Dataset Information

The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder.

ABSTRACT:

Introduction

Emotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of depressive patients' descriptions of their cognitive symptoms.

Methods

We compared cognitive status and structural and functional brain connectivity changes in the pulvinar and hippocampus between patients with total depression and healthy controls. The depressive group was also classified as "amnestic" or "nonamnestic," based on the members' subjective reports concerning their forgetfulness. We then sought to determine whether these patients would differ in terms of objective neuroimaging and cognitive findings.

Results

The right pulvinar exhibited altered connectivity in individuals with depression with objective cognitive impairment, a finding which was not apparent in depressive patients with subjective cognitive impairment.

Discussion

The pulvinar may play a role in depression-related cognitive impairments. Connectivity network changes may differ between objective and subjective cognitive impairment in depression and may play a role in the increased risk of dementia in patients with depression.

SUBMITTER: Yulug B

PROVIDER: S-EPMC10865482 | biostudies-literature | 2024 Jan-Mar

REPOSITORIES: biostudies-literature

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Publications

The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder.

Yulug Burak B Ayyildiz Sevilay S Sayman Dila D Karaca Ramazan R Ipek Lutfiye L Cankaya Seyda S Salar Ali Behram AB Ayyildiz Behcet B Mikuta Christian C Yagci Nilay N Oktem Ece Ozdemir EO Ozsimsek Ahmet A Velioglu Halil Aziz HA Hanoglu Lutfu L

Alzheimer's & dementia (New York, N. Y.) 20240101 1

<h4>Introduction</h4>Emotionally driven cognitive complaints represent a major diagnostic challenge for clinicians and indicate the importance of objective confirmation of the accuracy of depressive patients' descriptions of their cognitive symptoms.<h4>Methods</h4>We compared cognitive status and structural and functional brain connectivity changes in the pulvinar and hippocampus between patients with total depression and healthy controls. The depressive group was also classified as "amnestic" ...[more]

PMID: 38356480

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Project description:BackgroundPatients diagnosed withmajor depressive disorder (MDD) usually experience impaired cognitive functioning, which might negatively impact their clinical and functional outcomes. This study aimed to investigate the association of specific clinical factors with cognitive dysfunction in a group of MDD patients.MethodsA total of 75 subjects diagnosed with recurrent MDD were evaluated during the acute stage. Their cognitive functions were assessed using the THINC-integrated tool (THINC-it) for attention/alertness, processing speed, executive function, and working memory. Clinical psychiatric evaluations, such as the Hamilton Anxiety Scale (HAM-A), the Young Mania Rating Scale (YMRS), the Hamilton Depression Scale (HAM-D), and the Pittsburgh Sleep Quality Index(PSQI), were used to assess patients' levels of anxiety, depression and sleeping problems. The investigated clinical variables were age, years of education, age at onset, number of depressive episodes, disease duration, presence of depressive and anxiety symptoms, sleep problems, and number of hospitalizations.ResultsThe results revealed that significant differences were observed between the two groups in the THINC-it total scores, Spotter, Codebreaker, Trails, and PDQ-5-D scores (P < 0.001). The THINC-it total scores, Spotter, Codebreaker, Trails, and Symbol Check were significantly associated with age and age at onset(P < 0.01). In addition, regression analysis found that years of education was positively associated with the Codebreaker total scores (P < 0.05). the THINC-it total scores, Symbol Check, Trails, and Codebreaker were correlated with the HAM-D total scores(P < 0.05). Additionally, the THINC-it total scores, Symbol Check, PDQ-5-D and Codebreaker significantly correlated with the PSQI total scores (P < 0.05).ConclusionWe found a significant statistical association between almost all cognitive domains and different clinical aspects in depressive disorder, such asage, age at onset, severity of depression, years of education, and sleep problems. Additionally, education was shown to be a protective factor against processing speed impairments. Special considerations of these factors might help outline better management strategies to improve cognitive functions in MDD patients.

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:Major depressive disorder (MDD) is associated with an increased risk of developing dementia. The present study aimed to better understand this risk by comparing resting state functional connectivity (rsFC) in the executive control network (ECN) and the default mode network (DMN) in older adults with MDD or mild cognitive impairment (MCI). Additionally, we examined the association between rsFC in the ECN or DMN and cognitive impairment transdiagnostically. We assessed rsFC alterations in ECN and DMN in 383 participants from five groups at-risk for dementia-remitted MDD with normal cognition (MDD-NC), non-amnestic mild cognitive impairment (naMCI), remitted MDD + naMCI, amnestic MCI (aMCI), and remitted MDD + aMCI-and from healthy controls (HC) or individuals with Alzheimer's dementia (AD). Subject-specific whole-brain functional connectivity maps were generated for each network and group differences in rsFC were calculated. We hypothesized that alteration of rsFC in the ECN and DMN would be progressively larger among our seven groups, ranked from low to high according to their risk for dementia as HC, MDD-NC, naMCI, MDD + naMCI, aMCI, MDD + aMCI, and AD. We also regressed scores of six cognitive domains (executive functioning, processing speed, language, visuospatial memory, verbal memory, and working memory) on the ECN and DMN connectivity maps. We found a significant alteration in the rsFC of the ECN, with post hoc testing showing differences between the AD group and the HC, MDD-NC, or naMCI groups, but no significant alterations in rsFC of the DMN. Alterations in rsFC of the ECN and DMN were significantly associated with several cognitive domain scores transdiagnostically. Our findings suggest that a diagnosis of remitted MDD may not confer functional brain risk for dementia. However, given the association of rs-FC with cognitive performance (i.e., transdiagnostically), rs-FC may help in stratifying this risk among people with MDD and varying degrees of cognitive impairment.

Dataset Information

The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder.

Introduction

Methods

Results

Discussion

Publications

The functional role of the pulvinar in discriminating between objective and subjective cognitive impairment in major depressive disorder.

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