In the first neuroimaging study of changes in the limbic system and prefrontal cortex caused by long-term psychotherapy, researchers in Germany and the United States compared 16 recurrently depressed, unmedicated outpatients and 17 matched controls. Patients’ left anterior hippocampus/amygdala, subgenual cingulate, and medial prefrontal cortex showed higher activation before treatment. After 15 months, a reduction of activation was associated with improvement in depressiveness specifically, and in the medial prefrontal cortex with symptom improvement more generally. Results were published in PLoS One.