Changes in Prefrontal-Limbic Function in Major Depression after 15 Months of Long-Term Psychotherapy

Anna Buchheim,Henrik Kessler,Carol George,Horst Kächele,Roberto Viviani,Svenja Taubner,Otto F Kernberg,Gerhard Roth,Georg Bruns,Manfred Cierpka,Amanda Bruce

doi:10.1371/journal.pone.0033745

Abstract

Neuroimaging studies of depression have demonstrated treatment-specific changes involving the limbic system and regulatory regions in the prefrontal cortex. While these studies have examined the effect of short-term, interpersonal or cognitive-behavioural psychotherapy, the effect of long-term, psychodynamic intervention has never been assessed. Here, we investigated recurrently depressed (DSM-IV) unmedicated outpatients (N = 16) and control participants matched for sex, age, and education (N = 17) before and after 15 months of psychodynamic psychotherapy. Participants were scanned at two time points, during which presentations of attachment-related scenes with neutral descriptions alternated with descriptions containing personal core sentences previously extracted from an attachment interview. Outcome measure was the interaction of the signal difference between personal and neutral presentations with group and time, and its association with symptom improvement during therapy. Signal associated with processing personalized attachment material varied in patients from baseline to endpoint, but not in healthy controls. Patients showed a higher activation in the left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex before treatment and a reduction in these areas after 15 months. This reduction was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. This is the first study documenting neurobiological changes in circuits implicated in emotional reactivity and control after long-term psychodynamic psychotherapy.

Highlights

Neuroimaging approaches have been used to investigate neurobiological changes in depressive patients in studies that address remission after psychotherapy or antidepressant medication [1,2]
We extended our analysis of the association of changes with response to the Global Severity Index (GSI [42]), a more general index of psychic well being than BDI
When exposed to personally attachment-relevant material, patients undergoing long-term psychodynamic psychotherapy showed changes in brain activation that were not observed in a sample of control participants

Summary

Introduction

Neuroimaging approaches have been used to investigate neurobiological changes in depressive patients in studies that address remission after psychotherapy or antidepressant medication [1,2] The majority of these studies focused on the effect of treatment on brain metabolism or perfusion at rest. This study detected changes in the amygdalaanterior hippocampus and posterior cingulate-precuneus regions as well as the superior frontal gyrus, suggesting that areas associated in previous studies with increased reactivity to emotional stimuli and mechanisms of control are relevant for psychotherapy effects. When both psychotherapy and pharmacotherapy were compared [37], there was limited overlap between changes found in these two therapy modalities While all these studies appear to be broadly compatible with the involvement of limbic and prefrontal areas, more studies of task-related activation are needed to provide a comprehensive picture of changes associated with remission

Materials and Methods

Results

Discussion