Christopher F Murphy

Weill Cornell Medical College, New York City, NY, USA

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Publications (28)106.19 Total impact

  • Article: Functional connectivity in the cognitive control network and the default mode network in late-life depression.
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    ABSTRACT: 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. 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. 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. 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.
    Journal of affective disorders 03/2012; 139(1):56-65. · 3.76 Impact Factor
  • Article: Neural correlates of reward processing in late-life depression.
    Zhiru Jia, Christopher F Murphy, George S Alexopoulos
    International Journal of Geriatric Psychiatry 02/2012; 27(2):217-8. · 2.42 Impact Factor
  • Article: Semantic organizational strategy predicts verbal memory and remission rate of geriatric depression.
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    ABSTRACT: 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. 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. 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). 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.
    International Journal of Geriatric Psychiatry 05/2011; 27(5):506-12. · 2.42 Impact Factor
  • Article: Executive function and short-term remission of geriatric depression: the role of semantic strategy.
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    ABSTRACT: This study tested the hypothesis that use of semantic organizational strategy in approaching the Mattis Dementia Rating Scale (MDRS) complex verbal initiation/perseveration (CV I/P) task, a test of semantic fluency, is the function specifically associated with remission of late-life depression. Seventy elders with major depression participated in a 12-week escitalopram treatment trial. Neuropsychologic performance was assessed at baseline after a 2-week drug washout period. Patients with a Hamilton Depression Rating Scale Score ≤7 for 2 consecutive weeks and who no longer met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were considered to be remitted. Cox's proportional hazards survival analysis was used to examine the relationship between subtests of the I/P, other neuropsychologic domains, and remission rate. Participants' performance on the CV I/P subscale was coded for perseverations, and use of semantic strategy. The relationship between the performance on the CV I/P subscale and remission rate was significant. No other subtest of the MDRS I/P evidenced this association. There was no significant relationship between speed, confrontation naming, verbal memory, or perseveration with remission rate. Remitters' use of verbal strategy was significantly greater than nonremitters. Geriatric depressed patients who showed decrements in performance on a semantic fluency task showed poorer remission rates than those who showed adequate performance on this measure. Executive impairment in verbal strategy explained performance. This finding supports the concept that executive functioning exerts a "top down" effect on other basic cognitive processes, perhaps as a result of frontostriatal network dysfunction implicated in geriatric depression.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 02/2011; 19(2):115-22. · 3.35 Impact Factor
  • Article: Hippocampal volumes and the brain-derived neurotrophic factor val66met polymorphism in geriatric major depression.
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    ABSTRACT: 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. 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. 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. 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.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 01/2011; 19(1):13-22. · 3.35 Impact Factor
  • Article: Hippocampal Volumes and the Brain-Derived Neurotrophic Factor val66met Polymorphism in Geriatric Major Depression
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    ABSTRACT: 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.
    American Journal of Geriatric Psychiatry 12/2010; 19(1):13–22. · 3.64 Impact Factor
  • Article: Cognitive control in late-life depression: response inhibition deficits and dysfunction of the anterior cingulate cortex.
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    ABSTRACT: Geriatric depression is associated with frontolimbic functional deficits, and this frontal dysfunction may underlie the marked executive control deficits often seen in this population. The authors' goal was to assess the integrity of frontal cortical functioning in geriatric depression, while these individuals performed a standard cognitive control task. The N2 component of the event-related potential (ERP), an evoked response generated within the anterior cingulate cortex (ACC), is significantly enhanced when nondepressed individuals successfully inhibit a response, providing an excellent metric of frontal inhibitory function. The authors used a variant of a demanding Go/NoGo task-switching paradigm that required participants to inhibit response execution during NoGo trials by overcoming a potent response tendency established by frequent Go trials. The authors compared a cohort of depressed geriatric outpatients (N = 11) with a similarly aged group of nondepressed participants (N = 11). Reaction times, accuracy, and high-density event-related potential recordings from a 64-channel electrode montage were obtained. A significantly enhanced N2 to NoGo trials was observed in nondepressed elderly participants, with generators localized to the ACC. In contrast, this enhancement was strongly reduced in the depressed sample. Source analysis and topographic mapping pointed to a displacement of N2 generators toward more posterior areas of the middle frontal gyrus in depressed subjects. Findings confirm previous reports of an inhibitory control deficit in depressed elderly who show significantly increased rates of commission errors (i.e., failures to inhibit responses on NoGo trials). Electrophysiologic data suggest underlying dysfunction in ACC as the basis for this deficit.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 11/2010; 18(11):1017-25. · 3.35 Impact Factor
  • Article: Visual inspection of independent components: defining a procedure for artifact removal from fMRI data.
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    ABSTRACT: 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.
    Journal of neuroscience methods 04/2010; 189(2):233-45. · 2.30 Impact Factor
  • Article: BDNF val66met polymorphism, white matter abnormalities and remission of geriatric depression.
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    ABSTRACT: The polymorphism BDNF val66met of the brain derived neurotrophic factor (BDNF) is common, may increase the risk for depression, and affects BDNF secretion, critical for neuronal survival, plasticity, neurogenesis, and synaptic connectivity. Our objectives were: 1) to test the hypothesis that BDNF(val/met) status influences the remission rate of geriatric depression; 2) to explore whether the relationship between BDNF allelic status to remission is influenced by the presence of microstructural white matter abnormalities. Non-demented older subjects with major depression had a 2-week placebo period, after which those with a Hamilton Depression Rating Scale (HDRS) of 18 or greater received escitalopram 10 mg daily for 12 weeks. Fractional anisotropy was determined in specific regions using the Reproducible Object Quantification Scheme (ROQS) software that operates on non-normalized data. BDNF(met) carriers were more likely to achieve remission than BDNF(val/val) homozygotes after 12 weeks of treatment with escitalopram 10 mg daily. Microstructural abnormalities in the corpus callosum, left superior corona radiata, and right inferior longitudinal fasciculum were also associated with lower remission rate. However, there were no significant interactions between BDNF(val66met) status and microstructural abnormalities in predicting remission. Small number of subjects, focus on a single BDNF polymorphism, fixed antidepressant dose. Depressed older BDNF(met) carriers had a higher remission rate than BDNF(val/val) homozygotes. This effect was not related to microstructural white matter abnormalities, which predicted remission independently. We speculate that the relationship between BDNF(val66met) and remission is due to different effects of BDNF in brain structures related to mood regulation.
    Journal of affective disorders 03/2010; 125(1-3):262-8. · 3.76 Impact Factor
  • Article: Hybrid ICA-Seed-Based Methods for fMRI Functional Connectivity Assessment: A Feasibility Study.
    Int. J. Biomedical Imaging. 01/2010; 2010.
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    Article: Hybrid ICA-Seed-Based Methods for fMRI Functional Connectivity Assessment: A Feasibility Study.
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    ABSTRACT: Brain functional connectivity (FC) is often assessed from fMRI data using seed-based methods, such as those of detecting temporal correlation between a predefined region (seed) and all other regions in the brain; or using multivariate methods, such as independent component analysis (ICA). ICA is a useful data-driven tool, but reproducibility issues complicate group inferences based on FC maps derived with ICA. These reproducibility issues can be circumvented with hybrid methods that use information from ICA-derived spatial maps as seeds to produce seed-based FC maps. We report results from five experiments to demonstrate the potential advantages of hybrid ICA-seed-based FC methods, comparing results from regressing fMRI data against task-related a priori time courses, with "back-reconstruction" from a group ICA, and with five hybrid ICA-seed-based FC methods: ROI-based with (1) single-voxel, (2) few-voxel, and (3) many-voxel seed; and dual-regression-based with (4) single ICA map and (5) multiple ICA map seed.
    International Journal of Biomedical Imaging 01/2010; 2010.
  • Article: Anterior cingulate cortical volumes and treatment remission of geriatric depression
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    ABSTRACT: 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).ResultsRepeated 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. Copyright © 2009 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 06/2009; 24(8):829 - 836. · 2.42 Impact Factor
  • Article: Serotonin transporter polymorphisms, microstructural white matter abnormalities and remission of geriatric depression.
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    ABSTRACT: 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. 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. 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. Small number of subjects, lack of random sampling, fixed antidepressant dose, short follow-up. 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.
    Journal of affective disorders 05/2009; 119(1-3):132-41. · 3.76 Impact Factor
  • Article: Blood pressure and white matter integrity in geriatric depression.
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    ABSTRACT: Cerebrovascular disease may increase vulnerability to geriatric depression, a syndrome often accompanied by frontal-subcortical lesions. High blood pressure is a risk factor for cerebrovascular disease and white matter changes. This study examined whether and in which brain regions blood pressure is associated with compromised white matter integrity in elderly depressed patients. We studied the association between blood pressure and white matter integrity assessed by diffusion tensor imaging (fractional anisotropy, FA) in 41 older patients with major depression. Correlations between FA and blood pressure, after controlling for age, were examined with a voxelwise analysis. Significant associations between FA and blood pressure were detected throughout the anterior cingulate and in multiple frontostriatal and frontotemporal regions. This study did not employ a healthy control group. Moreover, the relatively small sample size precluded a comparison of patients with and without hypertension. Compromised frontal-striatal white matter integrity may be the anatomical background through which blood pressure confers vulnerability to depression.
    Journal of affective disorders 10/2008; 115(1-2):171-6. · 3.76 Impact Factor
  • Article: Executive dysfunction in elderly bipolar manic patients.
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    ABSTRACT: This study used neuropsychological measures of executive skills to examine the functioning of frontostriatal networks in elderly bipolar patients. The authors hypothesized that elders with bipolar mania would exhibit poor executive functions relative to both elderly comparison subjects and depressed patients. The study was conducted in the geriatric psychiatry services of a university hospital. Participants: Nondemented elders: 14 with bipolar disorder I, manic (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), 14 with unipolar major depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and 14 nonpsychiatric comparison (NC) subjects. Executive functions were assessed with the initiation/perseveration subscale of the Dementia Rating Scale and the manual Go/No-Go tasks from the extended initiation/perseveration scale. Manic elders demonstrated poor performance on tasks of initiation/perseveration and response inhibition, and performed significantly worse than both depressed patients and NC subjects. In this sample, there was no evidence for a relationship between severity of manic symptoms and executive performance. These findings extend the observation that elderly bipolar manic patients have deficits in executive functioning compared with NC samples and provide evidence that the executive deficits demonstrated by bipolar manic elders can be more severe than those in unipolar depressed elders. As executive functions require frontostriatal integrity, these observations support investigation of specific frontostriatal network abnormalities in late-life bipolar disorder.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 07/2008; 16(6):506-12. · 3.35 Impact Factor
  • Article: Population projection of US adults with lifetime experience of depressive disorder by age and sex from year 2005 to 2050.
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    ABSTRACT: To estimate the projected population of US adults aged 18 years or older with lifetime experience of doctor-diagnosed depressive disorder from 2005-2050. Based on nationally representative survey data from the year 2006 Behavioral Risk Factor Surveillance Survey (BRFSS), prevalence estimates of doctor-diagnosed depression (minor or major, and dysthymia) were weighted to incorporate the complex sampling design and increase generalizability of the findings. The weighted prevalence data by age and sex in 2006 were then used to estimate the projected adult population with lifetime experience of depressive disorder based on the sex-specific US Census national population projections from year 2005-2050. In year 2006 the (weighted) prevalence of lifetime experience of depressive disorder was 15.7% among 188,292 respondents aged 18 years or older. Female prevalence was 20.6%, which was about twice as high as the prevalence among males (11%). From year 2005-2050, the total number of US adults with depressive disorder will increase from 33.9 million to 45.8 million, a 35% increase. The increase is projected to be greater in the elderly population aged >or=65 years (3.8-8.2, a 117% increase) than in the young population aged <65 years (30.1-37.7, a 25% increase). By year 2050, approximately 46 million US adults aged 18 years or older will be diagnosed with a depressive disorder. The increase will be more pronounced in adults aged 65 or older. Prevention, detection, and treatment of depressive disorders might attenuate the magnitude of this estimate.
    International Journal of Geriatric Psychiatry 05/2008; 23(12):1266-70. · 2.42 Impact Factor
  • Article: Anterior cingulate dysfunction in geriatric depression.
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    ABSTRACT: Although several brain abnormalities have been identified in geriatric depression, their relationship to the pathophysiological mechanisms leading to the development and perpetuation of this syndrome remain unclear. This paper reviews findings on the anterior cingulate cortex (ACC) function and on the relationship of ACC abnormalities to the clinical presentation and the course of geriatric depression in order to elucidate the pathophysiological role of ACC in this disorder. The ACC is responsible for conflict detection and emotional evaluation of error and is connected to brain structures that regulate mood, emotional valence of thought and autonomic and visceral responses, which are functions disturbed in depression. Geriatric depression often is accompanied by abnormalities in some executive functions and has a clinical presentation consistent with ACC abnormalities. Indices of ACC dysfunction are associated with adverse outcomes of geriatric depression. Converging findings suggest that at least some ACC functions are abnormal in depression and these abnormalities are pathophysiologically meaningful. Indices of ACC dysfunction may be used to identify subgroups of depressed elderly patients with distinct illness course and treatment needs and serve as the theoretical background for novel treatment development.
    International Journal of Geriatric Psychiatry 05/2008; 23(4):347-55. · 2.42 Impact Factor
  • Article: Macromolecular white matter abnormalities in geriatric depression: a magnetization transfer imaging study.
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    ABSTRACT: 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. 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. The study was conducted in a university-based, geriatric psychiatry clinic. Fifty-five older patients with major depression and 24 elderly comparison subjects were assessed. Voxel-based analysis of MTR data were conducted with a general linear model using age as a covariate. 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. 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.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 05/2008; 16(4):255-62. · 3.35 Impact Factor
  • Article: Microstructural white matter abnormalities and remission of geriatric depression.
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    ABSTRACT: 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. 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. 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. 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.
    American Journal of Psychiatry 03/2008; 165(2):238-44. · 12.54 Impact Factor
  • Article: Relationship between the Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale in depressed elderly: a meta-analysis.
    Moonseong Heo, Christopher F Murphy, Barnett S Meyers
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    ABSTRACT: To determine whether the sensitivity of the Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) to treatment effects are comparable in geriatric antidepressant randomized controlled trials by developing and validating an equation that links between the two instruments. Literature search for this meta-analysis was based on three sources: MEDLINE, a recent related meta-analysis, and experts in geriatric antidepressant trials. The search resulted in 11 relevant geriatric antidepressant trial studies that administered both instruments for symptom ratings. The authors used baseline ratings as a model-building sample and postrandomization ratings as a validation sample. HDRS scores were prorated into HDRS17, a 17-item HDRS, for analysis. The development and validation was based on a total number of 1,874 subjects. The correlations were high between baseline mean HDRS17 and MADRS ratings (r = 0.80; Fisher's z = 1.09, N = 25, p <0.0001) and between postrandomization ratings (r = 0.88, Fisher's z = 1.39, N = 65, p <0.0001). The following equation was derived: HDRS17 = -1.58 + 0.86 x MADRS. The difference between observed and estimated HDRS17 in a validation sample consisting of postrandomization follow-up means did not depend on magnitudes of HDRS17. Although generalizability of findings into a broader population could be limited, and the authors could not assess concordance of changes of particular item constructs between HDRS and MADRS ratings, both ratings are comparable in assessing changes in overall depressive symptom severity in response to antidepressants in depressed elderly at aggregated group mean levels.
    American Journal of Geriatric Psychiatry 11/2007; 15(10):899-905. · 3.64 Impact Factor