Polyunsaturated fatty acid associations with dopaminergic indices in major depressive disorder.

Dopaminergic function is thought to be altered in major depression and, in animal studies, is reduced in omega-3 polyunsaturated fatty acid (PUFA) deficiency states. Therefore we studied PUFAs and resting prolactin, a marker for dopaminergic tone, and cerebrospinal fluid homovanillic acid (HVA), the chief dopamine metabolite. In medication-free adults (n = 23) with DSM-IV major depressive disorder (MDD), we measured plasma phospholipid levels of omega-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the omega-6 PUFA arachidonic acid (AA), and plasma prolactin levels before and after administration of dl-fenfluramine (FEN). In a subset of patients (n = 14), cerebrospinal fluid levels of HVA and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were obtained through lumbar puncture. Baseline prolactin was negatively correlated with omega-3 PUFAs (logDHA, F(1,21) = 20.380, p < 0.001; logEPA, F(1,21) = 10.051, p = 0.005) and positively correlated with logAA:DHA (F(1,21) = 15.263, p = 0.001), a measure of omega-6/omega-3 balance. LogDHA was negatively correlated with CSF HVA (Spearman's ρ = -0.675, p = 0.008) but not 5-HIAA (Spearman's ρ = -0.143, p = 0.626) after controlling for sex and HVA - 5-HIAA correlation. PUFAs did not predict the magnitude of the FEN-stimulated change in prolactin, considered to be a serotonin effect. The robust relationship of omega-3 PUFAs with dopaminergic but not serotonergic indices suggests that omega-6:omega-3 balance may impact depression pathophysiology through effects on the dopaminergic system.

Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid.

BACKGROUND: Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems. METHODS AND MATERIALS: Patients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale. RESULTS: Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA. CONCLUSIONS: Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients.

Clinical examiners, simulated patients, and student self-assessed empathy in medical students during a psychiatry objective structured clinical examination.

OBJECTIVES: This study aims to assess and compare objective and subjective scores of empathy in final-year medical students by using firstly a validated student self-assessment just prior to the psychiatry objective structured clinical examination (OSCE), and then comparing this to clinical examiner's and simulated patient's (SP's) assessments of empathy of students using a Global Rating of Empathy scale (GRE) during a psychiatry OSCE. METHODS: In 2011, all final-year medical students in the University College Dublin were invited to complete a subjective, self-assessed empathy questionnaire (The Jefferson scale of physician empathy-student version (JSPE-S)). They were also assessed for empathy in four OSCEs by the clinical examiner and the SP acting in that OSCE scenario. RESULTS: Included in the analysis were 163 of 184 final-year students JSPE-S (88.6%) questionnaires. The female students scores on the JSPE-S were significantly higher than those of their male peers (t=3.34, p=0.001). Concurrent validity was greater between the SPs' assessments of empathy in the OSCE and the JSPE-S score than between the clinical examiners assessments of empathy and the JSPE-S score (r=0.23, p<0.005; r=0.14, p<0.08). Inter-rater reliability of SP's and clinical examiner's using the GRE was found to be high (F=0.868 (df=171, 171), p value<0.001). CONCLUSIONS: SPs may be valid assessors of empathy in medical students during an OSCE.

Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) who attempt or complete suicide have elevated inflammation compared to nonsuicidal patients with MDD. However, greater severity of depression and the medical lethality of suicide attempts could account for such elevated inflammation in suicide attempters and suicide completers. METHODS: To clarify, we measured inflammatory markers in patients with MDD with and without high levels of suicidal ideation and in nondepressed controls (N = 124). Levels of suicidal ideation, depression severity, and recent suicide attempts were assessed by structured clinical interviews. A composite score including the inflammatory markers tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) was used as an inflammatory index. Analysis of covariance models were used to assess group differences with adjustments for age and gender. RESULTS: Patients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial η(2) = .25, P < .001, and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial η(2) = .15, P = .009. In contrast, patients with lower suicidal ideation were not significantly different from controls on the inflammatory index, F(1,63) = .52, partial η(2) = .01, P = .47. Follow-up analyses indicated that differences between patients with MDD and high versus lower suicidal ideation were independent of depression severity and recent suicide attempts. CONCLUSIONS: Suicidal ideation may be uniquely associated with inflammation in depressed patients.

Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms.

BACKGROUND: Suicidal behaviour is known to aggregate in families. Patients with psychiatric disorders are at higher risk for suicide attempts (SA), however protective and risk genetic variants for suicide appear to be independent of underlying psychiatric disorders. Here we investigate genetic variants in genes important for neurobiological pathways linked to suicidal behaviour and/or associated endophenotypes, for association with SA among patients with co-existing psychiatric illness. Selected gene-gene and gene-environment interactions were also tested. METHODS: DNA was obtained from bloods of 159 patients (76 suicide attempters and 83 non-attempters), who were profiled for DSM-IV Axis I psychiatric diagnosis. Twenty-eight single nucleotide polymorphisms (SNPs) from 18 candidate genes (COMT, 5-HT2A, 5-HT1A, 5-HTR1B, TPH1, MAO-A, TPH2, DBH, CNR1, BDNF, ABCG1, GABRA5, GABRG2, GABRB2, SLC1A2, SLC1A3, NTRK2, CRHR1) were genotyped. Genotyping was performed by KBioscience. Tests of association between genetic variants and SA were conducted using Chi squared and Armitage Trend tests. Binary logistical regression analyses were performed to evaluate the contribution of individual genetic variants to the prediction of SA, and to examine SNPs for potential gene-gene and gene-environment interactions. RESULTS: Our analysis identified 4 SNPs (rs4755404, rs2269272, rs6296 and rs1659400), which showed evidence of association with SA compared to a non-attempter control group. We provide evidence of a 3-locus gene-gene interaction, and a putative gene-environment interaction, whereby genetic variation at the NTRK2 locus may moderate the risk associated with history of childhood abuse. CONCLUSION: Preliminary findings suggest that allelic variability in SLC1A2/3, 5-HTR1B and NTRK2 may be relevant to the underlying diathesis for suicidal acts.

Lived Lives at Fort Dunree: a rural Irish community perspective.

Background:  Elevated suicide rates have alarmed policy makers and communities. In these circumstances, the value of understanding more about communities and their potential role in suicide intervention is becoming more apparent. This study involved evaluating feedback from individuals with and without previous suicidal thinking who participated in an arts-science rural community-based intervention project around suicide in County Donegal, Ireland ( Lived Lives at Fort Dunree). Methods:  A combined quantitative and qualitative questionnaire was used to evaluate individual and community responses to the Lived Lives project. Results:  Participants ( n = 83), with and without a mental health history and previous suicidal ideation, reported they believed Lived Lives could have potential to help suicide-bereaved families, people with mental illness and people with suicidal thinking.  Qualitative results suggested its' suitability for specific groups affected by suicide. Discussion:  The evaluation of the Lived Lives project indicated that supervised, "safe-space" community intervention projects around suicide have inherent value with positive impacts for bereaved individuals and communities, including those who have experienced suicidal feelings. Future research should explore the transferability of these findings to other communities, and at-risk groups.

Bringing Lived Lives to Swift's Asylum: a psychiatric hospital perspective.

Background: Few "interventions" around suicide and stigma have reached into psychiatric institutions. Lived Lives is a science-arts approach to addressing suicide and stigma, informed by a psychobiographical and visual arts autopsy. The resulting artworks and mediated exhibition ( Lived Lives), has facilitated dialogue, response and public action around stigma-reduction, consistent with a community intervention. Recent evidence from Lived Lives moved us to consider how it may situate within a psychiatric hospital. Methods: Lived Lives manifested in St. Patrick's University Hospital (Ireland's oldest and largest psychiatric hospital) in November 2017.   A mixed-methods approach was used to evaluate the exhibition as a potential intervention to address stigma around suicide, with quantitative and qualitative data collected via written questionnaire and oral data collected via video documentation.  Bereavement support was available. A Clinician and an artist also provided independent evaluation. Results:  86 participants engaged with the exhibition, with 68 completing questionnaire data. Audiences included service users, policy makers, health professionals, senior hospital administrators and members of the public. 62% of participants who completed questionnaires were suicide-bereaved; 46% had experienced a mental health difficulty, and 35% had been suicidal in the past. 91% thought Lived Lives could be of benefit in the aftermath of a suicide death. Half of participants thought Lived Lives could help reduce suicidal feelings, whereas 88% thought it could benefit those with Mental Health difficulties. The emotional response was of a visceral nature, including fear, anger, sadness, disgust and anxiety. Conclusions: Lived Lives sits comfortably in discomfort, unafraid to call out the home-truths about stigma and its pervasive and pernicious impact, and with restoring identity at its core. Lived Lives can operate within a psychiatric hospital, as well as in community. The challenge is to move it forward for greater exposure and impacts in at-risk communities.

Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships.

Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases.

Limiting psychotropic medication prescription on discharge from psychiatric inpatient care: a possible suicide intervention?

OBJECTIVES: Restricting access to lethal means is an effective suicide prevention strategy. However, there is little discussion in the literature about the potential contribution of prescribing practices on discharge from inpatient psychiatric care (which has been established as a high-risk period for suicide) to suicide deaths by overdose of prescribed medication. This study aimed to assess the quantity, toxicity and potential lethality of psychotropic medication being prescribed on discharge from psychiatric care to those with and without indices of suicidality. METHODS: Patient demographic, clinical and prescription data were collected from 50 randomly selected charts following discharge from inpatient psychiatric care. Psychotropic medications (dose × duration) on discharge were converted to their equivalent doses of neuroleptics, antidepressants and anxiolytics to rate toxicity and potential lethality, using the Maudsley Prescribing Guidelines. Mood stabilizing medications were also documented. RESULTS: 39% of prescriptions analysed contained toxic and potentially fatal doses of either neuroleptic or antidepressant equivalent medication. CONCLUSIONS: Patient discharge from inpatient psychiatric care presents a golden opportunity to moderate access to potentially fatal psychotropic medication. Iatrogenic provision of lethal means for suicide during a period of increased risk and in a group at increased suicide risk may impact suicide prevention efforts and requires further in-depth research. Current prescribing practices may be a missed opportunity to intervene in this regard.

Worried, weary and worn out: mixed-method study of stress and well-being in final-year medical students.

OBJECTIVE: Although there is much focus on burnout and psychological distress among doctors, studies about stress and well-being in medical students are limited but could inform early intervention and prevention strategies. DESIGN: The primary aim of this mixed-method, cross-sectional survey was to compare objective and subjective levels of stress in final-year medical students (2017) and to explore their perspectives on the factors they considered relevant to their well-being. SETTING: University College Dublin, the largest university in Ireland. PARTICIPANTS: 161 of 235 medical students participated in this study (response rate 69%). RESULTS: 65.2% of students scored over accepted norms for the Perceived Stress Scale (34.8% low, 55.9% moderate and 9.3% high). 35% scored low, 28.7% moderate and 36.3% high on the Subjective Stress Scale. Thematic analysis identified worry about exams, relationships, concern about the future, work-life balance and finance; one in three students reported worry, irritability and hostility; many felt worn out. Cognitive impacts included overthinking, poor concentration, sense of failure, hopelessness and procrastination. Almost a third reported sleep and appetite disturbance, fatigue and weariness. A quarter reported a 'positive reaction' to stress. Positive strategies to manage stress included connection and talking, exercise, non-study activity and meditation. Unhelpful strategies included isolation and substance use. No student reported using the college support services or sought professional help. CONCLUSION: Medical students experience high levels of psychological distress, similar to their more senior doctor colleagues. They are disinclined to avail of traditional college help services. Toxic effects of stress may impact their cognition, learning, engagement and empathy and may increase patient risk and adverse outcomes. The focus of well-being in doctors should be extended upstream and embedded in the curriculum where it could prevent future burnout, improve retention to the profession and deliver better outcomes for patients.

Plasma polyunsaturated fatty acids and regional cerebral glucose metabolism in major depression.

Deficiencies in polyunsaturated essential fatty acids (PUFA) are implicated in mood disorders, although mechanisms of action and regional specificity in the brain are unknown. We hypothesized that plasma phospholipid PUFA levels are correlated with regionally specific relative cerebral metabolic rates of glucose (rCMRglu). Medication-free depressed subjects (N=29) were studied using [(18)F]-fluoro-2-deoxyglucose positron emission tomography. Docosahexaenoic acid (22:6n-3), arachidonic acid (20:4n-6), and eicosapentaenoic acid (20:5n-3) were assessed as a percentage of total phospholipid PUFA (DHA%, AA%, and EPA%, respectively). DHA% and AA% correlated positively with rCMRglu in temporoparietal cortex. In addition, DHA% correlated negatively with rCMRglu in prefrontal cortex and anterior cingulate. No correlations were seen with EPA%. Thus, under conditions of low plasma DHA, rCMRglu was higher in temporoparietal cortex and lower in anterior cingulate/prefrontal cortex. Opposing effects of DHA on these regions is a hypothesis that could be addressed in future prospective studies with n-3 supplementation. This pilot study is the first to demonstrate fatty acid and regionally specific correlations in the brain between plasma PUFA and rCMRglu in humans.

Stress in Irish dentists: developing effective coping strategies.

Recent research has highlighted the need to recognise occupation-specific risk factors contributing to stress and burnout. As health professionals, it is important for dentists to recognise the symptoms and the effects of stress on physical, psychological and professional well being. This article reviews the relevant scientific evidence, and provides practical cognitive psychological measures to guide improved well-being for dentists. Any stigma-related factors need to be acknowledged and addressed for the wellbeing of dentists and their patients, and the dental profession is well placed to provide leadership on this issue. Peer support is central to meeting this challenge.

The intra-day dynamics of affect, self-esteem, tiredness, and suicidality in Major Depression.

Despite growing interest in the temporal dynamics of Major Depressive Disorder (MDD), we know little about the intra-day fluctuations of key symptom constructs. In a study of momentary experience, the Experience Sampling Method captured the within-day dynamics of negative affect, positive affect, self-esteem, passive suicidality, and tiredness across clinical MDD (N= 31) and healthy control groups (N= 33). Ten symptom measures were taken per day over 6 days (N= 2231 observations). Daily dynamics were modeled via intra-day time-trends, variability, and instability in symptoms. MDD participants showed significantly increased variability and instability in negative affect, positive affect, self-esteem, and suicidality. Significantly different time-trends were found in positive affect (increased diurnal variation and an inverted U-shaped pattern in MDD, compared to a positive linear trend in controls) and tiredness (decreased diurnal variation in MDD). In the MDD group only, passive suicidality displayed a negative linear trend and self-esteem displayed a quadratic inverted U trend. MDD and control participants thus showed distinct dynamic profiles in all symptoms measured. As well as the overall severity of symptoms, intra-day dynamics appear to define the experience of MDD symptoms.

Resting regional brain activity correlates of verbal learning deficit in major depressive disorder.

Memory deficits are reported in major depressive disorder (MDD). Prefrontal cortical and mesiotemporal cortical (MTC)/subcortical regions are involved in the Buschke Selective Reminding Task (SRT), a verbal list-learning task. To determine whether depression-related changes in resting brain metabolism explain (in part) the deficits in SRT performance found in MDD, statistical correlation maps were calculated between SRT total recall score (TR) and relative regional cerebral metabolic rate for glucose (rCMRglu), measured by [18F]-flourodeoxyglucose (FDG) positron emission tomography (PET), in unmedicated, depressed MDD patients (N = 29). Subsequently, to explore hypothesized loss of top-down control in MDD, we compared the correlations between rCMRglu of SRT-relevant regions of the dorsolateral prefrontal cortex (dlPFC) and amygdala in a larger cohort of MDD (N = 60; 29 inclusive) versus healthy controls (HC) (N = 43). SRT performance of patients is on average 0.5 standard deviation below published normative mean. TR and rCMRglu positively correlate in bilateral dorsomedial PFC, dlPFC, dorsal anterior cingulate; negatively correlate in bilateral MTC/subcortical regions, and cerebellum. rCMRglu in dlPFC correlates negatively with that in amygdala in HC but not in MDD. Depression-related changes present in FDG-PET measured resting brain activity may be in part responsible for memory deficit found in MDD.

Serotonergic responses in depressed patients with or without a history of alcohol use disorders and healthy controls.

Dysfunction of serotonergic neurotransmission has been implicated in the etiopathogenesis of major depression (MDD) and alcohol use disorders (AUD). To compare serotonin function in MDD with co-occurring AUD (MDD/AUD), MDD without co-occurring AUD (MDD only) and healthy controls (HC) we sought to study differences in prolactin responses to fenfluramine administration in patients with MDD/AUD, patients with MDD only and HC. In all, 169 subjects (62 MDD/AUD, 75 MDD only, and 32 HC) were entered into the study. Controlling for gender, prolactin responses were lower in the MDD/AUD group compared to the MDD only or the HC group. Controlling for gender and aggression, prolactin responses in the MDD/AUD group remained significantly lower compared to the HC group but the difference between the MDD/AUD and the MDD only groups disappeared. The difference in prolactin responses between MDD/AUD and MDD only could be attributed to higher aggression scores in the MDD/AUD group compared to the MDD group.

Positron emission tomography study of regional brain metabolic responses to a serotonergic challenge in major depressive disorder with and without comorbid lifetime alcohol dependence.

This is the first study contrasting regional glucose metabolic rate (rCMRglu) responses to a serotonergic challenge in major depressive disorder (MDD) with and without comorbid alcohol dependence. In a university hospital, patients with MDD without a history of alcohol dependence (MDD only) and patients with MDD and comorbid alcohol dependence (MDD/ALC) were enrolled in this study. Subjects with comorbid borderline personality disorder were excluded. A bolus injection of approximately 5 mCi of (18)fluorodeoxyglucose was administered 3 h after the administration of placebo or fenfluramine. We found an anterior medial prefrontal cortical area where MDD/ALC subjects had more severe hypofrontality than MDD only patients. This area encompassed the left medial frontal and left and right anterior cingulate gyri. This group difference disappeared after fenfluramine administration. The fact that the observed group difference disappeared after the fenfluramine challenge suggests that serotonergic mechanisms play a role in the observed differences between the groups.

Lived Lives: A Pavee Perspective. An arts-science community intervention around suicide in an indigenous ethnic minority.

Background: Suicide is a significant public health concern, which impacts on health outcomes. Few suicide research studies have been interdisciplinary. We combined a psychobiographical autopsy with a visual arts autopsy, in which families donated stories, images and objects associated with the lived life of a loved one lost to suicide. From this interdisciplinary research platform, a mediated exhibition was created (Lived Lives) with artist, scientist and families, co-curated by communities, facilitating dialogue, response and public action around suicide prevention. Indigenous ethnic minorities (IEMs) bear a significant increased risk for suicide. Irish Travellers are an IEM with social and cultural parallels with IEMs internationally, experiencing racism, discrimination, and poor health outcomes including elevated suicide rates (SMR 6.6). Methods: An adjusted Lived Lives exhibition, Lived Lives: A Pavee Perspective manifested in Pavee Point, the national Traveller and Roma Centre. The project was evaluated by the Travelling Community as to how it related to suicide in their community, how it has shaped their understanding of suicide and its impacts, and its relevance to other socio-cultural contexts, nationally and internationally. The project also obtained feedback from all relevant stakeholders. Evaluation was carried out by an international visual arts research advisor and an independent observer from the field of suicide research. Results: Outputs included an arts-science mediated exhibition with reference to elevated Irish Traveller suicide rates. Digital online learning materials about suicide and its aftermath among Irish Travellers were also produced. The project reached its target audience, with a high level of engagement from members of the Travelling Community. Discussion: The Lived Lives methodology navigated the societal barriers of stigma and silence to foster communication and engagement, working with cultural values, consistent with an adapted intervention. Feedback from this project can inform awareness, health promotion, education and interventions around suicide and its aftermath in IEMs.

Neuroanatomic correlates of psychopathologic components of major depressive disorder.

BACKGROUND: The Hamilton Depression Rating Scale (HDRS) is widely used to measure the severity of depression in mood disorders. Total HDRS score correlates with brain metabolism as measured by fludeoxyglucose F 18 ([(18)F]-FDG) positron emission tomography. The HDRS comprises distinct symptom clusters that may be associated with different patterns of regional brain glucose metabolism. OBJECTIVE: To examine associations between HDRS component psychopathologic clusters and resting glucose cerebral metabolism assessed by [(18)F]-FDG positron emission tomography. Patients We evaluated 298 drug-free patients who met the DSM-III-R criteria for major depressive disorder. MAIN OUTCOME MEASURES: Five principal components were extracted from the 24-item HDRS for all subjects and ProMax rotated: psychic depression, loss of motivated behavior, psychosis, anxiety, and sleep disturbance. The [(18)F]-FDG scans were acquired in a subgroup of 43 drug-free patients in twelve 5-minute frames. Voxel-level correlation maps were generated with HDRS total and factor scores. RESULTS: Total HDRS score correlated positively with activity in a large bilateral ventral cortical and subcortical region that included limbic, thalamic, and basal ganglia structures. Distinct correlation patterns were found with the 3 individual HDRS factors. Psychic depression correlated positively with metabolism in the cingulate gyrus, thalamus, and basal ganglia. Sleep disturbance correlated positively with metabolism in limbic structures and basal ganglia. Loss of motivated behavior was negatively associated with parietal and superior frontal cortical areas. CONCLUSIONS: Different brain regions correlate with discrete symptom components that compose the overall syndrome of major depression. Future studies should extend knowledge about specific regional networks by identifying responsible neurotransmitters related to specific psychopathologic components of mood disorders.

Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy.

BACKGROUND: Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT. METHODS: 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion. RESULTS: At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-ß than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-ß levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-ß changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-α and CRP levels were found in relation to melancholia or response to ECT. LIMITATIONS: As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use. CONCLUSIONS: Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-ß, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotrophin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation.