Effects of Psychotherapy on Brain Function

Unipolar major depressive disorder (MDD) is a debilitating condition with a lifetime prevalence of 17%.¹ Recent epidemiological evidence indicates that MDD is the fourth leading cause of disease burden and the leading cause of disability-adjusted life years.² Fortunately, a wide range of MDD treatments are available, including psychotherapy and psychopharmacology. Available data suggest that psychotherapy for MDD is effective, protects against relapse, and does not carry the same risks of adverse effects as comparably effective psychopharmacology. Despite the evidence that psychotherapy is an effective intervention for MDD, relatively little is known about its potential neurobiological mechanisms of action. That is, how does psychotherapy affect brain function? This stands in stark contrast to the wealth of research documenting brain changes that accompany psychopharmacological treatments for MDD.

The potential reasons for this disparity are unclear, although probable contributors include:

• The considerable resources required to administer psychotherapy in a research setting.
• The time and expense of verifying adherence to a particular psychotherapeutic modality (eg, cognitive-behavioral therapy [CBT], interpersonal therapy [IPT]) when the effects of a single modality are of interest.
• The challenges associated with recruiting a sufficiently large sample of medication-naive study participants for psychotherapy.

Despite these challenges, several studies of brain imaging have examined the effects of psychotherapy on brain function and compared these changes to those of various psychopharmacological interventions. The overall conclusions of these initial reports are that effective psychotherapy can robustly change brain functioning in specific brain areas related to cognitive control, self-referential processing, reward based decision making, and assigning emotional salience to external events. However, the short-term effects of psychotherapy on brain function appear to be in different brain areas than psychopharmacological treatment, despite comparable symptom outcomes. The reasons for these disparities are a current focus of study and speak to how little is presently understood about the pathophysiology of MDD, as well as the multiple ways that brain functioning can normalize with the remission of depression symptoms.

Psychotherapy for unipolar MDD

Treatment guidelines formulated by the American Psychiatric Association recommend psychotherapy, pharmacotherapy, or a combination of the 2 as first-line treatment for mild to moderate MDD. Most notably, the protective effects of psychotherapy against MDD relapse after termination of treatment is impressive.³ A study of more than 100 patients who responded to treatment found that relapse occurred in 76.2% of those who had received medication. The relapse rate was only 30.8% among those who had received psychotherapy.⁴

The most common empirically validated modalities of psychotherapy for MDD include cognitive therapy (CT), behavioral activation therapy (BAT), CBT, problem-solving therapy, and IPT. In outpatients with mild MDD, there do not appear to be outcome differences between psychotherapy, psychopharmacological intervention, and placebo, although in outpatients with moderate to severe MDD, both treatment approaches outperform placebo.⁵ In addition, there is growing evidence that certain psychotherapies are as effective as psychopharmacology for acute, severe major depression.⁵

For example, in a randomized, triple-blind study that compared BAT, CT, medication, and placebo for depression, Dimidjian and colleagues⁶ reported that symptom remission rates were not significantly different between BAT and paroxetine(Drug information on paroxetine) treatment for participants with severe MDD. In addition, psychotherapy appears to have more enduring effects than antidepressants. Hollon and colleagues⁴ reported that CT was as effective as psychopharmacology during the acute phase of treatment, yet more effective than psychopharmacology at preventing relapse during continuation phases of treatment. The investigators argued that although psychotherapy may be more expensive than psychopharmacology in the short term, psychotherapy becomes less expensive after the eighth month of treatment.

Brain imaging

A host of brain imaging techniques are available, including computed tomography, single photon emission computed tomography, and positron emission tomography (PET), and MRI. MRI has become the tool of choice in psychiatric treatment-outcome research because of its excellent contrast properties and its noninvasive nature (a particularly important feature given that longitudinal treatment-outcome research requires repeated scanning).

Research MRI uses a clinical scanner with specific pulse sequences. MRI detects signal changes when hydrogen nuclei fall back into alignment after a strong radio pulse. These signal changes may be converted to an image based on different types of body tissue. Structural MRI assesses precise volumetric measurements of brain structures, whereas functional MRI (fMRI) measures regional brain activity during particular task conditions. These 2 modalities may be coregistered to allow for structural localization of changes in brain function brought about by effective interventions (for an in-depth review of the technical aspects of fMRI, see Huettel et al⁷).