Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.

Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards). Using a hierarchical model, ranking the psychotic diagnoses according to clinical severity, we show that high schizophrenia PGS (SZ-PGS) was associated with progression from lower ranked psychotic disorders to schizophrenia (OR = 1.32 [1.23-1.43], p = 1.26e-12). This development manifested already at psychotic illness onset as a higher psychiatric hospitalization burden, the proxy for disease-course severity. In schizophrenia (n = 5 479), both a high SZ-PGS and a low educational attainment PGS (EA-PGS) were associated with increased psychiatric hospitalization burden (p = 1.00e-04 and p = 4.53e-10). The SZ-PGS and the EA-PGS associated with distinct patterns of hospital usage. In individuals with high SZ-PGS, the increased hospitalization burden was composed of longer individual hospital stays, while low EA-PGS associated with shorter but more frequent hospital visits. The negative effect of a low EA-PGS was found to be partly mediated via substance use disorder, a major risk factor for hospitalizations. In conclusion, we show that high SZ-PGS and low EA-PGS both impacted psychotic disease-course development negatively but resulted in different disease-course trajectories.

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.

Borderline personality disorder and depression severity predict suicidal outcomes: A six-month prospective cohort study of depression, bipolar depression, and borderline personality disorder.

BACKGROUND: Suicide risk is high in patients with major depressive disorder (MDD), bipolar disorder (BD) and borderline personality disorder (BPD). Whether risk levels of and risk factors for suicidal ideation (SI) and suicide attempts (SA) are similar or different in these disorders remains unclear, as few directly comparative studies exist. The relationship of short-term changes in depression severity and SI is underinvestigated, and might differ across groups, for example, between BPD and non-BPD patients. METHODS: We followed, for 6 months, a cohort of treatment-seeking, major depressive episode (MDE) patients in psychiatric care (original n = 124), stratified into MDE/MDD, MDE/BD and MDE/BPD subcohorts. We examined risks of suicide-related outcomes and their risk factors prospectively. We examined the covariation of SI and depression over time with biweekly online modified Patient Health Questionnaire 9 surveys and analysed this relationship through multi-level modelling. RESULTS: Risk of SA in BPD (22.2%) was higher than non-BPD (4.23%) patients. In regression models, BPD severity was correlated with risk of SA and clinically significant SI. During follow-up, mean depression severity and changes in depression symptoms were associated with SI risk regardless of diagnosis. CONCLUSIONS: Concurrent BPD in depression seems predictive for high risk of SA. Severity of BPD features is relevant for assessing risk of SA and SI in MDE. Changes in depressive symptoms indicate concurrent changes in risk of SI. BPD status at intake can index risk for future SA, whereas depressive symptoms appear a useful continuously monitored risk index.

Prospective study of antidepressant treatment of psychiatric patients with depressive disorders: treatment adequacy and outcomes.

BACKGROUND: Despite numerous national depression care guidelines (DCGs), suboptimal antidepressant treatment may occur. We examined DCG concordance and depression treatment outcomes in psychiatric settings. METHODS: We evaluated treatment received and outcomes of 128 psychiatric out- and inpatients participating in the PEGAD (Pharmacoepidemiology and Pharmacogenetics of Antidepressant Treatment for Depressive Disorders) study at baseline, two weeks, and eight weeks using interviews and questionnaires. Inclusion criteria were ICD-10 diagnosis of a depressive disorder, a Patient Health Questionnaire-9 symptom (PHQ-9) score ≥ 10, and a new antidepressant prescribed. The primary outcome of the study was within-individual change in PHQ-9 scores. RESULTS: At baseline, patients had predominately recurrent (83%) and in 19% treatment-resistant depression (TRD). The median preceding duration of the current episode was 6.5 months. At eight weeks, 85% of the patients (n = 107) used a DCG-concordant antidepressant dose. However, due to the scarcity of antidepressant combinations and augmentations, fewer TRD than non-TRD patients (25% vs. 84%, p < 0.005) received adequate antidepressant treatment. Additionally, one-third of the patients received inadequate follow-up. Overall, only 53% received treatment compatible with DCG recommendations for adequate pharmacotherapy and follow-up. The mean decline in PHQ-9 scores (-3.8 ± SD 5.7) was significant (p < 0.0005). Nearly 40% of the patients reached a subthreshold level of depression (PHQ-9 < 10), predicted by a lower baseline PHQ-9 score, recurrent depression, and female sex. However, 45% experienced no significant clinical improvement (PHQ-9 score reduction < 20%). CONCLUSIONS: Our findings suggest that inadequate treatment continues to occur in psychiatric care settings, particularly for TRD patients.

Nordic region suicide trends 2000-2018; sex and age groups.

BACKGROUND AND AIM: Overall, suicide rates in the Nordic region, Denmark, Finland, Iceland, Norway and Sweden, have declined in the past 40 years. The aim of this study was to determine trends in suicide mortality from 2000 to 2018. METHODS: Data were obtained from official suicide statistics for men and women, 15 years and older. Gender and age groups in four calendar periods were analyzed using Joinpoint Estimated Regression Coefficient. RESULTS: The crude regional suicide rate was 17.1, 2000-2004, decreased to 14.1 per 100,000 inhabitants in 2015-2018. Age-standardized rates are 13.6-11.3. The crude rate decreased by 19.5% (16.3% age-standardized), 19.3% for males and 20.5% for females. The largest decrease was found in Finland (34.9%), the smallest in Norway (1.4%). In males, the exception was an increased suicide rate among all Icelandic except 15-24-year olds, and in 45-64 year-old Norwegians. Among females, an increase was seen among 15-24-year olds in all countries except Iceland, in all age groups in Norway, and in 25-44-year olds in Sweden. In males, a decline of the suicide rated lower than 10% was noted in 25-44 olds in Norway and in 15-64 year-olds in Sweden. DISCUSSION: A robust decrease was observed in the overall regional suicide rate in recent years. Exceptions are rising rates in Icelandic males, in Norwegian females, and the youngest female groups in all except Iceland. The small decline among middle-aged males in Norway and Sweden is of concern.

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.

Variants in regulatory elements of PDE4D associate with major mental illness in the Finnish population.

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, ß = -0.033). Specifically, the cognitive domains represented verbal learning and memory (p = 0.0091, ß = -0.044) and verbal working memory (p = 0.0062, ß = -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.

Smartphone-based interventions in bipolar disorder: Systematic review and meta-analyses of efficacy. A position paper from the International Society for Bipolar Disorders (ISBD) Big Data Task Force.

BACKGROUND: The clinical effects of smartphone-based interventions for bipolar disorder (BD) have yet to be established. OBJECTIVES: To examine the efficacy of smartphone-based interventions in BD and how the included studies reported user-engagement indicators. METHODS: We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random-effects meta-analysis to calculate the standardized difference (Hedges' g) in pre-post change scores between smartphone intervention and control conditions. The study was pre-registered with PROSPERO (CRD42021226668). RESULTS: The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta-analyses comparing the pre-post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta-analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user-engagement indicators. CONCLUSION: We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field.

A Randomized Clinical Trial of Attempted Suicide Short Intervention Program versus Crisis Counseling in Preventing Repeat Suicide Attempts: A Two-Year Follow-Up Study.

INTRODUCTION: The Attempted Suicide Short Intervention Program (ASSIP) is a brief psychotherapeutic intervention, and a pivotal study found it to be remarkably effective in reducing repeat suicide attempts. OBJECTIVE: To compare the effectiveness of ASSIP to crisis counseling (CC) in a randomized clinical trial (ISRCTN13464512). METHODS: Adult patients receiving treatment for a suicide attempt in a Helsinki City general hospital emergency room in 2016-2017 were eligible to participate. We excluded psychotic or likely non-adherent substance-abusing or substance-dependent patients. Eligible patients (n = 239) were randomly allocated to one of two interventions. (a) ASSIP comprised three visits, including a videotaped first visit, a case formulation, and an individualized safety plan, plus letters from the therapist every 3 months for 1 year, and then, every 6 months for the next year. (b) CC typically involved 2-5 (median 3) face-to-face individual sessions. In addition, all participants received their usual treatment. One and 2 years after baseline, information related to participants' suicidal thoughts and attempts, and psychiatric treatment received was collected via telephone and from medical and psychiatric records. RESULTS: Among randomized patients, two-thirds initiated either ASSIP (n = 89) or CC (n = 72), with 73 (82%) completing ASSIP and 58 (81%) CC. The proportion of patients who attempted suicide during the 2-year follow-up did not differ significantly between ASSIP and CC (29.2% [26/89] vs. 35.2% [25/71], OR 0.755 [95% Cl 0.379-1.504]). CONCLUSIONS: We found no difference in the effectiveness of the two brief interventions to prevent repeat suicide attempts.

White Matter Hyperintensities after Five-Year Follow-Up and a Cross-Sectional FA Decrease in Bipolar I and Major Depressive Patients.

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.

A randomized clinical trial of the ASSIP vs. crisis counselling in preventing suicide attempt repetition: a two-year follow-up study.

BACKGROUND: 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). METHODS: 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 (N = 239) were randomly allocated to two interventions. (a) The ASSIP comprised three visits, including a videotaped first visit, a case formulation, individualized safety plan, plus letters from their therapist every 3 months for 1 year and then every 6 months for the next year. (b) The CC involved on average four face-to-face individual sessions. In addition, all participants received treatments as usual. One and two years after the baseline, the participants' suicidal thoughts and attempts and psychiatric treatments received during the follow-up were investigated by telephone and from psychiatric records. RESULTS: Of patients randomized, two thirds initiated either ASSIP (n = 89) or CC (n = 72), with 73 (82%) completing the ASSIP and 58 (81%) the CC. There was no significant difference between the ASSIP vs. the CC patients having at least one suicide attempt during the 2-year follow-up (29.2% (26/89) vs. 35.2% (25/71), χ21 = 0.654, p = 0.419). CONCLUSION: We found no evidence for a difference in effectiveness of the two active interventions in preventing the repetition of suicide attempts.

Escitalopram enhances synchrony of brain responses during emotional narratives in patients with major depressive disorder.

One-week treatment with escitalopram decreases amygdala responses to fearful facial expressions in depressed patients, but it remains unknown whether it also modulates processing of complex and freely processed emotional stimuli resembling daily life emotional situations. Inter-subject correlation (ISC) offers a means to track brain activity during complex, dynamic stimuli in a model-free manner. Twenty-nine treatment-seeking patients with major depressive disorder were randomized in a double-blind study design to receive either escitalopram or placebo for one week, after which functional magnetic resonance imaging (fMRI) was performed. During fMRI the participants listened to spoken emotional narratives. Level of ISC between the escitalopram and the placebo group was compared across all the narratives and separately for the episodes with positive and negative valence. Across all the narratives, the escitalopram group had higher ISC in the default mode network of the brain as well as in the fronto-temporal narrative processing regions, whereas lower ISC was seen in the middle temporal cortex, hippocampus and occipital cortex. Escitalopram increased ISC during positive parts of the narratives in the precuneus, medial prefrontal cortex, anterior cingulate and fronto-insular cortex, whereas there was no significant synchronization in brain responses to positive vs negative events in the placebo group. Increased ISC may imply improved emotional synchronization with others, particularly during observation of positive events. Further studies are needed to test whether this contributes to the later therapeutic effect of escitalopram.

Reduced visual contrast suppression during major depressive episodes.

Background: Previous studies have suggested that processing of visual contrast information could be altered in major depressive disorder. To clarify the changes at different levels of the visual hierarchy, we behaviourally measured contrast perception in 2 centre-surround conditions, assessing retinal and cortical processing. Methods: As part of a prospective cohort study, our sample consisted of controls (n = 29; 21 female) and patients with unipolar depression, bipolar disorder and borderline personality disorder who had baseline major depressive episodes (n = 111; 74 female). In a brightness induction test that assessed retinal processing, participants compared the perceived luminance of uniform patches (presented on a computer screen) as the luminance of the backgrounds was varied. In a contrast suppression test that assessed cortical processing, participants compared the perceived contrast of gratings, which were presented with collinearly or orthogonally oriented backgrounds. Results: Brightness induction was similar for patients with major depressive episodes and controls (p = 0.60, d = 0.115, Bayes factor = 3.9), but contrast suppression was significantly lower for patients than for controls (p < 0.006, d = 0.663, Bayes factor = 35.2). We observed no statistically significant associations between contrast suppression and age, sex, or medication or diagnostic subgroup. At follow-up (n = 74), we observed some normalization of contrast perception. Limitations: We assessed contrast perception using behavioural tests instead of electrophysiology. Conclusion: The reduced contrast suppression we observed may have been caused by decreased retinal feedforward or cortical feedback signals. Because we observed intact brightness induction, our results suggest normal retinal but altered cortical processing of visual contrast during a major depressive episode. This alteration is likely to be present in multiple types of depression and to partially normalize upon remission.

Effectiveness of brief schema group therapy for borderline personality disorder symptoms: a randomized pilot study.

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.

Diagnostic conversion from unipolar depression to bipolar disorder, schizophrenia, or schizoaffective disorder: A nationwide prospective 15-year register study on 43 495 inpatients.

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.

Schizophrenia and pregnancy: a national register-based follow-up study among Finnish women born between 1965 and 1980.

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.

Clinical course predicts long-term outcomes in bipolar disorder.

BACKGROUND: The 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. METHODS: A 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. RESULTS: Dimensional 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. CONCLUSIONS: Differential 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.

Machine learning and big data analytics in bipolar disorder: A position paper from the International Society for Bipolar Disorders Big Data Task Force.

OBJECTIVES: The International Society for Bipolar Disorders Big Data Task Force assembled leading researchers in the field of bipolar disorder (BD), machine learning, and big data with extensive experience to evaluate the rationale of machine learning and big data analytics strategies for BD. METHOD: A task force was convened to examine and integrate findings from the scientific literature related to machine learning and big data based studies to clarify terminology and to describe challenges and potential applications in the field of BD. We also systematically searched PubMed, Embase, and Web of Science for articles published up to January 2019 that used machine learning in BD. RESULTS: The results suggested that big data analytics has the potential to provide risk calculators to aid in treatment decisions and predict clinical prognosis, including suicidality, for individual patients. This approach can advance diagnosis by enabling discovery of more relevant data-driven phenotypes, as well as by predicting transition to the disorder in high-risk unaffected subjects. We also discuss the most frequent challenges that big data analytics applications can face, such as heterogeneity, lack of external validation and replication of some studies, cost and non-stationary distribution of the data, and lack of appropriate funding. CONCLUSION: Machine learning-based studies, including atheoretical data-driven big data approaches, provide an opportunity to more accurately detect those who are at risk, parse-relevant phenotypes as well as inform treatment selection and prognosis. However, several methodological challenges need to be addressed in order to translate research findings to clinical settings.

Self-reported treatment adherence among psychiatric in- and outpatients.

BACKGROUND: Poor adherence to psychiatric treatment is a common clinical problem, leading to unfavourable treatment outcome and increased healthcare costs. AIM: The aim of this study was to investigate the self-reported adherence and attitudes to outpatient visits and pharmacotherapy in specialized care psychiatric patients. METHODS: 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. RESULTS: 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 ß = -2.418, BD ß = -3.417, DD ß = -2.766; p < .001 in all). Another independent correlate of non-adherence was substance use disorder (SSA ß = -1.555, p = .001; BD ß = -1.535, p = .006; DD ß = -2.258, p < .000). No other socio-demographic or clinical factor was significantly associated with poor adherence in multivariate regression models. CONCLUSIONS: 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.

Incidence and predictors of suicide attempts in bipolar I and II disorders: A 5-year follow-up study.

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.