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Carol Franz

University of California, San Diego, Psychiatry, Faculty Member

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Papers by Carol Franz

Do Patient Requests for Antidepressants Enhance or Hinder Physicians’ Evaluation of Depression?

Medical Care, Dec 1, 2006

Objective: We sought to ascertain whether patients' requests for antidepressants affect visit dur... more Objective: We sought to ascertain whether patients' requests for antidepressants affect visit duration or history taking by primary care physicians (PCPs) for patients with depressive symptoms and a coexisting musculoskeletal disorder and to determine whether more thorough history taking is associated with diagnostic accuracy or with provision of minimally acceptable initial care for major depression. Design: This was a randomized trial using standardized patients (SPs). Six roles involved 2 conditions (major depression and adjustment disorder, both with coexisting musculoskeletal conditions) and 3 patient request types (brand-specific, general, or none). We conducted the study in 152 PCP offices in Northern California and Rochester, New York. Physicians were assigned randomly to see 2 SPs with depression/wrist pain or adjustment disorder/back pain. Main Outcome Measures: Physician history-taking for depression and the musculoskeletal condition; depression diagnosis in the medical record; antidepressant prescriptions/samples; referral/follow-up recommendations; visit duration; and provision of minimally acceptable initial depression care. Results: General antidepressant requests were associated with more depression history-taking (Adjusted Parameter Estimate ϭ 0.80 more questions of 10 (95% confidence interval ϭ 0.31-1.29, P Ͻ 0.001); brand-specific requests were marginally associated with more depression history-taking (Adjusted Parameter Estimate ϭ 0.45, 95% confidence interval ϭ Ϫ0.04-0.93, P ϭ 0.07). Antide-pressant medication requests were not related to musculo-skeletal question asking (P Ͼ 0.3) or visit length (P Ͼ 0.8). Depression history taking was directly associated with the likelihood of a chart diagnosis of depression and the provision of minimally acceptable initial depression care. Conclusion: General antidepressant requests increase depression history taking, including screening for suicide. Patients' requests for medication do not appear to short-circuit history taking for depression or distract the physician's attention from coexisting musculoskeletal conditions.

format_quotePatient requests for antidepressants increased depression history taking, yet did not shorten visit duration or significantly alter musculoskeletal assessments.format_quote

The CODATwins Project: The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits

Twin Research and Human Genetics, May 27, 2015

Direct-to-consumer advertising and physician prescribing [2] (multiple letters)

Direct-to-Consumer Advertising and Physician Prescribing--Reply

JAMA, Aug 10, 2005

Erratum to: Genetic and Environmental Contributions to the Relationships Between Brain Structure and Average Lifetime Cigarette Use

Behavior Genetics, Apr 26, 2016

The original publication of the article has errors that need to be corrected as follows: 1. In th... more

Genetic and Environmental Contributions to the Relationships Between Brain Structure and Average Lifetime Cigarette Use

Behavior Genetics, Feb 18, 2015

Chronic cigarette use has been consistently associated with differences in the neuroanatomy of sm... more Chronic cigarette use has been consistently associated with differences in the neuroanatomy of smokers relative to nonsmokers in case-control studies. However, the etiology underlying the relationships between brain structure and cigarette use is unclear. A community-based sample of male twin pairs ages 51-59 (110 monozygotic pairs, 92 dizygotic pairs) was used to determine the

Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

eLife, Dec 14, 2016

Human height variation is determined by genetic and environmental factors, but it remains unclear... more Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.

Association of current and former smoking with body mass index: A study of smoking discordant twin pairs from 21 twin cohorts

PLOS ONE, Jul 12, 2018

Data Availability Statement: The data used in this study is owned by the third parties (the indiv... more Data Availability Statement: The data used in this study is owned by the third parties (the individual twin cohorts) and made available to us in condition that they will be used only in this meta-analysis. For this reason, we do not have legal rights to redeliver the data or to provide it to other third parties without permissions from the data owners. In order to replicate the results, each researcher need to apply the data set from each individual twin cohort owners and to harmonize the data as a metafile. Contact information for all the 21 Twin Cohorts where the requests to use the data can be

Parent Expectations for Antibiotics, Physician-Parent Communication, and Satisfaction

Archives of pediatrics & adolescent medicine, Jul 1, 2001

To explore how parents communicate their preferences for antibiotics to their child's physician a... more To explore how parents communicate their preferences for antibiotics to their child's physician and to examine whether physicians can communicate why antibiotics are not being prescribed in a way that maintains satisfaction with the visit. Design: Previsit survey of parents, audiotaping of the study encounters, and a postvisit survey of parents and physicians. Setting: Two private pediatric practices. Participants: Ten physicians (response rate = 77%) and a consecutive sample of 295 eligible parents (response rate = 86%) who attended acute care visits for their children between October 1996 and March 1997. Main Outcome Measures: Physician-perceived pressure to prescribe antibiotics and parental visit-specific satisfaction. Results: Fifty percent of parents expressed a previsit expectation for antibiotics. Among these parents, only 1% made a direct verbal request for them. Even when no direct requests for antibiotics were made, physicians still perceived an expectation for antibiotics 34% of the time. Among parents who did not receive expected antibiotics, those offered a contingency plan from the physician (ie, the possibility of receiving antibiotics in the future if their child did not get better) had a higher mean satisfaction score than parents not receiving a contingency plan (76 vs 58.9; PϽ.05). Conclusion: Physicians should consider providing a contingency plan to parents who expect antibiotics for their children when there is no clinical indication. Further study is needed to determine how parents indirectly communicate their desire for antibiotics and what additional communication techniques physicians can use to resist the overprescribing of antibiotics.

Conceptions of Dementia in a Multiethnic Sample of Family Caregivers

Journal of the American Geriatrics Society, Aug 1, 2005

Understanding variability in conceptions of dementia in multiethnic populations is important to i... more Understanding variability in conceptions of dementia in multiethnic populations is important to improve care and guide research. The objectives of this study were to describe caregiver conceptions of dementia using a previously developed typology and to examine the correlates of conceptions of dementia in a multiethnic sample. This is a cross-sectional study conducted in Boston and the San Francisco Bay area. Participants were a convenience sample of 92 family dementia caregivers from four ethnic/racial groups: African-American, Anglo European-American, Asian-American, and Latino. In-depth, qualitative interviews explored the caregivers' ideas about the nature and cause of dementia (i.e., explanatory models). Explanatory models of caregivers were categorized as biomedical, folk, or mixed (folk/biomedical). Quantitative analyses examined the association between ethnicity and other caregiver characteristics, and explanatory model type. Overall, 54% of caregivers, including 41% of Anglo European Americans, held explanatory models that combined folk and biomedical elements (i.e., mixed models). For example, many families attributed Alzheimer's disease and related dementias to psychosocial stress or normal aging. Ethnicity, lower education, and sex were associated with explanatory model type in bivariate analyses. In multiple logistic regression analysis, minority caregivers (Po.02) and those with less formal education (Po.02) were more likely to hold mixed or folk models of dementia. Although minority and nonminority caregivers often incorporated folk models into their understanding of dementia, this was more common in minority caregivers and those with less formal education. Further research on cross-ethnic differences in a larger, more-representative sample is needed.

Hierarchical Genetic Organization of Human Cortical Surface Area

Science, Mar 30, 2012

Surface area of the cerebral cortex is a highly heritable trait, yet little is known about geneti... more Surface area of the cerebral cortex is a highly heritable trait, yet little is known about genetic influences on regional cortical differentiation in humans. Using a data-driven, fuzzy clustering technique with magnetic resonance imaging data from 406 twins, we parceled cortical surface area into genetic subdivisions, creating a human brain atlas based solely on genetically informative data. Boundaries of the genetic divisions corresponded largely to meaningful structural and functional regions; however, the divisions represented previously undescribed phenotypes different from conventional (non-genetically based) parcellation systems. The genetic organization of cortical area was hierarchical, modular, and predominantly bilaterally symmetric across hemispheres. We also found that the results were consistent with human-specific regions being subdivisions of previously described, genetically based lobar regionalization patterns.

Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education

Scientific Reports, May 14, 2020

Genetic factors explain a major proportion of human height variation, but differences in mean sta... more Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socioeconomic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregatelevel data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis. Since the late 19 th and early 20 th centuries 1-3 , family, twin and adoption studies have revealed that stature is among the most heritable quantitative traits in humans 4. Genetic linkage studies have elucidated the location of genetic markers in the genome 5 and genome-wide association (GWA) studies identified hundreds of loci related to height in different ancestry populations 6-10. On the other hand, numerous environmental factors in childhood are known to affect growth; disadvantageous environmental conditions may decline the physical growth of open

format_quoteMeta-regression analysis revealed significant differences in environmental variance components between middle and low parental education categories in height.format_quote

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins

Twin Research and Human Genetics, Jul 31, 2019

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) projec... more The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m 2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across culturalgeographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Genetic and environmental variation in educational attainment: an individual-based analysis of 28 twin cohorts

Scientific Reports, Jul 29, 2020

We investigated the heritability of educational attainment and how it differed between birth coho... more We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural-geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a 2 = 0.43; 0.41-0.44), but also environmental variation shared by co-twins was substantial (c 2 = 0.31; 0.30-0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900-1949 (a 2 = 0.44; 0.41-0.46) than in the later cohorts born in 1950-1989 (a 2 = 0.38; 0.36-0.40), with a corresponding lower influence of common environmental factors (c 2 = 0.31; 0.29-0.33 and c 2 = 0.34; 0.32-0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.

$Research paper thumbnail of Heritability of white matter microstructure in late middle age: A twin study of tract-based fractional anisotropy and absolute diffusivity indices$

Heritability of white matter microstructure in late middle age: A twin study of tract-based fractional anisotropy and absolute diffusivity indices

Human Brain Mapping, Dec 29, 2016

There is evidence that differences among individuals in white matter microstructure, as measured ... more There is evidence that differences among individuals in white matter microstructure, as measured with diffusion tensor imaging (DTI), are under genetic control. However, little is known about the relative contribution of genetic and environmental effects on different diffusivity indices among late middle‐aged adults. Here, we examined the magnitude of genetic influences for fractional anisotropy (FA), and mean (MD), axial (AD), and radial (RD) diffusivities in male twins aged 56–66 years old. Using an atlas‐based registration approach to delineate individual white matter tracts, we investigated mean DTI‐based indices within the corpus callosum, 12 bilateral tracts and all these regions of interest combined. All four diffusivity indices had high heritability at the global level (72%–80%). The magnitude of genetic effects in individual tracts varied from 0% to 82% for FA, 0% to 81% for MD, 8% to 77% for AD, and 0% to 80% for RD with most of the tracts showing significant heritability estimates. Despite the narrow age range of this community‐based sample, age was correlated with all four diffusivity indices at the global level. In sum, all diffusion indices proved to have substantial heritability for most of the tracts and the heritability estimates were similar in magnitude for different diffusivity measures. Future studies could aim to discover the particular set of genes that underlie the significant heritability of white matter microstructure. Hum Brain Mapp 38:2026–2036, 2017. © 2017 Wiley Periodicals, Inc.

format_quoteAdditive genetic effects explain 80% of the variance in all-fiber tract FA, suggesting significant heritability across brain regions.format_quote

What drives referral from primary care physicians to mental health specialists? A randomized trial using actors portraying depressive symptoms

Journal of General Internal Medicine, Jun 1, 2006

BACKGROUND: Referral from primary care to the mental health specialty sector is important but poo... more BACKGROUND: Referral from primary care to the mental health specialty sector is important but poorly understood. OBJECTIVE: Identify physician characteristics influencing mental health referral. DESIGN: Randomized controlled trial using Standardized Patients (SPs). SETTING: Offices of primary care physicians in 3 cities. PARTICIPANTS: One hundred fifty-two family physicians and general internists recruited from 4 broad practice settings; 18 middle aged Caucasian female actors. INTERVENTION: Two hundred and ninety-eight unannounced SP visits, with assignments constrained so physicians saw 1 SP with major depression and 1 with adjustment disorder. MEASUREMENTS: Mental health referrals via SP written reports; physician and system characteristics through a self-administered physician questionnaire. RESULTS: Among 298 SP visits, 107 (36%) resulted in mental health referral. Referrals were less likely among physicians with greater selfconfidence in their ability to manage antidepressant therapy (adjusted odds ratio [AOR] 0.39, 95% confidence interval [CI] 0.17 to 0.86) and were more likely if physicians typically spent X10% of professional time on nonclinical activities (AOR 3.42, 95% CI 1.45 to 8.07), had personal life experience with psychotherapy for depression (AOR 2.74, 95% CI 1.15 to 6.52), or usually had access to mental health consultation within 2 weeks (AOR 2.94, 95% CI 1.26 to 6.92). LIMITATION: The roles portrayed by SPs may not reflect the experience of a typical panel of primary care patients. CONCLUSIONS: Controlling for patient and health system factors, physicians' therapeutic confidence and personal experience were important influences on mental health referral. Research is needed to determine if addressing these factors can facilitate more appropriate care.

Presence of ApoE ε4 Allele Associated with Thinner Frontal Cortex in Middle Age

Journal of Alzheimer's Disease, Oct 4, 2011

The presence of an ApoE ε4 allele (ε4+) increases the risk of developing Alzheimer's disease (AD)... more The presence of an ApoE ε4 allele (ε4+) increases the risk of developing Alzheimer's disease (AD). Previous studies support an adverse relationship between ε4+ status and brain structure and function in mild cognitive impairment and AD; in contrast, the presence of an ε2 allele may be protective. Whether these findings reflect disease-related effects or pre-existing endophenotypes, however, remains unclear. The present study examined the influence of ApoE allele status on brain structure solely during middle-age in a large, national sample. Participants were 482 men, ages 51-59, from the Vietnam Era Twin Study of Aging (VETSA). T1-weighted images were used in volumetric segmentation and cortical surface reconstruction methods to measure regional volume and thickness. Primary linear mixed effects models predicted structural measures with ApoE status (ε3/3, ε2/3, ε3/4) and control variables for effects of site, non-independence of twin data, age, and average cranial vault or cortical thickness. Relative to the ε3/3 group, the ε3/4 group demonstrated significantly thinner cortex in superior frontal and left rostral and right caudal midfrontal regions; there were no significant effects of ε4 status on any temporal lobe measures.

format_quoteContinuous cortical surface maps indicate broader thinning in frontal and thicker fusiform regions among ε4+ carriers compared to non-carriers.format_quote

Differences in genetic and environmental variation in adult BMI by sex, age, time period, and region: an individual-based pooled analysis of 40 twin cohorts

The American Journal of Clinical Nutrition, Aug 1, 2017

Background: Genes and the environment contribute to variation in adult body mass index [BMI (in k... more Background: Genes and the environment contribute to variation in adult body mass index [BMI (in kg/m 2)], but factors modifying these variance components are poorly understood. Objective: We analyzed genetic and environmental variation in BMI between men and women from young adulthood to old age from the 1940s to the 2000s and between cultural-geographic regions representing high (North America and Australia), moderate (Europe), and low (East Asia) prevalence of obesity. Design: We used genetic structural equation modeling to analyze BMI in twins $20 y of age from 40 cohorts representing 20 countries (140,379 complete twin pairs). Results: The heritability of BMI decreased from 0.77 (95% CI: 0.77, 0.78) and 0.75 (95% CI: 0.74, 0.75) in men and women 20-29 y of age to 0.57 (95% CI: 0.54, 0.60) and 0.59 (95% CI: 0.53, 0.65) in men 70-79 y of age and women 80 y of age, respectively. The relative influence of unique environmental factors correspondingly increased. Differences in the sets of genes affecting BMI in men and women increased from 20-29 to 60-69 y of age. Mean BMI and variances in BMI increased from the 1940s to the 2000s and were greatest in North America and Australia, followed by Europe and East Asia. However, heritability estimates were largely similar over measurement years and between regions. There was no evidence of environmental factors shared by co-twins affecting BMI. Conclusions: The heritability of BMI decreased and differences in the sets of genes affecting BMI in men and women increased from young adulthood to old age. The heritability of BMI was largely similar between cultural-geographic regions and measurement years, despite large differences in mean BMI and variances in BMI. Our results show a strong influence of genetic factors on BMI, especially in early adulthood, regardless of the obesity level in the population.

format_quoteHeritability of BMI decreased from young adulthood to old age, while differences in genetic sets between men and women expanded.format_quote

What Drives Referral from Primary Care Physicians to Mental Health Specialists

BACKGROUND: Referral from primary care to the mental health specialty sector is important but poo... more BACKGROUND: Referral from primary care to the mental health specialty sector is important but poorly understood. OBJECTIVE: Identify physician characteristics influencing mental health referral. DESIGN: Randomized controlled trial using Standardized Patients (SPs). SETTING: Offices of primary care physicians in 3 cities. PARTICIPANTS: One hundred fifty-two family physicians and general internists recruited from 4 broad practice settings; 18 middle aged Caucasian female actors. INTERVENTION: Two hundred and ninety-eight unannounced SP visits, with assignments constrained so physicians saw 1 SP with major depression and 1 with adjustment disorder. MEASUREMENTS: Mental health referrals via SP written reports; physician and system characteristics through a self-administered physician questionnaire. RESULTS: Among 298 SP visits, 107 (36%) resulted in mental health referral. Referrals were less likely among physicians with greater selfconfidence in their ability to manage antidepressant therapy (adjusted odds ratio [AOR] 0.39, 95% confidence interval [CI] 0.17 to 0.86) and were more likely if physicians typically spent X10% of professional time on nonclinical activities (AOR 3.42, 95% CI 1.45 to 8.07), had personal life experience with psychotherapy for depression (AOR 2.74, 95% CI 1.15 to 6.52), or usually had access to mental health consultation within 2 weeks (AOR 2.94, 95% CI 1.26 to 6.92). LIMITATION: The roles portrayed by SPs may not reflect the experience of a typical panel of primary care patients. CONCLUSIONS: Controlling for patient and health system factors, physicians' therapeutic confidence and personal experience were important influences on mental health referral. Research is needed to determine if addressing these factors can facilitate more appropriate care.

Evidence of Overlapping Genetic Diathesis of Panic Attacks and Gastrointestinal Disorders in a Sample of Male Twin Pairs

Twin Research and Human Genetics, Feb 1, 2011