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Research on neurobiological effects of psychotherapy in depression facilitates the improvement of treatment strategies. The cortico-limbic dysregulation model serves as a framework for numerous studies on neurobiological changes in depression. In this model, depression is described as hypoactivation of dorsal cortical brain regions in conjunction with hyperactivation of ventral paralimbic regions. This assumption has been supported by various studies of structural and functional brain abnormalities in depression. However, also regions not included in the original cortico-limbic dysregulation model, such as the dorsomedial prefrontal cortex, seem to play an important role in depression. Functional connectivity studies of depression have revealed an enhanced connectivity within the so-called default mode network which is involved in self-referential thinking. Studies also point to a normalization of limbic and cortical brain activity, especially in the anterior cingulate cortex, during psychotherapy. Some neurobiological markers like the activity of the anterior cingulate cortex, striatum and insula as well as hippocampal volume have been proposed to predict treatment response on a group-level. The activity of the anterior insula appears to be a candidate bio-marker for differential indication for psychotherapy or pharmacotherapy. The cortico-limbic dysregulation model and following research have inspired new forms of treatment for depression like deep brain stimulation of the subgenual anterior cingulate cortex, repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex, neurofeedback and attention training.

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