Common Brain Circuits in Patients with Depression

Post by Leanna Kalinowski

What's the science?

The mapping of psychiatric symptoms onto specific brain circuits is typically based on a correlation between the symptoms and brain activity, leading to difficulties in attempting to causally translate this information into effective treatments for psychotic disorders. Three modalities, brain lesions, transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS), have been used to link depression symptoms to specific brain circuits based on the location of lesions or stimulation sites that affect symptom severity. However, it is unclear whether these three modalities converge on the same brain circuit or therapeutic target. This week in Nature Human Behaviour, Siddiqi and colleagues analyzed datasets of patients with depression symptoms to determine whether brain lesions, TMS, and DBS sites converge on the same brain circuits.

How did they do it?

The authors examined 14 datasets that included magnetic resonance imaging or computed tomography scans of 461 brain lesions, 151 TMS sites, and 101 DBS sites, in addition to scores on a continuous scale from a validated depression questionnaire for each patient. They then mapped each lesion or stimulation site onto a brain circuit using a normative human connectome database based on data from 1,000 healthy subjects. This method was used to create a circuit map of each patient’s lesion or stimulation site. Then, to determine whether the three modalities converge on the same circuit, the circuit maps were compared to each other by computing correlations between the depression score and brain lesion/stimulation site.

The authors also compared circuit maps derived from patients with major depressive disorder with those derived from patients with other disorders to determine whether this circuit is associated with depression severity irrespective of baseline diagnosis. Finally, they extended this approach to additional datasets of patients with brain lesions or DBS sites associated with motor symptoms of Parkinson’s disease to determine whether this approach is relevant beyond depression.

What did they find?

First, the authors found that brain lesion and stimulation sites that modulate depressive symptoms are connected to a similar circuit, providing evidence that these three modalities converge on common brain circuitry. This convergent circuit included brain regions and circuits previously implicated in depression. Next, they identified similar depression circuits in patients with major depressive disorder, penetrating brain injury, stroke, epilepsy, and Parkinson’s disease. This indicates that depression symptoms map to a common circuitry regardless of baseline diagnosis. Finally, they found that this approach could be extended beyond depression by demonstrating that brain lesion and stimulation sites associated with Parkinson’s disease symptoms map onto similar circuits.

What's the impact?

This study demonstrates that brain lesions, TMS, and DBS all converge on common brain circuitry, representing potentially improved therapeutic targets for depression symptoms regardless of diagnosis. The methods used to determine these common circuits generalize to Parkinson’s disease, indicating that this approach may also be used to identify brain circuits involved in other neuropsychiatric diseases. Further work is needed to determine whether this approach provides improved therapeutic targets in patients with neuropsychiatric diseases.

Siddiqi et al. Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease. Nature Human Behaviour (2021). Access the original scientific publication here.