Transcript Treating The Whole Person: Pediatric Polycystic Ovary

Rethinking obesity interventions:
Polycystic Ovary Syndrome as a
Model Physical Illness
Dana L Rofey PhD
University of Pittsburgh
Department of Psychiatry, Pediatrics, and Psychology
Obesity Journal Club
February 26, 2015
Western Psychiatric
Institute & Clinic
Overview

Brief background and rationale

Results of past and current studies

Future directions

Clinical implications
Definition of obesity
CDC
BMI
%ile
Underweight
< 5th
Healthy
5th-85th
At Risk for
Overweight
85th=95th
>95th
Obese
International
Obesity Task
Force
WHO
BMI
BMI
<18.5
>2 SDs above the growth standard
median
18.5 – 24.9
25.0 – 29.9
30.0 and Above
>1 SD above the growth standard
median
>2 SDs above the growth standard
median
Defining PCOS
Diagnostic complexity of Polycystic Ovary Syndrome
NIH 1990
-
Chronic
anovulation
Clinical and/or
biochemical signs
of
Rotterdam 2003
-
hyperandrogenism
-
(with exclusion of other etiologies,
e.g., congenital
adrenal
hyperplasia)
Both criteria
needed
Oligo- and/or
anovulation
Clinical and/or
biochemical signs
of
AE-PCOS Society 2006
-
Clinical and/or
biochemical signs
of
hyperandrogenism
-
hyperandrogenism
Polycystic ovaries
Two of three
criteria needed
-
Ovarian
dysfunction
(oligo-anovulation
and/or polycystic
ovarian
morphology)
Both criteria
needed
Etiology of PCOS

Two opposing theories:
– Gonadotrophin over-stimulation of the
ovaries
– High insulin levels are stimulating ovarian
androgen production
Diagnosis of PCOS
Hormonal and Metabolic Features in adolescents with hyperandrogenism
Free Testosterone
Androstenedione
Luteinizing Hormone (LH)
Follicle-Stimulating Hormone (FSH)
Insulin
Insulin-like growth factor binding
protein-1 (IGF-BP1)
Sex Hormone Binding Globulin
(SHBG)
(Warren-Ulanch et al., 2006)
Treatment of PCOS

Medication management, depending
on severity:
– Oral contraceptive pills
– Insulin sensitizer
Innovative Behavioral Intervention
PCOS as a model illness
PCOS
Physiological
Behavioral
(obesity, sleep, metabolic)
(eating, physical activity)
Emotional
(depression)
Viewing PCOS as a model
physical illness

Behavioral intervention to target high
rates of:
– Obesity
– Depression
– Sleep disturbances

Behavioral intervention affects
physiological outcomes
Co-occurrence in PCOS

Physiological
– Obesity: ~75%
– Sleep: 5 fold increased likelihood,
compared to controls, to have obstructive
sleep apnea
– Metabolic: insulin resistance,
hyperinsulinemia, beta-cell dysfunction
Co-occurrence in PCOS

Psychological
– Depression: Severe presentation
– Anxiety Disorder: Precipitating factor for
depression
– Binge Eating Disorder: Atypical
presentation
Co-occurrence in PCOS

Behavioral
– Caloric intake
– Energy expenditure
Targeting inter-regulatory
processes

Leveraging synergistic relationships

Focus on positive spirals

Window of opportunity during adolescence
Rofey/McMakin et al., 2013
Aims of the current investigation

Aim 1: Behavioral
– Change in weight
– Increase in energy expenditure

Aim 2: Emotional
– Change in depression

Aim 3: Physiological
– Sleep
– Metabolic parameters
Screening Process
Step 1
Participants are screened for depression (≥10 on the CDI)
↓
Step 2a
Participants meet other inclusion criteria: PCOS (hyperandrogenism; oligoovulation; exclusion of other endocrine disorders) and are between the ages
of 11 and 21
↓
↓
Step 2b
Participants complete a semi-structured clinical interview, K-SADS
↓
Step 2c
Participants meet DSM-IV criteria for minor/major depressive disorder
↓
Step 3
Participants sign the consent to participate in the intervention (11 sessions)
Rofey/Szigethy et al.,17 2009
Methods

Eighty-three adolescents with PCOS
– Ages 11-21, M=15
– 85% Caucasian
– Mean BMI=38

11 sessions of one-on-one coaching within the
community
– Evidence-based treatment
– Family-based component
Methods
Weight Management
Solution: Armband and
Feedback Device
Answer-only cellular phone
Total physical activity
Caloric intake
Number of steps
Sleep duration/efficiency
20
21
Results
Paired T-Tests Documenting Behavioral, Emotional, and Physiological Parameters
in Adolescents with PCOS Pre- and Post-Intervention (Baseline – 6-months)
________________________________________________________
Variables (N=83) Pre-Tx
Post-Tx
t Value
Effect
Mean (SD) Mean (SD)
Size
________________________________________________________
Depressive
Symptoms
CDI
14.1(8.2)
9.4(8.6)
4.45**
.81
Weight
BMI z-score
2.1(.5)
2.0(.5)
4.82**
1.6
Sleep
PSQ
2.4(1.5)
1.5 (1.6)
2.87**
.4
________________________________________________________
Note: CDI – Children’s Depression Inventory; PSQ – Pediatric Sleep
Questionnaire, Sleepiness; ** p = .00.
Physiological findings



High rates of depression in adolescents with PCOS
(45%) compared to obese (20%) and control (8%)
youth.
However, there was no relationship between depressive
symptoms in adolescents with PCOS and free
testosterone, rho=-.02, p=.46 or insulin resistance,
rho=-.06, p=.37.
In a larger obese sample, after controlling for race and
BMI, there was a negative partial correlation between
depression and insulin sensitivity (oDI; r=-0.49,
p<.001).
Rofey et al., 2012
Hannon/Rofey et al., 2013
Psychological presentation

An exploratory factor analysis (maximum likelihood) of
participants’ self-report on the CDI at baseline revealed three
novel factors compared to the non-obese clinical and
normative samples:
1.
2.
3.
4.
5.

Stigma
Internalization
Negative Self-Esteem (5th in instrument samples)
School
Negative Mood (1st in instrument samples)
Results failed to replicate three of the original factors: 1)
Interpersonal Problems, 2) Ineffectiveness and, 3) Anhedonia
Black/Rofey et al., 2014
EMA Results

Ecological Momentary Assessment Pilot Data
– Compliance rate for armband: 74.7±.3%
– Compliance rate for phone calls: 64.2 ±.3%
– Higher BMIs were more likely to be compliant
with EMA methods, rho=.78, p<.01.
– No association between compliance rates for
EMA and level of depressive symptoms.
Rofey/Dahl et al., 2012
EMA Results:
A focus on physical activity



Sixty percent of adolescents averaged at least one daily physical
activity bout lasting > 10 minutes, and 14% averaged a daily
physical activity bout lasting > 30 minutes
BMI was negatively correlated with physical activity bout duration (p
= 0.04)
Parental ratings of depression were predictive of youths’:
– Total physical activity (β = -0.46; p = 0.01)
– Bouts of physical activity > 10 minutes (β = -0.35; p = 0.05)


Physical activity was associated with increased positive affect post
exercise, (F (1, 314) = 5.01, p = .026).
Sleep > 8 hours per night led to more steps taken the next day,
r=.52, p<.01
Michael/Rofey et al., 2014 / Rofey/Jakubowski et al., 2014
If PCOS/obesity affects multiple
systems, what does it do to the brain?
Conceptual framework for next steps
Brain-obesity links




Cognitive function
Gray matter volume
White matter integrity
Impact of a weight management
program, with varying degrees of diet
and physical activity change, on brain
health
Preliminary brain findings
Youth who are obese perform more
poorly than normal weight controls
Right Hippocampus
Volume (mm2)
5000
Obese<Controls with regards to
hippocampal volume
4000
3000
2000
1000
0
Control
Overweight
Type II
Diabetes
Obese<Controls with regards to
white matter integrity
Rofey, Arslanian, Verstynen/Erickson et al., 2013
Cognitive Deficits



Executive functioning: Umbrella term
including planning, execution, and ability to
solve problems
Working memory: Actively holding multiple
pieces of transitory information in the mind
Psychomotor speed: Coordination of a
sensory or cognitive process and motor
activity
Hannon/Rofey et al., 2013
Brain Morphology Results
Preliminary results suggest that obesity is associated with reduced
gray matter volume in the caudate and thalamus, with all other
regions following a similar trend, compared to control youth.
Brain Morphology Results
Using Diffusion Tensor Imaging (DTI) we found that obese
adolescents had reduced integrity of the white matter projections
into the caudate from the lateral frontal regions compared to the
control group
Clinical implications




Rule out PCOS, as well as other illnesses
that affect multiple systems
Assess not only for physiological, but also
psychological and behavioral disturbances
Provide broad, evidence-based programs (or
refer to folks who can)
Do not under-estimate how behavioral,
cognitive, and psychological disturbances
affect physical illness
Clinical Implications





Address weight issues
Be empathetic and ask
open-ended questions
before delivering advice
(e.g., “what do you think
about your health
behaviors?”)
Implementation not
information problem
Explore barriers
Refer, if necessary
Next steps

Dissemination and Implementation
– Multi-site within Adolescent Medicine Clinics
– Crossing interconnected processes
– Utilizing existent providers to extend services


If obesity is associated with brain-based deficits, how
do cognitive deficits (pre-intervention) affect weight
management outcomes
If obesity persists, what else can we do for patients
– Trauma
– Interpersonal relationships/sexual practices
Thank you Mentors
Liz Miller, MD, PhD
Ronald Dahl, MD
Silva Arslanian, MD
Thank you Collaborators
Kirk Erickson, PhD
Robert Noll, PhD
Eva Szigethy, MD, PhD
Nermeen El Nokali, PhD
Marguerite O’Hara, MA
Ronette Blake, MS
Jodi Krall, PhD
Tamara Hannon, MD
Kara Hughan, MD
Barb Cardinal-Busse, CRNP
Gina Sucato, MD
Emily Filippelli, MBA
Marsha Marcus, PhD
Anne Marie Kuchera, RD, MA
Jennifer Silk, PhD
Aletha Akers, MD
Selma Witchel, MD
Neal Ryan, MD
Chris Ryan, PhD
KayLoni Olson, Angela Vincent, Kelly Rabenstein, Katherine Belendiuk, Britney Brinkman, Erica Stein, Glory Ojiere,
Amy Gillio, Jenn Jones, Jill Matlock, Brittany Musselman, Meaghan Beckner, Rachel Metz, Megan Barna, Ashley
Rowden, Brian Thoma, Dee Astute, Dana Schreiber, Sara Andrasy, Bryan Powell, Kat Belendiuk, Christina
Wallace, Amanda Peterson, Deana Ekas, Jessica Black, Ikechukwu Onyewuenyi, Juliet Cameron, Clare Newlon,
Sammy Dhaliwal, Meredith Dillon, Alyssa Spector, BreAnne Herline, Renae Sweeney, Deepika Singapogu
36
Weight Management & Wellness Center
Polycystic Ovary Syndrome Center
Adolescent Medicine Clinic
Questions
Thank you for your time!