Lecture 2: Psychological side effects of cancer treatment

1. C83MLP Mechanisms of Learning and Psychopathology Lecture 2: Psychological side effects of cancer treatment Dr. Mark Haselgrove

2. 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

3. Content of Lecture (1) What are the Psychological side effects? (2) Taste aversion learning (3) Anorexia – Acquired food aversions (4) Anticipatory Nausea and Vomiting - Is it a CR? - Prospective studies - Susceptibility to ANV (5) Treatments for side effects - The scapegoat effect - Other treatments

4. 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)

5. Smith & Roll (1968) 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

6. Anorexia Bernstein (1991) Could be the result of learned aversions to specific foods that were eaten 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?

7. Anorexia (Cont.) Bernstein & Borson (1986) • Evidence that rats learn aversion to specific novel foods during: • Period of tumour, or • Radiotherapy induced nausea - Rescorla (1968) Contingency is important for learning…! Discussion point: Aversion develops even though nausea is extended in time, why?

8. 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 Is ANV a classically conditioned response? i.e. Stimuli during/ preceding infusion Nausea/vomiting which follows infusion CS US/UR

9. 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 → Illness Context B → nothing Sucrose in A: 12 ml Sucrose 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)

10. Anticipatory Nausea & Vomiting Retrospective studies have shown ANV associated with: • Increasing number of infusions • The severity of post nausea and vomiting (PNV) • Younger patients (who get strongly emetic drugs) • All consistent with conditioning (see also Bovbjerg, 2006) • 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

11. 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 extraversion Before 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 infusion Age, drug, infusion technique, type of cancer.

12. 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

13. 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 who gets ANV? Simple r = correlation between ANV and variable Discussion point: Does this support a conditioning account of ANV?

14. Anticipatory Nausea & Vomiting If ANV is classically conditioned, then it should co-vary with individual differences known to affect classical conditioning Kvale & Hugdahl (1994) – ANV and Autonomic conditionability 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) Ss had to press button when they heard noise HR recorded 3 s pre and 10s post both CSs CS+ → Noise CS- → No Noise RTs to Noise US – ANV group faster than n-ANV group Discussion point: Is this really conditioning?

15. 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 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

16. Potential treatments Andresen et al (1990) – The scapegoat effect Suggested novel tasting food eaten after “normal” food which precedes CT will acquire 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)

17. 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

18. 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 desensitization Video game play during infusion Possible mechanisms… Nonspecific/placebo effect Counter-conditioning Diversion of attention Discussion point: How might these work (in terms of conditioning)?

19. Further reading…