N-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis

OBJECTIVE: To assess the utility of N-acetylcysteine administration for depressive symptoms in subjects with psychiatric conditions using a systematic review and meta-analysis. DATA SOURCES: A computerized literature search was conducted in MEDLINE, Embase, the Cochrane Library, SciELO, PsycINFO, Scopus, and Web of Knowledge. No year or country restrictions were used. The Boolean terms used for the electronic database search were (NAC OR N-acetylcysteine OR acetylcysteine) AND (depression OR depressive OR depressed) AND (trial). The last search was performed in November 2014. STUDY SELECTION: The literature was searched for double-blind, randomized, placebo-controlled trials using N-acetylcysteine for depressive symptoms regardless of the main psychiatric condition. Using keywords and cross-referenced bibliographies, 38 studies were identified and examined in depth. Of those, 33 articles were rejected because inclusion criteria were not met. Finally, 5 studies were included. DATA EXTRACTION: Data were extracted independently by 2 investigators. The primary outcome measure was change in depressive symptoms. Functionality, quality of life, and manic and anxiety symptoms were also examined. A full review and meta-analysis were performed. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% CIs were calculated. RESULTS: Five studies fulfilled our inclusion criteria for the meta-analysis, providing data on 574 participants, of whom 291 were randomized to receive N-acetylcysteine and 283 to placebo. The follow-up varied from 12 to 24 weeks. Two studies included subjects with bipolar disorder and current depressive symptoms, 1 included subjects with MDD in a current depressive episode, and 2 included subjects with depressive symptoms in the context of other psychiatric conditions (1 trichotillomania and 1 heavy smoking). Treatment with N-acetylcysteine improved depressive symptoms as assessed by Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale when compared to placebo (SMD = 0.37; 95% CI = 0.19 to 0.55; P < .001). Subjects receiving N-acetylcysteine had better depressive symptoms scores on the Clinical Global Impressions-Severity of Illness scale at follow-up than subjects on placebo (SMD = 0.22; 95% CI = 0.03 to 0.41; P < .001). In addition, global functionality was better in N-acetylcysteine than in placebo conditions. There were no changes in quality of life. With regard to adverse events, only minor adverse events were associated with N-acetylcysteine (OR = 1.61; 95% CI = 1.01 to 2.59; P = .049). CONCLUSIONS: Administration of N-acetylcysteine ameliorates depressive symptoms, improves functionality, and shows good tolerability.

Negative reactivity and parental warmth in early adolescence, and depressive symptoms in emerging adulthood

ObjectiveCross-sectional research suggests that relationships between temperamental negative reactivity and adolescent depressive symptoms may be moderated by parental warmth. The primary purpose of this study was to conduct the first prospective analysis of this relationship.MethodData from 1,147 families in an Australian population-based longitudinal study were used to examine: (1) temporal relationships between negative reactivity in early adolescence (13–14 years) and depressive symptoms in emerging adulthood (19–20 years); (2) the moderating role of parent-reported warmth in early adolescence (13–14 years); and (3) the moderating role of child gender. Hierarchical multiple regression was conducted to test the hypothesis that parental warmth would moderate the relationship between early adolescent negative reactivity and depressive symptoms in emerging adulthood.ResultsAfter accounting for previous depressive symptoms at age 13–14 years, negative reactivity was positively associated with later depressive symptoms. By contrast, parental warmth at 13–14 years was negatively associated with later depressive symptoms for females but not males. Parental warmth did not moderate the association between early adolescent negative reactivity and subsequent depressive symptoms.ConclusionsThis study was the first to use prospective data to assess the protective effects of early adolescent parental warmth on the association between negative reactive temperaments and early adult depressive symptoms. Findings suggest that parental warmth for negatively reactive children provides only concurrent protection against subsequent depressive risk. This study did not examine parent–child transactional models, which may, in future longitudinal research, improve understanding of how trajectories of parent–child goodness-of-fit contribute to depressive symptoms.

Neighbourhood environment, physical activity, quality of life and depressive symptoms in Hong Kong older adults: a protocol for an observational study

INTRODUCTION: The neighbourhood environment can assist the adoption and maintenance of an active lifestyle and affect the physical and mental well-being of older adults. The psychosocial and behavioural mechanisms through which the environment may affect physical and mental well-being are currently poorly understood. AIM: This observational study aims to examine associations between the physical and social neighbourhood environments, physical activity, quality of life and depressive symptoms in Chinese Hong Kong older adults.

METHODS AND ANALYSES: An observational study of the associations of measures of the physical and social neighbourhood environment, and psychosocial factors, with physical activity, quality of life and depressive symptoms in 900 Hong Kong older adults aged 65+ years is being conducted in 2012-2016. The study involves two assessments taken 6 months apart. Neighbourhood walkability and access to destinations are objectively measured using Geographic Information Systems and environmental audits. Demographics, socioeconomic status, walking for different purposes, perceived neighbourhood and home environments, psychosocial factors, health status, social networks, depressive symptoms and quality of life are being assessed using validated interviewer-administered self-report measures and medical records. Physical functionality is being assessed using the Short Physical Performance Battery. Physical activity and sedentary behaviours are also being objectively measured in approximately 45% of participants using accelerometers over a week. Physical activity, sedentary behaviours, quality of life and depressive symptoms are being assessed twice (6 months apart) to examine seasonality effects on behaviours and their associations with quality of life and depressive symptoms.

ETHICS AND DISSEMINATION: The study received ethical approval from the University of Hong Kong Human Research Ethics Committee for Non-Clinical Faculties (EA270211) and the Department of Health (Hong Kong SAR). Data are stored in a password-protected secure database for 10 years, accessible only to the named researchers. Findings will be submitted for publication in peer-reviewed journals.

Nurse-led group consultation intervention reduces depressive symptoms in men with localised prostate cancer: a cluster randomised controlled trial

BACKGROUND: Radiotherapy for localised prostate cancer has many known and distressing side effects. The efficacy of group interventions for reducing psychological morbidity is lacking. This study investigated the relative benefits of a group nurse-led intervention on psychological morbidity, unmet needs, treatment-related concerns and prostate cancer-specific quality of life in men receiving curative intent radiotherapy for prostate cancer.

METHODS: This phase III, two-arm cluster randomised controlled trial included 331 men (consent rate: 72 %; attrition: 5 %) randomised to the intervention (n = 166) or usual care (n = 165). The intervention comprised four group and one individual consultation all delivered by specialist uro-oncology nurses. Primary outcomes were anxious and depressive symptoms as assessed by the Hospital Anxiety and Depression Scale. Unmet needs were assessed with the Supportive Care Needs Survey-SF34 Revised, treatment-related concerns with the Cancer Treatment Scale and quality of life with the Expanded Prostate Cancer Index -26. Assessments occurred before, at the end of and 6 months post-radiotherapy. Primary outcome analysis was by intention-to-treat and performed by fitting a linear mixed model to each outcome separately using all observed data.

RESULTS: Mixed models analysis indicated that group consultations had a significant beneficial effect on one of two primary endpoints, depressive symptoms (p = 0.009), and one of twelve secondary endpoints, procedural concerns related to cancer treatment (p = 0.049). Group consultations did not have a significant beneficial effect on generalised anxiety, unmet needs and prostate cancer-specific quality of life.

CONCLUSIONS: Compared with individual consultations offered as part of usual care, the intervention provides a means of delivering patient education and is associated with modest reductions in depressive symptoms and procedural concerns. Future work should seek to confirm the clinical feasibility and cost-effectiveness of group interventions.

Depressive and anxiety symptoms through late pregnancy and the first year post birth : an examination of prospective relationships

One hundred and fifty-nine women were measured for depressive and anxiety symptoms from late pregnancy through to 12 months postpartum. Partial correlations revealed stability of depressive and anxiety symptoms across time. Depressive symptoms did not predict anxiety at any time point. Anxiety predicted increases in depressive symptoms from late pregnancy to early postpartum, but not from early postpartum to mid postpartum. Anxiety predicted depressive symptoms from mid postpartum to late postpartum, however, not when social support in late pregnancy was controlled for.

The inter-relationship between depressive, anxiety and stress symptoms in fathers during the antenatal period

Objective: The aim of this study was to examine whether depressive symptoms predict anxiety and stress or whether anxiety and stress precede depressive symptoms in fathers during the antenatal period. Background: The findings of previous studies suggest that there is an association between paternal depression, anxiety and stress during the antenatal period. However, the temporal inter-relationship between these variables has yet to be investigated. Method: Data were collected from 150 expectant couples at approximately 18, 25 and 33 weeks’ gestation. Results: After accounting for the relative stability of depression, anxiety and stress over time, for men higher levels of anxiety earlier in pregnancy predicted higher levels of depression and stress in middle pregnancy, which predicted higher depression during late pregnancy. A similar relationship remained after partialling out the effects of partner’s depression, perceived social support and sleep quality. Further analyses also revealed significant differences in the manifestation of distress symptoms between men and women, but not between first-time and non-first-time fathers. Conclusion: Our findings indicated a possible inter-relationship between depression, anxiety and stress for men antenatally. Our findings also showed that men who reported elevated depression, anxiety and stress earlier in the antenatal period also reported elevated symptomology at later time points. Finally, the current findings revealed that antenatal paternal stress may play a key role in the development of depression and anxiety later in pregnancy. Therefore, it may be important to screen for early levels of antenatal stress in men, as well as depression and anxiety.

The Relationship of Childhood Family Characteristics and Current Attachment Styles to Depression and Depressive Vulnerability

The role of adult romantic attachment style in the relationship between childhood experiences and current depression was examined. Childhood maltreatment, parental separation/divorce, family adaptability and cohesion during childhood, current attachment style in romantic relationships, vulnerability to depression, and current depressive symptoms were measured in a self-selected sample of adults (N = 133). A large degree of overlap was found in the experience of different types of maltreatment during childhood. Depressive symptoms were uniquely predicted by the sexual abuse and neglect scales, with significant additional variance explained after entering the degree to which respondents' current romantic attachment style was “secure”. Maltreatment and family dysfunction in childhood were significant predictors of depression and vulnerability to depression. Although maltreatment scores did not differentiate between different attachment styles, the degree to which respondents were securely attached may explain -in part -the association between early childhood environment and depressive symptoms in adulthood.

Frequency, severity and effect of life of physical symptoms experienced during pregnancy

This study aimed to: 1) describe the number, frequency, severity of discomfort and effect of symptoms on life of 29 physical symptoms women experienced at 15 to 25 weeks of gestation; 2) explore whether experiencing this group of physical symptoms more frequently and intensely was associated with a higher score of depressive symptoms and lower self-esteem; (3) examine whether discomfort and effect ratings aided prediction of well being over and above symptom frequency; and (4) investigate which individual physical symptoms contributed most to predicting depressive symptoms and self-esteem. Pregnant women (n = 215) completed the Beck Depression Inventory, Rosenberg Self-Esteem Scale, and a physical symptoms questionnaire. Frequency, discomfort, and the effect of physical symptoms all consistently correlated with higher scores for depressive symptoms, but less consistently with lower self-esteem. Discomfort and the effect of symptoms predicted variance in depressive symptoms after accounting for symptom frequency. Higher frequency, more discomfort, and the effect of fatigue and effect of flatulence were related to depressive symptoms. Relationships between pregnancy-related physical symptoms, depressive symptoms, and low self-esteem suggest that when women report any of these constellation of factors, further screening is indicated. A comprehensive assessment of physical symptoms includes frequency, discomfort, and effect on life.

Examination of a multi-factorial model of body-related experiences during pregnancy : the relationships among physical symptoms, sleep quality, depression, self-esteem, and negative body attitudes

The aim of this cross-sectional study was to investigate relationships among women's body attitudes, physical symptoms, self-esteem, depression, and sleep quality during pregnancy. Pregnant women (N = 215) at 15–25 weeks gestation completed a questionnaire including four body image subscales assessing self-reported feeling fat, attractiveness, strength/fitness, and salience of weight and shape. Women reported on 29 pregnancy-related physical complaints, and completed the Beck Depression Inventory, Rosenberg Self-esteem Scale, and Pittsburgh Sleep Quality Index. In regressions, controlling for retrospective reports of body image, more frequent and intense physical symptoms were related to viewing the self as less strong/fit, and to poorer sleep quality and more depressive symptoms. In a multi-factorial model extending previous research, paths were found from sleep quality to depressive symptoms to self-esteem; self-esteem was found to be a mediator associated with lower scores on feeling fat and salience of weight and shape, and on higher perceived attractiveness.

Malondialdehyde plasma concentration correlates with declarative and working memory in patients with recurrent depressive disorder

Oxidative stress has been implicated in the cognitive decline, especially in memory impairment. The purpose of this study was to determine the concentration of malondialdehyde (MDA) in patients with recurrent depressive disorders (rDD) and to define relationship between plasma levels of MDA and the cognitive performance. The study comprised 46 patients meeting criteria for rDD. Cognitive function assessment was based on: The Trail Making Test , The Stroop Test, Verbal Fluency Test and Auditory-Verbal Learning Test. The severity of depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Statistically significant differences were found in the intensity of depression symptoms, measured by the HDRS on therapy onset versus the examination results after 8 weeks of treatment (P < 0.001). Considering the 8-week pharmacotherapy period, rDD patients presented better outcomes in cognitive function tests. There was no statistically significant correlation between plasma MDA levels, and the age, disease duration, number of previous depressive episodes and the results in HDRS applied on admission and on discharge. Elevated levels of MDA adversely affected the efficiency of visual-spatial and auditory-verbal working memory, short-term declarative memory and the delayed recall declarative memory. 1. Higher concentration of plasma MDA in rDD patients is associated with the severity of depressive symptoms, both at the beginning of antidepressants pharmacotherapy, and after 8 weeks of its duration. 2. Elevated levels of plasma MDA are related to the impairment of visual-spatial and auditory-verbal working memory and short-term and delayed declarative memory.

Total antioxidant status correlates with cognitive impairment in patients with recurrent depressive disorder

Depressive disorder is a multifactorial diseases, that one of the typical feature are cognitive impairments. The aim of this study was to determine the total antioxidant status (TAS) in patients with recurrent depressive disorder (rDD) and to define relationship between plasma levels of TAS and the cognitive performance. Design and methods: the study comprised 74 subjects: patients with rDD (n = 45) and healthy subjects (n = 29). Cognitive function assessment was based on: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Statistically significant differences were found in the intensity of depression symptoms, measured by the Hamilton Depression Rating Scale (HDRS) on therapy onset versus the examination results after 8 weeks of treatment (p < 0.001). The level of TAS was substantially higher in patients with rDD (p = 0.01). For rDD patients, elevated TAS levels were associated with worse cognitive test performance. The higher was the concentration of plasma TAS, the greater was the severity of depressive symptoms measured by HDRS before and after pharmacotherapy. (1) Higher concentration of plasma TAS in rDD patients is associated with the severity of depressive symptoms. (2) Elevated levels of plasma TAS are related to impairment of short-term declarative memory, long-term declarative-memory, verbal fluency and working memory.

Validation of patient health questionnaire (PHQ) for major depression in Chinese outpatients with multiple somatic symptoms: A multicenter cross-sectional study

Background: Despite the high co-morbidity of depressive symptoms in patients with multiple somatic symptoms, the validity of the 9-item Patient Health Questionnaire (PHQ-9) has not yet been investigated in Chinese patients with multiple somatic symptoms. Methods: The multicenter cross-sectional study was conducted in ten outpatient departments located in four cities in China. The psychometric properties of the PHQ-9 were examined by confirmative factor analysis (CFA). Criterion validation was undertaken by comparing results with depression diagnoses obtained from the Mini International Neuropsychiatric Interview (MINI) as the gold standard. Results: Overall, 491 patients were recruited of whom 237 had multiple somatic symptoms (SOM+ group, PHQ-15 ≥ 10). Cronbach's α of the PHQ-9 was 0.87, 0.87, and 0.90 for SOM+ patients, SOM- patients, and total sample respectively. All items and the total score were moderately correlated. The factor models of PHQ-9 tested by CFA yielded similar diagnostic performance when compared to sum score estimation. Multi-group confirmatory factor analysis based on unidimensional model showed similar psychometric properties over the groups with low and high somatic symptom burden. The optimal cut-off point to detect depression in Chinese outpatients was 10 for PHQ-9 (sensitivity=0.77, specificity=0.76) and 3 for PHQ-2 (sensitivity=0.77, specificity=0.74). Limitations: Potential selection bias and nonresponse bias with applied sampling method. Conclusions: PHQ-9 (cut-off point=10) and PHQ-2 (cut-off point=3) were reliable and valid to detect major depression in Chinese patients with multiple somatic symptoms.