Psychotherapy: The Biological Dimension Ismail sadek
Psychotherapy: The Biological DimensionIsmail sadek
The great mistake in an over-ambitious science has been the desire to
study man altogether as a mere sum of parts, if possible of atoms, or
now of electrons and as a machine, detached by itself, because at least
some points in the simple sciences could be studied to the best
advantage with this method of so called elementalist.
Adolph Meyer, 1921
It was a long time before willingness to see the large
group of facts, in their broad relations as well as in their
inner structure, finally gave us the concept and vision of
integration which now fits man as alive unit and
transformer of energy into the world of facts and makes
him frankly a conscious integrated psychobiological
individual and member of a social group Adolph Meyer, 1921
Psychotherapy outcomes and the mechanisms of
change that are related to its effects have
traditionally been investigated on the psychological
and social levels, by measuring changes in
symptoms, psychological abilities, personality, or
social functioning.
Many psychiatrists have also held the
unfortunate dichotomized position that
psychotherapy is a treatment for
“psychologically based” disorders, while
medication is for “biologically based”
disorders
During the past several decades, it has become clear that all mental processes derive from mechanisms of the brain. This means that any change in our psychological processes is reflected by changes in the functions or structures of the brain. Straightforward reductionistic stances, however, are unfounded because there is clear evidence that our subjective experiences affect the brain.
Plastic changes in the brain have been difficult to study in humans, but there has been more success in animal studies. Changes in the brain in relation to experience have been detected at the cellular and molecular levels in animals using different experimental approaches.
The advent of functional neuroimaging, including single photon emission CT (SPECT), positron emission tomography (PET), and functional MRI, has made it possible to study changes at the brain systems level (by measuring changes in brain blood flow or metabolisms) and, increasingly, also on the molecular level using SPECT and PET in the living human brain.
Brain system level studies on the effects of psychotherapy
So far, nearly 20 studies on brain changes after psychotherapy for depression, anxiety disorders, and borderline personality disorder have been published.
The first study was published nearly 20 years ago, in 1992.
In this study, the researchers compared behavior therapy with fluoxetine treatment. Both treatment modalities demonstrated similar changes in the brain—especially in the caudate nucleus.
Brain system level studies on the effects of psychotherapy
Drawn together, these system level studies suggest that cognitive-behavioral therapy (CBT), dialectic behavior therapy (DBT), psychodynamic psychotherapy, and interpersonal psychotherapy alter brain function in patients suffering from major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder, social anxiety disorder, specific phobias, posttraumatic stress disorder, and borderline personality disorder (BPD).
When a therapist speaks to a patient and the patient listens, the therapist is not only making eye contact and voice contact, but the action of neuronal machinery in the therapist brain is having an indirect and, one hopes, long lasting effect on the neuronal machinery in the patient’s brain. Our words produce changes in our
patient’s mind
Eric Kandel, 1998
How Psychotherapy stimulates the Brain
1. Psychotherapy affects cerebral metabolic rates.
2. Psychotherapy affects serotonin metabolism.
3. Psychotherapy affects the thyroid axis.
4. Psychotherapy stimulates processes to brain plasticity.
5. Psychotherapy normalizes pathognomonic biological features.
Functional imaging studies of psychotherapy effects
Obsessive-compulsive disorder
Increased activity in the right caudate was the common finding of symptom provocation studies in OCD across imaging modalities.
Correspondingly, all studies of the effects of cognitive behavioural therapy (CBT) in OCD on resting state glucose metabolism or blood flow so far reported a decrease in right caudate activity in treatment responders.
This decrease of caudate activity correlated with clinical improvement in one of the studies, and showed no difference between CBT and treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine.
Two studies reported a correlation between caudate, OFC and thalamus activity before treatment, which would conform to current pathophysiological models of OCD. This correlation disappeared after treatment with either CBT or fluoxetine.
Psychotherapy effects in OCD
Authors Trial size/interventions and pre–post interval
Functional imaging technique
Post-treatment decreases
Post-treatment increases
Baxter et al. 24
N=9 CBT, N=9 fluoxetine, N=4 healthy controlsa, all 102 weeks
FDG (fluoro-deoxyglucose)-PET, resting state, normalised data, no PVCb
Responders: right caudate; correlation between right OFC, caudate and thalamus
None
Schwartz et al. 25 N=9 CBT, 102 weeksFDG-PET, resting state, normalised data, no PVC
Responders: caudate bilaterally; correlation between right OFC, caudate and thalamusc
None
Nakatani et al. 26
N=22 CBT (some also received clomipramine), duration based on clinical improvement
Xenon-enhanced CT (measures rCBF), resting state
Right head of caudate None
Nakao et al. 29
N=6 CBT, N=4 fluvoxamine, 12 weeks
fMRI during Stroop task and symptom provocation
Bilateral OFC, DLPFC, ACC (symptom provocation)d
Bilateral parietal cortex, cerebellum (Stroop task)d
Phobias
Simple phobias are particularly suited to the investigation
of treatment effects with fMRI because symptom
provocation is relatively straightforward. Whereas in most
studies of OCD, PTSD and depression, the inducing triggers
had to be tailored individually, the symptoms of spider
phobia could be mimicked by standardised images or film
sequences of spiders.
Paquette et al. used this symptom provocation technique in order to assess the effect of symptom reduction by CBT directly. Before the intervention, patients showed increased activity of right dorsolateral PFC and parahippocampal gyrus to the aversive sequences. This difference disappeared after four intensive exposure sessions in a group setting.
Several studies of patients with social phobia have also shown hyperactivity of the amygdala, even with a weak form of symptom provocation, presentation of human faces. After successful treatment, either with CBT or citalopram, activation of amygdala and hippocampus was reduced in the symptom provocation study by Furmark et al.,
Psychotherapy effects in phobias and panic disorder
AuthorsTrial size/interventions and pre–post interval
Functional imaging technique
Post-treatment decreases Post-treatment increases
Furmark et al. 34
Patients with social phobia, N=6: CBT, N=6: citalopram, N=6: waiting list, all 9 weeks
PET with oxygen 15-labeled water, symptom provocation, normaliseddata, no PVC
Both treatment groups: bilateral amygdala, hippocampus, parahippocampal gyrus, further paralimbic areas
None
Paquette et al. 30
Patients with spider phobia, N=12: CBT, 5 weeks
fMRI, symptom provocation
Right dorsolateral PFC, parahippocampal gyrus
Visual association areas; right inferior frontal gyrus
Straube et al. 31
Patients with spider phobia, N=14: CBT, 2 sessions, N=14: waiting list
fMRI, symptom provocation
Bilateral insula, thalamus, ACC in treatment but not waiting list group
None
Prasko et al. 75
Patients with panic disorder, N=6: CBT, N=6: different antidepressants, both groups 3 months
FDG-PET, resting state, normalised data
Both treatment groups: mainly right frontal and temporal regions, with partial overlap across groups
Both treatment groups: mainly left frontal and temporal regions, with partial overlap across groups
Depression
While symptom provocation and resting state studies produced fairly consistent signatures of pathological metabolism for OCD (right caudate hyperactivity) and phobias (limbic and paralimbichyperactivity),
the situation is more complicated for major depressive disorder (MDD). Most studies of resting state blood flow or metabolism reported an anterior prefrontal hypoperfusion that normalised after the remission of symptoms of depression
Conversely, the intervention study by Brody et al. started from an initial prefrontal hypermetabolism that normalised in both the IPT- and the SSRI-treated group. Decreases in lateral prefrontal metabolism were also observed after successful treatment with CBT.
Psychotherapy effects in major depressive disorder
AuthorsTrial size/interventions and pre–post interval
Functional imaging technique
Post-treatment decreases
Post-treatment increases
Brody et al. 37
N=14: IPT, N=10: paroxetine, N=16: healthy controls, all 12 weeks
FDG-PET, resting state, global normalised data, image fusion with MRI
Both treatment groups: bilateral PFC; IPT: left ventral ACC; paroxetine: left middle ACC
Both treatment groups: left temporal lobe
Martin et al. 39
N=13: IPT, N=15: venlafaxine, all 6 weeks
HMPAO-SPECT, resting state, normalised data, no PVC
None
IPT: Right basal ganglia, posterior CC; Venlafaxine: right basal ganglia, posterior temporal cortexa
Goldapple et al. 38
N=14: CBT, 267 weeks (standard deviation), N=13: paroxetine, 6 weeks (sample from different study)
FDG-PET, resting state, normalised data, no PVC
CBT: bilateral PFC; Paroxetine: right hippocampus
CBT: bilateral hippocampus, dorsal CC; Paroxetine: left dorsolateral PFC
Molecular psychodynamics
To understand the more basic mechanisms related to psychotherapy, possible molecular and cellular changes should also be studied.
In the study by Lehto and colleagues, depressive outpatients received psychodynamic psychotherapy for 12 months. Of the patients, 8 were classified as having atypical depression. Midbrain serotonin transporter and striatum dopamine transporter densities were recorded using
SPECT brain imaging with the [123I]nor-β-CIT radioligand before and after psychotherapy.
The researchers showed that midbrain serotonin
transporter density significantly increased during
psychotherapy in patients with atypical depression,
but not among patients with standard depression.
There were no changes in the levels of striatum
dopamine transporter.
In other Finnish study, patients with MDD were randomized to receive either short-term psychodynamic psychotherapy or fluoxetine.
Before being treated and after 4 months of treatment, they underwent a brain scan with PET using [carbonyl-11C]WAY-100635 (measures the density of serotonin type 1A [5-HT1A] receptors) and [11C]raclopride(measures density of dopamine type 2/3 receptors).
The researchers reported that the clinical
outcome in both treatment groups was
similar in terms of standard symptom
ratings (symptom remission was achieved in
59% of the patients and 77% of the patients
met criteria for response).
However, an analysis of the change in the 5-HT1A receptor density in the treatment groups revealed a significant increase in the psychotherapy group compared with the medication group, for which no change was detected.
Fluoxetine increased raclopride binding in the lateral thalamus; no change was seen in the group that received psychotherapy.
Several previous studies have found changes in 5-HT1A receptor binding in MDD that is not reversed by SSRI treatment.
This could mean that the recovery process in MDD after psychotherapy is different from recovery after medication.
Currently, the clinical implications of these findings are unknown, but they may be related to the finding that suggests that the relapse rate for MDD is lower in patients treated with psychotherapy than in those treated with antidepressants.
Changes in depression with treatment
Cognitive Behavior Therapy:
frontal cortex decrease
hippocampal increase
medial frontal cortex changes
orbital frontal cortex changes
Pharmacotherapy:
frontal cortex increase
hippocampal decrease
brainstem changes
thalamic changes
Electro Convulsive Therapy:
frontal cortex decrease
hippocampal decrease
Parallels between brain physiology and schools of Psychotherapy
A. Behavior Psychotherapy
Dysfunction in simple forms of learning and memory (operant and associative conditioning) and related motor behavior.
Brain structures in amygdala, basal ganglia, hippocampus
B. Cognitive Psychotherapy
Dysfunction in define specific verbal thoughts and assumptions or schemata (automatic negative thoughts)
Brain structures in neocortex, specifically the frontal cortex
Parallels between brain physiology and schools of Psychotherapy
C. Psychodynamic Psychotherapy
Dysfunction in interpersonal representations and especially the expectations about self, others and their relationship that organizes affect, thought and behavior.
Brain structures are complex eurocircuitryincorporating lateralized cerebral hemispheres and subcortical areas.
The theory of man as person loses its way if it falls into an account of man as machine or as an organism of it-processes
Ronald Laing
CLINICAL IMPLICATIONS AND LIMITATIONS
CLINICAL IMPLICATIONS
Family therapy that modifies parent—child interaction may be able to alter gene expression in the child.
Psychotherapy and medication may affect the brain similarly in certain disorders.
Medication may target temperament in personality disorders while psychotherapy may affect character.
LIMITATIONS
The studies of brain changes in psychotherapy are preliminary and require replication.
We do not yet know if the findings of some of the animal studies are applicable to human subjects.
The action mechanisms of psychotherapy at the brain level are largely speculative at this time.