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How Stress Affects Health and Behaviour; Strategies for Prevention and Treatment G. M. Landsberg DVM, DACVB, Dip. ECVBM-CA North Toronto Animal Clinic, northtorontovets.com CanCog Technologies, Director Veterinary Affairs 2

Presentation Outline Diagnostic dilemma: «behaviour» or «medical»? Normal vs. abnormal behaviour Fear prevention & enrichment Integrated approach to common stress-related behaviour problems  Behaviour modification program  Natural products and drugs Case study Question period 3

Veterinarian’s Role Assess behaviour at each visit Maintain health, welfare, bond Behavior – may be first or only sign of medical issue  Central nervous system (CNS), metabolic, cognitive dysfunction syndrome (CDS), sensory, Pain Welfare (5 freedoms)  expression of normal behaviour  freedom from fear, discomfort, pain, hunger Veterinarian’s role to prevent, diagnose, treat Do the pet a favour ► ask about behaviour 4

Diagnostic Dilemma: Is it «Behaviour» or is it «Medical»? Medical: Behaviour Signs Stress: Effects on health / behaviour Behaviour: Normal vs. Abnormal / Pathological Combined 5

Medical Causing Behavioural Neurologic / Central / Peripheral / CDS Internal medicine  Endocrine – increase / decrease (e.g. thyroid)  Metabolic (e.g. encephalopathy) Pain / welfare: Behavioural change, mobility Sensory: Response to stimuli Dermatology (e.g. self – trauma) Drug effects (e.g. steroids / irritability) 6

Stress Altered homeostasis: Affects health and behaviour  Endocrine, immune, psychological Hypothalamic-pituitary-adrenal axis (cortisol)  acute / chronic effects on behaviour health Noradrenergic system  Acute / chronic  sympathetic arousal – lack conscious control Prolactin: Lower in acute stress, higher in chronic Hyperglycemia with stress in cats Opioid / beta-endorphin 7

Stress Effects on Medical Health Acute vs. chronic effects Chronic  Immune: Increased sensitivity to pathogens  Oxidative damage: stress, disease, age, drugs Stress related diseases in human / dogs / cats  GI, urinary, dermatologic, respiratory, aging  Feline example: stressful events and skin, GI / appetite, urinary, respiratory, avoidance (Stella et al, JAVMA) 8

Stress: Ingestive and GI Signs Humans  Alter bacterial flora, gastric emptying, heartburn, colonic activity, intestinal permeability, irritable bowel, ulcerative colitis Pets  Anorexia (particularly problematic in some cats)  gastrointestinal signs / colitis  psychogenic polydypsia  pica (lick, suck, gulp, gorge, coprophagia)  obesity 9

Is it «Medical» or is it «Behavioural»? Environmental licking n = 20 (Frank et al, ACVIM 2009)  Full workup including GI, scope, biopsy  GI disorders 14/20 dogs / resolved 10 of 18 10

11 Video: LICK3

12 Video: CAT01

Stress and the Urinary Health Feline Interstitial Cystitis (FIC) and stress  Altered bladder permeability, noradrenaline ↑ MEMO (multi-modal environmental modification)  reduce FIC, respiratory, fear, nervous, IBD, aggression ( Feliway diffuser – less bouts 13

Stress and the Urinary Health FIC – Seawright et al., Cameron et al.  Higher risk with recent move, recent injury, dogs in home, movement restricted by other cat  Improvement over placebo by reducing anxiety, increasing space, separating resources 14

Stress and Dermatology Brain-skin connection Stress may be a trigger for skin disease Psycho-neuro-immuno-endocrinological response Human  Stress and atopic dermatitis, psoriasis, urticaria  Stress increase cytokines, IgE, eosinophils, vasoactive peptides in atopic vs. non-atopic  Stress and increased epidermal permeability 15

Stress and Dermatology Pets  Increased severity and frequency of skin disorders in separation anxiety, non-social fear  Psychogenic and recurrent pyoderma in dogs  Psychogenic and pruritus in dogs  Allergen penetration if increased permeability? 16

Stress and Mental Health Enrichment, behavioural needs / time budget Undesirable may fill void 17

Stress and Mental Health Conflict: Competing motivation Frustration: Unable to achieve goal Displacement: Lick, circle, yawn, suck, drink 18

19 Video: GREETCIRCLE

20 Video: CIMG6542

Contributing Factors Medical complications Owner response 21

Stress and Mental Health Recurrent / Chronic stress  Cope vs. unable to achieve homeostasis 22

Stress and Mental Health Correlates to humans  phobia, generalized anxiety disorder, compulsive behaviour  post traumatic stress, impulsivity, panic 23

Behaviour Pathology Deprivation: Prenatal / neonatal / maternal Insufficient early socialization / habituation Genetics  Abnormal serotonin and aggression  English Cocker Spaniel, Springer Spaniel  Compulsive – outside situations of conflict  Repetitive, exaggerated, sustained  Attention to particular goal  Self-trauma, neurologic, ingestive 24

Compulsive Behaviour Doberman exhibiting obsessive flank-sucking. Photo: Tufts University. 25

26 Video: P

Is it «Behavioural» or «Medical»? 27

Evaluation of 21 Cats with a Presumptive Diagnosis of Psychogenic Alopecia Non-seasonal, no primary lesions, no scratch Exam, blood / urine, derm assessment Revolution (3 tx), food (Feline z/d - 8 weeks)  Response assessed – food challenge if improved Methylprednisolone acetate at 8 / 11 weeks  Response to therapy assessed S. E. Waisglass, G. M. Landsberg, J.A. Yager, J. A. Hall, JAVMA

Polling question Of the 21 cats referred with psychogenic alopecia, how many had an entirely medical cause?

Results Medical: 16/21 (76.2%)  Food 57% / Multifactorial 52% Psychogenic + Medical: 3/21 (14.3%) Psychogenic alopecia (PA): 2/21 (9.5%) Histology not confirmatory 30

Diagnosis - Behaviour Problems Normal?  Inappropriate / undesirable: Time / place / target  No drugs indicated but natural products may help Abnormal?  Fear / anxiety, attention deficit, hyperactivity disorder (ADHD), panic, phobia, compulsive  Rule out medical  Drugs and/or natural products are indicated 31

Normal behaviour  Eliminate /mark  Climb / explore  Scratching  Play / nocturnal  Vocalize  Predation  Mating Common problems  Eliminate /mark  Climb / explore  Scratching  Play / nocturnal  Vocalize  Predation  Mating (neuter) Feline Behaviour 32

Common problems  Eliminate /mark  Climb / explore  Scratching  Play / nocturnal  Vocalize  Predation  Mating (neuter) Canine Behaviour Normal behaviour  Age, breed, Individual  Hunt / scavenge  Eliminate / mark  Social / object play  Territorial – vocal  Sexual 33

Fear, Anxiety, Stress Fear: Response to perceived threat Anxiety: Anticipation of threat / danger Genetics / development / socialization / experience Insufficient outlets / enrichment Unpredictable consequences Lack of environment control Punishment – owner emotional state 34

Signs of Fear, Anxiety Behavioral – anxiety, stress, fear  Fight / threat, flight (avoid), freeze  Ears, eyes, lips, tail, posture  Autonomic: Heart and respiratory rates, salivation, trembling 35

36 Video: Snapping dog on table - no GL

Fear Prevention Socialize/Habituate: 7-9 wks. cats, wks. Dogs Reward desirable, not punish undesirable Provide outlets – enrichment Environmental control Natural products to adapt 37

Understand normal behaviour Age/breed/health appropriate Social intraspecific Social interspecific – pets, people Object play – work for food Canine Enrichment 38

Canine Enrichment - Humain Social time, play, exercise, train for rewards Consider canine, breed, individual needs 39

Canine Object Play Explore, scavenge, chew Provide outlets Work / train for food  Stuff, freeze, manipulate  Search and find 40

41 Dog playing with Konk toy Video: CIMG9745

Understand normal behaviour Multiple small meals / play sessions – mouse size  Predation 8-10 mice per day – 2 of 3 missed Object play / explore Social: intraspecific / interspecific Feline Enrichment – Indoor Housing 42

Play: Novelty wears off but interest heightens Individual: Movement, texture, food, size Play: Increase with hunger, end with food Reward train Enrichment – Social (human) 43

44 Video: cattrain

45 Video: play2CIMG5043

Food toys: Hunt / work for food  Hunt independent of kill Explore: Climb, perch, scratch Rest / comfort / security Object Play / Explore 46

Provide outlets - reward use Prevent – positive confine  Control, security Supervise – inhibit - deterrents Set Up to Succeed 47

48 Cat on counter - deterrrent Video: Case39part3

Adoption – new home – moving – change Boarding, confinement, travel Unfamilar people / pets Veterinary clinic, groomer Urine marking Separation related problems Noise / Storm / Fireworks Fear, Anxiety, Stress 49

Physiologic, emotional, behavioral outcomes Identify fear stimuli: Avoid Expose below threshold: Desensitize (DS) Response substitution (RS)  Train / reward behavior Countercondition (CC)  Positive association Natural products / drugs: Start early! Fear, Anxiety, Stress - Treatment 50

May decrease behaviour: Avoid / retreat Does not decrease fear or train desirable Herron et al, AABS, 2009  Confront – alpha roll, yelling «NO» can increase aggression expecially if aggressive to family Blackwell et al, JVB – 2008  Punish: Increase fear / avoidance  Punish + reinforce: higher risk of aggression Confrontation and Punishment 51

Start early! Build confidence, reduce stress Reduce arousal – anxiety  Low: Conscious control – allows for learning  High: Immediate response vs. learning Alter neurotransmitters / receptors Natural products  Safer? Adverse effects?  Standardization? Show me the evidence! Natural Products / Drugs 52

Randomized Control Trial – Placebo Effect up to 50% Clinical trials – owner measures – subjective?  Time / expense – inclusions / exclusions  Placebo effect - No one wants placebo Laboratory trials – lab measures – objective?  Standardized population - Less time / expense  Need to validate model – does it predict clinical Behaviour Therapeutic Trials 53

Polling question – Check all that apply 54 Which of these natural supplements have you already used for anxious pets? Bach’s flower remedies L-theanine (Anxitane) L-tryptophan Pheromones (DAP, Feliway) Alpha-casozepine (Zylkène) None

Natural products  Veterinary labelled: Zylkène, Anxitane, DAP/Feliway, Harmonease (USA)  Tryptophan/low protein, aromatherapy, melatonin Drugs  Veterinary labelled: Reconcile, Clomicalm, Anipryl  Buspirone, benzodiazepines, propranolol, trazodone, clonidine, carbamazepine, memantine Evidence-Based Products 55

Tryptic hydrolysis of milk as in newborn  Bovine milk hydrolysate - alpha S-1 casein  Calming - Safe – Crosses blood-brain barrier  Affinity for GABA receptors – inhibitory, anxiolytic Dose > 15 mg/kg  Cat: Open into food sid / Dog: Sid or divided  Up to 30 mg/kg for situational (e.g. travel, noise) Trial: 2 weeks to 2 months. May be used long term if successful Alone or combine with other natural / drug Zylkène ® 56

Social stress, development, age related stress Environmental stress  change, moving, adoption Fear: Animate, inanimate, situations Urine marking (cats) Indications – Dogs / Cats 57

JVB 2007– Beata et al. 38 dogs, 56 days trial – alpha-casozephine vs. Selegiline Evaluation of Dog's Emotional Disorder (EDED)  Feed, drink (pu/pd), groom, sleep, explore  Aggression, social, learning, stereotypic / acral lick dermatitis  Physical: HR, RR, gastrointestinal, obesity Comparable in improving EDED score Effects of Alpha-Casozepine on Anxiety Disorders in Dogs 58

JVB 2007 – Beata, Beaumont-Graff, Coll et al. 34 cats, 56 day trial – placebo trial Anxious disorders – emotional scale for cats  Tolerance of contact familiar people  Contact with strangers  Aggression, fear  Physical signs / autonomic signs Significant improvement in global score Effects of Alpha-Casozepine on Anxiety Disorders in Cats 59

Feliway: Feline facial pheromones (F3)  Marking, scratching, transport, moving  Idiopathic cystitis DAP (Adaptil) – Lactating bitch sebaceous pheromones  Separation anxiety, storm / fireworks  New home, socialization  Travel, veterinary clinic Evidence - Pheromones 60

L-theanine (Anxitane) – JVB - Laboratory trial (CanCog) – fear of unfamiliar human Magnolia / Phellodendron (Harmonease, USA) JVB - Laboratory trial (CanCog) – induced thunder L-tryptophan / low protein diet – JAVMA – canine territorial and aggression Aromatherapy – lavender – JAVMA – travel Evidence – Other Natural Products 61

Fluoxetine – RCT – separation anxiety – ongoing  Compulsive, marking (feline), generalized anxiety Clomipramine – RCT - separation anxiety – ongoing  Compulsive, marking (feline), storms Buspirone / benzodiazepines / propranolol Trazodone, Clonidine, Carbamazepine, Memantine  Adjunctive or as needed Could combine with natural Drugs 62

Control, reward train, predictable, enrich, routine Set up to succeed / safe area Puppy – second dog, other dogs Age of adoption, puppy class, socialize Avoid fear evoking stimuli Anxiety: DS / CC / RS Natural products / drugs Positive Adoption 63

Positive from outset:  Car – reception – exam  Owner – staff – DVM  Treats, toys - avoid negative Fear / anxiety: DS / CC – safety – natural / drugs Positive Veterinary Visits 64

Positive association with restraint / carrier / car  Secure restraint – head halter  Other pet – owner - treats / toys Fear / anxiety: Avoid till DS / CC / RS Natural products early Drugs – as needed Positive Car Travel 65

Reactive – Anxious – Territorial – Hormonal Identify stimuli  Prevent / block / deter stimulus access to cat  Prevent / block / deter cat access to stimulus Determine cause – resolve (e.g. conflicts) Evidence - pheromones, fluoxetine, clomipramine Other natural products Feline Urine Marking 66

Anxiety / distress panic during departure, not spite Destructive, soil, vocal, ANS signs (pant, salivate) Separation Distress 67

Behaviour Modification Program (BMP)  Reward relaxed / settled behaviour - safe location  Structure interactions: No attention on demand  Avoid punishment  Habituate to cues - departure exercises  Schedule – enrich – toys / settle pre-departure Natural product if mild / early / adjunctive or labelled drug (e.g. fluoxetine, clomipramine) Separation Distress 68

40-50% of dogs - increases with age  Fireworks 32 %, Thunder 31%, Gunshots 18% Noise Sensitivity / Aversion 69

Safe haven Visual (home, pet) Reduce sound Static Environmental Modification 70

Reward train settle / relax – comfort location DS / CC and RS with recordings Products: Head halter, anxiety wrap, thundershirt Natural products / Drugs – ongoing +/- as needed Behavior Modification 71

13.5 yr F(S) soft coated Wheaten Terrier – 15 kg Recent stressors: Divorce – shared custody – in two homes - loss of dog housemate of 12.5 years No health issues – ruled out cognitive dysfunction Increasingly nervous – shakes, trembles, pants Sensitive to noises - wind, coffee maker, ice maker Worst in car – shake, drool, climb on owner Jumps on owner or anyone for comfort Maggie the Anxious Wheaten 72

Can’t continue to see Maggie this way Numerous previous products with no effect Rx Zylkène – 225 mg tablet daily (15 mg/kg) Effect within few days Maggie 73

2 months - More relaxed / calm (not perfect)  Car rides – biggest relief – lies down, no shaking / panting but does not yet enjoy Medication discontinued  Immediate recurrence of nervous, noise fear 6 month follow-up – well controlled Happier dog – happier owner Follow-up 74

The Happy Ending 75

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