Melancholic Depressed Patients Research Articles

Prevalence of restless legs symptoms according to depressive symptoms and depression type: a cross-sectional study

Background: Restless legs syndrome is a sensorimotor disorder and it is associated with several other diseases especially mental illnesses.Aims: To analyze the relationship between the symptoms of restless legs syndrome and the severity of depressive symptoms and the prevalence of restless legs symptoms in depression subtypes.Methods: A cross-sectional study of primary care patients in the Central Finland Hospital District. The prevalence of restless legs symptoms was studied in 706 patients with increased depressive symptoms and 426 controls without a psychiatric diagnosis by using a structured questionnaire. The depressive symptoms were evaluated with the Beck Depression Inventory (BDI) and the psychiatric diagnosis was confirmed by means of a diagnostic interview (Mini-International Neuropsychiatric Interview). The subjects with increased depressive symptoms were divided into three groups (subjects with depressive symptoms without a depression diagnosis, melancholic depression and non-melancholic depression).Results: In the whole study population, the prevalence of restless legs symptoms increased with the severity of depressive symptoms. The prevalence of restless legs symptoms was highest in the melancholic and non-melancholic depressive patients (52 and 46%, respectively) and then in subjects with depressive symptoms without a depression diagnosis (43.4%), but the prevalence was also substantial (24.6%) in subjects without a psychiatric diagnosis.Conclusions: Restless legs symptoms are very common in primary care among subjects with depression, regardless of the depression type. The prevalence of restless legs symptoms increased with increasing severity of depressive symptoms, regardless of the diagnosis. These findings should be considered in clinical evaluation and treatment of patients visiting their physician due to restless legs or depressive symptoms.

HPA Axis Function as Biomarker for Atypical and Melancholic Depression

HPA Axis Function as Biomarker for Atypical and Melancholic Depression

Metabolomic biosignature differentiates melancholic depressive patients from healthy controls

BackgroundMajor depressive disorder (MDD) is a heterogeneous disease at the level of clinical symptoms, and this heterogeneity is likely reflected at the level of biology. Two clinical subtypes within MDD that have garnered interest are “melancholic depression” and “anxious depression”. Metabolomics enables us to characterize hundreds of small molecules that comprise the metabolome, and recent work suggests the blood metabolome may be able to inform treatment decisions for MDD, however work is at an early stage. Here we examine a metabolomics data set to (1) test whether clinically homogenous MDD subtypes are also more biologically homogeneous, and hence more predictiable, (2) devise a robust machine learning framework that preserves biological meaning, and (3) describe the metabolomic biosignature for melancholic depression.ResultsWith the proposed computational system we achieves around 80 % classification accuracy, sensitivity and specificity for melancholic depression, but only ~72 % for anxious depression or MDD, suggesting the blood metabolome contains more information about melancholic depression.. We develop an ensemble feature selection framework (EFSF) in which features are first clustered, and learning then takes place on the cluster centroids, retaining information about correlated features during the feature selection process rather than discarding them as most machine learning methods will do. Analysis of the most discriminative feature clusters revealed differences in metabolic classes such as amino acids and lipids as well as pathways studied extensively in MDD such as the activation of cortisol in chronic stress.ConclusionsWe find the greater clinical homogeneity does indeed lead to better prediction based on biological measurements in the case of melancholic depression. Melancholic depression is shown to be associated with changes in amino acids, catecholamines, lipids, stress hormones, and immune-related metabolites. The proposed computational framework can be adapted to analyze data from many other biomedical applications where the data has similar characteristics.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2953-2) contains supplementary material, which is available to authorized users.

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

BackgroundImmune 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. Methods55 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. ResultsAt baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-β than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-β 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-β 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. LimitationsAs a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use. ConclusionsMelancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-β, 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.

Cognitive function after clinical remission in patients with melancholic and non-melancholic depression: A 6 month follow-up study

BackgroundCognitive symptoms are core symptoms with an impact on functioning in depression. Remission is considered as the main objective of the management and treatment of depression. This study was aimed to compare cognitive performance between melancholic (MelD) and non-melancholic depression (NMelD) and to determine whether these cognitive alterations remain after clinical remission. MethodsWe performed a 6 month follow-up study of 88 melancholic and non-melancholic depressive patients. Sociodemographic and clinical characteristics were recorded. Depression was examined using the Hamilton Depression Rating Scale and the CORE Index for Melancholia. Cognitive performance was assessed with the Trail Making Test (TMT), the Digit Span subtest of the WAIS-III, Stroop Colour Word Test (SCWT), the Tower of London (TOL DX), the Controlled Oral Word Association Test (FAS), Semantic Verbal Fluency and Finger Tapping Test (FTT). ResultsMelD patients show worse performance than N-MelD at baseline, with significant differences at Digit Span subtest of WAIS Part I and Part II, SCWT Part I and Part II, TOL DX, Total Problem Solving, Total Execution Time and FTT- Preferred hand. Cognitive impairment remains at six months follow-up after clinical remission in MelD. In the comparison between remitted and non-remitted patients, cognitive impairment in Trail Making Test Part B and Verbal and Semantic Fluency (Animals) remains after clinical remission in MelD group but not in non-melancholic patients. LimitationsThe use of psychopharmacological treatment and the small sample of melancholic patients. ConclusionsPatients with MelD do not improve cognitive performance despite clinical remission compared with remitted NMelD patients. The persistence of some cognitive dysfunctions in MelD remitted patients could represent a trait marker of a different depressive subtype and not be secondary to disease severity.

Electroconvulsive therapy's mechanism of action: neuroendocrine hypotheses.

Despite a range of etiological theories since the introduction of electroconvulsive therapy (ECT) more than 75 years ago, its mechanism of action remains poorly understood. The neuroendocrine hypothesis is based on the seizure-related release of hypothalamic hormones into the blood and cerebrospinal fluid and evidence of endocrine dysfunction in many patients with severe mood disorder. The specific effect of ECT was hypothesized to result from the transverse passage of current through the brain with direct stimulation of axial structures including the diencephalon. The prompt release of adrenocorticotropic hormone, cortisol, and prolactin into blood followed ECT with a return to pretreatment baseline levels in several hours. The elevated levels of hormones were absorbed by the cerebrospinal fluid, providing contact with brain cells and central nervous system structures. An apparently specific pattern of ECT-induced hormone changes, limited to prolactin and cortisol, suggested that ECT released a substance with dopaminergic antagonist and antipsychotic properties. As hypothalamic dysfunction is a key finding in endogenomorphic depression and the abnormal endocrine and physiological functions usually normalize with recovery, this led to a search for biological markers that would supplement clinical assessment of diagnosis and treatment response. One of these, the overnight dexamethasone suppression test found that 40% to 50% of melancholic depressed patients had abnormal results, whereas 90% of control patients suppressed normally. This was followed by a period of uncritical overenthusiasm followed by wholesale rejection of the clinical neuroendocrine strategies. Several key methodological issues received inadequate attention, and there have been calls to revisit this topic.

Does age impact on rating melancholic and non-melancholic depressive symptoms?

BackgroundMelancholic depression has long evaded attempts at accurate definition. A range of factors may influence symptom reporting and so compromise definitional attempts. One possible factor is age, and its possible influence led to the current study examining the impact of age on the reporting of melancholic and non-melancholic depressive symptoms. MethodsA set of 32 self-rated depression items from the SDS depression measure and weighted to both melancholic and non-melancholic depressions were analysed for any impact of age in clinically diagnosed melancholic and non-melancholic depressed patients. ResultsMelancholic and non-melancholic patients did not differ by gender, severity of depression or duration of current episode. None of the melancholic items from the SDS showed a linear increase with age. Analyses of factor analytic derived constructs identified one factor as evidencing a linear decrease (rather than increase) in scores with age in the melancholic patients. Differential item functioning was only found for melancholic patients’ scores on the ‘non-melancholic scale’, with a decrease across age. Simulated data revealed, for the same scale, a decrease in both melancholic and non-melancholic patients. LimitationsOur assessment strategies effectively excluded those with severe melancholia and who were unable to complete self-report measures, and may have contributed to study findings. As we had few patients over the age of 70, age effects in elderly patients may have missed identification. ConclusionsWe found no evidence for melancholic symptoms to increase in severity with age. To the contrary, some items decreased in severity with age in both melancholic and non-melancholic patients. Overall study results are reassuring in indicating that age is unlikely to distort analyses seeking to differentiate those with melancholic and non-melancholic depressive conditions.

The superiority of antidepressant medication to cognitive behavior therapy in melancholic depressed patients: a 12-week single-blind randomized study

To pursue the previously long-standing but formally untested clinical view that melancholia is preferentially responsive to antidepressant medication in comparison with psychotherapy [specifically Cognitive Behavior Therapy (CBT)]. Second, to determine whether a broader action antidepressant medication sequencing regimen is superior to a Selective Serotonin Reuptake Inhibitor (SSRI) alone. We sought to recruit a large sample of participants with melancholic depression for a 12-week trial but inclusion criteria compromised recruitment and testing the second hypothesis. The first hypothesis was evaluated by comparing 18 participants receiving antidepressant medication to 11 receiving CBT. Primary study measures were the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Endogenous Subscale (HES), rated blindly, while several secondary measures also evaluated outcome. Participants receiving medication had a superior 12-week outcome to those receiving CBT, with significant differences present on primary measures as early as 4 weeks. At trial conclusion, the percentage improvement in HAM-D scores was 61.1% vs. 34.4%, respectively [Number Needed to Treat (NNT) = 3.7] and with those in receipt of medication returning non-significantly higher HAM-D responder (66.6% vs. 36.4%, NNT = 2.8) and remission (66.7% vs. 45.4%, NNT = 4.7) rates. As the sample size was small and participants evidenced only moderate levels of depression severity, the study risked being underpowered and idiosyncratic. Despite the small sample, the superiority of antidepressant medication to CBT in those with a melancholic depression was distinctive in this pilot study.

Melancholic and atypical major depression — Connection between cytokines, psychopathology and treatment

Growing scientific evidence indicates that there is a correlation between depression and alternations in the immune system. The main aim of the study was to investigate serum levels of Interleukin-6 (IL-6) and Tumour Necrosis Factor-alpha (TNF-α) in melancholic and atypical depressive patients during acute exacerbations of illness, compared to healthy subjects. The secondary aim was to explore a possible association between cytokine levels and clinical characteristics, as well as total duration of prior antidepressant treatment. We measured serum levels of IL-6 and TNF-α in 47 patients suffering from major depressive disorder (MDD) (29 melancholic and 18 atypical) in exacerbation of illness, compared to 39 healthy controls, matched by sex, body mass index (BMI) and smoking habits. Serum levels of IL-6 and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). The severity of psychopathology was assessed using the Hamilton Depression Rating Scale (HDRS). IL-6 was significantly elevated in melancholic depressive patients (MDD-M) compared to healthy controls, while no difference was found between the patients with atypical depression (MDD-A) and the healthy group. Lower TNF-α serum level was found both in melancholic and in patients with atypical depression, compared with healthy subjects. We detected a positive correlation between cytokine levels in atypical, but not in melancholic subjects. Sex, age, smoking habits and BMI were not associated to cytokine levels in neither group. Clinical parameters (duration of illness, current episode, age of onset) were related to cytokine levels in atypical depression, while the duration of lifetime exposure to antidepressant treatment correlated to IL-6 serum levels in both melancholic and atypical depression. Our results suggest that the difference in pro-inflammatory cytokine levels could reflect a biological difference between melancholic and atypical depression. A positive correlation between the cytokines (TNF-α and IL-6) observed in depressive patients with atypical features, might be influenced by chronic course of illness, while IL-6 elevation could represent a state indicator for acute exacerbation, especially in melancholic patients. Total duration of antidepressant treatment could be a relevant factor influencing the immune status of patients who suffer either from melancholic or atypical depression.

The impact of depression heterogeneity on cognitive control in major depressive disorder

Depressed patients display a variety of deficits in neuropsychological function, and contradictory findings in the literature may be due to disorder heterogeneity. The aim of this study was to examine the impact of severity, subtype and symptoms on cognitive control. Neuropsychological function across a range of cognitive control tasks was examined in melancholic (n = 65) and non-melancholic depressed patients (n = 59) relative to controls (n = 124). The relationship between subtype (melancholia vs non-melancholia) and anxiety was also examined. Melancholia was characterised by attention and working memory deficits typically associated with the dorsolateral prefrontal cortex, while non-melancholia was characterised by verbal memory recall deficits indicative of left frontal lobe and medial temporal lobe function. The severity of anxious arousal and psychomotor disturbance contributed to cognitive impairment more than the severity of depression symptoms and anxious apprehension. Findings highlight a differential impact of depression subtype and severity, and suggest that anxious arousal and psychomotor disturbance may contribute to poorer performance on neuropsychological tasks associated with dorsolateral prefrontal cortex function.

CRF test in melancholic depressive patients with partial versus complete relapses: A 2-year follow-up study

Background: Patients with depressive disorders present abnormalities in the hypothalamic pituitary adrenal (HPA) axis. The effects of a partial relapse with regard to HPA axis has not been studied so far. Aim: To assess whether patients with partial relapse have a different neuroendocrine profile compared with those with complete relapse and with those without relapse over a 2-year follow-up. Methods: The adrenocorticotropin hormone (ACTH) and cortisol responses to corticotrophin releasing factor (CRF) stimulation was assessed in 62 outpatients diagnosed with unipolar depressive disorder with melancholic features according to DSM-IV. Twenty-three healthy controls were included in the study for comparison. Monthly follow-up visits were performed over a 2-year period after remission; partial and complete relapses were established using the Hamilton Depression Rating Scale (HDRS) and according to Frank's criteria. Fifty-four patients completed the study. A comparative statistical analysis was performed. Results: Stratifying the net area under cortisol curve (NAUCC) (µg/ml/min) at three levels—< 150, 150–350 and ≤ 350—significant differences appear between the three depressive groups of patients (non-relapsers, partial relapsers and complete relapsers). Particularly, there are more patients with a NAUCC ≤ 350 who show partial or complete relapses than patients with a NAUCC ≤ 350 who do not relapse (P ≤ 0.05). Conclusions: Our results show an increasingly altered HPA axis in those depressive patients with complete or partial relapses compared with those who did not relapse or with healthy controls, but there are not differences in HPA axis between partial and complete relapsers.

The impact of depression heterogeneity on inhibitory control

Major depressive disorder (MDD) is associated with deficits in executive cognitive function, including inhibitory control. However, inconsistencies have been found across studies. Depression is a heterogeneous disorder and these inconsistencies may therefore relate to heterogeneity in relatively small samples. Here we sought to examine event-related potentials (ERPs) during a cognitive Go/No-Go task in melancholic (n = 60) and non-melancholic depressed patients (n = 54) relative to controls (n = 114). Behavioural responses indicate that inhibitory control processes are differentially affected by subtypes of depression such that melancholic patients exhibit a greater number of commission errors and more variable response rates in comparison to non-melancholic patients and controls respectively. However, ERPs do not differ during a cognitive Go/No-Go task when ERPs associated with correct responses are examined. These findings indicate that while patients with melancholia differ from patients without melancholia and controls, no neurophysiological differences are observed when controlling for observable behavioural impairment.

Is treatment-resistance in unipolar melancholic depression characterized by decreased serotonin2A receptors in the dorsal prefrontal – Anterior cingulate cortex?

ObjectivesQuite a number of patients diagnosed with major depression are resistant to several well carried-out psychopharmacological interventions. It remains unclear as to how the serotonergic system is implicated in the phenomenon of treatment-resistance. MethodsWe examined the involvement of post-synaptic 5-HT2A receptors in the pathophysiology of treatment-resistance in unipolar melancholic major depression with 123I-5-I-R91150 SPECT. 15 antidepressant-naïve (ADN) first-episode depressed patients, 15 antidepressant-free treatment-resistant depressed (TRD) patients and 15 never-depressed individuals, matched for age and gender were studied. ResultsCompared to ADN patients and healthy controls, TRD patients displayed significantly lower 5-HT2A receptor binding index (BI) in the dorsal regions of the prefrontal and the anterior cingulate cortex. No significant 5-HT2A receptor BI differences between ADN patients and controls were observed. ConclusionsAt the cortical level, 5-HT2A receptor BI does not significantly differ in first-episode melancholic depressed patients compared to healthy controls. This observation might imply a limited short-term impact on the serotonergic system in first episode depression. Our results also suggest that when encountered with treatment-resistance, the 5-HT2A receptors in the DPFC-ACC axis are significantly down-regulated. However, whether this assumed underlying pathophysiological mechanism is due solely to abnormalities in the serotonergic system remains to be answered.This article is part of a Special Issue entitled ‘Anxiety and Depression’.

Is context everything to the definition of clinical depression? A test of the Horwitz and Wakefield postulate

In arguing for the need to distinguish clinical depression from sadness, Horwitz and Wakefield argued for weighting consideration to nuances of life event stressors. Their definition of clinical depression corresponds to the concept of endogenous depression or melancholia, while their model would position reactive (or context specific) non-melancholic depressive disorders more as manifestations of 'sadness' rather than as clinical depression. We test their postulate by examining the extent to which 141 clinically diagnosed melancholic and non-melancholic depressed patients reported episodes as being preceded by a life event stressor or not--and the salience of any life stressor to episode onset and severity. While melancholic patients were more likely than non-melancholic patients to report episodes coming 'out of the blue' and to be more severe than might be expected from the severity of antecedent stressors, differences were more ones of degree and not absolute. Such context variables appeared, however, to differentiate melancholic and non-melancholic patients more consistently than depression symptom variables. As depression severity and impairment levels did not differ across the melancholic and non-melancholic patients, findings were unlikely to be artefacts of such factors. The study finds some support for the Horwitz and Wakefield hypothesis of clinical (or, at least melancholic) depression requiring independence of context or an antecedent stressor, but with precision likely to be compromised by nuances intrinsic to assessment of life event stressors and their contribution to depression onset, difficulties in defining valid 'melancholic' and 'non-melancholic' depressive sub-groups and the parsimony of the hypothesis.

Melancholic versus non-melancholic depression: differences on cognitive function. A longitudinal study protocol

BackgroundCognitive dysfunction is common among depressed patients. However, the pattern and magnitude of impairment during episodes of major depressive disorder (MDD) through to clinical remission remains unclear. Heterogeneity of depressive patients and the lack of longitudinal studies may account for contradictory results in previous research.Methods/DesignThis longitudinal study will analyze cognitive differences between CORE-defined melancholic depressed patients (n = 60) and non-melancholic depressed patients (n = 60). A comprehensive clinical and cognitive assessment will be performed at admission and after 6 months. Cognitive dysfunction in both groups will be longitudinally compared, and the persistence of cognitive impairment after clinical remission will be determined.DiscussionThe study of neuropsychological dysfunction and the cognitive changes through the different phases of depression arise a wide variety of difficulties. Several confounding variables must be controlled to determine if the presence of depression could be considered the only factor accounting for group differences.

Reduced left subgenual anterior cingulate cortical activity during withdrawal-related emotions in melancholic depressed female patients

Background Research regarding the neurocircuitry in mood disorders suggests an important role for affective information processing of the subgenual part of the anterior cingulate cortex (Cg25: Brodmann area 25). Objective In this study, we focused on Cg25 neuronal responses in depressed females using a paradigm in which emotions are elicited without explicit cognitive control, relying on the salient nature of the mood inducing stimuli eliciting approach-related emotions (like happiness) or withdrawal-related emotions (like disgust). Methods Twelve treatment-resistant melancholic depressed women and 12 healthy female control subjects were asked to passively view blocks of emotionally valenced baby faces while undergoing functional magnetic resonance imaging (fMRI). Results Compared to the healthy females, the depressed patients displayed significantly higher bilateral Cg25 neuronal activities in both emotional conditions. In melancholically depressed women, we found significantly less left-sided than right-sided Cg25 neuronal activity during the withdrawal-related emotions, while right-sided Cg25 activity was comparable for both emotional responses. Conclusions Our results indicate that in depressed women the left Cg25 modulates intense visceral emotional responses to aversive visual stimuli. This could help explain why the left Cg25 provides a valid target region for antidepressant treatment strategies in unipolar melancholic depression.

HF-rTMS treatment decreases psychomotor retardation in medication-resistant melancholic depression

Repetitive Transcranial Magnetic Stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising treatment strategy for depression. As one of the key features of melancholic depression is disturbances in psychomotor activity, we wanted to evaluate whether HF-rTMS treatment could influence psychomotor symptoms. Twenty antidepressant-free unipolar melancholic depressed patients, all at least stage III medication-resistant, were studied. All were treated with 10 sessions of High-Frequency (HF)-rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) under MRI guidance. Forty percent of the patients showed a reduction of at least 50% on their initial 17-item Hamilton Depression Rating Score (HDRS) scale and were defined as clinical responders. Regardless of clinical outcome HF-rTMS treatment resulted in significant decreases on the Depressive Retardation Rating Scale (DRRS) scores. Although this was an open study in a relatively small sample, our results suggest that HF-rTMS might act on the ‘psychomotor’ level and these findings could add some further information as to why this kind of treatment can be beneficial for severely depressed patients of the melancholic subtype.

A “hypersensitive” hypothalamic-pituitary-adrenal system could be indicative for a negative clinical high-frequency repetitive transcranial magnetic stimulation outcome in melancholic depressed patients

Depressed patients are currently treated with daily high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) sessions applied to the left dorsolateral prefrontal cortex (DLPFC), spread over a period of 2 weeks or more.1-3 An important aspect of the physiology of rTMS could be related to the endocrinologic response of the hypothalamic-pituitary-adrenal (HPA) system.4-9 Keck10 proposed that TMS influences occur at the hypothalamic level, suggesting that the prefrontal cortex participates in the rTMS-induced blunted response of HPA activity.

Prediction of relapse in melancholic depressive patients in a 2-year follow-up study with corticotropin releasing factor test

Purpose To study the power of CRF stimulation test to predict relapse in a sample of melancholic depressive patients in depressed phase, followed-up over a two-year period from the moment they achieved complete remission of depressive symptoms. Methods Fifty-one outpatients diagnosed with unipolar depressive disorder with melancholic features according to DSM-IV were assessed with the CRF test. The Structured Clinical Interview for DSM-IV (SCID-IV) was used for diagnosis. Monthly follow-up visits were held over a two-year period after remission; relapse was established using HDRS according to Frank's criteria [Frank E, Prien RF, Jarret RB, Keller MB, Kupfer DJ, Lavori PW, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991;48:851–5]. Forty-three patients completed the study. Non-controlled antidepressant treatment protocols were used. Predictive statistical analysis was performed through logistic regression. Findings The final predictive model included three variables: net area under cortisol curve (NAUCC), previous suicide attempt, and stress during follow-up. Sensitivity was of 89%, and specificity was of 92%. NAUCC has shown a predictive power of 80%, with an optimal cut-off point of 251.24 μg/ml/min. Conclusions Cortisol is the hormone of the HPA axis which shows the highest power to predict relapse. NAUCC is the most relevant variable. The complete predictive model is a complex combination of biological, clinical and psychoenvironmental variables (NAUCC, previous suicide attempts, and stress during follow-up). Further studies with better control of the psychoenvironmental variables are required to obtain more precise neuroendocrine findings.

P02-77 Can salivary cortisol assessment from a single HF-rTMS session predict clinical outcome in melancholic depressed patients? A pilot study

Aim:The underlying physiological mechanisms as to why repetitive transcranial magnetic stimulation (rTMS) can treat depressed patients remains unclear and no clear biological markers are available to indicate a positive outcome for a given patient. Some data suggest that rTMS can influence hypothalamic-pituitary-adrenal (HPA) processes. In this study, we wanted to evaluate whether one session of high frequency (HF)-rTMS applied on the left dorsolateral prefrontal cortex (DLPFC) can predict a successful treatment outcome in a sample of antidepressant free unipolar depressed patients of the melancholic subtype.Methods:Twenty one right-handed treatment resistant depressed patients were studied. Fifty two percent of the patients were considered as treatment responders, as defined by a 50% reduction in her/his baseline 17-item Hamilton Depression Rating Scale (HDRS) score. To examine acute HF-rTMS effects on the HPA- axis, we analyzed salivary cortisol levels, using a sham-controlled, ‘single’ blind, crossover design. Areas under the curves (AUC) were calculated for both real and sham HF-rTMS.Results:Real HF-rTMS resulted in salivary cortisol decreases, however only in HF-rTMS non-responders. No HF-rTMS influences were found in the responder group. Sham stimulation did not affect the HPA-axis. Non-responders were found to display a higher level of co-morbid personality disorders.Conclusion:Our results may provide more insight into the underlying working mechanisms of HF-rTMS and could add further information about endocrinological functioning in affective disorders. Furthermore, personality features in combination with a ‘super-sensitive’ HPA system could be of importance to predict clinical outcome.