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Emotional Processing Functional Magnetic Resonance Imaging Is Associated with Treatment Response in Late Life Depression
2015 AAGP Annual Meeting 1
Harvard South Shore Psychiatry Residency Program, Brockton, MA VA Boston Healthcare System, Boston, MA 3 McLean Hospital, Belmont, MA 4 Tripler Army Medical Center, Honolulu, HI 2
Introduction: Senior physicians are the most valuable teaching resources in medical field. There is also a risk of medical error due to physical ailment, compassion fatigue, and age-related cognitive decline. For decades, many studies emphasized the positive correlation between cognitive decline and how it affects performance. Methods: In this paper, authors review existed literature on this sensitive issue and give practical recommendations regarding how to help manage this problem. The ultimate goal is to meet physicians’ needs and reassure safe practices. Results: Authors break down the approach to age-related cognitive decline into multiple steps systematically. The steps include screening, assessment, planning, remediation, and follow up. In brief, there should be a population-based screening on physician performance by multidisciplinary team, in order to detect physicians who may need help. Once dyscompetence is suspected, neurocognitive assessment should be routinely incorporated with competency evaluation. Even though evidence that support the cognitive recovery after remediation is still scarce, some physicians do benefit from remediation and able to continue their practice for some period of time with support. Discussion about retirement upfront is highly recommended. Mandatory retirement age is not applicable in this profession comparing with others, such as pilots, firefighters, federal law enforcement officers, etc. We also reiterate the importance of having medical board, and regulatory authorities facilitate physicians’ career paths and support the most appropriate retirement planning for our senior physicians. Conclusions: Multiple steps need to be taken in order to meet physicians’ needs and reassure public safety. Age-related cognitive decline is inevitable, but how we address it in the system-level is what we have to address and study more. This research was funded by: n/a.
Poster Number: EI 67
Emotional Processing Functional Magnetic Resonance Imaging Is Associated with Treatment Response in Late Life Depression Alexander M. Khalaf, BA; Helmet Karim, BS; Dana L. Tudorascu, BSc, MSc, PhD; Charles F. Reynolds, III, MD; Howard Aizenstein, MD, PhD University of Pittsburgh, Pittsburgh, PA Introduction: Late-life depression (LLD) is a distinct clinical entity which has been estimated to affect 8-16% of elderly patients. Its disease burden is considerable with effects on mortality, development of dementia, functional status, and healthcare utilization. Research has established functional magnetic resonance imaging (fMRI) markers as reliable predictors of treatment in response in LLD, including differential activity and connectivity between various neural structures and networks. However, an underexplored area of previous fMRI studies is whether neural activity during affective tasks may be associated with treatment response in LLD. It was the goal of this study to investigate emotional processing related neural activity as measured by fMRI at multiple time points throughout an antidepressant treatment course in LLD. Methods: For this study patients were recruited from an open-label LLD study with venlafaxine. Inclusion criteria included age 60 years or greater, diagnosis of major depressive disorder, and a score of greater than 15 on the Montgomery-Asberg Depression Rating Scale (MADRS). Patients were treated with venlafaxine for 12 weeks, during which they underwent 5 fMRI scans. Scan 1 occurred immediately upon enrollment. Scan 2 occurred following a 1-day placebo lead in, with scan 3 occurring 1 day after the first venlafaxine administration. Scan 4 and 5 occurred at day 7, and at 12 weeks, respectively. At 12 weeks a MADRS score of < 10 was used to classify patients as treatment responsive. During each fMRI patients were asked to perform the Affective Perception and Regulation Task. In this task patients are presented with neutral, negative, and somewhat negative images from a standardized set. Accompanying each image is 1 of 2 possible instruction sets. “Look” entails the patient viewing the image and allowing them to respond naturally to its content. “Decrease” tasks the patient with actively altering the emotions provoked by the image through reappraisal. Contrast maps were created from each subject’s pre-processed fMRI images, and included the difference between signal intensity during the “Look” instruction with negative images, and “Look” with neutral images (Look Negative > Look Neutral). A second contrast map was made which was comprised of the difference between signal intensity during the “Decrease” instruction with negative images, and “Look” with negative images. These contrast maps were then compared at the group level between treatment responders and non-responders at each of the time points with a two sample t-test using a threshold of 20 voxel clusters with a p-value of 0.005.
S132
Am J Geriatr Psychiatry 23:3, Supplement 1
2015 AAGP Annual Meeting Results: Thirty-one patients met inclusion criteria for this study, and have completed their 12 week treatment course with all five scans. Based on the 12 week MADRS scores, 18 patients were classified as treatment responders, and 13 as non-responders. There were no significant differences in age, gender, MMSE scores, or baseline MADRS scores between these groups. Patient characteristics are reported in table 1. At baseline no difference in fMRI activity was observed between responders and nonresponders in either contrast. However, in scans 2, 3, 4 and 5 there were multiple areas with significantly different activity between the groups. Of particular interest, is the observation that as early as 1-day after medication initiation a divergence in fMRI activity patterns appears between responders and non-responders. Specifically, during scan 3 with the contrast Decrease Negative > Look Negative non-responders demonstrated a significant increase (relative to responders) in fMRI activity in the gray matter of the superior frontal gyrus (SFG) bilaterally (right SFG t ¼ 4.39, p < 0.001, and left SFG t ¼ 3.76, p ¼ 0.001). Conclusions: The majority of patients in this study demonstrated appropriate treatment response to venlafaxine, and it did not appear that age, gender, MMSE scores, or baseline MADRS scores influenced treatment response. There were no significant differences in fMRI activity at the baseline scan, which seems to suggest that before treatment is initiated, there is minimal difference in neural activity between responders and non-responders. However, later scans reveal significant differences in fMRI activity patterns between the groups, which may indicate that this emotional regulation task is able to elucidate functional alterations between the groups that only emerge after treatment initiation. It is particularly interesting that after only 1 day of treatment, there was a bilateral increase in fMRI activity in the SFG with the Decrease Negative > Look Negative contrast. This finding suggests that non-responders may differ from responders with respect to emotional processing and regulation. It will be the goal of future work to characterize the remaining differences in activity between these groups, and explore the broader meaning of these findings. Table 1. Patient Characteristics and Depression Ratings Responders (n ¼ 18) Age (yrs) 68.6 6.8 Gender (M/F) 4/14 MMSE 28.2 2.5 Baseline MADRS 24.1 7.8 12 Weeks MADRS 3.7 3.0
Non-responders (n ¼ 13) 66.5 4.1 6/7 28.9 1.1 26.5 6.3 17.5 5.6
p-value 0.30 0.16 (Chi-squared) 0.35 0.35 <0.01*
* ¼ statistical significance (p < 0.05); MMSE ¼ Mini-Mental State Exam; MADRS ¼ Montgomery Asberg Depression Rating Scale. This research was funded by: The preceding research was funded generously by the following organizations and grants: NIH grant RO1 MH076079 NIH grant P30 MH090333 University of Pittsburgh Clinical Scientist Training Program (CSTP) and Clinical and Translational Science Institute (UL1 TL1TR000005) NIMH Medical Student Research Fellowship administered by University of Pittsburgh (R25 MH054318-18).
Poster Number: EI 68
The Effect of Weather on Psychiatric Emergency Room Visit and Hospitalization in the Geriatric Population
Ching Yu, MD1; Kyra Harris, BSc1; Jean Daniel Sylvestre, MD1; Karl Looper, MD, FRCPC1; Marilyn Segal, MD, FRCPC1; Soham Rej, MD, FRCPC2,1 1 2
McGill University, Montreal, QC, Canada University of Toronto, Toronto, ON, Canada
Introduction: Many patients with severe mental illness are approaching late life. In this population, we expect a high prevalence of frequent psychiatric emergency room visit and hospitalization. Little is known on the impact of seasonal changes, climate and weather on this population. Our objectives are to identify specific weather conditions or patterns that might affect our geriatric psychiatric patients and predispose them to more frequent psychiatric emergency room visits and hospitalization. Methods: This is a retrospective study of 226 geriatric psychiatric patients admitted to a tertiary care Canadian inpatient psychiatric unit between 2003 and 2008. We have ascertained their psychiatric diagnoses, their psychosocial parameters (ie. marital status, living situation). The main outcomes are psychiatric emergency room visits and hospitalizations in 5 years following their index psychiatric hospitalization (e.g. 2008-2013 if a patient had been first admitted in 2008). Our main exposure of interest are daily weather conditions during the same time period (including max and min temperature, precipitation, humidity, sun exposure, etc).
Am J Geriatr Psychiatry 23:3, Supplement 1
S133
Harvard South Shore Psychiatry Residency Program, Brockton, MA VA Boston Healthcare System, Boston, MA 3 McLean Hospital, Belmont, MA 4 Tripler Army Medical Center, Honolulu, HI 2
Introduction: Senior physicians are the most valuable teaching resources in medical field. There is also a risk of medical error due to physical ailment, compassion fatigue, and age-related cognitive decline. For decades, many studies emphasized the positive correlation between cognitive decline and how it affects performance. Methods: In this paper, authors review existed literature on this sensitive issue and give practical recommendations regarding how to help manage this problem. The ultimate goal is to meet physicians’ needs and reassure safe practices. Results: Authors break down the approach to age-related cognitive decline into multiple steps systematically. The steps include screening, assessment, planning, remediation, and follow up. In brief, there should be a population-based screening on physician performance by multidisciplinary team, in order to detect physicians who may need help. Once dyscompetence is suspected, neurocognitive assessment should be routinely incorporated with competency evaluation. Even though evidence that support the cognitive recovery after remediation is still scarce, some physicians do benefit from remediation and able to continue their practice for some period of time with support. Discussion about retirement upfront is highly recommended. Mandatory retirement age is not applicable in this profession comparing with others, such as pilots, firefighters, federal law enforcement officers, etc. We also reiterate the importance of having medical board, and regulatory authorities facilitate physicians’ career paths and support the most appropriate retirement planning for our senior physicians. Conclusions: Multiple steps need to be taken in order to meet physicians’ needs and reassure public safety. Age-related cognitive decline is inevitable, but how we address it in the system-level is what we have to address and study more. This research was funded by: n/a.
Poster Number: EI 67
Emotional Processing Functional Magnetic Resonance Imaging Is Associated with Treatment Response in Late Life Depression Alexander M. Khalaf, BA; Helmet Karim, BS; Dana L. Tudorascu, BSc, MSc, PhD; Charles F. Reynolds, III, MD; Howard Aizenstein, MD, PhD University of Pittsburgh, Pittsburgh, PA Introduction: Late-life depression (LLD) is a distinct clinical entity which has been estimated to affect 8-16% of elderly patients. Its disease burden is considerable with effects on mortality, development of dementia, functional status, and healthcare utilization. Research has established functional magnetic resonance imaging (fMRI) markers as reliable predictors of treatment in response in LLD, including differential activity and connectivity between various neural structures and networks. However, an underexplored area of previous fMRI studies is whether neural activity during affective tasks may be associated with treatment response in LLD. It was the goal of this study to investigate emotional processing related neural activity as measured by fMRI at multiple time points throughout an antidepressant treatment course in LLD. Methods: For this study patients were recruited from an open-label LLD study with venlafaxine. Inclusion criteria included age 60 years or greater, diagnosis of major depressive disorder, and a score of greater than 15 on the Montgomery-Asberg Depression Rating Scale (MADRS). Patients were treated with venlafaxine for 12 weeks, during which they underwent 5 fMRI scans. Scan 1 occurred immediately upon enrollment. Scan 2 occurred following a 1-day placebo lead in, with scan 3 occurring 1 day after the first venlafaxine administration. Scan 4 and 5 occurred at day 7, and at 12 weeks, respectively. At 12 weeks a MADRS score of < 10 was used to classify patients as treatment responsive. During each fMRI patients were asked to perform the Affective Perception and Regulation Task. In this task patients are presented with neutral, negative, and somewhat negative images from a standardized set. Accompanying each image is 1 of 2 possible instruction sets. “Look” entails the patient viewing the image and allowing them to respond naturally to its content. “Decrease” tasks the patient with actively altering the emotions provoked by the image through reappraisal. Contrast maps were created from each subject’s pre-processed fMRI images, and included the difference between signal intensity during the “Look” instruction with negative images, and “Look” with neutral images (Look Negative > Look Neutral). A second contrast map was made which was comprised of the difference between signal intensity during the “Decrease” instruction with negative images, and “Look” with negative images. These contrast maps were then compared at the group level between treatment responders and non-responders at each of the time points with a two sample t-test using a threshold of 20 voxel clusters with a p-value of 0.005.
S132
Am J Geriatr Psychiatry 23:3, Supplement 1
2015 AAGP Annual Meeting Results: Thirty-one patients met inclusion criteria for this study, and have completed their 12 week treatment course with all five scans. Based on the 12 week MADRS scores, 18 patients were classified as treatment responders, and 13 as non-responders. There were no significant differences in age, gender, MMSE scores, or baseline MADRS scores between these groups. Patient characteristics are reported in table 1. At baseline no difference in fMRI activity was observed between responders and nonresponders in either contrast. However, in scans 2, 3, 4 and 5 there were multiple areas with significantly different activity between the groups. Of particular interest, is the observation that as early as 1-day after medication initiation a divergence in fMRI activity patterns appears between responders and non-responders. Specifically, during scan 3 with the contrast Decrease Negative > Look Negative non-responders demonstrated a significant increase (relative to responders) in fMRI activity in the gray matter of the superior frontal gyrus (SFG) bilaterally (right SFG t ¼ 4.39, p < 0.001, and left SFG t ¼ 3.76, p ¼ 0.001). Conclusions: The majority of patients in this study demonstrated appropriate treatment response to venlafaxine, and it did not appear that age, gender, MMSE scores, or baseline MADRS scores influenced treatment response. There were no significant differences in fMRI activity at the baseline scan, which seems to suggest that before treatment is initiated, there is minimal difference in neural activity between responders and non-responders. However, later scans reveal significant differences in fMRI activity patterns between the groups, which may indicate that this emotional regulation task is able to elucidate functional alterations between the groups that only emerge after treatment initiation. It is particularly interesting that after only 1 day of treatment, there was a bilateral increase in fMRI activity in the SFG with the Decrease Negative > Look Negative contrast. This finding suggests that non-responders may differ from responders with respect to emotional processing and regulation. It will be the goal of future work to characterize the remaining differences in activity between these groups, and explore the broader meaning of these findings. Table 1. Patient Characteristics and Depression Ratings Responders (n ¼ 18) Age (yrs) 68.6 6.8 Gender (M/F) 4/14 MMSE 28.2 2.5 Baseline MADRS 24.1 7.8 12 Weeks MADRS 3.7 3.0
Non-responders (n ¼ 13) 66.5 4.1 6/7 28.9 1.1 26.5 6.3 17.5 5.6
p-value 0.30 0.16 (Chi-squared) 0.35 0.35 <0.01*
* ¼ statistical significance (p < 0.05); MMSE ¼ Mini-Mental State Exam; MADRS ¼ Montgomery Asberg Depression Rating Scale. This research was funded by: The preceding research was funded generously by the following organizations and grants: NIH grant RO1 MH076079 NIH grant P30 MH090333 University of Pittsburgh Clinical Scientist Training Program (CSTP) and Clinical and Translational Science Institute (UL1 TL1TR000005) NIMH Medical Student Research Fellowship administered by University of Pittsburgh (R25 MH054318-18).
Poster Number: EI 68
The Effect of Weather on Psychiatric Emergency Room Visit and Hospitalization in the Geriatric Population
Ching Yu, MD1; Kyra Harris, BSc1; Jean Daniel Sylvestre, MD1; Karl Looper, MD, FRCPC1; Marilyn Segal, MD, FRCPC1; Soham Rej, MD, FRCPC2,1 1 2
McGill University, Montreal, QC, Canada University of Toronto, Toronto, ON, Canada
Introduction: Many patients with severe mental illness are approaching late life. In this population, we expect a high prevalence of frequent psychiatric emergency room visit and hospitalization. Little is known on the impact of seasonal changes, climate and weather on this population. Our objectives are to identify specific weather conditions or patterns that might affect our geriatric psychiatric patients and predispose them to more frequent psychiatric emergency room visits and hospitalization. Methods: This is a retrospective study of 226 geriatric psychiatric patients admitted to a tertiary care Canadian inpatient psychiatric unit between 2003 and 2008. We have ascertained their psychiatric diagnoses, their psychosocial parameters (ie. marital status, living situation). The main outcomes are psychiatric emergency room visits and hospitalizations in 5 years following their index psychiatric hospitalization (e.g. 2008-2013 if a patient had been first admitted in 2008). Our main exposure of interest are daily weather conditions during the same time period (including max and min temperature, precipitation, humidity, sun exposure, etc).
Am J Geriatr Psychiatry 23:3, Supplement 1
S133