Vegetative Symptoms Of Depression Research Articles

Treatment-resistant depression and peripheral C-reactive protein.

C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.AimTo explore CRP in MDD and its phenotypic associations. We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes. Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood. CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.Declaration of interestS.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.

Two distinct symptom-based phenotypes of depression in epilepsy yield specific clinical and etiological insights.

Depression is common but underdiagnosed in epilepsy. A quarter of patients meet criteria for a depressive disorder, yet few receive active treatment. We hypothesize that the presentation of depression is less recognizable in epilepsy because the symptoms are heterogeneous and often incorrectly attributed to the secondary effects of seizures or medication. Extending the ILAE's new phenomenological approach to classification of the epilepsies to include psychiatric comorbidity, we use data-driven profiling of the symptoms of depression to perform a preliminary investigation of whether there is a distinctive symptom-based phenotype of depression in epilepsy that could facilitate its recognition in the neurology clinic. The psychiatric and neuropsychological functioning of 91 patients with focal epilepsy was compared with that of 77 healthy controls (N=168). Cluster analysis of current depressive symptoms identified three clusters: one comprising nondepressed patients and two symptom-based phenotypes of depression. The 'Cognitive' phenotype (base rate=17%) was characterized by symptoms taking the form of self-critical cognitions and dysphoria and was accompanied by pervasive memory deficits. The 'Somatic' phenotype (7%) was characterized by vegetative depressive symptoms and anhedonia and was accompanied by greater anxiety. It is hoped that identification of the features of these two phenotypes will ultimately facilitate improved detection and diagnosis of depression in patients with epilepsy and thereby lead to appropriate and timely treatment, to the benefit of patient wellbeing and the potential efficacy of treatment of the seizure disorder. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy".

A Cluster Model of Temperament as an Indicator of Antidepressant Response and Symptom Severity in Major Depression

ObjectiveNot enough is known about which patients suffering from major depressive disorder benefit from antidepressant drug treatment. Individual temperament is relatively stable over a person's lifespan and is thought to be largely biologically predefined. We assessed how temperament profiles are related to depression and predict the efficacy of antidepressant treatment.MethodsWe recruited one hundred Finnish outpatients (aged 19 to 72) suffering from major depressive disorder, of whom 86 completed the 6-week study. We assessed their temperament features with the Temperament and Character Inventory and used cluster analysis to determine the patient's temperament profile. We also categorized the patients according to the vegetative symptoms of major depressive disorder.ResultsThere was an association between skewed temperament profile and severity of major depressive disorder, but the temperament profiles alone did not predict antidepressant treatment response. Those with higher baseline vegetative symptoms score had modest treatment response. Our model with baseline Montgomery Åsberg Depression Rating Scale (MADRS) vegetative symptoms, age and temperament clusters as explanatory variables explained 20% of the variance in the endpoint MADRS scores.ConclusionThe temperament clusters were associated both with severity of depression and antidepressive treatment response of depression. The effect of the temperament profile alone was modest but, combined with vegetative symptoms of depression, their explanatory power was more marked suggesting that there could be an association of these two in the biological basis of MDD.

Transcranial direct current stimulation (tDCS) for depression: Analysis of response using a three-factor structure of the Montgomery–Åsberg depression rating scale

BackgroundThere is growing evidence that transcranial direct current stimulation (tDCS) may be an effective treatment for depression. However, no study to date has profiled the antidepressant effects of tDCS using items or factors on depression symptom severity rating scales. This could potentially provide information about the mechanisms by which tDCS achieves its antidepressant effects and also identify clinical predictors of response. MethodsThe present study analysed scores on the Montgomery–Åsberg depression rating scale (MADRS) from a randomised, sham-controlled trial of tDCS (Loo et al., 2012. British Journal of Psychiatry. 200, 52–59) using a three-factor model of MADRS items (Suzuki et al., 2005. Depression and Anxiety. 21, 95–97) encompassing dysphoria, retardation and vegetative symptoms. ResultsParticipants in the active tDCS treatment group showed significant improvement in dysphoria while participants in the sham treatment group did not. While both groups showed improvement in retardation symptoms, improvement was significantly greater in the active tDCS group. Both groups also showed improvement in vegetative symptoms but there were no between-group differences. LimitationsFurther studies with larger sample sizes are warranted to investigate the generalisability of results and whether the MADRS factor structure may change as a result of the specific treatment used. ConclusionstDCS appears to be particularly effective in treating dysphoria and retardation, but not vegetative symptoms of depression. This may have implications for selection of types of depression most likely to respond to this treatment.

Is Increased Libido an Atypical Symptom of Bipolar Depression? An Interesting Case

Decreased libido is recognized as one of the vegetative symptoms of depression. Increased libido has not been acknowledged as one of its symptoms, neither has it been reported, particularly in depressed bipolar patients. We hereby report a case of atypical presentation of increased sexual function in a patient in depressed phase of bipolar II thereby querying the fact, whether increased libido is actually an unrecognized atypical symptom of bipolar depression. A 48-year-old male presented with mood swings whereby his sexual function was increased during his depressive phase. Antidepressant, mood stabilizer, and antipsychotic medication were administered. Electroconvulsive therapy (ECT) was offered for augmentation therapy. When sexual dysfunction is not identified, there is a risk of misdiagnosis and mismanagement. Patient did not attain full remission with medication. Compliance with medication was an issue, most probably due to the sexual side effects. The patient refused ECT. This case highlights atypical presentation of high libido in a patient in the depressive phase of bipolar II disorder. The uncommon presentation of a common illness posed a diagnostic challenge and complicated the subsequent management. It was concluded that increased sexual function deserves further consideration as a symptom of bipolar depression.

Associations of interleukin-6 with vegetative but not affective depressive symptoms in terminally ill cancer patients

Previous studies have reported associations of depressive symptoms with pro-inflammatory cytokines, especially with interleukin-6 (IL-6) in noncancer subjects and cancer patients. Meanwhile, symptoms such as tiredness and appetite loss may be vegetative symptoms of depression when associated with other diagnostic criteria of depression. Such vegetative-type symptoms worsen during the last 6 months of life in cancer patients and may not be associated with affective depressive symptoms such as sadness and nervousness. This study explored associations between depressive symptoms and plasma IL-6 in terminally ill cancer patients whose survival period was confirmed to be less than 6 months by follow-up, with attention to differences in vegetative and affective depressive symptoms. Data from 112 consecutively recruited terminally ill cancer patients who registered at a palliative care unit without any active anticancer treatment were used. Plasma IL-6 levels were measured using an electrochemiluminescence assay. Depressive symptoms included in the DSM-IV and Cavanaugh criteria were assessed by structured interviews and were categorized into affective symptoms and vegetative symptoms. Affective symptoms were also measured with the depression subscale of the Hospital Anxiety and Depression Scale, which does not include vegetative symptoms. Vegetative symptoms, such as appetite loss, insomnia, and fatigue, were significantly associated with IL-6 levels. However, neither of the affective symptoms nor their severity was associated with IL-6 levels. IL-6 was associated with vegetative depressive symptoms in terminally ill cancer patients but not with affective depressive symptoms, suggesting possible differences in the pathophysiological mechanisms between these sets of symptoms.

Detection of altered hippocampal morphology in multiple sclerosis-associated depression using automated surface mesh modeling

Depression is very common in multiple sclerosis (MS) but the underlying biological mechanisms are poorly understood. The hippocampus plays a key role in mood regulation and is implicated in the pathogenesis of depression. This study utilizes volumetric and shape analyses of the hippocampus to characterize neuroanatomical correlates of depression in MS. A cross-section of 109 female patients with MS was evaluated. Bilateral hippocampi were segmented from MRI scans (volumetric T1 -weighted, 1 mm(3) ) using automated tools. Shape analysis was performed using surface mesh modeling. Depression was assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale. Eighty-three subjects were classified as low depression (CES-D 0-20) versus 26 subjects with high depression (CES-D ≥ 21). Right hippocampal volumes (P = 0.04) were smaller in the high depression versus the low depression groups, but there was no significant difference in left hippocampal volumes. Surface rendering analysis revealed that hippocampal shape changes in depressed patients with MS were clustered in the right hippocampus. Significant associations were found between right hippocampal shape and affective symptoms but not vegetative symptoms of depression. Our results suggested that regionally clustered reductions in hippocampal thickness can be detected by automated surface mesh modeling and may be a biological substrate of MS depression in female patients.

Homocysteine level and depression in patients with ischaemic heart disease

Background High levels of homocysteine are associated with vascular disease, changes in the levels of monoamine neurotransmitters and depression. A plausible hypothesis for these associations is that high homocysteine levels are implicated in vascular disease and neurotransmitter deficiency, which are in turn linked to depression. Aim To investigate the association between elevated homocysteine levels and depressive symptoms in patients with ischaemic heart disease (IHD). Participants and methods Eighty patients with a confirmed diagnosis of IHD were consecutively selected in a cross-sectional study from the inpatient and outpatient cardiology department of Kasr-Al-Ainy hospital. All IHD patients were diagnosed according to the criteria of the American College of Cardiology. Depression was evaluated using the Present State Examination-10 Short English–Arabic Version and the Beck Depressive Inventory. The serum level of homocysteine was determined using the chemiluminescent technique. Results Thirty-six ischaemic heart patients (45%) had depressive disorders. Depressed patients were older and had a longer duration of the IHD. The level of homocysteine was higher in depressed patients ( P =0.098). Positive correlations were found between age and the serum level of homocysteine ( P =0.028) but no correlations were found between the serum level of homocysteine and the severity of depression. Sleep disturbances correlated significantly with homocysteine levels irrespective of age. Conclusion Depressive symptoms are common in IHD patients, especially patients with prolonged duration of the disease. They are more apparent in IHD patients at times of emergency and intervention. In IHD patients, the serum level of homocysteine is associated with the occurrence of vegetative depressive symptoms.

Neurovegetative Symptoms in Patients with Multiple Sclerosis: Fatigue, not Depression

Elucidating the relationship between fatigue and depression in multiple sclerosis (MS) patients is complicated by ambiguity regarding how these two constructs should be delineated. Neurovegetative symptoms of depression may reflect depression in MS patients, as they do in non-neurological populations; instead these items may measure disease-related fatigue; or disease-related fatigue and depression may reflect the same syndrome in MS patients. The present study sought to evaluate these possibilities by characterizing the underlying factor structure of self-report items designed to measure fatigue and depression symptoms. Questionnaires designed to measure fatigue and depression were administered to 174 MS patients and 84 healthy controls, and these items were subject to factor analysis. Results suggest that neurovegetative symptoms are poor indicators of depression in MS patients. Neurovegetative depression items were removed from the final model due to poor psychometric properties, or they loaded on Fatigue or Sleep Disturbance factors. The correlation between latent factors Depression and Fatigue was large (.47), but does not indicate that these phenomena are manifestations of the same construct. Hence, the results of this study support the notion that vegetative symptoms of depression do not reflect depression in MS patients, but instead measure symptoms of fatigue and sleep disturbance.

Cognitive and daily functioning in older adults with vegetative symptoms of depression.

In primary care 50-95% of patients with depression present with vegetative symptoms (VS). Based on the extant literature, older adults showing VS (but no dysphoria) may show functional impairment but this hypothesis has not been empirically tested. The goal of this study was to examine neurocognitive and daily functioning of elderly patients showing exclusively VS in comparison with patients presenting with VS and dysphoria. Seven hundred and eighty-seven primary care patients received measures of neurocognition and daily functioning. Neurocognition was measured with the repeatable battery for the assessment of neuropsychological status (RBANS). Three groups were compared: (1) patients with two or more VS of depression without dysphoria (VS - D), (2) patients with at least one VS and dysphoria (VS + D), and (3) comparison patients without multiple VS or dysphoria. Nearly one third of the sample (31%) fell into the VS - D group, whereas 15% fell into the VS + D group. Both VS groups showed poorer neurocognition and activities of daily living than comparisons. Only one subtest of the RBANS (i.e., picture naming) showed a significant difference between VS + D and VS - D, and there was no significant difference on daily functioning. VS - D patients reported less frequent past history of depression and endorsed less anxiety compared to VS + D. Elderly patients presenting with clusters of VS with or without dysphoria show poorer neurocognitive and functional performance. Relative poorer cognition and daily functioning in VS - D are potential harbingers of further decline and consistent with under-reporting of sadness in older age.

Endorsement of self-report neurovegetative items of depression is associated with multiple sclerosis disease symptoms

Some researchers have suggested that general self-report depression scales may be inadequate for assessing depression among individuals with Multiple Sclerosis (MS), because many of such items represent MS disease symptoms. However, research has been mixed on this issue: whereas some studies provide support for symptom overlap, others have found opposing evidence. We investigated this issue in two different MS samples with three different strategies. We (1) examined reliable change in depression symptom categories at two time points over three years, (2) assessed the relationship between variables associated with depression and different depression symptom subscales, and (3) assessed the relationship between symptom subscales and physical disability. In each instance we found significant evidence that items meant to assess vegetative symptoms of depression may be influenced by presence of MS disease symptoms or were not associated with other core elements or central correlates of depression.

Nondysphoric Depression Following Stroke

Nondysphoric Depression Following Stroke

Letter

Back to table of contents Previous article Next article LetterFull AccessLetterFarr A. Curlin M.D.Keith G. Meador M.D.Harold G. Koenig M.D.Farr A. Curlin M.D.Search for more papers by this authorKeith G. Meador M.D.Search for more papers by this authorHarold G. Koenig M.D.Search for more papers by this authorPublished Online:1 Nov 2007https://doi.org/10.1176/ps.2007.58.11.1500AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Psychiatrists and Religious Belief: ReplyIn Reply: Dr. Pies' effort to distinguish pathological religiosity from the religious impulse reveals a tendency to evaluate "maturity" of faith commitments that may be most appropriately left to clergy and religious scholars rather than to therapists. As an example of pathological religiosity, Dr. Pies describes someone who believes that his religion is the only true faith. As an example of "mature" religious impulse, he describes someone who is not religiously observant and looks to psychotherapy to find answers to her existential questions. This dichotomizing of pathological and mature religiosity is inherently problematic, particularly when characterized in this fashion. For many, being religious means observing the teachings and traditions of a particular religion precisely because one believes that religion most adequately answers the sorts of questions that Dr. Pies' "seeker" asks. In Freud's terms, such religious persons believe in an illusion, but they are hardly mentally ill otherwise, and the knowledge that other people disagree with their convictions leads few to "fits of rage" and fantasies about revenge.Tensions between psychiatry and religion likely emerge when one of the two tries to explain and treat a human experience that the other believes it alone has proper authority and resources to address. For example, religious traditions might encourage the "seeker" in Dr. Pies' example to turn to her particular religion rather than to psychotherapy if she wants to "figure out who I am and where I'm headed—is there a purpose to life beyond just working and getting by?" With respect to Dr. Hicks' frustrated colleague, the close connection between existential questions and care of those with mental health concerns is demonstrated both by the fact that his patients did not want to talk with him about their Catholic faith and by the fact that their refusal seemingly limited his ability to care for them.Although our study did not address the issue directly, we would hypothesize that physicians turn to psychiatry more consistently as patients' experiences move along a gradient from milder to more severe psychiatric symptoms. As Dr. Hicks' noted, the normal yet painful consciousness of responsibility for doing wrong is not the same as the experience of oppressive feelings of guilt over actions for which one cannot reasonably be held responsible. We would expect religious physicians to show more preference for religious resources in responding to the former than they would in responding to the latter. Likewise with respect to the vignette in our survey, we think it likely that many physicians would classify the complicated grief of a widower as belonging to the category of human experiences better addressed by religious communities and practices than by behavioral sciences. Yet, had the vignette involved suicidality and vegetative symptoms of depression, we expect that physicians' preferences would have varied less with respect to their religious characteristics and would have been more consistently in favor of referral to a psychiatrist.Finally, the study by Dr. Cutting and her colleagues gives a word of caution to those who might too sanguinely encourage individuals with mental illness to find help in religious communities. Such encouragement will be unhelpful to the extent that patients either do not have the means to participate in religious communities or have found such communities to be unwelcoming to those who suffer from mental illness. FiguresReferencesCited byDetailsCited byNone Volume 58Issue 11 November, 2007Pages 1500-1501PSYCHIATRIC SERVICES November 2007 Volume 58 Number 11 Metrics PDF download History Published online 1 November 2007 Published in print 1 November 2007

Psychiatrists and Religious Belief: Reply

Back to table of contents Previous article Next article LetterFull AccessLetterFarr A. Curlin M.D.Keith G. Meador M.D.Harold G. Koenig M.D.Farr A. Curlin M.D.Search for more papers by this authorKeith G. Meador M.D.Search for more papers by this authorHarold G. Koenig M.D.Search for more papers by this authorPublished Online:1 Nov 2007https://doi.org/10.1176/ps.2007.58.11.1500AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Psychiatrists and Religious Belief: ReplyIn Reply: Dr. Pies' effort to distinguish pathological religiosity from the religious impulse reveals a tendency to evaluate "maturity" of faith commitments that may be most appropriately left to clergy and religious scholars rather than to therapists. As an example of pathological religiosity, Dr. Pies describes someone who believes that his religion is the only true faith. As an example of "mature" religious impulse, he describes someone who is not religiously observant and looks to psychotherapy to find answers to her existential questions. This dichotomizing of pathological and mature religiosity is inherently problematic, particularly when characterized in this fashion. For many, being religious means observing the teachings and traditions of a particular religion precisely because one believes that religion most adequately answers the sorts of questions that Dr. Pies' "seeker" asks. In Freud's terms, such religious persons believe in an illusion, but they are hardly mentally ill otherwise, and the knowledge that other people disagree with their convictions leads few to "fits of rage" and fantasies about revenge.Tensions between psychiatry and religion likely emerge when one of the two tries to explain and treat a human experience that the other believes it alone has proper authority and resources to address. For example, religious traditions might encourage the "seeker" in Dr. Pies' example to turn to her particular religion rather than to psychotherapy if she wants to "figure out who I am and where I'm headed—is there a purpose to life beyond just working and getting by?" With respect to Dr. Hicks' frustrated colleague, the close connection between existential questions and care of those with mental health concerns is demonstrated both by the fact that his patients did not want to talk with him about their Catholic faith and by the fact that their refusal seemingly limited his ability to care for them.Although our study did not address the issue directly, we would hypothesize that physicians turn to psychiatry more consistently as patients' experiences move along a gradient from milder to more severe psychiatric symptoms. As Dr. Hicks' noted, the normal yet painful consciousness of responsibility for doing wrong is not the same as the experience of oppressive feelings of guilt over actions for which one cannot reasonably be held responsible. We would expect religious physicians to show more preference for religious resources in responding to the former than they would in responding to the latter. Likewise with respect to the vignette in our survey, we think it likely that many physicians would classify the complicated grief of a widower as belonging to the category of human experiences better addressed by religious communities and practices than by behavioral sciences. Yet, had the vignette involved suicidality and vegetative symptoms of depression, we expect that physicians' preferences would have varied less with respect to their religious characteristics and would have been more consistently in favor of referral to a psychiatrist.Finally, the study by Dr. Cutting and her colleagues gives a word of caution to those who might too sanguinely encourage individuals with mental illness to find help in religious communities. Such encouragement will be unhelpful to the extent that patients either do not have the means to participate in religious communities or have found such communities to be unwelcoming to those who suffer from mental illness. FiguresReferencesCited byDetailsCited ByNone Volume 58Issue 11 November, 2007Pages 1500-1501PSYCHIATRIC SERVICES November 2007 Volume 58 Number 11 Metrics PDF download History Published online 1 November 2007 Published in print 1 November 2007

Depression Can Break Heart in Unexpected Way

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessDepression Can Break Heart in Unexpected WayJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:16 Mar 2007https://doi.org/10.1176/pn.42.6.0021Remember all the hype about the type-A personality a few years ago? This is a person bristling with aggression and hostility. And certainly hostility and anger have been linked with an increased risk of having a heart attack.However, neither hostility nor anger seems to pave the way for the very early stages of cardiovascular disease, a study published in the February Archives of General Psychiatry suggested.The researchers found no link between hostility or anger and thickening of the carotid arteries in subjects who were followed over a three-year period. The investigators did find, however, an association between the vegetative symptoms of depression and such thickening over the same time span.The lead investigator was Jesse Stewart, Ph.D., an assistant professor of psychology at Indiana University-Purdue University, Indianapolis. He conducted the inquiry while he was a postdoctoral fellow at the University of Pittsburgh.Although depression and anxiety, as well as hostility or anger, have been associated in the past with an increased risk of cardiovascular disease, Stewart and his colleagues wanted to evaluate the relative contributions of these four negative emotions to the early disease process. They assessed 324 healthy older men and women for anxiety, depression, anger, and hostility over a five-month period; measured the thickness of the subjects' carotid arteries both at the start of the study and during a three-year follow-up period; and then attempted to see whether they could link each of the four types of negative emotions to thickening of the carotid arteries. In doing so, they took numerous possibly distorting factors—demographics, cardiovascular risk, medication use, medical conditions, and the other negative emotions of interest—into consideration.The scientists were not able to link hostility, anger, or anxiety to thickening of the carotid arteries, but they did find a significant association, and a dose-response relationship, between depression and the latter. In other words, the more depressed subjects were, the thicker their carotid arteries became.The investigators then looked to see whether particular depressive symptoms could be coupled with thickening of the carotid arteries. Regarding the cognitive symptoms of depression (sadness, pessimism, and indecisiveness), the answer was no, but regarding the vegetative symptoms of depression (loss of appetite and pleasure in life, fatigue, and sleep disturbances), the answer was yes.“Our findings suggest that the somatic-vegetative features of depression, but perhaps not anxiety, hostility, and anger, may play an important role in the earlier stages of the development of coronary artery disease,” Stewart and his group concluded in their study report.Stewart told Psychiatric News that the absence of a link between the negative emotions they evaluated and early thickening of the carotid arteries was unexpected. And, he said, “It was also somewhat surprising that only the vegetative symptoms of depression were predictive of greater thickening of the carotid arteries over time.”He pointed out, however, that hostility, anger, anxiety, and the cognitive symptoms of depression may still play a role in the later development of coronary artery disease. He also conjectured that while the means by which negative emotions might contribute to coronary artery disease are not known, inflammation may mediate the process.In fact, he reported, “I am currently examining the relationships between multiple negative emotions and inflammatory markers relevant to cardiovascular disease such as the proinflammatory cytokine interleukin-6 and the acute phase reactant C-reactive protein.”The study was funded by the National Institutes of Health and the Pittsburgh Mind-Body Center.An abstract of “Negative Emotions and Three-Year Progression of Subclinical Atherosclerosis” is posted at<http://archpsyc.ama-assn.org/cgi/content/abstract/64/2/225>.▪ ISSUES NewArchived

Early prediction of major depression in chronic hepatitis C patients during peg-interferon α-2b treatment by assessment of vegetative-depressive symptoms after four weeks

To study the predictive value of the vegetative-depressive symptoms of the Zung Depression Rating Scale for the occurrence of depression during treatment with peg-interferon alpha-2b of chronic hepatitis C (CHC) patients. The predictive value of vegetative-depressive symptoms at 4 wk of treatment for the occurrence of a subsequent diagnosis of major depressive disorder (MDD) was studied in CHC patients infected after substance use in a prospective, multi-center treatment trial in Belgium. The presence of vegetative-depressive symptoms was assessed using the Zung Scale before and 4 wk after the start of antiviral treatment. Out of 49 eligible patients, 19 (39%) developed MDD. The area under the ROC curve of the vegetative Zung subscale was 0.73, P = 0.004. The sensitivity at a cut-point of > 15/35 was 95% (95% CI: 74-100). The positive predictive value equalled 44% (95% CI: 29-60). In this group of Belgian CHC patients infected after substance use, antiviral treatment caused a considerable risk of depression. Seven vegetative-depressive symptoms of the Zung scale at wk 4 of treatment predicted 95% of all emerging depressions, at a price of 56% false positive test results.

Short‐term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus

The pathomechanism of major depressive disorder and the neurobiological basis of antidepressant therapy are still largely unknown. It has been proposed that disturbed hippocampal activity could underlie some of the cognitive and vegetative symptoms of depression, at least in part because of loss of pyramidal cell synaptic contacts, a process that is likely to be reversed by antidepressant treatment. Here we provide evidence that daily administration of the antidepressant fluoxetine to ovariectomized female rats for 5 days induces a robust increase in pyramidal cell dendritic spine synapse density in the hippocampal CA1 field, with similar changes appearing in CA3 after 2 weeks of treatment. This rapid synaptic remodelling might represent an early step in the fluoxetine-induced cascade of responses that spread across the entire hippocampal circuitry, leading to the restoration of normal function in the hippocampus. Hippocampal synaptic remodelling might provide a potential mechanism to explain certain aspects of antidepressant therapy and mood disorders, especially those associated with changes in reproductive state in women, that cannot be reconciled adequately with current theories for depression.

Metabolic depression in hibernation and major depression: An explanatory theory and an animal model of depression

Metabolic depression, an adaptive biological process for energy preservation, is responsible for torpor, hibernation and estivation. We propose that a form of metabolic depression, and not mitochondrial dysfunction, is the process underlying the observed hypometabolism, state-dependent neurobiological changes and vegetative symptoms of major depression in humans. The process of metabolic depression is reactivated via differential gene expression in response to perceived adverse stimuli in predisposed persons. Behavior inhibition by temperament, anxiety disorders, genetic vulnerabilities, and early traumatic experiences predispose persons to depression. The proposed theory is supported by similarities in the presentation and neurobiology of hibernation in bears and major depression and explains the yet unexplained neurobiological changes of depression. Although, gene expression is suppressed in other hibernators by deep hypothermia, bears were chosen because they hibernate with mild hypothermia. Pre-hibernation in bears and major depression with atypical features are both characterized by fat storage through overeating, oversleeping, and decreased mobility. Hibernation in bears and major depression with melancholic features are characterized by withdrawal from the environment, lack of energy, loss of weight from not eating and burning stored fat, changes in sleep pattern, and the following similar neurobiological findings: reversible subclinical hypothyroidism; increased concentration of serum cortisol; acute phase protein response; low respiratory quotient; oxidative stress response; decreased neurotransmitter levels; and changes in cyclic-adenosine monophosphate-binding activity. Signaling systems associated with protein phosphorylation, transcription factors, and gene expression are responsible for the metabolic depression process during pre-hibernation and hibernation. Antidepressants and mood stabilizers interfere with the hibernation process and produce their therapeutic effects by normalizing the fluctuation of activities in the different signaling systems, which are down-regulated during hibernation and depression and up-regulated during exodus from hibernation and the hypomanic or manic phase of mood disorders. The ways individuals cognitively perceive, understand, communicate, and react to the vegetative symptoms of depression, from downregulation in energy production, and in the absence of known medical causes, produce the other characteristics of depression including guilt, helplessness, hopelessness, suicidal phenomena, agitation, panic attacks, psychotic symptoms, and sudden switch to hypomanic or manic episodes. The presence of one or more of these characteristics depends on the person's neuropsychological function, its social status between the others, and the other's response to the person. Neurobiological changes associated with metabolic depression during entrance, maintenance, and exodus from hibernation in bears is suggested as a natural animal model of human depression and mood disorders.

Early increase in vegetative symptoms predicts IFN-α-induced cognitive-depressive changes

The vegetative symptoms of depression resemble the symptoms of malaise associated with activation of the inflammatory response system (IRS), and can be regarded as an expression of a central motivational state that resets the organism's priorities to promote recovery from infection. Early vegetative symptoms, however, may also contribute to the high rates of depression seen later in the course of immune activation. We hypothesized that the onset of vegetative-depressive symptoms early in the treatment with the pro-inflammatory cytokine IFN-alpha in chronic hepatitis C patients would increase the risk for subsequent depressive cognitions. Sixteen patients eligible for IFN-alpha treatment and free of psychiatric disorders were recruited. The DSM-IV, the Multidimensional Fatigue Inventory, and the Montgomery-Asberg Depression Rating Scale (MADRS) were administered at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. Cognitive-depressive and vegetative-depressive symptom clusters were constructed. Fatigue and depression scores increased significantly during IFN-alpha treatment. Depression scores were highest at week 8 of treatment. First week increase in vegetative-depressive symptom score predicted cognitive-depressive symptom score at week 8 and at week 24. During IFN-alpha treatment, vegetative symptoms of depression appear earlier than, and are predictive of, their cognitive counterparts. This finding suggests that low mood state may in part be driven by the increase in early vegetative-depressive symptoms in the course of IFN-alpha-induced immune activation.

The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans.

Administration of the cytokines interferon-alpha and interleukin-2 is used for the treatment of various disorders, such as hepatitis C and various forms of cancer. The most serious side-effects are symptoms associated with depression, including fatigue, increased sleepiness, irritability, loss of appetite as well as cognitive changes. However, great differences exist in the prevalence of the development of depressive symptoms across studies. Differences in doses and duration of therapy may be sources of variation as well as individual differences of patients, such as a history of psychiatric illness. In addition, sensitization effects may contribute to differential responses of patients to the administration of cytokines. In animals administration of pro-inflammatory cytokines induces a pattern of behavioural alterations called 'sickness behaviour' which resembles the vegetative symptoms of depression in humans. Changes in serotonin (5-HT) receptors and in levels of 5-HT and its precursor tryptophan in depressed people support a role for 5-HT in the development of depression. In addition, evidence exists for a dysregulation of the noradrenergic system and a hyperactive hypothalamic-pituitary-adrenal (HPA) axis in depression. Some mechanisms exist which make it possible for cytokines to cross the blood-brain barrier. Pro-inflammatory cytokines such as IL-1beta, IFN-alpha, IFN-gamma and TNF-alpha affect the 5-HT metabolism directly and/or indirectly by stimulating the enzyme indoleamine 2,3-dioxygenase which leads to a peripheral depletion of tryptophan. IL-1, IL-2 and TNF-alpha influence noradrenergic activity and IL-1, IL-6 and TNF-alpha are found to be potent stimulators of the HPA axis. Altogether, administration of cytokines may induce alterations in the brain resembling those found in depressed patients, which leads to the hypothesis that cytokines induce depression by their influence on the 5-HT, noradrenergic and HPA system.