Effectiveness of an add-on brief group behavioral activation treatment for depression in psychiatric care: a randomized clinical trial.

Objective: Behavioral activation (BA) is an effective treatment for depression. We investigated the effectiveness of add-on group-format BA and peer support (PS) with treatment as usual (TAU) in a registered randomized clinical trial in psychiatric outpatient settings (ISRCTN10647845). Methods: Adult outpatients (N = 140) with major depressive disorder (MDD) and Patient Health Questionnaire (PHQ-9) score ≥10 were randomized into a) group BA, consisting of eight 90-minute weekly group sessions plus TAU; b) group PS, including eight 90-minute weekly group sessions plus TAU; or c) TAU alone. The primary outcome was a within-individual change in PHQ-9 score between baseline and 8 weeks. Secondary outcomes were 1) response, 2) remission, and 3) functional impairment at 8 weeks, plus 4) change in PHQ-9 at 6 months. Results: Of the randomized patients, 100 (71.4%) completed treatments, including 29/45 (64.4%) patients in the BA group, 39/49 (79.6%) in the PS group, and 32/46 (69.6%) in the TAU group. By 8 weeks, PHQ-9 scores declined most in the TAU group [BA -0.28 (95% CI -2.48, 1.92), PS -0.58 (-2.09, 0.94) vs. TAU -3.32 (-5.21, -1.44); group-difference test, p = 0.034]. The secondary outcomes in the BA or PS arms did not significantly differ from those in TAU. Videotaped sessions revealed marked variation in briefly trained therapists' adherence to the treatment manual. Conclusions: In this randomized trial, the effectiveness of treatments with the added BA and PS groups did not exceed that of TAU alone. The preconditions in which brief BA or PS group interventions benefit outpatients with depression in psychiatric settings warrant critical investigation.

Antipsychotic medications and sleep problems in patients with schizophrenia.

BACKGROUND: Sleep problems are common and related to a worse quality of life in patients with schizophrenia. Almost all patients with schizophrenia use antipsychotic medications, which usually increase sleep. Still, the differences in subjective sleep outcomes between different antipsychotic medications are not entirely clear. METHODS: This study assessed 5466 patients with schizophrenia and is part of the nationwide Finnish SUPER study. We examined how the five most common antipsychotic medications (clozapine, olanzapine, quetiapine, aripiprazole, and risperidone) associate with questionnaire-based sleep problems in logistic regression analyses, including head-to-head analyses between different antipsychotic medications. The sleep problems were difficulties initiating sleep, early morning awakenings, fatigue, poor sleep quality, short (≤6 h) and long sleep duration (≥10 h). RESULTS: The average number of antipsychotic medications was 1.59 per patient. Clozapine was associated with long sleep duration (49.0 % of clozapine users vs 30.2 % of other patients, OR = 2.05, 95 % CI 1.83-2.30, p < .001). Olanzapine and risperidone were in head-to-head analyses associated with less sleep problems than patients using aripiprazole, quetiapine, or no antipsychotic medication. Aripiprazole and quetiapine were associated with more insomnia symptoms and poorer sleep quality. Patients without antipsychotic medications (N = 159) had poorer sleep quality than patients with antipsychotic use, and short sleep duration was common (21.5 % of patients using antipsychotics vs 7.8 % of patients using antipsychotics, OR = 2.97, 95 % CI 1.98-4.44, p < .001). CONCLUSIONS: Prevalence of sleep problems is markedly related to the antipsychotic medication the patient uses. These findings underline the importance of considering and assessing sleep problems when treating schizophrenia patients with antipsychotics.

Psychological Pain as a Risk Factor for Suicidal Ideation: An Ecological Momentary Assessment Study on Inpatients With Depression With and Without Comorbid Borderline Personality Disorder.

Objective: Psychological pain (PP) is a potentially important risk factor for suicide. However, its temporal stability and association with suicidal ideation (SI) remain obscure. Whether PP represents a risk factor for SI independently of depression, anxiety, and hopelessness or is more prominent and temporally unstable in patients with depression and borderline personality disorder (BPD) is also unclear.Methods: From November 2020 to December 2022, psychiatric inpatients with depression without (N = 37) and with (N = 30) BPD were recruited to an ecological momentary assessment (EMA) study, wherein their PP, severity of depression, SI, and hopelessness were assessed 3 times daily using visual analog scales. Multilevel regression models were estimated.Results: Altogether, 4,320 EMA observations were collected. PP correlated with hopelessness (r = 0.417), depression (r = 0.339), and anxiety (r = 0.496), but the between-patient variance of PP remained at 1.26 (95% CI, 1.025-1.533) after controlling for these variables. The within-patient variance of PP was associated with SI (ß = 0.17 [95% CI, 0.12-0.22]) with a magnitude comparable to hopelessness (ß = 0.1 [95% CI, 0.05-0.15]) and depression (ß = 0.12 [95% CI, 0.08-0.17]). Patients with depression and BPD reported higher daily PP and SI (P < .001) and a more prominent within-patient variation in PP.Conclusions: In psychiatric inpatients with depression, besides depression and hopelessness, PP represents an independent risk factor for SI, varying within a timescale of days. Depressive patients with BPD may experience more prominent and temporally unstable PP, likely underlying their higher vulnerability to SI.

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.

Association of antidepressant and benzodiazepine use, and anticholinergic burden with cognitive performance in schizophrenia.

Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016-2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use.

Variations in Suicide Risk and Risk Factors After Hospitalization for Depression in Finland, 1996-2017.

Importance: Although incidence of suicide in depression varies remarkably temporally, risk factors have been modeled as constant and remain uncharted in the short term. How effectively factors measured at one point in time predict risk at different time points is unknown. Objective: To examine the absolute risk and risk factors for suicide in hospitalized patients with depression starting from the first days after discharge up to 2 years and to evaluate whether the size of relative risk by factor displays temporal patterns over consecutive phases of follow-up. Design, Setting, and Participants: This population-based study using Finnish registers (hospital discharge, population, and cause of death registers) included all hospitalizations for depression as the principal diagnosis in Finland from 1996 to 2017, with a maximum follow-up of 2 years. Data were analyzed from January 2022 to November 2023. Main Outcomes and Measures: Incidence rate (IR), IR ratios, hazard functions, and hazard ratios for suicide by consecutive time periods (0 to 3 days, 4 to 7 days, 7 to 30 days, 31 to 90 days, 91 to 365 days, and 1 to 2 years) since discharge. Results: This study included 193 197 hospitalizations among 91 161 individuals, of whom 51 197 (56.2%) were female, and the mean (SD) age was 44.0 (17.3) years. Altogether, patients were followed up to 226 615 person-years. A total of 1219 men and 757 women died of suicide. Incidence of suicide was extremely high during the first days after discharge (IR of 6062 [95% CI, 4963-7404] per 100 000 on days 0 to 3; IR of 3884 [95% CI, 3119-4835] per 100 000 on days 4 to 7) and declined thereafter. Several factors were associated with risk of suicide over the first days after discharge. Current suicide attempt by hanging or firearms increased the risk of suicide most on days 0 to 3 (IR ratio, 18.9; 95% CI, 3.1-59.8) and on days 0 to 7 (IR ratio, 10.1; 95% CI, 1.7-31.5). Temporal patterns of the size of the relative risk diverged over time, being constant, declining, or increasing. Clinical factors had the strongest association immediately. Relative risk remained constant among men and even increased among those with alcohol or substance use disorder. Conclusions and Relevance: In this study, patients hospitalized for depression had extremely high risk of suicide during the first days after discharge. Thereafter, incidence declined steeply but remained high. Within the periods of the highest risk of suicide, several factors increased overall risk manyfold. Risk factors' observed potencies varied over time and had characteristic temporal patterns.

How changes in depression severity and borderline personality disorder intensity are linked - a cohort study of depressed patients with and without borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is often complicated by comorbid major depressive episodes (MDEs), which can occur as part of major depressive disorder (MDD) or bipolar disorder (BD). Such comorbidity is related to worse outcomes in both disorders. Subsyndromal features of BPD are also common in depression. However, studies of simultaneous changes in BPD and depression severities are scarce, and their interactions are poorly understood. AIMS: Studying the associations between changes in BPD and depression symptoms over the course of an MDE. METHODS: In a 6-month naturalistic cohort study of MDE/BPD, MDE/MDD, and MDE/BD patients (N = 95), we measured change in BPD features between baseline and six months with the Borderline Personality Disorder Severity Index (BPDSI), an interviewer-rated instrument quantifying recent temporal frequency of BPD symptoms. We examined changes in BPD severity and their correlation with depression severity and other clinical measures and compared these across patient groups. RESULTS: There were significant reductions in BPD severity, both in number of positive BPD criteria (-0.35, sd 1.38, p = 0.01672) and in BPDSI scores (-4.23, SD 6.74, p < 0.001), reflecting mainly a reduction in temporal frequency of symptoms. These were similar in all diagnostic groups. In multivariate regression models, changes in depression severity independently associated with changes in symptoms in the BDSI. This relationship was strongest in MDE/BPD patients but was not found in MDD patients without BPD. CONCLUSIONS: In the six-month follow-up, BPD features in MDE patients alleviated mainly by decreasing temporal symptom frequency and intensity. In BPD patients with comorbid MDE, changes in both conditions are strongly correlated.

Predicting a short-term change of suicidal ideation in inpatients with depression: An ecological momentary assessment.

INTRODUCTION: Patients with depression often require inpatient treatment due to their high suicide risk. Ecological momentary assessment (EMA) studies have shown that suicidal ideation (SI) fluctuates over time. As affective instability and psychological pain (PP) are common experiences in borderline personality disorder (BPD), often comorbid with depression, we examined factors predicting short-term changes of SI in depressive inpatients with or without BPD. METHODS: Psychiatric inpatients with depression with (N = 30) or without (N = 37) comorbid BPD assessed their anxiety, PP, severity of depression, SI, and hopelessness three times daily using visual analogue scales. Multilevel regression models were estimated. RESULTS: Altogether 4320 EMA observations, spanning on average 3.4 successive days, were collected. Only severity of depression (ß = 0.19; [95 % CI = 0.06, 0.32]) and previous SI (ß = 0.32; [95 % CI = 0.23, 0.41]) predicted near-future SI within several hours. PP predicted near-future SI in inpatients with depression and BPD (ß = 0.28; [95 % CI = 0.11, 0.46]), but not in patients without BPD. LIMITATIONS: The follow-up data represents only the first days of hospitalization. The context of the EMA is the acute psychiatric ward, affecting generalizability to outpatients. CONCLUSIONS: Short-terms changes in SI are predicted by changes in severity of depression and previous SI in depressed inpatients without BPD, and also by changes in PP in depressed inpatients with BPD. As SI and its risk factors may oscillate within a time scale of hours, frequent monitoring of momentary severity of depression, PP, and SI may be warranted in inpatient settings.

Affect dimensions and variability during major depressive episodes: Ecological momentary assessment of unipolar, bipolar, and borderline patients and healthy controls.

Differentiating major depressive episodes (MDEs) of major depressive disorder (MDD), bipolar disorder (MDE/BD) and the MDEs comorbid with borderline personality disorder (MDE/BPD) is crucial for appropriate treatment, and knowledge of phenomenological differences may aid this. However, studies comparing affect experiences of these three patient groups and healthy subjects are scarce. In our study, participants (N = 114), including patients with MDD (n = 34), MDE/BD (n = 27), and MDE/BPD (n = 24), and healthy controls (HC, n = 29) responded to ecological momentary assessment (EMA) with ten circumplex model affect items ten times daily for seven days (7709 recordings). Explorative factor analysis resulted in two affect dimensions. The positive dimension included active, excited, cheerful (high arousal), and content (low arousal) affects, and the negative dimension irritated, angry, and nervous (high arousal) affects. Relative to HC, patients reported 3.5-fold negative affects (mean MDD 1.36 (SD 0.92), MDE/BD 1.43 (0.76), MDE/BPD 1.81 (0.95) vs. HC 0.44 (0.49) (p < 0.01)) but 0.5-fold positive affects (2.01 (0.90), 1.95 (0.89), 2.24 (1.03), vs. 3.2 (0.95), respectively (p < 0.01)). We used multilevel modelling. Negative-affect within-individual stability was lowest in MDE/BPD and highest in MDD. Negative affect predicted concurrent positive affect more in MDE/BPD than in MDD. Moderate size of subcohorts and no inpatients were limitations. Despite apparently similar MDEs, affective experiences may differ between BPD, BD, and MDD patients. Clinical subgroups of patients with depression may vary in affective instability and concurrent presence of negative and positive affects during depression.

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.

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.

Health-related quality of life-based definition of remission from depression among primary care patients.

Background: Depression undermines health-related quality of life (HRQoL). Remission is the central aim of all treatments for depression, but the degree of remission necessary for depressive patients' HRQoL to correspond to the normal range of the general population remains unknown. Methods: The Vantaa Primary Care Depression Study prospectively followed-up a screening-based cohort of depressive primary care patients for 5 years. The Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) was used to diagnose major depressive disorder. HRQoL was measured by the generic 15D instrument at baseline and at 5 years (N = 106, 77% of baseline patients), and compared with the 15D results of an age-standardized general population sample from the Finnish Health 2011 Survey (N = 4,157). Receiver operating characteristic analyses determined the optimal Hamilton Depression Rating Scale (HAMD), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) cut-offs for remission, using the 15D score as the construct validator. Remission was defined as the score at which HRQoL reached the general population range (minimum mean - 1 SD). As age may influence HRQoL, patients older and younger than the median 52 years were investigated separately. Results: For HAMD, the optimal cut-off point score was 8.5, for BDI 10.5, and for BAI 11.5. The differences between the findings of the younger and older patients were small. Limitations: Cross-sectional analysis, small number of patients in the cohort. Conclusion: Depressive primary care patients' HRQoL reaches the normal variation range of the general population when their depression and anxiety scores reach the conventional clinical cut-offs for remission.

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

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

Depression core network-based individualized targeting for transcranial magnetic stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for major depressive disorder (MDD). Recent attempts to improve TMS efficacy by individually targeting DLPFC subregions that are functionally connected to the subgenual anterior cingulate cortex (sgACC) appear promising. However, sgACC covers only a small subset of core MDD-related areas. Further, fMRI connectivity of sgACC is poorly repeatable within subjects. METHODS: Based on an fMRI database analysis, we first constructed a novel core network model (CNM), capturing voxelwise emotion regulation- and MDD-related DLPFC connectivity. Then, in a sample of 15 healthy subjects and 29 MDD patients, we assessed (i) within-subject repeatability of the DLPFC connectivity patterns computed from time segments of varying lengths of individual-level fMRI data and (ii) association of MDD severity with the individual DLPFC connectivity strengths. We extracted group-level connectivity strengths in CNM from individual DLPFC coordinates stimulated with neuronavigated TMS in a separate sample of 25 MDD patients. These connectivity strengths were then correlated with individual TMS efficacy. RESULTS: Compared with sgACC connectivity, CNM increased intraindividual repeatability 5-fold. DLPFC connectivity strength from CNM was associated with MDD severity and TMS efficacy. While the locations of CNM-based individual TMS targets remained constant within individuals, they varied considerably between individuals. CONCLUSIONS: CNM increased repeatability of functional targeting to a clinically feasible level. The observed association of MDD severity and TMS efficacy with DLPFC connectivity supports the validity of the CNM. The interindividual differences in target locations motivate future individualized clinical trials leveraging the CNM.

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.

Relationship between daily rated depression symptom severity and the retrospective self-report on PHQ-9: A prospective ecological momentary assessment study on 80 psychiatric outpatients.

BACKGROUND: Depression-related negative bias in emotional processing and memory may bias accuracy of recall of temporally distal symptoms. We tested the hypothesis that when responding to the Patient Health Questionnaire (PHQ-9) the responses reflect more accurately temporally proximal than distal mood states. METHODS: Currently, depressed psychiatric outpatients (N = 80) with depression confirmed in semi-structured interviews had the Aware application installed on their smartphones for ecological momentary assessment (EMA). The severity of "low mood", "hopelessness", "low energy", "anhedonia", and "wish to die" was assessed on a Likert scale five times daily during a 12-day period, and thereafter, the PHQ-9 questionnaire was completed. We used auto- and cross-correlation analyses and linear mixed-effects multilevel models (LMM) to investigate the effect of time lag on the association between EMA of depression symptoms and the PHQ-9. RESULTS: Autocorrelations of the EMA of depressive symptom severity at two subsequent days were strong (r varying from 0.7 to 0.9; p < 0.001). "Low mood" was the least and "wish to die" the most temporally stable symptom. The correlations between EMA of depressive symptoms and total scores of the PHQ-9 were temporally stable (r from 0.3 to 0.6; p < 0.001). No effect of assessment time on the association between EMA data and the PHQ-9 emerged in the LMM. LIMITATIONS: Altogether 11.5 % of observations were missing. CONCLUSIONS: Despite fluctuations in severity of some of the depressive symptoms, patients with depression accurately recollect their most dominant symptoms, without a significant recall bias favouring the most recent days, when responding to the PHQ-9.

ASSIP vs. Crisis Counseling for Preventing Suicide Re-attempts: Outcome Predictor Analysis of a Randomized Clinical Trial Data.

OBJECTIVE: 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. METHODS: Consenting adult patients receiving treatment for a suicide attempt in Helsinki City general hospital emergency rooms in 2016-2017 (n = 239) were randomly allocated to (a) the Attempted Suicide Short Intervention Program (ASSIP) or (b) Crisis Counseling (CC). Participants also received their usual treatment. Information on primary outcome repeat attempts and secondary outcomes was collected via telephone and from medical and psychiatric records for 2 years. As proportions of re-attempts did not differ significantly between ASSIP and CC (29.2 vs. 35.2%), patients were pooled and predictors for suicide re-attempts were analyzed using Kaplan-Meier and logistic regression analyses. RESULTS: 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]). CONCLUSIONS: 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.