The Hanse-Neuro-Psychoanalysis-Study

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• The Hanse-Neuro-Psychoanalysis-Study
• Neurobiological changes in patients
• with chronic depressive disorders
• treated in psychoanalytic therapy
• Development of a paradigm
• Kächele H1, Buchheim A1,7 ,Cierpka M2, Münte T3,
  Kessler H1,4,
• Wiswede D1,4, Taubner S1,5, Bruns G6, Roth G4
• 1 Klinik für Psychosomatische Medizin und
  Psychotherapie, Universitätsklinikum Ulm
• 2 Institut für Psychosomatische
  Kooperationsforschung und Familientherapie,
  Universität Heidelberg
• 3 Abteilung Neuropsychologie, Otto-von-Guericke-Un
  iversität Magdeburg
• 4 Hanse-Wissenschaftskolleg, Delmenhorst

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• A genuine dialogue between biology and
  psychoanalysis is necessary if we want to achieve
  a coherent understanding of mind.
• Eric Kandel, Biology and the Future of
  Psychoanalysis, 1999

Introduction

Brain and Therapy

The Study


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As a result, when I speak to someone and he or
she listens to me, we not only make eye contact
and voice contact but the action of the neuronal
machinery in my brain is having a direct and, I
hope, long-lasting effect on the neuronal
machinery in his or her brain, and vice versa.
Indeed I would argue that it is only insofar as
our words produce change in each others brains
that psychotherapeutic intervention produces
change in patients mind (Kandel 1979, cit.
2005, p. 23).
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Kandel (1998, 1999) devised a program for the
cooperation of psychiatry, psychoanalysis and
neurosciences which follows five principals
1) All mental processes have neural basis. 2)
Genes and their protein products determine neural
connections. 3) Experience alters gene
expression. 4) Learning changes neuronal
connections. 5) Psychotherapy changes gene
expression.
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Medication, Psychotherapy and Imaging Studies
White bars Medication Black bars Psychotherapy
Roffman, J. et al. (2005) Neuroimaging and the
functional neuroanatomy of psychotherapy Psycholog
ical Medicine 35 1-14. Linden D (2006) How
psychotherapy changes the brain - the
contribution of functional neuroimaging.
Molecular Psychiatry 11 528-538
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Limitations

• CBT and IPT and other short-time therapies (6-12
  weeks)
• No psychodynamic / psychoanalytic treatments
• Often resting state measure No specific
  activity
• Often no healthy controls
• No process measurement

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Symptomatic vs Structural Change

• Controlled treatment studies comparing low
  frequency with high frequency psychoanalytic
  therapy show equal change on the level of
  symptomatology
• The privileged notion of structural change and
  its biological underpinnings might become the
  testing ground to differentiate effects of low
  and high dose treatments.

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• Which kind of change?
• Symptom improvement
• Insight in and changes in coping with central
  conflicts / dysfunctional patterns
• Attachment representations, reflective
  functioning

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• Measures used as the basis for the
  neurobiological stimuli
• 1) Operationalized Psychodynamic Diagnosis (OPD)
• 2) Adult Attachment Projective (AAP)
• Additional Interview Based Measures
• SCID I/II Structured Clinical Interview DSM-IV
• AAI Adult Attachment Interview
• RF Reflective Functioning Scale
• SPC Scales of Psychological Capacities
• SWAP Shedler-Westen-Assessment-Procedure
• HSCS Heidelberg-Structural-Change-Scale
• Questionnaires
• SCL 90 Symptom Check List
• BDI Beck Depression Inventory
• DEQ Depressive Experience Questionnaire
• ERQ Emotional Regulation Questionnaire
• LEAS Levels of Emotional Awareness Scale
• Reading the mind in the eyes

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HNPS-Design
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Methods for Core Conflicts

• Operationalised Psychodynamic Diagnosis (OPD-2)
• and
• the Adult Attachment Projective

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Recruitment

• What are the scientific challenges
• What kind of analyst participates?
• What kind of patient participates?
• Ethical implications of recruitment?

Taubner, S. et al. (2008). "Psychoanalysts and
their patients as research subjects." Int J
Psychoanal, submitted.
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Case illustration

• From the OPD-interview and the OPD-diagnosis to
  the generation of the stimuli sentences for the
  fMRT and EEG-investigation.
• For the first time in my life I became aware
  that my life has been permeated by a deep
  sadness. I want to get rid of this sadness or at
  least change it in something that does not pull
  me down. I have the feeling that life and also
  myselfs ask too much from me. I shoulder the
  burden of everyone. I do not understand why this
  should be so and still I find myself again and
  again.

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OPD-Diagnosis

• need for care vs self-sufficiency
• and
• submission vs control conflict
• the patient feels ignored by others (contact) as
  a consequence she is caring (care), and due to
  her anxiety to be rejected like in childhood -,
  she adapts to others (control).
• At the same time she unconsciously has high
  demands towards others (care) and tends to
  dominate (control).
• The significant others first try to resist to her
  dominance (control), but withdraw disappointedly,
  because they have the feeling, not to do justice
  to her expectations (contact, care).

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Recruitment facts

• 20 experienced psychoanalysts of two
  psychoanalytic institutes
• 24 patients with chronic depression
• Comorbidity 11 anxiety disorders, 1 eating
  disorder (SCID)
• 5 drop-outs
• 20 matched controls (sex, age, education)

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Demographics of final study group
Patients (N19) Controls (N20)
Age 39,2 (12,7) 20-64 y. 37,1 (11,6) 21-64 y.
Sex 15 f 4 m 16 f 4 m
Education middle 7 high 12 middle 4 high 16
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Psychometric Data
Patients (n19) Controls (n20) p
SCL90/ GSI (m) 1.3 (.68) .20 (.13) plt.001
BDI (m) 23.12 (10.8) 2.23 (2.8) plt.001
DEQ (m) anaclitic .42 (1.15) -.45 (.66) plt.01
DEQ (m) introj. 1.32 (.86) -.28 (.85) plt.001
LEAS (m) 33.1 (5.5) 32.5 (5.8) n. s.
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The Brain and Depression
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Problems with brain data
- Heterogeneity across studies
- More heterogeneity across subjects
- Unspecific, non-personal stimuli
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Operationalized Psychodynamic Diagnosis (OPD-2)

• 19 patients and 20 controls interviewed
• Rated by 2-3 independent raters
• Axis II of OPD
• repetitive dysfunctional interpersonal patterns
• Production of 4 individual sentences capturing
  dysfunctional relations
  as Stimuli in fMRI scanner and EEG

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Relational themes

• Virtually the same relational themes in patients
  and controls
• Sentences per se did not distinguish between
  patients and controls
• Not a source for differences in brain imaging
  data!

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Experimental Paradigm for fMRT

• fMRI Scanner (3 Tesla)
• Patients read sentences for three alternating
  conditions
• Relaxation
• Unspecific stress in traffic situation
• OPD generated individual sentences
• 30 minutes exposure time

• Patients knew the sentences in advance

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Experiment 1-3
Relaxation Traffic Stress OPD-Sentences
Think of a safe place Someone does not react to a green traffic light I wish that other see what I suffer
Relax You are angry about him I experience that no one cares about me
Empty your head You react emotional This hurts me and I feel rejected
Think of nothing The person shows you his bad finger I feel impotent and helpless
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Subjective Rating of Stimuli

• Sentences were fitting
• They did cause emotional arousal
• No differences between patients and controls
• Not a source for differences in brain imaging
  data!

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OPD sentences gt traffic stress (across all
subjects) (1)
Medial Prefrontal Cortex
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OPD sentences gt traffic stress (across all
subjects) (2)
Superior Temporal Sulcus
Temporal Pole
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OPD sentences gt traffic stressPatients gt
Controls (1)
Amygdala
Putamen
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OPD sentences gt traffic stressPatients gt
Controls (2)
Cingulate Motor Area
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Summary

• Individually tailored OPD sentences produced
  activity in areas relevant for
• mentalizing, emotional processing
• self-reflection, conflict monitoring,
• autobiographical memory
• Patients showed increased activity in
• amygdala, basal ganglia (previously shown)
• pre-motor areas (meaning?)