Publications by authors named "Kamber L Hart"

20 Publications

  • Page 1 of 1

Effect of citalopram on hippocampal volume in first-episode schizophrenia: Structural MRI results from the DECIFER trial.

Psychiatry Res Neuroimaging 2021 Apr 7;312:111286. Epub 2021 Apr 7.

Department of Psychiatry, NYU Langone Health, 1 Park Avenue, New York, NY 10016, United States of America; Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, United States of America. Electronic address:

Hippocampal volume loss is prominent in first episode schizophrenia (FES) and has been associated with poor clinical outcomes and with BDNF genotype; antidepressants are believed to reverse hippocampal volume loss via release of BDNF. In a 12-month, placebo-controlled add-on trial of the antidepressant, citalopram, during the maintenance phase of FES, negative symptoms were improved with citalopram. We now report results of structural brain imaging at baseline and 6 months in 63 FES patients (34 in citalopram group) from the trial to assess whether protection against hippocampal volume loss contributed to improved negative symptoms with citalopram. Hippocampal volumetric integrity (HVI) did not change significantly in the citalopram or placebo group and did not differ between treatment groups, whereas citalopram was associated with greater volume loss of the right CA1 subfield. Change in cortical thickness was associated with SANS change in 4 regions (left rostral anterior cingulate, right frontal pole, right cuneus, and right transverse temporal) but none differed between treatment groups. Our findings suggest that minimal hippocampal volume loss occurs after stabilization on antipsychotic treatment and that citalopram's potential benefit for negative symptoms is unlikely to result from protection against hippocampal volume loss or cortical thinning.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111286DOI Listing
April 2021

Association of Aripiprazole With Reduced Hippocampal Atrophy During Maintenance Treatment of First-Episode Schizophrenia.

J Clin Psychopharmacol 2021 May-Jun 01;41(3):244-249

Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai.

Purpose/background: Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation.

Methods/procedures: Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2).

Findings/results: Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES.

Implications/conclusions: These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.
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http://dx.doi.org/10.1097/JCP.0000000000001391DOI Listing
April 2021

Authorship inequality: a bibliometric study of the concentration of authorship among a diminishing number of individuals in high-impact medical journals, 2008-2019.

BMJ Open 2021 01 6;11(1):e046002. Epub 2021 Jan 6.

Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA

Objective: Authorship and number of publications are important criteria used for making decisions about promotions and research funding awards. Given the increase in the number of author positions over the last few decades, this study sought to determine if there had been a shift in the distribution of authorship among those publishing in high-impact academic medical journals over the last 12 years.

Design: This study analysed the distribution of authorship across 312 222 original articles published in 134 medium-impact to high-impact academic medical journals between 1 January 2008 and 31 December 2019. Additionally, this study compared the trends in author distributions across nine medical specialties and a collection of cross-specialty high-impact journal articles.

Primary Outcome Measures: The distribution of authorship was assessed using the Gini coefficient (GC), a widely used measure of economic inequality.

Results: The overall GC for all articles sampled across the 12-year study period was 0.49, and the GCs for the first and last authorship positions were 0.30 and 0.44, respectively. Since 2008, there was a significant positive correlation between year and GC for the overall authorship position (r=0.99, p<0.001) the first author position (r=0.75, p=0.007) and the last author position (r=0.85, p<0.001) indicating increasingly uneven distribution in authorship over time. The cross-specialty high-impact journals exhibited the greatest rate of increase in GC over the study period for the first and last author position of any specialty analysed.

Conclusion: Overall, these data suggest a growing inequality in authorship across authors publishing in high-impact academic medical journals, especially among the highest impact journals. These findings may have implications for processes such as promotions and allocation of research funding that use authorship metrics as key criteria for making decisions.
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http://dx.doi.org/10.1136/bmjopen-2020-046002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789455PMC
January 2021

Distribution of agitation and related symptoms among hospitalized patients using a scalable natural language processing method.

Gen Hosp Psychiatry 2021 Jan-Feb;68:46-51. Epub 2020 Nov 10.

Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA. Electronic address:

Background: Agitation is a common feature of many neuropsychiatric disorders.

Objective: Understanding the prevalence, implications, and characteristics of agitation among hospitalized populations can facilitate more precise recognition of disability arising from neuropsychiatric diseases.

Methods: We developed two agitation phenotypes using an expansion of expert curated term lists. These phenotypes were used to characterize five years of psychiatric admissions. The relationship of agitation symptoms and length of stay was examined.

Results: Among 4548 psychiatric admissions, 1134 (24.9%) included documentation of agitation based on the primary agitation phenotype. These symptoms were greater among individuals with public insurance, and those with mania and psychosis compared to major depressive disorder. Greater symptoms were associated with longer hospital stay, with ~0.9 day increase in stay for every 10% increase in agitation phenotype.

Conclusion: Agitation was common at hospital admission and associated with diagnosis and longer length of stay. Characterizing agitation-related symptoms through natural language processing may provide new tools for understanding agitated behaviors and their relationship to delirium.
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http://dx.doi.org/10.1016/j.genhosppsych.2020.11.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855889PMC
November 2020

D-cycloserine augmentation of cognitive behavioral therapy for delusions: A randomized clinical trial.

Schizophr Res 2020 08 23;222:145-152. Epub 2020 Jun 23.

Department of Psychiatry, NYU Langone Health, New York, NY, United States of America; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States of America. Electronic address:

Objective: D-cycloserine (DCS) promotes consolidation of extinction learning. This study extends earlier work by examining whether DCS can enhance cognitive behavioral therapy (CBT) for delusions.

Methods: Adults reporting moderate or greater delusions were randomly assigned to receive 50 mg of DCS or placebo prior to 10 weekly CBT sessions. The primary outcome was change in severity of delusions measured with the Psychotic Symptom Rating Scale delusion subscale (PSYRATS-D). Secondary outcomes included persistence of response at 3 and 6 month follow-up and the effects of DCS on memory consolidation and cognitive flexibility. Fifty-eight participants were randomized and 44 completed the trial.

Results: The DCS and placebo groups did not differ in change from baseline to end of CBT on PSYRATS-D, nor did DCS improve memory consolidation or cognitive flexibility compared to placebo. However, at the 3 month follow-up visit (week 24), 47% of participants who completed treatment with DCS reported a 20% or greater decrease on PSYRATS-D compared to 15% in the placebo group (p = .04). Change in distress across CBT sessions interacted with treatment group to predict change from baseline to week 24 in PSYRATS-D total score (p = .03) such that response at week 24 was greatest in DCS-treated participants who experienced a decrease in distress during CBT sessions.

Conclusions: DCS augmentation of CBT did not improve delusions compared to placebo during treatment; however, DCS was associated with a higher response rate at 3-month follow-up. DCS may produce a delayed therapeutic effect, associated with successful CBT sessions, but this finding requires replication.
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http://dx.doi.org/10.1016/j.schres.2020.06.015DOI Listing
August 2020

Trends in Female Authorship in High Impact Surgical Journals Between 2008 and 2018.

Ann Surg 2020 Jun 24. Epub 2020 Jun 24.

Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, Massachusetts.

Objective: This study evaluates the distribution of authorship by sex over the last 10 years among the top 25 surgical journals.

Summary Of Background Data: Despite an increase in women entering surgical residency, there remains a sex disparity in surgical leadership. Scholarly activity is the foundation for academic promotion. However, few studies have evaluated productivity by sex in surgical literature.

Methods: Original research in the 25 highest-impact general surgery/subspecialty journals were included (1/2008-5/2018). Journals with <70% identified author sex were excluded. Articles were categorized by sex of first, last, and overall authorship. We examined changes in proportions of female first, last, and overall authorship over time, and analyzed the correlation between these measurements and journal impact factor.

Results: There were 71,867 articles from 19 journals included. Sex was successfully predicted for 87.3% of authors (79.1%-92.5%). There were significant increases in the overall percentage of female authors (β = 0.55, P < 0.001), female first authors (β = 0.97, P < 0.001), and female last authors (β = 0.53, P < 0.001) over the study period. Notably, all cardiothoracic subspecialty journals did not significantly increase the proportion of female last authors over the study period. There were no correlations between journal impact factor and percentage of overall female authors (rs = 0.39, P = 0.09), female first authors (rs = 0.29, P = 0.22), or female last author (rs = 0.35, P = 0.13).

Conclusions: This study identifies continued but slow improvement in female authorship of high-impact surgical journals during the contemporary era. However, the improvement was more apparent in the first compared to senior author positions.
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http://dx.doi.org/10.1097/SLA.0000000000004057DOI Listing
June 2020

The Variable Effects of NSAIDs on Osteotomy Healing and Opioid Consumption.

J Am Acad Orthop Surg Glob Res Rev 2020 04 6;4(4). Epub 2020 Apr 6.

Department of Clinical Orthopaedics, Weill Medical College of Cornell University, The Hospital for Special Surgery (Dr. Fragomen and Dr. Rozbruch); Limb Lengthening and Complex Reconstruction Service, The Hospital for Special Surgery (Dr. Fragomen and Dr. Rozbruch); Hospital for Special Surgery (Ms. Suh), New York, NY; Geisinger Commonwealth School of Medicine, Scranton, PA (Ms. Matta); Department of Medicine and Psychiatry, Harvard Medical School, Center for Quantitative Health, Simches Research Building, Massachusetts General Hospital and Harvard Medical School (Dr. McCoy); and Center for Quantitative Health, Simches Research Building, Massachusetts General Hospital and Harvard Medical School (Ms. Hart), Boston, MA.

In an effort to fight the opioid epidemic, an NSAID pain protocol was created for osteotomy patients. The study asked if NSAIDs negatively affect bone healing or reduce the need for opioids.

Methods: This was a retrospective review of 155 limbs that underwent osteotomy of a long bone with fixation. Patients received an NSAID-free protocol or an NSAID protocol. Time to union and bone healing index were recorded.

Results: There was not a significant difference in the time to union ( = 0.89) or bone healing index ( = 0.07). In the deformity correction group, the total milligrams of morphine equivalents prescribed after discharge was significantly less in patients receiving NSAIDs ( < 0.001).

Conclusions: The use of NSAIDs after osteotomy surgery did not negatively affect bone healing and resulted in a dramatic decrease in narcotic consumption for deformity correction patients.

Level Of Evidence: Level III retrospective cohort study.
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http://dx.doi.org/10.5435/JAAOSGlobal-D-20-00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188274PMC
April 2020

What do patients learn about psychotropic medications on the web? A natural language processing study.

J Affect Disord 2020 01 10;260:366-371. Epub 2019 Sep 10.

Center for Quantitative Health, Massachusetts General Hospital, 185 Cambridge Street, 6th Floor, Boston, MA 02114, USA. Electronic address:

Background: Low rates of medication adherence remain a major challenge across psychiatry. In part, this likely reflects patient concerns about safety and adverse effects, accurate or otherwise. We therefore sought to characterize online information about common psychiatric medications in terms of positive and negative sentiment.

Methods: We applied a natural language processing tool to score the sentiment expressed in web search results for 51 psychotropic medications across 3 drug classes (antidepressants, antipsychotics, and mood stabilizers), as a means of seeing if articles referencing these medications were generally positive or generally negative in tone. We compared between medications of the same class, and across medication classes.

Results: Across 12,733 web search results, significant within-class differences in positive (antidepressants: F(24,2682) = 2.97, p < 0.001; antipsychotics: F(16,4029) = 3.25, p < 0.001; mood stabilizers: F(8,2371) = 6.88, p < 0.001) and negative sentiment (antidepressants: F(24,6282) = 11.17, p < 0.001; antipsychotics: F(16, 4029)  = 12.13, p < 0.001; mood stabilizers: F(8, 2371) = 13.28, p < 0.001) were identified. Among these were significantly greater negative sentiment for the antidepressants sertraline, duloxetine, venlafaxine, and paroxetine, and for the antipsychotics, quetiapine and risperidone. Conversely, lithium preparations and valproate exhibited less negative sentiment than other mood stabilizing medications.

Limitations: While these results provide a novel means of comparing medications, the present analyses cannot be linked to individual patient consumption of this information, or to its influence on their future clinical interactions.

Conclusions: Overall, a subset of psychotropic medications were associated with significantly more negative sentiment. Characterizing these differences may allow clinicians to anticipate patient willingness to initiate or continue medications.
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http://dx.doi.org/10.1016/j.jad.2019.09.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921244PMC
January 2020

Trends in Proportion of Women as Authors of Medical Journal Articles, 2008-2018.

JAMA Intern Med 2019 Sep;179(9):1285-1287

Center for Quantitative Health, Division of Clinical Research, Massachusetts General Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1001/jamainternmed.2019.0907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547141PMC
September 2019

Gender Trends in Authorship in Psychiatry Journals From 2008 to 2018.

Biol Psychiatry 2019 10 19;86(8):639-646. Epub 2019 Feb 19.

Center for Quantitative Health, Division of Clinical Research, Massachusetts General Hospital, Boston, Massachusetts. Electronic address:

Background: Women are currently underrepresented in academic psychiatry. As publication activity reflects both leadership and participation in academia, we examined temporal trends in women's authorship by conducting a large-scale bibliometric study of psychiatry journals.

Methods: We examined changes in proportions of women in the first, last, and overall authorship positions over time; relationship to journal impact factor and editorial board makeup; and rates of transition to senior author status using original research articles published in the 24 highest-impact psychiatry journals between January 2008 and May 2018.

Results: In 30,934 articles, women represented 40.0% of all authors in 2008 and 44.8% in 2018, with a significant increase in the percentage of women as first authors (2008: 43.5%, 2018: 49.5%; B = 0.64, p = .002) and last authors over time (2008: 30.0%, 2018: 35.7%; B = 0.64, p = 1 × 10). Articles with women as last authors were significantly more likely than those with men as last authors to have a woman as first author (χ = 126.1, p < 2.2 × 10). Women exhibited slower rates of transition to the last author position (log rank p = 2 × 10); time to 10% transition was 5 years for men and 9 years for women.

Conclusions: These results indicate continued improvement in the representation of women authors in psychiatry journals, resulting in near parity in first authors. However, slower rates of transition to the senior author position and continued underrepresentation of women as senior authors suggest ongoing challenges in achieving gender parity in academic leadership. At the present rate of change for last authors (0.64% increase per year), women would achieve parity in senior authorship in ∼20 to 25 years.
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http://dx.doi.org/10.1016/j.biopsych.2019.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6699930PMC
October 2019

Risk tolerance measured by probability discounting among individuals with primary mood and psychotic disorders.

Neuropsychology 2019 Mar 28;33(3):417-424. Epub 2019 Jan 28.

Massachusetts General Hospital and Harvard Medical School.

Objective: Change in risk tolerance is a feature of multiple psychiatric disorders and may contribute to adverse outcomes. We used a probability discounting (PD) task to measure risk-taking behavior among individuals with bipolar disorder (BPAD), major depressive disorder (MDD), schizoaffective disorder (SCAD), and schizophrenia (SCZ).

Method: A PD task was administered to 117 patients and 88 healthy controls (HCs), along with a cognitive battery using the Cambridge Neuropsychological Test Automated Battery, and relevant symptomatology scales. We examined differences in PD rates between diagnostic groups, and compared with HCs, while controlling for potential confounding factors including measures of cognitive functioning.

Results: Individuals with a diagnosis of BPAD or SCAD/SCZ prefer smaller, more guaranteed rewards rather than larger, less likely rewards as compared with healthy controls (p = .002 and p = .034, respectively). There was no effect of performance on cognitive tasks, antipsychotic treatment, or symptomatology on the rate of probability discounting.

Conclusion: This study supports the transdiagnostic measurement of risk-taking behaviors, even when such behaviors are not the primary area of psychopathology. Quantifying risk-taking may enable targeted therapeutic strategies across disorders. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000506DOI Listing
March 2019

Genomewide Association Study of Fracture Nonunion Using Electronic Health Records.

JBMR Plus 2019 Jan 20;3(1):23-28. Epub 2018 Jun 20.

Center for Quantitative Health Massachusetts General Hospital and Harvard Medical School Boston MA USA.

Nonunion is a clinically significant complication of fracture associated with worse outcomes, including increased pain, disability, and higher healthcare costs. The risk for nonunion is likely to be complex and multifactorial, and as such, the biology underlying such risk remains poorly understood. Genetic studies represent one approach to identify implicated biology for further investigation, but to date the lack of large cohorts for study has limited such efforts. We utilized the electronic health records of two large academic medical centers in Boston to identify individuals with fracture nonunion and control individuals with fracture but no evidence of nonunion. We conducted a genomewide association study among 1760 individuals of Northern European ancestry with upper or lower extremity fracture, including 131 with nonunion, to examine whether common variants were associated with nonunion in this cohort. In all, one locus in the Calcyon (CALY) gene exceeded a genomewide threshold for statistical significance ( = 1.95e-8), with eight additional loci associated with < 5e-7. Previously reported candidate genes were not supported by this analysis. Electronic health records should facilitate identification of common genetic variations associated with adverse orthopedic outcomes. The loci we identified in this small cohort require replication and further study to characterize mechanism of action, but represent a starting point for the investigation of genetic liability for this costly outcome.
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http://dx.doi.org/10.1002/jbm4.10063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339539PMC
January 2019

PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia.

J Clin Invest 2019 01 10;129(1):364-372. Epub 2018 Dec 10.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.

Background: Patients with schizophrenia (SCZ) experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymes that regulate cognitive circuitry; however, the role of HDACs in cognitive disorders, including SCZ, remains unknown in humans. We previously determined that HDAC2 mRNA levels were lower in dorsolateral prefrontal cortex (DLPFC) tissue from donors with SCZ compared with controls. Here we investigated the relationship between in vivo HDAC expression and cognitive impairment in patients with SCZ and matched healthy controls using [11C]Martinostat positron emission tomography (PET).

Methods: In a case-control study, relative [11C]Martinostat uptake was compared between 14 patients with SCZ or schizoaffective disorder (SCZ/SAD) and 17 controls using hypothesis-driven region-of-interest analysis and unbiased whole brain voxel-wise approaches. Clinical measures, including the MATRICS consensus cognitive battery, were administered.

Results: Relative HDAC expression was lower in the DLPFC of patients with SCZ/SAD compared with controls, and HDAC expression positively correlated with cognitive performance scores across groups. Patients with SCZ/SAD also showed lower relative HDAC expression in the dorsomedial prefrontal cortex and orbitofrontal gyrus, and higher relative HDAC expression in the cerebral white matter, pons, and cerebellum compared with controls.

Conclusions: These findings provide in vivo evidence of HDAC dysregulation in patients with SCZ and suggest that altered HDAC expression may impact cognitive function in humans.

Funding: National Institute of Mental Health (NIMH), Brain and Behavior Foundation, Massachusetts General Hospital (MGH), Athinoula A. Martinos Center for Biomedical Imaging, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH Shared Instrumentation Grant Program.
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http://dx.doi.org/10.1172/JCI123743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307962PMC
January 2019

Cohort study of the relationship between individual psychotherapy and pregnancy outcomes.

J Affect Disord 2018 10 6;239:253-257. Epub 2018 Jul 6.

Center for Experimental Drugs and Diagnostics, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, Unites States. Electronic address:

Introduction: Antenatal depression is associated with poor obstetric outcomes, but it has not been determined if treatment improves these outcomes. We hypothesized that psychotherapy for antenatal depression would decrease rates of low Apgar score, preterm birth, low birthweight, and high maternal weight gain.

Methods: Using longitudinal clinical data from the electronic health record (EHR) of a large academic medical center, we examined the association between exposure to psychotherapy during pregnancy among women with a history of major depressive disorder and obstetric outcomes. We compared outcomes between women with and without psychotherapy treatment during pregnancy, and included a dose response analysis.

Results: Of 50,856 women with pregnancies between 1998 and 2013, 5413 had a lifetime diagnosis of depression (948 had a diagnosis of depression during pregnancy), and 536 received psychotherapy at least once during pregnancy. Women who received one or more psychotherapy sessions during pregnancy had increased odds of preterm delivery and decreased odds of high maternal weight gain (more than 40 pounds). Individuals who received four or more psychotherapy sessions during pregnancy had increased odds of preterm birth and low infant birth weight and decreased odds of high maternal weight gain.

Limitations: Patients may have pursued treatment outside of this hospital's EHR data, and we cannot control for the quality of treatment or type of psychotherapy.

Discussion: Psychotherapy was associated with negative obstetric outcomes. While treatment of depression in pregnant women has been shown to benefit the mother, the absence of benefit in terms of pregnancy outcomes merits further investigation.
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http://dx.doi.org/10.1016/j.jad.2018.05.083DOI Listing
October 2018

Impairment in delay discounting in schizophrenia and schizoaffective disorder but not primary mood disorders.

NPJ Schizophr 2018 May 28;4(1). Epub 2018 May 28.

Department of Psychiatry, Center for Quantitative Health, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

A measure of planning and impulse control, the delay-discounting (DD) task estimates the extent to which an individual decreases the perceived value of a reward as the reward is delayed. We examined cross-disorder performance between healthy controls (n = 88), individuals with bipolar disorder (n = 23), major depressive disorder (n = 43), and primary psychotic disorders (schizophrenia and schizoaffective disorder; n = 51) on the DD task (using a $10 delayed larger reward), as well as the interaction of DD scores with other symptom domains (cognition, psychosis, and affect). We found that individuals with schizophrenia and schizoaffective disorder display significantly greater rates of discounting compared to healthy controls, while individuals with a primary mood disorder do not differ from healthy controls after adjustment for IQ. Further, impairment in working memory is associated with higher discounting rates among individuals with schizophrenia and schizoaffective disorder, but cognitive dysfunction alone does not account for the extent of impairment in DD. Taken together, these results suggest an impaired ability to plan for the future and make adaptive decisions that are specific to individuals with psychotic disorders, and likely related to adverse functional outcomes. More generally, this work demonstrates the presence of variation in impulsivity across major psychiatric illnesses, supporting the use of a trans-diagnostic perspective.
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http://dx.doi.org/10.1038/s41537-018-0050-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972152PMC
May 2018

Genome-wide Association Study of Dimensional Psychopathology Using Electronic Health Records.

Biol Psychiatry 2018 06 26;83(12):1005-1011. Epub 2018 Feb 26.

Center for Quantitative Health and Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: Genetic studies of neuropsychiatric disease strongly suggest an overlap in liability. There are growing efforts to characterize these diseases dimensionally rather than categorically, but the extent to which such dimensional models correspond to biology is unknown.

Methods: We applied a newly developed natural language processing method to extract five symptom dimensions based on the National Institute of Mental Health Research Domain Criteria definitions from narrative hospital discharge notes in a large biobank. We conducted a genome-wide association study to examine whether common variants were associated with each of these dimensions as quantitative traits.

Results: Among 4687 individuals, loci in three of five domains exceeded a genome-wide threshold for statistical significance. These included a locus spanning the neocortical development genes RFPL3 and RFPL3S for arousal (p = 2.29 × 10) and one spanning the FPR3 gene for cognition (p = 3.22 × 10).

Conclusions: Natural language processing identifies dimensional phenotypes that may facilitate the discovery of common genetic variation that is relevant to psychopathology.
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http://dx.doi.org/10.1016/j.biopsych.2017.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972060PMC
June 2018

High Throughput Phenotyping for Dimensional Psychopathology in Electronic Health Records.

Biol Psychiatry 2018 06 26;83(12):997-1004. Epub 2018 Feb 26.

Center for Quantitative Health and Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: Relying on diagnostic categories of neuropsychiatric illness obscures the complexity of these disorders. Capturing multiple dimensional measures of neuropathology could facilitate the clinical and neurobiological investigation of cognitive and behavioral phenotypes.

Methods: We developed a natural language processing-based approach to extract five symptom dimensions, based on the National Institute of Mental Health Research Domain Criteria definitions, from narrative clinical notes. Estimates of Research Domain Criteria loading were derived from a cohort of 3619 individuals with 4623 hospital admissions. We applied this tool to a large corpus of psychiatric inpatient admission and discharge notes (2010-2015), and using the same cohort we examined face validity, predictive validity, and convergent validity with gold standard annotations.

Results: In mixed-effect models adjusted for sociodemographic and clinical features, greater negative and positive symptom domains were associated with a shorter length of stay (β = -.88, p = .001 and β = -1.22, p < .001, respectively), while greater social and arousal domain scores were associated with a longer length of stay (β = .93, p < .001 and β = .81, p = .007, respectively). In fully adjusted Cox regression models, a greater positive domain score at discharge was also associated with a significant increase in readmission risk (hazard ratio = 1.22, p < .001). Positive and negative valence domains were correlated with expert annotation (by analysis of variance [df = 3], R = .13 and .19, respectively). Likewise, in a subset of patients, neurocognitive testing was correlated with cognitive performance scores (p < .008 for three of six measures).

Conclusions: This shows that natural language processing can be used to efficiently and transparently score clinical notes in terms of cognitive and psychopathologic domains.
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http://dx.doi.org/10.1016/j.biopsych.2018.01.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972065PMC
June 2018

Efficient genome-wide association in biobanks using topic modeling identifies multiple novel disease loci.

Mol Med 2017 11 31;23:285-294. Epub 2017 Aug 31.

Center for Quantitative Health, Division of Clinical Research and Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114.

Biobanks and national registries represent a powerful tool for genomic discovery, but rely on diagnostic codes that may be unreliable and fail to capture the relationship between related diagnoses. We developed an efficient means of conducting genome-wide association studies using combinations of diagnostic codes from electronic health records (EHR) for 10845 participants in a biobanking program at two large academic medical centers. Specifically, we applied latent Dirichilet allocation to fit 50 disease topics based on diagnostic codes, then conducted genome-wide common-variant association for each topic. In sensitivity analysis, these results were contrasted with those obtained from traditional single-diagnosis phenome-wide association analysis, as well as those in which only a subset of diagnostic codes are included per topic. In meta-analysis across three biobank cohorts, we identified 23 disease-associated loci with p<1e-15, including previously associated autoimmune disease loci. In all cases, observed significant associations were of greater magnitude than for single phenome-wide diagnostic codes, and incorporation of less strongly-loading diagnostic codes enhanced association. This strategy provides a more efficient means of phenome-wide association in biobanks with coded clinical data.
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http://dx.doi.org/10.2119/molmed.2017.00100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681697PMC
November 2017

Characterizing and predicting rates of delirium across general hospital settings.

Gen Hosp Psychiatry 2017 05 26;46:1-6. Epub 2017 Jan 26.

Center for Quantitative Health, Division of Clinical Research, Massachusetts General Hospital, Simches Research Building 6th Floor, 185 Cambridge St, Boston, MA 20114, United States.

Objective: To better understand variation in reported rates of delirium, this study characterized delirium occurrence rate by department of service and primary admitting diagnosis.

Method: Nine consecutive years (2005-2013) of general hospital admissions (N=831,348) were identified across two academic medical centers using electronic health records. The primary admitting diagnosis and the treating clinical department were used to calculate occurrence rates of a previously published delirium definition composed of billing codes and natural language processing of discharge summaries.

Results: Delirium rates varied significantly across both admitting diagnosis group (X=12786, p<0.001) and department of care (X=12106, p<0.001). In both cases obstetrical admissions showed the lowest incidences of delirium (86/109764; 0.08%) and neurological admissions the greatest (2851/25450; 11.2%). Although the rate of delirium varied across the two hospitals the relative rates within departments (r=0.96, p<0.001) and diagnostic categories (r=0.98, p<0.001) were consistent across the two institutions.

Conclusions: The frequency of delirium varies significantly across admitting diagnosis and hospital department. Both admitting diagnosis and department of care are even stronger predictors of risk than age; as such, simple risk stratification may offer avenues for targeted prevention and treatment efforts.
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http://dx.doi.org/10.1016/j.genhosppsych.2017.01.006DOI Listing
May 2017

Enhancing Delirium Case Definitions in Electronic Health Records Using Clinical Free Text.

Psychosomatics 2017 Mar - Apr;58(2):113-120. Epub 2016 Oct 27.

Division of Clinical Research, Center for Quantitative Health, Massachusetts General Hospital, Boston, MA.

Background: Delirium is an acute confusional state, associated with morbidity and mortality in diverse medically ill populations. Delirium is preventable and treatable when diagnosed but the diagnosis is often missed. This important and difficult diagnosis is an attractive candidate for computer-aided decision support if it can be reliably identified at scale.

Objective: Here, using an electronic health record-based case definition of delirium, we characterize incidence of this highly morbid condition in 2 large academic medical centers.

Methods: Using the electronic health record of 2 large New England academic medical centers, we calculated and compared the rate of the diagnosis of delirium using a range of administrative and discharge summary text-based case definitions over an 8-year period.

Results: Depending on case definitions, the overall delirium rate ranged from 2.0-5.4% of 809,512 admissions identified. The identified rate of delirium increased between 2005 and 2013, such that by the final year of the study, one of the two sites reported delirium in 7.0% of cases. The concordance between case definitions was low; only half of the cases identified by text analysis were captured by administrative data.

Conclusion: Delirium may be better captured by composite outcomes, including both administrative claims data and elements drawn from unstructured data sources. That the rate of delirium observed in this study is far lower than the current literature estimates suggests that further work on case definitions, identification, and documented diagnosis is required.
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http://dx.doi.org/10.1016/j.psym.2016.10.007DOI Listing
November 2017