Emotion and Cognition - The Zurich Depression Studies

Prof. Dr. med. H. Böker Clinic of Affective Disorders and General Psychiatry Zurich East

SFI International Symposium 2011 Chronic Depression - Clinical, Conceptual and Empirical Research

University Frankfurt, Campus Bockenheim, 28. - 30.10.2011

1.  Introduction: The empirical basis for neuro-psychodynamic hypotheses

2.  The Problem of depressive inhibition

2.1 Negative affective bias

2.2 Psychomotoric disorders

3.  Single-case research in depressed patients

4.  Results from combined fMRI/MRS and neuropsychological studies

Emotion and Cognition - The Zurich Depression Studies

5.  A neuro-psychodynamic model for the disturbed emotional self-reference in depressed patients

6.  Future steps in anhedonia research

7.  The Zurich Neuroimaging Study on Psychodynamic Psychotherapy in Depressed Patients

8.  Conclusion: Scientific implications

Emotion and Cognition - The Zurich Depression Studies

Emotion, Cognition and Actions in Depressed Patients

- Clinical Observations -

Ø  Why do negative thoughts get locked into place in depression?

Ø  Neurophysiological correlates of inhibition/blockade: „My right foot is on the accelerator, my left one on the brakes“

Negative affective Bias

•  Cognitive triad (Beck 1974) •  Network models for depression (Segle et al. 1996)

•  Negative emotions are over-represented in semantic networks •  Basic shift of the emotional assessment of new und early experiences

•  Mood congruent recall •  Memories from the respective emotional situation are recalled more easily

(Blaney 1986) •  The cognitive-affective spiral of depression promotes negative thoughts

and negative associations (Teasdale 1988, Ackermann-Engel, De Rubeis 1993)

•  Therapeutic implications!

Experiencing extremely intensive and uncontrollable emotions: “Numb with fear”

Depressive Stupor as a Psychomotoric Syndrome

Böker et al. Psychiat. Prax. 2000 Northoff, Böker et al. Neuro-Psychoanalysis 2003

-  Single-case approach: (Landfield categories)

•  Lack of social contact •  „Low“ self-esteem •  „Low“ emotional arousal

Self-image and Object Relationships in Depressed Patients

Ø  Qualitative personality studies (depressed subjects in remission)

-  Negative self-image

-  Idealising significant others

-  Significance of the inter-personal dimension

Boeker 1999 Boeker et al., J. Affect. Disord., 2000

Emotional Experience and Decision-Making

2.Step: Decision-making

1. Step: Experience and judgement of emotions

Aristoteles

Result: Catatonics and depressed subjects unable to take action (blockade)

Healthy Subjects Catatonics

Catatonia/Stupor: VMPFC and Emotional Experience

Northoff et al. 2004 Northoff u. Böker 2005 Böker u. Northoff 2005

0

500

1000

1500

2000

2500

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catatonics (n=6)psychiatric controls (n=5)healthy controls (n=11) a*,b*

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Right Left

2500 2000 1500 1000 500

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Signal

Catatonics Psychiat. Cont. Healthy Cont.

• Healthy subjects: Activation in VMPFC

• Subjects previously with depression and stupor: Low activation (particularly after negative stimuli)

Emotional Experience: Correlation with Actions/IGT

Connection between emotional experience, the VMPFC and decision-making

Northoff und Böker 2003 Böker und Northoff 2005 Northoff et al. 2005

The more activity in the VMPFC, the better the decision-making

→ Healthy subjects: In the long-term more successful low-risk cards → Previous stupor: No change in decision-making despite negative consequenses

Subjective Emotional Experience

Journal of Consciousness Studies, 1014-48, 2003

Correlation between experience data and fMRI data concerning emotions

Emotional stimulation in the fMRT with pictures

Visual analogue scales for emotional experience

International Affective Picture System (IAPS, Lang 1999)

Expectancy: Emotional judgement: 8 - 11.5 sec

Emotional judgement: 4 sec

Fixation cross: 6 - 8 sec

Expectancy: Emotional perception: 8-11.5 sec -

Emotional perception: 4 sec

Fixation cross: 6 - 8 se c

A Emotional judgement:

4 sec Fixation cross:

6 - 8 sec

Emotional perception: 4 sec

Fixation cross: 6 - 8 sec

A/A

A/A E

C

0 8 12 18 22 28 s

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Emotionale perception Fixation cross Emotional

perception Fixation cross

B

J J P/N

P/N

Emotional judgemeng Fixation cross Emotional

judgement

0 8 12 18 22 28 s

Fixation cross Expectancy period

Expectancy period

Brain activation during “Experience” and “Judgement”

(in Healthy Subjects)

Grimm et al. 2006, 2007

Neural activity in the VMPFC is correlated with negative emotional experience

VMPFC: Ventromedial prefrontal Cortex

Neural activity in the DLPFC is correlated with positive emotional judgement

DLPFC: Dorsolateral prefrontal Cortex

VMPFC: Depressed > Healthy

Hyperactivity in the VMPFC = Abnormal negative experience

DLPFC: Healthy > Depressed

Hypoactivity in the DLPFC = Abnormal negative judgement

Brain activity during “Experience” and “Judgement”

Comparison between Depressed and Healthy Subjects

Left DLPFC Hypofunction: Negative cognitions

VMPFC Hyperactivity: Negative emotional perception Right DLPFC

Hyperfunction: Attention/expectation of negative emotions

Severity of depression (BDI, HAMD) correlates with activation in the right amygdala and in the VMPFC

Northoff et al. 2004 Böker u. Northoff 2005 Northoff und Böker 2007

Psychiatry Research, 141(1):1-13, 2006

Depression: Abnormal reciprocal Modulation between the VMPFC/ACC and left and right DLPFC

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In patients with no symptoms brain activity unchanged in medial and right forehead region, but pattern of activity normalised in left forehead area. Activity in left forehead region normalised following successful treatment of depression. Lasting changes in brain activity in right and medial forehead region despite improvement of depression: Sustained attention, executive function and working memory

Ventromedial hyperactivation and dorsolateral hypoactivation connected to neuropsychological deficits

Cognitive and psychopathological symptoms become dissociated in the course of the illness!

controls

acute patients remitted patients

Inhibition phenomena and disruption of emotional self-reference in depressed patients:

Brain activity after improvement of depression

Boeker and Grimm, submitted

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Controls MDD patients

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Depressed subjects: Signal changes in the left DLPFC show an opposite or no correlation when judging positive / negative pictures

MDD patients

Pathophysiology of the Negative Affective Bias

• Depression: Reduced activity in the left DLPFC, increased activity in the right DLPFC

• Activity in the left DLPFC not or contrarily modulated by emotional valence Activity can not be modulated according to the degree of negative emotions Negativer Bias

• Activity in the right DLPFC correlated to severity of depression

Grimm et al. Biol. Psychiatry, 2008

Depressive Hopelessness and reduced Deactivation (PACC, PCC)

•  MDD: Reduced deactivation in the PACC and PCC (Default Mode Network)

•  Deactivation only in medial regions, other regions show activation (specific to region!)

•  Activation in the case of inwardly-directed attention

•  Depressed subjects: No connection between deactivation and negative emotional content

•  The less deactivation, the more pronounced the hopelessness and depressive symptoms

Grimm et al. 2008, Neuropsychopharmacology

Relationship between reduced Deactivation and emotional Valence

Conclusion:

Ø  Severity of depression is correlated with reduced deactivation, depressive experience (BDI) and hopelessness

Northoff et al. 2007, Nature Neuroscience

Physiology and Neurochemistry of Emotional Processing

The more GABA in the ACC, the more pronounced the deactivation in this Region during emotional stimulation

Ø  Healthy subjects: GABA-induced deactivation during emotional stimulation

Walter, Grimm et al. 2009, Arch. Gen. Psychiat.

Pathophysiology and Neurochemistry of Emotionalen Processing in Depression

Deficits in glutamatergic metabolism: Neurotoxic factor in depression?

Mayberg, 2003

Model of Limbic-Cortical Disregulation in Depression

(a) Induced sadness in HC (b) Cg25 during Fluoxetine (MDD) (c) Cg25 during Fluoxetine (Depression/ M. Parkinson) (d) Cg25 during placebo (MDD) (e) Cg25 as a predictor for therapy

response (f) Cg25 during citalopram and CBT

Ressler & Mayberg, 2007

Cg25 as the Key Region for Therapy Response and Prediction

Ø  Neurophysiological adaptation in ACC region after treatment with antidepressants, placebo and CBT

Goldapple, K. et al. Arch Gen Psychiatry 2004;61:34-41.

Top-Down und Bottom-Up Effects: Changes in the Regional Glucose Metabolism (PET) after Successful

Treatment with CBT and Paroxetine

Treatement reaction after CBT: Increase in metabolism in the hippocampus and dorsal cingulum (BA 24), reduction in the dorsal (BA 9/46), ventral (BA 47/11) and medial (BA 9/10/11) frontal Cortex

Treatment recation after Paroxetine: Prefrontal increase, reduction in the hippocampus and subgenual cingulum

Conclusion: Therapy-specific, opposite effects (CBT: Increase in the hippocampus, reduction in the frontal cortex; Paroxetine: hippocampal reduction, frontal increase)

CBT → Top-down effects Paroxetine → Bottom-up effects

Increase in metabolism: orange Reduction: blue

Limbic-Cortical Networks in Major Depression: Group Characteristics as a Therapy Indicator

(Seminowicz et al. 2004)

•  Antidepressive Responders: -  Activation of limbic-cortical networks (LPFC - subgenual

cingulum - OMPFC - hippocampus), in contrast to non-responders

•  Antidepressiva Non-Responders: -  More disfunction in limbic-cortical networks

(ant. thalamus – AC – subgenual cingulum – OMPFC – hippocampus)

•  CBT Responders: -  Activation of surrounding limbic-cortical (Hippocampus – LPFC) and

cortical-cortical (OMPFC, OF 11 - mF 10) networks

→  Characterisation of depressive phenotypes on a neuronal system level

→  Neuronal-based algorhythms for the individual treatment of depression?

Ø  Response Ø  Not simply a „correction“ of „pre-treatment abnormalities“, but a more complex

adaptation process incl. normalization of the cortical hypometabolism and changes in specific subcortical and paralimbic regions, in which there were previously no metabolic abnormalities

Ø  Limbic-striatal reduction of glucose metabolism: Subgenual cingulum, hippocampus, insula, pallidum

Ø  Dorsal cortical increase (PFC, parietal, anterior/posterior cingulum

Ø  Increase in glucose metabolism in the brain stem

Ø  Delayed Effect Ø  Lack of changes in the cerebral glucose metabolismus in the region of the subgenual

cingulum and PFC

Ø  Persistence of the 1-week pattern (subcortical reduction, increase in the brain stem and limbic-paralimbic regions)

Ø  Lack of modification and adaptation of previous metabolic changes in the further course (week 6)

Functional Cerebral Correlations of Response and Delayed Effectiveness after Antidepressivants (Mayberg et al. 2000)

Changes in midbrain serotonin transporter availability in atypically depressed subjects after one year of

Psychotherapy (Lehto et al., 2008)

•  Sample: 19 patients (8 with atypical depression and 11 with „non-atypical“ depression)

•  Treatment: Psychodynamic Psychotherapy for 1 year

•  Reduction of symptoms in all patients

•  SPECT -  No change in dopamine transporter density (striatum) -  Change in serotonine transporter density (mid-brain) in

patients with atypical depression, but not in those with „non-atypical“ depression

Desymbolisation in Severe Depression and the Inhibition Problem

(Böker, Northoff 2005)

Ø  Depression = Psychic pain indicating a loss of the self which can not be overcome

(A. Miller)

A Neuro-Psychodynamic Model for the Disturbed Emotional Self-

Reference in Depression

Northoff, Böker (2002) Neuro-Psychoanalysis

Böker, Northoff (2005) Psyche

Northoff, Böker (2007) Psychother Psychosom

CAUTION: ROAD WORKS!

Ø  Focus on the psychoanalytical point of view: •  Condition of the self •  Nature of the experience •  How are experiences decoded and symbolised? •  Predominant emotions •  Defence and coping mechanisms

Ø  Requirements: Defence and coping mechanisms are complex emotional-

cognitive interactions and as such require neuronal integration (between different brain regions, functional connectivity)

Ø  4 principles of neuronal integration, which may be associated with specific defence mechanisms 1)  Top-down modulation and somatisation 2)  Reciprocal modulation and introjection 3)  Modulation by functional unit and sensori-motor regression 4)  Higher level of processing of internal somatic stimuli/reduction of emotional

stimuli and ego-inhibition

A Neuro-Psychodynamic Model for the Disturbed Emotional Self-Reference in

Depression

Trends in Cognitive Sciences, 98-102, 2004

Definition of the Cortical Midline Regions

Processing of physical stimuli: Bottom-up modulation

Processing of emotional stimuli: Top-down modulation

Bottom-Up and Top-Down Modulation and Somatisation: Reciprocal Adjustment between

Emotional Processing an Processing of Internal Physical Functions

Somatisation: Predominance of internal physical processing over emotional processing

Emotional Task: Experience

Cognitive Task: Judgement

Emotional-Cognitive Interaktion

B. ‘Reciprocal Reduction’

A. ‘Reciprocal Modulation’

Reciprocal Modulation and Reduction: Introjection

Introjection: •  Disruption of the emotional- cognitive readjustment •  Experiencing the outside world is transformed into experiencing the inner self (internal focus)

Attention

Unexpected emotional judgement Expected emotional judgement

Development of Functional Units Over Time: Modulation by Reversal

•  Cortical midline structures (CMS): Continually high level of neuronal activity even in resting state

•  Increase in the functional connectivity between anterior and posterior regions in resting state

•  Decrease in active cognitive tasks

Modulation by Functional Unit and Sensori-Motor Regression

•  Disrupted functional connectivity between orbitofrontal cortex, medial prefrontal and premotor/motor cortex in patients who previously had stupor

•  Conversion of emotional into motor symptoms

•  Symptomatic overlap of stupor and conversion

Self-Referential Processing and Ego-Inhibition

Ø  Self-referential stimuli (sensory, emotional, cognitive): •  Reference set to one's own person •  Essential to be able to form a concept of one's own self: Mental,

phenomenal self as the subject of experience (Damasio 1999, Panksepp 1998, Northoff, Böker 2004)

Ø  Ego-inhibition (in depression): •  Greater processing of internal somatic stimuli •  Reduced processing of emotional stimuli •  Imbalance between internal somatic and emotional stimuli:

•  Stronger perception of the body •  Emotional inhibition changes into ego-emptiness and ego-

inhibition •  Dysfunction of cortical midline structures (CMS): Disruption in the

interaction of the CMS as a functional unit

Subjective Components: What Can We Learn from Imaging?

•  Cortical and subcortical midline regions: Related to emotional perception and subjective experience

•  Cognitive components should be distinguished

•  Abnormal activation in cortical midline regions in depression

•  Dissociation between neuronal activity and subjective experience in depression

•  Modulation of “high-resting-state-activity” in depressed subjects after psychotherapy

Neurochemistry: Role of DA, GABA and glutamat and their modulation of the NBR

Neuronal function of the reward system: Specification of reward disfunction as a “diagnostic marker” ?

Therapy: Distinction between „state-“ and „trait-“ marker and „therapeutic marker“?

Future Steps in Anhedonia Research

Depression in Humans: Hyperactivity in Resting State in Corcial-Subcortical Midline

Regions

Depression in Humans: Signs of Hypoactivity in Resting State in Lateral

Regions

Pathophysiology of Anhedonia and Depressive Symptoms

Abnormal perception and experience of positive emotions

Reduced deactivation /NBR in the VMPFC

Abnormal judgement and perception of negative emotions

Changed activation in the left and right DLPFC

Anhedonia: Abnormal affective evaluation of positive emotions in the VS and VMPFC

Northoff, J of Affective Disorders, 2007

Increased self-focus, increased body-focus and reduced environmental focus

Zurich Depression Study:

The change of mental structure due to Psychodynamic Psychotherapy

modulates brain activity during aversive stimulation in depression

ZurichDepressionStudy-Aims

•  Findingneurobiologicalcorrelatesindepressivepa;entsofs;muliwhichare

-  personallyrelatedandpsychodynamicallyrelevantforthepa;ents(e.g.interpersonalrela;onshipthemes)

-  relatedtoaversion

•  Examiningthepsychologicalandpsychodynamicdimensionsofdepressivepa;ents(symptoms,interpersonalproblems,conflicts,psychicstructure,defensesetc.)

•  Comparingthedepressivepa;entswithhealthycontrols

•  Measuringneurobiological,psychologicalandpsychodynamicchangesinthedepressivepa;entsduring/aHerpsychodynamicpsychotherapy

•  Lookinginhowfarneurobiologicalandpsychological/psychodynamicchangesdocorrelate

ZurichDepressionStudy–Design(1)

1ststep:Inves;ga;onofhealthycontrols(n≥20-30)•  Inclusioncr;teria:nodiagnosisaccordingtoICD-10Fx,HAMD<8•  Ques;onnaires:BDI,BAI,BHI,FKBS,IIP,IMI•  PsychodynamicDiagnos;cs:OPD-2,OPD-SF•  Neuroimaging:fMRI àevalua;onof2fMRIparadigms

2ndstep:Inves;ga;onofdepressivepa;ents(n≥40-60)•  Inclusioncriteria:diagnosisaccordingtoICD-10:F32,F33,F34,F4,HAMD>8•  Ques;onnaires:BDI,BAI,BHI,FKBS,IIP,IMI•  PsychodynamicDiagnos;cs:OPD-2(HSCSincl.),OPD-SF•  Neuroimaging:fMRI(2fMRIparadigms)•  2therapycondi;ons(n≥20-30pergroup):

o  PsychodynamicPsychotherapy(accordingtoTayloretal.2010)o  Body-centeredPsychotherapy(accordingtoMaurer2009)

•  T1:beforetherapyT2:endoftherapyoratthelatestaHer1yearoftherapy(6-12months)T3:follow-up

HAMD>8ICD-10F3,F4

MRI MRI

recruitment

firstinterview

ZurichDepressionStudy–Design(2)

BDIBAIBHI

FKBSIIPIMI

OPD-2HSCSOPD-SF

BDIBAIBHI

FKBSIIPIMI

OPD-2HSCSOPD-SF

(follow-up)

2.psychodynamicpsychotherapy* (followingTaylor2010)

3.body-centeredpsychotherapy (followingMaurer2009)

T1 T2 T3

*withcon;nuous(peergroup)supervision

(6-7months)

npergroup=20-30

1.healthycontrols(HAMD<8)

Opera;onalizedPsychodynamicDiagnosis

(OPD2)

OPD-2

•  Mul;axialsystemwith5axes(3psychodynamicaxes)

•  AxisI:Experienceofillnessandprerequisitesfortreatment

•  AxisII:Interpersonalrela;ons

•  AxisIII:Conflicts

•  AxisIV:Structure

•  AxisV:Mentaldisorders(accordingICD-10,DSM-IV)

•  HeidelbergStructuralChangeScale(HSCS):5focifromAxesII,III,IVàDegreeofpa;ent‘sinsightin,acceptanceofandworkingthroughthefoci

HeidelbergStructuralChangeScale(HSCS)

Integra;on,agreementwithself,experienceconformstoreality,newforma;ons

7-77+

7.Dissolu;onofthefocus

Conciliatoryapproachtotheproblemarea,spontaneousemergenceofnewwaysofexperiencingandbehaving

6-66+

6.Reorganiza;oninthefocusarea

Defensebecomesfragile,sadness,feelingexposed,confusion,possiblyhopelessness

5-55+

5.Dissolu;onofoldstructuresinthefocusarea

Interestedinunderstandingtheproblem,workingrela;onship,ac;ve„coping“andpreoccupa;on

4-44+

4.Acceptanceandawarenessoffocus

Passivepreoccupa;onwithfocus,partlyacknowledgingtheproblem,no;onofresponsibility

3-33+

3.Vagueawarenessoffocus

Symptompressure,interpersonalproblems,unreasonabledemandsexperiencedasexternal

2-22+

2.Unwantedpreoccupa;onwiththefocus

Completedenial/defense,avoidingfocus,„There‘snoproblem“

11+

1.Focusproblemwardedoff

Coping

StructuralChange

Neuroimagingparadigms

fMRI-Aversionparadigm

• Punishment:Anyaversiveeventahumantriestoavoidorminimize(Seymouretal.2007)

• Someevidencethatcommonbrainareasareinvolvedinaversion-relatedprocessing:Amygdala,anteriorInsula,ACC,PFCandStriatum(Borsooketal.2007,Costafredaetal.2008,Delgado2008,Seymouretal.2007)

• Altera;onsinaversion-relatedprocessingmaybeinvolvedinthepathophysiologyofmanyneuropsychiatricdisordersincludingdepression(Hooleyetal.2009,Strigoetal.2008)

• Aimofparadigm:Usingaversivesoundstoac;vateaversion-relatedcircuityandexploringtherela;onshipbetweensubjec;veexpecta;onandobjec;veexperienceandresponding

• fMRIscanningwhileperformingareac;on;metask(RTT)underfivecondi;ons

fMRI-Aversionparadigm

passivelistening fixa;oncrossaversivesound1

fixa;oncrossnon-aversivesoundpassivelistening2

fixa;oncrossaversivesoundYoucancontrolthesound3

fixa;oncrossaversivesoundYoucan‘tcontrolthesound4

fixa;oncrossnon-aversivesound

Youcan‘tcontrolthesound5

(6-10s)(8-16s)(6-10s)(6-10s)(8-16s)(6-10s)

Reac;on;metask(RTT)

Exampletrials.Thecondi;on„controlexpectancy“and„non-controlexpectancy“(withsubsequent(non)aversivesoundpercep;on)are:

fMRI-Aversionparadigm

non-controlexpectancy

aversivesoundandRTT

aversivesoundandRTT

fixa;oncross

controlexpectancy

passivelistening

tolera2ngidealizingapologe2charmonizingtakingcareobtrusiveinvasivecontrollingrestric2ngdevaluingaccusinga@ackingneglec2ngignorantisola2ng

Rela;onshipThemeRa;ngParadigm

+ VAS

VAS

+ VAS

Rela;onshipThemeRa;ngParadigm

25min

VAS

trials8,12,16sblock180-240s

Hypotheses1

•  Depressivepa;entswilldiffersignificantlyfromthehealthycontrolswithrespecttopsychopathology,resultsintheOPDandotherpsychodynamicmeasures

•  Exposi;ontoaversives;muliands;muliinconnec;onwithnega;veinterpersonalexperienceswillshowincreasedhemodynamicac;va;oninmidlinestructuresandsubcor;calregionsofdepressivepa;ents(comparedtohealthycontrols)

•  Exposi;ontos;muliconnectedwithposi;veandnega;veinterpersonalexperienceswillproducedifferenthemodynamicac;va;onparernsinthebrain

Hypotheses2

•  Aversives;mulidon‘tmodulatetheres;ngstateac;vityintheCMSindepressivepa;entsastheydoinhealthycontrols

•  Depressivepa;entswillshowsignificantimprovementsoftheir

symptoms,interpersonalproblemsandintrapsychicdisturbancesaHer/inthecourseofpsychodynamicpsychotherapy

•  AHerpsychodynamicpsychotherapytheincreasedregionalbrainac;va;onwillnormalizeinthedepressivepa;entsandthedifferencestothecontrolswilldiminish

Personality, Empathy

Structure, Defence Style

Psychotherapist Client/Patient

Brain and neuronal Activity

Researcher

Behavioral Task: Activation Paradigm

Therapeutic Relationship

Scientific Implications I: Input and Design Problem

Personality

Neuronal

Psychodynamic

Processal

First-Person Perspective

Third-Person Perspective

Brain: Neuronal Organisation

Scientific Implications II: The Different Levels and the Translation Problem

Scientific Implications III

•  Depression as psychosomatoses of the emotional regulation •  Prospective long-term therapy studies with high-risk groups •  Prospective controlled therapy studies and naturalistic studies •  Instead of „horse race“ studies: Combination of therapy research and

fundamental research •  Development of functional subtypes •  Non-response: To what extent treatment specific?

Neuronal characteristics? •  Consideration of self-referential aspects •  Scope of psychoanalytic theories of depression (personality theory,

questions about the connection between personality and depression, but not depression theory as such)

•  Multiple factor approach (E. Jacobson 1971) •  Development of multi-dimensional therapeutic conzepts •  Investigation of patients in remission: Distinguishing state and trait

markers

Dr. rer. nat. Simone Grimm Dr. med. Holger Himmighoffen Dr. med. André Richter Dr. rer. nat. Milan Scheidegger Dipl. Psych. Silke Braun lic. phil. Martina Trafoier med. pract. Jan Schulze Dr. med. Dipl. Psych. Markus Rezk cand. rer. nat. Jutta Ernst Dr. rer. nat. Anke Henning cand. lic. Jeannette Zahner Dr. phil. Elena Hofmann med. pract. Miriam Straub

Therapy and Process Research (TPR) Head: Prof. Dr. med. Heinz Böker

In cooperation with: - Abteilung für Biomedizinische Technik der ETH und Universität Zürich

(Prof. Dr. rer. nat. Peter Bösiger) - University of Ottawa, Institute of Mental Health Research

(Prof. Dr. med. Dr. med. habil. Georg Northoff) - Molekulargenetische Forschungsgruppe der Psychiatrischen Universitätsklinik Zürich

(Prof. Dr. rer. nat. Hans Stassen) - Sigmund-Freud-Institut Frankfurt/M. (Prof. Dr. phil. Marianne Leuzinger-Bohleber) - Universität Tübingen, Abt. für Klinische und Physiologische Psychologie, Psychologisches Institut

(Prof. Dr. phil. Martin Hautzinger) - Max-Delbruck-Institut, Charité, Berlin - Psychiatrische Universitätsklinik Heidelberg

Thank you very much for your attention!