Ian M Anderson

The University of Manchester, Manchester, England, United Kingdom

Are you Ian M Anderson?

Claim your profile

Publications (131)608.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order 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 September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. 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. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made. © The Author(s) 2015.
    Journal of Psychopharmacology 05/2015; 29(5). DOI:10.1177/0269881115581093 · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity. In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression and anxiety in a European population cohort of over 2300 subjects. Recent negative life events (RLE), childhood adversity (CHA), lifetime depression, Brief Symptoms Inventory (BSI) depression and anxiety scores were determined in each subject. Besides traditional statistical analysis we calculated Bayesian effect strength and relevance of 5-HTTLPR genotypes in specified models. The short (s) low expressing allele showed association with increased risk of depression related phenotypes, but all nominally significant effects would turn to non-significant after correction for multiple testing in the traditional analysis. Bayesian effect strength and relevance analysis, however, confirmed the role of 5-HTTLPR. Regarding current (BSI) and lifetime depression 5-HTTLPR-by-RLE interactions were confirmed. Main effect, with other words direct association, was supported with BSI anxiety. With more frequent RLE the prevalence or symptoms of depression increased in ss carriers. Although CHA failed to show an interaction with 5-HTTLPR, in young subjects CHA sensitized towards the depression promoting effect of even mild RLE. Furthermore, the direct association of anxiety with the s allele was driven by young (≤30) individuals. Our study is cross-sectional and applies self-report questionnaires. Albeit 5-HTTLPR has only weak/moderate effects, the s allele is directly associated with anxiety and modulates development of depression in homogeneous subgroups.
    PLoS ONE 03/2015; 10(3):e0116316. DOI:10.1371/journal.pone.0116316 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prosocial emotions related to self-blame are important in guiding human altruistic decisions. These emotions are elevated in major depressive disorder (MDD), such that MDD has been associated with guilt-driven pathological hyper-altruism. However, the impact of such emotional impairments in MDD on different types of social decision-making is unknown.
    Psychological Medicine 10/2014; 45(06):1-13. DOI:10.1017/S0033291714002414 · 5.43 Impact Factor
  • Source
    Kate Williams, Ian Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: Psychological therapies can be effective in the treatment of depression and are valued by patients. Here, the authors provide an overview of the main psychological therapies available, their evidence base and their use in practice.
    Prescriber 10/2014; 25(20). DOI:10.1002/psb.1260
  • European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 10/2014; 24(S2):S388. DOI:10.1016/S0924-977X(14)70619-4 · 5.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background / Purpose: This study aimed to investigate the neural basis of working and episodic memory, including the encoding and retrieval of emotional memories, in patients with treatment resistant depression (TRD). Main conclusion: We demonstrated neural activity abnormalities in working & episodic memory in TRD. Decreased activity of the dlPFC in the n-back task could be a manifestation of the frontal hypoactivity found in depression; this is probably related to attentional and cognitive impairments. Posterior cingulate hypoactivity, shown during encoding, may represent the greater effort required for TRD patients due to attentional difficulties. Manifested by a greater need to switch off the default mode network. The anterior cingulate is associated with emotional processing and the emotion-specific under activity to positive image retrieval may contribute to memory/evaluation biases in TRD. Posterior insula activation has been associated with emotional significance during image recognition; increased activity in TRD may contribute to emotional bias.
    69th Society of Biological Psychiatry Annual Meeting 2014; 07/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is increasing evidence that genetic factors play a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling plays a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between 8 NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller 3 SNP haplotype (rs10507279, rs1004356, rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression.Neuropsychopharmacology accepted article preview online, 11 June 2014; doi:10.1038/npp.2014.137.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 06/2014; DOI:10.1038/npp.2014.137 · 8.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Major depressive disorder (MDD) is associated with functional abnormalities in fronto-meso-limbic networks contributing to decision-making, affective and reward processing impairments. Such functional disturbances may underlie a tendency for enhanced altruism driven by empathy-based guilt observed in some patients. However, despite the relevance of altruistic decisions to understanding vulnerability, as well as everyday psychosocial functioning, in MDD, their functional neuroanatomy is unknown. Methods Using a charitable donations experiment with fMRI, we compared 14 medication-free participants with fully remitted MDD and 15 demographically-matched control participants without MDD. Results Compared with the control group, the remitted MDD group exhibited enhanced BOLD response in a septal/subgenual cingulate cortex (sgACC) region for charitable donation relative to receiving simple rewards and higher striatum activation for both charitable donation and simple reward relative to a low level baseline. The groups did not differ in demographics, frequency of donations or response times, demonstrating only a difference in neural architecture. Conclusions We showed that altruistic decisions probe residual sgACC hypersensitivity in MDD even after symptoms are fully remitted. The sgACC has previously been shown to be associated with guilt which promotes altruistic decisions. In contrast, the striatum showed common activation to both simple and altruistic rewards and could be involved in the so-called “warm glow” of donation. Enhanced neural response in the depression group, in areas previously linked to altruistic decisions, supports the hypothesis of a possible association between hyper-altruism and depression vulnerability, as shown by recent epidemiological studies.
    04/2014; 4:701–710. DOI:10.1016/j.nicl.2014.04.010
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.
    Journal of Psychopharmacology 04/2014; 28(5). DOI:10.1177/0269881114525674 · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Galanin is a stress-inducible neuropeptide and cotransmitter in serotonin and norepinephrine neurons with a possible role in stress-related disorders. Here we report that variants in genes for galanin (GAL) and its receptors (GALR1, GALR2, GALR3), despite their disparate genomic loci, conferred increased risk of depression and anxiety in people who experienced childhood adversity or recent negative life events in a European white population cohort totaling 2,361 from Manchester, United Kingdom and Budapest, Hungary. Bayesian multivariate analysis revealed a greater relevance of galanin system genes in highly stressed subjects compared with subjects with moderate or low life stress. Using the same method, the effect of the galanin system genes was stronger than the effect of the well-studied 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4). Conventional multivariate analysis using general linear models demonstrated that interaction of galanin system genes with life stressors explained more variance (1.7%, P = 0.005) than the life stress-only model. This effect replicated in independent analysis of the Manchester and Budapest subpopulations, and in males and females. The results suggest that the galanin pathway plays an important role in the pathogenesis of depression in humans by increasing the vulnerability to early and recent psychosocial stress. Correcting abnormal galanin function in depression could prove to be a novel target for drug development. The findings further emphasize the importance of modeling environmental interaction in finding new genes for depression.
    Proceedings of the National Academy of Sciences 03/2014; 111(16). DOI:10.1073/pnas.1403649111 · 9.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Evidence suggests that depression is a risk factor for dementia; however, the relationship between the two conditions is not fully understood. A novel gene (TOMM40) has been consistently associated with Alzheimer's disease (AD), but has received no attention in depression. We conducted a three-level cross-sectional study to investigate the association of the TOMM40 rs2075650 SNP with depression. We recruited a community sample of 1220 participants (571 controls, 649 lifetime depression) to complete a psychiatric background questionnaire, the Brief Symptom Inventory, and Big Five Inventory at Level-1, 243 (102 controls, 97 remitted, 44 currently depressed) to complete a face-to-face clinical interview and neuropsychological testing at Level-2 and 58 (33 controls, 25 remitted) to complete an emotional face-processing task during fMRI at Level-3. Our results indicated that the TOMM40 rs2075650 G allele was a significant risk factor for lifetime depression (p=0.00006) and, in depressed subjects, was a significant predictor of low extraversion (p=0.009). Currently depressed risk allele carriers showed subtle executive dysfunction (p=0.004) and decreased positive memory bias (p=0.021) together with reduced activity in the posterior (p(FWE)=0.045) and anterior (p(FWE)=0.041) cingulate during sad face emotion processing. Our results suggest that TOMM40 rs2075650 may be a risk factor for the development of depression characterized by reduced extraversion, impaired executive function, and decreased positive emotional recall, and reduced top-down cortical control during sad emotion processing.Neuropsychopharmacology advance online publication, 19 February 2014; doi:10.1038/npp.2014.22.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 01/2014; DOI:10.1038/npp.2014.22 · 7.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Major depressive disorder (MDD) is associated with abnormalities in financial reward processing. Previous research suggests that patients with MDD show reduced sensitivity to frequency of financial rewards. However, there is a lack of conclusive evidence from studies investigating the evaluation of financial rewards over time, an important aspect of reward processing that influences the way people plan long-term investments. Beck's cognitive model posits that patients with MDD hold a negative view of the future that may influence the amount of resources patients are willing to invest into their future selves. We administered a delay discounting task to 82 participants: 29 healthy controls, 29 unmedicated participants with fully remitted MDD (rMDD) and 24 participants with current MDD (11 on medication). Patients with current MDD, relative to remitted patients and healthy subjects, discounted large-sized future rewards at a significantly higher rate and were insensitive to changes in reward size from medium to large. There was a main effect of clinical group on discounting rates for large-sized rewards, and discounting rates for large-sized rewards correlated with severity of depressive symptoms, particularly hopelessness. Higher discounting of delayed rewards in MDD seems to be state dependent and may be a reflection of depressive symptoms, specifically hopelessness. Discounting distant rewards at a higher rate means that patients are more likely to choose immediate financial options. Such impairments related to long-term investment planning may be important for understanding value-based decision making in MDD, and contribute to ongoing functional impairment.
    Psychological Medicine 11/2013; 44(9):1-10. DOI:10.1017/S0033291713002584 · 5.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Some patients with depression do not respond to first and second line conventional antidepressants and are therefore characterised as suffering from treatment refractory depression (TRD). On-going psychosocial stress and dysfunction of the hypothalamic-pituitary-adrenal axis are both associated with an attenuated clinical response to antidepressants. Preclinical data shows that co-administration of corticosteroids leads to a reduction in the ability of selective serotonin reuptake inhibitors to increase forebrain 5-hydroxytryptamine, while co-administration of antiglucocorticoids has the opposite effect. A Cochrane review suggests that antiglucocorticoid augmentation of antidepressants may be effective in treating TRD and includes a pilot study of the cortisol synthesis inhibitor, metyrapone. The Antiglucocorticoid augmentation of anti-Depressants in Depression (The ADD Study) is a multicentre randomised placebo controlled trial of metyrapone augmentation of serotonergic antidepressants in a large population of patients with TRD in the UK National Health Service.Methods/design: Patients with moderate to severe treatment refractory Major Depression aged 18 to 65 will be randomised to metyrapone 500 mg twice daily or placebo for three weeks, in addition to on-going conventional serotonergic antidepressants. The primary outcome will be improvement in Montgomery-Asberg Depression Rating Scale score five weeks after randomisation (i.e. two weeks after trial medication discontinuation). Secondary outcomes will include the degree of persistence of treatment effect for up to 6 months, improvements in quality of life and also safety and tolerability of metyrapone. The ADD Study will also include a range of sub-studies investigating the potential mechanism of action of metyrapone. Strengths of the ADD study include broad inclusion criteria meaning that the sample will be representative of patients with TRD treated within the UK National Health Service, longer follow up, which to our knowledge is longer than any previous study of antiglucocorticoid treatments in depression, and the range of mechanistic investigations being carried out. The data set acquired will be a rich resource for a range of research questions relating to both refractory depression and the use of antiglucocorticoid treatments.Trial registration: Current Controlled Trials: ISRCTN45338259; EudraCT Number: 2009-015165-31.
    BMC Psychiatry 08/2013; 13(1):205. DOI:10.1186/1471-244X-13-205 · 2.24 Impact Factor
  • Ian M Anderson
    BMJ (online) 04/2013; 346:f2307. DOI:10.1136/bmj.f2307 · 16.38 Impact Factor
  • Ian M Anderson, Peter M Haddad, Jan Scott
    BMJ (online) 12/2012; 345:e8508. DOI:10.1136/bmj.e8508 · 16.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The catechol-o-methyltransferase (COMT) gene has been extensively investigated in depression with somewhat contradictory results but the role of impulsivity, as a possible intermediate phenotype in this disorder, has not been considered yet. In our study, four tagging SNPs in the COMT gene (rs933271, rs740603, rs4680, rs4646316) were genotyped in two independent population cohorts: Manchester (n = 1267) and Budapest (n = 942). First, we investigated the association between COMT genotypes, impulsivity, neuroticism and depression using haplotype trend regression, and constructed a model using structural equation modeling to investigate the interaction between these factors. Secondly, we tested the effect of executive function on this model in a smaller interviewed sample (n = 207). Our results demonstrated that COMT haplotypes were significantly associated with impulsivity in the combined cohort, showing the same direction of effects in both populations. The COMT effect on depressive symptoms (in subjects without history of depression) and on executive function (interviewed sample) showed the opposite pattern to impulsivity. Structural equation models demonstrated that COMT and impulsivity acted, both together (through neuroticism) and independently, to increase the risk of depression. In addition, better executive function also operated as a risk factor for depression, possibly though reduced ability to flexibly disengage negative emotions. In conclusion, variations in the COMT gene exert complex effects on susceptibility to depression involving various intermediate phenotypes, such as impulsivity and executive function. These findings emphasise that modeling of disease pathways at phenotypic level are valuable for identifying genetic risk factors. © 2012 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 12/2012; 159B(8). DOI:10.1002/ajmg.b.32098 · 3.27 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Reduced hippocampal volume has been reported in depression and may be involved in the aetiology of depressive symptoms and vulnerability to depressive relapse. Neuroplasticity following antidepressant drug treatment in the hippocampus has been demonstrated in animal models but adaptive changes after such treatment have not been shown in humans. In this study, we determined whether grey matter loss in the hippocampus in depression (1) is present in medication-free depressed (2) changes in response to antidepressant treatment and (3) is present as a stable trait in medication-free remitted patients. Sixty-four medication-free unipolar depressed patients: 39 currently depressed and 25 in remission, and 66 healthy controls (HC) underwent structural magnetic resonance imaging in a cross-sectional and longitudinal design. Thirty-two currently depressed participants were then treated with the antidepressant citalopram for 8 weeks. Adherence to treatment was evaluated by measuring plasma citalopram concentration. We measured regional variation in grey matter concentration by using voxel-based morphometry-Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra. Patients with current depression had bilaterally reduced grey matter in the hippocampus compared with HC and untreated patients in stable remission with the latter groups not differing. An increase in grey matter was observed in the hippocampus following treatment with citalopram in currently depressed patients. Grey matter reduction in the hippocampus appears specific to the depressed state and is a potential biomarker for a depressive episode.Molecular Psychiatry advance online publication, 6 November 2012; doi:10.1038/mp.2012.150.
    Molecular Psychiatry 11/2012; 18(12). DOI:10.1038/mp.2012.150 · 15.15 Impact Factor
  • Catherine Symonds, Ian M. Anderson
    [Show abstract] [Hide abstract]
    ABSTRACT: Depression is a common relapsing disorder that causes significant distress and impairment in social and occupational functioning. It is associated with an increased risk of death, not only through suicide but also from physical illnesses such as cardiovascular disease. It is under-recognized and undertreated and it should be screened for in those at high-risk for depression such as those suffering from chronic physical health problems. Its aetiology is multifactorial and comorbidity with other psychiatric disorders is common. Assessment of depression requires the clinician to determine the duration, symptom severity, suicide risk and functional impairment in the current episode, co-morbid diagnoses, past mood and treatment history, as well as a developmental, social and family history. Treatment is guided by illness severity, presentation and prior history and includes psychosocial interventions, medication and their combination, with antidepressant medication reserved for persistent and moderate-to-severe depression. Prevention of relapse is a priority and risk factors for this should be assessed and used to guide prophylactic drug and psychological treatment.
    Medicine 11/2012; 40(11):591-595. DOI:10.1016/j.mpmed.2012.08.006 · 4.35 Impact Factor