Abstract Background Abnormalities have been identified in the Cognitive Control Network (CCN) and the Default Mode Network (DMN) during episodes of late-life depression. This study examined whether ...functional connectivity at rest (FC) within these networks characterizes late-life depression and predicts antidepressant response. Methods 26 non-demented, non-MCI older adults were studied. Of these, 16 had major depression and 10 had no psychopathology. Depressed patients were treated with escitalopram (target dose 20 mg) for 12 weeks after a 2-week placebo phase. Resting state time series was determined prior to treatment. FC within the CCN was determined by placing seeds in the dACC and the DLPFC bilaterally. FC within the DMN was assessed from a seed placed in the posterior cingulate. Results Low resting FC within the CCN and high resting FC within the DMN distinguished depressed from normal elderly subjects. Beyond this “double dissociation”, low resting FC within the CCN predicted low remission rate and persistence of depressive symptoms and signs, apathy, and dysexecutive behavior after treatment with escitalopram. In contrast, resting FC within the DMN was correlated with pessimism but did not predict treatment response. Conclusions If confirmed, these findings may serve as a signature of the brain's functional topography characterizing late-life depression and sustaining its symptoms. By identifying the network abnormalities underlying biologically meaningful characteristics (apathy, dysexecutive behavior, pessimism) and sustaining late-life depression, these findings can provide a novel target on which new somatic and psychosocial treatments can be tested.
The study aimed to: (1) Identify distinct trajectories of change in depressive symptoms by mid-treatment during psychotherapy for late-life depression with executive dysfunction; (2) examine if ...nonresponse by mid-treatment predicted poor response at treatment end; and (3) identify baseline characteristics predicting an early nonresponse trajectory by mid-treatment. A sample of 221 adults 60 years and older with major depression and executive dysfunction were randomized to 12 weeks of either problem-solving therapy or supportive therapy. We used Latent Growth Mixture Models (LGMM) to detect subgroups with distinct trajectories of change in depression by mid-treatment (6th week). We conducted regression analyses with LGMM subgroups as predictors of response at treatment end. We used random forest machine learning algorithms to identify baseline predictors of LGMM trajectories. We found that ~77.5% of participants had a declining trajectory of depression in weeks 0-6, while the remaining 22.5% had a persisting depression trajectory, with no treatment differences. The LGMM trajectories predicted remission and response at treatment end. A random forests model with high prediction accuracy (80%) showed that the strongest modifiable predictors of the persisting depression trajectory were low perceived social support, followed by high neuroticism, low treatment expectancy, and low perception of the therapist as accepting. Our results suggest that modifiable risk factors of early nonresponse to psychotherapy can be identified at the outset of treatment and addressed with targeted personalized interventions. Therapists may focus on increasing meaningful social interactions, addressing concerns related to treatment benefits, and creating a positive working relationship.
Artifacts in functional magnetic resonance imaging (fMRI) data, primarily those related to motion and physiological sources, negatively impact the functional signal-to-noise ratio in fMRI studies, ...even after conventional fMRI preprocessing. Independent component analysis’ demonstrated capacity to separate sources of neural signal, structured noise, and random noise into separate components might be utilized in improved procedures to remove artifacts from fMRI data. Such procedures require a method for labeling independent components (ICs) as representing artifacts to be removed or neural signals of interest to be spared. Visual inspection is often considered an accurate method for such labeling as well as a standard to which automated labeling methods are compared. However, detailed descriptions of methods for visual inspection of ICs are lacking in the literature. Here we describe the details of, and the rationale for, an operationalized fMRI data denoising procedure that involves visual inspection of ICs (96% inter-rater agreement). We estimate that dozens of subjects/sessions can be processed within a few hours using the described method of visual inspection. Our hope is that continued scientific discussion of and testing of visual inspection methods will lead to the development of improved, cost-effective fMRI denoising procedures.
Objective:
White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that ...depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression.
Method:
The subjects were nondemented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate.
Results:
Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions.
Conclusions:
Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder.
Objective:
Apathy is a common phenomenon in late-life depression and is associated with poor outcomes. Apathy is often unrecognized in older depressed adults, and efficacious treatment options are ...lacking. This review provides a systematic review of the neuroanatomical abnormalities associated with apathy in late-life depression. In addition, the review summarizes the neuroimaging findings from studies of neurodegenerative and focal brain injury conditions that frequently present with apathy. The goal is to elucidate cerebral network abnormalities that give rise to apathy in older adults with mood disturbances and to inform future treatment targets.
Method:
Systematic literature review.
Results:
The few studies that have directly examined the neuroanatomical abnormalities of apathy in late-life depression suggest disturbances in the anterior cingulate cortex, insula, orbital and dorsal prefrontal cortex, striatum, and limbic structures (ie, amygdala, thalamus, and hippocampus). Studies examining the neuroanatomical correlates of apathy in other aging populations are consistent with the pattern observed in late-life depression.
Conclusions:
Apathy in late-life depression appears to be accompanied by neuroanatomical abnormalities in the salience and reward networks. These network findings are consistent with that observed in individuals presenting with apathy in other aging-related conditions. These findings may inform future treatments that target apathy.
Long COVID, a term used to describe ongoing symptoms after COVID-19 infection, parallels the course of other postviral syndromes. Neuropsychiatric symptoms of long COVID can be persistent and ...interfere with quality of life and functioning. Within the biopsychosocial framework of chronic illness, rehabilitation professionals can address the neuropsychiatric sequelae of long COVID. However, current practice models are not designed to address concurrent psychiatric and cognitive symptoms in adults living with long COVID. Thus, we present a biopsychosocial framework for long COVID and provide treatment strategies based on evidence from current literature of postviral chronic illness. These recommendations will guide rehabilitation professionals in identifying common neuropsychiatric symptoms in long COVID that can be targeted for intervention and addressing these symptoms via integrative interventions taking into account the biopsychosocial presentation of long COVID symptoms.
Post-stroke depression and executive dysfunction co-occur and are highly debilitating. Few treatments alleviate both depression and executive dysfunction after stroke. Understanding the brain network ...changes underlying post-stroke depression with executive dysfunction can inform the development of targeted and efficacious treatment. In this review, we synthesize neuroimaging findings in post-stroke depression and post-stroke executive dysfunction and highlight the network commonalities that may underlie this comorbidity. Structural and functional alterations in the cognitive control network, salience network, and default mode network are associated with depression and executive dysfunction after stroke. Specifically, post-stroke depression and executive dysfunction are both linked to changes in intrinsic functional connectivity within resting state networks, functional over-connectivity between the default mode and salience/cognitive control networks, and reduced cross-hemispheric frontoparietal functional connectivity. Cognitive training and noninvasive brain stimulation targeted at these brain network abnormalities and specific clinical phenotypes may help advance treatment for post-stroke depression with executive dysfunction.
Objectives Structural abnormalities in the hippocampus have been implicated in the pathophysiology of major depressive disorder (MDD). The brain-derived neurotrophic factor ( BDNF ) val66met ...polymorphism may contribute to these abnormalities and therefore confer vulnerability to MDD. This study examined whether there is a relationship among BDNF genotype, hippocampal volumes, and MDD in older adults. Methods Thirty-three older adults with MDD and 23 psychiatrically normal comparison subjects were studied. Structural magnetic resonance imaging analysis was used to quantify hippocampal volumes. A repeated-measures analysis of covariance examined the relationships among BDNF val66met (val/val, met carrier), diagnosis (depressed, nondepressed), and hippocampal volumes (right, left). Age, gender, education, and whole brain volume were included as covariates. Results Elderly MDD BDNF val/val homozygotes had significantly higher right hippocampal volumes compared with nondepressed val/val subjects. However, there was no difference between the depressed and healthy nondepressed met carriers. In addition, depressed met carriers had an earlier age of onset of depressive illness than val/val homozygotes, but age of onset did not moderate the relationship between hippocampal volumes and MDD diagnosis. Conclusion These results provide preliminary evidence of a neuroprotective role of the val/val genotype, suggesting that neurotrophic factor production protects against pathophysiological processes triggered by depression in older adults with later age of onset of MDD. The BDNF val66met polymorphism may play a salient role in structural alterations of the hippocampus in older adults with MDD.
Background COPD is a major cause of all-cause mortality. We examined predictors of 1-year mortality in patients with severe COPD and major depression after inpatient treatment in a rehabilitation ...hospital. Methods We screened 898 consecutively admitted patients. Of these, 138 patients received the diagnoses of COPD according to American Thoracic Society Guidelines and major depression by Diagnostic and Statistical Manual of Mental Disorders, 4th edition and signed consent; 67 were randomized to a treatment adherence enhancement intervention and 71 to usual care. We assessed history of falls, dyspnea-related disability, severity of depression, medical burden, and cognitive functioning. Following discharge from inpatient rehabilitation, participants were prospectively followed, and mortality was ascertained over 52 weeks from hospital notes and reports of primary care physicians and relatives. Results One-year, all-cause mortality was 22% (31 of 138). Multivariate Cox regression analysis showed that history of falls in the 6 months preceding hospital admission was the strongest predictor of mortality (OR, 3.05; 95% CI, 1.40-6.66; P < .005). Dyspnea during activities (Pulmonary Functional Status and Dyspnea Questionnaire-Modified domain) was also associated with mortality (OR, 1.05; 95% CI, 1.02-1.08; P < .002). Depression severity, medical burden, and cognitive impairment were not predictors of mortality. Conclusions Recent falls and dyspnea during activities identify subgroups of depressed patients with COPD at increased risk for all-cause mortality. These subgroups are in need of clinical attention and follow-up and can serve as targets for prevention research aiming to inform clinical strategies and public health planning.
Poststroke depression (PSD) has a heterogeneous presentation and is often accompanied by cognitive impairment. This study aimed to identify distinct dimensions of depressive symptoms in older adults ...with PSD and to evaluate their relationship to cognitive functioning.
Cross-sectional factor and correlational analyses of patients with poststroke depression.
Patients were recruited from the community and from acute inpatient stroke rehabilitation hospitals.
Participants had suffered a stroke and met DSM-IV criteria for major depression (≥18 Montgomery Åsberg Depression Scale; MADRS).
None.
MADRS was used to quantify depression severity at study entry. Neuropsychological assessment at the time of study entry consisted of measures of Global Cognition, Attention, Executive Function, Processing Speed, Immediate Memory, Delayed Memory, and Language.
There were 135 (age ≥50) older adult participants with PSD and varying degrees of cognitive impairment (MMSE Total ≥20). Factor analysis of the MADRS identified three factors, that is sadness, distress, and apathy. Items comprising each factor were totaled and correlated with neuropsychological domain z-score averages. Symptoms of the apathy factor (lassitude, inability to feel) were significantly associated with greater impairment in executive function, memory, and global cognition. Symptoms of the sadness and distress factors had no relationship to cognitive impairment.
PSD consists of three correlated dimensions of depressive symptoms. Apathy symptoms are associated with cognitive impairment across several neuropsychological domains. PSD patients with prominent apathy may benefit from careful attention to cognitive functions and by interventions that address both psychopathology and behavioral deficits resulting from cognitive impairment.
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