Joanna K. Seirup

Functional connectivity in apathy of late-life depression: A preliminary study

BACKGROUND Apathy is common in late-life depression and is associated with disability and poor antidepressant response. This study examined whether resting functional connectivity (FC) of the nucleus accumbens (NAcc) and the dorsal anterior cingulate (dACC) with other structures can distinguish apathetic depressed older patients from non-apathetic depressed patients and normal subjects. METHODS Twenty-six non-demented, non-MCI older adults were studied. Of these, 16 had major depression (7 also had apathy) and 10 had no psychopathology. Resting state fMRI was performed prior to treatment in subjects who were psychotropic-free for at least two weeks. FC was determined by placing seeds in the NAcc and the dACC bilaterally. RESULTS Apathetic depressed patients had lower FC of the NAcc with the amygdala, caudate, putamen, globus pallidus, and thalamus and increased FC with the dorsomedial prefrontal cortex, the superior frontal cortex, and the insula than non-apathetic patients. Further, apathetic patients had lower FC of the dACC with dorsolateral and ventrolateral prefrontal cortices and higher FC with the insula and the orbitofrontal cortex than non-apathetic patients. LIMITATIONS Small number of subjects, lack of random sampling, use of a 1.5T MRI scanner. CONCLUSIONS This preliminary study suggests that FC between the NAcc and the dACC and structures related to reward and related behavioral responses constitute the functional topography of abnormalities characterizing apathy of late life depression. However, replication is needed.

The salience network in the apathy of late-life depression.

Apathy is prevalent in late‐life depression and predicts poor response to antidepressants, chronicity of depression, disability, and greater burden to caregivers. However, little is known about its neurobiology. Salience processing provides motivational context to stimuli. The aim of this study was to examine the salience network (SN) resting‐state functional connectivity (rsFC) pattern in elderly depressed subjects with and without apathy.

Neuroplasticity-based computerized cognitive remediation for treatment-resistant geriatric depression.

Executive dysfunction (ED) in geriatric depression (GD) is common, predicts poor clinical outcomes and often persists despite remission of symptoms. Here we develop a neuroplasticity-based computerized cognitive remediation treatment (CCR-GD) to target ED in GD. Our assumption is that remediation of these deficits may modulate the underlying brain network abnormalities shared by executive dysfunction and depression. We compare CCR-GD to a gold standard treatment (escitalopram: 20mgs/12 weeks) in 11 treatment resistant older adults with major depression; and 33 matched historical controls. We find that 91% of participants complete CCR-GD. CCR-GD is equally as effective at reducing depressive symptoms as escitalopram but does so in 4 weeks instead of 12. In addition CCR-GD improves measures of executive function more than the escitalopram. We conclude that CCR-GD may be equally effective as escitalopram in treating GD. In addition, CCR-GD participants showed greater improvement in executive functions than historical controls treated with escitalopram.

Apathy in Late-Life Depression: Common, Persistent, and Disabling

OBJECTIVE The aims of this study were to examine: (1) the relationship between apathy and disability in late-life depression, and (2) the functional significance of improvement in apathy following escitalopram treatment in terms of its relationship to disability. METHODS Subjects were 71 non-demented elderly with non-psychotic major depression. After a 2-week single-blind placebo period, subjects who had Hamilton Depression Rating Scale (HDRS) ≥ 18 received escitalopram 10 mg daily for 12 weeks. Apathy and disability were assessed with the Apathy Evaluation Scale (AES) and the World Health Organization Disability Assessment Scale II (WHODAS), respectively. These measures and the HDRS were administered at baseline and again following 12 weeks of treatment. RESULTS At baseline, 38% of depressed subjects had significant apathy (AES ≥ 36.5). Severity of apathy at baseline significantly correlated with severity of disability. In a multivariate regression model, baseline severity of apathy, but not the overall depressive syndrome (HDRS), significantly correlated with baseline disability. Following escitalopram treatment, improvement in apathy significantly correlated with improvement in disability measures, while change in the rest of the depressive syndrome did not. The overall change in apathy and disability in response to escitalopram treatment was significant but small. CONCLUSION Apathy is common in late-life depression and is associated with disability above and beyond the influence of other depressive symptoms. Given the strong relationship between apathy and disability, understanding the neurobiology of apathy and developing treatments for apathy may improve the functional outcomes of late-life depression.

Personalised intervention for people with depression and severe COPD

Chronic obstructive pulmonary disease (COPD) is often complicated by depression and exemplifies the challenge in managing chronic illnesses that require active patient participation in care. In a clinical trial (NCT00151372), we compared a novel personalised intervention for depression and COPD (PID-C) targeting treatment adherence with treatment as usual (TAU). In 138 patients with major depression and severe COPD, PID-C led to a higher remission rate and a greater reduction in depressive symptoms and in dyspnoea-related disability than TAU over 28 weeks and 6 months after the last session. If replicated, PID-C may serve as a care model for patients with both depression and medical illnesses with a deteriorating course.

Executive Functioning Complaints and Escitalopram Treatment Response in Late-Life Depression

OBJECTIVE Executive dysfunction may play a key role in the pathophysiology of late-life depression. Executive dysfunction can be assessed with cognitive tests and subjective report of difficulties with executive skills. The present study investigated the association between subjective report of executive functioning complaints and time to escitalopram treatment response in older adults with major depressive disorder (MDD). METHODS 100 older adults with MDD (58 with executive functioning complaints and 42 without executive functioning complaints) completed a 12-week trial of escitalopram. Treatment response over 12 weeks, as measured by repeated Hamilton Depression Rating Scale scores, was compared for adults with and without executive complaints using mixed-effects modeling. RESULTS Mixed effects analysis revealed a significant group × time interaction, F(1, 523.34) = 6.00, p = 0.01. Depressed older adults who reported executive functioning complaints at baseline demonstrated a slower response to escitalopram treatment than those without executive functioning complaints. CONCLUSION Self-report of executive functioning difficulties may be a useful prognostic indicator for subsequent speed of response to antidepressant medication.

Untangling therapeutic ingredients of a personalized intervention for patients with depression and severe COPD.

OBJECTIVE We developed a personalized intervention for depressed patients with COPD (PID-C) aimed to mobilize patients to participate in the care of both conditions. We showed that PID-C reduced depressive symptoms and dyspnea-related disability more than usual care over 28 weeks. This study focused on untangling key therapeutic ingredients of PID-C. DESIGN Randomized controlled trial. SETTING Community. PARTICIPANTS 138 patients who received the diagnoses of COPD and major depression after screening 898 consecutive admissions for acute inpatient pulmonary rehabilitation. INTERVENTION Nine sessions of PID-C compared with usual care over 28 weeks. MEASUREMENTS Primary outcome measures were the 17-item Hamilton Depression Rating Scale and the Pulmonary Functional Status and Dyspnea Questionnaire-Modified. Other measures were adherence to rehabilitation exercise (≥2 hours per week) and adherence to adequate antidepressant prescriptions. RESULTS Low severity of dyspnea-related disability and adherence to antidepressants predicted subsequent improvement of depression. Exercise and low depression severity predicted improvement of dyspnea-related disability. CONCLUSIONS PID-C led to an interacting spiral of improvement in both depression and disability in a gravely medically ill population with a 17% mortality rate over 28 weeks and an expected deterioration in disability. The interrelationship of the course of depression and dyspnea-related disability underscores the need to target adherence to both antidepressants and chronic obstructive pulmonary disease rehabilitation. PID-C may serve as a care management model for depressed persons suffering from medical illnesses with a deteriorating course.

Predictors of All-Cause Mortality in Patients With Severe COPD and Major Depression Admitted to a Rehabilitation Hospital

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.

Cognitive control, reward-related decision making and outcomes of late-life depression treated with an antidepressant

BACKGROUND Executive processes consist of at least two sets of functions: one concerned with cognitive control and the other with reward-related decision making. Abnormal performance in both sets occurs in late-life depression. This study tested the hypothesis that only abnormal performance in cognitive control tasks predicts poor outcomes of late-life depression treated with escitalopram. METHOD We studied older subjects with major depression (N = 53) and non-depressed subjects (N = 30). Executive functions were tested with the Iowa Gambling Test (IGT), Stroop Color-Word Test, Tower of London (ToL), and Dementia Rating Scale - Initiation/Perseveration domain (DRS-IP). After a 2-week placebo washout, depressed subjects received escitalopram (target daily dose: 20 mg) for 12 weeks. RESULTS There were no significant differences between depressed and non-depressed subjects on executive function tests. Hierarchical cluster analysis of depressed subjects identified a Cognitive Control cluster (abnormal Stroop, ToL, DRS-IP), a Reward-Related cluster (IGT), and an Executively Unimpaired cluster. Decline in depression was greater in the Executively Unimpaired (t = -2.09, df = 331, p = 0.0375) and the Reward-Related (t = -2.33, df = 331, p = 0.0202) clusters than the Cognitive Control cluster. The Executively Unimpaired cluster (t = 2.17, df = 331, p = 0.03) and the Reward-Related cluster (t = 2.03, df = 331, p = 0.0433) had a higher probability of remission than the Cognitive Control cluster. CONCLUSIONS Dysfunction of cognitive control functions, but not reward-related decision making, may influence the decline of symptoms and the probability of remission of late-life depression treated with escitalopram. If replicated, simple to administer cognitive control tests may be used to select depressed older patients at risk for poor outcomes to selective serotonin reuptake inhibitors who may require structured psychotherapy.

An evaluation of national birth certificate data for neonatal seizure epidemiology

Seizures are a common manifestation of neurologic dysfunction in neonates and carry a high risk for mortality and adverse long‐term outcomes. U.S. birth certificates are a potentially valuable source for studying the epidemiology of neonatal seizures. However, the quality of the data is understudied.