1. Institute of Experimental Medicine
Anxiety, agression, depression
Functions and disfunctions of complex systems
József Haller

2. Three phases of coping with challenges
Potential
threat
„Defeat"
Environmental events
Anxiety
Alarm
"Depression"
Emotional responses
Behavioral responses
Risk avoidance
(„precutionary programs")
Fight/flight
(„action programs")
Activity avoidance
(„survival programs")

3. („precutionary programs")
Coping and psychiatric problems
Emotional responses
Conditions psychopathology
Anxiety
Risk avoidance
(„precutionary programs")
Axiety disorders
Aggression-related
psychopathologies
Depression
These
occur inadequately
are persistent
cause suffering
Alarm
Fight/flight
(„action programs")
"Depression"
Activity avoidance
(„survival programs")

4. Dysregulated coping – list of psychiatric disorders
Anxiety
Generalized
Panic
Agoraphobia
Specific phobias
Social phobia
Post-traumatic stress disorder
Agression-related
Intermittent Explosive disorder
Conduct disorder
Oppositional-defiant disorder
Antisocial personality disorder
Borderline personality disorder
Other disorders
Schizophrenia
Drug dependence (including alcohol)
Attention deficit-hyperactivity disorder
Neurological diseases
Brain damage
Epilepsy
Alzheimer disease
Depression
Minor
Major
Bipolar
General features
comorbidity
large frequency
challenging in terms of suffering and costs
Solutions
Psychotherapy
recognition of the problem (cognitíve therapy)
problem-solving strategies (behavioral therapy)
Pharmacotherapy
understanding brain mechanisms
identifying targets of intervention
drug development

5. The first step of pharmacotherapy: understanding brain mechanisms
The scientific model is a simplified artificial system,
which is isomorphic
in key features of the modelled phenomenon
(alike but not the same)
What makes psychiatric modelling possible?
the universality of neural functions
the universality of emotions
the unversality of the stress-emotions relationship
the homology of etiological factors

6. * Agression models Models of the natural phenomenon
Psychopathology models
Hypothalamic aggression
The resident/intruder test
Trait selection
Stress models
Developmental models 2 4 6 8 10
Soft bites
Hard bites
All bites
Attack counts *

7. Circuits of aggression - „phenomenon" and psychopathology
Are people different?
Mainly electrophysiologic techniques ( )
Psychosurgery
Brain imaging
Hess (1928)
Siegel et al. ( )
Activated by fighting
Over-activatied in socially isolated rats
Three-dimensional representation of the right-hand side of the brain by the Blender software, based on Paxinos and Watson (1998)
PrL
Cg1 MO IL VO LO
NacSh LS
BNST
PVN
HAA LH
MeA
CeA LA
BLA
dmPAG
lPAG
vlPAG
dlPAG LC
VTA
Bregma -5.0 mm
Bregma 0.0 mm
+5.0
Mainly immuncytochemistry and pharmacology ( )
Kruk et al. ( )

8. Anterior limbic cortex
Aggression-related psychopathologies – treatments based on the natural phenomenon 1 2
Prefrontal cortex
Anterior limbic cortex
N. accumbens
Amygdala
Forebrain bundle
Striatum
Substantia nigra (dopamine)
1= nigrostriatal pathway (motor functions)
2= mezolimbic pathway (rewards)
ventrális tegmentl area (dopamine)
Dorsal raphe (serotonin)
Locus coeruleus (noradrenaline)
Current pharmacotherapies are based on these pathways
Therapies based on psychopathologic models?

9. Anxiety models Models of the natural phenomenon Psychopatology models
Selection lines, transgenic animals, etc...
Vogel test

10. The circuits of anxiety
Internal cues
Raph Lc
Agyk NE
CRF
hip
Emotional memory
Environmental cues Am
processing
Thal
Thal ht
sgc
flight
/avoidance
perseverence
panic

11. global inhibition (GABA)
Anxiety – treatments based on the natural phenomenon
global inhibition (GABA)
anxiety decreases
global excitation
(glutamate, glicine)
anxiety increases
The dynamics of global excitation and inhibition 1 2
Prefrontal cortex
Anterior limbic cortex
N. accumbens
Amygdala
Forebrain bundle
Striatum
Substantia nigra (dopamine)
1= nigrostriatal pathway (motor functions)
2= mezolimbic pathway (rewards)
ventrális tegmentl area (dopamine)
Dorsal raphe (serotonin)
Locus coeruleus (noradrenaline)
Current pharmacotherapies are based on these pathways
Therapies based on psychopathologic models?

12. Depression models – psychopatological symptom models
Chronic mild stress - anhedonia

13. Circuits of depression

14. Anterior limbic cortex
The treatment of depression
sleep deprivation
combined melatonin-serotonin therapy
light therapy
electroshock 1 2
Prefrontal cortex
Anterior limbic cortex
N. accumbens
Amygdala
Forebrain bundle
Striatum
Substantia nigra (dopamine)
1= nigrostriatal pathway (motor functions)
2= mezolimbic pathway (rewards)
ventrális tegmentl area (dopamine)
Dorsal raphe (serotonin)
Locus coeruleus (noradrenaline)

15. Environmental effects Developmental conditions
The treatment of psychiatric disorders – current strategies
Environmental effects
neuromodulation
anxiolytics
anti-agressive drugs
antidepressant
Prefrontális ktx
Szaglógumó
Gyrus Cinguli
Hippocampus
Amygdala
Hypothalamus
Thalamus
Centrális
szürkeállomány
Developmental conditions
"Background"
(endocrine, metabolic, etc.)
Genetic background

16. Strategies of the future
Search for mechanisms
Search for targets
Testing
Treatment
what was changed
in the brain (pathology!)
are changes causative?
does the „repairing” of
brain changes
„repair” behavior?
is it applicable
to humans?
new generation
of therapies

17. Thanks for your attention