Stacey Kigar, PhD
Neuroscience · Neuroimmunology
Research

Why does early-life stress shape mental health for a lifetime?

Mental illness rarely has a single cause; risk accumulates across a lifetime, and yet some people exposed to early adversity develop disorders while others stay well. I use the immune system as a window into how early-life stress is written into the brain and body, tracing that signal from development, through adult stress reactivity, into later-life aging.

The question

Why do some towers stand while others fall?

Mental illness rarely has a single cause. Think of vulnerability as a Jenga tower: heredity, early development, and life experience each shift a brick. Some towers absorb the losses and stand; others reach a tipping point and fall. My work focuses on one especially load-bearing brick — early-life stress — to understand who is susceptible, who is resilient, and why.

Heredity
Development
Early-life stress
Adult stress
Aging
EARLY LIFE

Brain and immune systems co-assemble. Adversity here is embedded in both.

ADULTHOOD

Chronic stress remodels immune signaling at the brain's borders, altering behavior.

LATER LIFE

Early marks may surface as accelerated immune aging and cognitive risk.

01 · ADULT CHRONIC STRESS

Stress reshapes immunity at the brain's borders

In a mouse model of chronic social stress, I showed that immune cells called neutrophils accumulate in the meninges — the brain's protective lining — by trafficking directly from skull bone marrow rather than crossing the blood–brain barrier. This build-up is driven by type I interferon signaling, and blocking that signal in the periphery rescues both the cellular change and the depressive- and anxiety-like behavior. A coordinated shift in B cells acts further upstream.

Kigar & Lynall et al., Nature Communications (2025) · Lynall & Kigar et al., Brain, Behavior & Immunity (2021)
Immune cells along cerebral vasculature
Immune cells (green) tracking along cerebral vasculature (red) at the brain's borders. Two-photon microscopy.
T-cell subsets
T-cell subsets (Th1 · Th2 · Th17 · Treg) sorted and profiled from clinical cohorts.
02 · FROM MICE TO PEOPLE

How early-life stress is imprinted on immune cells

T cells are among the strongest peripheral immune predictors of depression, and psychiatric genetic risk is concentrated in the regions of the genome these cells use. At Cambridge I ask whether early-life adversity leaves a lasting epigenetic mark on circulating T cells — profiling sorted cells from clinical cohorts with a purpose-built, openly shared analysis pipeline. Because these same marks track biological age, the work also asks how early stress may accelerate immune aging.

Clinical cohort analyses ongoing · Smith & Kigar et al., BBI–Health (2025)
03 · THE DEVELOPING BRAIN

Epigenetics, sex, and social behavior

My doctoral work identified Gadd45b — an epigenetic regulator expressed more highly in females — as a switch for juvenile social behavior. Briefly reducing it in the newborn amygdala reorganized social play in adolescence and transiently quieted pro-inflammatory signaling, an early link between the epigenome, the immune system, and sex-specific behavior.

Kigar et al., Scientific Reports (2017) · Kigar et al., Brain, Behavior & Immunity (2015)
Mouse brain regions
Neonatal amygdala — site-targeted epigenetic manipulation in the developing brain.

Approaches & techniques

Confocal & cleared-tissue light-sheet imagingHigh-dimensional flow cytometrySingle-cell RNA-seqGenome-wide DNA methylation (EWAS)Custom bioinformatic pipelinesRodent stress & behavioral modelsClinical cohort studies
Future directions · The EMBiR Lab

My lab will open the black box between early adversity and adult psychiatric risk — building a developmental model of stress that asks when vulnerability is installed, where in the body it acts, and who is susceptible.

EMBiR — Early-life Mechanisms shaping Brain and immune Risk

AIM 1 · WHEN

When is stress embedded?

Mapping the developmental windows — across both sexes — when the brain and immune system are most sensitive to adversity.

AIM 2 · WHERE

Where does it act — and what's targetable?

Testing causal, already-druggable pathways to ask whether the psychiatric effects of early adversity can be prevented or reversed.

AIM 3 · WHO

Who is resilient?

Using natural variation in stress outcomes — and sex as a candidate resilience factor — to find what protects the brain across the lifespan.