Week 2 - Lecture
o Utilizing a new approach
§ Can now conceptualize disease/wellness as the outcome variable of a multiple
regression equation consisting of all 3 PDN variables for that individual at a
specific point in time:
• Disease = {(Social Network)(Disease Module) (Metabolic Network)}
§ Now it would be possible to assess how much of the variance of each individual’s
PDN is explained by the Social, Disease and Metabolic networks.
§ Can then individualize the intervention customized to the person’s set of
contributing factors
o PDN model explains some recent literature
§ Diet & physical activity has been proven in multiple studies to improve features
associated with T2D:
• Maintenance of normal blood glucose levels & insulin action
• Improving lipids
• Blood pressure
• Cardiovascular events
• Weight loss
• Mortality
• QOL
§ Exercise changed DNA methylation & expression of genes
• These changes may play a role in reducing risk of Type 2 Diabetes (T2D) in
men with family history
• 1st degree relatives with T2D 3x more likely to develop disease than those
without positive family history
• These interactions are both understandable & predictable with Network
Medicine
o Applying the concept
§ During the following vignette, keep these questions in mind:
• How do the components interact?
• What do you perceive as being important for your area(s) of interest?
• Which components are most pertinent?
o Key Points
§ Paying attention to a patient’s larger networks could produce more positive
outcomes
§ Having a common language to communicate across professions could expedite a
more effective, integrated care model.
§ Because utilizing Network Medicine allows for answering our more modern and
complex medical questions.
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Week 2 - Lecture
Ecological Network:
o Expanded Disease Module
§ Current literature argues an integrated approach may provide a useful guide to
delineate individuals with disease susceptibility & customize therapeutic
strategies.
§ Analyzing one’s PDN could potentially anticipate negative disease outcomes.
o Why a new approach?
§ To successfully implement comprehensive interventions, the ability to “intercept”
disease is crucial.
§ This involves a paradigm shift from a reductionist “diagnose and treat” approach
to a systems based “predict & pre-empt” model.
§ Intervening early enough in the disease process to prevent serious effects of the
disease associated with progression will be important.
§ This could lead to a future characterized by integrated healthcare models involving
comprehensive approaches that include monitoring, helping with adherence, &
disease interception.
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Week 2 - Lecture
Identifies individual network components (disease interactions, metabolic,
social/environmental, diversity/culture, psychological) that significantly
contribute to the individual’s disease expression in order to create a more
complete disease conceptualization
o Assists in understanding the way(s) in which the disease presents for a specific
individual
o Provides a model for understanding the full array of the multiply determined nature
of an individual’s disease(s)
§
Page 10 of 12
Week 2 - Lecture
o Data Supporting Expanded Network Med. Approach:
§ Framingham Heart Study Data set: 12,067 people from 1971 to 2003
(Christakis & Fowler, 2007)
• Results:
o Having a friend with obesity increases chances of obesity by
57%.
o An obese sibling increases chances by 40%
o An obese spouse increases chances by 37%
§ Smoking:
• Increased likelihood of smoking:
• 1st degree = 36%; 3rd degree = 11%
• If a person at a small firm quit smoking, colleagues
had a 34%
chance of quitting
§ Drinking spread socially, as did happiness & loneliness
• Social stress found to increase serum B-hydroxybutyrate,
epinephrine, norepinephrine, &
• cortisol greater in normal weight men than in obese counterpart
v Clinical Extension of the Disease Model
o Patient’s disease network (PDN)
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Week 2 - Lecture
o Within the disease module it is difficult to consider
components to be independent from one another due to the
interrelated relationships of each component.
§ Job of healthcare team including psychology to pull it
all together and understand what it means for the
individual
o 1993 study – so could be one explanation for why giving the
same amount of cold virus to people results in:
§ 1/3 severe sx
§ 1/3 mild sx
§ 1/3 no sx
§ Network Medicine
• Allows for a common language for all healthcare professionals.
• Implication is that an integrated approach cannot leave out
disciplines focusing on cognitions, emotions, and behavioral aspects
of health and disease.
o Perception of our environment = goes into cognitions and
emotions à affects behavior
• Currently the health care system is moving away from fee for
service to P for P (pay for performance)
o Problem with fee for service = getting paid for bad care
o PCPs = primary screener for MDD because people usually tell
them
§ Use PHQ9 as a screener and get paid for this, instead
of referring to psychologists
o An Expanded Clinical Disease Module
§ Would include an analysis of the interactions between the:
• Disease Networks,
• Metabolic/Genetic Networks
• Social, Psychological & Environmental Networks
o Proposed name: Ecological network (which would include
the psychological aspect)
§ To understand & intervene in their contributions to the underlying
physiological processes leading to health and disease.
Page 8 of 12
Week 2 - Lecture
•
•
Barabasi et al model
o Applying network medicine on a macro level demonstrates
every person’s illness has its own multidirectional
interactions within its specific network & disease module
o Awareness of patients’ larger networks produces increased
individualized outcomes
o Should be most effective with the complex illnesses
evidenced in 10% of patients accounting for 70-80% of U.S.
healthcare costs (Houle & Fleece, 2011).
Disease Module
o Every illness has its own interactions within its network &
disease module
o Each disease has its own unique module – the components of
which may overlap with another disease module
o Each component, whether or not it is involved in the same
module, will be expressed differently dependent upon the
specific disease & how the components interact within the
patient’s unique metabolic network.
o Components belonging to the same module have a high
likelihood of interacting with one another, effecting how the
disease is expressed
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Week 2 - Lecture
§
•
•
Metabolic Network including interactions among the
following systems:
• Genetic
• Regulatory
• Metabolic
• Protein-protein
Epigenetics
o Environmental variables and Social networks have been
demonstrated to effect gene expression
o Social network examples:
§ Gaining/losing weight
§ Stopping smoking/drinking
• If people who stop smoking around you, you
are at a higher risk to stop smoking
Network Medicine
o Proposes that any individual’s level of health or illness is a
result of the idiosyncratic interactions of the Metabolic,
disease module and social/environmental networks
operating on that person at a specific point in time
o Helps fingerprint the relevant factors operating for and on an
individual at a specific point in time.
o Can now move from “diagnose & treat” to “intercept and
prevent”
§ Physiologically, you should include psychology when
looking at a patient and how to help them
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Week 2 - Lecture
•
between muscle and fat) à
instead of BMI now we use waist
circumference (this is now being
used because not all body fat is
created equal, visceral body fat
is metabolically fat; visceral body
fat is in your gut) à rubric about
what your waist should be,
metabolically (ideal waist
circumference = half of your
height) à critical turning point =
5 inches above your ideal waist
circumference; if you are at your
ideal waist circumference à
visceral body fat puts out a great
deal of antinflammatory markers
aka interoleukins and cytokines
à go over 5 inches above your
waist circumference à more
pro-inflammatory neuroimmune
markers, which are highly
correlated with stroke, heart
disease, and cancer as well as
MDD
o For those with MDD = higher ratio of interoleukins and
cytokines
§ Some of the interoleukins and cytokines are strictly
anti- and some are pro-inflammatory, while some
swing both ways depending on circumstances
o When applying Graph theory on metabolic syndrome:
§ Find things that are connected to it are stroke, cardiac
events, cancer and MDD
§ People with Bipolar disease more likely to have
asthma, certain cancers and diabetes
§ People with autism more likely to have cardiac
disease
§ When you have 2 or more things that are correlated, it
does not mean causation, instead it almost always
means they are correlated through a mediating
variable
• I.e. ice cream cones and shark bites (mediator =
time of the year)
Correlation, NOT causation
o Mediating variable for this is the metabolic network
Page 5 of 12
Week 2 - Lecture
o An Alternative Integrative Approach: Barabasi et al (2007) Network Medicine
Model
§ Method allowing examination of multiple determinants of modern chronic
illnesses
§ Barabasi et al (2007) demonstrates how to view the patient as a whole,
rather than a person with a singular illness, in an effort to identify variables
which may be contributing to, and maintaining, diseases.
§ May be way to improve upon and expand Engel’s Biopsychosocial model
• Network medicine helps operationalize what Engels intended to do
§ It’s better to have integrated care vs. organ based care (what is currently
going on)
o Assumption is that health and disease outcomes “depend on adaptive interactions
between a multitude of genetic and environmental factors occurring over a
lifetime.” (Loscalzo, 2014)
o Disease module
§ In order to understand the complexity of the disease network, one must first
be cognizant of the Disease Module
§ According to Barabasi, ‘Disease module’ represents a group of network
components that together contribute to the ultimate expression of the
disease.
§ Disease module components
• Patient with the Disease
o Potential interrelationships among diseases in which 2
diseases are connected by a common or genetic functional
origin (e.g., obesity & diabetes)
o Utilizing a statistical tool termed Graph Theory, can highlight
hidden correlations between factors
o Some correlations already known and understood
o Strong relationships between metabolic syndrome, stroke,
cardiac events
§ Metabolic syndrome – people with it are 2x as likely
than people without it to have depression
• Syndrome itself = cluster of 5 factors that
when a person has all 5, they are now eligible
for type-2 diabetes
o 5 factors:
§ Hyperlipidemia aka high
cholesterol
§ Terrible ratio
§ High blood pressure
§ Insulin resistance
§ Obesity (BMI has no longer been
used since 2012 – this was
because it did not differentiate
Page 4 of 12
Week 2 - Lecture
o Pituitary, hypothalamus and adrenal work together by controlling behavior
v HPA-gut-microbiome communication & effect (sherwin et al 2016)
o Serotonin = produced in the gut
o Article findings state that bacterial flora in gut interacts with HPA axis and controls
neurodevelopment and behavior
§ Ability of stress to control you = partially mediated by microbiome in gut
§ Has found dysregulation of gut microbiota in numerous psychiatric d/o
including depression
§ Psychobiotics/Neutroceuticals – change the microbiome in the gut à
changes how it communicates with the HPA axis à mediates stress à
influences the expression of psychiatric d/o
§ Why antibiotics are not helpful, when prescribed even for the common cold
• Antibiotics are geared to kill bacteria
• Antibiotics do nothing for viruses (what causes a cold)
§ When you have a client that is a child and randomly starts having difficulties
à Important to ask what is going on externally but also what they’re eating,
including probiotics and prebiotics
• Try to give them a new diet
v Death by despair
o Suicide rates are on the rise in this century in the US
o Microbiome and HPA axis and the role of stress à reason why despair and suicide
are reactions to stress
v Network Medicine Model
o States that operating solely from an independent organ based medical model no
longer respects recent data demonstrating that especially in chronic illness it is the
interactions within and between organ systems that most often dictates:
§ etiology,
§ course,
§ prognosis
§ and treatment.
Page 3 of 12
Week 2 - Lecture
o Pituitary
§ called the 'master gland' because the hormones produced control several
crucial physical processes.
§ secretes hormones that act on the adrenal glands, thyroid
gland, ovaries and testes, which in turn produce other hormones.
§ Thus, it ultimately controls metabolism, growth, sexual maturation,
reproduction, blood pressure etc.
§ Again balancing the internal and external environments
• Again about how the brain is perceiving the external environment
o Adrenal glands
§ Sit on top of each kidney
§ produce hormones that help regulate:
• metabolism,
• immune system,
• blood pressure,
• response to stress
• and other essential functions.
Page 2 of 12
Week 2 - Lecture
v Epigenetics: how the environment determines how genes express themselves; which genes
get turned on and off and under what conditions
v Triple threat = majority of people have 3 things going on: diagnosis of a chronic medical
condition, DSM condition & substance abuse and/or alcohol
o Each one of these things makes the other worse
o Has resulted in health care costs increasing
v Commonwealth Fund – compares healthcare across countries
v Biopsychosocial Model
o Outcomes in health = product of biological, psychological and social factors
o This model is operationalized differently by everyone – everyone has a different
understanding of what it is and how it should be done
o Most people still believe in Cartesian Dualism – difficulty understanding and
integrating BPS model
§ Cartesian Dualism – mind and body function under different principles and
need to be studied separately
v HPA Axis (Hypothalamus-Pituitary-Adrenal) Interactions
o Links perception of external circumstances to internal physiological process that
interact with behavior
o Mediates stress
o That subsequently effect and are effected by mental health status
o Hypothalamus
§ Primary function is homeostasis of the body - maintaining the body's
balanced status quo system-wide.
• Homeostasis = maintaining a balance or equilibrium
• You are at your healthiest state when you are balanced
• Controls some of the major processes that result in homeostasis
§ Accomplishes this by controlling release of 8 major hormones by the
pituitary gland.
§ secretes hormones that stimulate or suppress the release of hormones in
the pituitary gland, in addition to controlling water balance, sleep,
temperature, appetite, and blood pressure
§ In order to control body temperature, food and water intake, hunger and
thirst it must respond to signals from both the internal and external
environment
• I.e. dehydrated and thirsty à engage in behavior to quench thirst
• Regulates behavior in a sense
§ The end result is that it has a role in behavior to accomplish homeostatsis
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