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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-Universität Magdeburg
•   4 Hanse-Wissenschaftskolleg, Delmenhorst
•   5 Bremer Institut für Theoretische und Angewandte Psychoanalyse (BITAP)
•   6 Bremer Psychoanalytische Vereinigung (BPV)
•   7 Institut für Psychologie, Universität Innsbruck


                                                                                                         1
               “A genuine dialogue
               between biology and
Introduction   psychoanalysis is
               necessary if we want to
               achieve a coherent
Brain and      understanding of mind.”
Therapy
               Eric Kandel, Biology and the
               Future of Psychoanalysis,
The Study
               1999




                                              2
„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 other’s brains that
psychotherapeutic intervention
produces change in patient’s mind“
(Kandel 1979, cit. 2005, p. 23).


                                           3
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.


                                                4
                     Medication, Psychotherapy
                       and Imaging Studies


Intro
Design
Recruitment
Diagnostics

                         White bars: Medication           Black bars: Psychotherapy

         Roffman, J. et al. (2005) Neuroimaging and the functional neuroanatomy of psychotherapy
         Psychological Medicine 35: 1-14.
         Linden D (2006) How psychotherapy changes the brain - the contribution of functional
         neuroimaging. Molecular Psychiatry 11: 528-538
                                                                                                   5
                          Limitations
            • CBT and IPT and other short-time therapies (6-
              12 weeks)
Intro       • No psychodynamic / psychoanalytic treatments
            • Often resting state measure – No specific activity
Design
            • Often no healthy controls
Recruitment • No process measurement
Diagnostics




                                                               6
                Symptomatic vs Structural
                       Change
            • Controlled treatment studies comparing low
              frequency with high frequency psychoanalytic
Intro         therapy show equal change on the level of
              symptomatology
Design      •
Recruitment • The privileged notion of structural change and its
              biological underpinnings might become the
Diagnostics   testing ground to differentiate effects of low and
              high dose treatments.




                                                               7
              Which kind of change?
                  • Symptom improvement
                  • Insight in and changes in coping with central
Intro               conflicts / dysfunctional patterns
                  • Attachment representations, reflective
Design
                    functioning
Recruitment
Diagnostics




                                                              8
• 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
                                                               9
HNPS-Design




              10
Methods for Core Conflicts
 • Operationalised Psychodynamic
   Diagnosis (OPD-2)
 • and
 • the Adult Attachment Projective




                                     11
                             Recruitment
              •   What are the scientific challenges
Intro
              •   What kind of analyst participates?
Design
              •   What kind of patient participates?
Recruitment
              •   Ethical implications of recruitment?
Diagnostics

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


                                                                          12
                          Case illustration
              • From the OPD-interview and the OPD-diagnosis to the
                generation of the stimuli sentences for the fMRT and EEG-
                  investigation.
Intro
              •    „For the first time in my life I became aware that my life has
Design            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
Recruitment       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
Diagnostics       why this should be so and still I find myself again and again.“




                                                                                 13
                                OPD-Diagnosis

              •   „need for care vs self-sufficiency“
              •   and
              •   „submission vs control“ conflict:
Intro
              •   the patient feels ignored by others (contact); as a consequence
Design            she is caring (care), and due to her anxiety – to be rejected like in
                  childhood -, she adapts to others (control).
Recruitment   •   At the same time she unconsciously has high demands towards
                  others (care) and tends to dominate (control).
Diagnostics   •   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).




                                                                                      14
                 Recruitment facts
            • 20 experienced psychoanalysts of two
              psychoanalytic institutes
Intro
            • 24 patients with chronic depression
            • Comorbidity: 11 anxiety disorders, 1
Design
              eating disorder (SCID)
Recruitment • 5 drop-outs
Diagnostics • 20 matched controls (sex, age, education)




                                                     15
Demographics of final
   study group
            Patients (N=19) Controls (N=20)

Age         39,2 (12,7)     37,1 (11,6)
            20-64 y.        21-64 y.

Sex         15 f : 4 m      16 f : 4 m


Education   middle: 7       middle: 4
            high: 12        high: 16




                                              16
   Psychometric Data
               Patients      Controls       p
                (n=19)        (n=20)
SCL90/      1.3 (.68)      .20 (.13)    p<.001
GSI (m)
BDI (m)     23.12 (10.8)   2.23 (2.8)   p<.001

DEQ (m)     .42 (1.15)     -.45 (.66)   p<.01
anaclitic
DEQ (m)     1.32 (.86)     -.28 (.85)   p<.001
introj.
LEAS (m)    33.1 (5.5)     32.5 (5.8)   n. s.

                                                 17
The Brain and Depression
            decreased activity at rest and
 Areas with increased activity at rest and
  after induction of negative emotions




                                        Putamen
Anterior Cingulate Cortex   Dorsolateral Prefrontal Cortex

                                                       18
Problems with brain data
- Heterogeneity across studies
- More heterogeneity across subjects

- Unspecific, non-personal stimuli




                                       19
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



                                                  20
    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!




                                            21
 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




                                                  22
        Experiment 1-3
Relaxation   Traffic Stress   OPD-Sentences
Think of a   Someone does I wish that other see
safe place   not react to a what I suffer
             green traffic
             light

Relax        You are angry    I experience that no
             about him        one cares about me
Empty your You react          This hurts me and I
head       emotional          feel rejected
Think of     The person       I feel impotent and
nothing      shows you his    helpless
             bad finger


                                                     23
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!



                                        24
       OPD sentences > traffic stress
         (across all subjects) (1)
                             Posterior Cingulate Cortex




Medial       Anterior
Prefrontal   Cingulate
Cortex       Cortex                               25
OPD sentences > traffic stress
  (across all subjects) (2)
                      Superior Temporal
                      Sulcus




 Temporal
 Pole
                                    26
OPD sentences > traffic stress
  Patients > Controls (1)




Putamen   Amygdala
                                 27
OPD sentences > traffic stress
  Patients > Controls (2)




   Cingulate Motor Area

                                 28
            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?)



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