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.

Healthcare workers' heterogeneous mental-health responses to prolonging COVID-19 pandemic: a full year of monthly follow up in Finland.

BACKGROUND: The COVID-19 pandemic strained healthcare workers but the individual challenges varied in relation to actual work and changes in work. We investigated changes in healthcare workers' mental health under prolonging COVID-19 pandemic conditions, and heterogeneity in the mental-health trajectories. METHODS: A monthly survey over a full year was conducted for employees of the HUS Helsinki University Hospital (n = 4804) between 4th June 2020 to 28th May 2021. Pandemic-related potentially traumatic events (PTEs), work characteristics (e.g., contact to COVID-19 patients), local COVID-19 incidence, and demographic covariates were used to predict Mental Health Index-5 (MHI-5) and Insomnia Severity Index (ISI) in generalized multilevel and latent-class mixed model regressions. RESULTS: Local COVID-19 log-incidence (odds ratio, OR = 1.21, with 95% CI = 1.10-1.60), directly caring for COVID-19 patients (OR = 1.33, CI = 1.10-1.60) and PTEs (OR = 4.57, CI = 3.85-5.43) were all independently associated with psychological distress, when (additionally) adjusting for age, sex, profession, and calendar time. Effects of COVID-19 incidence on mental health were dissociable from calendar time (i.e., evolved in time) whereas those on sleep were not. Latent mental-health trajectories were characterized by a large class of "stable mental health" (62% of employees) and minority classes for "early shock, improving" (14%) and "early resilience, deteriorating" mental health (24%). The minority classes, especially "early shock, improving", were more likely to live alone and be exposed to PTEs than the others. CONCLUSIONS: Healthcare workers faced changing and heterogeneous mental-health challenges as the COVID-19 pandemic prolonged. Adversity and mental ill-being may have accumulated in some employees, and factors like living arrangements may have played a role. Knowledge on employees' demographic and socioeconomic background, as well as further research on the factors affecting employees' resilience, may help in maintaining healthy and efficient workforce in the face of a prolonging pandemic.

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.

COVID-19 Pandemic and Helsinki University Hospital Personnel Psychological Well-Being: Six-Month Follow-Up Results.

The COVID-19 pandemic has caused an unequally distributed extra workload to hospital personnel and first reports have indicated that especially front-line health care personnel are psychologically challenged. A majority of the Finnish COVID-19 patients are cared for in the Helsinki University Hospital district. The psychological distress of the Helsinki University Hospital personnel has been followed via an electronic survey monthly since June 2020. We report six-month follow-up results of a prospective 18-month cohort study. Individual variation explained much more of the total variance in psychological distress (68.5%, 95% CI 65.2-71.9%) and negative changes in sleep (75.6%, 95% CI 72.2-79.2%) than the study survey wave (1.6%, CI 0.5-5.5%; and 0.3%, CI 0.1-1.2%). Regional COVID-19 incidence rates correlated with the personnel's psychological distress. In adjusted multilevel generalized linear multiple regression models, potentially traumatic COVID-19 pandemic-related events (OR 6.54, 95% CI 5.00-8.56) and front-line COVID-19 work (OR 1.81, 95% CI 1.37-2.39) was associated with personnel psychological distress but age and gender was not. While vaccinations have been initiated, creating hope, continuous follow-up and psychosocial support is still needed for all hospital personnel.

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.

Do Suicide Attempts of Mood Disorder Patients Directly Increase the Risk for a Reattempt?

Background: Preceding suicide attempts strongly predict future suicidal acts. However, whether attempting suicide per se increases the risk remains undetermined. We longitudinally investigated among patients with mood disorders whether after a suicide attempt future attempts occur during milder depressive states, indicating a possible lowered threshold for acting. Methods: We used 5-year follow-up data from 581 patients of the Jorvi Bipolar Study, Vantaa Depression Study, and Vantaa Primary Care Depression Study cohorts. Lifetime suicide attempts were investigated at baseline and during the follow-up. At follow-up interviews, life-chart data on the course of the mood disorder were generated and suicide attempts timed. By using individual-level data and multilevel modeling, we investigated at each incident attempt the association between the lifetime ordinal number of the attempt and the major depressive episode (MDE) status (full MDE, partial remission, or remission). Results: A total of 197 suicide attempts occurred among 90 patients, most during MDEs. When the dependencies between observations and individual liabilities were modeled, no association was found between the number of past suicide attempts at the time of each attempt and partial remissions. No association between adjusted inter-suicide attempt times and the number of past attempts emerged during follow-up. No indication for direct risk-increasing effects was found. Conclusion: Among mood disorder patients, repeated suicide attempts do not tend to occur during milder depressive states than in the preceding attempts. Previous suicide attempts may indicate underlying diathesis, future risk being principally set by the course of the disorder itself.

Personnel Well-Being in the Helsinki University Hospital during the COVID-19 Pandemic-A Prospective Cohort Study.

In March 2020, strict measures took place in Finland to limit the COVID-19 pandemic. Majority of Finnish COVID-19 patients have been located in southern Finland and consequently cared for at the Hospital District of Helsinki and Uusimaa (HUS) Helsinki University Hospital. During the pandemic, HUS personnel's psychological symptoms are followed via an electronic survey, which also delivers information on psychosocial support services. In June 2020, the baseline survey was sent to 25,494 HUS employees, 4804 (19%) of whom answered; altogether, 62.4% of the respondents were nursing staff and 8.9% were medical doctors. While the follow-up continues for a year and a half, this report shares the sociodemographic characteristics of the respondents and the first results of psychological symptoms from our baseline survey. Out of those who were directly involved in the pandemic patient care, 43.4% reported potentially traumatic COVID-19 pandemic-related events (PTEs) vs. 21.8% among the others (p < 0.001). While over a half of the personnel were asymptomatic, a group of respondents reported PTEs and concurrent depression, insomnia, and anxiety symptoms. This highlights the need to ensure appropriate psychosocial support services to all traumatized personnel; especially, nursing staff may require attention.

Role of Hopelessness in Suicidal Ideation Among Patients With Depressive Disorders.

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.

Efficacy of a real-time patient feedback system: patient satisfaction study in psychiatry.

Aim: The aim of the study was two-fold: first, to assess the efficacy of an electronic real-time feedback system; second, to examine patient satisfaction.Methods: This was a mixed-method study. Data were collected from two psychiatric outpatient clinics using electronic patient feedback devices. The efficacy of the real-time feedback system was assessed by calculating the overall response rate, and the response rate to each individual five-point Likert scale statement and open-ended question by using descriptive statistics. Patient satisfaction was examined by analyzing the response rate to each statement. Open-ended feedback was analyzed by using inductive qualitative content analysis.Results: The overall response rate was 21.0% (n = 1658) and response rates varied by statements. Most of the patients saw that they received the appointment to the outpatient clinic quickly enough (n = 1404, 85%), the personnel treated them well (n = 1126, 95%), the information about the care was understandable (n = 1066, 94%), and decisions regarding their care were made together with them (n = 1051, 94%). Of the patients, 94% (n = 1052) would recommend the service. Positive open-ended feedback highlighted good service, skilled staff, perceived benefits and help from care. Critique and development areas dealt with the large number of forms that required filling out beforehand, subjective experience of long waiting times, and having too many collaborative professionals present during treatment.Conclusions: The real-time feedback system proved to be an efficient method of gathering patient feedback. Patient satisfaction seemed to be high with received care in all fields.

State and trait hopelessness in a prospective five-year study of patients with depressive disorders.

BACKGROUND: Hopelessness is a common experience of patients with depressive disorders (DD) and an important predictor of suicidal behaviour. However, stability and factors explaining state and trait variation of hopelessness in patients with DD over time are poorly known. METHODS: Patients with DD (n = 406) from the Vantaa Depression Study and the Vantaa Primary Care Depression Study filled in the 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, at six and eighteen months, and at five years. We conducted a multilevel linear regression analyses predicting BHS with these covariates. RESULTS: During the five-year follow-up half of the variance in BHS was attributable to between-patient variance (50.6%, CI = 41.2-61.5%), and the rest arose from within-patient variance and measurement errors. BDI and BAI explained 5.6% of within-patient and 28.4% of between-patient variance of BHS. High Neuroticism and low Extraversion explained 2.6% of the between-patient variance of BHS. PSSS-R explained 5% of between-patient variance and 1.7% of within-patient variance of BHS. LIMITATIONS: No treatment effects were controlled. CONCLUSIONS: Hopelessness varies markedly over time both within and between patients with depression; it is both state- and trait-related. Concurrent depressive and anxiety symptoms and low social support explain both state and trait variance, whereas high Neuroticism and low Extraversion explain only trait variance of hopelessness. These variations influence the utility of hopelessness as an indicator of suicide risk.

Single dose of mirtazapine modulates whole-brain functional connectivity during emotional narrative processing.

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 15mg 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.

Temperament, character, and suicide attempts in unipolar and bipolar mood disorders.

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 (ß = -0.266, P = .004, and ß = -0.294, P < .001, respectively) and high self-transcendence (ß = 0.287, P = .002, and ß = 0.233, P = .002, respectively). Total suicide attempts were linked to high novelty seeking (ß = 0.195, P = .05). Prospective, but not total, suicide attempts were associated with high harm avoidance (ß = 0.322, P < .001, and ß = 0.184, P = .062, respectively) and low reward dependence (ß = -0.274, P < .001, and ß = -0.134, P = .196, respectively), cooperativeness (ß = -0.181, P = .005, and ß = -0.096, P = .326, respectively), and novelty seeking (ß = -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 (ß = 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.

A single dose of mirtazapine attenuates neural responses to self-referential processing.

Increased self-focus is a core factor in the psychopathology of depression. Cortical midline structures (CMS) are implicated in the neurobiology of self, depression and antidepressant treatment response. Mirtazapine, an antidepressant that increases serotonin and norepinephrine release, enhances processing of positive and attenuates processing of negative emotional information in healthy volunteers after a single dose. These early changes, which are opposite to the negative information bias in depression, may be important for the therapeutic effect of mirtazapine. It nevertheless remains unresolved whether/how mirtazapine specifically influences processing of self-referential emotional information.Half of the healthy volunteers (n=15/30) received a single dose of mirtazapine, in an open-label design, two hours before functional magnetic resonance imaging (fMRI), and the other half was scanned as a control group without medication. During fMRI the participants categorized positive and negative self-referential adjectives.Mirtazapine attenuated responses to self-referential processing in the medial prefrontal cortex and the anterior cingulate cortex. Mirtazapine further decreased responses to positive self-referential processing in the posterior cingulate cortex and parietal cortex.These decreased responses of the CMS suggest that mirtazapine may rapidly improve the ability of the CMS to down-regulate self-referential processing. In depressed patients, this could lead to decreased self-focus and rumination, contributing to the antidepressant effect.

Personality disorders and suicide attempts in unipolar and bipolar mood disorders.

BACKGROUND: Comorbid personality disorders may predispose patients with mood disorders to suicide attempts (SAs), but factors mediating this effect are not well known. METHODS: Altogether 597 patients from three prospective cohort studies (Vantaa Depression Study, Jorvi Bipolar Study, and Vantaa Primary Care Depression Study) were interviewed at baseline, at 18 months, and in VDS and PC-VDS at 5 years. Personality disorders (PDs) at baseline, number of previous SAs, life-charted time spent in major depressive episodes (MDEs), and precise timing of SAs during follow-up were determined and investigated. RESULTS: Overall, 219 (36.7%) patients had a total of 718 lifetime SAs; 88 (14.7%) patients had 242 SAs during the prospective follow-up. Having any PD diagnosis increased the SA rate, both lifetime and prospectively evaluated, by 90% and 102%, respectively. All PD clusters increased the rate of new SAs, although cluster C PDs more than the others. After adjusting for time spent in MDEs, only cluster C further increased the SA rate (by 52%). Mediation analyses of PD effects on prospectively ascertained SAs indicated significant mediated effects through time at risk in MDEs, but also some direct effects. LIMITATIONS: Findings generalizable only to patients with mood disorders. CONCLUSIONS: Among mood disorder patients, comorbid PDs increase the risk of SAs to approximately two-fold. The excess risk is mostly due to patients with comorbid PDs spending more time in depressive episodes than those without. Consequently, risk appears highest for PDs that most predispose to chronicity and recurrences. However, also direct risk-modifying effects of PDs exist.

The effect of personality on daily life emotional processes.

Personality features are associated with individual differences in daily emotional life, such as negative and positive affectivity, affect variability and affect reactivity. The existing literature is somewhat mixed and inconclusive about the nature of these associations. The aim of this study was to shed light on what personality features represent in daily life by investigating the effect of the Five Factor traits on different daily emotional processes using an ecologically valid method. The Experience Sampling Method was used to collect repeated reports of daily affect and experiences from 104 healthy university students during one week of their normal lives. Personality traits of the Five Factor model were assessed using NEO Five Factor Inventory. Hierarchical linear modeling was used to analyze the effect of the personality traits on daily emotional processes. Neuroticism predicted higher negative and lower positive affect, higher affect variability, more negative subjective evaluations of daily incidents, and higher reactivity to stressors. Conscientiousness, by contrast, predicted lower average level, variability, and reactivity of negative affect. Agreeableness was associated with higher positive and lower negative affect, lower variability of sadness, and more positive subjective evaluations of daily incidents. Extraversion predicted higher positive affect and more positive subjective evaluations of daily activities. Openness had no effect on average level of affect, but predicted higher reactivity to daily stressors. The results show that the personality features independently predict different aspects of daily emotional processes. Neuroticism was associated with all of the processes. Identifying these processes can help us to better understand individual differences in daily emotional life.

Temperament and character traits predict future burden of depression.

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.

Do antidepressants change personality?--a five-year observational study.

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.

Neuroticism mediates the effect of P2RX7 on outcomes of mood disorders.

BACKGROUND: We previously reported an association between P2RX7 variant rs208294, diagnosis, and the longitudinal course of mood disorders. Here, we test whether the personality trait neuroticism mediates the effect of P2RX7 on the course of mood disorders. METHODS: Patients with DSM-IV mood disorder (256 with major depressive disorder and 168 with bipolar disorder [BD]) were diagnosed with semistructured interviews, genotyped, and followed up for a median of 60 (range 6-83) months. The primary outcome was the prospectively assessed proportion of time spent in any DSM-IV mood episode (time ill). Three types of genetic effect were tested in structural equations models: Model 1: genes directly affect outcome independent of neuroticism, Model 2: neuroticism mediates the effect of genes on outcome, and Model 3: neuroticism and the genetic variant interact in their effect on outcome. RESULTS: Neuroticism mediated the P2RX7 genetic effect on outcome. The T allele of rs208294 was associated with higher neuroticism, which in turn predicted a higher proportion of time spent in mood episodes (the bootstrap-based test of indirect effect, P = .02). There was no significant interaction between neuroticism and the genotype. CONCLUSION: Neuroticism is likely to lie on the causal pathway between the rs208294 T variant and the adverse long-term course of major depressive and BDs.

P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts.

We investigated the effect of nine candidate genes on risk for mood disorders, hypothesizing that predisposing gene variants not only elevate the risk for mood disorders but also result in clinically significant differences in the clinical course of mood disorders. We genotyped 178 DSM-IV bipolar I and II and 272 major depressive disorder patients from three independent clinical cohorts carefully diagnosed with semistructured interviews and prospectively followed up with life charts for a median of 60 (range 6-83) months. Healthy control subjects (n = 1322) were obtained from the population-based national Health 2000 Study. We analyzed 62 genotyped variants within the selected genes (BDNF, NTRK2, SLC6A4, TPH2, P2RX7, DAOA, COMT, DISC1, and MAOA) against the presence of mood disorder, and in post-hoc analyses, specifically against bipolar disorder or major depressive disorder. Estimates for time ill were based on life charts. The P2RX7 gene variants rs208294 and rs2230912 significantly elevated the risk for a familial mood disorder (OR = 1.35, P = 0.0013, permuted P = 0.06, and OR = 1.44, P = 0.0031, permuted P = 0.17, respectively). The results were consistent in all three cohorts. The same risk alleles predicted more time ill in all cohorts (OR 1.3, 95% CI 1.1-1.6, P = 0.0069 and OR 1.7, 95% CI 1.3-2.3, P = 0.0002 with rs208294 and rs2230912, respectively), so that homozygous carriers spent 12 and 24% more time ill. P2RX7 and its risk alleles predisposed to mood disorders consistently in three independent clinical cohorts. The same risk alleles resulted in clinically significant differences in outcome of patients with major depressive and bipolar disorder.

Differences in neuroticism and extraversion between patients with bipolar I or II and general population subjects or major depressive disorder patients.

BACKGROUND: Whether levels of neuroticism or extraversion differ between patients with bipolar disorder (BD), major depressive disorder (MDD) and subjects from the general population, or between BD I and BD II patients, remains unclear. METHODS: BD patients (n=191) from the Jorvi Bipolar Study, and MDD patients (n=358) from both the Vantaa Depression Study and the Vantaa Primary Care Depression Study cohorts, were interviewed at baseline and at 18 months. A general population comparison group (n=347) was surveyed by mail. BD patients' neuroticism and extraversion scores, measured by Eysenck Personality Inventory, were compared at an index interview, when the levels of depression and mania were lowest, with scores of MDD patients and general population controls. Comparisons were also made between BD I (n=99) and BD II (n=92) patients. RESULTS: In multinomial logistic regression, BD patients had higher neuroticism (OR=1.17, p<0.001) and lower extraversion (OR=0.92, p=0.003) than the general population. When entered simultaneously into the model, the effect of extraversion disappeared. In logistic regression, the levels of neuroticism and extraversion did not differ between BD and MDD patients, or between BD I and II patients. LIMITATIONS: Patients' personality scores were not pre-morbid. CONCLUSIONS: Levels of neuroticism and extraversion are unlikely to differ between BD and MDD patients, or between BD I and II patients. The overall level of neuroticism is moderately higher and extraversion somewhat lower in BD patients than in the general population. High neuroticism may be an indicator of vulnerability to both bipolar and unipolar mood disorders.