Neurobiology of Neurobiology of Burn-Out and Burn-Out and Depression: Depression:

Same or Different?Same or Different?

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Prof. Philippe CortenProf. Philippe CortenUniversité Libre de Université Libre de

BruxellesBruxellesClinique du stress CHU-Clinique du stress CHU-

BrugmannBrugmannBCNBP Brussels 2014BCNBP Brussels 2014

Hypothesis of Hypothesis of depressiondepression

NeurotrophicMono-aminergic

Inflammatory

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

Anisman et al. 2008

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StressStress

►Stress: rhinencephalic activity Stress: rhinencephalic activity related to the sympathetic related to the sympathetic nervous systemnervous system

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Physiology of stressPhysiology of stress

LipolysisLipogenesisGlucogenesis

Cortisol

Cholesterol

Androsterone

ACTHCRF

Stress

DHEA

KREBS Cycle

Triglyceride

Liver (GammaGT, LDH)

Thyroid

Food sugars

Hyperglycemia

Parathyroid

Muscles (CPK)

Boon (Ostéoporosis)

Effect of cortisolEffect of cortisol

► Decrease of the volume Decrease of the volume of the hippocampusof the hippocampus RôleRôle

► Working MemoryWorking Memory► Episodic and Semantic Episodic and Semantic MemoryMemory

► Management of emotionsManagement of emotions

Effet du cortisolEffet du cortisol

► Modification of the Modification of the volume of the volume of the amygdalaamygdala Decrease (acute Decrease (acute stress) then stress) then increase (chronic increase (chronic stress)stress)

► Role: basic Role: basic emotionsemotions Fear, irritability, Fear, irritability, agressivityagressivity

Stress: decrease of the Stress: decrease of the prefrontal blood flowprefrontal blood flow

► Role of the Role of the prefrontal cortex: prefrontal cortex: anticipationanticipation.. It allows to put in It allows to put in perspective perspective informations from the informations from the amygdala that it amygdala that it cannot manage anymorecannot manage anymore

►=> Helplessness fellings to answer => Helplessness fellings to answer adequately to the requirements of the adequately to the requirements of the tasktask

Stress and decrease of Stress and decrease of the activity of the the activity of the

Girus CinguliGirus Cinguli► The Girus Ciguli The Girus Ciguli activity is activity is related to the related to the pain and the pain and the pleasure. pleasure. If it activity If it activity decreases,decreases,► andand the pain the pain ► and and the pleasure decreasethe pleasure decrease

It can trigger real It can trigger real physical and emotional physical and emotional anesthesias anesthesias (sideration)(sideration)

Effect of cortisolEffect of cortisol

► Decrease of the Decrease of the activity of the activity of the nucleus accumbensnucleus accumbens Effects: Effects:

► Reaction of social Reaction of social aversion aversion

► inhibition of the flight inhibition of the flight or fight behavioror fight behavior

► Increase of the Increase of the inhibition behavior inhibition behavior (freeze)(freeze)

Related to the ventral Related to the ventral tegmental area: reward tegmental area: reward circuitry and dopamine circuitry and dopamine releaserelease

Effects of the stress on locus Effects of the stress on locus coeruleuscoeruleus

► Locus coeruleus:Locus coeruleus: Noradrenergic centerNoradrenergic center Activation of the Activation of the sympathetic nervous sympathetic nervous systemsystem

Concentration and Concentration and awarenessawareness►Impact on the Impact on the memorizationmemorization

►Regulation of awakening Regulation of awakening and the sleeping and the sleeping

►Early morning awakeningEarly morning awakening

Nerve centers involved with stress Nerve centers involved with stress reactionsreactions

► HippocampusHippocampus: : memory problemsmemory problems

► Amygdala: Amygdala: fear, irritability (sérotonin)fear, irritability (sérotonin)

► Prefrontal cortex: Prefrontal cortex: helplessness feelingshelplessness feelings

► Gyrus cinguli: Gyrus cinguli: emotional anesthesiaemotional anesthesia

► Nucleus accumbens: Nucleus accumbens: social aversion and inhibition of the social aversion and inhibition of the action (dopamine)action (dopamine)

► Locus coeruleus: Locus coeruleus: sympathetic reaction, concentration, sympathetic reaction, concentration, early morning awaking (norepinephrine and noradrenaline)early morning awaking (norepinephrine and noradrenaline)

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And in case of And in case of depression?depression?

The same!The same!

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A terrible mix in the A terrible mix in the ethological research on ethological research on

depressiondepression► Ethological modelEthological model

Animal studies on Animal studies on depression = effects of depression = effects of stress conditionsstress conditions

► A rat is put a plexyglas A rat is put a plexyglas box. This box is too box. This box is too little to move inside. little to move inside. All arounds the box: All arounds the box: cats!cats!

► Depression criteria: « So Depression criteria: « So it is impossible to it is impossible to measure the seadness of a measure the seadness of a rat. Thus we measure the rat. Thus we measure the inhibition of the motor inhibition of the motor activity and the quantity activity and the quantity of glucose that the rat of glucose that the rat drinks in order to drinks in order to reinforce pleasure »reinforce pleasure »

A terrible mix in the A terrible mix in the ethological research on ethological research on

depressiondepression► Others Others methodological methodological approachs in the approachs in the ethological studies ethological studies of depression:of depression: The time during wich The time during wich a rat rebels against a rat rebels against if it is kept by if it is kept by the tailthe tail

The time during wich The time during wich a rat goes round and a rat goes round and round after an round after an electrical shock. electrical shock.

A terrible mix in the A terrible mix in the ethological research on ethological research on

depressiondepression► Most of the time the Most of the time the pharmacological pharmacological researchs based on researchs based on ethological methods ethological methods arebased on arebased on following syllogism:following syllogism:

► Are considered as Are considered as depressive behavior depressive behavior these one wich these one wich answer favorably to answer favorably to antidepressive antidepressive drugs!drugs!

Then, it means that there are no Then, it means that there are no differences between depression differences between depression

and Burn-Out ?and Burn-Out ?

What is Burn-Out?What is Burn-Out?

• To cope with stress To cope with stress we use three we use three adaptative behavioursadaptative behaviours– 1: To become 1: To become emotionaly hardenedemotionaly hardened

– 2: To put in 2: To put in perspective and to put perspective and to put limitslimits

– 3: To adapt the 3: To adapt the ambitions to the ambitions to the realityreality

• Burn-Out : ceaseless Burn-Out : ceaseless repetition of the repetition of the same behavior , even same behavior , even in the private lifein the private life– 1: It is impossible 1: It is impossible to be hardened only to be hardened only against negative against negative emotions. All the emotions. All the emtions are involved, emtions are involved, even the positive even the positive onesones

– 2: Due to put always 2: Due to put always in perspective we in perspective we become cynical become cynical

– 3: Due to always 3: Due to always reduce the ambitions reduce the ambitions we become demotivatewe become demotivate

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Advantages and disadvantages Advantages and disadvantages of emotional and sensations of emotional and sensations

anesthesiaanesthesia

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Advantages and disadvantages Advantages and disadvantages to put limits and to get to put limits and to get

some spacesome space

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Advantages and disadvantages Advantages and disadvantages

to reduce the ambitionsto reduce the ambitions

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But never stop to dream!But never stop to dream!

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Differential diagnosesDifferential diagnosesRelationships between Burn-Out and depressive symptomsS. Terrasse & al. 2009

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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)

Differential diagnosesDifferential diagnosesBlack Dog Institute Black Dog Institute HypothesisHypothesis

► Burn-Out should be a Burn-Out should be a paculiar form paculiar form depression by people depression by people with an external locus with an external locus of controlof control

► => Irritability in => Irritability in place of sadnessplace of sadness

Burn-Out severity versus others Burn-Out severity versus others pathological stress.pathological stress.

P. Dewell & al. 2009P. Dewell & al. 2009 N=480Locus of control

BO Max

BO=0 p

Internalist

2,6 3,34 .0060

Externalist

2,07 1,2 .0002

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Then, no differences? Then, no differences? YES and NO YES and NO