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. 2019 Feb;4(2):160-170.
doi: 10.1016/j.bpsc.2018.09.003. Epub 2018 Sep 21.

Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression

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Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression

Jason A Gandelman et al. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Feb.

Abstract

Background: Late-life depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the default mode network (DMN), cognitive control network (CCN), and salience network. However, these findings often derive from small samples, and it is not well understood how network findings relate to clinical and cognitive symptomatology.

Methods: We studied 100 older adults (n = 79 with LLD, n = 21 nondepressed) and collected resting-state functional magnetic resonance imaging, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and salience network) as seeds in seed-to-voxel analysis. We compared connectivity between the depressed and nondepressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance.

Results: LLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ21 = 22.33, p < .001). No significant group differences in connectivity were found for the CCN or salience network. However, in the LLD group, increased CCN connectivity was associated with increased depression severity (Wald χ21 > 20.14, p < .001), greater anhedonia (Wald χ21 = 7.02, p = .008) and fatigue (Wald χ21 = 6.31, p = .012), and poorer performance on tests of episodic memory (Wald χ21 > 4.65, p < .031), executive function (Wald χ21 = 7.18, p = .007), and working memory (Wald χ21 > 4.29, p < .038).

Conclusions: LLD is characterized by differences in DMN connectivity, while CCN connectivity is associated with LLD symptomology, including poorer performance in several cognitive domains.

Keywords: Aging; Cognition; Cognitive control network; Default mode network; Functional connectivity; Geriatric.

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Conflict of interest statement

The authors report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1.
Figure 1.. DMN Functional Connectivity Differences in Depressed Elders
A) Resting functional connectivity pattern with lower connectivity in depressed subjects compared to nondepressed subjects using the posterior cingulate cortex (PCC) seed for the Default Mode Network. B) Comparison of 95% Confidence Intervals of beta-value between depressed and nondepressed diagnostic groups. C) X-axis is functional connectivity beta-value, Y-axis is MADRS. MADRS = Montgomery Asberg Depression Rating Scale.
Figure 2.
Figure 2.. CCN Functional Connectivity Differences Associated with Depression Severity in Depressed Elders
A) Resting functioal connectivity pattern associated with higher MADRS in depressed subjects using the Left dorsolateral prefrontal cortex (dlPFC) seed for the Cognitive Control Network. B and D) Comparison of 95% Confidence Intervals of beta-value between depressed and nondepressed diagnostic groups. C and E) X-axis is functional connectivity beta-value, Y-axis is MADRS. MADRS = Montgomery Asberg Depression Rating Scale.
Figure 3.
Figure 3.. Functional Connectivity Relationship with Neuropsychiatric Symptoms
X-axis is functional connectivity beta-value for dlPFC-SMC, Y-axis is severity of specified neuropsychiatric symptom. Higher scores on both scales indicate greater symptom severity. SHAPS = Snaith-Hamilton Pleasure Scale, FSS = Fatigue Severity Scale.
Figure 4.
Figure 4.. Functional Connectivity Relationship with Cognitive Test Performance
X-axis is functional connectivity beta-value for the specified functionally connected pair, Y-axis is performance on the specified cognitive test. SDMT= Symbol Digit Modality Test.

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