Neurobiology of Burn-Out and Depression: Same or Different?

1. Neurobiology of Burn-Out and Depression: Same or Different? Prof. Philippe Corten Université Libre de Bruxelles Clinique du stress CHU-Brugmann BCNBP Brussels 2014

2. Hypothesis of depression Mono-aminergic Neurotrophic Inflammatory Anisman et al. 2008 ACTH = adrenocorticotropic hormone; AVP = arginine vasopressin; CORT = cortisol; DA = dopamine; GRP = gastrin-releasing peptide; IL = interleukin; NE = norepinephrin; NMB = neuromedin B; TNF = tumour necrosis factor. JAK: Janus kinase, STAT: signal transducer and transcription activator, MAP: mitogen-activated protein

3. Stress Stress: rhinencephalic activity related to the sympathetic nervous system www.cliniquedustress.be

4. Physiology of stress Stress Boon (Ostéoporosis) CRF ACTH Parathyroid Thyroid Muscles (CPK) Cortisol DHEA Hyperglycemia Lipolysis KREBS Cycle Androsterone Lipogenesis Glucogenesis Triglyceride Food sugars Cholesterol Liver(GammaGT, LDH)

5. Effect of cortisol • Decrease of the volume of the hippocampus • Rôle • Working Memory • Episodic and Semantic Memory • Management of emotions

6. Effet du cortisol • Modification of the volume of the amygdala • Decrease (acute stress) then increase (chronic stress) • Role: basic emotions • Fear, irritability, agressivity

7. Stress: decrease of the prefrontal blood flow • Role of the prefrontal cortex: anticipation. • It allows to put in perspective informations from the amygdala that it cannot manage anymore • => Helplessness fellings to answer adequately to the requirements of the task

8. Stress and decrease of the activity of the Girus Cinguli • The Girus Ciguli activity is related to the pain and the pleasure. • If it activity decreases, • and the pain • and the pleasure decrease • It can trigger real physical and emotional anesthesias (sideration)

9. Effect of cortisol • Decrease of the activity of the nucleus accumbens • Effects: • Reaction of social aversion • inhibition of the flight or fight behavior • Increase of the inhibition behavior (freeze) • Related to the ventral tegmental area: reward circuitry and dopamine release

10. Effects of the stress on locus coeruleus • Locus coeruleus: • Noradrenergic center • Activation of the sympathetic nervous system • Concentration and awareness • Impact on the memorization • Regulation of awakening and the sleeping • Early morning awakening

11. Nerve centers involved with stress reactions • Hippocampus: memory problems • Amygdala: fear, irritability (sérotonin) • Prefrontal cortex: helplessness feelings • Gyrus cinguli: emotional anesthesia • Nucleus accumbens: social aversion and inhibition of the action (dopamine) • Locus coeruleus: sympathetic reaction, concentration, early morning awaking (norepinephrine and noradrenaline)

12. And in case of depression? The same!

13. A terrible mix in the ethological research on depression • Ethological model • Animal studies on depression = effects of stress conditions • A rat is put a plexyglas box. This box is too little to move inside. All arounds the box: cats! • Depression criteria: « So it is impossible to measure the seadness of a rat. Thus we measure the inhibition of the motor activity and the quantity of glucose that the rat drinks in order to reinforce pleasure »

14. A terrible mix in the ethological research on depression • Others methodological approachs in the ethological studies of depression: • The time during wich a rat rebels against if it is kept by the tail • The time during wich a rat goes round and round after an electrical shock.

15. A terrible mix in the ethological research on depression • Most of the time the pharmacological researchs based on ethological methods arebased on following syllogism: • Are considered as depressive behavior these one wich answer favorably to antidepressive drugs!

16. Then, it means that there are no differences between depression and Burn-Out ?

17. What is Burn-Out? • To copewith stress we use three adaptative behaviours • 1: To becomeemotionalyhardened • 2: To put in perspective and to put limits • 3: To adaptthe ambitions to the reality • Burn-Out : ceaseless repetition of the same behavior , even in the private life • 1: It is impossible to be hardened only against negative emotions. All the emtions are involved, even the positive ones • 2: Due to put always in perspective we become cynical • 3: Due to always reduce the ambitions we become demotivate www.cliniquedustress.be

18. Advantages and disadvantages of emotional and sensations anesthesia www.cliniquedustress.be

19. Advantages and disadvantages to put limits and to get some space www.cliniquedustress.be

20. Advantages and disadvantages to reduce the ambitions www.cliniquedustress.be

21. But never stop to dream! www.cliniquedustress.be

22. Differential diagnoses Relationships between Burn-Out and depressive symptoms S. Terrasse & al. 2009 The scale wich differentiate the most BO and depression is the BDI (loss of pleasure) and the less is the GHQ depression (pessimism). But only 45% of the people with Burn-Out are depressives. The MADRS includes the most of BP (Irritability) www.cliniquedustress.be

23. Differential diagnoses Black Dog Institute Hypothesis Burn-Out severity versus others pathological stress. P. Dewell & al. 2009 • Burn-Out should be a paculiar form depression by people with an external locus of control • => Irritability in place of sadness www.cliniquedustress.be

24. Then, no differences? YES and NO