mb of thePDE4Dgenomic locus in 20 families (consisting of 96 individuals, and 79 independent chromosomes), followed by two stages of genotyping across 6,668 individuals from multiple Finnish cohorts for major mental illnesses. We identified 4,570 SNPs across thePDE4Dgene, with 380 associated to schizophrenia (p≤0.05). Importantly, two of these variants, rs35278 and rs165940, are located at transcription factor binding sites, and displayed replicable association in the two-stage enlargement of the familial schizophrenia cohort, (combined statistics for rs35278 p=0.0012; OR=1.18, 95% CI 1.06-1.32; and rs165940 p=0.0016; OR=1.27, 95% CI 1.13-1.41). Further analysis using additional cohorts and endophenotypes revealed that rs165940 principally associates within the psychosis (p=0.025, OR=1.18, 95% CI 1.07-1.30) and cognitive domains of major mental illnesses (g-score p=0.044, beta=-0.033). Specifically, the cognitive domains represented verbal learning and memory (p=0.0091, beta=-0.044) and verbal working memory (p=0.0062, beta=-0.036). Moreover, expression data from the GTEx database demonstrated that rs165940 significantly correlates with the mRNA expression levels ofPDE4Din the cerebellum (p-value=0.04; m-value=0.9), demonstrating a potential functional consequence for this variant. Thus, rs165940 represents the most likely functional variant for major mental illness at thePDE4Dlocus in the Finnish population, increasing risk broadly to psychotic disorders.

BackgroundThe long-term outcomes of bipolar disorder range from lasting remission to chronic course or frequent recurrences requiring admissions. The distinction between bipolar I and II disorders has limited utility in outcome prediction. It is unclear to what extent the clinical course of bipolar disorder predicts long-term outcomes.MethodsA representative sample of 191 individuals diagnosed with bipolar I or II disorder was recruited and followed for up to 5 years using a life-chart method. We previously described the clinical course over the first 18 months with dimensional course characteristics and latent classes. Now we test if these course characteristics predict long-term outcomes, including time ill (time with any mood symptoms) and hospital admissions over a second non-overlapping follow-up period in 111 individuals with available data from both 18 months and 5 years follow-ups.ResultsDimensional course characteristics from the first 18 months prospectively predicted outcomes over the following 3.5 years. The proportion of time depressed, the severity of depressive symptoms and the proportion of time manic predicted more time ill. The proportion of time manic, the severity of manic symptoms and depression-to-mania switching predicted a greater likelihood of hospital admissions. All predictions remained significant after controlling for age, sex and bipolar I v. II disorder.ConclusionsDifferential associations with long-term outcomes suggest that course characteristics may facilitate care planning with greater predictive validity than established types of bipolar disorders. A clinical course dominated by depressive symptoms predicts a greater proportion of time ill. A clinical course characterized by manic episodes predicts hospital admissions.

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.

Background: Increased self-focus and negative self-concept play an important role in depression. Antidepressants influence self-referential processing in healthy volunteers, but their function in self-processing of depressed patients remains unknown. Methods: Thirty-two depressed patients were randomly allocated to receive either escitalopram 10 mg or placebo for one week. After one week, neural responses to positive and negative self-referential adjectives and neutral control stimuli were assessed with functional magnetic resonance imaging. A group of matched healthy volunteers served as a control group. Results: Escitalopram decreased responses of medial fronto-parietal regions to self-referential words relative to non-emotional control stimuli, driven by increased responses to the control condition. Escitalopram also increased responses in the pre-defined region of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) to positive relative to negative words. Importantly, the changes in neural responses occurred before any effect on depressive symptoms, implying a direct effect of escitalopram. Furthermore, the placebo group had decreased responses of the MPFC and the ACC to positive self-referential processing relative to the matched healthy controls. However, neural responses of the escitalopram group and the healthy unmedicated controls were similar. Limitations: Differences between the groups in self-reported depression symptoms and personality traits may have influenced the results. Conclusion: One-week treatment with escitalopram normalized aberrant self-referential processing in depressed patients, shifting the focus from the self to the external environment and potentiating positive self-referential processing. This may be an important factor in mechanism of action of antidepressants.

We have previously reported a replicable association between variants at the PDE4D gene and familial schizophrenia in a Finnish cohort. In order to identify the potential functional mutations underlying these previous findings, we sequenced 1.5 Mb of the PDE4D genomic locus in 20 families (consisting of 96 individuals and 79 independent chromosomes), followed by two stages of genotyping across 6668 individuals from multiple Finnish cohorts for major mental illnesses. We identified 4570 SNPs across the PDE4D gene, with 380 associated to schizophrenia (p ≤ 0.05). Importantly, two of these variants, rs35278 and rs165940, are located at transcription factor-binding sites, and displayed replicable association in the two-stage enlargement of the familial schizophrenia cohort (combined statistics for rs35278 p = 0.0012; OR = 1.18, 95% CI: 1.06-1.32; and rs165940 p = 0.0016; OR = 1.27, 95% CI: 1.13-1.41). Further analysis using additional cohorts and endophenotypes revealed that rs165940 principally associates within the psychosis (p = 0.025, OR = 1.18, 95% CI: 1.07-1.30) and cognitive domains of major mental illnesses (g-score p = 0.044, β = -0.033). Specifically, the cognitive domains represented verbal learning and memory (p = 0.0091, β = -0.044) and verbal working memory (p = 0.0062, β = -0.036). Moreover, expression data from the GTEx database demonstrated that rs165940 significantly correlates with the mRNA expression levels of PDE4D in the cerebellum (p-value = 0.04; m-value = 0.9), demonstrating a potential functional consequence for this variant. Thus, rs165940 represents the most likely functional variant for major mental illness at the PDE4D locus in the Finnish population, increasing risk broadly to psychotic disorders.

Background Patients with bipolar disorder (BD) differ in their relative predominance of types of episodes, yielding predominant polarity, which has important treatment implications. However, few prospective studies of predominant polarity exist. Methods In the Jorvi Bipolar Study (JoBS), a regionally representative cohort of 191 BD I and BD II in- and outpatients was followed for five years using life-chart methodology. Differences between depressive (DP), manic (MP), and no predominant polarity (NP) groups were examined regarding time ill, incidence of suicide attempts, and comorbidity. Results At baseline, 16% of patients had MP, 36% DP, and 48% NP. During the follow-up the MP group spent significantly more time euthymic, less time in major depressive episodes, and more time in manic states than the DP and NP groups. The MP group had significantly lower incidence of suicide attempts than the DP and NP group, lower prevalence of comorbid anxiety disorders but more psychotic symptoms lifetime and more often (hypo)manic first phase of the illness than the DP group. Classification of predominant polarity was influenced by the timeframe used. Limitations The retrospective counting of former phases is vulnerable to recall bias. Assignment of dominant polarity may necessitate a sufficient number of illness phases. Conclusions Predominant polarity has predictive value in predicting group differences in course of illness, but individual patients’ classification may change over time. Patients with manic polarity may represent a more distinct subgroup than the two others regarding illness course, suicide attempts, and psychiatric comorbidity.

Objectives: Many factors influence the likelihood of suicide attempts or deaths in persons with bipolar disorder. One key aim of the International Society for Bipolar Disorders Task Force on Suicide was to summarize the available literature on the presence and magnitude of effect of these factors. Methods: A systematic review of studies published from 1 January 1980 to 30 May 2014 identified using keywords ‘bipolar disorder’ and ‘suicide attempts or suicide’. This specific paper examined all reports on factors putatively associated with suicide attempts or suicide deaths in bipolar disorder samples. Factors were subcategorized into: (1) sociodemographics, (2) clinical characteristics of bipolar disorder, (3) comorbidities, and (4) other clinical variables. Results: We identified 141 studies that examined how 20 specific factors influenced the likelihood of suicide attempts or deaths. While the level of evidence and degree of confluence varied across factors, there was at least one study that found an effect for each of the following factors: sex, age, race, marital status, religious affiliation, age of illness onset, duration of illness, bipolar disorder subtype, polarity of first episode, polarity of current/recent episode, predominant polarity, mood episode characteristics, psychosis, psychiatric comorbidity, personality characteristics, sexual dysfunction, first-degree family history of suicide or mood disorders, past suicide attempts, early life trauma, and psychosocial precipitants. Conclusion: There is a wealth of data on factors that influence the likelihood of suicide attempts and suicide deaths in people with bipolar disorder. Given the heterogeneity of study samples and designs, further research is needed to replicate and determine the magnitude of effect of most of these factors. This approach can ultimately lead to enhanced risk stratification for patients with bipolar disorder.

Objectives The long-term outcome of bipolar disorder (BD) has been extensively investigated. However, previous studies may be biased towards hospitalized patients with bipolar I disorder (BD-I), and generalizability to the current treatment era remains uncertain. In this naturalistic study, we followed a secondary-care cohort of patients with BD. Methods In the Jorvi Bipolar Study, 191 patients with BD-I and bipolar II disorder (BD-II) were followed using a life-chart method. Interviews were conducted at six months, 18 months, and five years. Time to full remission, time to first recurrence, total time ill, their predictors, and BD-I versus BD-II differences were investigated among the 151 patients remaining in follow-up. Results Nearly all subjects recovered from the index episode, but almost all (90%) had a recurrence, and most had multiple recurrences. The patients spent about one-third of their time in illness episodes and 15% of their time with subthreshold symptoms; half of the time they were euthymic. After controlling for confounders, no difference in time spent in depressive states between patients with BD-I and BD-II persisted. Among patients with a depressive index phase, cluster C personality disorders [hazard ratio (HR) = 0.452, p = 0.040] and higher 17-item Hamilton Depression Scale score (HR = 0.951, p = 0.022) predicted longer time to remission, whereas lifetime psychotic symptoms (HR = 2.162, p = 0.016) predicted shorter time to first recurrence. Conclusions Among patients with BD, chronicity as uninterrupted persistence of illness was rare, but multiple recurrences were the norm. Patients with BD spent only half of their time euthymic. Patients with BD-I and BD-II may differ little in proneness to depressive states. Severity of depression, cluster C personality disorders, and psychotic symptoms predicted outcome.

Objective:To study prevalence of and predictors for functional and work disability among primary care (PC) patients with depressive disorders in prospective long-term follow-up.Methods:The Vantaa Primary Care Depression Study followed up prospectively 137 patients with depressive disorders for 5 years with a life chart. Information on level of functioning in general and in different dimensions, employment, sick leaves and disability pensions were obtained from interviews and patient records.Results:Level of functioning and work ability were strongly associated with time spent depressed and/or current severity of depression. Patients who belonged to the labour force at baseline spent one-third of the follow-up off work due to depression; two-thirds were granted sick leaves, and one-tenth a disability pension due to depression. Longer duration of depression, co-morbid disorders and having received social assistance predicted dropping out from work.Conclusion:Duration of depressive episodes appears decisive for long-term disability among PC patients with depression. Patients spent one-third of the follow-up off work due to depression, and remaining outside the labour force is a common outcome. Psychiatric and somatic co-morbidities, education and socio-economic means influence the level of functioning and ability to work, but are not equally important for all areas of life.

Over 800 000 people are estimated to die worldwide by suicide. Based on psychological autopsy studies, nine out of ten subjects who die by suicide have likely suffered from a diagnosable mental disorder preceding death. Because primary health care in most countries provides services for the majority of patients with depressive or substance use disorders, this setting should be the first point of call for suicide prevention. However, despite this central importance, research on incidence and prevalence of suicide deaths, attempts, ideation, or risk factors for suicidal behaviour in primary care settings is quite limited. Information on risk factors is mostly extrapolated from psychiatric or general population epidemiological studies. For purposes of prevention, improving quality and continuity of care of depression and substance use disorders, as well as integrating brief psychosocial interventions into primary care to target suicidal behaviour, are factors of central importance.

OBJECTIVES: Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder. METHODS: Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ≥ 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies. RESULTS: Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide. CONCLUSIONS: This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder. Language: en

BackgroundHow different ways of assessing suicidal ideation influence its prevalence, correlates and predictive validity among patients with major depressive disorder (MDD) remains unclear.MethodsWithin the Vantaa Primary Care Depression Study (PC-VDS, 91 patients) and the Vantaa Depression Study (VDS, 153 psychiatric out-and 41 inpatients), suicidal ideation was assessed with the Scale for Suicidal Ideation (SSI), Hamilton Depression Scale (HAM-D) item 3 and Beck Depression Inventory (BDI) item 9, and by asking whether patients had seriously considered suicide during the episode. The positive and negative predictive values (PPV, NPV) for suicide attempts during a six-month follow-up were investigated.ResultsDepending on the setting, 56–88% of patients had suicidal ideation in some of the assessments, but only 8–44% in all of them. Agreement ranged from negligible to moderate (kappa 0.06–0.64), being lowest among primary care patients. The correlates of suicidal ideation overlapped. No assessment had optimal sensitivity, specificity, PPV and NPV. Nevertheless, PPVs ranged up to 43%.ConclusionsWhich MDD patient is classified as having suicidal ideation depends strongly on the method of assessment, with the greatest variation likely in primary care. Differences in assessments may cause inconsistency in risk factors. Predicting suicide attempts is difficult, but not futile.

Background Personality traits are associated with depressive symptoms and psychiatric disorders. Evidence for their value in predicting accumulation of future dysphoric episodes or clinical depression in long-term follow-up is limited, however. Methods Within a 15-year longitudinal study of a general-population cohort (N=751), depressive symptoms were measured at four time points using Beck׳s Depression Inventory. In addition, 93 primary care patients with DSM-IV depressive disorders and 151 with bipolar disorder, diagnosed with SCID-I/P interviews, were followed for five and 1.5 years with life-chart methodology, respectively. Generalized linear regression models were used to predict future number of dysphoric episodes and total duration of major depressive episodes. Baseline personality was measured by the Temperament and Character Inventory (TCI). Results In the general-population sample, one s.d. lower Self-directedness predicted 7.6-fold number of future dysphoric episodes; for comparison, one s.d. higher baseline depressive symptoms increased the episode rate 4.5-fold. High Harm-avoidance and low Cooperativeness also implied elevated dysphoria rates. Generally, personality traits were poor predictors of depression for specific time points, and in clinical populations. Low Persistence predicted 7.5% of the variance in the future accumulated depression in bipolar patients, however. Limitations Degree of recall bias in life charts, limitations of statistical power in the clinical samples, and 21–79% sample attrition (corrective imputations were performed). Conclusion TCI predicts future burden of dysphoric episodes in the general population, but is a weak predictor of depression outcome in heterogeneous clinical samples. Measures of personality appear more useful in detecting risk for depression than in clinical prediction.

Objective:About one-half to two-thirds of all suicides are by people who suffer from mood disorders; preventing suicides among those who suffer from them is thus central for suicide prevention. Understanding factors underlying suicide risk is necessary for rational preventive decisions.Method:The literature on risk factors for completed and attempted suicide among subjects with depressive and bipolar disorders (BDs) was reviewed.Results:Lifetime risk of completed suicide among psychiatric patients with mood disorders is likely between 5% and 6%, with BDs, and possibly somewhat higher risk than patients with major depressive disorder. Longitudinal and psychological autopsy studies indicate suicidal acts usually take place during major depressive episodes (MDEs) or mixed illness episodes. Incidence of suicide attempts is about 20- to 40-fold, compared with euthymia, during these episodes, and duration of these high-risk states is therefore an important determinant of overall risk. Substance use and cluster B personality disorders also markedly increase risk of suicidal acts during mood episodes. Other major risk factors include hopelessness and presence of impulsive–aggressive traits. Both childhood adversity and recent adverse life events are likely to increase risk of suicide attempts, and suicidal acts are predicted by poor perceived social support. Understanding suicidal thinking and decision making is necessary for advancing treatment and prevention.Conclusion:Among subjects with mood disorders, suicidal acts usually occur during MDEs or mixed episodes concurrent with comorbid disorders. Nevertheless, illness factors can only in part explain suicidal behaviour. Illness factors, difficulty controlling impulsive and aggressive responses, plus predisposing early exposures and life situations result in a process of suicidal thinking, planning, and acts.

Background Studies of depressive disorders with concurrent borderline personality disorder (BPD) in primary health care are scarce and methodologically weak. Limited epidemiological evidence suggests BPD may be common among users of primary care services. Prevalence, characteristics and outcome of primary care depressive patients with co-morbid BPD are unknown. Methods The Vantaa Primary Care Depression Study is a prospective five-year cohort study. A stratified random sample of 1119 patients aged 20 to 69 years was screened for depression using the Prime-MD. SCID-I/P and SCID-II interviews were used to diagnose depressive all co-morbid axis I and II disorders. Of the 137 depressive patients at baseline, 82% completed the five-year follow-up. Characteristics and outcome of patients with or without concurrent BPD were compared. Results BPD cases accounted for 26% at baseline and 19% at follow-up. At baseline, BPD patients had a two-fold prevalence of anxiety and previous depressive episodes; a three-fold prevalence of substance use disorders, suicidal ideation and severe economic difficulties, and a four-fold prevalence of preceding suicide attempts or unemployment compared to those without BPD. By follow-up, patients with BPD had spent more time depressed, achieved full remission slower and a higher proportion were chronically depressed. Limitations Diagnostic reliability of depressive disorders was excellent, but of BPD not tested. Generalizability to other primary care settings remains unknown. Conclusions Concurrent BPD may be relatively common among depressed primary care patients. These patients have specific, adverse characteristics and poor long-term outcome, which should be considered when developing treatments for depression in primary care.

BackgroundNo previous study has prospectively investigated incidence and risk factors for suicide attempts among primary care patients with depression.MethodIn the Vantaa Primary Care Depression Study, a stratified random sample of 1119 patients was screened for depression, and Structured Clinical Interviews for DSM-IV used to diagnose Axis I and II disorders. A total of 137 patients were diagnosed with a DSM-IV depressive disorder. Altogether, 82% of patients completed the 5-year follow-up. Information on timing of suicide attempts, plus major depressive episodes (MDEs) and partial or full remission, or periods of substance abuse were examined with life charts. Incidence of suicide attempts and their stable and time-varying risk factors (phases of depression/substance abuse) were investigated using Cox proportional hazard and Poisson regression models.ResultsDuring the follow-up there were 22 discrete suicide attempts by 14/134 (10.4%) patients. The incidence rates were 0, 5.8 and 107 during full or partial remission or MDEs, or 22.2 and 142 per 1000 patient-years during no or active substance abuse, respectively. In Cox models, current MDE (hazard ratio 33.5, 95% confidence interval 3.6–309.7) was the only significant independent risk factor. Primary care doctors were rarely aware of the suicide attempts.ConclusionsOf the primary care patients with depressive disorders, one-tenth attempted suicide in 5 years. However, risk of suicidal acts was almost exclusively confined to MDEs, with or without concurrent active substance abuse. Suicide prevention among primary care patients with depression should focus on active treatment of major depressive disorder and co-morbid substance use, and awareness of suicide risk.

Background Whether antidepressants influence personality is a major clinical and societal issue due to their widespread use. In an observational study, we investigated whether depressive patients' neuroticism and extraversion scores covary with antidepressant pharmacotherapy, and if so, whether this remains significant after accounting for depressive or anxiety symptoms. Methods Major depressive disorder patients (N=237) were interviewed at up to four time-points in a five-year prospective longitudinal study. Changes in neuroticism plus extraversion scores were compared with changes in antidepressant pharmacotherapies and depressive plus anxiety symptoms to uncover any covariation between them. Autoregressive path models were used to examine this covariation at the sample level. Within-subject change was estimated using a random-effects latent change model. Results Significant covariation is present in the change trajectories between personality scores and depressive symptoms; declining depression scores were associated with rising extraversion and declining neuroticism. Although the personality scores of many patients changed significantly over the five-year study, none of these changes were associated with changes in antidepressant pharmacotherapy. Limitations The study covered only two dimensions of personality. Single drug-specific analysis could not be done. Antidepressant blood levels were not measured. Conclusion No evidence emerged for significant covariation of antidepressant pharmacotherapy with neuroticism or extraversion scores. By contrast, changes in both personality dimensions were associated with changes in depressive symptoms, those in neuroticism also in anxiety symptoms. If antidepressants influence these personality dimensions, the effect size is likely markedly smaller than that of the disorders for which they are prescribed.

The link between neurotransmitter-level effects of antidepressants and their clinical effect remain poorly understood. A single dose of mirtazapine decreases limbic responses to fearful faces in healthy subjects, but it is unknown whether this effect applies to complex emotional situations and dynamic connectivity between brain regions. Thirty healthy volunteers listened to spoken emotional narratives during functional magnetic resonance imaging (fMRI). In an open-label design, 15 subjects received 15 mg of mirtazapine two hours prior to fMRI while 15 subjects served as a control group. We assessed the effects of mirtazapine on regional neural responses and dynamic functional connectivity associated with valence and arousal. Mirtazapine attenuated responses to unpleasant events in the right fronto-insular cortex, while modulating responses to arousing events in the core limbic regions and the cortical midline structures (CMS). Mirtazapine decreased responses to unpleasant and arousing events in sensorimotor areas and the anterior CMS implicated in self-referential processing and formation of subjective feelings. Mirtazapine increased functional connectivity associated with positive valence in the CMS and limbic regions. Mirtazapine triggers large-scale changes in regional responses and functional connectivity during naturalistic, emotional stimuli. These span limbic, sensorimotor, and midline brain structures, and may be relevant to the clinical effectiveness of mirtazapine.

openaire: EC/H2020/662725/EU//IBSEN Background: Mental and behavioral disorders are the main cause of disability worldwide. However, their diagnosis is challenging due to a lack of reliable biomarkers; current detection is based on structured clinical interviews which can be biased by the patient’s recall ability, affective state, changing in temporal frames, etc. While digital platforms have been introduced as a possible solution to this complex problem, there is little evidence on the extent of usability and usefulness of these platforms. Therefore, more studies where digital data is collected in larger scales are needed to collect scientific evidence on the capacities of these platforms. Most of the existing platforms for digital psychiatry studies are designed as monolithic systems for a certain type of study; publications from these studies focus on their results, rather than the design features of the data collection platform. Inevitably, more tools and platforms will emerge in the near future to fulfill the need for digital data collection for psychiatry. Currently little knowledge is available from existing digital platforms for future data collection platforms to build upon. Objective: The objective of this work was to identify the most important features for designing a digital platform for data collection for mental health studies, and to demonstrate a prototype platform that we built based on these design features. Methods: We worked closely in a multidisciplinary collaboration with psychiatrists, software developers, and data scientists and identified the key features which could guarantee short-term and long-term stability and usefulness of the platform from the designing stage to data collection and analysis of collected data. Results: The key design features that we identified were flexibility of access control, flexibility of data sources, and first-order privacy protection. We also designed the prototype platform Non-Intrusive Individual Monitoring Architecture (Niima), where we implemented these key design features. We described why each of these features are important for digital data collection for psychiatry, gave examples of projects where Niima was used or is going to be used in the future, and demonstrated how incorporating these design principles opens new possibilities for studies. Conclusions: The new methods of digital psychiatry are still immature and need further research. The design features we suggested are a first step to design platforms which can adapt to the upcoming requirements of digital psychiatry.