Publications by authors named "Nagy A Youssef"

75 Publications

Should Catatonia Be Conceptualized as a Pathological Response to Trauma?

J Nerv Ment Dis 2021 May;209(5):320-323

Dwight Eisenhower Army Medical Center, Ft. Gordon.

Abstract: Although catatonia is related to several medical conditions, catatonia as a response to trauma and posttraumatic stress disorder (PTSD) is less clear. The aim of this review is to explore the small emerging body of preliminary evidence that suggests a possible correlation between psychological trauma and catatonia. Initial data suggests a correlation between episodes of intense fear associated with trauma and PTSD and some forms of catatonic responses. Although this relationship is still speculative to be causative, it can have important implications if confirmed. This is especially salient when it is examined alongside existing studies of the response to fear in animals and the phenomenon of tonic immobility, which bears a striking resemblance to catatonia in humans. If prospective studies further support the initial findings, it could change our conceptual understanding of the etiology of a subtype of catatonia substantially while pointing to likely targets of further research to understand the biological mechanisms that underlie the illness.
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http://dx.doi.org/10.1097/NMD.0000000000001300DOI Listing
May 2021

Characteristics of patients who received deep brain stimulation in obsessive-compulsive disorder versus major depressive disorder.

J Psychiatr Res 2021 Apr 16;136:384-387. Epub 2021 Feb 16.

Department of Psychiatry, Griffin Memorial Hospital, 900 E Main St, Norman, OK, 73071, USA; Department of Psychiatry and Behavioral Science, Oklahoma State University, 1111 W 17th St, Tulsa, OK, 74107, USA. Electronic address:

Objective: Deep brain stimulation (DBS) is cleared for treatment of obsessive-compulsive disorder (OCD) but is an investigational treatment for major depressive disorder (MDD). The aim of this study is to compare the characteristics of patients who received DBS as part of standard care for OCD versus those who received it a part of a research protocol for MDD.

Methods: The inpatient sample (N = 110) was drawn from the 2012-2014 Nationwide Inpatient Sample (NIS), and included adults with a primary discharge diagnosis of MDD (N = 50) or OCD (N = 60) and primary procedure of DBS. The study compared various patient demographics, clinical, hospital and insurance variables between the 2 groups.

Results: DBS recipients with OCD were younger compared to those with MDD. DBS recipients with MDD tended to be from high-income families compared to those with OCD. DBS patients with MDD were in the South region, while DBS patients with OCD were in the Midwest and South regions of the United States (US). The study did not detect a significant difference in the length of stay and total charges among DBS recipients with OCD versus MDD.

Conclusions: DBS patients with MDD are typically older with more financial resources compared to those with OCD. DBS is federally cleared for OCD, but not for MDD, demonstrating the need for further investigation to establish DBS as a federally cleared treatment for difficult to treat MDD if well-powered randomized trials further support its use.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.032DOI Listing
April 2021

Characteristics of patients who received deep brain stimulation in obsessive-compulsive disorder versus major depressive disorder.

J Psychiatr Res 2021 Apr 16;136:384-387. Epub 2021 Feb 16.

Department of Psychiatry, Griffin Memorial Hospital, 900 E Main St, Norman, OK, 73071, USA; Department of Psychiatry and Behavioral Science, Oklahoma State University, 1111 W 17th St, Tulsa, OK, 74107, USA. Electronic address:

Objective: Deep brain stimulation (DBS) is cleared for treatment of obsessive-compulsive disorder (OCD) but is an investigational treatment for major depressive disorder (MDD). The aim of this study is to compare the characteristics of patients who received DBS as part of standard care for OCD versus those who received it a part of a research protocol for MDD.

Methods: The inpatient sample (N = 110) was drawn from the 2012-2014 Nationwide Inpatient Sample (NIS), and included adults with a primary discharge diagnosis of MDD (N = 50) or OCD (N = 60) and primary procedure of DBS. The study compared various patient demographics, clinical, hospital and insurance variables between the 2 groups.

Results: DBS recipients with OCD were younger compared to those with MDD. DBS recipients with MDD tended to be from high-income families compared to those with OCD. DBS patients with MDD were in the South region, while DBS patients with OCD were in the Midwest and South regions of the United States (US). The study did not detect a significant difference in the length of stay and total charges among DBS recipients with OCD versus MDD.

Conclusions: DBS patients with MDD are typically older with more financial resources compared to those with OCD. DBS is federally cleared for OCD, but not for MDD, demonstrating the need for further investigation to establish DBS as a federally cleared treatment for difficult to treat MDD if well-powered randomized trials further support its use.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.032DOI Listing
April 2021

Need for Standardization of Measurement of Time to Reorientation as a Predictor of Cognitive Adverse Effects of Electroconvulsive Therapy.

J ECT 2021 Mar;37(1):13-17

From the Department of Psychiatry and Health Behavior.

Abstract: Testing for time to reorientation (TRO) after electroconvulsive therapy (ECT) has been one of the most predictive measures for cognitive adverse effects of ECT. However, measuring TRO varies between clinical trials, and there is no standardized approach on its measurement between studies. The objective of this report is to systematically review the literature on the different ways of measuring TRO. This would be a first step to establish a consensus on a standard method for TRO. We performed a systematic literature review from 1968 to October 2019 for clinical trials with a sample size of more than 50 and published in English that describe measures of TRO. We searched both PubMed and Web of Science databases. The literature search generated 12 clinical trials, which met the inclusion criteria. Studies measured TRO using 3-, 5-, or 10-item questionnaires. Most studies measured full orientation as answering 4/5 questions. Other studies smaller than 50 required 14/14 items to be answered correctly. There was wide variation between studies on how often and when orientation questions were initiated. These factors have obvious implications to the results and interpretation of the ECT literature.There was no clear consensus on measuring TRO in a uniform fashion. Research and clinical care would benefit from a standardized approach to measuring TRO. Measuring TRO using a 4/5 method seems the most common and quickest way, whereas using a 14/14 method seems to be the most rigorous and sensitive to change in trials.
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http://dx.doi.org/10.1097/YCT.0000000000000703DOI Listing
March 2021

Is There Evidence That Stimulus Parameters and Electrode Placement Affect the Cognitive Side Effects of Electroconvulsive Therapy in Patients With Schizophrenia and Schizoaffective Disorder?: A Systematic Review.

J ECT 2020 Dec 22;Publish Ahead of Print. Epub 2020 Dec 22.

From the Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich Psychiatrisches Zentrum Appenzell Ausserrhoden, Herisau, Switzerland Department of Psychiatry & Health Behavior, Medical College of Georgia at Augusta University, Augusta, GA Departments of Psychiatry and Radiology, Columbia University, New York, NY Dwight Eisenhower Army Medical Center, Ft. Gordon, GA.

Abstract: Seventy percent of patients with treatment-resistant schizophrenia do not respond to clozapine. Electroconvulsive therapy (ECT) can potentially offer significant benefit in clozapine-resistant patients. However, cognitive side effects can occur with ECT and are a function of stimulus parameters and electrode placements. Thus, the objective of this article is to systematically review published clinical trials related to the effect of ECT stimulus parameters and electrode placements on cognitive side effects. We performed a systematic review of the literature up to July of 2020 for clinical studies published in English or German examining the effect of ECT stimulus parameters and/or electrode placement on cognitive side effects in patients with schizophrenia or schizoaffective disorder. The literature search generated 3 randomized, double-blind, clinical trials, 1 randomized, nonblinded trial, and 1 retrospective study. There are mixed findings regarding whether pulse width and stimulus dose impact on cognitive side effects. One study showed less cognitive side effect for right unilateral (RUL) than bitemporal (BT) electrode placement, and 2 studies showed a cognitive advantage for bifrontal (BF) compared with BT ECT. Only 1 retrospective study measured global cognition and showed post-ECT cognitive improvement with all treatment modalities using Montreal Cognitive Assessment in comparison to pre-ECT Montreal Cognitive Assessment scores. Current data are limited, but evolving. The evidence suggests that RUL or BF ECT have more favorable cognitive outcomes than BT ECT. Definitive larger clinical trials are needed to optimize parameter and electrode placement selection to minimize adverse cognitive effects.
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http://dx.doi.org/10.1097/YCT.0000000000000737DOI Listing
December 2020

Double-Blinded Randomized Pilot Clinical Trial Comparing Cognitive Side Effects of Standard Ultra-Brief Right Unilateral ECT to 0.5 A Low Amplitude Seizure Therapy (LAP-ST).

Brain Sci 2020 Dec 13;10(12). Epub 2020 Dec 13.

Department of Psychiatry and Health Behavior, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA.

Background: Concerns over cognitive side effects (CSE) of electroconvulsive therapy (ECT) still limit its broader usage for treatment-resistant depression (TRD). The objectives of this study were to (1) examine the CSE of Low Amplitude Seizure Therapy (LAP-ST) at 0.5 A compared to Ultra-brief Right Unilateral (UB-RUL) ECT using Time to Reorientation (TRO) as the main acute primary outcome, and (2) to compare effects on depressive symptoms between the two treatment groups.

Methods: Participants were referred for ECT, consented for the study, and were randomized to a course of LAP-ST or standard UB-RUL ECT. TRO and depression were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS).

Results: Eleven patients consented. Of these, eight with a current major depressive episode (MDE) of unipolar or bipolar disorders were randomized. TRO was faster for the LAP-ST (mean = 6.8 min; SE = 4.9) than standard RUL ECT (mean = 15.5 min; SE = 6.5). Depression improved similarly in the two arms of the study from baseline (MADRS: LAP-ST = 41.0; SE = 2.0, RUL = 39.0; SE = 3.8) to endpoint (MADRS score: LAP-ST = 8.0; SE7.2, RUL = 9.5; SE = 3.8).

Conclusions: This pilot, randomized and blinded clinical trial, suggests that the LAP-ST (at 0.5 A) has faster reorientation and possibly lower CSE compared to standard RUL-UB ECT. Caution is advised in interpreting these results due to the small sample size of this pilot study. Thus, future studies with similar design are warranted for replicating these findings.
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http://dx.doi.org/10.3390/brainsci10120979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763063PMC
December 2020

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.

Nat Commun 2020 11 24;11(1):5965. Epub 2020 Nov 24.

University of California San Diego, Department of Psychiatry, La Jolla, CA, USA.

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.
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http://dx.doi.org/10.1038/s41467-020-19615-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686485PMC
November 2020

Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR.

Nat Commun 2020 11 24;11(1):5965. Epub 2020 Nov 24.

University of California San Diego, Department of Psychiatry, La Jolla, CA, USA.

Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.
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http://dx.doi.org/10.1038/s41467-020-19615-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686485PMC
November 2020

Treating Posttraumatic Stress Disorder Symptoms With Low Amplitude Seizure Therapy (LAP-ST) Compared With Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial.

J ECT 2020 Dec;36(4):291-295

From the Department of Psychiatry and Health Behavior.

Objectives: An important barrier to further studying electroconvulsive therapy (ECT) in posttraumatic stress disorder (PTSD) is the cognitive adverse effects. However, recent data suggest that low amplitude seizure therapy (LAP-ST) has no or minimal cognitive adverse effects. The aims of this report were to examine the efficacy of LAP-ST in PTSD and to compare LAP-ST with standard right unilateral (RUL) ECT using a pilot randomized clinical trial.

Methods: Patients were randomized to LAP-ST or RUL ECT. Posttraumatic stress disorder was assessed using clinical interview based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and symptom severity with PTSD Checklist (PCL). The scores pertaining to PCL were analyzed using descriptive analysis for this pilot study.

Results: Eleven patients consented to be enrolled. Seven were randomly allocated to LAP-ST or RUL ECT. Five completed the study and had completed PCL before and after the course. In both groups, PTSD symptoms showed fast improvement. The effect size of improvement seems promising. The mean baseline PCL score for patients in the LAP-ST group was 42.5 (SD = 16.26) and the mean end point PCL score after treatment was 31 (SD = 15.56). The mean baseline PCL score for patients in the standard RUL ECT group was 64.7 (SD = 1.15) and the mean end point was 41 (SD = 15.62).

Conclusions: Both LAP-ST and standard RUL ECT showed reduction in PTSD symptoms with fast improvement. This first PTSD LAP-ST study adds support to the prior LAP-ST proof-of-concept clinical trial that LAP-ST can produce effective therapeutic outcomes. Replication of this trial is warranted in larger clinical trials (ClinicalTrials.gov ID: NCT02583490).
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http://dx.doi.org/10.1097/YCT.0000000000000701DOI Listing
December 2020

Comparative effectiveness clinical trial of magnetic seizure therapy and electroconvulsive therapy in major depressive disorder.

Ann Clin Psychiatry 2020 11;32(4):239-248

Department of Psychiatry and Health Behavior, Medical College of Georgia at Augusta University and Charlie Norwood VA Medical Center, Augusta, Georgia 30912 USA. E-MAIL:

Background: Magnetic seizure therapy (MST) has demonstrated fewer cognitive side effects than electroconvulsive therapy (ECT) in antidepressant efficacy trials. However, there are no effectiveness trials examining antidepressant efficacy and cognitive side effects against ECT. The aims of this study were to evaluate the comparative effectiveness of MST vs ECT in major depressive disorder (MDD), and compare the cognitive side effects of MST and ECT.

Methods: In this open-label study, patients were assigned to either ECT or high-dose MST twice a week for 5 sessions based on the clinician's and the patient's decision-making. Efficacy was primarily assessed by the Hamilton Depression Rating Scale-21 (HAMD-21); cognitive side effects were assessed by time to reorientation (TRO) and cognitive battery.

Results: Sixty patients were enrolled. Efficacy was similar between those assigned to MST (n = 30) and ECT (n = 30). Post-treatment HAMD-21 mean scores were 12.33 after MST, 12.80 after bitemporal (BT) ECT (n = 15), and 27.93 after right unilateral (RUL) ECT (n = 15). Magnetic seizure therapy had a significantly faster TRO of 1.8 minutes (standard deviation [SD] = 0.37) compared with ECT (RUL: 18.9 minutes [SD = 8.25]; BT: 50.2 minutes [SD = 5.89]) and had fewer cognitive side effects.

Conclusions: Magnetic seizure therapy was effective for the treatment of MDD in real-world clinical care, with fewer cognitive side effects than ECT. Future studies are warranted to replicate these findings.
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http://dx.doi.org/10.12788/acp.0005DOI Listing
November 2020

A primary care guide to bipolar depression treatment.

J Fam Pract 2020 09;69(7):344-352

Department of Psychiatry and Health Behavior, Medical College of Georgia at Augusta University, Augusta, USA.

Manage uncomplicated cases following guidelines on medical therapy and with adjunctive psychotherapy. Refer complicated and severe cases to Psychiatry.
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September 2020

A two-site, open-label, non-randomized trial comparing Focal Electrically-Administered Seizure Therapy (FEAST) and right unilateral ultrabrief pulse electroconvulsive therapy (RUL-UBP ECT).

Brain Stimul 2020 Sep - Oct;13(5):1416-1425. Epub 2020 Jul 29.

Departments of Psychiatry and Radiology, Columbia University, NY, USA.

Background: Focal Electrically-Administered Seizure Therapy (FEAST) is a form of electroconvulsive therapy (ECT) that spatially focuses the electrical stimulus to initiate seizure activity in right prefrontal cortex. Two open-label non-comparative studies suggested that FEAST has reduced cognitive side effects when compared to historical data from other forms of ECT. In two different ECT clinics, we compared the efficacy and cognitive side effects of FEAST and Right Unilateral Ultrabrief Pulse (RUL-UBP) ECT.

Methods: Using a non-randomized, open-label design, 39 depressed adults were recruited after referral for ECT. Twenty patients received FEAST (14 women; age 45.2 ± 12.7), and 19 received RUL-UBP ECT (16 women; age 43.2 ± 16.4). Key cognitive outcome measures were the postictal time to reorientation and the Columbia University Autobiographical Memory Interview: Short-Form (CUAMI-SF). Antidepressant effects were assessed using the Hamilton Rating Scale for Depression (HRSD).

Results: In the Intent-to-treat sample, a repeated measures mixed model suggested no between group difference in HRSD score over time (F = 0.82, p = 0.37), while the response rate favored FEAST (FEAST: 65%; RUL-UBP ECT: 57.9%), and the remission rate favored RUL-UBP ECT (FEAST: 35%; RUL-UBP ECT: 47.4%). The FEAST group had numeric superiority in average time to reorientation (FEAST: 6.6 ± 5.0 min; RUL-UBP ECT: 8.8 ± 5.8 min; Cohens d = 0.41), and CUAMI-SF consistency score (FEAST: 69.2 ± 14.2%; RUL-UBP ECT: 63.9 ± 9.9%; Cohens d = 0.43); findings that failed to meet statistical significance.

Conclusions: FEAST exerts similar efficacy relative to an optimal form of conventional ECT and may have milder cognitive side effects. A blinded, randomized, non-inferiority trial is needed.
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http://dx.doi.org/10.1016/j.brs.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500956PMC
March 2021

A two-site, open-label, non-randomized trial comparing Focal Electrically-Administered Seizure Therapy (FEAST) and right unilateral ultrabrief pulse electroconvulsive therapy (RUL-UBP ECT).

Brain Stimul 2020 Sep - Oct;13(5):1416-1425. Epub 2020 Jul 29.

Departments of Psychiatry and Radiology, Columbia University, NY, USA.

Background: Focal Electrically-Administered Seizure Therapy (FEAST) is a form of electroconvulsive therapy (ECT) that spatially focuses the electrical stimulus to initiate seizure activity in right prefrontal cortex. Two open-label non-comparative studies suggested that FEAST has reduced cognitive side effects when compared to historical data from other forms of ECT. In two different ECT clinics, we compared the efficacy and cognitive side effects of FEAST and Right Unilateral Ultrabrief Pulse (RUL-UBP) ECT.

Methods: Using a non-randomized, open-label design, 39 depressed adults were recruited after referral for ECT. Twenty patients received FEAST (14 women; age 45.2 ± 12.7), and 19 received RUL-UBP ECT (16 women; age 43.2 ± 16.4). Key cognitive outcome measures were the postictal time to reorientation and the Columbia University Autobiographical Memory Interview: Short-Form (CUAMI-SF). Antidepressant effects were assessed using the Hamilton Rating Scale for Depression (HRSD).

Results: In the Intent-to-treat sample, a repeated measures mixed model suggested no between group difference in HRSD score over time (F = 0.82, p = 0.37), while the response rate favored FEAST (FEAST: 65%; RUL-UBP ECT: 57.9%), and the remission rate favored RUL-UBP ECT (FEAST: 35%; RUL-UBP ECT: 47.4%). The FEAST group had numeric superiority in average time to reorientation (FEAST: 6.6 ± 5.0 min; RUL-UBP ECT: 8.8 ± 5.8 min; Cohens d = 0.41), and CUAMI-SF consistency score (FEAST: 69.2 ± 14.2%; RUL-UBP ECT: 63.9 ± 9.9%; Cohens d = 0.43); findings that failed to meet statistical significance.

Conclusions: FEAST exerts similar efficacy relative to an optimal form of conventional ECT and may have milder cognitive side effects. A blinded, randomized, non-inferiority trial is needed.
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http://dx.doi.org/10.1016/j.brs.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500956PMC
March 2021

Examining the characteristics of patients who continue participation in vs those who drop out of a PTSD clinical trial

Ann Clin Psychiatry 2020 08;32(3):164-169

Background: Patients who drop out of clinical trials examining posttraumatic stress disorder (PTSD) may have different characteristics than patients who continue. These characteristics have never been examined in prior PTSD and attrition trials. Our goal was to examine how demographic and clinical characteristics of patients with PTSD impact attrition in a randomized controlled trial.

Methods: A total of 18 participants were recruited. Data were collected through questionnaires to assess PTSD, depression, and mood disorders. Fisher’s exact test was used to examine the association of various categorical demographic and clinical variables with dropout. A Wilcoxon rank sum test was used to examine differences in medians.

Results: The median total PTSD Checklist for DSM-5 score was 38 for patients who dropped out and 53 for those who did not. The depression scale total was also lower for the dropout group (7 vs 15). The insomnia index was lower for those who did not remain in the study (15 vs 21).

Conclusions: Posttraumatic stress disorder symptoms, depression, and insomnia were less severe in patients who dropped out compared with those who did not. Larger studies are needed to further examine these findings. This study could help guide future recruitment efforts for clinical trials examining PTSD.
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August 2020

Editorial: Neuromodulation in Basic, Translational and Clinical Research in Psychiatry.

Front Hum Neurosci 2019 20;13:438. Epub 2019 Dec 20.

Department of Neuropsychiatry, Wakayama Medical University, Wakayama, Japan.

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http://dx.doi.org/10.3389/fnhum.2019.00438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933419PMC
December 2019

Examining the Overlap Between Moral Injury and PTSD in US Veterans and Active Duty Military.

J Nerv Ment Dis 2020 01;208(1):7-12

School of Sociology, University of Arizona, Tucson, Arizona.

Moral injury (MI) is a syndrome thought to be separate from posttraumatic stress disorder (PTSD), yet having some overlap. To determine the overlap, we examined the relationship between MI and the four DSM-5 PTSD symptom clusters (B, C, D, E) in US veterans and active duty military (ADM). The 45-item Moral Injury Symptom Scale (MISS-M) was administered to 591 veterans and ADM who had served in a combat theater and had PTSD symptoms. PTSD symptoms were measured with the PTSD Symptom Checklist-5, which assesses the four PTSD symptom clusters. Total MISS-M scores were more strongly associated with PTSD symptom cluster D (negative cognitions and emotions) in both bivariate and multivariate analyses. Findings for a 10-item version of the MISS-M (MISS-M-SF) closely followed those of the MISS-M. Although the overlap between MI and PTSD occurs to some extent across all PTSD symptoms clusters, the largest overlap tends to be with the negative cognitions and emotions cluster.
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http://dx.doi.org/10.1097/NMD.0000000000001077DOI Listing
January 2020

Can epigenetic biomarkers lead us to precision medicine in predicting treatment response and remission for patients being considered for ECT?

Psychiatry Res 2020 02 28;284:112659. Epub 2019 Oct 28.

Department of Psychiatry & Health Behavior, Medical College of Georgia at Augusta University, Augusta, GA, United States; Academic Affairs, Medical College of Georgia, Augusta University, Augusta, GA, United States. Electronic address:

While electroconvulsive therapy (ECT) is the gold standard for the treatment of depression, there is currently a lack of clinically useful biomarkers predictive of treatment response. Epigenetics provides reasonable potential as a biomarker for treatment response for ECT, given that the study of epigenetics combines both the impact of biology and environment in the shaping of psychopathology. Initial limited studies are promising. Further studies to establish precision medicine in term of ECT treatment response using epigenetics predictors can provide great benefit to both patients and physicians in saving time, money, and frustration.
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http://dx.doi.org/10.1016/j.psychres.2019.112659DOI Listing
February 2020

Can epigenetic biomarkers lead us to precision medicine in predicting treatment response and remission for patients being considered for ECT?

Psychiatry Res 2020 02 28;284:112659. Epub 2019 Oct 28.

Department of Psychiatry & Health Behavior, Medical College of Georgia at Augusta University, Augusta, GA, United States; Academic Affairs, Medical College of Georgia, Augusta University, Augusta, GA, United States. Electronic address:

While electroconvulsive therapy (ECT) is the gold standard for the treatment of depression, there is currently a lack of clinically useful biomarkers predictive of treatment response. Epigenetics provides reasonable potential as a biomarker for treatment response for ECT, given that the study of epigenetics combines both the impact of biology and environment in the shaping of psychopathology. Initial limited studies are promising. Further studies to establish precision medicine in term of ECT treatment response using epigenetics predictors can provide great benefit to both patients and physicians in saving time, money, and frustration.
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http://dx.doi.org/10.1016/j.psychres.2019.112659DOI Listing
February 2020

Combination of lithium and electroconvulsive therapy (ECT) is associated with higher odds of delirium and cognitive problems in a large national sample across the United States.

Brain Stimul 2020 Jan - Feb;13(1):15-19. Epub 2019 Aug 22.

Department of Psychiatry and Health Behavior, Medical College of Georgia at Augusta University, Augusta, GA, USA; Academic Affairs, Medical College of Georgia at Augusta University, Augusta, GA, USA; Charlie Norwood VA Medical Center, Augusta, GA, USA.

Background: Lithium is a helpful adjunct to patients undergoing ECT. However, only case reports and limited data suggest increase risk of delirium. Thus, this continues to be a controversial issue.

Objective: In this study, we examine 1) The association and odds of delirium and cognitive problems with ECT and lithium (ECT + Li) combination compared to ECT alone, 2) If positively associated, would this association vary by both type of mood episode and type of disorder?

Methods: A national sample of 64,728 adult psychiatric inpatients across the US (identified from a total data of about 70 million total discharges annually) was analyzed using linear-by-linear association and logistic regression to assess the odds ratio (OR) for delirium and cognitive impairment for those treated with lithium (N = 158), ECT (N = 64148), or ECT + Li (N = 422) after adjusting for demographics and psychiatric diagnoses.

Results: The prevalence of delirium was higher in the ECT + Lithium group (5.7%) vs. ECT only (0.6%) or lithium only groups (0%). Patients managed with ECT + Lithium have 11.7-fold higher odds (95% CI 7.55-17.99, P < 0.001) of delirium compared to ECT alone. In the ECT + Li group, delirium prevalence was 7.8% in unipolar depression, 3.4% in bipolar depressed, 0% in bipolar mania.

Conclusion: These results are surprising given the fading concern about delirium association with ECT + lithium combination. The high odds in the combination group warrant clinical caution, use of lower lithium doses (if combinations cannot be avoided), and vigilance regarding early signs of delirium. These results warrant replication in future studies.
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http://dx.doi.org/10.1016/j.brs.2019.08.012DOI Listing
June 2020

Can catatonia be a pathological response to fear and trauma?

Ann Clin Psychiatry 2019 08;31(3):222-223

Nagy A. Youssef, MD, Department of Psychiatry and Human Behavior, Office of Academic Affairs, Medical College of Georgia, Augusta University, Augusta, GA USA. E-MAIL:

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August 2019

A national study for regional variation of inpatient ECT utilization from 4,411 hospitals across the United States.

Ann Clin Psychiatry 2019 08;31(3):200-208

Department of Psychiatry and Health Behavior, Office of Academic Affairs, Medical College of Georgia, Augusta University, Augusta, GA 30912 USA. E-MAIL"

Background: We conducted a study to examine regional variation in the utilization of inpatient electroconvulsive therapy (ECT) across the United States, and its impact on length of hospital stay and cost.

Methods: Analysis of the Nationwide Inpatient Sample databases to compare patient and hospital characteristics, and regional variation of ECT administration across different regions of the United States.

Results: The study included 41,055 inpatients who had ECT from 4,411 hospitals. Electroconvulsive therapy use is significantly higher in the Midwest. A higher proportion of females (65.2%) than males received ECT across the United States. Medicaid beneficiaries were less likely to undergo ECT compared with patients with Medicare (52.2%) or private insurance (32%). Electroconvulsive therapy was used mainly for mood disorders (84.3%). There were marked reductions of inpatient costs ($25,298 to $38,244) and average hospital stay (16 days) when ECT was initiated within the first 5 days of admission compared with later during the hospitalization.

Conclusions: There is a wide variability of utilization of ECT, depending on the region, type of hospital, and type of insurance carrier. The utilization of ECT services is reduced across the United States. Appropriate utilization of this effective treatment can greatly help patients who are not responding to standard therapeutics, reduce overall health care cost and length of stay, and, most importantly, alleviate suffering.
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August 2019

A national study for regional variation of inpatient ECT utilization from 4,411 hospitals across the United States.

Ann Clin Psychiatry 2019 08;31(3):200-208

Department of Psychiatry and Health Behavior, Office of Academic Affairs, Medical College of Georgia, Augusta University, Augusta, GA 30912 USA. E-MAIL"

Background: We conducted a study to examine regional variation in the utilization of inpatient electroconvulsive therapy (ECT) across the United States, and its impact on length of hospital stay and cost.

Methods: Analysis of the Nationwide Inpatient Sample databases to compare patient and hospital characteristics, and regional variation of ECT administration across different regions of the United States.

Results: The study included 41,055 inpatients who had ECT from 4,411 hospitals. Electroconvulsive therapy use is significantly higher in the Midwest. A higher proportion of females (65.2%) than males received ECT across the United States. Medicaid beneficiaries were less likely to undergo ECT compared with patients with Medicare (52.2%) or private insurance (32%). Electroconvulsive therapy was used mainly for mood disorders (84.3%). There were marked reductions of inpatient costs ($25,298 to $38,244) and average hospital stay (16 days) when ECT was initiated within the first 5 days of admission compared with later during the hospitalization.

Conclusions: There is a wide variability of utilization of ECT, depending on the region, type of hospital, and type of insurance carrier. The utilization of ECT services is reduced across the United States. Appropriate utilization of this effective treatment can greatly help patients who are not responding to standard therapeutics, reduce overall health care cost and length of stay, and, most importantly, alleviate suffering.
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August 2019

A national study for regional variation of inpatient ECT utilization from 4,411 hospitals across the United States.

Ann Clin Psychiatry 2019 08;31(3):200-208

Department of Psychiatry and Health Behavior, Office of Academic Affairs, Medical College of Georgia, Augusta University, Augusta, GA 30912 USA. E-MAIL"

Background: We conducted a study to examine regional variation in the utilization of inpatient electroconvulsive therapy (ECT) across the United States, and its impact on length of hospital stay and cost.

Methods: Analysis of the Nationwide Inpatient Sample databases to compare patient and hospital characteristics, and regional variation of ECT administration across different regions of the United States.

Results: The study included 41,055 inpatients who had ECT from 4,411 hospitals. Electroconvulsive therapy use is significantly higher in the Midwest. A higher proportion of females (65.2%) than males received ECT across the United States. Medicaid beneficiaries were less likely to undergo ECT compared with patients with Medicare (52.2%) or private insurance (32%). Electroconvulsive therapy was used mainly for mood disorders (84.3%). There were marked reductions of inpatient costs ($25,298 to $38,244) and average hospital stay (16 days) when ECT was initiated within the first 5 days of admission compared with later during the hospitalization.

Conclusions: There is a wide variability of utilization of ECT, depending on the region, type of hospital, and type of insurance carrier. The utilization of ECT services is reduced across the United States. Appropriate utilization of this effective treatment can greatly help patients who are not responding to standard therapeutics, reduce overall health care cost and length of stay, and, most importantly, alleviate suffering.
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August 2019

Bedtime doses of prazosin do not affect daytime salivary amylase markers in PTSD.

Heliyon 2019 May 11;5(5):e01709. Epub 2019 May 11.

Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, 997 St Sebastian Way, Augusta, GA, 30912, USA.

Overactivity of the noradrenergic (NE) system within the central nervous system (CNS) has been postulated as a key pathophysiology of posttraumatic stress disorder (PTSD). The activity of the enzyme salivary α-amylase (sAA) has been proposed as an indirect measure of CNS NE activity, and sAA is elevated in PTSD. As an antagonist of the α-1 NE receptor, prazosin would be expected to alter sAA values in PTSD patients. However, given its short half-life, it is not clear whether bedtime doses would have an effect on daytime sAA. In the present study, we assayed daytime sAA in 20 suicidal PTSD patients who were randomized to prazosin versus placebo at bedtime-only, and found no effect in daytime sAA. These findings are consistent with studies showing an advantage for twice daily dosing of prazosin in PTSD.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517516PMC
May 2019

Bedtime doses of prazosin do not affect daytime salivary amylase markers in PTSD.

Heliyon 2019 May 11;5(5):e01709. Epub 2019 May 11.

Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, 997 St Sebastian Way, Augusta, GA, 30912, USA.

Overactivity of the noradrenergic (NE) system within the central nervous system (CNS) has been postulated as a key pathophysiology of posttraumatic stress disorder (PTSD). The activity of the enzyme salivary α-amylase (sAA) has been proposed as an indirect measure of CNS NE activity, and sAA is elevated in PTSD. As an antagonist of the α-1 NE receptor, prazosin would be expected to alter sAA values in PTSD patients. However, given its short half-life, it is not clear whether bedtime doses would have an effect on daytime sAA. In the present study, we assayed daytime sAA in 20 suicidal PTSD patients who were randomized to prazosin versus placebo at bedtime-only, and found no effect in daytime sAA. These findings are consistent with studies showing an advantage for twice daily dosing of prazosin in PTSD.
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http://dx.doi.org/10.1016/j.heliyon.2019.e01709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517516PMC
May 2019

Dimensions of Religiosity and PTSD Symptom Clusters in US Veterans and Active Duty Military.

J Relig Health 2019 Jun;58(3):805-822

School of Sociology, University of Arizona, Social Sciences 400, PO Box 210027, Tucson, AZ, 85721-0027, USA.

We examined multiple dimensions of religiosity and their relationship to the four DSM-5 PTSD symptom clusters among US Veterans and Active Duty Military (ADM), hypothesizing that religiosity would be most strongly inversely related to negative cognitions/emotions (Criterion D symptoms) and less strongly to neurobiologically based symptom clusters (B, C, and E). This cross-sectional multisite study involved 591 Veterans and ADM from across the southern USA. Inclusion criteria were having served in a combat theater and the presence of PTSD symptoms. Measures of religious beliefs/practices, social involvement, and PTSD symptoms were administered, and bivariate and multivariate analyses were conducted in the overall sample, and in exploratory analyses, in the sample stratified by race (White, Black, and Hispanic). In the overall sample, multivariate analyses revealed that the only PTSD symptom cluster inversely related to religiosity was Criterion D, and only to organizational (b = - 0.08, P = 0.028) and cognitive/intrinsic religiosity (b = - 0.06, P = 0.049), relationships that were fully explained by social factors. Religious struggles, in contrast, were positively related to all four symptom clusters. Inverse relationships with Criterion D symptoms were particularly strong in Blacks, in whom inverse relationships were also present with Criterion E symptoms. In contrast, only positive relationships with PTSD symptom clusters were found in Hispanics, and no relationships (except for religious struggles) were present in Whites. As hypothesized, the inverse relationship between religious involvement and PTSD symptoms in Veterans and ADM was strongest (though modest) for Criterion D negative cognitions/emotions, especially in Blacks.
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http://dx.doi.org/10.1007/s10943-019-00817-7DOI Listing
June 2019

Electroconvulsive Treatment Utilization for the Inpatient Management of Severe Manic Episodes of Bipolar Disorder.

J ECT 2019 Sep;35(3):195-200

Department of Psychiatry and Health Behavior.

Objective: Main objectives of the study are to (1) describe the utilization of electroconvulsive treatment (ECT) for the treatment of manic episodes (ME) and (2) examine the effect of early inpatient use of ECT (within 7 days of admission) compared with delayed use on length of stay and cost of inpatient care.

Method: The total sample of 14,005 inpatients with a principal diagnosis of bipolar disorder, ME (2012-2014), from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project were analyzed using univariate and logistic regressions. This represented data from 4411 hospitals from 45 states in the United States.

Results: The rate of ECT use was higher in young adults (<50 years), female patients, and whites from high-income families. Electroconvulsive treatment was preferred more in private, nonprofit, urban, and teaching hospitals. The percentages of overall hospitals where ECT was administered for mania by region were as follows: 22% in the Northeast, 23% in Midwest. 17% in the South, and 10% in the West. Approximately half (55.3%) of patients received initial ECT session within the first 7 days (median) after admission. Early ECT was associated with significantly shorter (-14.7 days) and less costly (-$41,976) inpatient care per patient.

Conclusions: Patients treated with ECT are generally sicker and more treatment resistant. However, ECT should not be considered only as a "last resort" in the treatment algorithm. Inpatient ECT for patients with MEs if initiated during the first 7 days of hospitalization reduces length of stay and cost.
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http://dx.doi.org/10.1097/YCT.0000000000000587DOI Listing
September 2019

Intensity-dependent, disabling exercise-induced depression and irritability without primary mood disorder.

Ann Clin Psychiatry 2019 02;31(1):70-71

Department of Psychiatry and Health Behavior, Office of Academic Affairs, Medical College of Georgia, Augusta University, Augusta, GA 30912 USA. E-MAIL:

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February 2019

Resilience Against Traumatic Stress: Current Developments and Future Directions.

Front Psychiatry 2018 14;9:676. Epub 2018 Dec 14.

Department of Psychiatry and Neuropsychology, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands.

Given the high prevalence of stress-related mental disorders, their impact on person, family, and society and the paucity of treatment options for most of these disorders, there is currently a pressing need for innovative approaches to deal with these issues and enhance well-being. One approach which has received increasing attention over the last decade is to shift our scientific and clinical focus from risk factors for psychopathology to factors promoting resilience and mental well-being. In order to summarize and evaluate the current state of scientific affairs on the biological basis of resilience, we provide an overview of the literature on animal and human studies of resilience. Because resilience can only truly be operationalized through longitudinal data collection and analyses, we focus primarily on longitudinal studies. This review shows that the concept of resilience is currently being operationalized, measured and even defined in widely variable manners, both within animal and human studies. We further provide an overview of existing and new strategies that could help promote resilience and which are proposed to be implemented more often in clinical situations. Finally, we summarize the challenges the field is facing and provide recommendations for future research.
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http://dx.doi.org/10.3389/fpsyt.2018.00676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315131PMC
December 2018

Interest among veterans in spiritually-oriented therapy for inner conflict/moral injury in the setting of PTSD.

Ann Clin Psychiatry 2018 11;30(4):262-270

Department of Psychiatry and Health Behavior, Office of Academic Affairs, Medical College of Georgia at Augusta University, Augusta, GA 30912 USA; E-mail:

Background: We examined U.S. veterans' interest in spiritually-oriented therapy (SOT) for treating inner conflict/moral injury (ICMI); identified combat-related, demographic, religious, and psychological characteristics of those interested in this treatment modality; and determined which participants would prefer SOT therapy.

Methods: This study was a cross-sectional multi-site study of 464 veterans with posttraumatic stress disorder (PTSD) related to war time experiences. Participants were recruited from several U.S. Department of Veterans Affairs (VA) hospitals and interest in SOT was assessed. Bivariate and multivariate analyses were used to examine the prevalence and correlates of participants' willingness to participate.

Results: More than 85% of participants indicated willingness to participate in SOT, including 41% who indicated they "definitely" would participate. Logistic regression examining correlates of definitely wanting to participate found it was associated with less time since deployment, more education, not being married, more severe PTSD, and greater religiosity. Level of ICMI was not related to willingness to engage in SOT. Active duty military were less likely than veterans to show interest in SOT. Most participants preferred VA psychologists to provide the therapy, except those who indicated religion was important or very important.

Conclusions: Many U.S. veterans with PTSD are interested in SOT, particularly when delivered by psychologists. Given widespread ICMI among veterans, the development and empirical testing of such treatments is warranted.
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November 2018