Neural Circuit Taxonomy and Precision Psychiatry in Major Depression

Adv Exp Med Biol. 2026;1502:31-45. doi: 10.1007/978-981-95-6872-7_3.

ABSTRACT

Patients with major depressive disorder (MDD) demonstrate a relatively higher relapse risk and exhibit considerable clinical and biological heterogeneity with possible distinct neurophysiological mechanisms. In this chapter, we adapt an approach of neural circuit taxonomy and will demonstrate brain network-based correlates of clinical symptom subtypes in MDD. First, anhedonia might encompass negative-affect circuit dysfunction and reward-processing dysfunctions. Structural covariance of brain gray matter morphologies within the salience and limbic networks, and among the salience limbic default-mode somatomotor visual networks are reflective of anhedonia in depression. Second, hyperactivation of default-mode network and lowered functioning of frontoparietal network underlie thought rumination. Third, altered functioning of salience network could contribute to difficulty distinguishing relevant salient cues and anxious avoidance. Fourth, hyperactivation of limbic network and increased connectivity with default-mode network might contribute to heightened negative bias and negative affect. Fifth, hypofunctioning of frontoparietal network and dorsal attention network might underlie inattentiveness and cognitive dyscontrol. Finally, limbic, salience, frontoparietal, and subcortical networks, including the thalamus orchestrate in suicidality of MDD.

PMID:42036560 | DOI:10.1007/978-981-95-6872-7_3