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.