Mental Health and Biomarkers Andrew Oswald IZA and Warwick

Now let’s broaden the idea of human well-being (beyond ‘happiness’).

We’ll discuss biomarkers

We’ll discuss biomarkers Heart rate Systolic blood pressure Diastolic blood pressure C-reactive protein Fibrinogen

But let’s start with mental health.

I will say almost nothing about really serious mental illness.

Psychosis occurs in about 1% of the population. I will say almost nothing about really serious mental illness. Psychosis occurs in about 1% of the population.

Instead we can think of mental ill-health (depression, anxiety, and mental strain).

Happiness and life-satisfaction equations typically have similar structures to mental-health equations.

A psychological-ill-health measure used a lot in the psychiatry literature is a GHQ score (which stands for General Health Questionnaire).

Typical GHQ mental-strain questions Have you: Lost much sleep over worry?

Typical GHQ mental-strain questions Have you: Lost much sleep over worry? Felt constantly under strain?

Typical GHQ mental-strain questions Have you: Lost much sleep over worry? Felt constantly under strain? Felt you could not overcome your difficulties?

Typical GHQ mental-strain questions Have you: Lost much sleep over worry? Felt constantly under strain? Felt you could not overcome your difficulties? Been feeling unhappy and depressed?

It was developed as a way to judge who needs psychiatric treatment.

The exact 12 questions that make up a GHQ score “Have you lost much sleep over worry?”; “Been able to concentrate on things?”; “Felt you are playing a useful part in things?”; “Felt capable of making decisions about things?”; “Felt constantly under strain?”; “Felt you could not overcome your difficulties?”;

“Been able to enjoy your normal day-to-day activities”; “Been able to face up to your problems”; “Been feeling unhappy and depressed?”; “Been losing confidence in yourself?”; “Been thinking of yourself as a worthless person?”; “Been feeling reasonably happy all things considered?”.

Each of the 12 questions is scored out of 3.

On a 36-point scale Mean of GHQ 10.4975 Standard deviation 4.89

You will remember:

The pattern of a typical person’s happiness through life

This holds in various settings

This holds in various settings For example, we see the same age pattern in mental health among a recent sample of 800,000 UK citizens: [Blanchflower and Oswald, Social Science & Medicine, 2008]

The probability of depression by age Males, LFS data set 2004-2006 0.02 0.015 0.01 Regression coefficient 0.005 -0.005 -0.01 1938 1942 1946 1950 1954 1958 1962 1966 1970 1974 1978 1982 1986 1990 Year of birth

Depression by age among females: LFS data 2004-2006Q2 0.002 -0.002 -0.004 Regression coefficient -0.006 -0.008 -0.01 -0.012 -0.014 1942 1946 1950 1954 1958 1962 1966 1970 1974 1978 1982 1986 1990 Year of birth

An important border is between happiness and medicine

An important border is between happiness and medicine Is it possible that we could find physiological correlates with human well-being? Perhaps to broaden the standard policy goal of GDP?

We are studying mental well-being and physiological data on a random sample of 100,000 English citizens.

We are interested in equations for

We are interested in equations for Heart rate Systolic blood pressure Diastolic blood pressure C-reactive protein Fibrinogen

Blood pressure = cardiac output X peripheral resistance.

Systolic pressure is the force of blood in the arteries as the heart beats. It is shown as the top number in a blood pressure reading. High blood pressure is 140 and higher for systolic pressure.

Diastolic pressure is the force of blood in the arteries as the heart relaxes between beats. It's shown as the bottom number in a blood pressure reading.

C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation (i.e. C-reactive protein is an acute-phase protein). It is synthesized in the liver.

Fibrinogen is a protein that plays a key role in blood clotting Fibrinogen is a protein that plays a key role in blood clotting. Fibrinogen is a sticky, fibrous coagulant in the blood that increases the risk of experiencing one of the leading causes of death and disability - stroke.

Why would we care?

It is known that heart rate rises under stress.

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Stress comes in different forms

Nicolas Troubat et al (2009) European Journal of Applied Physiology 20 chess players – international and national-level players. They all played against a computer.

The computer standard was deliberately set one level higher.

The computer standard was deliberately set one level higher. So all the players lost against the computer.

What happened? Average heart-rate rose 11 beats a minute On average, players used up 140 calories playing the game Overall, the physiological changes were “similar…those … in moderate physical exercise”.

Question Could physiological measures -- biomarkers -- be used as proxies for well-being?

Good time for points or questions?

Or maybe in the long run in western society we can blend well-being survey responses with biomarker data.

For example Cortisol is produced by the adrenal gland in the zona fasciculata, the second of three layers comprising the outer adrenal cortex. This release is controlled by the hypothalamus, a part of the brain.

Main functions of cortisol in the body increasing blood sugar through glycogenolysis and reduction of glucose uptake into cells. suppressing the immune system aiding in fat, protein, and carbohydrate metabolism

The amount of cortisol present in the blood undergoes diurnal variation; the level peaks in the early morning (approximately 8 am) and reaches its lowest level at about midnight-4 am, or three to five hours after the onset of sleep.

Important work by Andrew Steptoe of UCL: Whitehall II data

Salivary cortisol (Steptoe data) Cortisol across the working day by happiness quintile 8 samples (08:00 – 22:30) Adjusted for gender, age, occupational grade, smoking, bmi, and GHQ

Heart rate P = .017 in men Adjusted for age, occupational grade, concurrent physical activity, smoking, bmi, and GHQ score Steptoe et al, 2005 PNAS

Some of our latest work: Joint with Nicholas Christakis (Harvard) and David Blanchflower (Dartmouth) Statistical links between the heart and income and happiness.

Pulse: Average heart rate is about 72 beats per minute.

Interesting patterns emerge First, there are well-determined income gradients in (and only in) heart-rate and C-reactive protein equations.

Second, heart rate seems to have potential as a proxy measure for mental strain, so might eventually be usable as a measure of negative ‘utility’ in an economist’s framework.

Third, education has little effect within biomarker equations.

Fourth, it is more important to control for diet than has been traditionally recognized in the health-economics literature.

Fifth, biomarker variables work powerfully in well-being equations.

To clinicians High blood pressure is potentially a sign of mental strain and low well-being

But how about high blood pressure as a national measure of well-being?

Across nations, hypertension and happiness are inversely correlated (Blanchflower and Oswald, 2008 Journal of Health Economics)

Happiness and mental well-being are of interest in themselves.

But, more broadly, there seem to be deep links between mind and body.

Author(s): Ebrecht M, Hextall J, Kirtley LG, Taylor A, Dyson M, Weinman J PSYCHONEUROENDOCRINOLOGY     Volume: 29    Issue: 6    Pages: 798-809    Published: JUL 2004 

“Every subject received a standard 4mm-punch biopsy, and the healing progress was monitored via high-resolution ultrasound scanning.”

“Every subject received a standard 4mm-punch biopsy, and the healing progress was monitored via high-resolution ultrasound scanning.”

Ebrecht et al 2004 The overall results showed a significant negative correlation between speed of wound healing and GHQ scores (r = -.59; p < .01)

In other words, happier human beings heal more quickly.

A more recent paper

A more recent paper “Enhanced wound healing after emotional disclosure intervention” Weinman, Ebrecht et al BRITISH JOURNAL OF HEALTH PSYCHOLOGY    Volume: 13    Pages: 95-102    Part: Part 1    Published: FEB 2008

Participants who wrote about traumatic events had significantly smaller wounds 14 and 21 days after the biopsy compared with those who wrote about time management.

Also There is some evidence that happiness seems to make you live longer.

Journal of Personality and Social Psychology, 2001 The ‘Nuns Study’ Journal of Personality and Social Psychology, 2001

“Positive emotions in early life and longevity: Findings from the nun study.” By Danner, Deborah D.; Snowdon, David A.; Friesen, Wallace V. Journal of Personality and Social Psychology, Vol 80(5), May 2001, 804-813.

Handwritten autobiographies from 180 Catholic nuns, composed when participants were a mean age of 22 years, were scored for emotional content and related to survival during ages 75 to 95.

One of the nuns wrote: “God started my life off well by bestowing upon me grace of inestimable value… The past year which I spent as a candidate studying at Notre Dame has been a very happy one. Now I look forward with eager joy to receiving the Holy Habit of Our Lady and to a life of union with Love Divine”

Whilst another nun wrote: “I was born on September 26, 1909, the eldest of seven children, five girls and two boys… My candidate year was spent in the motherhouse, teaching chemistry and second year Latin at Notre Dame Institute. With God’s grace, I intend to do my best for our Order, for the spread of religion and for my personal sanctification.”

After joining the order their lives were almost exactly the same - same food, same work, same routine But not the same life expectancy… Among the less-positive nuns, 65% died before their 85th birthday. Among the happy nuns, 90% were still alive.

A strong inverse association was found between positive emotional content in these writings and risk of mortality in late life (p < .001).

As the quartile ranking of positive emotion in early life increased, there was a stepwise decrease in risk of mortality resulting in a 2.5-fold difference between the lowest and highest quartiles.

Positive emotional content in early-life autobiographies was strongly associated with longevity 6 decades later.

An early, famous paper Title: PSYCHOLOGICAL STRESS AND SUSCEPTIBILITY TO THE COMMON COLD Author(s): COHEN S, TYRRELL DAJ, SMITH AP Source: NEW ENGLAND JOURNAL OF MEDICINE Volume: 325 Issue: 9 Pages: 606-612 Published: AUG 29 1991

Researchers need to understand these mind-body interconnections better.

Another interesting issue is how we might match (or validate) well-being data with measures of mental health.

Consider the famous U shape in well-being through life. Say a sceptic disbelieved all well-being data and just would not change his or her mind.

One route would be to use data that independently confirm the patterns in happiness regression equations.

One route would be to use data that independently confirm the patterns in happiness regression equations. Here is an example.

Antidepressants Work joint with Blanchflower on antidepressant consumption in Europe.

Proportion of Europeans taking antidepressants (regression-adjusted) through life

What about causality?

Forthcoming paper by Nick Powdthavee (in the Journal of Human Capital)

Nick Powdthavee’s work on blood pressure and education

The drop in hypertension

His regression equations

Results for males

Results for females

Some conclusions today

#1 Mixed evidence on ‘education gradients’ in heart biomarker equations.

#2 A variable for the consumption of fruit and vegetables works strongly.

#3 After we control for fruit and vegetables, income plays a clear role only in heart-rate and C-reactive protein equations...

#3 After we control for fruit and vegetables, income plays a clear role only in heart-rate and C-reactive protein equations... and the income gradient looks small.

Heart Rate (Page 24 of Blanchflower et al)

Could you go back to the Blanchflower et al biomarkers paper (hard copy).