Neurobiology of Depression

Heather C. Abercrombie, Ph.D.Department of PsychiatryUW School of Medicine & Public Health

Neural circuitry in depression

• Neuroanatomy of emotion

• Neural circuitry associated with core psychological features of depression

• Alterations in neuroplasticity

• Treatment implications

Neuroanatomy of emotionDorsolateral PFC: Approach-related positive affect (left)

Orbitofrontal cortex: Affective evaluation; decoding punishment and reward value

Amygdala: Vigilance for motivationally salient events; threat detection; emotional memory

Anterior cingulate cortex (ACC):Top-down modulation; conflict detection

Insula: Representation of the body’s internal state; interoception

Withdrawal-related negative affect; threat-related vigilance (right)

Hippocampus: Declarative memory; spatial navigation; contextual fear

Insula and ACC: Integration of sensory, affective, cognitive, and autonomic processing

Neuroanatomy of emotion

Nucleus Accumbens: Reward processing; positive emotion; salience detection

Core Psychological Features of Depression

• Rumination• Inward-focused attention• Low reward sensitivity• Difficulty with emotion

regulation

Subgenual PFC connectivity – Inward attention at rest and during introspective tasks

Buckner et al. (2008) Annals NY Acad Sci.

Increased subgenual PFC connectivity associated with rumination in depression

Berman et al. (2011) SCAN.

Increased subgenual PFC connectivity in depression

Grecius et al. (2007) Biological Psychiatry.

Nejad, Fossati, & Lemogne (2013) Front Hum Neurosci.

Self-related processing and anterior cortical midline in depression

Reduced ventral striatal activation in depression associated with low reward sensitivity

Auerback, Admon, Pizzagalli (2014).

Loosening of regulatory control of PFC over amygdala

Adapted from Johnstone et al. (2007) J Neuroscience.

Reeck, Ames, & Ochsner (2016) Trends Cogn Sci.

PFC modulation of subcortical areas during emotion regulation

Anatomical projections between PFC and amygdala in rhesus monkeys

Ghashghaei, Hilgetag, & Barbas (2007) NeuroImage.Also see Salzman & Fusi (2010) Annu Rev Neurosci.

Antidepressants alter many neuroplastic mechanisms that underlie “cells that fire together wire together”

From Castren & Hen (2013) Trends in Neurosciences.

Increase in PFC-amygdala functional connectivity with 6 wks sertraline

Anand, et al. (2007) J Neuropsychiatry & Clin Neurosci.

Neural circuitry & therapeutic learning in depression

• Relevant circuits and neural connectivity

• Altered connectivity of medial PFC & other brain areas – self-related processing

• Alterations in neural circuitry related to emotion regulation, including altered connections between PFC and:

• Ventral striatum and nucleus accumbens – low reward sensitivity

• Amygdala – impaired down-regulation of negative affect

• Pair medical treatments with biologically-informed behavioral interventions

• Promote therapeutic learning

• “Sculpt” neural circuits

• Require practice and repetition of new skills