Dataset Information

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.

ABSTRACT: Depression is a major health problem with a high prevalence and a heavy socioeconomic burden in western societies. It is associated with atrophy and impaired functioning of cortico-limbic regions involved in mood and emotion regulation. It has been suggested that alterations in neurotrophins underlie impaired neuroplasticity, which may be causally related to the development and course of depression. Accordingly, mounting evidence suggests that antidepressant treatment may exert its beneficial effects by enhancing trophic signaling on neuronal and synaptic plasticity. However, current antidepressants still show a delayed onset of action, as well as lack of efficacy. Hence, a deeper understanding of the molecular and cellular mechanisms involved in the pathophysiology of depression, as well as in the action of antidepressants, might provide further insight to drive the development of novel fast-acting and more effective therapies. Here, we summarize the current literature on the involvement of neurotrophic factors in the pathophysiology and treatment of depression. Further, we advocate that future development of antidepressants should be based on the neurotrophin theory.

SUBMITTER: Levy MJF

PROVIDER: S-EPMC6061771 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.

Levy Marion J F MJF Boulle Fabien F Steinbusch Harry W HW van den Hove Daniël L A DLA Kenis Gunter G Lanfumey Laurence L

Psychopharmacology 20180630 8

Depression is a major health problem with a high prevalence and a heavy socioeconomic burden in western societies. It is associated with atrophy and impaired functioning of cortico-limbic regions involved in mood and emotion regulation. It has been suggested that alterations in neurotrophins underlie impaired neuroplasticity, which may be causally related to the development and course of depression. Accordingly, mounting evidence suggests that antidepressant treatment may exert its beneficial ef ...[more]

PMID: 29961124

Similar Datasets

Project description:Therapeutic seizures may work for treatment-resistant depression (TRD) by producing neuroplasticity. We evaluated whether magnetic seizure therapy (MST) produces changes in suicidal ideation and neuroplasticity as indexed through transcranial magnetic stimulation and electroencephalography (TMS-EEG) of the dorsolateral prefrontal cortex (DLPFC). Twenty-three patients with TRD were treated with MST. Changes in suicidal ideation was assessed through the Scale for Suicidal Ideation (SSI). Before and after the treatment course, neuroplasticity in excitatory and inhibitory circuits was assessed with TMS-EEG measures of cortical-evoked activity (CEA) and long-interval cortical inhibition (LICI) from the left DLPFC, and the left motor cortex as a control condition. As in our previous report, the relationship between TMS-EEG measures and suicidal ideation was examined with the SSI. Results show that 44.4% of patients experienced resolution of suicidal ideation. Based on DLPFC assessment, MST produced significant CEA increase over the frontal central electrodes (cluster p < 0.05), but did not change LICI on a group level. MST also reduced the SSI scores (p < 0.005) and the amount of reduction correlated with the decrease in LICI over the right frontal central electrodes (cluster p < 0.05; rho = 0.73 for Cz). LICI change identified patients who were resolved of suicidal ideation with 90% sensitivity and 88% specificity (AUC = 0.9, p = 0.004). There was no significant finding with motor cortex assessment. Overall, MST produced significant rates of resolution of suicidal ideation. MST also produced neuroplasticity in the frontal cortex, likely through long-term potentiation (LTP)-like mechanisms. The largest reduction in suicidal ideation was demonstrated in patients showing concomitant decreases in cortical inhibition-a mechanism linked to enhanced LTP-like plasticity. These findings provide insights into the mechanisms through which patients experience resolution of suicidal ideation following seizure treatments in depression.

Project description:ObjectiveThis study aimed to investigate the roles of neurotrophic factors (NTFs), monoamine neurotransmitters, and inflammatory processes in the pathophysiology of the comorbidity of epilepsy and depression.MethodsA retrospective analysis was conducted with 57 epilepsy patients (PWE), 50 patients with epilepsy and comorbid depression (PWECD), and 47 healthy controls (HC) admitted between June 2020 and June 2024. Serum levels of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), 5-hydroxytryptamine (5-HT), norepinephrine (NE), dopamine (DA), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, BDNF and GDNF levels in cerebrospinal fluid (CSF) samples were analyzed from selected patients in the PWE and PWECD groups.ResultsSerum BDNF levels were significantly lower in both PWE and PWECD groups compared to HC, while no differences between the former two groups. GDNF levels were lower in PWECD compared to HC, but not between PWE and HC. Serum 5-HT was significantly reduced in PWECD compared to both HC and PWE groups. No significant differences were observed in serum DA, NE, and IL-6 levels across the groups. Serum IL-1β levels were elevated in the PWECD group compared to the HC group. The Self-Rating Depression Scale (SDS) score negatively correlated with serum 5-HT and GDNF levels. In terms of predictive ability, serum BDNF demonstrated higher accuracy for the diagnosis of epilepsy [area under the curve, AUC = 0.701, 95% confidence intervals (95% CI) 0.601 ~ 0.801], while serum 5-HT was the best marker for predicting the development of depression in epilepsy patients (AUC = 0.727, 95% CI 0.632 ~ 0.821). No significant correlation was found between serum and CSF BDNF levels within the same subject (r = 0.155; p = 0.221; Spearman correlation), and CSF GDNF levels were too low to be clinically informative.ConclusionThe findings suggest the involvement of NTFs, monoamine neurotransmitters, and inflammatory processes in the pathogenesis of epilepsy and depression. Decreased serum BDNF levels correlate with epilepsy but not necessarily with comorbid depression, while serum GDNF and 5-HT show potential clinical value in diagnosing this comorbidity. However, the deficient levels of NTFs in CSF suggest a need for more sensitive detection methods.

Dataset Information

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.

Publications

Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets