The percentage of cognitive impairment in patients with major depressive disorder over the course of the depression: A longitudinal study.

BACKGROUND: Cognitive impairments (CI) are prevalent and persistent in patients with major depressive disorder (MDD). There is a lack of longitudinal studies exploring the changes of the percentage of CI among MDD patients before and after a long-term antidepressant treatment and the risk factors that predict the residual CI. METHODS: A neurocognitive battery was performed to assess four domains of cognitive function, including executive function, processing speed, attention, and memory. CI was set as cognitive performance scoring 1.5 SDs lower than the mean scores of healthy controls (HCs). Logistic regression models were conducted to examine the risk factors for the after-treatment residual CI. RESULTS: Over 50 % of patients showed at least one kind of CI. After the antidepressant treatment, the overall cognitive performance among remitted MDD patients was identical to HCs, however, there were still 24 % of the remitted MDD patients had at least one type of CI, especially in executive function and attention. Additionally, the percentage of CI among non-remitted MDD patients was still significantly different from HCs. Our regression analysis further identified that except for the non-remission of MDD, CI at baseline could also predict the residual CI in MDD patients. LIMITATIONS: A relatively high drop-out rate at follow-ups. CONCLUSIONS: Cognitive impairment in executive function and attention is persistent even in remitted patients with MDD, and baseline cognitive performance can predict the post-treatment cognitive performance. Our findings emphasize the integral role of early cognitive intervention in MDD treatment.

State-independent and -dependent behavioral and neuroelectrophysiological characteristics during dynamic decision-making in patients with current and remitted depression.

BACKGROUND: It is unclear whether the altered decision-making (DM) observed in patients with major depressive disorder (MDD) is neurophysiological and whether it improves with remission of depressive symptoms. The aim of this study was to identify developmental patterns of DM behavior, related cognitive characteristics, and electrophysiological abnormalities in patients with MDD across clinical stages. METHODS: A sample of 48 first-episode MDD patients (FD group), 41 remitted MDD patients (RD group), and 43 healthy controls (HCs) completed psychometric assessments and performed the balloon analogue risk task (BART) while event-related potentials (ERPs) were recorded. RESULTS: The RD group had lower depressiveness, self-blame, rumination, and catastrophizing tendencies, and higher mental resilience scores than the FD group, but retained significant differences from HCs. MDD patients showed a more conservative DM strategy than HCs, with no significant difference between the FD and RD groups. Compared to the FD group, the RD group had a smaller FRN for negative feedback and a trend toward a smaller P3 for positive feedback. Compared with HCs, the RD group had a smaller P3 during the positive feedback phase. FRN amplitude correlated positively with depression level and negatively with mental resilience. LIMITATIONS: Because a comparative cross-section design was employed, longitudinal studies are needed to make causal inferences. CONCLUSION: MDD patients presented a stable risk-avoidance bias in actively depressed and remission periods, consistent with a state-independent impairment pattern. Significantly reduced FRN amplitudes during remission indicated a state-dependent impairment pattern, and FRN amplitudes correlated with depression level. An abnormal feedback P3 component may be a state-independent characteristic that may become more pronounced with MDD progression.

Functional connectivity evidence for state-independent executive function deficits in patients with major depressive disorder.

BACKGROUND: Persistent neurocognitive deficits are often associated with poor outcomes of major depressive disorder (MDD). Executive dysfunction is the most common cognitive deficit in MDD. However, it remains unclear which subcomponent of executive dysfunction is state-independent with distinct neural substrates. METHODS: A comprehensive neurocognitive test battery was used to assess four subcomponents of executive function (working memory, inhibition, shifting, and verbal fluency) in 95 MDD patients and 111 matched healthy controls (HCs). After 6 months of paroxetine treatment, 56 patients achieved clinical remission (rMDD) and completed the second-time neurocognitive test. Network-based statistics analysis was utilized to explore the changes in functional connectivity (FC). RESULTS: Compared with the HCs, all the four subcomponents of MDD patients were significantly impaired. After treatment, there was a significant improvement in working memory, inhibition, and verbal fluency in the rMDD group. And shifting and verbal fluency of the rMDD group remained impaired compared with the HCs. Fifteen functional connections were interrupted in the MDD group, and 11 connections remained in a disrupted state after treatment. Importantly, verbal fluency was negatively correlated with the disrupted FC between the right dorsal prefrontal cortex and the left inferior parietal lobule in patients with MDD and remitted MDD. LIMITATIONS: The correlation analysis of the association between cognitive impairment and connectivity alterations precluded us from making causal inferences. CONCLUSIONS: Verbal fluency is the potential state-independent cognitive deficit with distinct neural basis in patients with MDD.

Potential structural trait markers of depression in the form of alterations in the structures of subcortical nuclei and structural covariance network properties.

It has been proposed recently that major depressive disorder (MDD) could represent an adaptation to conserve energy after the perceived loss of an investment in a vital source, such as group identity, personal assets, or relationships. Energy conserving behaviors associated with MDD may form a persistent marker in brain regions and networks involved in cognition and emotion regulation. In this study, we examined whether subcortical regions and volume-based structural covariance networks (SCNs) have state-independent alterations (trait markers). First-episode drug-naïve currently depressed (cMDD) patients (N = 131), remitted MDD (RD) patients (N = 67), and healthy controls (HCs, N = 235) underwent structural magnetic resonance imaging (MRI). Subcortical gray matter volumes (GMVs) were calculated in FreeSurfer software, and group differences in GMVs and SCN were analyzed. Compared to HCs, major findings were decreased GMVs of left pallidum and pulvinar anterior of thalamus in the cMDD and RD groups, indicative of a trait marker. Relative to HCs, subcortical SCNs of both cMDD and RD patients were found to have reduced small-world-ness and path length, which together may represent a trait-like topological feature of depression. In sum, the left pallidum, left pulvinar anterior of thalamus volumetric alterations may represent trait marker and reduced small-world-ness, path length may represent trait-like topological feature of MDD.

State-Independent and -Dependent Structural Connectivity Alterations in Depression.

Some brain abnormalities persist at the remission phase, that is, the state-independent abnormalities, which may be one of the reasons for the high recurrence of major depressive disorder (MDD). Hence, it is of great significance to identify state-independent abnormalities of MDD through longitudinal investigation. Ninety-nine MDD patients and 118 healthy controls (HCs) received diffusion tensor imaging scanning at baseline. After 6-month antidepressant treatment, 68 patients received a second scan, among which 59 patients achieved full clinical remission. Differences in whole-brain structural connectivity (SC) between patients with MDD at baseline and HCs were estimated by two-sample t-tests. Masked with significantly changed SCs in MDD, two-sample t-tests were conducted between the remitted MDD subgroup at follow-up and HCs, and paired t-tests were implemented to compare the differences of SC in the remitted MDD subgroup before and after treatment. Significantly decreased SC between the right insula and the anterior temporal cortex (ATC), between the right ATC and the posterior temporal cortex (PTC), between the left ATC and the auditory cortex as well as increased connectivity between the right posterior cingulate cortex (PCC) and the left medial parietal cortex (MPC) were observed in the MDD group compared with the HC group at baseline (p < 0.05, FDR corrected). The decreased connectivity between the right insula and the ATC and increased connectivity between the right PCC and the left MPC persisted in the remitted MDD subgroup at follow-up (p < 0.05, FDR corrected). The decreased SC between the right insula and the ATC and increased SC between the right PCC and left MPC showed state-independent characters, which may be implicated in the sustained negative attention bias and motor retardation in MDD. In contrast, the decreased SC between the right ATC and the PTC and between the left ATC and the auditory cortex seemed to be state-dependent.

State-Independent Microstructural White Matter Abnormalities in Major Depressive Disorder.

BACKGROUND: Even with continuous antidepressant treatment, residual symptoms and the risk of relapse can persist in remitted major depressive disorder (MDD) patients. Hence, having a clear recognition of the persistent abnormalities of the underlying neural substrate in MDD through a longitudinal investigation is of great importance. METHODS: A total of 127 adult medication-free MDD patients with an acute depressive episode and 118 matched healthy controls (HCs) underwent diffusion tensor imaging. Over a 6-month treatment course, 62 remitted patients underwent a second scan. Remission was defined as a 24-item Hamilton Depression Rating Scale (HAMD24) score ≤7 for at least two weeks. Diffusion tensor imaging was performed with a 3.0 T scanner. Differences in whole-brain fractional anisotropy (FA) between MDD patients and HCs were assessed by an independent t-test using gender, age, and education as covariates. RESULTS: Significant FA reductions in the left insula, left middle occipital gyrus, right thalamus, left pallidum and left precuneus were observed in current MDD (cMDD) patients compared with HCs. Moreover, significant FA reductions in the left insula were observed in remitted (rMDD) patients compared to HCs. However, no significant differences in FA values were found when comparing cMDD and rMDD patients. CONCLUSIONS: The abnormalities in the insula showed state-independent characteristics, while the abnormalities in the middle occipital gyrus, thalamus, pallidum and precuneus seemed to be state-dependent impairments in MDD patients.