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Item Metadata only 5-HTTLPR Biases Amygdala Activity in Response to Masked Facial Expressions in Major Depression(Elsevier Science Inc, 2008) Dannlowski, U.; Ohrmann, P.; Bauer, J.; Deckert, J.; Hohoff, C.; Kugel, H.; Arolt, V.; Heindel, W.; Kersting, A.; Baune, B.; Suslow, T.The amygdala is a key structure in a limbic circuit involved in the rapid and unconscious processing of facial emotions. Increased amygdala reactivity has been discussed in the context of major depression. Recent studies reported that amygdala activity during conscious emotion processing is modulated by a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in healthy subjects. In the present study, amygdala reactivity to displays of emotional faces was measured by means of fMRI at 3T in 35 patients with major depression and 32 healthy controls. Conscious awareness of the emotional stimuli was prevented via backward-masking to investigate automatic emotion processing. All subjects were genotyped for the 5-HTTLPR polymorphism. Risk allele carriers (S or LG) demonstrated increased amygdala reactivity to masked emotional faces, which in turn was significantly correlated with life-time psychiatric hospitalization as an index of chronicity. This might indicate that genetic variations of the serotonin transporter could increase the risk for depression chronification via altering limbic neural activity on a preattentive level of emotion processing.Item Open Access A 6-month assessment of the alcohol-related clinical burden at emergency rooms (ERs) in 11 acute care hospitals of an urban area in Germany(BioMed Central Ltd., 2005) Baune, B.; Mikolajczyk, R.; Reymann, G.; Duesterhaus, A.; Kratz, H.; Sundermann, U.BACKGROUND: The purpose of the study was to identify and to profile alcohol-related attendances to emergency rooms (ERs) of 11 hospitals of various medical specialties covering a large urban population, to assess risk factors associated with short-stay cases, repeat attendances and higher degree of alcohol consumption and to estimate their impact on the alcohol-related burden at ERs. METHODS: A 6-months study was carried out to obtain clinical and administrative data on single and multiple attendances at ERs in 11 governmental acute hospitals in a large city in Germany. All alcohol-related attendances at ERs of study hospitals were eligible. A broad definition of alcohol-related attendances independently from alcohol diagnosis and various demographic, clinical and administrative measures were used. Odds ratios for the associations of these measures with duration of stay, repeat attendances and higher degrees of alcohol consumption were derived from multivariate binomial and multinomial logistic regression models. RESULTS: 1,748 patients with symptoms of alcohol consumption or withdrawal (inclusion rate 83.8%) yielded 2,372 attendances (3% of all medical admissions), and resulted in 12,629 inpatient-days. These patients accounted for 10.7 cases per 1,000 inhabitants. The average duration of inpatient stay was 10 days. 1,451 of all patients (83%) presented once, whereas the median of repeat attendances was three for the remaining 297 patients. Short-stay cases (<24 hours) were significantly linked with male gender, alcohol misuse, trauma (or suspicion of a trauma) and medical specialties. Increased levels of alcohol consumption at first attendance were significantly associated with repeat attendances in due course. In a multinomial logistic regression model higher degrees of alcohol consumption were significantly associated with male gender, trauma, short-stays, attendance outside regular working time, and with repeat attendances and self-discharge. CONCLUSION: Apart from demographic factors, the alcohol-related clinical burden is largely determined by short-stay cases, repeat attendances and cases with higher levels of alcohol consumption at first attendance varying across medical specialties. These findings could be relevant for the planning of anti-alcoholic interventions at ERs.Item Metadata only A Brain Capital Grand Strategy: toward economic reimagination(Springer, 2021) Smith, E.; Ali, D.; Wilkerson, B.; Dawson, W.D.; Sobowale, K.; Reynolds, C.; Berk, M.; Lavretsky, H.; Jeste, D.; Ng, C.H.; Soares, J.C.; Aragam, G.; Wainer, Z.; Manji, H.K.; Licinio, J.; Lo, A.W.; Storch, E.; Fu, E.; Leboyer, M.; Tarnanas, I.; et al.Abstract not availableItem Open Access A broad autism phenotype expressed in facial morphology(Springer Science and Business Media, 2020) Tan, D.W.; Maybery, M.T.; Gilani, S.Z.; Alvares, G.A.; Mian, A.; Suter, D.; Whitehouse, A.J.O.Autism spectrum disorder is a heritable neurodevelopmental condition diagnosed based on social and communication differences. There is strong evidence that cognitive and behavioural changes associated with clinical autism aggregate with biological relatives but in milder form, commonly referred to as the 'broad autism phenotype'. The present study builds on our previous findings of increased facial masculinity in autistic children (Sci. Rep., 7:9348, 2017) by examining whether facial masculinity represents as a broad autism phenotype in 55 non-autistic siblings (25 girls) of autistic children. Using 3D facial photogrammetry and age-matched control groups of children without a family history of ASD, we found that facial features of male siblings were more masculine than those of male controls (n = 69; p < 0.001, d = 0.81 [0.36, 1.26]). Facial features of female siblings were also more masculine than the features of female controls (n = 60; p = 0.005, d = 0.63 [0.16, 1.10]). Overall, we demonstrated for males and females that facial masculinity in non-autistic siblings is increased compared to same-sex comparison groups. These data provide the first evidence for a broad autism phenotype expressed in a physical characteristic, which has wider implications for our understanding of the interplay between physical and cognitive development in humans.Item Metadata only A Case of Multiple Sclerosis Masked by Depression and Diabetic Neuropathy(Amer Psychiatric Press Inc, 2006) Schilling, M.; Breuckner-Totonji, C.; Arolt, V.; Baune, B.Item Metadata only A case series on the development of rest-activity rhythm and quality of sleep in patients hospitalized for treatment of uni- or bipolar depression: a potential role for quetiapine(Martin Dunitz Ltd, 2006) Baune, B.; Caliskan, S.; Todder, D.Objectives. To assess the development of the rest–activity rhythm and quality of sleep during course of treatment of patients with major depressive episode receiving antidepressant treatment plus quetiapine. Methods. Ten patients with major depressive episode were followed over 4 weeks. Motor activity was measured with actigraphy, sleep with the Pittsburgh Sleep Quality Index (PSQI), and depression was followed with HAM-D-21 and BDI. Correlations and associations were calculated with non-parametric statistical tests. Results. Circadian motor activity improved during the 4 weeks treatment period only for daytime-related motor activity (M10), but not for night-time-related motor activity (L5). Patients with statistically significant higher sleep efficiency scores and sleep fraction on the actigraph after week 1 showed clinical improvement on the HAM-D score after week 4. Patients with good sleep efficiency at week 1 (assessed by PSQI) showed statistically significant clinical improvement of depression after week 4. Conclusions. Various sleep parameters at week 1 of treatment seem to be predictive for treatment outcome of depression after week 4. Actigraphy and subjective sleep assessment with PSQI are useful tools to predict treatment outcome of depression. The positive effects of quetiapine on motor activity and sleep show the clinical significance of our findings.Item Metadata only A clinical approach to treatment resistance in depressed patients: what to do when the usual treatments don’t work well enough?(Taylor & Francis, 2021) Dodd, S.; Bauer, M.; Carvalho, A.F.; Eyre, H.; Fava, M.; Kasper, S.; Kennedy, S.H.; Khoo, J.P.; Lopez Jaramillo, C.; Malhi, G.S.; McIntyre, R.S.; Mitchell, P.B.; Castro, A.M.P.; Ratheesh, A.; Severus, E.; Suppes, T.; Trivedi, M.H.; Thase, M.E.; Yatham, L.N.; Young, A.H.; et al.Major depressive disorder is a common, recurrent, disabling and costly disorder that is often severe and/or chronic, and for which non-remission on guideline concordant first-line antidepressant treatment is the norm. A sizeable percentage of patients diagnosed with MDD do not achieve full remission after receiving antidepressant treatment. How to understand or approach these 'refractory', 'TRD' or 'difficult to treat' patients need to be revisited. Treatment resistant depression (TRD) has been described elsewhere as failure to respond to adequate treatment by two different antidepressants. This definition is problematic as it suggests that TRD is a subtype of major depressive disorder (MDD), inferring a boundary between TRD and depression that is not treatment resistant. However, there is scant evidence to suggest that a discrete TRD entity exists as a distinct subtype of MDD, which itself is not a discrete or homogeneous entity. Similarly, the boundary between TRD and other forms of depression is predicated at least in part on regulatory and research requirements rather than biological evidence or clinical utility.
Aim: This paper aims to investigate the notion of treatment failure in order to understand (i) what is TRD in the context of a broader formulation based on the understanding of depression, (ii) what factors make an individual patient difficult to treat, and (iii) what is the appropriate and individualised treatment strategy, predicated on an individual with refractory forms of depression? Method: Expert contributors to this paper were sought internationally by contacting representatives of key professional societies in the treatment of MDD - World Federation of Societies for Biological Psychiatry, Australasian Society for Bipolar and Depressive Disorders, International Society for Affective Disorders, Collegium Internationale Neuro-Psychopharmacologium and the Canadian Network for Mood and Anxiety Treatments. The manuscript was prepared through iterative editing. Outcomes: The concept of TRD as a discrete subtype of MDD, defined by failure to respond to pharmacotherapy, is not supported by evidence. Between 15 and 30% of depressive episodes fail to respond to adequate trials of 2 antidepressants, and 68% of individuals do not achieve remission from depression after a first-line course of antidepressant treatment. Failure to respond to antidepressant treatment, somatic therapies or psychotherapies may often reflect other factors including; biological resistance, diagnostic error, limitations of current therapies, psychosocial variables, a past history of exposure to childhood maltreatment or abuse, job satisfaction, personality disorders, co-morbid mental and physical disorders, substance use or non-adherence to treatment. Only a subset of patients not responding to antidepressant treatment can be explained through pharmacokinetic or pharmacodynamics mechanisms. We propose that non remitting MDD should be personalised, and propose a strategy of 'deconstructing depression'. By this approach, the clinician considers which factors contribute to making this individual both depressed and 'resistant' to previous therapeutic approaches. Clinical formulation is required to understand the nature of the depression. Many predictors of response are not biological, and reflect a confluence of biological, psychological, and sociocultural factors, which may influence the illness in a particular individual. After deconstructing depression at a personalised level, a personalised treatment plan can be constructed. The treatment plan needs to address the factors that have contributed to the individual's hard to treat depression. In addition, an individual with a history of illness may have a lot of accumulated life issues due to consequences of their illness, and these should be addressed in a recovery plan. Limitations: A 'deconstructing depression' qualitative rubric does not easily provide clear inclusion and exclusion criteria for researchers wanting to investigate TRD. Conclusions: MDD is a polymorphic disorder and many individuals who fail to respond to standard pharmacotherapy and are considered hard to treat. These patients are best served by personalised approaches that deconstruct the factors that have contributed to the patient's depression and implementing a treatment plan that adequately addresses these factors. The existence of TRD as a discrete and distinct subtype of MDD, defined by two treatment failures, is not supported by evidence.Item Metadata only A clinical repetitive transcranial magnetic stimulation service in Australia: 6 years on(SAGE Publications, 2015) Galletly, C.; Clarke, P.; Carnell, B.; Gill, S.Objective: There is considerable research evidence for the effectiveness of repetitive transcranial magnetic stimulation in the treatment of depression. However, there is little information about its acceptability and outcomes in clinical settings. Method: This naturalistic study reports on a clinical repetitive transcranial magnetic stimulation service that has been running in Adelaide, South Australia, SA, for, years. During this time, complete acute courses were provided to patients with treatment-resistant Major Depressive Disorder. Patients received either sequential bilateral or right unilateral repetitive transcranial magnetic stimulation treatment involving either, or, sessions given over, or, weeks respectively. Data included patient demographic details, duration of depression, and medication at the beginning of their repetitive transcranial magnetic stimulation course. The Hamilton Depression Rating Scale was used to assess response to repetitive transcranial magnetic stimulation. Results: Of those undergoing a first-time acute treatment course of repetitive transcranial magnetic stimulation, N, achieved remission, while a further, met the criteria for a response to treatment. Most patients, N, had previously been treated with five or more antidepressant medications, and, had previously received electroconvulsive therapy. Referral rates remained high over the, years, indicating acceptance of the treatment by referring psychiatrists. There were no significant adverse events, and the treatment was generally well tolerated. In all, patients, had a second course of repetitive transcranial magnetic stimulation and, patients had a third course, patients subsequently received maintenance repetitive transcranial magnetic stimulation. Conclusion: This naturalistic study showed that repetitive transcranial magnetic stimulation was well accepted by both psychiatrists and patients, and has good efficacy and safety. Furthermore, repetitive transcranial magnetic stimulation can provide a useful treatment alternative as part of outpatient mental health services for people with depression.Item Metadata only A comparison of the efficacy and safety of olanzapine and risperidone in the treatment of elderly patients with schizophrenia: an open study of six months duration(John Wiley & Sons Ltd, 2006) Ritchie, C.; Chiu, E.; Harrigan, S.; Macfarlane, S.; Mastwyk, M.; Halliday, G.; Hustig, H.; Hall, K.; Hassett, A.; O'Connor, D.; Opie, J.; Nagalingam, V.; Snowdon, J.; Ames, D.Background: Following an earlier study in which elderly patients with schizophrenia had their typical antipsychotic medication changed to olanzapine or risperidone, the 61 patients were followed for up to a further six months to see if either treatment was superior in terms of efficacy or side effects. Aims: To determine whether either olanzapine or risperidone was superior in terms of efficacy or side effects when treating schizophrenia in late life. Methods: Psychiatric symptoms, side effects and quality of life were rated every six weeks for 24 weeks of open label comparative treatment using standard measures. Group differences were examined using analysis of covariance and within-group changes over time were assessed using paired t-tests. Results: There were 34 olanzapine and 32 risperidone patients who entered the study, but intention to treat data was only available for 61 of the 66 patients. There were no clinical or demographic differences between the groups. Parkinsonism, positive and negative symptoms of schizophrenia improved in both groups both from baseline switch to olanzapine or risperidone and during the six month follow-up after completion of crossover. No significant differences were seen between groups on most measures. However, patients treated with olanzapine showed a significantly greater improvement in quality of life from baseline compared to risperidone patients. Conclusions: Both drugs were well tolerated and their use was associated with fewer symptoms of schizophrenia and less adverse effects than were seen when the patients were taking a typical antipsychotic at baseline. Olanzapine appears to have particular benefit with regard to quality of life.Item Metadata only A confirmatory factor analysis of the Acute Stress Disorder Interview(Kluwer Academic/Plenum Publ, 2008) Brooks, R.; Silove, D.; Bryant, R.; O'Donnell, M.; Creamer, M.; McFarlane, A.Acute stress disorder (ASD) was introduced in 1994 to describe posttraumatic stress reactions that occur in the initial month after trauma exposure. Although it comprises the distinct symptom clusters of dissociation, reexperiencing, avoidance, and arousal, there have been no confirmatory factor analyses of the construct. In this study, 587 individuals admitted to five major hospitals after traumatic injury were administered the Acute Stress Disorder Interview. Forty-four participants met criteria for ASD. Confirmatory factor analysis based on the four symptom clusters described the Acute Stress Disorder Interview responses. These data provide the first confirmatory factor analysis of the ASD symptoms, and are discussed in terms of the 4-factor models repeatedly found in samples of chronic posttraumatic stress disorder.Item Metadata only A Controlled Study of Facial Mobility Treatment in Parkinson's Disease(Elsevier BV, 1996) Katsikitis, M.; Pilowsky, I.Item Metadata only A controlled study of facial mobility treatment in Parkinson's disease. Proceedings of 22nd Annual Experimental Psychology Conference(Australian Branch of the British Psychological Society by Melbourne University Press, 1995) Katsikitis, M.; Pilowsky, I.Item Metadata only A critical review of the efficacy of non-steroidal anti-inflammatory drugs in depression(Elsevier, 2015) Eyre, H.; Air, T.; Proctor, S.; Rositano, S.; Baune, B.Abstract not availableItem Metadata only A cross-national study of posttraumatic stress disorder in Dutch-Australian immigrants(Blackwell Publishing Asia, 2000) Op den Velde, W.; Hovens, J.; Bramsen, I.; McFarlane, A.; Aarts, P.; Falger, P.; de Groen, J.; van Duijn, H.OBJECTIVE: Studying the rates of posttraumatic stress disorder (PTSD) in people who experienced World War II, but who have subsequently lived in different environments is a way of looking at the impact of recovery environment on PTSD. Immigrants had less support in terms of the social cohesion in their home country, but were not subjected to the same triggers of war-related intrusions. METHOD: Posttraumatic stress disorder was investigated in citizens from the Netherlands who emigrated to Australia in the post-World War II years (n = 251). Immigrants born between 1920 and 1930 (n = 171) were compared with a same-aged group living in Holland (n = 1461) for stressful war experiences and the extent of PTSD. RESULTS: Those who had been exposed to the most severe war stress were over-represented in the immigrant group. Immigrants with current PTSD more often stated that motives for migration were threat of a third world war, disappointment with Dutch society and personal problems. We were unable to demonstrate specific effects of emigration on the prevalence of current PTSD. CONCLUSIONS: This study suggests that exposure to severe war stress promoted the need to emigrate. The comparable PTSD scores of the groups of war victims living in Australia and the Netherlands support the notion that extreme war stress may be considered the primary determining factor in the development of PTSD, and that actual post-war living circumstances are, in the long term, of subordinate importance.Item Metadata only A double-blind, multicentre study to assess the tolerability and efficacy of paroxetine compared with amitriptyline in the treatment of depressed patients in Australian general practice(SAGE Publications, 1999) Freed, E.; Goldney, R.; Lambert, T.; Tiller, J.; Johnston, R.Objective
This study compared the tolerability and efficacy of paroxetine and amitriptyline in the treatment of depression in general practice.Methods
In this double-blind, multicentre study conducted in the general practice, patients with depression (Montgomery Asberg Depression Rating Scale [MADRS] score > or = 20) who were regarded as requiring antidepressant therapy were randomly assigned to receive paroxetine (20 mg, n = 184) or amitriptyline (50-100 mg, n = 191) once daily for 9 weeks.Results
More patients completed treatment with paroxetine than with amitriptyline (71.1% vs 56.1%, p = 0.009). Depression rating scores (MADRS and Clinical Global Impression [CGI]) were improved with both agents, but at week 9, paroxetine achieved more favourable scores compared with amitriptyline on MADRS (p=0.019), CGI severity of depression (p=0.044), and CGI efficacy index (p = 0.038).Conclusions
Depressed patients treated in general practice respond more quickly and are more likely to complete the treatment regimen with paroxetine than with amitriptyline.Item Metadata only A follow-up case-control association study of tractable (druggable) genes in recurrent major depression(Wiley-Liss, 2011) Schosser, A.; Gaysina, D.; Cohen-Woods, S.; Domenici, E.; Perry, J.; Tozzi, F.; Korszun, A.; Gunasinghe, C.; Gray, J.; Jones, L.; Binder, E.; Holsboer, F.; Craddock, N.; Owen, M.; Craig, I.; Farmer, A.; Muglia, P.; McGuffin, P.The High-Throughput Disease-specific target Identification Program (HiTDIP) aimed to study case-control association samples for 18 common diseases. Here we present the results of a follow-up case-control association study of HiTDIP in major depressive disorder (MDD). The HiTDIP in MDD was conducted in a sample of 974 cases of recurrent MDD of white German origin collected at the Max-Planck Institute (MP-GSK) and 968 ethnically matched controls screened for lifetime absence of depression. Six genes were identified as of interest for a follow-up, based on the strength of the association and based on the interest as potential candidate target for developing new treatment for depression: Solute Carrier Family 4 Member 10 (SLC4A10), Dipeptidyl Peptidase IV (DPP4), Dopamine Receptor D3 (DRD3), Zinc Finger Protein 80 (ZNF80), Nitric Oxide Synthase 2A (NOS2A) and Peroxisome Proliferator-Activated Receptor-Gamma, Coactivator 1, Alpha (PPARGC1A). Within the current study, we attempted to follow-up these findings in a sample from the UK, the Depression Case Control (DeCC) sample consisting of 1,196 cases and 842 screened controls, phenotyped using exactly the same methods as the MP-GSK sample. Performing Cochran-Mantel-Haenzel statistics to test for genotypic and/or allelic differences between the DeCC and MP-GSK samples, we found no significant differences, thus being able to combine the two samples for association testing. In the combined sample of 2,170 MDD cases and 1,810 controls, there were positive findings in the Nitric Oxide Synthase 2A (NOS2A) gene both using single SNP analysis and haplotype analysis.Item Metadata only A General Approach to Treatment of Post-Traumatic Stress Disorder.(Guilford Press, 1996) van der Kolk, B.; McFarlane, A.; van der Hart, O.Item Open Access A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling(Nature Publishing Group, 2017) Li, D.; Chang, X.; Connolly, J.J.; Tian, L.; Liu, Y.; Bhoj, E.J.; Robinson, N.; Abrams, D.; Li, Y.R.; Bradfield, J.P.; Kim, C.E.; Li, J.; Wang, F.; Snyder, J.; Lemma, M.; Hou, C.; Wei, Z.; Guo, Y.; Qiu, H.; Mentch, F.D.; et al.We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.Item Metadata only A genome-wide significant linkage for severe depression on chromosome 3: the depression network study(Amer Psychiatric Press Inc, 2011) Breen, G.; Webb, B.; Butler, A.; van den Oord, E.; Tozzi, F.; Craddock, N.; Gill, M.; Korszun, A.; Maier, W.; Middleton, L.; Mors, O.; Owen, M.; Cohen-Woods, S.; Perry, J.; Galwey, N.; Upmanyu, R.; Craig, I.; Lewis, C.; Ng, M.; Brewster, S.; et al.OBJECTIVE: The purpose of this study was to find loci for major depression via linkage analysis of a large sibling pair sample. METHOD: The authors conducted a genome-wide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression, comprising waves I and II of the Depression Network Study cohort. In addition to examining affected status, linkage analyses in the full data set were performed using diagnoses restricted by impairment severity, and association mapping of hits in a large case-control data set was attempted. RESULTS: The authors identified genome-wide significant linkage to chromosome 3p25-26 when the diagnoses were restricted by severity, which was a maximum LOD score of 4.0 centered at the linkage marker D3S1515. The linkage signal identified was genome-wide significant after correction for the multiple phenotypes tested, although subsequent association mapping of the region in a genome-wide association study of a U.K. depression sample did not provide significant results. CONCLUSIONS: The authors report a genome-wide significant locus for depression that implicates genes that are highly plausible for involvement in the etiology of recurrent depression. Despite the fact that association mapping in the region was negative, the linkage finding was replicated by another group who found genome-wide-significant linkage for depression in the same region. This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication.Item Metadata only A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression(Amer Medical Assoc, 2009) Ising, M.; Lucae, S.; Binder, E.; Bettecken, T.; Uhr, M.; Ripke, S.; Kohli, M.; Hennings, J.; Horstmann, S.; Menke, A.; Bondy, B.; Repprecht, R.; Domschke, K.; Baune, B.; Arolt, V.; Rush, A.; Holsboer, F.; Muller-Myhsok, B.Context
The efficacy of antidepressant drug treatment in depression is unsatisfactory; 1 in 3 patients does not fully recover even after several treatment trials. Genetic factors and clinical characteristics contribute to the failure of a favorable treatment outcome.Objective
To identify genetic and clinical determinants of antidepressant drug treatment outcome in depression.Design
Genomewide pharmacogenetic association study with 2 independent replication samples.Setting
We performed a genomewide association study in patients from the Munich Antidepressant Response Signature (MARS) project and in pooled DNA from an independent German replication sample. A set of 328 single-nucleotide polymorphisms highly related to outcome in both genomewide association studies was genotyped in a sample of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study.Participants
A total of 339 inpatients with a depressive episode (MARS sample), a further 361 inpatients with depression (German replication sample), and 832 outpatients with major depression (STAR*D sample).Main outcome measures
We generated a multilocus genetic variable that described the individual number of alleles of the selected single nucleotide polymorphisms associated with beneficial treatment outcome in the MARS sample ("response" alleles) to evaluate additive genetic effects on antidepressant drug treatment outcome.Results
Multilocus analysis revealed a significant contribution of a binary variable that categorized patients as carriers of a high vs low number of response alleles in the prediction of antidepressant drug treatment outcome in both samples (MARS and STAR*D). In addition, we observed that patients with a comorbid anxiety disorder combined with a low number of response alleles showed the least favorable outcome.Conclusion
These results demonstrate the importance of multiple genetic factors combined with clinical features in the prediction of antidepressant drug treatment outcome, which underscores the multifactorial nature of this trait.