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.

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.

Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression.

OBJECTIVE: This study tests the hypothesis that the use of semantic organizational strategy during the free-recall phase of a verbal memory task predicts remission of geriatric depression. METHODS: Sixty-five older patients with major depression participated in a 12-week escitalopram treatment trial. Neuropsychological performance was assessed at baseline after a 2-week drug washout period. The Hopkins Verbal Learning Test-Revised was used to assess verbal learning and memory. Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7 for 2 consecutive weeks and no longer meeting the DSM-IV-TR criteria for major depression. The association between the number of clusters used at the final learning trial (trial 3) and remission was examined using Cox's proportional hazards survival analysis. The relationship between the number of clusters utilized in the final learning trial and the number of words recalled after a 25-min delay was examined in a regression with age and education as covariates. RESULTS: Higher number of clusters utilized predicted remission rates (hazard ratio, 1.26 (95% confidence interval, 1.04-1.54); χ(2) = 4.23, df = 3, p = 0.04). There was a positive relationship between the total number of clusters used by the end of the third learning trial and the total number of words recalled at the delayed recall trial (F(3,58) = 7.93; p < 0.001). CONCLUSIONS: Effective semantic strategy use at baseline on a verbal list learning task by older depressed patients was associated with higher rates of remission with antidepressant treatment. This result provides support for previous findings indicating that measures of executive functioning at baseline are useful in predicting antidepressant response.

Self-injurious behavior in the nursing home setting.

BACKGROUND: Self-injurious behavior (SIB) in older adults is defined as harm inflicted on oneself without conscious suicidal intent. SIB as a separate entity distinct from suicidal intent is poorly understood. However, it is of great concern to the patients' families and caregivers and it poses serious clinical challenges for clinicians. METHODS: We searched the database of PubMed, Ovid Medline, and ScienceDirect for reports published between 1970 and 2009 using combination of the following keywords: "self-injurious behavior", "self-destructive behavior", "self-mutilating behavior", "older adults", "geriatric population", and "nursing homes". The term "self-harm behavior" which also appears in the literature is broader in scope than "self-injurious behavior". It encompasses high suicide intent and failed suicide attempts; therefore, we excluded this term in order to focus purely on "self-injurious behavior". Our search yielded 10 publications concerning SIB in older adults, four of which included studies investigating SIB in nursing homes. RESULTS: Clinical studies of SIB in older adult nursing home residents are sparse. This limited literature suggests that SIB is a prevalent phenomenon and is reported to be as high as 14% in one study of nursing home subjects aged 65 and older. It is reported to be strongly associated with dementia and a risk of accidental death. It has been suggested that SIB among demented patients occurs in the context of poor impulse control and physical isolation. CONCLUSION: SIB is likely a common phenomenon in older adult nursing home residents. There is little evidence-based treatment guidance for SIB in older population.

An intervention to improve nurse-physician communication in depression care.

OBJECTIVES: Depression in older adult home care recipients is frequently undetected and inadequately treated. Failed communication between home healthcare personnel and the patient's physician has been identified as a barrier for depression care. The purpose of this pilot intervention study was to improve nurse competency for communicating depression-related information to the physician. DESIGN: A single group pre-post experimental design. SETTING: Two Medicare-certified home healthcare agencies serving an urban and suburban area in New York. PARTICIPANTS: Twenty-eight home care nurses, all female Registered Nurses. INTERVENTION: Two-hour skills training workshop. MEASUREMENTS: To evaluate the intervention, pre-post changes in effective nurse communication using Objective Structured Clinical Examinations and nurse survey reports. RESULTS: The intervention significantly improved the ability of the home care nurse to perform a case presentation in a complete and standard organized format pre versus postintervention. The intervention also increased nurse-reported certainty to communicate depression-related information to the physician. CONCLUSIONS: Our findings provide support for the ability of a brief, depression-focused communication skills training intervention to improve home care nurse competency for effectively communicating depression-related information to the physician.

Anterior cingulate cortical volumes and treatment remission of geriatric depression.

BACKGROUND: Structural abnormalities of the anterior cingulate cortex (ACC) may interfere with the interaction of cortical and limbic networks involved in emotional regulation and contribute to chronic depressive syndromes in the elderly. This study examined the relationship of regional anterior cingulate cortical volumes with treatment remission of elderly depressed patients. We hypothesized that patients who failed to remit during a 12-week controlled treatment trial of escitalopram would exhibit smaller anterior cingulate gray matter volumes than patients who remitted. METHODS: The participants were 41 non-demented individuals with non-psychotic major depression. After a 2-week single-blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for at least 2 consecutive weeks. The patient sample consisted of 22 depressed patients who achieved remission during the study and 19 depressed patients who remained symptomatic. High-resolution magnetization-prepared rapidly acquired gradient echo (MPRAGE) sequences were acquired on a 1.5 T scanner and regional ACC volumes were manually outlined (dorsal, rostral, anterior subgenual, and posterior subgenual). RESULTS: Repeated measure analyses revealed that patients who failed to remit following escitalopram treatment had smaller dorsal and rostral anterior cingulate gray matter volumes than patients who remitted, whereas subgenual cortical volumes did not differ between the groups. CONCLUSIONS: Structural abnormalities of the dorsal and rostral anterior cingulate may perpetuate late-life depression.

Microstructural white matter abnormalities and remission of geriatric depression.

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.

Macromolecular white matter abnormalities in geriatric depression: a magnetization transfer imaging study.

OBJECTIVE: Geriatric depression consists of complex and heterogeneous behaviors unlikely to be caused by a single brain lesion. However, abnormalities in specific brain structures and their interconnections may confer vulnerability to the development of late-life depression. The objective of this study was to identify subtle white matter abnormalities in late-life depression. DESIGN: The authors used magnetization transfer ratio (MTR) imaging, a technique that is thought primarily to reflect myelin integrity, to examine the hypothesis that individuals with late-life depression would exhibit white matter abnormalities in frontostriatal and limbic regions. SETTING: The study was conducted in a university-based, geriatric psychiatry clinic. PARTICIPANTS: Fifty-five older patients with major depression and 24 elderly comparison subjects were assessed. MEASUREMENT: Voxel-based analysis of MTR data were conducted with a general linear model using age as a covariate. RESULTS: Relative to comparison subjects, patients demonstrated lower MTR in multiple left hemisphere frontostriatal and limbic regions, including white matter lateral to the lentiform nuclei, dorsolateral and dorsomedial prefrontal, dorsal anterior cingulate, subcallosal, periamygdalar, insular, and posterior cingulate regions. Depressed patients had lower MTR in additional left hemisphere locales including the thalamus, splenium of the corpus callosum, inferior parietal, precuneus, and middle occipital white matter regions. CONCLUSION: These findings suggest that geriatric depression may be characterized by reduced myelin integrity in specific aspects of frontostriatal and limbic networks, and complement diffusion tensor studies of geriatric depression that indicate decreased organization of white matter fibers in specific frontal and temporal regions.

Event-related potentials in an emotional go/no-go task and remission of geriatric depression.

Anterior cingulate integrity may be required for antidepressant response. To assess anterior cingulate processes related to treatment response, we studied error-related negativity and error positivity produced during an emotional go/no-go challenge, a task activating the rostral anterior cingulate. Twelve elderly patients with major depression, treated with escitalopram 10 mg daily, were studied. Patients who remained symptomatic after 8 weeks of treatment had larger error-related negativity and smaller error positivity amplitude compared with patients who achieved remission. The error-related negativity is elicited during conflict detection and the error positivity reflects the emotional reaction to error. Thus, these findings suggest that two distinct conflict-processing functions of the anterior cingulate are important for antidepressant response of geriatric depression.

Why Not Wait? Eight Institutions Share Their Experiences Moving United States Medical Licensing Examination Step 1 After Core Clinical Clerkships.

The majority of medical students complete the United States Medical Licensing Examination Step 1 after their foundational sciences; however, there are compelling reasons to examine this practice. This article provides the perspectives of eight MD-granting medical schools that have moved Step 1 after the core clerkships, describing their rationale, logistics of the change, outcomes, and lessons learned. The primary reasons these institutions cite for moving Step 1 after clerkships are to foster more enduring and integrated basic science learning connected to clinical care and to better prepare students for the increasingly clinical focus of Step 1. Each school provides key features of the preclerkship and clinical curricula and details concerning taking Steps 1 and 2, to allow other schools contemplating change to understand the landscape. Most schools report an increase in aggregate Step 1 scores after the change. Despite early positive outcomes, there may be unintended consequences to later scheduling of Step 1, including relatively late student reevaluations of their career choice if Step 1 scores are not competitive in the specialty area of their choice. The score increases should be interpreted with caution: These schools may not be representative with regard to mean Step 1 scores and failure rates. Other aspects of curricular transformation and rising national Step 1 scores confound the data. Although the optimal timing of Step 1 has yet to be determined, this article summarizes the perspectives of eight schools that changed Step 1 timing, filling a gap in the literature on this important topic.

Neuroanatomical correlates of apathy in late-life depression and antidepressant treatment response.

BACKGROUND: Apathy is a prominent feature of geriatric depression that predicts poor clinical outcomes and hinders depression treatment. Yet little is known about the neurobiology and treatment of apathy in late-life depression. This study examined apathy prevalence in a clinical sample of depressed elderly, response of apathy to selective serotonin reuptake inhibitor (SSRI) treatment, and neuroanatomical correlates that distinguished responders from non-responders and healthy controls. METHODS: Participants included 45 non-demented, elderly with major depression and 43 elderly comparison individuals. After a 2-week single-blind placebo period, depressed participants received escitalopram 10mg daily for 12 weeks. The Apathy Evaluation Scale (AES) and 24-item Hamilton Depression Rating Scale (HDRS) were administered at baseline and 12 weeks. MRI scans were acquired at baseline for concurrent structural and diffusion tensor imaging of anterior cingulate gray matter and associated white matter tracts. RESULTS: 35.5% of depressed patients suffered from apathy. This declined to 15.6% (p<0.1) following treatment, but 43% of initial sufferers continued to report significant apathy. Improvement of apathy with SSRI was independent of change in depression but correlated with larger left posterior subgenual cingulate volumes and greater fractional anisotropy of left uncinate fasciculi. LIMITATIONS: Modest sample size, no placebo control, post-hoc secondary analysis, use of 1.5T MRI scanner CONCLUSIONS: While prevalent in geriatric depression, apathy is separable from depression with regards to medication response. Structural abnormalities of the posterior subgenual cingulate and uncinate fasciculus may perpetuate apathetic states by interfering with prefrontal cortical recruitment of limbic activity essential to motivated behavior.

MRI signal hyperintensities and treatment remission of geriatric depression.

BACKGROUND: White matter abnormalities may interfere with limbic-cortical balance and contribute to chronic depressive syndromes in the elderly. This study sought to clarify the relationship of SH to treatment response. We hypothesized that patients who failed to remit during a 12-week controlled treatment trial of escitalopram would exhibit greater SH burden than patients who remitted. METHODS: The participants were 42 non-demented individuals with non-psychotic major depression and 25 elderly comparison subjects. After a 2-week single blind placebo period, subjects who still had a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. FLAIR sequences were acquired on a 1.5 T scanner and total SH were quantified using a semi-automated thresholding method. RESULTS: The patient sample consisted of 22 depressed patients who achieved remission during the study and 20 depressed patients who remained symptomatic. ANCOVA, with age and gender as covariates, revealed that depressed subjects had greater total SH burden relative to non-depressed controls. Furthermore, patients who failed to remit following escitalopram treatment had significantly greater SH burden than both patients who remitted and elderly comparison subjects, whereas SH burden did not differ between depressed patients who remitted and elderly comparison subjects. LIMITATIONS: Patients were treated with a fixed dose of antidepressants and the index of SH is an overall measure that does not permit examination of the relationship of regional SH to treatment remission. DISCUSSION: SH may contribute to a "disconnection state" both conferring vulnerability to and perpetuating late-life depression.

Patients' depression treatment preferences and initiation, adherence, and outcome: a randomized primary care study.

OBJECTIVE: The authors examined the association of treatment preferences with treatment initiation, adherence, and clinical outcome among nonsenior adult and senior primary care patients with depression. METHODS: Sixty primary care participants meeting DSM-IV criteria for major depression were randomly assigned to receive treatment congruent or incongruent with their primary stated preference. Participants received either 20 weeks of escitalopram, with monitoring by a care manager, or 12 weekly sessions of interpersonal psychotherapy followed by two monthly booster sessions. Adherence to treatment and depression severity were reassessed at weeks 4, 8, 12, and 24. RESULTS: Participants expressed stronger preferences for psychotherapy than for antidepressant medication. Preference strength was a more sensitive measure of outcome than was congruence versus incongruence of preference with the assigned treatment. Across age groups, preference strength was significantly associated with treatment initiation and 12-week adherence rate but not with depression severity or remission. CONCLUSIONS: A continuous measure of preference strength may be a more useful measure in clinical practice than preferences per se. Future research should focus on whether and how greater facilitation of the treatment decision-making process between patient and clinician influences clinical outcome.

Serotonin transporter polymorphisms, microstructural white matter abnormalities and remission of geriatric depression.

OBJECTIVE: This study compared microstructural abnormalities in depressed elders and controls and studied the association of the serotonin transporter gene status to white matter abnormalities and to remission of depression. METHODS: The subjects were Caucasians with non-psychotic major depression and normal elders. Depressed subjects received escitalopram 10 mg daily for 12 weeks. Remission was defined as a HDRS score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed and voxel-based analysis of fractional anisotropy (FA) was conducted using age and mean diffusivity as covariates. RESULTS: Depressed elders (N=27) had lower FA than controls (N=27) in several frontolimbic areas. Depressed elderly S-allele carriers also had lower FA than L homozygotes in frontolimbic brain areas, including the dorsal and rostral anterior cingulate, posterior cingulate, dorsolateral prefrontal and medial prefrontal regions, thalamus, and in other regions. S-allele carriers had a lower remission rate than L homozygotes. LIMITATIONS: Small number of subjects, lack of random sampling, fixed antidepressant dose, short follow-up. CONCLUSIONS: Lower FA was observed in several frontolimbic and other regions in depressed elders compared to controls. Depressed S-allele carriers had both microstructural white matter abnormalities in frontolimbic networks and a low remission rate. It remains unclear whether the risk for chronicity of geriatric depression in S-allele carriers is mediated by frontolimbic compromise. However, these observations set the stage for studies aiming to identify the relationship of S allele to impairment in specific frontolimbic functions interfering with response of geriatric depression to antidepressants.

Age and ratings of manic psychopathology.

OBJECTIVES: Clinicians have suggested that manic psychopathology in adulthood changes with advanced age. We used rating scale evaluations of manic psychopathology in adult patients with bipolar (BP) disorder to test whether older age is associated with scores on items related to excesses of behaviors: i.e., Sexual Interest, Increased Activity-Energy, Speech--Rate and Amount, and Disruptive-Aggressive Behavior. METHODS: The association of Young Mania Rating Scale item scores with current age was studied in symptomatic inpatients meeting DSM-IV criteria for BP disorder, manic. RESULTS: The sample consisted of 149 patients ranging in age from 18 to 89 years; 48 of these were male. Age was not associated with differences in overall severity reflected in total score. Age was associated with lower scores on the Sexual Interest item (r = - 0.26, p < 0.001). A trend for higher scores with age on Speech--Rate and Amount (r = 0.19, p < 0.02) did not meet criteria for significance. Increased Activity-Energy, Disruptive-Aggressive Behavior and other item scores were not associated with age. In an exploratory analysis, age and Sexual Interest and Speech item scores were associated in female patients but not in male patients. CONCLUSIONS: These findings suggest that age minimally influences manic psychopathology in patients with BP disorder. The modest correlation between age and Sexual Interest item scores warrants further investigation and the trend for an association between age and Speech--Rate and Amount can be examined in future studies. Possible gender differences in the associations between age and these item scores also invite future study.

Clinical presentation of the "depression-executive dysfunction syndrome" of late life.

It has been proposed that a "depression-executive dysfunction (DED) syndrome" occurs in late life. This assertion was based on clinical, neuropathological, and neuroimaging findings suggesting that frontostriatal dysfunctions contribute to the development of both depression and executive dysfunction and influence the course of depression. The authors describe the clinical presentation of DED and its relationship to disability, studying 126 elderly subjects with major depression and evaluating depressive symptoms, cognitive functioning, disability, and personality dimensions. Patients with the DED syndrome had reduced fluency, impaired visual naming, paranoia, loss of interest in activities, and psychomotor retardation, but showed a rather mild vegetative syndrome. Depressive symptomatology, and especially psychomotor retardation and loss of interest in activities, contributed to disability in DED patients, whereas paranoia was associated with disability independently of executive dysfunction. These findings may aid clinicians in identifying patients needing vigilant follow-up, because depression with executive dysfunction was found to be associated with disability, poor treatment response, relapse, and recurrence.