Depression: Lewis G

Anderson IM, Ferrier IN, Baldwin RC, Cowen PJ, Howard L, Lewis G, Matthews K, McAllister-Williams RH, Peveler RC, Scott J, Tylee A. · Senior Lecturer and Honorary Consultant Psychiatrist, Neuroscience and Psychiatry Unit, University of Manchester, UK. · J Psychopharmacol. · Pubmed #18413657 No free full text.

Abstract: A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.

Kessler D, Sharp D, Lewis G. · No affiliation provided · Br J Gen Pract. · Pubmed #16176729 links to  free full text

This publication has no abstract.

Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M, Lewis G. · Academic Unit of Psychiatry, University of Bristol, Bristol, UK. · Lancet. · Pubmed #17662880 No free full text.

Abstract: BACKGROUND: Whether cannabis can cause psychotic or affective symptoms that persist beyond transient intoxication is unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or affective mental health outcomes. METHODS: We searched Medline, Embase, CINAHL, PsycINFO, ISI Web of Knowledge, ISI Proceedings, ZETOC, BIOSIS, LILACS, and MEDCARIB from their inception to September, 2006, searched reference lists of studies selected for inclusion, and contacted experts. Studies were included if longitudinal and population based. 35 studies from 4804 references were included. Data extraction and quality assessment were done independently and in duplicate. FINDINGS: There was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled adjusted odds ratio=1.41, 95% CI 1.20-1.65). Findings were consistent with a dose-response effect, with greater risk in people who used cannabis most frequently (2.09, 1.54-2.84). Results of analyses restricted to studies of more clinically relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately. Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, than for psychosis. A substantial confounding effect was present for both psychotic and affective outcomes. INTERPRETATION: The evidence is consistent with the view that cannabis increases risk of psychotic outcomes independently of confounding and transient intoxication effects, although evidence for affective outcomes is less strong. The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies such as those reviewed here. However, we conclude that there is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life.

Barbui C, Hotopf M, Freemantle N, Boynton J, Churchill R, Eccles MP, Geddes JR, Hardy R, Lewis G, Mason JM. · University of Verona, Department of Medicine and Public Health, Section of Psychiatry, Ospedale Policlinico, 37134 Verona, Italy. · Cochrane Database Syst Rev. · Pubmed #17636706 No free full text.

Abstract: BACKGROUND: Selective serotonin reuptake inhibitors are thought to have better discontinuation rates (i.e. less people dropping out) than tricyclic and heterocyclic antidepressant drugs. It is important to quantify the drop-out rates of different antidepressant drugs in order to have a better understanding of the relative tolerability of these drugs. OBJECTIVES: To assess the comparative tolerability of selective serotonin reuptake inhibitors and tricyclic/heterocyclic antidepressant drugs. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (1997 to 1999), MEDLINE (1966 to 1999), EMBASE (1974 to 1999) We also searched specialist journals, the reference lists of relevant papers and previous systematic reviews, conference abstracts and government documents. Representatives of the pharmaceutical industry were contacted. SELECTION CRITERIA: Parallel group randomised controlled trials comparing selective serotonin reuptake inhibitors with tricyclic or heterocyclic antidepressants in people with depression. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and a third reviewer checked any cases of disagreement. MAIN RESULTS: We included 136 trials. The selective serotonin reuptake inhibitors showed less participants dropping out compared to the tricyclic/heterocyclic group (odds ratio 1.21, 95% confidence interval 1.12 to 1.30). A statistically significant difference was found in total drop-outs between the selective serotonin reuptake inhibitors and the old tricyclics as well as the newer tricyclics. When the selective serotonin reuptake inhibitors were compared to the heterocyclic antidepressants, there was a non significant difference favouring the selective serotonin reuptake inhibitors. The poor tolerability profile of the old tricyclics was explained by differences in drop-outs for side-effects, but not for inefficacy. AUTHORS' CONCLUSIONS: Whilst selective serotonin reuptake inhibitors do appear to show an advantage over tricyclic drugs in terms of total drop-outs, this advantage is relatively modest. This has implications for pharmaco-economic models, some of which may have overestimated the difference of drop-out rates between selective serotonin reuptake inhibitors and tricyclic antidepressants. These results are based on short-term randomised controlled trials, and may not generalise into clinical practice.

Anderson L, Lewis G, Araya R, Elgie R, Harrison G, Proudfoot J, Schmidt U, Sharp D, Weightman A, Williams C. · Academic Unit of Psychiatry, University of Bristol. · Br J Gen Pract. · Pubmed #15904559 links to  free full text

Abstract: BACKGROUND: Depression is a common and important public health problem most often treated by GPs. A self-help approach is popular with patients, yet little is known about its effectiveness. AIM: Our primary aim was to review and update the evidence for the clinical effectiveness of bibliotherapy in the treatment of depression. Our secondary aim was to identify which of these self-help materials are generally available to buy and to examine the evidence specific to these publications. METHOD: Medline, CINAHL, EMBASE, PsycINFO, CCTR, PsiTri and the National Research Register were searched for randomised trials that evaluated self-help books for depression which included participants aged over 16 years with a diagnosis or symptoms of depression. Clinical symptoms, quality of life, costs or acceptability to users were the required outcome measures. Papers were obtained and data extracted independently by two researchers. A meta-analysis using a random effects model was carried out using the mean score and standard deviation of the Hamilton Rating Scale for Depression at the endpoint of the trial. RESULTS: Eleven randomised controlled trials were identified. None fulfilled CONSORT guidelines and all were small, with the largest trial having 40 patients per group. Nine of these evaluated two current publications, Managing Anxiety and Depression (UK) and Feeling Good (US). A meta-analysis of 6 trials evaluating Feeling Good found a large treatment effect compared to delayed treatment (standardised mean difference = -1.36; 95% confidence interval [CI] = -1.76 to -0.96). Five self-help books were identified as being available and commonly bought by members of the public in addition to the two books that had been evaluated in trials. CONCLUSION: There are a number of self-help books for the treatment of depression readily available. For the majority, there is little direct evidence for their effectiveness. There is weak evidence that suggests that bibliotherapy, based on a cognitive behavioural therapy approach is useful for some people when they are given some additional guidance. More work is required in primary care to investigate the cost-effectiveness of self-help and the most suitable format and presentation of materials.

Whitehead C, Moss S, Cardno A, Lewis G. · Bro Taf Health Authority and University of Wales College of Medicine, Cardiff. · Psychol Med. · Pubmed #12785461 No free full text.

Abstract: BACKGROUND: Depression is common in people with schizophrenia and is associated with substantial morbidity and an increased risk of suicide. Our aim was to review systematically all the randomized controlled trials that have investigated the clinical effectiveness of antidepressant medication in the treatment of depression in people who also suffer with schizophrenia. METHOD: Electronic searches of ClinPsych, the Cochrane Library, the Cochrane Schizophrenia Group's Register of Trials, EMBASE and Medline were completed. Reference lists from identified articles were hand searched. RESULTS: Eleven small studies were identified and all randomized fewer than 30 subjects to each group. We could only perform analyses on a subset of the trials. For five trials (aggregate N = 209) the proportion improved in the antidepressant group was 26% (95% CI 10% to 42%) higher than in the placebo group. In six studies (aggregate N = 267) the standardized mean difference on the Hamilton Rating Scale for Depression at the end of the trial was -0.27 (95 % CI -0.7 to 0.2). There was no evidence that antidepressant treatment given during the stable phase of illness led to a deterioration of psychotic symptoms in the included trials. CONCLUSIONS: The literature reviewed was, overall, of poor quality and only a small number of trials could contribute towards the meta-analysis. The results provide weak evidence for the effectiveness of antidepressants in those with schizophrenia and depression and could be explained by publication bias. We need further research to determine the best approach towards treating depression in people with schizophrenia.

Stimpson N, Agrawal N, Lewis G. · University of Wales College of Medicine, Department of Psychological Medicine, Cardiff, Wales, UK. · Br J Psychiatry. · Pubmed #12356654 links to  free full text

Abstract: BACKGROUND: About 30% of people with depression do not respond to an antidepressant at the recommended dose and can be described as having treatment-refractory depression. AIMS: To summarise the findings from all randomised controlled trials (RCTs) that have assessed the efficacy of a pharmacological or psychological intervention for treatment-refractory depression. METHOD: We used a systematic search strategy to identify RCTs that included adults aged 18-75 years with a diagnosis of unipolar depression that had not responded to a 4-week course of a recommended dose of an antidepressant. RESULTS: We identified 16 RCTs. None of the included trials assessed the efficacy of psychotherapy. All the trials were too small to detect an important clinical response. We found only two trials on lithium augmentation, which randomised 50 subjects in total. CONCLUSIONS: There is little evidence to guide the management of depression that has not responded to a course of antidepressants. Treatment-refractory depression is an important public health problem and large pragmatic trials are needed to inform clinical practice.

Whitehead C, Moss S, Cardno A, Lewis G. · Public Health and Policy, Bro Taf Health Authority, Temple of Peace & Health, Cathays Park, Cardiff, South Wales, UK, CF10 3NW. · Cochrane Database Syst Rev. · Pubmed #12076447 No free full text.

Abstract: BACKGROUND: Depressive symptoms, often of substantial severity, are found in 50% of newly diagnosed suffers of schizophrenia and 33% of people with chronic schizophrenia who have relapsed. Depression is associated with dysphoria, disability, reduction of motivation to accomplish tasks and the activities of daily living, an increased duration of illness and more frequent relapses. OBJECTIVES: To determine the clinical effects of antidepressant medication for the treatment of depression in people who also suffer with schizophrenia. SEARCH STRATEGY: We undertook electronic searches of the Cochrane Schizophrenia Group's Register (October 2000), ClinPsych (1988-2000), The Cochrane Library (Issue 3, 2000), EMBASE (1980-2000) and MEDLINE (1966-2000). This was supplemented by citation searching, personal contact with authors and pharmaceutical companies. SELECTION CRITERIA: All randomised clinical trials that compared antidepressant medication with placebo for people with schizophrenia or schizoaffective disorder who were also suffering from depression. DATA COLLECTION AND ANALYSIS: Data were independently selected and extracted. For homogeneous dichotomous data the fixed effects risk difference (RD), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences. Statistical tests for heterogeneity were also undertaken. MAIN RESULTS: Eleven studies met the inclusion criteria. All were small, and randomised fewer than 30 people to each group. Most included people after the most acute phase of psychosis and investigated a wide range of antidepressants. The quality of reporting varied a great deal. For the outcome of 'no important clinical response' antidepressants were significantly better than placebo (n=209, 5 RCTs, summary risk difference fixed effects -0.26, 95% CI -0.39 to -0.13, NNT 4 95% CI 3 to 8). The depression score at the end of the trial, as assessed by the Hamilton Rating Scale (HAM-D), seemed to suggest that using antidepressants was beneficial, but this was only statistically significant when a fixed effects model was used (n=261, 6 RCTs, WMD fixed effects -2.2 95% CI -3.8 to -0.6; WMD random effects -2.1 95% CI -5.04 to 0.84). There was no evidence that antidepressant treatment led to a deterioration of psychotic symptoms in the included trials. Heterogeneous data on 'any adverse effect' are equivocal (n=110, 2 RCTs, RD fixed 0.11 CI -0.03 to 0.25, Chi square 7.5, df=1, p=0.0062). In one small study extrapyramidal adverse effects were reported less often by those allocated to antidepressant (n=52, 1 RCT, RD fixed -0.28 CI -0.5 to -0.04). Only about 10% of people left these studies by 12 weeks. There was no apparent difference between those allocated placebo and those given an antidepressant (n=426, 10 RCTs, RD fixed 0.04 CI -0.02 to 0.1). REVIEWER'S CONCLUSIONS: Overall, the literature was of poor quality, and only a small number of trials made useful contributions. Though our results provide some evidence to indicate that antidepressants may be beneficial for people with depression and schizophrenia, the results, at best, are likely to overestimate the treatment effect, and, at worst, could merely reflect selective reporting of statistically significant results and publication bias. At present, there is no convincing evidence to support or refute the use of antidepressants in treating depression in people with schizophrenia. We need further well-designed, conducted and reported research to determine the best approach towards treating depression in people with schizophrenia.

Lewis G, Araya R. · Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK. · Br Med Bull. · Pubmed #11719921 No free full text.

Abstract: Depression is a common and disabling illness. For some time the disability has been relatively neglected by those interested in public health. Public health priorities have largely been determined by statistics on mortality. The World Health Organization has argued for some time that public health should be concerned with 'adding life to years' as well as 'adding years to life'. This article will argue that depression should be a key priority for public health research.

Barbui C, Hotopf M, Freemantle N, Boynton J, Churchill R, Eccles MP, Geddes JR, Hardy R, Lewis G, Mason JM. · Department of Psychological Medicine, Institute of Psychiatry, De Crespigny Park, London, UK, SE5 8AF. · Cochrane Database Syst Rev. · Pubmed #11034764 No free full text.

Abstract: BACKGROUND: Selective serotonin reuptake inhibitors are thought to have better discontinuation rates (i.e. less people dropping out) than tricyclic and heterocyclic antidepressant drugs. It is important to quantify the drop-out rates of different antidepressant drugs in order to have a better understanding of the relative tolerability of these drugs. OBJECTIVES: To assess the comparative tolerability of selective serotonin reuptake inhibitors and tricyclic/heterocyclic antidepressant drugs. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (1997 to 1999), MEDLINE (1966 to 1999), EMBASE (1974 to 1999) We also searched specialist journals, the reference lists of relevant papers and previous systematic reviews, conference abstracts and government documents. Representatives of the pharmaceutical industry were contacted. SELECTION CRITERIA: Parallel group randomised controlled trials comparing selective serotonin reuptake inhibitors with tricyclic or heterocyclic antidepressants in people with depression. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and a third reviewer checked any cases of disagreement. MAIN RESULTS: We included 136 trials. The selective serotonin reuptake inhibitors showed less participants dropping out compared to the tricyclic/heterocyclic group (odds ratio 1.21, 95% confidence interval 1.12 to 1.30). A statistically significant difference was found in total drop-outs between the selective serotonin reuptake inhibitors and the old tricyclics as well as the newer tricyclics. When the selective serotonin reuptake inhibitors were compared to the heterocyclic antidepressants, there was a non significant difference favouring the selective serotonin reuptake inhibitors. The poor tolerability profile of the old tricyclics was explained by differences in drop-outs for side-effects, but not for inefficacy. REVIEWER'S CONCLUSIONS: Whilst selective serotonin reuptake inhibitors do appear to show an advantage over tricyclic drugs in terms of total drop-outs, this advantage is relatively modest. This has implications for pharmaco-economic models, some of which may have overestimated the difference of drop-out rates between selective serotonin reuptake inhibitors and tricyclic antdepressants. These results are based on short-term randomised controlled trials, and may not generalise into clinical practice.

Bell T, Watson M, Sharp D, Lyons I, Lewis G. · Dept. of Epidemiology, Statistics and Public Heath, Wales College of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. · Soc Psychiatry Psychiatr Epidemiol. · Pubmed #15902411 No free full text.

Abstract: BACKGROUND: The General Health Questionnaire (GHQ) has been used extensively in community and primary care research as an alternative to longer, time-consuming and more expensive assessments of the common mental disorders of depression and anxiety. The sensitivity and specificity of the GHQ compared with longer more detailed assessments is between 70 and 80%. Though satisfactory, this raises the concern about the possibility of bias in relation to longer assessments. We studied socio-demographic factors that were associated with being a false positive on the GHQ in order to investigate any ascertainment bias in relation to more detailed assessments. METHOD: A total of 7,357 consecutive patients aged 16 and over, in five general practices in Cardiff, Bristol and Pontypridd, were invited to complete the 12-item GHQ. Of these, 1,154 patients scored 3 or more, our case definition on the GHQ, and completed a computerised version of the Revised Clinical Interview Schedule (CIS-R) together with a short socio-demographic questionnaire. RESULTS: Of the 1,154 subjects who were cases on the GHQ, 344 (30 %) (95% CI 27%-32%) were false positive and were not cases on the CIS-R. After adjustment for the other variables, including GHQ score, false positive subjects were more likely to be employed [odds ratio (OR) 2.7, 95% CI 1.4-5.3], owner-occupiers (OR 1.6, 95% CI 1.0-2.4) and to have a close friend or relative to talk to about personal problems (OR 2.2, 95 % CI 1.4-3.5). CONCLUSION: Our results suggest that in this study there was an ascertainment bias on the GHQ in relation to the CIS-R. Studies that use the GHQ to study the relationship between socio-economic status and common mental disorder could lead to biased estimates of association compared to studies that use the CIS-R. It is likely that the GHQ will lead to a higher estimate of prevalence than the CIS-R in subjects who are better off financially and who have better social support.

Thomas HV, Lewis G, Watson M, Bell T, Lyons I, Lloyd K, Weich S, Sharp D. · Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK. · Br J Gen Pract. · Pubmed #15527609 links to  free full text

Abstract: BACKGROUND: A large proportion of people with depression and anxiety go unrecognised by their general practitioner (GP). Case-finding does not appear to be effective on its own. AIM: To compare the effectiveness of case-finding followed by computer-generated patient-specific guidelines with usual care for the management of common mental disorders in primary care.Design of study: Individual patient randomised controlled trial. SETTING: Five general practices in Bristol and Cardiff.METHOD: 762 individuals aged >/= 16 years scoring >/= 12 on the Clinical Interview Schedule Revised were randomised. The experimental intervention required participants to complete a computerised psychosocial assessment that generated a report for the GP including patient-specific treatment recommendations. The control patients were treated as usual with access to locally agreed guidelines.RESULTS: Participants' 12-item General Health Questionnaire (GHQ) score dropped irrespective of treatment allocation. The experimental group had a significantly lower GHQ score at 6 weeks, but not at 6 months. Recovery at 6 months was 3% greater among those receiving the experimental intervention (95% confidence interval [CI] = -4 to 10). Treatment was not significantly associated with quality of life or patient satisfaction.CONCLUSION: Only small benefits are likely from using case-finding followed by patient-specific guidelines to improve clinical management of common mental disorders in primary care. However, depression and anxiety are important public health problems so the utility of such systems should be further investigated.

Araya R, Hu X, Heron J, Enoch MA, Evans J, Lewis G, Nutt D, Goldman D. · University of Bristol, United Kingdom. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #19016475 No free full text.

Abstract: There has been a large but inconsistent literature on interactions between the 5-HTTLPR polymorphism of the serotonin transporter gene and adversity on emotional disorders. We investigated these interactions in 4,334 children from a birth longitudinal cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). We measured emotional symptoms at 7 years with the Strengths and Difficulties Questionnaire. Mothers rated stressful life events between ages 5 and 7 years. Maternal depression was defined as a score > or =12 on the Edinburgh Postnatal Depression Scale at 2 or 8 months postnatally. Triallelic genoptyping of the 5-HTTLPR polymorphism was performed. We found strong associations between stressful life events (OR 1.19; 1.12-1.26; P < 0.01) and maternal postnatal depression (OR 1.91; 1.63-2.24; P < 0.01) with emotional symptoms in the children. There were no main 5-HTTLPR genotype effects or significant interactions between genotype and life events or maternal postnatal depression on emotional symptoms. There was marginal evidence (P = 0.08) for an interaction between stressful life events and genotype in boys only, with those in the low and high 5-HTTLPR expression groups showing stronger associations. In these 7-year-old children, we did not replicate previously reported G x E interactions between 5-HTTLPR and life events for emotional symptoms. Gene by environment interactions may be developmentally dependent and show variation depending on the type and levels of exposure and sex. Young cohorts are essential to improve our understanding of the impact of development on gene and environment interactions.

Munafò MR, Durrant C, Lewis G, Flint J. · Department of Experimental Psychology, University of Bristol, Bristol, United Kingdom. · Biol Psychiatry. · Pubmed #18691701 No free full text.

Abstract: BACKGROUND: Although it is universally accepted that human disease and behavior depend upon both environmental and genetic variation, a view supported by family and twin studies, examples of environmental interactions with genes identified at the molecular level (G x E) are not so well established. METHODS: We carried out a systematic review and meta-analysis of the serotonin transporter (5-HTTLPR) polymorphic region x stressful life event (SLE) literature and investigated to what extent the main effects reported in this literature are consistent with a number of G x E hypotheses. Our aim was to provide a framework in which to assess the robustness of the claim for the presence of an interaction. RESULTS: The results from our systematic review and meta-analysis indicate that the main effect of 5-HTTLPR genotype and the interaction effect between 5-HTTLPR and SLE on risk of depression are negligible. We found that only a minority of studies report a replication that is qualitatively comparable to that in the original report. CONCLUSIONS: Given reasonable assumptions regarding likely genetic and environmental effect sizes, our simulations indicate that published studies are underpowered. This, together with other aspects of the literature, leads us to suggest that the positive results for the 5-HTTLPR x SLE interactions in logistic regression models are compatible with chance findings.

Zammit S, Horwood J, Thompson A, Thomas K, Menezes P, Gunnell D, Hollis C, Wolke D, Lewis G, Harrison G. · The Academic Unit of Psychiatry, University of Bristol, Bristol, UK. · Schizophr Res. · Pubmed #18562177 No free full text.

Abstract: Psychosis-like symptoms (PLIKS) occur in about 15% of the population, but it is unclear to what extent PLIKS share aetiological mechanisms in common with those for schizophrenia. We examined whether the presence of PLIKS was associated with a family history of schizophrenia (FH-SCZ), or with advancing paternal age, using data from 6356 children in the ALSPAC birth cohort who participated in a semi-structured PLIKS interview at 12 years of age. We found no evidence of association between FH-SCZ and suspected or definite PLIKS (adjusted OR=0.94, 95%CI 0.44, 2.00; p=0.880). There was weak evidence that advancing paternal age was associated with increased PLIKS (adjusted OR per 10-year age increase=1.23, 95%CI 0.99, 1.55; p=0.058). Although not a priori hypotheses, family history of depression (adjusted OR=1.28, 95%CI 1.04, 1.57; p=0.018), and younger maternal age (adjusted OR per 10-year age increase=0.62, 95% CI 0.47, 0.82; p<0.001) both showed stronger evidence of association with suspected or definite PLIKS. Overall our findings provide little evidence that these established risk factors for schizophrenia show a similar relationship with PLIKS, suggesting that the presence of PLIKS is unlikely to be a strong marker of early expression of the pathology underlying schizophrenia. Whether future studies of PLIKS will increase our understanding of mechanisms underlying the development of schizophrenia, or prove useful in prediction of this disorder, remains to be seen.

Evans J, Xu K, Heron J, Enoch MA, Araya R, Lewis G, Timpson N, Davies S, Nutt D, Goldman D. · University of Bristol, Cotham Hill, UK. · Am J Med Genet B Neuropsychiatr Genet. · Pubmed #18535998 No free full text.

Abstract: Early adversity predicts anxiety and depression but variation in response to adversity is not understood. We investigated whether association between early adversity and emotional symptoms in young children differs according to variation of the COMT gene. The main outcome measure was the emotionality subscale of the Strengths and Difficulties Questionnaire (SDQ) completed by mothers for 8,431 children aged 6-7 years old in the Avon Longitudinal Study of Parents and Children. Adversity measures included exposure to maternal postpartum depressive symptoms and adverse life events for children. DNA from the children was genotyped for five COMT polymorphisms including the COMT Val158Met locus. Maternal depression increased the odds of high emotionality in the children, (OR 1.99, 95% CI 1.73-2.29, P < 0.001) as did life events score, (OR 1.21 for each s.d. increase in life event score, 95% CI 1.15-1.27, P < 0.001). There was no main effect of Val158Met genotype on emotional symptoms (OR for effect of each copy of the methionine allele was 1.04, 95% CI 0.97-1.10, P = 0.284). The relationship between adversity and emotional symptoms did not vary by genotype (G x E for maternal depression chi(2) = 3.17, P = 0.205; G x E for life events chi(2) = 1.69, P = 0.430). There was no main effect of COMT haplotype, nor was there an interaction with adversity. Early adversity predicts emotional symptoms in children aged 6-7 years. Although some studies indicate a role for COMT in emotionality, anxiety, and depression in adults, no direct effect or interaction of COMT genotype was observed in this large sample of young children.

Thomas L, Mulligan J, Mason V, Tallon D, Wiles N, Cowen P, Nutt D, O'Donovan M, Sharp D, Peters T, Lewis G. · Department of Community Based Medicine, University of Bristol, 25 Belgrave Road, Bristol, BS8 2AA, UK. · Trials. · Pubmed #18498636 links to  free full text

Abstract: ABSTRACT: BACKGROUND: The most effective pharmacological treatments for depression inhibit the transporters that reuptake serotonin (Selective Serotonin Reuptake Inhibitors - SSRIs) and noradrenaline (Noradrenaline Reuptake Inhibitors - NaRIs) into the presynaptic terminal. There is evidence to suggest that noradrenaline and serotonin enhancing drugs work through separate mechanisms to produce their clinical antidepressant action. Although most of the current evidence suggests there is little difference in overall efficacy between SSRIs and NaRIs, there are patients who respond to one class of compounds and not another. This suggests that treatment response could be predicted by genetic and/or clinical characteristics.Firstly, this study aims to investigate the influence of a polymorphism (SLC6A4) in the 5HT transporter in altering response to SSRI medication. Secondly, the study will investigate whether those with more severe depression have a better response to NaRIs than SSRIs. METHODS/DESIGN: The GenPod trial is a multi-centre randomised controlled trial. GPs referred patients aged between 18-74 years presenting with a new episode of depression, who did not have any medical contraindications to antidepressant medication and who had no history of psychosis or alcohol/substance abuse. Patients were interviewed to ascertain their suitability for the study. Eligible participants (with a primary diagnosis of depression according to ICD10 criteria and a Beck Depression Inventory (BDI) score > 14) were randomised to receive one of two antidepressant treatments, either the SSRI Citalopram or the NaRI Reboxetine, stratified according to severity. The final number randomised to the trial was 601. Follow-up assessments took place at 2, 6 and 12 weeks following randomisation. Primary outcome was measured at 6 weeks by the BDI. Outcomes will be analysed on an intention-to-treat basis and will use multiple regression models to compare treatments. DISCUSSION: The results of the trial will provide information about targeting antidepressant treatment for individual patients; in turn this may increase prescribing efficacy, thereby speeding recovery and reducing the cost to the NHS. It will also help to understand the different roles that noradrenaline and serotonin might play in the biology of depression.The trial is expected to report in the autumn of 2008. TRIAL REGISTRATION: ISRCTN 31345163.

David AS, Zammit S, Lewis G, Dalman C, Allebeck P. · Section of Cognitive Neuropsychiatry, Institute of Psychiatry, King's College, London, UK. · Schizophr Bull. · Pubmed #18441331 No free full text.

Abstract: It is well established that cognitive deficits are an almost invariable component of the schizophrenia syndrome. Much less is known about the association of cognitive deficits and the range of psychiatric disorders. The current study made use of a Swedish conscript cohort which included an IQ assessment and full psychiatric evaluation at conscription of all 18- to 19-year-old males. It was found that reduced intellectual functioning was found in association with psychosis and neurotic disorders including depression, personality disorders, alcoholism, and drug dependence. The effect was particularly strong for alcoholism. This presumably represents a combination of premorbid deficits (as demonstrated in those who developed schizophrenia some years later) plus coincident impairments. The direction of causality of this latter association is likely to be both forward and reverse. Different cognitive subtests showed varied strengths of association: "mechanical ability/knowledge," which might reflect planning and reasoning more than the other subtests, had the strongest effect. Cognitive deficits are widespread in psychiatric disorders and should be taken into account in clinical interactions.

Rojas G, Fritsch R, Solis J, Jadresic E, Castillo C, González M, Guajardo V, Lewis G, Peters TJ, Araya R. · Hospital Clínico, Facultad de Medicina, Universidad de Chile, Santiago, Chile. · Lancet. · Pubmed #17993363 No free full text.

Abstract: BACKGROUND: The optimum way to improve the recognition and treatment of postnatal depression in developing countries is uncertain. We compared the effectiveness of a multicomponent intervention with usual care to treat postnatal depression in low-income mothers in primary-care clinics in Santiago, Chile. METHODS: 230 mothers with major depression attending postnatal clinics were randomly allocated to either a multicomponent intervention (n=114) or usual care (n=116). The multicomponent intervention involved a psychoeducational group, treatment adherence support, and pharmacotherapy if needed. Usual care included all services normally available in the clinics, including antidepressant drugs, brief psychotherapeutic interventions, medical consultations, or external referral for specialty treatment. The primary outcome measure was the Edinburgh postnatal depression scale (EPDS) score at 3 and 6 months after randomisation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00518830. FINDINGS: 208 (90%) of women randomly assigned to treatment groups completed assessments. The crude mean EPDS score was lower for the multicomponent intervention group than for the usual care group at 3 months (8.5 [95% CI 7.2-9.7] vs 12.8 [11.3-14.1]). Although these differences between groups decreased by 6 months, EPDS score remained better in multicomponent intervention group than in usual care group (10.9 [9.6-12.2] vs 12.5 [11.1-13.8]). The adjusted difference in mean EPDS between the two groups at 3 months was -4.5 (95% CI -6.3 to -2.7; p<0.0001). The decrease in the number of women taking antidepressants after 3 months was greater in the intervention group than in the usual care group (multicomponent intervention from 60/101 [59%; 95% CI 49-69%] to 38/106 [36%; 27-46%]; usual care from 18/108 [17%; 10-25%] to 11/102 [11%; 6-19%]). INTERPRETATION: Our findings suggest that low-income mothers with depression and who have newly born children could be effectively helped, even in low-income settings, through multicomponent interventions. Further refinements to this intervention are needed to ensure treatment compliance after the acute phase.

Haynes JC, Farrell M, Singleton N, Meltzer H, Araya R, Lewis G, Wiles NJ. · Avon and Wiltshire Partnership NHS Mental Healthcare Trust, and Academic Unit of Psychiatry, Department of Community Based Medicine, University of Bristol, Bristol, UK. · Psychol Med. · Pubmed #17977480 No free full text.

Abstract: BACKGROUND: Alcohol is commonly considered to be associated with persistence of common mental disorder (CMD; anxiety/depression). However no community-based longitudinal studies have investigated the direction of causality. METHOD: We examined the association between alcohol consumption and recovery from CMD using data on 706 community-based subjects with CMD who were followed for 18 months. Alcohol consumption at baseline was defined as hazardous drinking [Alcohol Use Disorders Identification Test (AUDIT) 8], binge drinking (defined as six or more units of alcohol on one occasion, approximately two to three pints of commercially sold beer) and dependence. RESULTS: When compared with a non-binge-drinking group, non-recovery at follow-up was associated with binge drinking on at least a monthly basis at baseline, although the confidence interval (CI) included unity [adjusted odds ratio (OR) 1.47, 95% CI 0.89-2.45]. There was also weak evidence that alcohol dependence was associated with non-recovery (adjusted OR 1.37, 95% CI 0.67-2.81). There was little evidence to support hazardous drinking as a risk factor for non-recovery (adjusted OR 1.12, 95% CI 0.67-1.88). CONCLUSIONS: Binge drinking may be a potential risk factor for non-recovery from CMD, although the possibility of no effect cannot be excluded. Larger studies are required to refute or confirm this finding.

Mason VL, Shaw A, Wiles NJ, Mulligan J, Peters TJ, Sharp D, Lewis G. · Psychology and Health Sciences, University of Worcester, Henwick Grove, Worcester, UK. · Fam Pract. · Pubmed #17698979 links to  free full text

Abstract: OBJECTIVE: To investigate the perceived barriers among GPs towards introducing participation in randomized controlled trials (RCTs) to patients presenting with depression during consultations. METHODS: Qualitative study using semi-structured interviews. Interviews were recorded using a digital voice recorder, transcribed verbatim and analysed using the Framework Approach. The participants were 41 GPs from five primary care trusts in the South West who were collaborating with the University of Bristol on an RCT recruiting patients with depression. RESULTS: Three themes were identified: (i) concern about protecting the vulnerable patient and the impact on the doctor-patient relationship; (ii) the perceived lack of skill and confidence of GPs to introduce a request for research participation within a potentially sensitive consultation; and (iii) the priority given to clinical and administrative issues over research participation. These themes were underpinned by GPs' observations that consultations with people about depression differed in content, style and perceived difficulty compared to other types of consultations. CONCLUSION: Depressed patients were often viewed as vulnerable and in need of protection and it was seen as difficult and intrusive to introduce research. Patients were not always given the choice to participate in research in the same way that they are encouraged to participate in treatment decision making. A lack of skills in introducing research could be addressed with training through the new Primary Care Research Network. A more radical change in clinician attitudes and policy may be needed in order to give research a higher priority within primary care.

Araya R, Gaete J, Rojas G, Fritsch R, Lewis G. · Academic Unit of Psychiatry, University of Bristol, Cotham House, Cotham Hill, Bristol, BS6 6JL, UK. · Soc Psychiatry Psychiatr Epidemiol. · Pubmed #17676252 No free full text.

Abstract: BACKGROUND: Smoking and common mental disorders (CMD), anxiety and depression, tend to co-exist and are important public health challenges for countries at all levels of development. We aimed to study the association between smoking and common mental disorders after adjusting for alcohol, illicit drug use and other confounders. METHODS: Cross-sectional household survey. CMD were assessed with a detailed psychiatric interview and smoking, alcohol, and illicit drug use with self-reported questionnaires. RESULTS: About 3,870 randomly selected adults were interviewed of whom 12.9% (95% CI 12-15) met criteria for ICD-10 CMD diagnoses. 38% (36-40) of the respondents were current smokers and 11% (10-13) ex-smokers. There was a robust association between heavier smoking and the presence and severity of CMD. However there were no major differences between non-smokers, ex-smokers and light smokers. In the fully adjusted models those individuals with ICD-10 CMD were significantly more likely to be current smokers [OR 1.6 (1.1-2.2)]. Smoking was also strongly associated with drinking heavily [OR 5.4 (4.0-7.3)] and illicit drug use [(OR 2.1 (1.1-4.1)] but there were no significant interactions. CONCLUSIONS: Smoking is highly prevalent and associated with CMD and other addictive behaviours in Chile. These are major public health problems in need of urgent action.

Torres AR, Prince MJ, Bebbington PE, Bhugra DK, Brugha TS, Farrell M, Jenkins R, Lewis G, Meltzer H, Singleton N. · Department of Neurology and Psychiatry, Botucatu Medical School, Universidade Estadual Paulista (UNESP), Distrito de Rubião Jr., Botucatu (São Paulo), Brazil, 18618-970. · Psychiatr Serv. · Pubmed #17602015 links to  free full text

Abstract: OBJECTIVE: For several reasons, many individuals with obsessive-compulsive disorder (OCD) do not seek treatment. However, data on treatment seeking from community samples are scant. This study analyzed service use by adults with OCD living in private households in Great Britain. METHODS: Data from the British Survey of Psychiatric Morbidity of 2000, in which 8,580 individuals were surveyed, were analyzed. Service use was compared for those with OCD, with other neuroses, with different subtypes of OCD (only obsessions, only compulsions, or both), and with OCD and comorbid neuroses. RESULTS: Persons with OCD (N=114) were more likely than persons with other neuroses (N=1,395) to be receiving treatment (40% compared with 23%, p<.001). However, those with OCD alone (N=38) were much less likely than those with OCD and a comorbid disorder to be in treatment (14% compared with 56%, p<.001). In the previous year, 9.4% of persons with OCD had seen a psychiatrist and 4.6% had seen a psychologist. Five percent were receiving cognitive-behavioral therapy, 2% were taking selective serotonin reuptake inhibitors, and 10% were taking tricyclics. CONCLUSIONS: Most persons with OCD were not in contact with a mental health professional, and apparently very few were receiving appropriate treatments. Very few persons with noncomorbid OCD were receiving treatment. Individuals with OCD who are in treatment may not be disclosing their obsessions and compulsions and may be discussing other emotional symptoms, leading to inappropriate treatment strategies. Public awareness of OCD symptoms should be raised, and primary care professionals should inquire about them with all patients who have depressive or anxiety disorders.

Wiles NJ, Haase AM, Gallacher J, Lawlor DA, Lewis G. · Academic Unit of Psychiatry, Department of Community-Based Medicine, Faculty of Medicine and Dentistry, University of Bristol, Bristol, United Kingdom. · Am J Epidemiol. · Pubmed #17272287 links to  free full text

Abstract: The authors examined associations between leisure-time and occupational physical activity and common mental disorder (CMD), defined as anxiety and depression, using data from a cohort of middle-aged men in Caerphilly, South Wales, United Kingdom, who were followed for 5 years (1989-1993) and 10 years (1993-1997). CMD was measured using the General Health Questionnaire. Total leisure-time activity and percentage of time spent in heavy-intensity activity were estimated from self-reports (Minnesota Leisure Time Physical Activity Questionnaire). Men were classified into four classes of occupational activity. Among 1,158 men with complete data, those who participated in any heavy-intensity leisure-time activity had reduced odds of CMD 5 years later (below median vs. none: adjusted odds ratio (OR(adj)) = 0.61, 95% confidence interval (CI): 0.40, 0.93); median or above vs. none: OR(adj) = 0.54, 95% CI: 0.35, 0.83). Analyses using multiple imputation to deal with missing data found weaker evidence for an association (OR(adj) = 0.79 (95% CI: 0.54, 1.15) and OR(adj) = 0.73 (95% CI: 0.49, 1.09), respectively). There was little evidence that men in the most physically demanding jobs had reduced odds of CMD after 5 years, and there was no association between physical activity and CMD 10 years later. Among these men, heavy-intensity leisure-time physical activity was associated with a small reduction in CMD over 5 years.

Torres AR, Prince MJ, Bebbington PE, Bhugra D, Brugha TS, Farrell M, Jenkins R, Lewis G, Meltzer H, Singleton N. · Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK. · Am J Psychiatry. · Pubmed #17074950 links to  free full text

Abstract: OBJECTIVE: There is little information about obsessive-compulsive disorder in large representative community samples. The authors aimed to establish obsessive-compulsive disorder prevalence and its clinical typology among adults in private households in Great Britain and to obtain generalizable estimates of impairment and help-seeking. METHOD: Data from the British National Psychiatric Morbidity Survey of 2000, comprising 8,580 individuals, were analyzed using appropriate measurements. The study compared individuals with obsessive-compulsive disorder, individuals with other neurotic disorders, and a non-neurotic comparison group. ICD-10 diagnoses were derived from the Clinical Interview Schedule-Revised. RESULTS: The authors identified 114 individuals (74 women, 40 men) with obsessive-compulsive disorder, with a weighted 1-month prevalence of 1.1%. Most individuals (55%) in the obsessive-compulsive group had obsessions only. Comorbidity occurred in 62% of these individuals, which was significantly greater than the group with other neuroses (10%). Co-occurring neuroses were depressive episode (37%), generalized anxiety disorder (31%), agoraphobia or panic disorder (22%), social phobia (17%), and specific phobia (15%). Alcohol dependence was present in 20% of participants, mainly men, and drug dependence was present in 13%. Obsessive-compulsive disorder, compared with other neurotic disorders, was associated with more marked social and occupational impairment. One-quarter of obsessive-compulsive disorder participants had previously attempted suicide. Individuals with pure and comorbid obsessive-compulsive disorder did not differ according to most indices of impairment, including suicidal behavior, but pure individuals were significantly less likely to have sought help (14% versus 56%). CONCLUSIONS: A rare yet severe mental disorder, obsessive-compulsive disorder is an atypical neurosis, of which the public health significance has been underestimated. Unmet need among individuals with pure obsessive-compulsive disorder is a cause for concern, requiring further investigation of barriers to care and interventions to encourage help-seeking.