Lecture 2:

Psychological side effects of cancer treatment

C83MLP Mechanisms of Learning and Psychopathology

Dr. Mark Haselgrove

Assessment:

(1) Dissertation (50%) 4000 words max

- Titles assigned 13th March 2013- Dissertation tutorials in small (N≈6) groups with MH/TB/CB/JR before and after Easter- Hand in by Tues 7th May 2013

(1) Examination (50%) May/June 2013

- Two Sections: (A) Content by JR/CB (B) Content by MH/TB- 4 questions in each section. YOU ANSWER ONE FROM EACH.- 2 hours long

All past papers for C83MLP now on Moodle

Content of Lecture

(2) Taste aversion learning

(3) Anorexia – Acquired food aversions

(1) What are the Psychological side effects?

- Is it a CR?

- Prospective studies

(5) Treatments for side effects

(4) Anticipatory Nausea and Vomiting

- The scapegoat effect

- Susceptibility to ANV

- Other treatments

What are the psychological side effects?

(1) Anorexia

- Reduced appetite, refusal of food- Particularly to protein rich (e.g. meat) food

(2) Anticipatory Nausea and Vomiting (ANV)

- Nausea (with or without vomiting) occurring during the hrs before scheduled drug infusions- Particularly when in (or thinking about) infusion setting

Possible sources of gastric distress in cancer patients:

- Tumour growth

- Radiotherapy

- Chemotherapy (CT)

Taste aversion learning

Animal is made ill after consuming a particular food

Food Lithium Chloride Injection

Animal subsequently avoids that food – Aversion developed

- Successful in only 1 trial

- Conditioning effective despite Intervals of several hrs between food and illness

Smith & Roll (1968)

Anorexia

Bernstein (1991)

Could be the result of learned aversions to specific foods that wereeaten during the period of tumour (or radiotherapy) induced nausea

Most patients learn aversions to numerous tastes, so anorexia appears general

Midkiff & Bernstein (1985)

- Questionnaire results suggest CT induced aversions more likely to:

- Eggs, Cheese Meat (high protein – stronger flavours)- Less likely to carbohydrates (weaker flavours)

- More likely to develop to novel foods

- More likely to develop to food eaten just before CT session

Discussion point:Why would these

variables affect food aversions?

Anorexia (Cont.)

Bernstein & Borson (1986)

- Evidence that rats learn aversion to specific novel foods during:Period of tumour, orRadiotherapy induced nausea

- Rescorla (1968) Contingency is important for learning…!

Discussion point:Aversion develops even though

nausea is extended in time, why?

Anticipatory Nausea & Vomiting

- Nausea (with or without vomiting) occurring during the hrs before scheduled drug infusions- Particularly when in (or thinking about) infusion setting

Morrow & Dobkin (1988); Carey & Burish (1988)

- Occurs in 20%-40% of CT patients (more with the most emetic drugs)- Not helped by antiemetic medication – A substantial clinical problem

i.e.

Is ANV a classically conditioned response?

Stimuli during/preceding infusion

Nausea/vomiting which follows infusion

CS US/UR

Anticipatory Nausea & Vomiting

Can nausea be conditioned to contextual cues?

e.g. Garcia & Koelling (1966) - Flavour → Illness

Light → Shock

Flavour →Shock

Light → Illness

Easy to Learn

Hard to Learn

Hall & Symonds (2006)

Context A → IllnessContext B → nothing

Sucrose in A: 12 mlSucrose in B: 16 ml

Alternative Hypothesis: It’s an anxiety symptom. But, its hardly found with other forms of cancer treatment (e.g. bone marrow aspiration – severe anticipatory anxiety, no nausea vomiting)

Anticipatory Nausea & Vomiting

Retrospective studies have shown ANV associated with:

- But, some effects could be artifacts. (e.g. (3), strong emetic drugs could “mark” ANV/PNV

-Thus prospective studies are needed to allow effects of variables to be dissociated

(1) Increasing number of infusions(2) The severity of post nausea and vomiting (PNV)(3) Younger patients (who get strongly emetic drugs)

- All consistent with conditioning (see also Bovbjerg, 2006)

Anticipatory Nausea & Vomiting

Andrykowski et al (1985)

If ANV is classically conditioned, predict increased incidence of ANV with(1) more severe PNV (greater US intensity)(2) Longer duration of infusion (longer CS-US pairing)(3) Higher pre-infusion state anxiety (greater conditionability)

80 adult patients starting first CT treatment. 71 completed study (mean 10 infusions)

Measures: Before each treatment: Spielberger trait anxiety, EPI extraversionBefore each infusion

(a) rated PNV severity after last infusion(b) Anxiety now and over past 24 hrs(c) Physical symptoms (e.g. vomiting [now and over 24 hrs])

Duration of 1st and 2nd infusionAge, drug, infusion technique, type of cancer.

Anticipatory Nausea & Vomiting

Andrykowski et al (1985) cont..

Results 26/71 (37%) showed ANV, No association with type of drug,technique, diagnosis, but all who showed PNV also reported ANV

Analysis of predictors – Multiple regression. DV = Did person ever show ANV (Yes/No)

Predictors: (1) Severity of PNV after infusion 1(2) Mean duration of infusions 1 and 2(3) State anxiety pre infusion 1 and 2(4) trait anxiety, extraversion, age

Anticipatory Nausea & Vomiting

Andrykowski et al (1985) still cont..

(“Hierarchical regression” tests whether a variable predicts difference in ANV after prediction by other variables has been accounted for)

F = Does this variable significantly predict whogets ANV?

Simple r = correlation between ANV and variable

Discussion point:Does this support a

conditioning account of ANV?

Anticipatory Nausea & Vomiting

Kvale & Hugdahl (1994) – ANV and Autonomic conditionability

If ANV is classically conditioned, then it should co-vary with individual differences known to affect classical conditioning

Looked at heart rate (HR) conditioning (like nausea, this is controlled by parasympathetic ANS)

2 CSs, 6 s tones (1200 and 2000 Hz. US = 1 s white noise burst)

CS+ → NoiseCS- → No Noise

Ss had to press button when they heard noiseHR recorded 3 s pre and 10s post both CSs

RTs to Noise US – ANV group faster than n-ANV group

Discussion point:Is this really

conditioning?

Anticipatory Nausea & Vomiting

Can a CR be learned to an arbitrary stimulus which precedes CT infusions

Bovbjerg et al (1992) – Conditioned taste aversion induced by CT

78 (47) women receiving CT for breast cancer – 8 infusions, over 3/4 week intervals.Informed that this was a study of CT side effects, no mention of taste aversion.

Exp Group: 150 ml lemon-lime drink in distinctive cup before infusion (N=25)Control Group: not offered lemon-lime drink (N=22)

Results: Exp grp often refused drink in clinic - Tested at home soon after (as were controls)

Exp Group Control Group

Nausea pre drink

post drink

Rating of drink

(1= good, 9= bad)

4

18

6.5

5

3.5

4.8

Exp grp: aversion to drink correlated with PNV only after 1st infusion

Of those who reported PNV after infusion 1: 8/14 developed aversion.

Of those who didn’t, 0/9 developed aversion

Potential treatments

Andresen et al (1990) – The scapegoat effect

Suggested novel tasting food eaten after “normal” food which precedes CT willacquire strong association and overshadow association to normal food (act as a scapegoat)

25 adult CT patients. Infusions received either 1/week to 1 every 6 weeks

Either a novel or a familiar food consumed 10-15 min before CT session

Hedonic rating scale used to asses preference for regular foods. (1 = dislike, 9 = like)

Novel group Familiar group

N increase in hedonic rating

N decrease in hedonic rating

N No change

22

11

20

11

24

22

Potential treatments

Klosterhalfen et al (2005) – Latent inhibition of ANV

Motion Sickness susceptibility questionnaire

7 item scale, Ss rated:

- Vertigo- Headache- Nausea- Urge to vomit- Tiredness- Sweating- Stomach awareness

Potential treatments

Carey & Burish (1988); Morrow & Dobkin (1988)

Types of treatment that have been reported:

Hypnosis to minimise PNV Relaxation & guided imagery during infusion

Systematic desensitizationVideo game play during infusion

Discussion point:How might these work

(in terms of conditioning)?

Possible mechanisms…

Nonspecific/placebo effectCounter-conditioningDiversion of attention

Further reading…