Life satisfaction mediates the association between childhood maltreatment and depressive symptoms: a study in a sample of Brazilian adolescents.

OBJECTIVE: To evaluate the interrelationships between childhood maltreatment, life satisfaction (LS), and depressive symptoms, and to investigate LS as a mediating factor in the association between childhood maltreatment and depressive symptoms. METHODS: The sample consisted of 342 adolescents, aged 11 to 17 years (mean = 13.3, SD = 1.52 years), recruited from a public school in Salvador, Brazil. Participants filled out instruments for the collection of sociodemographic data and evaluation of childhood maltreatment, LS, and depressive symptoms. Structural equation modeling (SEM) was used to evaluate the mediating effect of LS. RESULTS: We detected significant negative correlations between childhood maltreatment and LS and between LS and depressive symptoms. We observed a significant positive correlation between childhood maltreatment and depressive symptoms. LS partially mediated the association between childhood maltreatment and depressive symptoms, mitigating the impact of maltreatment. CONCLUSION: LS played an important mediating role in the association between childhood maltreatment and depressive symptoms. Longitudinal studies are recommended to fully elucidate these associations, reinforcing the need for attention and care of this vulnerable population.

Serotonin-1A receptor CC genotype is associated with persistent depression related to interferon-alpha in hepatitis C patients.

OBJECTIVE: The aim of this study is to investigate the development of depression during interferon-alpha (IFN-α) therapy and the variations in the expression of the serotonin receptor (5-HTR) and transporter (5-HTT) in hepatitis C patients. METHOD: Hepatitis C patients (n=277) were given the Mini International Neuropsychiatric Interview at the end of IFN-α therapy. Three polymorphisms were genotyped: the serotonin transporter repeat length polymorphic region [5-HTT gene-linked polymorphic region (5-HTTLPR)], as well as SNPs rs25531 and rs6295, located within the 5-HTTLPR and the transcriptional control region of the 5-HTR1A gene, respectively. RESULTS: The diagnosis of current depression, which was associated with IFN-α-related depression (P<.001), demonstrated a statistically significant association with the CC genotype of the 5-HTR1A gene (odds ratio=5.57, 95% confidence interval=1.61-19.24, P=.007). CONCLUSIONS: Persistent depression may represent a more specific type of IFN-α-related psychopathology. Future studies need to investigate the genetic risk factors for vulnerability associated with persistent depression. Limitations, such as the study's cross-sectional design, small sample size and retrospective assessment of IFN-α-induced depression diagnosis, must be taken into account while interpreting the results found in this study.

Reduced posterior corpus callosum area in suicidal and non-suicidal patients with bipolar disorder.

BACKGROUND: Impulsivity is a characteristic of bipolar disorder (BD) that can contribute to the risk for suicidal behavior. Evidence suggests that gray and white matter abnormalities are linked with impulsivity, but little is known about the association between corpus callosum (CC) and impulsivity in BD. We examined the CC area and impulsivity in euthymic bipolar I patients, with and without lifetime history of suicide attempts, and in healthy controls. METHODS: Nineteen bipolar patients with a suicide attempt history (BP-S), 21 bipolar patients without suicide attempt history (BP-NS), and 22 healthy controls (HC) underwent clinical assessment by the Structured Clinical Interview with the DSM-IV axis I (SCID-I), the Barratt Impulsiveness Scale (BIS-11), and MRI scan. RESULTS: No differences were observed for any CC subregion between BP-S and BP-NS groups. There was a significant reduction in the genu (p=0.04) and isthmus areas (p=0.01), in bipolar patients compared with HC. In the BP-S group, the BIS-11 total (p=0.01), attention (p=0.001) and non-planning (p=0.02) impulsivity scores were significantly higher than in the BP-NS and HC groups. LIMITATIONS: These results cannot establish causality because of the cross-sectional nature of the study. CONCLUSION: This report potentially provides evidence that a reduction in the CC area is present even in non-symptomatic bipolar patients, which may be evidence of a biological trait marker for BD. Furthermore, the study demonstrated that BP-S group had higher impulsivity even during euthymia, which points to a sustained association between lifetime history of suicide attempts and impulsivity in BD.

Amygdalar volume in borderline personality disorder with and without comorbid post-traumatic stress disorder: a meta-analysis.

INTRODUCTION: Four studies have found a smaller amygdalar volume in patients with borderline personality disorder (BPD) relative to controls, whereas four other studies have found similar amygdalar volume in BPD patients relative to controls. This study aims to compare amygdalar volumes of BPD patients with controls, and also to compare BPD patients with and without post-traumatic stress disorder (PTSD) with controls in order to determine whether PTSD can explain the heterogeneity of findings. METHOD: Systematic review and meta-analysis of magnetic resonance imaging studies that measured amygdalar volumes in BPD patients and healthy controls. FINDINGS: A significant reduction of amygdalar volumes in BPD patients was confirmed (p < .001). However, data from the studies that discriminated BPD patients with and without PTSD indicated that amygdalar volumes were significantly smaller in BPD patients without PTSD relative to controls (left: p = .02; right: p = .05), but not in BPD patients with PTSD relative to controls (left: p = .08; right: p = .20). CONCLUSION: This meta-analysis suggests that amygdalar volumes are reduced in patients with BPD. This pattern is confirmed in BPD patients without PTSD, but not in BPD patients with PTSD, raising the possibility that reduced amygdalar volume in BPD patients cannot be explained by comorbid PTSD.

Is there an association between suicide attempt and delay of initiation of mood stabilizers in bipolar I disorder?

BACKGROUND: Little is known about the extent to which delay of initiation of mood-stabilizing treatment may influence outcomes in bipolar patients (BP). In this study, our aim was to investigate the association between delay of mood stabilizer treatment in bipolar patients and lifetime history of suicide attempts. METHOD: A consecutive sample of 268 bipolar I outpatients from two teaching hospitals in Brazil was recruited. The assessment included a socio-demographic history form, a clinical interview regarding clinical variables and the Structured Clinical Interview for DSM-IV. Participants were divided into three groups: BP that initiated the first mood stabilizer in the same year of the first episode of the disease (FMS≤1), between 1 and 5 years after the first episode of the disease (15). RESULTS: The mean time from the first episode until the first mood stabilizer medication was 8.6 years (SD 9.8 years). The FMS>5 group, showed a higher lifetime prevalence of suicide attempts than the other two groups (PR=1.75, 95% CI: 1.24-2.47), p=0.001. These results remained significant after adjusting for potential confounders, (PR=1.82, 95% CI: 1.29-2.60), p=0.001. LIMITATIONS: This study evaluated patients retrospectively and does not permit a cause-effect relationship. CONCLUSION: The present study supports the importance of early diagnosis and early intervention for BP in order to limit the potentially lethal impact of the disease.

Lack of association of indoleamine 2,3-dioxygenase polymorphisms with interferon-alpha-related depression in hepatitis C.

BACKGROUND: Major depression is a frequent adverse effect of interferon-alpha (IFN-α) therapy. Although the indoleamine 2,3-dioxygenase (IDO) enzyme seems to be involved in the pathophysiology of IFN-α-induced depression, no pharmacogenetic study has investigated whether variation in the IDO gene modifies vulnerability to this adverse effect. METHODS: A cross-sectional study assessing 277 hepatitis C patients recruited in two specialized outpatient clinics of Brazil. They were interviewed with the Mini International Neuropsychiatric Interview (MINI) approximately 1 month after the end of IFN-α plus ribavirin therapy. Genomic DNA of individuals was extracted from venous blood. Three IDO single-nucleotide polymorphisms (SNPs) were genotyped (rs3824259; rs10089084 and rs35099072). RESULTS: MINI indicated that 21.3% of the sample met criteria for a major depressive episode during the course of IFN-α therapy. No association with the diagnosis of a major depressive episode during the course of IFN-α therapy was observed genotype or allele-wise (p>0.05). Current major depression and/or current anxiety disorder was significantly associated with IFN-α-related depression (p<0.005). However, gender, age, route of infection, result of the antiviral treatment, past history of substance use disorders, depression or any other psychiatric disorder showed no association with IFN-α-related depression (p>0.05). CONCLUSIONS: Our results suggest no influence of the variants in the IDO gene and the diagnosis of interferon-α-related depression in the Brazilian population. Interferon-α-related depression may impose persistent psychopathology on at least 15% of the depressed patients even 2 years after antiviral therapy termination. The cross-sectional design is a limitation of our study, predisposing memory bias. Prospective pharmacogenetic studies are warranted to continue investigation of the impact of IDO polymorphisms on the development of IFN-α-induced depression.

Is the interferon-α-triggered depressive episode a self-limited kind of depression? Four cases of persistent affective symptoms after antiviral treatment in HCV-infected individuals.

OBJECTIVES: To discuss relevant aspects in a series of cases in which interferon-α-triggered depressive symptoms persisted up to 4 years after therapy cessation in HCV-infected patients. METHODS: Two experienced psychiatrists (AGA and LCQ) identified these four cases in a systematic evaluation program of HCV patients in the Hepatology Unit of the Teaching Hospital at the Federal University of Bahia, Brazil. Lifetime psychiatric diagnoses were confirmed by the Mini International Neuropsychiatric Interview (MINI Plus), and a questionnaire was submitted in order to gather clinical and sociodemographic characteristics. RESULTS: In three out of the four cases identified, major depression diagnosis was reached after more than 12 months of interferon-α therapy interruption and, in one case, depression recurred 6 months after antiviral treatment cessation in a patient on antidepressants. The only case that referred a past history of psychiatric diagnosis reported no offer of mental health care despite the presence of a major depressive episode with psychotic features and suicidal behaviour during the cytokine usage. CONCLUSIONS: Interferon-α-triggered depression may remain undiagnosed even in tertiary university hospitals, may persist years after the antiviral therapy cessation, and may recur even in patients on adequate antidepressant treatment.

Can antidepressants prevent interferon-alpha-induced depression? A review of the literature.

OBJECTIVE: To review the literature about the efficacy of antidepressant prophylaxis during interferon-alpha (IFN-alpha) therapy. METHOD: We have performed a database search in PUBMED and ISI Web of Knowledge (1980-August 2009) for the available literature. The keywords "prevention" or "prophylaxis", and "depression", and "interferon", and "antidepressant" or "antidepressive agents" were used. RESULTS: The six eligible studies comprise three randomized controlled trials, two in hepatitis C virus (HCV) patients and one in individuals with melanoma, and three open-label studies with HCV patients. The results of the randomized controlled trials suggest that antidepressant prophylaxis may blunt the magnitude of depressive symptoms in HCV patients and raise the rates of treatment completion. In melanoma patients, this preventive strategy may reduce the incidence of depression during IFN-alpha treatment. In addition, the open-label studies with HCV patients suggest that this strategy may reduce the onset of major depression in specific samples (current psychiatric diagnosis, major depression in remission, past history of IFN-alpha-induced depression) on IFN-alpha (re-)treatment. CONCLUSIONS: In the face of so few trials about the usefulness of prophylaxis with antidepressants before IFN-alpha treatment, there is not enough information to sufficiently and widely support this strategy to prevent depression. However, this approach may, nonetheless, bring some beneficial outcomes, if applied to specific patient groups.

The impact of comorbid posttraumatic stress disorder on bipolar disorder patients.

BACKGROUND: Available data regarding posttraumatic stress disorder (PTSD) in bipolar disorder (BD) are scarce and usually from a limited sample size. The present report was carried out using the Brazilian Research Consortium for Bipolar Disorders and aimed to examine whether patients with BD and comorbid PTSD are at an increased risk for worse clinical outcomes. METHODS: A consecutive sample of bipolar I outpatients from two teaching hospitals in Brazil was recruited. Patients were assessed using the Structured Clinical Interview for DSM-IV, Young Mania Rating Scale, 17-item Hamilton Rating Scale for Depression, and quality of life instrument WHOQOL-BREF. Participants were divided into three groups: a. bipolar patients with PTSD, b. bipolar patients exposed to trauma without PTSD, and c. bipolar patients with no trauma exposure. RESULTS: Of the 405 patients who consented to participate, 87.7% completed the survey. All three groups were similar in terms of demographic parameters. The group with comorbid PTSD reported worse quality of life, more rapid cycling, higher rates of suicide attempts, and a lower likelihood of staying recovered. LIMITATIONS: The cross-sectional design excludes the opportunity to examine causal relationships among trauma, PTSD, and BD. CONCLUSIONS: The findings indicate that PTSD causes bipolar patients to have a worse outcome, as assessed by their lower likelihood to recover, elevated proportion of rapid cycling periods, increased risk of suicide attempts, and worse quality of life.

The effect of early virological response in health-related quality of life in HCV-infected patients.

Twenty-nine HCV-infected patients were treated with pegylated interferon alpha. Diagnosis was based on serum HCV RNA-PCR positive results and liver biopsy. All patients had elevated serum levels of alanine aminotransferase at the time of the study, but liver disease was compensated. Patients were evaluated at baseline treatment and after 4 and 12 weeks of antiviral treatment with the Medical Outcomes Study 36-item Short-Form Health Survey. The Mini-International Neuropsychiatric Interview was used to exclude previous or current psychiatric diagnoses. Both patients and psychiatrists were blind to the HCV RNA status, and serum HCV RNA test results only became available after the visit at week 12. After antiviral treatment, 16 patients (55.2%) were classified as nonresponders and 13 (44.8%) were classified as responders. When compared to nonresponders, responders had a greater improvement in the HRQOL scores for the mental health domain (P < .019). Differences in other domains were not significant. The present study confirms that active viral infection is one possible reason for the poor Health-Related Quality of Life in this population.

High frequency of unrecognized mental disorders in HCV-infected patients.

OBJECTIVE: This study indexed the frequency of psychiatric disorders among hepatitis C virus (HCV)-infected patients. METHOD: HCV-infected patients treated at a university hospital in the northeastern region of Brazil were evaluated in a cross-sectional study using the Mini International Neuropsychiatric Interview. RESULTS: Ninety HCV-infected outpatients were included in the study and 44 (49%) had at least one psychiatric diagnosis. Among the 26 patients (59.1%) with a current psychiatric morbidity, 22 (84.6%) had gone undiagnosed. CONCLUSIONS: HCV-infected patients have a high frequency of unrecognized psychiatric comorbidity.

Double-blind, randomized, placebo-controlled trial of topiramate plus cognitive-behavior therapy in binge-eating disorder.

OBJECTIVE: To evaluate the efficacy and tolerability of adjunctive topiramate compared to placebo in reducing weight and binge eating in obese patients with binge-eating disorder (BED) receiving cognitive-behavior therapy (CBT). METHOD: A double-blind, randomized, placebo-controlled trial of 21 weeks' duration was conducted at 4 university centers. Participants were 73 obese (body mass index >or= 30 kg/m(2)) outpatients with BED (DSM-IV criteria), both genders, and aged from 18 to 60 years. After a 2- to 5-week run-in period, selected participants were treated with group CBT (19 sessions) and topiramate (target daily dose, 200 mg) or placebo (September 2003-April 2005). The main outcome measure was weight change, and secondary outcome measures were binge frequencies, binge remission, Binge Eating Scale (BES) scores, and Beck Depression Inventory (BDI) scores. RESULTS: Repeated-measures random regression analysis revealed a greater rate of weight reduction associated with topiramate over the course of treatment (p < .001), with patients taking topiramate attaining a clinically significant weight loss (-6.8 kg) compared to patients taking placebo (-0.9 kg). Although rates of reduction of binge frequencies, BES scores, and BDI scores did not differ between groups during treatment, a greater number of patients of the topiramate plus CBT group (31/37) attained binge remission compared to patients taking placebo (22/36) during the trial (p = .03). No difference between groups was found in completion rates; 1 patient (topiramate group) withdrew for adverse effect. Paresthesia and taste perversion were more frequent with topiramate, and insomnia was more frequent with placebo (p < .05). CONCLUSIONS: Topiramate added to CBT improved the efficacy of the later, increasing binge remission and weight loss in the short run. Topiramate was well tolerated, as shown by few adverse events during treatment. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00307619.

Obsessive-compulsive disorder: an open-label pilot trial of escitalopram.

INTRODUCTION: Selective serotonin reuptake inhibitors are considered the most effective and well-established pharmacotherapy for the treatment of obsessive-compulsive disorder (OCD), a chronic and disabling condition. However, approximately 40% of patients do not have a significant improvement, suggesting that new medications are needed. This study was designed to investigate the treatment response to escitalopram in OCD patients. METHODS: This open-label study involved 11 adult OCD outpatients diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders. Data were collected and the treatment response was assessed by an experienced psychiatrist by using the Yale-Brown Obsessive-Compulsive Scale. Subjects received escitalopram 30 mg/day for 12 weeks starting at 10 mg/day. Dosage adjustments were made within 2 weeks, depending on the tolerability of the patient. RESULTS: Six of the 11 patients (54.5%) presented a reduction of at least 40% in the baseline total Yale-Brown Obsessive-Compulsive Scale scores. CONCLUSION: Despite the small sample size and the open-label nature of this trial, these data suggest that escitalopram may be a useful option for patients with OCD.