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Introduction A significant proportion of people attending Primary Care (PC) have anxiety-depressive symptoms and work-related burnout and there is a lack of resources to attend them. The COVID-19 pandemic has worsened this problem, particularly affecting healthcare workers, and digital tools have been proposed as a workaround. Objectives We present the development, feasibility and effectiveness studies of chatbot (Vickybot) aimed at screening, monitoring, and reducing anxiety-depressive symptoms and work-related burnout in PC patients and healthcare workers. Methods User-centered development strategies were adopted. Main functions included self-assessments, psychological modules, and emergency alerts. (1) Simulation: HCs used Vickybot for 2 weeks to simulate different possible clinical situations and evaluated their experience. (3) Feasibility and effectiveness study: People consulting PC or healthcare workers with mental health problems were offered to use Vickybot for one month. Self-assessments for anxiety (GAD-7) and depression (PHQ-9) symptoms, and work-related burnout (based on the Maslach Burnout Inventory) were administered at baseline and every two weeks. Feasibility was determined based on the combination of both subjective and objective user-engagement Indicators (UEIs). Effectiveness was measured using paired t-tests as the change in self-assessment scores. Results (1) Simulation: 17 HCs (73% female; mean age=36.5±9.7) simulated different clinical situations. 98.8% of the expected modules were recommended according to each simulation. Suicidal alerts were correctly activated and received by the research team. (2) Feasibility and effectiveness study: 34 patients (15 from PC and 19 healthcare workers; 77% female; mean age=35.3±10.1) completed the first self-assessments, with 34 (100%) presenting anxiety symptoms, 32 (94%) depressive symptoms, and 22 (64.7%) work-related burnout. Nine (26.5%) patients completed the second self-assessments after 2-weeks of use. No significant differences were found for anxiety [t(8) = 1.000, p = 0.347] or depressive [t(8) = 0.400, p = 0.700] symptoms, but work-related burnout was significantly reduced [t(8) = 2.874, p = 0.021] between the means of the first and second self-assessments. Vickybot showed high subjective-UEIs, but low objective-UEIs (completion, adherence, compliance, and engagement). Conclusions The chatbot proved to be useful in screening the presence and severity of anxiety and depressive symptoms, in reducing work-related burnout, and in detecting suicidal risk. Subjective perceptions of use contrasted with low objective-use metrics. Our results are promising, but suggest the need to adapt and enhance the smartphone-based solution in order to improve engagement. Consensus on how to report UEIs and validate digital solutions, especially for chatbots, are required. Disclosure of InterestNone Declared

Introduction Chronic Hepatitis C infection is considered a systemic disease with extrahepatic manifestations, mainly neuropsychiatric symptoms, which is associated with a chronic low-grade inflammatory state. Hepatitis C virus (HCV) eradication is currently achieved in >98% of cases with oral direct-acting antivirals (DAA). Objectives To study potential clinical neuropsychiatric changes (mood, cognition, sleep, gastrointestinal, sickness, and motion) in HCV-infected patients after HCV eradication with DAA. Methods Design: Cohort study. Subjects: 37 HCV-infected patients, aged

Introduction The close association among thyroid metabolism, mood disorders and behavior has long been known. The role of basal thyroid axis in antidepressant treatment response is less known. Objectives The aim of the present study was to study the association of basal serum thyrotropin (TSH) levels, with antidepressant treatment response in major depressive disorder. Methods Thirty-one depressed adult outpatients were included. Major depressive episode was diagnosed through the MINI (DSM-IV-TR) interview. Clinical symptomatology and blood samples were assessed at baseline, and at 4- and 8-weeks of either escitalopram or sertraline. Treatment response was defined by an improvement ≥50% in MADRS scores at 4-, and 8-weeks. Basal TSH levels were included in a linear regression model as predictor of treatment response. Results Twenty-seven patients finished 8-weeks of treatment. Response to treatment was of 74% at 4-weeks, and 63% at 8-weeks of antidepressant treatment. Basal median TSH levels were between normal ranges (M+SD=1.85+1,02 mlU/L). Basal TSH levels not correlated with basal MADRS scores, but with higher MADRS scores at week-4 (r=0,415, p=0,031) and at week-8 (r=0,392, p=0,043). Moreover, less baseline TSH levels trend to be a significant good predictor for treatment response at 4-weeks (R2=.116, p=.083); and a good predictor at 8-weeks treatment (R2=.147, p=.049). Conclusions Baseline TSH levels even within the normal range may play a role in predicting antidepressant response. Disclosure No significant relationships.

Introduction Hepatitis C virus (HCV) infection is known to be associated with neuropsychiatric manifestations as part of the disease. Previous neuroimaging studies showed brain connectivity dysfunction among HCV-infected patients Objectives To assess, by MR in resting state, the potential structural and connectivity changes before (BL) and after HCV eradication (FU12) with direct-acting antivirals (DAA), along with clinical parameters. Methods Twenty-one HCV-patients, aged≤55 years, without psychiatric history, nor advanced liver disease, and eligible for DAA, and 25 healthy controls were included. Evaluations were performed at BL and FU12. Brain volume and local gyrification index (LGI) were assessed in MR-T1, and functional connectivity by seed-based analysis (left insula). Depression (MADRS/PHQ9) and neurotoxicity symptomatology (NRS) were assessed. We compared patients between BL/FU12, and controls by means of paired/independent T-test analysis. Results Substained virologycal response was obtained in all patients (100%). Depressive and neurotoxicity symptomatology improved after cure (p

Background: Many people attending primary care (PC) have anxiety-depressive symptoms and work-related burnout compounded by a lack of resources to meet their needs. The COVID-19 pandemic has exacerbated this problem, and digital tools have been proposed as a solution., Objective: We aimed to present the development, feasibility, and potential effectiveness of Vickybot, a chatbot aimed at screening, monitoring, and reducing anxiety-depressive symptoms and work-related burnout, and detecting suicide risk in patients from PC and health care workers., Methods: Healthy controls (HCs) tested Vickybot for reliability. For the simulation study, HCs used Vickybot for 2 weeks to simulate different clinical situations. For feasibility and effectiveness study, people consulting PC or health care workers with mental health problems used Vickybot for 1 month. Self-assessments for anxiety (Generalized Anxiety Disorder 7-item) and depression (Patient Health Questionnaire-9) symptoms and work-related burnout (based on the Maslach Burnout Inventory) were administered at baseline and every 2 weeks. Feasibility was determined from both subjective and objective user-engagement indicators (UEIs). Potential effectiveness was measured using paired 2-tailed t tests or Wilcoxon signed-rank test for changes in self-assessment scores., Results: Overall, 40 HCs tested Vickybot simultaneously, and the data were reliably transmitted and registered. For simulation, 17 HCs (n=13, 76% female; mean age 36.5, SD 9.7 years) received 98.8% of the expected modules. Suicidal alerts were received correctly. For the feasibility and potential effectiveness study, 34 patients (15 from PC and 19 health care workers; 76% [26/34] female; mean age 35.3, SD 10.1 years) completed the first self-assessments, with 100% (34/34) presenting anxiety symptoms, 94% (32/34) depressive symptoms, and 65% (22/34) work-related burnout. In addition, 27% (9/34) of patients completed the second self-assessment after 2 weeks of use. No significant differences were found between the first and second self-assessments for anxiety (t 8 =1.000; P=.34) or depressive (t 8 =0.40; P=.70) symptoms. However, work-related burnout scores were moderately reduced (z=-2.07, P=.04, r=0.32). There was a nonsignificant trend toward a greater reduction in anxiety-depressive symptoms and work-related burnout with greater use of the chatbot. Furthermore, 9% (3/34) of patients activated the suicide alert, and the research team promptly intervened with successful outcomes. Vickybot showed high subjective UEI (acceptability, usability, and satisfaction), but low objective UEI (completion, adherence, compliance, and engagement). Vickybot was moderately feasible., Conclusions: The chatbot was useful in screening for the presence and severity of anxiety and depressive symptoms, and for detecting suicidal risk. Potential effectiveness was shown to reduce work-related burnout but not anxiety or depressive symptoms. Subjective perceptions of use contrasted with low objective-use metrics. Our results are promising but suggest the need to adapt and enhance the smartphone-based solution to improve engagement. A consensus on how to report UEIs and validate digital solutions, particularly for chatbots, is required., (©Gerard Anmella, Miriam Sanabra, Mireia Primé-Tous, Xavier Segú, Myriam Cavero, Ivette Morilla, Iria Grande, Victoria Ruiz, Ariadna Mas, Inés Martín-Villalba, Alejandro Caballo, Julia-Parisad Esteva, Arturo Rodríguez-Rey, Flavia Piazza, Francisco José Valdesoiro, Claudia Rodriguez-Torrella, Marta Espinosa, Giulia Virgili, Carlota Sorroche, Alicia Ruiz, Aleix Solanes, Joaquim Radua, María Antonieta Also, Elisenda Sant, Sandra Murgui, Mireia Sans-Corrales, Allan H Young, Victor Vicens, Jordi Blanch, Elsa Caballeria, Hugo López-Pelayo, Clara López, Victoria Olivé, Laura Pujol, Sebastiana Quesada, Brisa Solé, Carla Torrent, Anabel Martínez-Aran, Joana Guarch, Ricard Navinés, Andrea Murru, Giovanna Fico, Michele de Prisco, Vicenzo Oliva, Silvia Amoretti, Casimiro Pio-Carrino, María Fernández-Canseco, Marta Villegas, Eduard Vieta, Diego Hidalgo-Mazzei. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.04.2023.)

Background: A high proportion of health professionals in training suffer from work-related stress and may develop a burnout syndrome., Objectives: To study the incidence of burnout after the first year of residency in a teaching hospital and to identify baseline psychological, psychosocial work conditions, and biological risk factors., Methodology: We assessed the following in a prospective cohort of residents at baseline (first month residence) and after 1 year: background factors (socio-demographics, psychiatric history), perceived stress score (Perceived Stress Scale), Maslach Burnout Inventory score, and psychosocial factors (Job Content Questionnaire). Blood samples were obtained to study serum cortisol, IL-6, and TNF-α concentrations. The cumulative incidence was modelled by multivariate log-binomial regression analysis., Results: We included 71 participants with a female majority (64.8%), age 26.4 (2.65) years, psychiatric history in 20%, and burnout in 13%. Among those without burnout initially (N = 59), it had developed by 1 year in 22% of residents. Increased job demand (RR = 1.259, 95%CI = 1.019-1.556, p = 0.033) and decreased cortisol levels (RR = 0.877, 95%CI = 0.778-0.989, p = 0.032) predicted burnout after 1 year of residency among medical trainees., Conclusion: Burnout syndrome develops in 22% of residents by 1 year of training and can be predicted by increased work demands and decreased cortisol levels., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2022. Published by Elsevier Inc.)

Background: The relationship between antidepressant response and glial, inflammatory, and metabolic markers is poorly understood in depression. This study assessed the ability of biological markers to predict antidepressant response in major depressive disorder (MDD)., Methods: We included 31 MDD outpatients treated with escitalopram or sertraline for 8 consecutive weeks. The Montgomery-Åsberg Depression Rating Scale (MADRS) was administered at baseline and at week 4 and 8 of treatment. Concomitantly, blood samples were collected for the determination of serum S100B, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL)-C levels. Treatment response was defined as ≥50% improvement in the MADRS score from baseline to either week 4 or 8. Variables associated with treatment response were included in a linear regression model as predictors of treatment response., Results: Twenty-seven patients (87%) completed 8 weeks of treatment; 74% and 63% were responders at week 4 and 8, respectively. High S100B and low HDL-C levels at baseline were associated with better treatment response at both time points. Low CRP levels were correlated with better response at week 4. Multivariate analysis showed that high baseline S100B levels and low baseline HDL-C levels were good predictors of treatment response at week 4 (R2 = 0.457, P = .001), while S100B was at week 8 (R2 = 0.239, P = .011). Importantly, baseline S100B and HDL-C levels were not associated with depression severity and did not change over time with clinical improvement., Conclusions: Serum S100B levels appear to be a useful biomarker of antidepressant response in MDD even when considering inflammatory and metabolic markers., (© The Author(s) 2022. Published by Oxford University Press on behalf of CINP.)

Objectives: To determine how the COVID-19 lockdown influenced the lifestyle, eating behavior, use of substances, mental health, and weight in patients who had undergone bariatric surgery (BS) and explore the self-perception of one's own health and fears related to COVID-19., Methods: We performed a cross-sectional exploratory study in obesity patients who had undergone BS surgery > 1 year previously in a university hospital. Assessment was performed 40 days after initiating lockdown and included 2 periods: from April 24 until May 8 and during the initial de-escalation period: from May 9 until 22, 2020. A structured telephone interview and an online survey were administered., Results: One hundred eighty-eight patients were interviewed; 156 also responded to the online survey (77% females, mean age 53.46 ± 10.48 years, mean follow-up 5.71 ± 4.30 years). Dietary habits were affected in 72% of the participants, with 15% reporting better diet planning; 83.5% reported having more sedentary behaviors; 27% and 36% showed depression and anxiety, respectively; and 45% of participants reported bad sleep quality. In relation to changes in the use of any substance, the use increased in the majority of patients who were previously users. Self-perception of one's own health and fears related to COVID-19 were only moderate. Finally, emotional eating and time since BS were statistically significant risk factors for predicting weight gain., Conclusions: Lockdown during COVID-19 pandemic negatively influenced the lifestyle, mental health, substance use, and weight in BS patients. These alterations were somewhat similar to those observed in the general population but more severe and with important clinical implications., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Our aim was to assess personality traits associated with substance use during pregnancy in a population-based, multicentre study of 1804 pregnant women. On day 2-3 postpartum, participants completed a semi-structured interview, including self-reported drug use (alcohol, tobacco, caffeine, cannabis, cocaine, opioids) during pregnancy, and socio-demographic, reproductive and obstetric variables, personal and family psychiatric history, social support, and the Eysenck personality questionnaire, short version (EPQ-RS). Logistic regression models were conducted. Fifty per cent of women reported substance use during pregnancy: 40% caffeine, 21% tobacco, 3.5% alcohol, and 0.3 % cannabis. Mean T-scores (SD) for personality dimensions were 51.1 (9.6) for extraversion, 48 (8.9) for psychoticism, and 43.6 (8.5) for neuroticism. Extroversion (p = .029) and psychoticism (p = .009) were identified as risk factors after adjustment by age, level of education, employment status during pregnancy, low social support, and previous psychiatric history. For each increment of 10 units in their scores, the odds of substance use increased by 12% and 16% respectively. Low education, being on leave during pregnancy, and previous psychiatric history were independent factors (p < .05) associated with substance use during pregnancy. Primiparity was a protective factor (p = .001). The final models showed a good fit (p = .26). The screening of substance use during pregnancy should include personality dimensions apart from psychosocial variables and history of psychiatric disorders. It is important to identify the associated risk factors for substance use during pregnancy to prevent and improve foetal/neonatal and maternal health during perinatal period.

Despite rarely assessed, sexuality is a relevant domain in Quality of Life. We prospectively evaluated the impact of direct-acting antiviral therapy on sexuality in a cohort of 186 patients with chronic hepatitis C (HCV). Sexual dysfunction was assessed by validated scales CSFQ-14/CSFQ-VAS at baseline and one year after treatment finalization. Median age was 55 years and 87% had mild liver disease. Basal prevalence of sexual dysfunction (62%) and fear of HCV transmission (25%) were high. After HCV cure, both sexual dysfunction prevalence and CSFQ-VAS improved (P = .058 and P < .01, respectively), and fear of HCV transmission dropped to 16% (P = .02). These changes were especially relevant in young men (<55), where sexual dysfunction decreased from 48.6% to 29.7% (P = .04) and among non-depressed patients in whom sexual dysfunction decreased from 54.6% to 47% (P < .01). Age and major depression remained as independent factors of sexual dysfunction persistence after HCV cure. Our data suggest that HCV eradication is associated with an improvement in sexuality, in those patients without depression., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Postpartum depression (PPD) is a common mood disorder that occurs after delivery with a prevalence of approximately 10%. Recent reports have related placental corticotropin-releasing hormone (pCRH) to postpartum depressive symptoms. The aim of this study was to determine whether pCRH, ACTH, and cortisol (measured 48 h after delivery) and glucocorticoid and mineralocorticoid receptor genotypes (NR3C1 and NR3C2) and their interaction are associated with PPD. A longitudinal 32-week prospective study of five hundred twenty-five Caucasian depression-free women that were recruited from obstetric units at two Spanish general hospitals immediately after delivery. Of the women included in the sample, forty-two (8%) developed PPD. A strong association between PPD and the interaction between the pCRH and NR3C2 rs2070951 genotype was observed. The mean level of pCRH in rs2070951GG carriers with PPD was 56% higher than the mean in the CG and CC genotype groups (P < 0.00005). Carriers of the rs2070951GG genotype with high levels of pCRH had a higher risk of developing PPD (OR = 1.020, 95% CI 1.007-1.034, P = 0.002). This association remained even after controlling for variables such as neuroticism, obstetric complications and the number of stressful life events during pregnancy. There is an important interaction between pCRH 48 h postpartum and the NR3C2 rs2070951GG genotype. This interaction moderately associates with the presence of PPD. These results may open a new line of research and, if confirmed in other settings, will help to identify better risk predictors and the treatment for PPD.

Introduction: The Edinburgh Postnatal Depression Scale (EPDS) is considered the gold standard in screening for postpartum depression. Although the Spanish version has been widely used, its factorial structure has not yet been studied ., Methods: A total of 1,204 women completed the EPDS 32 weeks after delivery. To avoid multiple testing, we split the sample into two halves, randomly drawing two subsamples of 602 participants each. We conducted exploratory factor analysis (EFA), followed by an oblimin rotation with the first sub-sample. Confirmatory factor analysis (CFA) was conducted using a Weighted Least Squares Means and Variance (WLSMV) estimation of the data. We explored different solutions between two and four factors. We compared the factors between two groups with depression and non-depression (evaluated with the Diagnostic Interview for Genetic Studies (DIGS) for the DSM-IV)., Results: The EFA indicated a three-factor model consisting of anxiety, depression and anhedonia. The results of the CFA confirmed the three-factor model (&#967;2=99.203, p<0.001; RMSEA=0.06, 90% CI=0.04/0.07, CFI=0.87 and TLI=0.82). Women with depression in the first 32 weeks obtained higher scores for anxiety, depression and anhedonia dimensions (p<0.001)., Conclusions: This is the first study of confirmatory analysis with the Spanish version of EPDS in a large sample of women without psychiatric care during pregnancy. A three-factor model consisting of anxiety, depression and anhedonia was used. Women with depression had a higher score in the three dimensions of the EPDS.

The transition to motherhood is stressful as it requires several important changes in family dynamics, finances, and working life, along with physical and psychological adjustments. This study aimed at determining whether some forms of coping might predict postpartum depressive symptomatology. A total of 1626 pregnant women participated in a multi-centric longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the structured Diagnostic Interview for Genetic Studies (DIGS). The brief Coping Orientation for Problem Experiences (COPE) scale was used to measure coping strategies 2-3 days postpartum. Some coping strategies differentiate between women with and without postpartum depression. A logistic regression analysis was used to explore the relationships between the predictors of coping strategies and major depression (according to DSM-IV criteria). In this model, the predictor variables during the first 32 weeks were self-distraction (OR 1.18, 95 % CI 1.04-1.33), substance use (OR 0.58, 95 % CI 0.35-0.97), and self-blame (OR 1.18, 95 % CI 1.04-1.34). In healthy women with no psychiatric history, some passive coping strategies, both cognitive and behavioral, are predictors of depressive symptoms and postpartum depression and help differentiate between patients with and without depression.

Background: The role of inflammation in mood disorders has received increased attention. There is substantial evidence that cytokine therapies, such as interferon alpha (IFN-alpha), can induce depressive symptoms. Indeed, proinflammatory cytokines change brain function in several ways, such as altering neurotransmitters, the glucocorticoid axis, and apoptotic mechanisms. This study aimed to evaluate the impact on mood of initiating IFN-alpha and ribavirin treatment in a cohort of patients with chronic hepatitis C. We investigated clinical, personality, and functional genetic variants associated with cytokine-induced depression., Methods: We recruited 344 Caucasian outpatients with chronic hepatitis C, initiating IFN-alpha and ribavirin therapy. All patients were euthymic at baseline according to DSM-IV-R criteria. Patients were assessed at baseline and 4, 12, 24, and 48 weeks after treatment initiation using the Patient Health Questionnaire (PHQ), the Hospital Anxiety and Depression Scale (HADS), and the Temperament and Character Inventory (TCI). We genotyped several functional polymorphisms of interleukin-28 (IL28B), indoleamine 2,3-dioxygenase (IDO-1), serotonin receptor-1A (HTR1A), catechol-O-methyl transferase (COMT), glucocorticoid receptors (GCR1 and GCR2), brain-derived neurotrophic factor (BDNF), and FK506 binding protein 5 (FKBP5) genes. A survival analysis was performed, and the Cox proportional hazards model was used for the multivariate analysis., Results: The cumulative incidence of depression was 0.35 at week 24 and 0.46 at week 48. The genotypic distributions were in Hardy-Weinberg equilibrium. Older age (p = 0.018, hazard ratio [HR] per 5 years = 1.21), presence of depression history (p = 0.0001, HR = 2.38), and subthreshold depressive symptoms at baseline (p = 0.005, HR = 1.13) increased the risk of IFN-induced depression. So too did TCI personality traits, with high scores on fatigability (p = 0.0037, HR = 1.17), impulsiveness (p = 0.0200 HR = 1.14), disorderliness (p = 0.0339, HR = 1.11), and low scores on extravagance (p = 0.0040, HR = 0.85). An interaction between HTR1A and COMT genes was found. Patients carrying the G allele of HTR1A plus the Met substitution of the COMT polymorphism had a greater risk for depression during antiviral treatment (HR = 3.83) than patients with the CC (HTR1A) and Met allele (COMT) genotypes. Patients carrying the HTR1A CC genotype and the COMT Val/Val genotype (HR = 3.25) had a higher risk of depression than patients with the G allele (HTR1A) and the Val/Val genotype. Moreover, functional variants of the GCR1 (GG genotype: p = 0.0436, HR = 1.88) and BDNF genes (Val/Val genotype: p = 0.0453, HR = 0.55) were associated with depression., Conclusions: The results of the study support the theory that IFN-induced depression is associated with a complex pathophysiological background, including serotonergic and dopaminergic neurotransmission as well as glucocorticoid and neurotrophic factors. These findings may help to improve the management of patients on antiviral treatment and broaden our understanding of the pathogenesis of mood disorders., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)

Background: Variables such as the mother's personality, social support, coping strategies and stressful events have been described as risk factors for postpartum depression. Structural Equation Modelling (SEM) analysis was used to examine whether neuroticism, perceived social support, perceived life events, and coping strategies are associated with postpartum depressive symptoms at the 8th and 32nd weeks., Methods: A total of 1626 pregnant women participated in a longitudinal study. Different evaluations were performed 8 and 32weeks after delivery. Several measures were used: the Edinburgh Postnatal Depression Scale (EPDS), the Diagnostic Interview for Genetic Studies (DIGS), the Eysenck Personality Questionnaire (EPQ-RS), the St. Paul Ramsey life events scale and the Duke-UNC Functional Social Support Questionnaire. The brief COPE scale was used to measure coping strategies. SEM analysis was conducted for all women and in those women with a clinical diagnosis of postpartum depression., Results: Passive coping strategies were associated with postpartum depressive symptoms at both visits (8th and 32nd weeks). Neuroticism was associated with more passive coping strategies and less active coping strategies. Neuroticism and life stress were positively correlated, and social support was negatively correlated with life stress and neuroticism., Conclusions: Early identification of potential risk for symptomatology of depression postpartum should include assessment of neuroticism, life events, social support and coping strategies., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objective: To assess the utility of prophylactic administration of antidepressants in preventing a major depressive episode during antiviral treatment for chronic hepatitis C., Data Sources: A computerized literature search was conducted in MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and ClinicalTrials.gov to locate articles published in any language from the earliest available online year until October 2012, using the following phrase and Boolean logic algorithm: "hepatitis and c and (interferon-alpha OR peginterferon OR (pegylated and interferon)) and (depression OR mood) and (prevention OR prophylactic OR prophylaxis OR antidepressant).", Study Selection: Double-blind, randomized, placebo-controlled trials using antidepressants prophylactically before starting antiviral therapy for chronic hepatitis C were included. At baseline, none of the patients in the trials presented depression (DSM-IV-TR criteria). Using keywords and cross-referenced bibliographies, 144 studies were identified and examined in depth. 137 articles were rejected because inclusion criteria were not met. Finally, 7 studies were included., Data Extraction: Data were extracted independently by 2 investigators. The primary outcome measure was the onset of a major depressive episode during the antiviral treatment. Depressive symptoms, other side effects, and sustained virologic response were also examined. A full review and meta-analysis were performed. Odds ratios (ORs), mean differences, and estimated numbers needed to treat (NNTs) with 95% confidence intervals (CIs) were calculated., Results: 591 patients were randomly assigned to antiviral treatment and another intervention: escitalopram (n = 197), paroxetine (n = 42), citalopram (n = 53), or placebo (n = 299). Selective serotonin reuptake inhibitors (SSRIs), as a group, reduced the incidence of a major depressive episode during antiviral treatment (OR = 0.53; 95% CI, 0.33 to 0.84). The NNT was 12 (95% CI, 7.0 to 37.9). SSRIs reduced depressive symptoms at 24 weeks of treatment (mean difference -2.18; 95% CI, -4.25 to -0.10). With regard to side effects, only dizziness was associated with administration of antidepressants (OR = 2.65; 95% CI, 1.46 to 4.80). There were no differences in sustained virologic response (OR = 1.22; 95% CI, 0.58 to 2.57)., Conclusions: Administration of SSRIs before starting antiviral treatment reduces the incidence of interferon-induced depression, with a relatively moderate prophylactic impact and good tolerability., (© Copyright 2014 Physicians Postgraduate Press, Inc.)

Current treatments of depression include psychological, pharmacological and physical approaches. Pharmacological interventions to treat depression have previously focused on modifying dysfunctional neurotransmitter systems. Overall, these treatments have demonstrated an ability to manage major depression but otucomes continue to be poor in many patients, especially those with long term illness or with previous multiple relapses. This may be due to the fact that depression is a systemic and neuroprogressive illness involving multiple biological pathways such as immunological factors. There is substantial evidence that cytokine therapies induce depressive symptoms in clinical populations. The model of cytokine-induced depression has provided important information relative to the risk factors and biological pathways involved in the etiology of depressive symptoms and, most importantly, the identification and knowledge of these factors has allowed new treatment targets to be explored. When an exogenous cytokine such as interferon-alpha is administered, proinflammatory cytokines are activated, leading to alterations in neurotransmission and endocrine pathways and producing neurotoxicity. Several new treatments for depression acting through pathways other than amine neurotransmission have emerged in recent years. The regulation of the inflammatory response, the decrease in the activity of the hypothalamic-pituitary-adrenal axis and the prevention of neurotoxicity are potential targets for new drugs. Though these drugs are mostly at the proof-of-concept stage, some of them have already shown promising results for the treatment of depression.

Background & Aims: Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC., Methods: 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model., Results: Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes., Conclusions: MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Cytokines and serotonin neurotransmission may play an important role on the development of psychopathological symptoms during interferon (IFN) treatment. The aim of the present study was to investigate the association between IFN-induced depression, anxiety and fatigue and functional genetic variants at the interleukin-6 gene (IL-6) and serotonin transporter gene (SERT)., Methods: 385 consecutive Caucasian outpatients with chronic hepatitis C initiating treatment with IFN-alpha and ribavirin were included. All patients were interviewed at baseline using the Structured Clinical Interview for DSM-IV (SCID-I) and those with a current major depressive disorder or anxiety disorder before starting treatment were excluded. Depression and anxiety were assessed at baseline during the treatment (at 4, 12, 24 and 48 weeks) using the Hospital Anxiety and Depression Scale and fatigue was evaluated using a visual analogue scale. The 5-HTTLPR region of SERT gene and the functional polymorphism located at the promoter region of IL-6 gene (rs1800795) were genotyped., Results: Genotypic distribution was in the Hardy-Weinberg equilibrium for SERT (p=0.41) and for IL-6 (p=0.72) polymorphisms. At baseline we found only a significant effect of IL-6 polymorphism on fatigue symptoms. During antiviral treatment we reported that subjects with CC genotype (IL-6) presented significantly lower changes from baseline in IFN-induced depression (p=0.005) and IFN-induced anxiety (p=0.004). We did not find statistically significant differences on depression (p=0.21) or anxiety (p=0.15) between SS/SL and LL genotypes of SERT., Conclusions: Genetic variations in the IL-6 gene increase the risk of IFN-induced depression and anxiety. The IL-6 polymorphism was associated with fatigue rates in patients with chronic hepatitis C before treatment. Our study confirms the role of inflammatory mechanisms in IFN-induced psychopathological symptoms., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Distorted images of the observable self are considered crucial in the development and maintenance of social anxiety. We generated an experimental situation in which participants viewed themselves from an observer's perspective when exposed to scrutiny and evaluation by others. Method Twenty patients with social anxiety disorder (SAD) and 20 control subjects were assessed using functional magnetic resonance imaging (fMRI) during the public exposure of pre-recorded videos in which they were each shown performing a verbal task. The examiners acted as the audience in the experiment and rated performance. Whole-brain functional maps were computed using Statistical Parametric Mapping., Results: Robust activation was observed in regions related to self-face recognition, emotional response and general arousal in both study groups. Patients showed significantly greater activation only in the primary visual cortex. By contrast, they showed significant deactivation or smaller activation in dorsal frontoparietal and anterior cingulate cortices relevant to the cognitive control of negative emotion. Task-related anxiety ratings revealed a pattern of negative correlation with activation in this frontoparietal/cingulate network. Importantly, the relationship between social anxiety scores and neural response showed an inverted-U function with positive correlations in the lower score range and negative correlations in the higher range., Conclusions: Our findings suggest that exposure to scrutiny and evaluation in SAD may be associated with changes in cortical systems mediating the cognitive components of anxiety. Disorder severity seems to be relevant in shaping the neural response pattern, which is distinctively characterized by a reduced cortical response in the most severe cases.

Repeated self-harm usually presents with associated psychopathology, mostly in the form of obsessive-compulsive disorder, malingering, or personality disorders, and may persist for many years. This case presentation focuses on self-harm involving the deliberate ingestion of foreign bodies. This behavior remains poorly understood, and the relevant literature focuses almost entirely on gastroenterological and surgical management, with little or no discussion of underlying psychological mechanisms, psychopathology, or psychotherapeutic intervention. The goal of this article is to begin to fill that gap by presenting the case of a young woman who was diagnosed with borderline personality disorder and followed for 20 years, who repeatedly swallowed objects as a form of self-harming behavior. The nosological status and possible functions of this behavior are discussed, as are the difficulties of caring for patients with such long-standing, repeated selfinjury. This case illustrates how the boundaries between different self-injurious behaviors are blurred and also how different self-injurious behaviors are likely to share common patterns, functional integrity, and meanings. It should also serve to remind us how far we have to go in terms of understanding, classifying, and successfully treating certain patients who present with longterm and bizarre self-injurious behavior.

Objective: To carry out a systematic review of the risk factors for, and incidence of, major depressive episode (MDE) related to antiviral therapy for chronic hepatitis C., Data Sources: The MEDLINE, PsycINFO, and Cochrane databases were searched to locate articles published from the earliest available online year until June 2011 using the keywords hepatitis C, interferon-alpha, peginterferon, pegylated interferon, depression, and mood and Boolean operators. Articles written in English, Spanish, and French were included., Study Selection: Prospective studies reporting incidence of interferon-alpha-induced MDE were included. At baseline, patients did not present a DSM-IV/ICD depressive episode, and evaluation was performed by a trained clinician. Twenty-six observational studies met the inclusion criteria., Data Extraction: Extracted data included authors, year of publication, design, characteristics of the population, viral coinfection, adjunctive psychopharmacology, instruments to assess depression, dose and type of interferon-alpha, adjunctive ribavirin treatment, and follow-up time. Outcome of incidence of MDE (primary outcome measure) was abstracted, as were potential predictive variables., Data Synthesis: A full review was performed. Meta-analysis of the cumulative incidence of induced MDE as a function of time was carried out. Odds ratios (ORs) and mean differences were used to estimate the strength of association of variables., Results: Overall cumulative incidence of depression was 0.25 (95% CI, 0.16 to 0.35) and 0.28 (95% CI, 0.17 to 0.42) at 24 and 48 weeks of treatment, respectively. According to our analysis, high baseline levels of interleukin 6 (mean difference = 1.81; 95% CI, 1.09 to 2.52), female gender (OR = 1.40; 95% CI, 1.02 to 1.91), history of MDE (OR = 3.96; 95% CI, 2.52 to 6.21), history of psychiatric disorder (OR = 3.18; 95% CI, 1.60 to 6.32), subthreshold depressive symptoms (mean difference = 0.96; 95% CI, 0.31 to 1.61), and low educational level (mean difference = -0.99; 95% CI, -1.59 to -0.39) were predictive variables of MDE during antiviral treatment., Conclusions: One in 4 chronic hepatitis C patients who start interferon and ribavirin treatment will develop an induced major depressive episode. Clinicians should attempt a full evaluation of patients before starting antiviral treatment in order to identify those at risk of developing interferon-induced depression., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Unlabelled: Depression and anxiety in patients with hepatitis C virus (HCV) infection influence their health-related quality of life and their adherence to antiviral treatment., Objective: To study the psychometric properties of the Patient Health Questionnaire (PHQ) as a screening instrument for depression and anxiety in HCV patients., Methods: Criterion validity, using the structured clinical interview for DSM-IV-Axis I (SCID-I) to diagnose depression and anxiety disorders as diagnostic standard, was evaluated for both summed and algorithm-based PHQ in 500 HCV patients. Correlations with quality of life (Short-Form-36 Health Survey; SF-36) and severity of illness (Hospital Anxiety and Depression Scale; HADS) were calculated to assess construct validity. Test-retest reliability and patients' reaction to the PHQ were assessed in 120 HCV patients., Results: Twenty-three percent of patients (N=114) had a psychiatric disorder (any depressive disorder=18.2%; major depressive disorder=6.4%; generalized anxiety disorder=7.0% and panic disorder=5.8%). The questionnaire demonstrated good test-retest reliability for any depressive disorder (k=.847), major depressive disorder (k=.784), generalized anxiety disorder (k=.787), panic disorder (k=.848), and for any psychiatric disorder (k=.847). There was good agreement between PHQ and SCID-I diagnoses (for any PHQ disorder, k=.821; overall accuracy=90.43%, sensitivity=83.84%; specificity=97.01%). Patients with any PHQ disorder had higher impairment on the SF-36 (p<.001). HADS depression and anxiety scores showed high correlations with PHQ depression (p<.001) and anxiety (p<.001) scores respectively. PHQ administration was well accepted by 97% of patients., Conclusions: The Spanish version of the PHQ is a reliable, valid, and useful screening instrument to detect depression, generalized anxiety and panic disorders in HCV patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Although perfectionism from a multidimensional perspective has generally been associated with depressive illness, there are not many studies on its role in major depression in the postnatal period. The aim of the present study was to explore the relationship between perfectionism dimensions using the Frost Multidimensional Perfectionism Scale (FMPS) and major postpartum depression., Methods: One-hundred-twenty-two women with major postpartum depression (SCID-I; DSM-IV) and 115 healthy postpartum women were evaluated using the FMPS, an instrument for the assessment of six perfectionism dimensions: concern over mistakes, personal standards, parental expectations, parental criticism, doubt about actions and organisation. Other variables were also considered: neuroticism, psychiatric history, social support, life events and genotype combinations according to serotonin transporter expression (5-HTTLPR and Stin2 VNTR polymorphisms)., Results: The prevalence of high-perfectionism was higher in major postpartum depression group than in control group (34% vs. 11%; p<0.001). Multivariate models confirmed high-perfectionism as an independent factor associated with major postpartum depression. Specifically, the high-concern over mistakes dimension increased over four-fold the odds of major depression in postpartum period. (OR=4.14; 95% CI=1.24-13.81) Neuroticism, personal psychiatric history and 5-HTT low-expressing genotypes at one of the loci were also identified as independent factors., Conclusions: High-perfectionism, and particularly high-concern over mistakes is a personality dimension associated with major postpartum depression. The inclusion of perfectionism assessment, together with others factors, may be considered in order to improve the detection of women at risk of postpartum depression, in whom early intervention may be of benefit., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Prevalence and clinical correlates of depersonalization symptoms have been associated with panic disorder. Personality traits might increase the likelihood of experiencing depersonalization symptoms or depersonalization disorder in panic patients., Aims: The objectives of this study are to establish the prevalence of depersonalization symptoms during the panic attack and in depersonalization disorder and to examine the personality factors associated with the presence of depersonalization in patients with panic disorder., Methods: The sample comprised 104 consecutive adult outpatients with panic disorder, diagnosed according to the Semistructured Clinical Interview for DSM-IV (Axis I/II disorders). Participants were assessed with the Cambridge Depersonalization Scales, the Temperament and Character Inventory, and the Panic and Agoraphobia Scale., Results: Forty-eight percent of the sample had depersonalization symptoms during the panic attack, whereas 20% of patients had a depersonalization disorder. Women presented more depersonalization disorders than did men (P = .036). Patients with panic disorder with depersonalization disorder had a more severe panic disorder (P = .002). Logistic regression analysis showed that self-transcendence trait (odds ratio, 1.089; 95% confidence interval, 1.021-1.162; P = .010) and severity of panic (odds ratio, 1.056; 95% confidence interval, 1.005-1.110; P = .032) were independently associated with depersonalization disorder., Conclusions: A high prevalence of depersonalization symptoms and depersonalization disorder was confirmed in patients with panic disorder, supporting a dosage effect model for understanding depersonalization pathology. Self-transcendence trait and severity of panic disorder were reported as risk factors for depersonalization disorder., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Depression is one of the main reasons for treatment withdrawal and failure in chronic hepatitis C patients treated with interferon. Antidepressants are useful for its treatment, but whether they can also be used for prevention has yet to be established., Method: To evaluate the efficacy and safety of escitalopram for preventing interferon alfa-2a-induced depression, we conducted an investigator-initiated multicenter, randomized, double-blind, placebo-controlled trial in 133 chronic hepatitis C patients without baseline mental disorders who were randomly assigned to receive escitalopram or placebo during the first 12 weeks of treatment. Primary efficacy outcomes were the development of DSM-IV major depression and scores on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hospital Anxiety and Depression Scale (HADS). Primary safety end points were biochemical and virological responses. Patients were recruited between March 2005 and July 2006., Results: Rates of major depression were low (5.4%) and did not differ between placebo (3.2%) and escitalopram (7.6%). MADRS and HADS scores significantly increased during treatment (P < .001 and P = .028, respectively), but there were no differences between treatment groups. Sustained virological response was achieved by 69.2% of patients, 70.4% in the placebo group and 67.9% in the escitalopram group., Conclusions: Findings do not support the use of an antidepressant to prevent interferon-induced depression during the first 12 weeks of treatment in chronic hepatitis C patients at low psychiatric risk. Future studies should be directed to subpopulations of patients at high psychiatric risk., Trial Registration: clinicaltrials.gov Identifier: NCT00166296., (© Copyright 2011 Physicians Postgraduate Press, Inc.)

Background: The involvement of microRNAs (miRNAs) in neuronal differentiation and synaptic plasticity suggests a role for miRNAs in psychiatric disorders; association analyses and functional approaches were used to evaluate the implication of miRNAs in the susceptibility for panic disorder., Methods: Case-control studies for 712 single-nucleotide polymorphisms (SNPs) tagging 325 human miRNA regions were performed in 203 Spanish patients with panic disorder and 341 control subjects. A sample of 321 anxiety patients and 642 control subjects from Finland and 102 panic disorder patients and 829 control subjects from Estonia was used as a replica. Reporter-gene assays and miRNA overexpression experiments in neuroblastoma cells were used to functionally evaluate the spectrum of genes regulated by the associated miRNAs., Results: Two SNPs associated with panic disorder: rs6502892 tagging miR-22 (p < .0002), and rs11763020 tagging miR-339 (p < .00008). Other SNPs tagging miR-138-2, miR-488, miR-491, and miR-148a regions associated with different panic disorder phenotypes. Replication in the north-European sample supported several of these associations, although they did not pass correction for multiple testing. Functional studies revealed that miR-138-2, miR-148a, and miR-488 repress (30%-60%) several candidate genes for panic disorder--GABRA6, CCKBR and POMC, respectively--and that miR-22 regulates four other candidate genes: BDNF, HTR2C, MAOA, and RGS2. Transcriptome analysis of neuroblastoma cells transfected with miR-22 and miR-488 showed altered expression of a subset of predicted target genes for these miRNAs and of genes that might be affecting physiological pathways related to anxiety., Conclusions: This work represents the first report of a possible implication of miRNAs in the etiology of panic disorder., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Copy number variations (CNV) have become an important source of human genome variability noteworthy to consider when studying genetic susceptibility to complex diseases. As recent studies have found evidences for the potential involvement of CNVs in psychiatric disorders, we have studied the dosage effect of structural genome variants as a possible susceptibility factor for different psychiatric disorders in a candidate gene approach., Methods: After selection of 68 psychiatric disorders' candidate genes overlapping with CNVs, MLPA assays were designed to determine changes in copy number of these genes. The studied sample consisted of 724 patients with psychiatric disorders (accounting for anxiety disorders, mood disorders, eating disorders and schizophrenia) and 341 control individuals., Results: CNVs were detected in 30 out of the 68 genes screened, indicating that a considerable proportion of neuronal pathways genes contain CNVs. When testing the overall burden of rare structural genomic variants in the different psychiatric disorders compared to control individuals, there was no statistically significant difference in the total amount of gains and losses. However, 14 out of the 30 changes were only found in psychiatric disorder patients but not in control individuals. These genes include GRM7, previously associated to major depression disorder and bipolar disorder, SLC6A13, in anxiety disorders, and S100B, SSTR5 and COMT in schizophrenia., Conclusions: Although we have not been able to found a clear association between the studied CNVs and psychiatric disorders, the rare variants found only within the patients could account for a step further towards understanding the pathophysiology of psychiatric disorders., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Introduction: The serotonin-1A (5-HT1A) receptor subtypes are considered as targets of a variety of antidepressant drugs. Previous studies have suggested different adaptive changes in pre- and post-synaptic 5-HT receptors in the brain after treatment with non-selective tricyclic antidepressants (TCA) and selective 5-HT re-uptake inhibitors (SSRIs). The present study aimed to investigate the adaptive effect of the TCA imipramine on the post-synaptic 5-HT1A receptor function in the hypothalamus., Methods: A longitudinal design was used in 14 patients with major depressive disorder (DSM-IV) with endogenous features (Newcastle Scale) in order to assess the functional status of post-synaptic 5-HT1A receptors before and after successful antidepressant treatment with imipramine. The effect of the 5-HT1A receptor agonist, buspirone, on ACTH, cortisol, and prolactine (PRL) plasma levels was used to assess the functional status of hypothalamic 5-HT1A receptors. A group of 15 concurrent normal subjects were used as control., Results: Endogenous depressed patients in remission and currently receiving treatment with imipramine (mean length of treatment 145 days, SD=27) presented significantly lower buspirone responses to ACTH and cortisol than in the pre-treatment condition (Deltamax p< or =.05; AUC p<.001) and to ACTH in comparison with healthy controls (Deltamax p<.01; AUC p<.05). No significant differences were found between the post-treatment and pre-treatment PRL responses, or between patients in both conditions and controls; nevertheless, the PRL response in patients in remission and receiving treatment almost reached the values seen in controls., Conclusions: This study extends previous findings from our group using the SSRI citalopram as an antidepressant. Imipramine and citalopram induce similar changes in the endocrine response to buspirone in depressed patients. As the direction of change in ACTH-cortisol and PRL responses after treatment is the opposite, we cannot substantiate increases or decreases in the sensitivity of post-synaptic 5-HT1A receptors in the hypothalamus by long-term imipramine treatment and/or resolution of illness. Therefore, the hormonal changes may result from different or multiples unknown mechanisms., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Our objective was to study the clinical and management differences between primary and interferon (IFN)-induced depressive disorders in malignant melanoma patients visited by the consultation-liaison team during a two year period. This was a prospective study of 31 patients with malignant melanoma treated with IFN-alpha in a general teaching hospital. Clinical, psychiatric variables and DSM-IV-TR diagnosis were analyzed. The Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) of illness scales were administered at the time of consultation and at the end of hospitalization. The main diagnoses were depressive adjustment disorders in 14 patients (45.16%) followed by interferon-induced depressive disorders in 6 (19.36%). In patients with adjustment disorders, melanoma stage was significantly more advanced than in those with interferon-induced depressive disorder (p = 0.019). The latter scored higher in the CGI-S scale (p = 0.044) and in the CGI-I scale (p = 0.029). The interferon-induced depressive disorders, except one who required a reduction of IFN-alpha-2b dose, were successfully treated with antidepressant drugs. Clinical management and antidepressant treatment allowed the continuation of interferon therapy in malignant melanoma patients. Interferon-induced depression occurred in a few patients, which in turn were the most severe. Adjustment depressive disorder was the most common psychiatric diagnosis.

Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders., ((c) 2009 Wiley-Liss, Inc.)

Objective: Pegylated interferon (PegIFN) and ribavirin (RBV) treatment for the hepatitis C virus (HCV) infection can induce depressive episodes. Personality traits have been associated with mood disorders. The aim of this study was to evaluate the personality profile as a risk factor for induced depression by PegIFN and RBV treatment in patients with HCV., Method: In a prospective cohort study, 204 consecutive HCV outpatients who received PegIFN and RBV were assessed using the Structured Clinical Interview for DSM-IV Axis I Disorders and the Temperament and Character Inventory-Revised (TCI-R). Moreover, the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale were administered at baseline and at 4, 12, 24, and/or 48 weeks of treatment. Patients were recruited between September 2003 and December 2006., Results: One hundred eighteen patients (57.8%) were men. The mean (SD) age was 44.39 (10.4) years. The incidence of induced depression during the 48 weeks of antiviral treatment was 73 (42%). Low self-directedness dimension (HR = 0.63, 95% CI = 0.446 to 0.890, p = .009), baseline subclinical depression levels (HR = 1.113, 95% CI = 1.023 to 1.22, p = .013), and history of mood disorders (HR = 0.372, 95% CI = 0.220 to 0.629, p <.001) were independent predictive factors for induced depression during PegIFN and RBV treatment. Other predictive personality TCI-R subscales were enlightened second nature (HR = 2.939, 95% CI = 1.423 to 6.071, p = .004), fatigability (HR = 0.421, 95% CI = 0.237 to 0.749, p = .01), and disorderliness (HR = 0.449, 95% CI = 0.248 to 0.815, p = .008)., Conclusion: Low self-directedness, depressive symptoms at baseline, and history of previous mood disorders may predict induced depression by PegIFN and RBV in euthymic HCV patients., (Copyright 2009 Physicians Postgraduate Press, Inc.)

Unlabelled: Interactions between serotonergic and the endogenous opioid systems have been suggested to be involved in the etiopathogenesis of depression and in the mechanism of action of antidepressants. Activation of serotonin 5-HT1A receptors has been shown to increase plasma beta-endorphin (beta-END) levels in animal studies and in healthy humans., Objectives: To assess interaction abnormalities between 5-HT1A receptors and the endogenous opioid system in patients with major depression and the possible modulating effect of citalopram., Methods: The beta-END response to the 5-HT1A receptor agonist, buspirone (30 mg), was measured in 30 patients with major depression and in 30 age- and sex-matched healthy controls before and after an 8-week treatment with citalopram. Pre-treatment score of the Hamilton Rating Scale for Depression (HRSD) was >or=17. Antidepressant response was defined by a 50% decrease in the HRSD. Pre- and post-treatment maximum peak response (Deltamax) and the area under the curve (AUC) of beta-END response were compared. Three time points were measured (60, 90 and 120 min). We also examined the correlations between the beta-END response and the antidepressant response. Buspirone plasma levels were not measured., Results: At baseline, beta-END response was similar in patients and controls. After 8 weeks of citalopram treatment depressed patients showed a significant decrease in the beta-END response (Deltamax: p<.001; AUC: p<.001). A significant correlation between the beta-END reduction in the response and the reduction in the HRSD score (r=.656; p<.001) was observed., Conclusions: Changes in interaction between 5-HT1A receptor system and the endogenous opioid system may play a role both in the mechanism of action and response to antidepressant drugs.

We still lack operative and theoretically founded definitions of what a personality disorder (PD) is, as well as empirically validated and feasible instruments to measure the disorder construct. The Temperament and Character Inventory (TCI) is the only personality instrument that explicitly distinguishes personality style and disordered functioning. Here, we seek to (1) confirm in a clinical sample that the character dimensions of the TCI capture a general construct of PD across all specific PD subtypes, (2) determine whether such core features can be used to detect the presence of PD, and (3) analyze whether such detection is affected by the presence and severity of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I symptoms. Two hundred five anxious/depressed outpatients were evaluated with the Structural Clinical Interview for DSM-IV Axis I and II Disorders. Assessment also included the TCI, the Hamilton rating scales for depression and anxiety, and the Panic and Agoraphobia Scale. Sixty-one patients (29.8%) were diagnosed as having a DSM-IV PD. Self-directedness and Cooperativeness, but no other TCI dimensions, predicted the presence of PD (Nagelkerke R(2) = 0.35-0.45) and had a moderate diagnostic utility (kappa = 0.47-0.58) when Axis I symptoms were absent or mild. However, accuracy decreased in anxious or depressed patients. Our study supports the hypothesis of a disorder construct that is not related to the intensity of any specific PD subtype but which is common to all PDs. This construct relies largely on internal representations of the self revealing ineffectiveness and uncooperativeness.

Background: Depression and anxiety have been associated with interferon treatment and low treatment adherence., Aim: To study the incidence and associated risk factors of depressive and anxiety disorders during pegylated interferon plus ribavirin and treatment adherence in a prospective cohort of 176 patients with chronic hepatitis C patients., Methods: Patients were interviewed at baseline using the Structured Clinical Interview for DSM-IV Mental Disorders and the Patient Health Questionnaire and the Hospital Anxiety and Depression Scale were completed. Both questionnaires were completed also after 4, 12 and 24 weeks of treatment., Results: De novo depressive and/or anxiety disorders were diagnosed in 53 (36%) patients, in whom antidepressants and/or anxiolytics were administered. Higher baseline depression-subscale score (OR = 27.8, 95% CI = 2.82-333), primary education level (OR = 3.1, 95% CI = 1.40-7.03) and being an immigrant (OR = 3.2, 95% CI = 1.12-9.47) were predictors of psychiatric disorders during anti-viral therapy. The percentage of patients with good adherence was lower in those with depression and/or anxiety (79% vs. 90%, P < 0.04). Only one patient (1%) discontinued treatment because of a major depressive episode. Depression and/or anxiety disorders had no effect on attainment of sustained virological response., Conclusion: Early detection and treatment of depressive and anxiety disorders favours good adherence to anti-viral treatment in hepatitis C.

Objective: Studies examining the relationship between homeless persons and the use of psychiatric emergency services (PES) in a country with universal access to health care are lacking. This study aimed to determine the prevalence of homelessness in adults visiting a PES in Spain, identify the differences between homeless and non-homeless patients in the use of PES and analyze the factors associated with homelessness and the decision to hospitalize., Method: The study included a total of 11 578 consecutive admissions to a PES in a tertiary hospital in Barcelona, Spain, over a 4-year period. Data collected included socio-demographic and clinical information, and score on the Severity of Psychiatric Illness (SPI) scale. Multivariate logistic regression analyses were used to calculate odds ratios for the factors associated with homelessness and the decision to hospitalize., Results: Five hundred sixty (4.8%) admissions were considered homeless. Homeless patients had more psychotic and drug abuse disorders, greater severity of symptoms, more risk of being a danger to others and more frequent hospitalization needs than non-homeless patients. Factors related to homelessness were male gender, substance abuse and immigrant status from North Africa, Sub-Sahara Africa and Western countries. The decision to hospitalize homeless patients was associated with psychosis diagnosis, suicide risk, danger to others, symptom severity, medical problems and noncompliance with treatment., Conclusions: In an attempt to decrease the use of emergency resources and prevent the risk of homelessness, mental health planners in a universal healthcare system should improve outpatient access for populations with risk factors such as substance abuse and immigration.

It has been suggested that interactions between hypothalamic pituitary adrenal (HPA) axis and serotonin-1A (5-HT(1A)) receptor system are involved in the pathophysiology of major depression. Pharmacologic challenge test with 5-HT(1A) receptor agonists is a useful approach to study the sensitivity of 5-HT(1A) receptors in depressed patients and the interaction of these systems. A cross-sectional case-control study was designed to assess the effect of the 5-HT(1A) receptor agonist, buspirone, on 5-HT(1A) receptor function in 30 patients with major depression (DSM-IV) and in 30 age- and sex-matched healthy controls. Depressed patients showed a basal score in the Hamilton Rating Scale for Depression (HRSD) higher than 17. After the administration of a single oral dose of buspirone (30 mg), corticotrophin (ACTH), cortisol, and prolactin (PRL) peak response minus baseline (Delta) and area under the curve (AUC) were evaluated. No significant difference in the hormonal response between depressed patients and controls was observed. No correlation with the severity of depression (HRSD score) was found. These results indicate no consistent changes in the hormonal response to the 5-HT(1A) agonist buspirone in depressed patients. Therefore, this study does not support the hypothesis of an altered postsynaptic 5-HT(1A) receptor function in major depression., (Copyright 2007 John Wiley & Sons, Ltd.)