Dataset Information

Reduced cerebrospinal fluid levels of brain-derived neurotrophic factor is associated with cognitive impairment in late-life major depression.

ABSTRACT:

Objectives

Late-life depression (LLD) is associated with reduced neurotrophic support and abnormalities in neurodegenerative cascades. The aim of the present study is to determine the concentrations of brain-derived neurotrophic factor (BDNF), amyloid-?42, total Tau, and phosphorylated Tau in the cerebrospinal fluid (CSF) of patients with LLD and cognitive impairment compared to healthy older adults.

Method

We included 25 antidepressant-free patients with LLD (10 with mild cognitive impairment [LLD + MCI] and 15 with no cognitive decline [LLD + NCD]) and 25 healthy older adults as a comparison group. Depressive symptoms were assessed by the 21-item Hamilton Depression Rating Scale (HDRS-21) and cognitive performance by a comprehensive cognitive battery.

Results

Patients with LLD + MCI showed significantly lower CSF BDNF levels compared to LLD + NCD and healthy controls (p = .003). There were no significant differences in Alzheimer's disease-related CSF biomarkers between groups. CSF BDNF concentrations were positively correlated with Cambridge Cognitive Test (CAMCOG) scores (r = .36, p = .02).

Discussion

The present study adds to the growing body of evidence that abnormalities in the BDNF system are involved in the pathophysiology of LLD. The reduction of the availability of BDNF in the central nervous system may indicate increased vulnerability to the development of several age-related neuropsychiatric disorders as well as to adverse cognitive outcomes.

SUBMITTER: Diniz BS

PROVIDER: S-EPMC4217554 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Reduced cerebrospinal fluid levels of brain-derived neurotrophic factor is associated with cognitive impairment in late-life major depression.

Diniz Breno S BS Teixeira Antonio L AL Machado-Vieira Rodrigo R Talib Leda L LL Radanovic Marcia M Gattaz Wagner F WF Forlenza Orestes V OV

The journals of gerontology. Series B, Psychological sciences and social sciences 20140822 6

<h4>Objectives</h4>Late-life depression (LLD) is associated with reduced neurotrophic support and abnormalities in neurodegenerative cascades. The aim of the present study is to determine the concentrations of brain-derived neurotrophic factor (BDNF), amyloid-β42, total Tau, and phosphorylated Tau in the cerebrospinal fluid (CSF) of patients with LLD and cognitive impairment compared to healthy older adults.<h4>Method</h4>We included 25 antidepressant-free patients with LLD (10 with mild cogniti ...[more]

PMID: 25149921

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Project description:BACKGROUND:The autotaxin/lysophosphatidic acid axis is involved in diverse biological processes including neurodevelopment, inflammation, and immunological functioning. The lysophosphatidic acid 1 receptor has been implicated in the pathophysiology of major depressive disorder and in the mechanism of action of antidepressants. However, it is unclear whether central or peripheral autotaxin levels are altered in patients with major depressive disorder. METHODS:Serum autotaxin levels were measured by an enzyme-linked immunosorbent assay in 37 patients with major depressive disorder diagnosed using DSM-IV-TR who underwent electroconvulsive therapy and were compared with those of 47 nondepressed controls matched for age and sex between January 2011 and December 2015. Patient serum levels of autotaxin before and after electroconvulsive therapy were also compared. In a separate sample set, cerebrospinal fluid autotaxin levels were compared between 26 patients with major depressive disorder and 27 nondepressed controls between December 2010 and December 2015. A potential association was examined between autotaxin levels and clinical symptoms assessed with the Hamilton Depression Rating Scale. RESULTS:Before electroconvulsive therapy, both serum and cerebrospinal fluidautotaxin levels were significantly lower in major depressive disorder patients than in controls (serum: P = .001, cerebrospinal fluid: P = .038). A significantly negative correlation between serum, but not cerebrospinal fluid, autotaxin levels and depressive symptoms was observed (P = .032). After electroconvulsive therapy, a parallel increase in serum autotaxin levels and depressive symptoms improvement was observed (P = .005). CONCLUSION:The current results suggest that serum autotaxin levels are reduced in a state-dependent manner. The reduction of cerebrospinal fluidautotaxin levels suggests a dysfunction in the autotaxin/lysophosphatidic acid axis in the brains of patients with major depressive disorder.

Project description:IntroductionAlzheimer's disease (AD) is characterized by the deposition of tau and amyloid in the brain. Although the core cerebrospinal fluid (CSF) AD biomarkers amyloid β peptide 1-42 (Aβ1-42), total tau (t-tau) and phosphorylated tau 181 (p-tau181) show good diagnostic sensitivity and specificity, additional biomarkers that can aid in preclinical diagnosis or better track disease progression are needed. Activation of the complement system, a pivotal part of inflammation, occurs at very early stages in the AD brain. Therefore, CSF levels of complement proteins that could be linked to cognitive and structural changes in AD may have diagnostic and prognostic value.MethodsUsing xMAP® technology based assays we measured complement 3 (C3) and factor H (FH) in the CSF of 110 controls (CN), 187 mild cognitive impairment (MCI) and 92 AD subjects of the AD Neuroimaging Initiative (ADNI) at baseline. All ADNI participants underwent clinical follow-up at 12 month intervals and MCI subjects had additional visits at 6 and 18 months. The association between CSF biomarkers and different outcome measures were analyzed using Cox proportional hazard models (conversion from MCI to AD), logistic regression models (classification of clinical groups) and mixed-effects models adjusted for age, gender, education, t-tau/Aβ1-42 and APOE ϵ4 presence (baseline and longitudinal association between biomarkers and cognitive scores).ResultsAlthough no association was found between the complement proteins and clinical diagnosis or cognitive measures, lower levels of C3 (β = -0.12, p = 0.041) and FH (β = -0.075, p = 0.041) were associated with faster cognitive decline in MCI subjects as measured by the AD Assessment Scale-cognitive subscale (ADAS-Cog) test. Furthermore, lower FH levels were associated with larger lateral ventricular volume (p = 0.024), which is indicative of brain atrophy.ConclusionsOur study confirms a lack of suitability of CSF C3 and FH as diagnostic biomarkers of AD, but points to their modest potential as prognostic biomarkers and therapeutic targets in cognitively impaired patients.

Dataset Information

Reduced cerebrospinal fluid levels of brain-derived neurotrophic factor is associated with cognitive impairment in late-life major depression.

Objectives

Method

Results

Discussion

Publications

Reduced cerebrospinal fluid levels of brain-derived neurotrophic factor is associated with cognitive impairment in late-life major depression.

Similar Datasets

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