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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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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.

BackgroundPatients 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.MethodsTo 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.ResultsPatients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial η2 = .25, P < .001, and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial η2 = .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 η2 = .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.ConclusionsSuicidal ideation may be uniquely associated with inflammation in depressed patients.

Blunted neurohormonal responses to serotonergic agents are found in major depression and suicidal behavior, but there have been no prospective studies of their relationship to later suicide attempt. In this study, healthy volunteers and depressed subjects were administered a fenfluramine (FEN) and placebo challenge test at baseline and then followed for 2 years. Seven subjects made suicide attempts within the follow-up period. Healthy volunteers, depressed non-attempters, depressed past suicide attempters, and depressed future attempters were compared on plasma prolactin and cortisol responses, as well as on mood (Profile of Mood States; POMS) and behavioral measures that were assessed at baseline and at the end of each challenge testing day. Both past and future attempters had lower total prolactin output (area under the curve) in response to FEN relative to non-patients. Future attempters had lower cortisol response relative to all other groups. All subject groups reported a decrease in POMS Fatigue subscale score and increase in finger tapping rate after receiving FEN. Depressed subjects reported a significant decline in POMS Total, Depression, and Tension/Anxiety scores, but future attempters' did not, showing a slight mean increase. Lower cortisol response correlated with greater suicidal ideation 3 months and 1 year post-study. Logistic regression revealed that blunting of cortisol response and worsening of mood after FEN, and younger age could be used to predict later suicide attempt in the majority of cases (4/7). Results suggest that blunted cortisol and unfavorable acute mood response to serotonergic challenge, in the context of the general activating effects of these drugs, may be a risk factor for later suicide attempt. [ABSTRACT FROM AUTHOR]

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 ([18F]-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 [18F]-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 [18F]-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. [ABSTRACT FROM AUTHOR]

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. • The intra-day dynamics of five symptom constructs in Major Depression (MDD) were explored. • The MDD group had distinct dynamics to controls in affect, self-esteem, suicidality and tiredness. • Tiredness had decreased variability and all other symptoms increased variability in MDD. • Increased instability was found in affect, self-esteem and suicidality in MDD. • Positive affect had a more pronounced and tiredness a less pronounced diurnal time-trend in MDD. [ABSTRACT FROM AUTHOR]

Highlights • Performance of major depressive disorder (MDD) subjects on the Buschke Selective Reminding Task (SRT) is on average 0.5 standard deviation below published normative mean. • SRT total recall (TR) score and relative regional cerebral metabolic rate for glucose (rCMRglu) positively correlate in bilateral dorsomedial prefrontal cortex (PFC), dorsolateral PFC, and dorsal anterior cingulate. • TR and rCMRglu negatively correlate in bilateral mesiotemporal cortex (MTC) and basal ganglia. • rCMRglu in dorsolateral PFC correlates negatively with that in MTC in healthy comparison subjects but not in MDD subjects. Abstract 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. [ABSTRACT FROM AUTHOR]

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-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.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-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. [ABSTRACT FROM AUTHOR]

Abstract: Background: We compared brain-map correlations of relative cerebral glucose metabolism (rCMRglu) with psychopathologic factors derived from the self-rated Beck Depression Inventory (BDI) and factors from the clinician-rated Hamilton Depression Rating Scale (HDRS) factors, seeking an anatomic basis for differences in self and clinician ratings. Methods: [18F]-FDG Positron Emission Tomography generated rCMRglu, SPM-estimated, voxel-level, brain correlation maps with BDI factor scores and HDRS factor scores in medication-free major depressive disorder. Results: Regional brain correlates of BDI are more extensive than HDRS, even when adjusting for variance accounted for by the HDRS. Factors comprising the BDI were associated with distinct cortical and subcortical regions. The degree of overlap in factor correlation brain maps is explained by the variance shared by BDI and HDRS factor scores. Conclusion: Self and clinician-rated aspects of depression have common and distinct neuroanatomic correlates that reflect correlations between rating scales, but correlations between glucose metabolism and self-rated depression were anatomically more extensive in this sample. Findings highlight the importance and biological underpinnings of these subjective features of major depression. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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 18fluorodeoxyglucose 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. [Copyright &y& Elsevier]

Background: Short-term discontinuation of psychiatric medications is required in many types of research studies. Yet there are few studies of the clinical impact of psychotropic discontinuation. We studied the impact of a short-term medication washout in unipolar depressed patients consecutively admitted to hospital for neuroimaging and cerebrospinal fluid (CSF) studies.Method: Patients (n=51) with unipolar depression who were taking antidepressant or mood stabilizing medication at or within 1 week of admission, and who had not been responding satisfactorily, were assessed for severity of psychopathology within 1 week of hospital admission and 41 of the group were reassessed following an approximately 2-week medication washout.Results: On average, patients remained stable during the washout or improved on clinical measures. No serious adverse clinical changes were observed.Limitations: Potential sample bias, small sample size.Conclusion: The results suggest that similar studies can be conducted without causing undue worsening of symptoms. The benefit of medication washout may be related to the fact that many of the patients had been responding poorly to the medication they were taking. There is a need for further research on the effects of medication washout, for example in outpatients or those who are responding well to treatment, but have intolerable side-effects. [ABSTRACT FROM AUTHOR]