TY - JOUR
T1 - Differences in perceived life stress in bipolar I and II disorder
T2 - Implications for future epigenetic quantification
AU - Grzenda, Adrienne
AU - Veldic, Marin
AU - Jia, Yun Fang
AU - McElroy, Susan L.
AU - Bond, David J.
AU - Geske, Jennifer R.
AU - Ozerdem, Aysegul
AU - Singh, Balwinder
AU - Biernacka, Joanna M.
AU - Choi, Doo Sup
AU - Frye, Mark A.
N1 - Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Adrienne Grzenda has received support from the American Psychiatric Association Foundation Research Fellowship. Dr. Susan L. McElroy is a consultant to or member of the scientific advisory boards of Allergen, Alkermes, Corcept, Ironshore, MedAvante, Naurex, NovoNordisk, Shire, Sunovian, and Teva. She is a principal or co-investigator on studies sponsored by the Agency for Healthcare Research & Quality (AHRQ), Azevan, Alkermes, AstraZeneca, Cephalon, Eli Lilly and Company, Marriott Foundation, National Institute of Mental Health, Orexigen Therapeutics, Inc., Shire, Sunovian, Takeda Pharmaceutical Company Ltd., and Transcept Pharmaceutical, Inc. She is also an inventor on United States Patent No. 6323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patient's assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent. Dr David J. Bond has received research support from Myriad Genetics, NuBiyota, and NIDA, has been a consultant for Myriad Genetics and Alkermes. Dr. Doo-Sup Choi is on the scientific advisory board of Peptron Inc. Dr. Mark Frye has had grant support from Assurex, Myriad, and Pfizer and has served as an unpaid consultant for Janssen Global Services, LLC, Mitsubishi Tanabe Pharma Corporation, Myriad, Sunovion, Supernus Pharmaceuticals, and Teva Pharmaceuticals. The remaining authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript. The remaining authors report no competing interests in the past three years.
Funding Information:
Funding for the study was provided by the Marriott Foundation.
Publisher Copyright:
© 2022
PY - 2022/7/1
Y1 - 2022/7/1
N2 - Objective: Few instruments measuring life events over the course of bipolar disorder distinguish the valence of events or consider cumulative stress burden. In the current study, we used a valence-focused life event questionnaire to assess stress in the last 12 months in patients with bipolar I (n = 863) and bipolar II (n = 362) disorder. Methods: Associations between recent stress and lifetime illness severity features were evaluated via linear and logistic regression, adjusting for age and gender. We additionally investigated the feasibility of quantifying recent stress burden by measuring methylation at a known bipolar susceptibility locus, SLC1A2 in a subset of bipolar I patients (n = 150) with or without comorbid substance use. Results: Bipolar II patients endorsed higher total, negative, and positive stress burden than their bipolar I counterparts, but the latter displayed more significant stress-illness severity associations, notably to all forms of substance abuse (e.g., alcohol, nicotine, food, other drugs). Irrespective of bipolar subtype, negative stress burden was significantly associated with illness severity features. High versus low total stress predicted hypomethylation of the SLC1A2 promoter (p < 0.05). Conclusion: Together, these findings reveal substantial differences in how bipolar subtypes experience and perceive stress. The observed degree of association between recent stress and substance abuse in bipolar I lend further support to the multidirectional effects of stress, affective episodes, and substance abuse on illness severity. Quantification of recent total stress using the methylation status of the SLC1A2 promoter is feasible, although a whole-methylome approach will likely prove more effective in disaggregating other environmental influences.
AB - Objective: Few instruments measuring life events over the course of bipolar disorder distinguish the valence of events or consider cumulative stress burden. In the current study, we used a valence-focused life event questionnaire to assess stress in the last 12 months in patients with bipolar I (n = 863) and bipolar II (n = 362) disorder. Methods: Associations between recent stress and lifetime illness severity features were evaluated via linear and logistic regression, adjusting for age and gender. We additionally investigated the feasibility of quantifying recent stress burden by measuring methylation at a known bipolar susceptibility locus, SLC1A2 in a subset of bipolar I patients (n = 150) with or without comorbid substance use. Results: Bipolar II patients endorsed higher total, negative, and positive stress burden than their bipolar I counterparts, but the latter displayed more significant stress-illness severity associations, notably to all forms of substance abuse (e.g., alcohol, nicotine, food, other drugs). Irrespective of bipolar subtype, negative stress burden was significantly associated with illness severity features. High versus low total stress predicted hypomethylation of the SLC1A2 promoter (p < 0.05). Conclusion: Together, these findings reveal substantial differences in how bipolar subtypes experience and perceive stress. The observed degree of association between recent stress and substance abuse in bipolar I lend further support to the multidirectional effects of stress, affective episodes, and substance abuse on illness severity. Quantification of recent total stress using the methylation status of the SLC1A2 promoter is feasible, although a whole-methylome approach will likely prove more effective in disaggregating other environmental influences.
KW - Bipolar disorder
KW - Epigenetics
KW - Life events
KW - Methylation
KW - Stress
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U2 - 10.1016/j.pmip.2022.100093
DO - 10.1016/j.pmip.2022.100093
M3 - Article
AN - SCOPUS:85129913244
VL - 33-34
JO - Personalized Medicine in Psychiatry
JF - Personalized Medicine in Psychiatry
SN - 2468-1717
M1 - 100093
ER -