Serotonergic Dysfunction in Depression

1989 ◽  
Vol 155 (S8) ◽  
pp. 25-31 ◽  
Author(s):  
Herbert Meltzer
Keyword(s):  
Tryptophan Hydroxylase ◽  
Rating Scale ◽  
Blood Platelets ◽  
Antidepressant Drugs ◽  
Depression Score ◽  
Plasma Tryptophan ◽  
Depressed Patients ◽  
Hydroxyindoleacetic Acid ◽  
Serotonergic Function ◽  
Neuroendocrine Challenge

Various irregularities in serotonin (5-HT) function have been postulated as causes of affective disorders. Serotonin has been related to many of the major symptoms of depression, e.g. mood, appetite, sleep, activity, and cognitive dysfunction. Interference with 5-HT synthesis or storage has been shown to induce depression in vulnerable individuals. Decreased levels of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid, decreased plasma tryptophan, low tryptophan neutral amino acid ratio, abnormalities in serotonergic function indicated by neuroendocrine challenge tests and various platelet measures, have been reported in depressed patients. Concentrations of 5-HIAA, the major metabolite of 5-HT in plasma, were found to be significantly negatively correlated with severity of depression as measured by the Hamilton Rating Scale for Depression score and specific depressive symptoms, despite the fact that plasma 5-HIAA is largely peripheral in origin. Blood platelets, which have been suggested as models for serotonergic nerve terminals, have a significantly decreased number of 5-HT uptake sites and 3H-imipramine binding sites in depressed patients. Antidepressant drugs may act, in part, by enhancing serotonergic activity. The serotonergic deficit may occur at any of several levels: diminished availability of precursor, impaired activity of tryptophan hydroxylase, abnormalities in 5-HT release or uptake, 5-HT receptor abnormalities or interactions with other neurotransmitters.

Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter

1994 ◽  
Vol 40 (2) ◽  
pp. 288-295 ◽  
Author(s):  
M J Owens ◽  
C B Nemeroff
Keyword(s):  
Brain Tissue ◽  
Binding Sites ◽  
Antidepressant Treatment ◽  
Postmortem Brain ◽  
Atypical Depression ◽  
Plasma Tryptophan ◽  
Depressed Patients ◽  
Postmortem Brain Tissue ◽  
Hydroxyindoleacetic Acid ◽  
Drug Free

Abstract Considerable evidence has accrued in the last two decades to support the hypothesis that alterations in serotonergic neuronal function in the central nervous system occur in patients with major depression. These findings include the following: (a) reduced cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite of serotonin (5-HT) in drug-free depressed patients; (b) reduced concentrations of 5-HT and 5-HIAA in postmortem brain tissue of depressed and (or) suicidal patients; (c) decreased plasma tryptophan concentrations in depressed patients and a profound relapse in remitted depressed patients who have responded to a serotonergic antidepressant when brain tryptophan availability is reduced; (d) in general, all clinically efficacious antidepressants augment 5-HT neurotransmission following chronic treatment; (e) clinically efficacious antidepressant action by all inhibitors of 5-HT uptake; (f) increases in the density of 5-HT2 binding sites in postmortem brain tissue of depressed patients and suicide victims, as well as in platelets of drug-free depressed patients; (g) decreased number of 5-HT transporter (determined with [3H]imipramine or [3H]paroxetine) binding sites in postmortem brain tissue of suicide victims and depressed patients and in platelets of drug-free depressed patients. In our studies, this reduction in platelet 5-HT transporter binding is not due to prior antidepressant treatment of hypercortisolemia and is not observed in mania, Alzheimer disease, schizophrenia, panic disorder, fibromyalgia, or atypical depression. In a pilot study, this deficit predicted treatment response to an experimental antidepressant. These findings support the hypothesis that alterations in 5-HT neurons play a role in the pathophysiology of depression.

CSF monoamine metabolites and neuropeptides in depressed patients before and after electroconvulsive therapy

2008 ◽  
Vol 23 (5) ◽  
pp. 356-359 ◽  
Author(s):  
Georg Nikisch ◽  
Aleksander A. Mathé
Keyword(s):  
Electroconvulsive Therapy ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Treatment Modalities ◽  
Depressed Patients ◽  
Human Cerebrospinal Fluid ◽  
Rodent Brain ◽  
Before And After ◽  
Hydroxyindoleacetic Acid ◽  
The Common

AbstractAntidepressant drugs affect monoamines and neuropeptides in human cerebrospinal fluid (CSF) and in rodent brain. The purpose of this study was to investigate if also electroconvulsive therapy (ECT) affects these compounds in a similar manner in the CSF of depressed patients. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI) and neuropeptide Y (NPY)-LI were determined in CSF in six drug resistant patients with major depression. Lumbar puncture was performed at baseline and after completion of eight ECTs. ECT was associated with an increase in NPY-LI (p = 0.009) and a decrease in CRH-LI (p ≤ 0.001). HVA (p = 0.003) and 5-HIAA (p = 0.002) were significantly increased after the ECT. Findings of NPY increase and CRH decrease were similar to those following chronic treatment with citalopram, indicating that these changes might constitute one of the common underpinnings of antidepressant treatment modalities.

Depression Severity Is Related to Less Gross Body Movement: A Motion Energy Analysis

2021 ◽  
pp. 1-7
Author(s):  
Anna Sandmeir ◽  
Désirée Schoenherr ◽  
Uwe Altmann ◽  
Christoph Nikendei ◽  
Henning Schauenburg ◽  
...  
Keyword(s):  
Depressive Disorder ◽  
Energy Analysis ◽  
Rating Scale ◽  
Body Movement ◽  
Psychomotor Retardation ◽  
Diagnostic Interview ◽  
Depression Severity ◽  
Depressed Patients ◽  
Motion Energy ◽  
Objectively Measured

Psychomotor retardation is a well-known clinical phenomenon in depressed patients that can be measured in various ways. This study aimed to investigate objectively measured gross body movement (GBM) during a semi-structured clinical interview in patients with a depressive disorder and its relation with depression severity. A total of 41 patients with a diagnosis of depressive disorder were assessed both with a clinician-rated interview (Hamilton Depression Rating Scale) and a self-rating questionnaire (Beck Depression Inventory-II) for depression severity. Motion energy analysis (MEA) was applied on videos of additional semi-structured clinical interviews. We considered (partial) correlations between patients’ GBM and depression scales. There was a significant, moderate negative correlation between both measures for depression severity (total scores) and GBM during the diagnostic interview. However, there was no significant correlation between the respective items assessing motor symptoms in the clinician-rated and the patient-rated depression severity scale and GBM. Findings imply that neither clinician ratings nor self-ratings of psychomotor symptoms in depressed patients are correlated with objectively measured GBM. MEA thus offers a unique insight into the embodied symptoms of depression that are not available via patients’ self-ratings or clinician ratings.

scholarly journals Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Maximilian Pilhatsch ◽  
Thomas J Stamm ◽  
Petra Stahl ◽  
Ute Lewitzka ◽  
Anne Berghöfer ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Phenotypic Expression ◽  
Anxiety Symptoms ◽  
Controlled Study ◽  
Double Blind ◽  
Comorbid Anxiety ◽  
Depressed Patients ◽  
Depressive Episodes

Abstract Background Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. Methods Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). Results Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). Conclusions This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839

scholarly journals Methylome-wide change associated with response to electroconvulsive therapy in depressed patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lea Sirignano ◽  
Josef Frank ◽  
Laura Kranaster ◽  
Stephanie H. Witt ◽  
Fabian Streit ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Cpg Sites ◽  
Cpg Site ◽  
Depressed Patients ◽  
Resistant Depression ◽  
Functional Pathway ◽  
Regional Analyses ◽  
The Relationship

AbstractElectroconvulsive therapy (ECT) is a quick-acting and powerful antidepressant treatment considered to be effective in treating severe and pharmacotherapy-resistant forms of depression. Recent studies have suggested that epigenetic mechanisms can mediate treatment response and investigations about the relationship between the effects of ECT and DNA methylation have so far largely taken candidate approaches. In the present study, we examined the effects of ECT on the methylome associated with response in depressed patients (n = 34), testing for differentially methylated CpG sites before the first and after the last ECT treatment. We identified one differentially methylated CpG site associated with the effect of ECT response (defined as >50% decrease in Hamilton Depression Rating Scale score, HDRS), TNKS (q < 0.05; p = 7.15 × 10−8). When defining response continuously (ΔHDRS), the top suggestive differentially methylated CpG site was in FKBP5 (p = 3.94 × 10−7). Regional analyses identified two differentially methylated regions on chromosomes 8 (Šídák’s p = 0.0031) and 20 (Šídák’s p = 4.2 × 10−5) associated with ΔHDRS. Functional pathway analysis did not identify any significant pathways. A confirmatory look at candidates previously proposed to be involved in ECT mechanisms found CpG sites associated with response only at the nominally significant level (p < 0.05). Despite the limited sample size, the present study was able to identify epigenetic change associated with ECT response suggesting that this approach, especially when involving larger samples, has the potential to inform the study of mechanisms involved in ECT and severe and treatment-resistant depression.

scholarly journals Plasma Kynurenine Level is Associated With Left DLPFC Activity and Can Predict Treatment Response in Major Depressive Disorder

2021 ◽  
Author(s):  
Toshiharu Kamishikiryo ◽  
Go Okada ◽  
Eri Itai ◽  
Yoshikazu Masuda ◽  
Satoshi Yokoyama ◽  
...  
Keyword(s):  
Treatment Response ◽  
Rating Scale ◽  
Brain Activity ◽  
Low Frequency ◽  
Depression Score ◽  
Healthy Controls ◽  
Regional Brain ◽  
Left Dlpfc ◽  
Dorsolateral Prefrontal ◽  
Regional Brain Activity

Abstract To establish treatment response biomarkers that reflect the pathophysiology of depression, it is important to use an integrated set of features that are promising as biomarkers. This study aimed to determine the relationship between blood metabolites related to treatment response to escitalopram and regional brain activity at rest and to find the characteristics of depression that respond to treatment. Blood metabolite levels and resting brain activity were measured in patients with depression (N = 65) before and after 6 weeks treatment with escitalopram and healthy controls (N = 36). Thirty-two patients (49.2%) showed clinical response (>50% reduction in Hamilton Rating Scale for Depression score) and were classified as Responders, and the remaining 33 patients were classified as Nonresponders. Pretreatment plasma kynurenine level and fractional amplitude of low-frequency fluctuations (fALFF) of the left dorsolateral prefrontal cortex (DLPFC) were lower in Responders, and their elevations after treatment were correlated with improvement in symptoms. Moreover, fALFF of the left DLPFC was significantly correlated with plasma kynurenine level in pretreatment patients with depression and healthy controls. Decreased kynurenine level and resting-state regional brain activity of the left DLPFC may be involved in the pathophysiology of depression in response to escitalopram treatment.

A Multidisciplinary Approach to the Expression of Pain in Psychic Depression

1978 ◽  
Vol 47 (2) ◽  
pp. 379-390 ◽  
Author(s):  
Judith R. Ganchrow ◽  
Jacob E. Steiner ◽  
Murray Kleiner ◽  
Eliezer L. Edelstein
Keyword(s):  
Heart Rate ◽  
Multidisciplinary Approach ◽  
Rating Scale ◽  
Cold Pressor ◽  
Facial Display ◽  
Pain Stimulus ◽  
Verbal Responses ◽  
Depressed Patients ◽  
Facial Displays ◽  
Cold Pressor Pain

The expression of cold pressor pain was measured by recording simultaneously verbal magnitude estimates, heart rates, and facial displays of 16 recently hospitalized depressed patients, and 16 nondepressed adults. Independence of the two groups for the depression factor was verified using the Hamilton Scale for Depression and the 100-mm line self-rating scale. Verbal responses and amount of time the ice bath was tolerated, as well as heart-rate measures, indicated that depressed individuals were significantly more sensitive to the pain stimulus. However, this elevated intolerance to pain was not reflected by marked changes of facial display. Reasons for this discrepancy are discussed. Nondepressed subjects, although clearly able to verbalize intensity of pain, were much less reactive to the pain along all dimensions.

Depression in Geriatric Inpatients: Correlations with Nutritional State and Cognitive Functions

2016 ◽  
Vol 33 (S1) ◽  
pp. S472-S472
Author(s):  
I. Bonfitto ◽  
G. Moniello ◽  
L. Ariano ◽  
M. Pascucci ◽  
M.D. Zanasi ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Depressive Symptoms ◽  
Nutritional Status ◽  
Rating Scale ◽  
Assessment Tool ◽  
Mini Nutritional Assessment ◽  
Average Score ◽  
Depressed Patients ◽  
Increased Risk ◽  
Geriatric Inpatients

BackgroundAlthough the prevalence of malnutrition is relatively low among elderly people, the risk increases significantly among inpatients and even more in those with mental deterioration.AimsTo evaluate the possible association between the severity of depressive symptoms, the nutritional status and the cognitive decline in a sample of geriatric inpatients.MethodsFifty-one geriatric inpatients completed the following tests:– Hamilton Depression Rating Scale (HAM-D), to assess the severity of depressive symptoms;– Mini Nutritional Assessment (MNA), as a nutrition screening and assessment tool;– Mini Mental State Examination (MMSE), to assess the cognitive impairment.ResultsThere is a negative proportional relationship between HAM-D and MMSE scores (P = 0.001) and between HAM-D and MNA scores (P = 0.023). Depressed patients found to have a greater cognitive impairment and a worse nutritional status. Considering a HAM-D cut-off point of 14, distinguishing mild than moderate depression, it shows a significant correlation with the MNA scores (P = 0.008). Patients with HAM-D scores ≥ 14 have an average MNA score of 19.8, while patients with HAM-D scores < 14 have an MNA average score of 23.6. Euthymic or mildly depressed patients are not at risk of malnutrition, while those with moderate or severe depression have an increased risk of malnutrition.ConclusionsOur study shows significant correlations between the severity of depressive symptoms and the risk of malnutrition or cognitive impairment. A mild depression state does not seem to be associated with an increased risk of malnutrition.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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