Publications by authors named "William V Bobo"

127 Publications

Illness stage and predominant polarity in bipolar disorder: Correlation with burden of illness and moderation of treatment outcome.

J Psychiatr Res 2021 Aug 2;140:205-213. Epub 2021 Jun 2.

Dauten Family Center for Bipolar Treatment Innovation, Department of Psychiatry, Massachusetts General Hospital, 50 Staniford Street, Suite 580, Boston, MA, 02114, United States; Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, United States. Electronic address:

Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo/manic episodes (termed predominant hypo/manic polarity). We examined the associations between staging and predominant polarity with measures of illness burden and treatment outcome utilizing data from a six-month comparative effectiveness trial of lithium and quetiapine in bipolar disorder (Bipolar CHOICE). We used number of self-reported lifetime mood (depressive and hypo/manic) episodes as a proxy for staging and ratio of depressive to manic episodes to define predominant polarity. Polarity and staging were correlated with several measures of burden of illness. Childhood abuse was correlated with more lifetime mood episodes, while more depressive episodes and depressive polarity were correlated with more anxiety disorder comorbidity. Depressive polarity was also correlated with more past trials of psychotropics, particularly antidepressants. However, neither staging nor predominant polarity moderated the randomized treatment effect of lithium vs. quetiapine. Number of depressive episodes in the past year was identified as a potential predictor of overall worse treatment outcome, regardless of medication condition. In conclusion, though staging and predominant episode polarity correlated with several measures of illness burden, they were not associated with differential treatment outcomes. This could be because many of our patients presented for treatment at advanced stages of illness and further highlights the need for early intervention in bipolar disorder.
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http://dx.doi.org/10.1016/j.jpsychires.2021.05.082DOI Listing
August 2021

Implementing the US Department of Health and Human Services definition of multimorbidity: a comparison between billing codes and medical record review in a population-based sample of persons 4084 years old.

BMJ Open 2021 04 24;11(4):e042870. Epub 2021 Apr 24.

Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota, USA.

Objective: To assess the validity of the US Department of Health and Human Services (DHHS) definition of multimorbidity using International Classification of Diseases, ninth edition (ICD-9) codes from administrative data.

Design: Cross-sectional comparison of two ICD-9 billing code algorithms to data abstracted from medical records.

Setting: Olmsted County, Minnesota, USA.

Participants: An age-stratified and sex-stratified random sample of 1509 persons ages 40-84 years old residing in Olmsted County on 31 December 2010.

Study Measures: Seventeen chronic conditions identified by the US DHHS as important in studies of multimorbidity were identified through medical record review of each participant between 2006 and 2010. ICD-9 administrative billing codes corresponding to the 17 conditions were extracted using the Rochester Epidemiology Project records-linkage system. Persons were classified as having each condition using two algorithms: at least one code or at least two codes separated by more than 30 days. We compared the ICD-9 code algorithms with the diagnoses obtained through medical record review to identify persons with multimorbidity (defined as ≥2, ≥3 or ≥4 chronic conditions).

Results: Use of a single code to define each of the 17 chronic conditions resulted in sensitivity and positive predictive values (PPV) ≥70%, and in specificity and negative predictive values (NPV) ≥70% for identifying multimorbidity in the overall study population. PPV and sensitivity were highest in persons 65-84 years of age, whereas NPV and specificity were highest in persons 40-64 years. The results varied by condition, and by age and sex. The use of at least two codes reduced sensitivity, but increased specificity.

Conclusions: The use of a single code to identify each of the 17 chronic conditions may be a simple and valid method to identify persons who meet the DHHS definition of multimorbidity in populations with similar demographic, socioeconomic, and health care characteristics.
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http://dx.doi.org/10.1136/bmjopen-2020-042870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074567PMC
April 2021

Venlafaxine prescription claims among insured women of reproductive age and pregnant women, 2011-2016.

Birth Defects Res 2021 Apr 16. Epub 2021 Apr 16.

Division of Birth Defects and Infant Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Background: Some studies have reported associations between prenatal use of venlafaxine, a serotonin-norepinephrine reuptake inhibitor used for depressive and anxiety disorders, and some birth defects. We described the prevalence of venlafaxine prescription claims among privately insured women of reproductive age and pregnant women.

Methods: Venlafaxine prescription claims were examined using the IBM MarketScan Commercial Databases. We included women of reproductive age (15-44 years) who had ≤45 days of lapsed enrollment during the calendar year of interest (2011-2016) in a non-capitated healthcare plan sponsored by a large, self-insured employer with prescription drug coverage and no mental health service carve-out. Annual cohorts of pregnant women were identified among eligible women of reproductive age via pregnancy diagnosis and procedure codes. Venlafaxine prescriptions were identified via National Drug Codes in outpatient pharmacy claims and we estimated the annual proportion of women with venlafaxine claims by pregnancy trimester (pregnant women only), age, and Census division.

Results: Each year during 2011-2016, approximately 1.2% of eligible reproductive-aged and 0.3% of eligible pregnant women filled a venlafaxine prescription. Among pregnant women, the proportion with venlafaxine claims was highest during the first trimester and decreased during the second and third trimesters. Small temporal increases in venlafaxine claims were observed for reproductive-aged and pregnant women, with the largest among women aged 15-19 years.

Conclusions: Venlafaxine prescription claims were low among women of reproductive age and pregnant women during 2011-2016, with some increasing use over time among women aged 15-19 years.
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http://dx.doi.org/10.1002/bdr2.1897DOI Listing
April 2021

Multimorbidity, ageing and mortality: normative data and cohort study in an American population.

BMJ Open 2021 03 19;11(3):e042633. Epub 2021 Mar 19.

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.

Objectives: To describe the percentile distribution of multimorbidity across age by sex, race and ethnicity, and to demonstrate the utility of multimorbidity percentiles to predict mortality.

Design: Population-based descriptive study and cohort study.

Setting: Olmsted County, Minnesota (USA).

Participants: We used the medical records-linkage system of the Rochester Epidemiology Project (REP; http://www.rochesterproject.org) to identify all residents of Olmsted County, Minnesota who reached one or more birthdays between 1 January 2005 and 31 December 2014 (10 years).

Methods: For each person, we obtained the count of chronic conditions (out of 20 conditions) present on each birthday by extracting all of the diagnostic codes received in the 5 years before the index birthday from the electronic indexes of the REP. To compare each person's count to peers of same age, the counts were transformed into percentiles of the total population and displayed graphically across age by sex, race and ethnicity. In addition, quintiles 1, 2, 4 and 5 were compared with quintile 3 (reference) to predict the risk of death at 1 year, 5 years and through end of follow-up using time-to-event analyses. Follow-up was passive using the REP.

Results: We identified 238 010 persons who experienced a total of 1 458 094 birthdays during the study period (median of 6 birthdays per person; IQR 3-10). The percentiles of multimorbidity across age did not vary noticeably by sex, race or ethnicity. In general, there was an increased risk of mortality at 1 and 5 years for quintiles 4 and 5 of multimorbidity. The risk of mortality for quintile 5 was greater for younger age groups and for women.

Conclusions: The assignment of multimorbidity percentiles to persons in a population may be a simple and intuitive tool to assess relative health status, and to predict short-term mortality, especially in younger persons and in women.
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http://dx.doi.org/10.1136/bmjopen-2020-042633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986688PMC
March 2021

Bi-directional association between depression and HF: An electronic health records-based cohort study.

J Comorb 2020 Jan-Dec;10:2235042X20984059. Epub 2020 Dec 24.

Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.

Objective: To determine whether a bi-directional relationship exists between depression and HF within a single population of individuals receiving primary care services, using longitudinal electronic health records (EHRs).

Methods: This retrospective cohort study utilized EHRs for adults who received primary care services within a large healthcare system in 2006. Validated EHR-based algorithms identified 10,649 people with depression (depression cohort) and 5,911 people with HF (HF cohort) between January 1, 2006 and December 31, 2018. Each person with depression or HF was matched 1:1 with an unaffected referent on age, sex, and outpatient service use. Each cohort (with their matched referents) was followed up electronically to identify newly diagnosed HF (in the depression cohort) and depression (in the HF cohort) that occurred after the index diagnosis of depression or HF, respectively. The risks of these outcomes were compared (vs. referents) using marginal Cox proportional hazard models adjusted for 16 comorbid chronic conditions.

Results: 2,024 occurrences of newly diagnosed HF were observed in the depression cohort and 944 occurrences of newly diagnosed depression were observed in the HF cohort over approximately 4-6 years of follow-up. People with depression had significantly increased risk for developing newly diagnosed HF (HR 2.08, 95% CI 1.89-2.28) and people with HF had a significantly increased risk of newly diagnosed depression (HR 1.34, 95% CI 1.17-1.54) after adjusting for all 16 comorbid chronic conditions.

Conclusion: These results provide evidence of a bi-directional relationship between depression and HF independently of age, sex, and multimorbidity from chronic illnesses.
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http://dx.doi.org/10.1177/2235042X20984059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768856PMC
December 2020

Prediction of short-term antidepressant response using probabilistic graphical models with replication across multiple drugs and treatment settings.

Neuropsychopharmacology 2021 06 15;46(7):1272-1282. Epub 2021 Jan 15.

Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, FL, USA.

Heterogeneity in the clinical presentation of major depressive disorder and response to antidepressants limits clinicians' ability to accurately predict a specific patient's eventual response to therapy. Validated depressive symptom profiles may be an important tool for identifying poor outcomes early in the course of treatment. To derive these symptom profiles, we first examined data from 947 depressed subjects treated with selective serotonin reuptake inhibitors (SSRIs) to delineate the heterogeneity of antidepressant response using probabilistic graphical models (PGMs). We then used unsupervised machine learning to identify specific depressive symptoms and thresholds of improvement that were predictive of antidepressant response by 4 weeks for a patient to achieve remission, response, or nonresponse by 8 weeks. Four depressive symptoms (depressed mood, guilt feelings and delusion, work and activities and psychic anxiety) and specific thresholds of change in each at 4 weeks predicted eventual outcome at 8 weeks to SSRI therapy with an average accuracy of 77% (p = 5.5E-08). The same four symptoms and prognostic thresholds derived from patients treated with SSRIs correctly predicted outcomes in 72% (p = 1.25E-05) of 1996 patients treated with other antidepressants in both inpatient and outpatient settings in independent publicly-available datasets. These predictive accuracies were higher than the accuracy of 53% for predicting SSRI response achieved using approaches that (i) incorporated only baseline clinical and sociodemographic factors, or (ii) used 4-week nonresponse status to predict likely outcomes at 8 weeks. The present findings suggest that PGMs providing interpretable predictions have the potential to enhance clinical treatment of depression and reduce the time burden associated with trials of ineffective antidepressants. Prospective trials examining this approach are forthcoming.
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http://dx.doi.org/10.1038/s41386-020-00943-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134509PMC
June 2021

Next-Step Treatment Considerations for Patients With Treatment-Resistant Depression That Responds to Low-Dose Intravenous Ketamine.

Focus (Am Psychiatr Publ) 2020 Apr 23;18(2):181-192. Epub 2020 Apr 23.

Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, Florida (Bobo); Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta (Riva-Posse); Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore (Goes); Department of Psychiatry, University of Michigan, Ann Arbor (Parikh).

Numerous short-term randomized trials support the acute-phase efficacy of low-dose intravenous (IV) ketamine for patients with treatment-resistant unipolar or bipolar depression. Ketamine's antidepressive effects generally have limited duration, highlighting the need for maintenance treatment after an acute-phase response. It is increasingly likely that psychiatrists will be called upon to manage the care of patients with treatment-resistant unipolar or bipolar depression who have responded acutely to ketamine and to recommend or initiate next-step treatments. However, there is a paucity of controlled evidence to guide best practices for managing treatment of patients with treatment-resistant unipolar or bipolar depression who have had a positive initial response to ketamine. This article reviews the available evidence supporting specific strategies for extending and maintaining acute antidepressive responses to low-dose IV ketamine in patients with treatment-resistant unipolar or bipolar depression and provides some preliminary considerations for clinical practice.
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http://dx.doi.org/10.1176/appi.focus.20190048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587874PMC
April 2020

Maternal Use of Specific Antidepressant Medications During Early Pregnancy and the Risk of Selected Birth Defects.

JAMA Psychiatry 2020 Dec;77(12):1246-1255

Division of Birth Defects and Infant Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.

Importance: Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks.

Objective: To examine associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions.

Design, Setting, And Participants: The population-based, multicenter case-control National Birth Defects Prevention Study (October 1997-December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects. Mothers of cases and controls participated in an interview after the expected delivery date. The data were analyzed after the completion of the National Birth Defects Prevent Study's data collection.

Exposures: Self-reported antidepressant exposure was coded to indicate monotherapy exposure to antidepressants.

Main Outcomes And Measures: We used multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals for associations between maternal antidepressant use and birth defects. We compared early pregnancy antidepressant-exposed women with those without antidepressant exposure and, to partially account for confounding by underlying maternal conditions, those exposed to antidepressants outside of the birth defect development critical period.

Results: This study included 30 630 case mothers of infants with birth defects and 11 478 control mothers (aged 12-53 years). Early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%), for whom elevated aORs were observed for individual selective serotonin reuptake inhibitors (SSRIs) and selected congenital heart defects (CHD) (eg, fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93; this association was attenuated after partially accounting for underlying conditions: aOR, 1.89; 95% CI, 0.56-6.42). This pattern was observed for many SSRI-CHD combinations. Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (eg, citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24). Venlafaxine had elevated associations with multiple defects that persisted after partially accounting for underlying conditions (eg, anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83).

Conclusions And Relevance: We found some associations between maternal antidepressant use and specific birth defects. Venlafaxine was associated with the highest number of defects, which needs confirmation given the limited literature on venlafaxine use during pregnancy and risk for birth defects. Our results suggest confounding by underlying conditions should be considered when assessing risk. Fully informed treatment decision-making requires balancing the risks and benefits of proposed interventions against those of untreated depression or anxiety.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407327PMC
December 2020

Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes.

J Affect Disord 2020 03 30;264:90-97. Epub 2019 Nov 30.

Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, United States; Department of Medicine, Duke University, Durham, NC, United States; Duke Institute of Brain Sciences, Duke University, Durham, NC, United States. Electronic address:

Background: Acylcarnitines have important functions in mitochondrial energetics and β-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profiles can help biochemically distinguish the three phenotypic subtypes of major depressive disorder (MDD): core depression (CD+), anxious depression (ANX+), and neurovegetative symptoms of melancholia (NVSM+).

Methods: Depressed outpatients (n = 240) from the Mayo Clinic Pharmacogenomics Research Network were treated with citalopram or escitalopram for eight weeks. Plasma samples collected at baseline and after eight weeks of treatment with citalopram or escitalopram were profiled for short-, medium- and long-chain acylcarnitine levels using AbsoluteIDQ®p180-Kit and LC-MS. Linear mixed effects models were used to examine whether acylcarnitine levels discriminated the clinical phenotypes at baseline or eight weeks post-treatment, and whether temporal changes in acylcarnitine profiles differed between groups.

Results: Compared to ANX+, CD+ and NVSM+ had significantly lower concentrations of short- and long-chain acylcarnitines at both baseline and week 8. In NVSM+, the medium- and long-chain acylcarnitines were also significantly lower in NVSM+ compared to ANX+. Short-chain acylcarnitine levels increased significantly from baseline to week 8 in CD+ and ANX+, whereas medium- and long-chain acylcarnitines significantly decreased in CD+ and NVSM+.

Conclusions: In depressed patients treated with SSRIs, β-oxidation and mitochondrial energetics as evaluated by levels and changes in acylcarnitines may provide the biochemical basis of the clinical heterogeneity of MDD, especially when combined with clinical characteristics.
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http://dx.doi.org/10.1016/j.jad.2019.11.122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024064PMC
March 2020

Atypical antipsychotic use during pregnancy and birth defect risk: National Birth Defects Prevention Study, 1997-2011.

Schizophr Res 2020 01 21;215:81-88. Epub 2019 Nov 21.

National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 4770 Buford Highway, MS S-106, Atlanta, GA 30341, USA.

Purpose: To examine the prevalence of, and factors associated with, atypical antipsychotic use among U.S. pregnant women, and potential associations between early pregnancy atypical antipsychotic use and risk for 14 birth defects.

Methods: We analyzed data from the National Birth Defects Prevention Study (1997-2011), a U.S. population-based case-control study examining risk factors for major structural birth defects.

Results: Atypical antipsychotic use during pregnancy was more common among women with pre-pregnancy obesity, and women who reported illicit drug use before and during pregnancy, smoking during pregnancy, alcohol use during pregnancy, or use of other psychiatric medications during pregnancy. We observed elevated associations (defined as a crude odds ratio [cOR] ≥2.0) between early pregnancy atypical antipsychotic use and conotruncal heart defects (6 exposed cases; cOR: 2.3, 95% confidence interval [CI]: 0.9-6.1), and more specifically Tetralogy of Fallot (3 exposed cases; cOR: 2.5, 95% CI: 0.7-8.8), cleft palate (4 exposed cases, cOR: 2.5, 95% CI: 0.8-7.6), anorectal atresia/stenosis (3 exposed cases, cOR: 2.8, 95% CI: 0.8-9.9), and gastroschisis (3 exposed cases, cOR: 2.1, 95% CI: 0.6-7.3).

Conclusions: Our findings support the close clinical monitoring of pregnant women using atypical antipsychotics. Women treated with atypical antipsychotics generally access healthcare services before pregnancy; efforts to reduce correlates of atypical antipsychotic use might improve maternal and infant health in this population.
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http://dx.doi.org/10.1016/j.schres.2019.11.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036025PMC
January 2020

Effects of a multidisciplinary quality of life intervention on sleep quality in patients with advanced cancer receiving radiation therapy.

Palliat Support Care 2020 06;18(3):307-313

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.

Objectives: Sleep disturbances are prevalent in cancer patients, especially those with advanced disease. There are few published intervention studies that address sleep issues in advanced cancer patients during the course of treatment. This study assesses the impact of a multidisciplinary quality of life (QOL) intervention on subjective sleep difficulties in patients with advanced cancer.

Method: This randomized trial investigated the comparative effects of a multidisciplinary QOL intervention (n = 54) vs. standard care (n = 63) on sleep quality in patients with advanced cancer receiving radiation therapy as a secondary endpoint. The intervention group attended six intervention sessions, while the standard care group received informational material only. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), administered at baseline and weeks 4 (post-intervention), 27, and 52.

Results: The intervention group had a statistically significant improvement in the PSQI total score and two components of sleep quality and daytime dysfunction than the control group at week 4. At week 27, although both groups showed improvements in sleep measures from baseline, there were no statistically significant differences between groups in any of the PSQI total and component scores, or ESS. At week 52, the intervention group used less sleep medication than control patients compared to baseline (p = 0.04) and had a lower ESS score (7.6 vs. 9.3, p = 0.03).

Significance Of Results: A multidisciplinary intervention to improve QOL can also improve sleep quality of advanced cancer patients undergoing radiation therapy. Those patients who completed the intervention also reported the use of less sleep medication.
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http://dx.doi.org/10.1017/S1478951519000750DOI Listing
June 2020

Association of Cytomegalovirus and Toxoplasma gondii Antibody Titers With Bipolar Disorder.

JAMA Psychiatry 2019 12;76(12):1285-1293

Stanley Laboratory of Developmental Neurovirology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Importance: Infection-associated immune activation and inflammation are increasingly recognized in the pathophysiology of bipolar disorder.

Objective: To determine whether antibodies to common infectious agents, including cytomegalovirus (CMV), Toxoplasma gondii, and measles, as well as the inflammatory marker C-reactive protein, in serum samples differ between patients with bipolar disorder and control individuals without bipolar disorder.

Design, Setting, And Participants: In this case-control study, antibody titers were measured in serum samples from 1207 patients with bipolar disorder and 745 controls that were obtained from biobanks with participating sites in Rochester and Minneapolis, Minnesota (n = 1537), and Cincinnati, Ohio (n = 415), from January 5, 2009, through May 12, 2014. A subset of case patients and controls from Minnesota were matched by age, sex, and educational level. Bipolar type, age at onset, and history of psychosis were assessed for case patients as well as current drug treatment at the time of blood sample obtainment from the biobank. Data were analyzed from February 5, 2018, to January 4, 2019.

Exposures: The CMV and T gondii antibodies with IgM titers were expressed as z scores and IgG titers dichotomized into seropositive and seronegative based on expected prevalence in the US population and further classified based on the joint CMV-positive/T gondii-negative IgG status, C-reactive protein z score, and drug treatments with antitoxoplasma activity.

Main Outcomes And Measures: Patients were stratified by bipolar disorder type I or type II, nonearly (>19 years of age) and early (≤19 years of age) onset, and history of psychosis during mania or no psychosis.

Results: Of 1207 patients with bipolar disorder (mean [SD] age, 43.2 [15.1] years; 742 [61.5%] female), the CMV-positive/T gondii-negative IgG status was significantly higher (odds ratio [OR], 1.33; 95% CI, 1.09-1.62; P = .004) compared with that in the 745 controls (mean [SD] age, 44.5 [15.5] years; 444 [59.6%] female). The CMV-positive/T gondii-negative IgG status was associated with bipolar cases type I (OR, 1.41; 95% CI, 1.14-1.75; P = .001), nonearly age at onset (OR, 1.41; 95% CI, 1.16-1.72; P = .001), and history of manic psychosis (OR, 1.46; 95% CI, 1.13-1.88; P = .004). Patients with bipolar disorder who received drug treatment with antitoxoplasma activity (n = 272) had significantly lower T gondii IgM titers (median, 1.59; interquartile range, 1.30-2.07) compared with those (n = 900) who did not receive this treatment (median, 1.69; interquartile range, 1.35-2.25) (P = .03).

Conclusions And Relevance: In this sample, increased long-term antibody response to CMV and decreased long-term antibody response to T gondii were associated with bipolar disorder and the subphenotypes of bipolar type I, nonearly disease onset, and manic psychosis. Further work appears to be needed to better understand genetic vs environmental disease risk and infection or immune activation contribution to overall disease pathogenesis with particular reference to disease onset.
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http://dx.doi.org/10.1001/jamapsychiatry.2019.2499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751798PMC
December 2019

Mental health conditions diagnosed before bilateral oophorectomy: a population-based case-control study.

Menopause 2019 12;26(12):1395-1404

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

Objective: We studied eight mental health conditions diagnosed before bilateral oophorectomy performed for nonmalignant indications.

Methods: We identified 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication in Olmsted County, Minnesota, during a 20-year period (1988-2007). Each woman was matched by age (±1 year) to one population-based control who had not undergone bilateral oophorectomy before the index date (age range: 21-49 years). Both cases and controls were identified using the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org). For eight mental health conditions, we calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) adjusted for race, education, and income using conditional logistic regression.

Results: Pre-existing mood disorders, anxiety disorders, and somatoform disorders were associated with increased risk of bilateral oophorectomy in overall analyses. These associations were also significant in women ≤45 years of age at index date. Personality disorders were associated with increased risk only in overall analyses and adjustment disorders only in women 46 to 49 years of age. Some of the associations were significantly different across strata by age at index date and by indication. There was also a linear trend of increasing adjusted ORs from 1.55 (95% CI 1.31-1.83) for one mental health condition to 2.19 (95% CI 1.40-3.41) for three or more conditions (trend P < 0.001).

Conclusions: We identified several mental health conditions that were associated with bilateral oophorectomy for nonmalignant indications. Awareness of these associations may guide women and physicians in future decision-making and limit unindicated bilateral oophorectomies. VIDEO SUMMARY:: http://links.lww.com/MENO/A458.
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http://dx.doi.org/10.1097/GME.0000000000001413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893116PMC
December 2019

Mental health conditions diagnosed before bilateral oophorectomy: a population-based case-control study.

Menopause 2019 12;26(12):1395-1404

Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN.

Objective: We studied eight mental health conditions diagnosed before bilateral oophorectomy performed for nonmalignant indications.

Methods: We identified 1,653 premenopausal women who underwent bilateral oophorectomy for a nonmalignant indication in Olmsted County, Minnesota, during a 20-year period (1988-2007). Each woman was matched by age (±1 year) to one population-based control who had not undergone bilateral oophorectomy before the index date (age range: 21-49 years). Both cases and controls were identified using the records-linkage system of the Rochester Epidemiology Project (REP http://www.rochesterproject.org). For eight mental health conditions, we calculated odds ratios (ORs) and their 95% confidence intervals (95% CIs) adjusted for race, education, and income using conditional logistic regression.

Results: Pre-existing mood disorders, anxiety disorders, and somatoform disorders were associated with increased risk of bilateral oophorectomy in overall analyses. These associations were also significant in women ≤45 years of age at index date. Personality disorders were associated with increased risk only in overall analyses and adjustment disorders only in women 46 to 49 years of age. Some of the associations were significantly different across strata by age at index date and by indication. There was also a linear trend of increasing adjusted ORs from 1.55 (95% CI 1.31-1.83) for one mental health condition to 2.19 (95% CI 1.40-3.41) for three or more conditions (trend P < 0.001).

Conclusions: We identified several mental health conditions that were associated with bilateral oophorectomy for nonmalignant indications. Awareness of these associations may guide women and physicians in future decision-making and limit unindicated bilateral oophorectomies. VIDEO SUMMARY:: http://links.lww.com/MENO/A458.
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http://dx.doi.org/10.1097/GME.0000000000001413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893116PMC
December 2019

Complex polypharmacy in bipolar disorder: Side effect burden, adherence, and response predictors.

J Affect Disord 2019 10 2;257:17-22. Epub 2019 Jul 2.

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.

Background: Complex polypharmacy (CP) is common in bipolar disorder (BD). We assessed the associations between CP, adherence, and side effect burden, and patient traits associated with clinical improvement in relationship to CP.

Methods: We conducted a secondary analysis of 482 adult BD participants in the Bipolar CHOICE trial. We examined the associations between CP (use of ≥3 BD medications) and non-adherence (missing >30% of BD medication doses in the last 30 days) and side effect burden (Frequency, Intensity and Burden of Side Effects Rating scale) using multivariate models with patient random effects. We used logistic regression to assess the patient traits associated with remission among those with majority CP use (Clinical Global Impression-Severity for BD score ≤2 for 8+ weeks).

Results: 43% of patients had any CP and 25% had CP for the majority of the study. CP was associated with non-adherence (OR = 2.51, 95% CI [1.81, 3.50]), but not worse side effect burden. Among those with CP, 16% achieved remission; those with non-adherence, comorbid social or generalized anxiety disorder, or BD I vs. II were less likely to achieve remission among those with CP.

Limitations: There could be unmeasured confounding between use of CP and side effect burden or adherence. Adherence was measured by self-report, which could be subject to reporting error.

Conclusions: BD patients with CP were less likely to adhere to therapy, and those with worse adherence to CP were less likely to clinically respond. Clinicians should assess medication adherence prior to adding another agent to medication regimens.
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http://dx.doi.org/10.1016/j.jad.2019.06.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6711795PMC
October 2019

Pharmacogenomics-Driven Prediction of Antidepressant Treatment Outcomes: A Machine-Learning Approach With Multi-trial Replication.

Clin Pharmacol Ther 2019 10 29;106(4):855-865. Epub 2019 Jun 29.

Department of Psychiatry & Psychology, Mayo Clinic, Jacksonville, Florida, USA.

We set out to determine whether machine learning-based algorithms that included functionally validated pharmacogenomic biomarkers joined with clinical measures could predict selective serotonin reuptake inhibitor (SSRI) remission/response in patients with major depressive disorder (MDD). We studied 1,030 white outpatients with MDD treated with citalopram/escitalopram in the Mayo Clinic Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS; n = 398), Sequenced Treatment Alternatives to Relieve Depression (STAR*D; n = 467), and International SSRI Pharmacogenomics Consortium (ISPC; n = 165) trials. A genomewide association study for PGRN-AMPS plasma metabolites associated with SSRI response (serotonin) and baseline MDD severity (kynurenine) identified single nucleotide polymorphisms (SNPs) in DEFB1, ERICH3, AHR, and TSPAN5 that we tested as predictors. Supervised machine-learning methods trained using SNPs and total baseline depression scores predicted remission and response at 8 weeks with area under the receiver operating curve (AUC) > 0.7 (P < 0.04) in PGRN-AMPS patients, with comparable prediction accuracies > 69% (P ≤ 0.07) in STAR*D and ISPC. These results demonstrate that machine learning can achieve accurate and, importantly, replicable prediction of SSRI therapy response using total baseline depression severity combined with pharmacogenomic biomarkers.
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http://dx.doi.org/10.1002/cpt.1482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739122PMC
October 2019

Cytochrome P450 2C19 Poor Metabolizer Phenotype in Treatment Resistant Depression: Treatment and Diagnostic Implications.

Front Pharmacol 2019 19;10:83. Epub 2019 Feb 19.

Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States.

Pharmacogenomic testing, specifically for pharmacokinetic (PK) and pharmacodynamic (PD) genetic variation, may contribute to a better understanding of baseline genetic differences in patients seeking treatment for depression, which may further impact clinical antidepressant treatment recommendations. This study evaluated PK and PD genetic variation and the clinical use of such testing in treatment seeking patients with bipolar disorder (BP) and major depressive disorder (MDD) and history of multiple drug failures/treatment resistance. Consecutive depressed patients evaluated at the Mayo Clinic Depression Center over a 10-year study time frame (2003-2013) were included in this retrospective analysis. Diagnoses of BP or MDD were confirmed using a semi-structured diagnostic interview. Clinical rating scales included the Hamilton Rating Scale for Depression (HRSD), Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Adverse Childhood Experiences (ACE) Questionnaire. Clinically selected patients underwent genotyping of cytochrome P450 / and the serotonin transporter . PK and PD differences and whether clinicians incorporated test results in providing recommendations were compared between the two patient groups. Of the 1795 patients, 167/523 (31.9%) with BP and 446/1272 (35.1%) with MDD were genotyped. Genotyped patients had significantly higher self-report measures of depression and anxiety compared to non-genotyped patients. There were significantly more poor metabolizer (PM) phenotypes in BP (9.3%) vs. MDD patients (1.7%, = 0.003); among participants with an S-allele, the rate of PM phenotype was even higher in the BP (9.8%) vs. MDD (0.6%, = 0.003). There was a significant difference in the distribution of genotypes between BP ( = 28.1%, = 59.3%, = 12.6%) and MDD ( = 31.4%, = 46.1%, = 22.7%) patients ( < 0.01). There may be underlying pharmacogenomic differences in treatment seeking depressed patients that potentially have impact on serum levels of metabolized antidepressants (i.e., citalopram / escitalopram) contributing to rates of efficacy vs. side effect burden with additional potential risk of antidepressant response vs. induced mania. The evidence for utilizing pharmacogenomics-guided therapy in MDD and BP is still developing with a much needed focus on drug safety, side effect burden, and treatment adherence.
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http://dx.doi.org/10.3389/fphar.2019.00083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389687PMC
February 2019

Frequency and predictors of the potential overprescribing of antidepressants in elderly residents of a geographically defined U.S. population.

Pharmacol Res Perspect 2019 02 23;7(1):e00461. Epub 2019 Jan 23.

Department of Psychiatry & Psychology Mayo Clinic Rochester Minnesota.

The purpose of this study was to estimate the extent of potential antidepressant overprescribing in a geographically defined U.S. population, and to determine the indications and factors that account for it. We conducted a cohort study of new antidepressant prescriptions for elderly residents of Olmsted County, Minnesota, 2005-2012, using the Rochester Epidemiology Project medical records-linkage system. Indications for antidepressants were abstracted from health records for all cohort members. Potential antidepressant overprescribing was defined based on regulatory approval, the level of evidence identified from a standardized drug information database, and multidisciplinary expert review. Predictors of potential antidepressant overprescribing were investigated using logistic regression models, stratified by general antidepressant indication (general medical indication, specific psychiatric diagnosis, and non-specific psychiatric symptoms). Potential antidepressant overprescribing occurred in 24% of 3199 incident antidepressant prescriptions during the study period, and involved primarily newer antidepressants that were prescribed for non-specific psychiatric symptoms and subthreshold diagnoses. Potential antidepressant overprescribing was associated with nursing home residence, having a higher number of comorbid medical conditions and outpatient prescribers, taking more concomitant medications, having greater use of urgent or acute care services in the year preceding the index antidepressant prescription, and being prescribed antidepressants via telephone, e-mail, or patient portal. In conclusion, potential antidepressant overprescribing occurred in elderly persons and involved mainly newer antidepressants used for non-specific psychiatric symptoms and subthreshold diagnoses, and was associated with indicators of higher clinical complexity or severity and with prescribing without face-to-face patient contact.
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http://dx.doi.org/10.1002/prp2.461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6344796PMC
February 2019

The association of obesity and coronary artery disease genes with response to SSRIs treatment in major depression.

J Neural Transm (Vienna) 2019 01 4;126(1):35-45. Epub 2019 Jan 4.

Research Division Federal Institute for Drugs and Medical Devices, Bonn, Germany.

Selective serotonin reuptake inhibitors (SSRIs) are first-line antidepressants for the treatment of major depressive disorder (MDD). However, treatment response during an initial therapeutic trial is often poor and is difficult to predict. Heterogeneity of response to SSRIs in depressed patients is partly driven by co-occurring somatic disorders such as coronary artery disease (CAD) and obesity. CAD and obesity may also be associated with metabolic side effects of SSRIs. In this study, we assessed the association of CAD and obesity with treatment response to SSRIs in patients with MDD using a polygenic score (PGS) approach. Additionally, we performed cross-trait meta-analyses to pinpoint genetic variants underpinnings the relationship of CAD and obesity with SSRIs treatment response. First, PGSs were calculated at different p value thresholds (P) for obesity and CAD. Next, binary logistic regression was applied to evaluate the association of the PGSs to SSRIs treatment response in a discovery sample (ISPC, N = 865), and in a replication cohort (STAR*D, N = 1,878). Finally, a cross-trait GWAS meta-analysis was performed by combining summary statistics. We show that the PGSs for CAD and obesity were inversely associated with SSRIs treatment response. At the most significant thresholds, the PGS for CAD and body mass index accounted 1.3%, and 0.8% of the observed variability in treatment response to SSRIs, respectively. In the cross-trait meta-analyses, we identified (1) 14 genetic loci (including NEGR1, CADM2, PMAIP1, PARK2) that are associated with both obesity and SSRIs treatment response; (2) five genetic loci (LINC01412, PHACTR1, CDKN2B, ATXN2, KCNE2) with effects on CAD and SSRIs treatment response. Our findings implicate that the genetic variants of CAD and obesity are linked to SSRIs treatment response in MDD. A better SSRIs treatment response might be achieved through a stratified allocation of treatment for MDD patients with a genetic risk for obesity or CAD.
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http://dx.doi.org/10.1007/s00702-018-01966-xDOI Listing
January 2019

Comorbid anxiety in bipolar CHOICE: Insights from the bipolar inventory of symptoms scale.

J Affect Disord 2019 03 18;246:126-131. Epub 2018 Dec 18.

Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Background: Approximately 86-89% of patients with BD have a comorbid anxiety disorder associated with poor quality of life and reduced likelihood of recovery from an acute mood episode. The purpose of this study is to assess the prevalence and impact of comorbid anxiety using the Bipolar Inventory of Symptoms Scale (BISS) in patients with BD who participated in a 6-month pragmatic trial.

Methods: Participants (N = 482) in the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE) study were adults with BD I or II. Anxiety diagnoses were assessed with the MINI. Global illness severity was assessed using the Clinical Global Impression-Bipolar Version. Mood symptoms and anxiety severity were assessed using the BISS.

Results: 61% of the study sample met criteria for a current anxiety disorder. Patients with a higher BISS anxiety score at baseline had a higher overall BD illness severity, depressive severity, and manic episode severity (p < 0.001). A single cutoff value of BISS anxiety had great sensitivity, yet poor specificity for determining a comorbid anxiety diagnosis. There were no significant differences in outcomes for individuals treated for anxiety disorders with anxiolytics compared with those who were not treated with anxiolytics.

Limitations: Sample size limitations prevented an analysis of whether the BISS cutoff score of 10 performed differently across varied anxiety disorders.

Conclusions: Given its ability to identify patients with co-occurring anxiety, the BISS anxiety subscale shows clinical utility as a screening measure though its application as a clinical assessment measure may not be advisable.
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http://dx.doi.org/10.1016/j.jad.2018.12.039DOI Listing
March 2019

Pharmacokinetic-Pharmacodynamic interaction associated with venlafaxine-XR remission in patients with major depressive disorder with history of citalopram / escitalopram treatment failure.

J Affect Disord 2019 03 17;246:62-68. Epub 2018 Dec 17.

Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, United States. Electronic address:

Background: The purpose of this study was to identify specific pharmacokinetic (PK) and pharmacodynamics (PD) factors that affect the likelihood of treatment remission with a serotonin norepinephrine reuptake inhibitor (SNRI) in depressed patients whose initial selective serotonin reuptake inhibitor (SSRI) failed.

Methods: Multiple logistic regression modeling of PK and PD variation hypothesized to contribute to SNRI (i.e. duloxetine or venlafaxine) treatment remission in prior SSRI (i.e. citalopram or escitalopram) failure was conducted on 139 subjects from the Pharmacogenomics Research Network (PGRN) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies. Depressive symptoms were assessed with the Quick Inventory of Depressive Symptomatology Clinician-rated (QIDS-C).

Results: Venlafaxine-XR remission was associated with a significant interaction between CYP2D6 ultra-rapid metabolizer (URM) phenotype and SLC6A4 5-HTTLPR L/L genotype. A similar significant interaction effect was observed between CYP2D6 URM and SLC6A2 G1287A GA genotype. Stratifying by transporter genotypes, venlafaxine-XR remission was associated with CYP2D6 URM in patients with SLC6A4 L/L (p = 0.001) and SLC6A2 G1287A GA genotypes.

Limitations: The primary limitation of this post hoc study was small sample size.

Conclusion: Our results suggest that CYP2D6 ultra-rapid metabolizer status contributes to venlafaxine-XR treatment remission in MDD patients; in particular, there is a PK-PD interaction with treatment remission associated with CYP2D6 URM phenotype and SLC6A4 5-HTTLPR L/L or SLC6A2 G1287A G/A genotype, respectively. These preliminary data are encouraging and support larger pharmacogenomics studies differentiating treatment response to mechanistically different antidepressants in addition to further PK-PD interactive analyses.
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http://dx.doi.org/10.1016/j.jad.2018.12.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501809PMC
March 2019

Sex-specific effects of gain-of-function P2RX7 variation on bipolar disorder.

J Affect Disord 2019 02 3;245:597-601. Epub 2018 Nov 3.

Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.

Background: Patients with bipolar disorder demonstrate sex differences in clinical presentation, particularly in the sub-phenotypes related to periodicity of mood episodes, such as rapid cycling. Additionally, recent studies have linked P2RX7 gene variants with the risk of rapid cycling in clinical cohorts of patients with bipolar disorder, as well as other mood disorders. However, little is known about potential sex differences in the relationship between variants in P2RX7 and bipolar disorder.

Methods: We investigated sex-specific genetic associations between variants of P2RX7 (rs1621388 and rs2230912) in 756 patients with bipolar disorder and 787 control patients matched on age, sex, and ancestry. We examined sex-specific genetic associations with bipolar disorder by comparing cases and controls, as well as rapid cycling of mood episodes in cases. Findings were replicated in an independent dataset.

Results: P2RX7 variants implying an increased pore activity were more common in bipolar disorder, in females but not in males. Neither P2RX7 variants associated with rapid cycling among bipolar patients.

Limitations: Low sample size limited power for tests of SNP by sex interaction, and data about the onset of rapid cycling and the timing of medication use were not available.

Conclusion: The effects of P2RX7 variants on bipolar disorder may be sex-specific, with increased P2X7 activity potentially elevating risk for bipolar disorder in females. Future research to examine the effect of P2RX7 on bipolar disorder should consider sex-specific effects.
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http://dx.doi.org/10.1016/j.jad.2018.11.007DOI Listing
February 2019

Patterns of changes in bipolar depressive symptoms revealed by trajectory analysis among 482 patients with bipolar disorder.

Bipolar Disord 2019 06 1;21(4):350-360. Epub 2018 Dec 1.

Dauten Family Center for Bipolar Treatment Innovation, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts.

Introduction: Depressive episodes are often prevalent among patients with bipolar disorder, but little is known regarding the differential patterns of development over time. We aimed to determine and characterize trajectories of depressive symptoms among adults with bipolar disorder during 6 months of systematic treatment.

Methods: The pragmatic clinical trial, Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE), randomized 482 outpatients with bipolar disorder to lithium or quetiapine. Depressive symptoms were rated at up to 9 visits using the Montgomery-Asberg Depression Rating Scale (MADRS). Growth mixture modeling was utilized to identify trajectories and multinomial regression analysis estimated associations with potential predictors.

Results: Four distinct trajectories of depressive symptoms were identified. The responding class (60.3%) with a rapid reduction and subsequent low level; the partial-responding class (18.4%) with an initial reduction followed by an increase during the remaining weeks; the fluctuating class (11.6%) with a fluctuation in depressive symptoms; and the non-responding class (9.7%) with sustained moderate-severe depressive symptoms. Bipolar type I predicted membership of the non-responding class and randomization to quetiapine predicted membership of either the responding or the non-responding class.

Conclusion: Approximately 30% experienced a partial or fluctuating course, and almost 10% had a chronic course with moderate-severe depression during 6 months. Patients diagnosed with bipolar type 1 had higher risk of being categorized into a class with a worse outcome. While no differences in average overall outcomes occurred between the lithium and quetiapine groups, trajectory analysis revealed that the lithium group had more variable courses.
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http://dx.doi.org/10.1111/bdi.12715DOI Listing
June 2019

The impact of binge eating behavior on lithium- and quetiapine-associated changes in body weight, body mass index, and waist circumference during 6 months of treatment: Findings from the bipolar CHOICE study.

J Affect Disord 2020 04 12;266:772-781. Epub 2018 Sep 12.

Department of Psychiatry & Psychology, Mayo Clinic, Jacksonville, FL USA. Electronic address:

Background: Lithium and quetiapine can cause weight gain, but their comparative longer term anthropometric effects are unknown, as are the potential moderating effects of baseline binge-eating (BE) behavior.

Methods: We assessed 6 month changes in body weight, body mass index (BMI) and waist circumference in 482 adults with DSM-IV bipolar disorders who participated in a comparative effectiveness study of lithium and quetiapine with evidence-based adjunctive treatment (Bipolar CHOICE). Anthropometric measurements were obtained at baseline, and at 2, 4, 6, 8, 12, 16, 20, and 24 weeks. BE behavior was defined as affirmative responses to MINI items M1 and M3 at baseline. Data were analyzed using a mixed model repeated measures approach, adjusted for baseline values of dependent measures.

Results: On average, body weight and BMI increased over 6 months with lithium and quetiapine. However, those treated with quetiapine experienced greater increases from baseline in body weight (peak change, + 3.6 lbs. vs. + 1.4 lbs.) and BMI (peak change, + 0.6 kg/m vs. + 0.3 kg/m), starting at 2 weeks (group x time, F= 2.9, p = 0.003 for body weight, F= 3.0, p = 0.002 for BMI). Significant increases in waist circumference were observed only with quetiapine. The relationship between drug treatment and changes in body weight (group x time x binge eating status, F= 2.0, p = 0.002), BMI (F= 2.0, p = 0.002), and waist circumference (women only, F= 2.9, p < 0.0001) were moderated by BE behavior. The largest increases over 24 weeks in body weight and BMI, and waist circumference in women, occurred for quetiapine-treated patients with baseline binge-eating, relative to quetiapine-treated patients without binge eating and lithium-treated patients with or without baseline binge-eating.

Limitations: Bipolar CHOICE was not designed to study anthropometric outcomes.

Conclusions: Greater changes in body weight, BMI, and waist circumference occurred with quetiapine- versus lithium-based treatment over 6 months of treatment. The effects of study drugs on these anthropometric measures were moderated by BE behavior at baseline.
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http://dx.doi.org/10.1016/j.jad.2018.09.025DOI Listing
April 2020

Association of schizophrenia polygenic risk score with manic and depressive psychosis in bipolar disorder.

Transl Psychiatry 2018 09 10;8(1):188. Epub 2018 Sep 10.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.

Bipolar disorder (BD) is highly heterogeneous in symptomatology. Narrowing the clinical phenotype may increase the power to identify risk genes that contribute to particular BD subtypes. This study was designed to test the hypothesis that genetic overlap between schizophrenia (SZ) and BD is higher for BD with a history of manic psychosis. Analyses were conducted using a Mayo Clinic Bipolar Biobank cohort of 957 bipolar cases (including 333 with history of psychosis during mania, 64 with history of psychosis only during depression, 547 with no history of psychosis, and 13 with unknown history of psychosis) and 778 controls. Polygenic risk score (PRS) analysis was performed by calculating a SZ-PRS for the BD cases and controls, and comparing the calculated SZ risk between different psychosis subgroups and bipolar types. The SZ-PRS was significantly higher for BD-I cases with manic psychosis than BD-I cases with depressive psychosis (Nagelkerke's R = 0.021; p = 0.045), BD-I cases without psychosis (R = 0.015; p = 0.007), BD-II cases without psychosis (R = 0.014; p = 0.017), and controls (R = 0.065; p = 2 × 10). No other significant differences were found. Our results show that BD-I with manic psychosis is genetically more similar to SZ than any other tested BD subgroup. Further investigations on genetics of distinct clinical phenotypes composing major psychoses may help refine the current diagnostic classification system.
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http://dx.doi.org/10.1038/s41398-018-0242-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131184PMC
September 2018

Guidelines for the Evaluation and Treatment of Perimenopausal Depression: Summary and Recommendations.

J Womens Health (Larchmt) 2019 02 5;28(2):117-134. Epub 2018 Sep 5.

11 Department of Psychiatry, Queen's University School of Medicine, Ontario Canada.

There is a new appreciation of the perimenopause-defined as the early and late menopause transition stages as well as the early postmenopause-as a window of vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: (1) epidemiology; (2) clinical presentation; (3) therapeutic effects of antidepressants; (4) effects of hormone therapy; and (5) efficacy of other therapies (e.g., psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (i.e., vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (i.e., antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.
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http://dx.doi.org/10.1089/jwh.2018.27099.mensocrecDOI Listing
February 2019

Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations.

Menopause 2018 10;25(10):1069-1085

Department of Psychiatry, Queen's University School of Medicine, Ontario CA.

There is a new appreciation of the perimenopause - defined as the early and late menopause transition stages as well as the early postmenopause - as a window of vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: 1) epidemiology; 2) clinical presentation; 3) therapeutic effects of antidepressants; 4) effects of hormone therapy; and 5) efficacy of other therapies (eg, psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (ie, vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (ie, antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.
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http://dx.doi.org/10.1097/GME.0000000000001174DOI Listing
October 2018
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