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What makes us human, and where does this mysterious property of

“humanness” come from? President and Professor Rusty Gage, along

with co-first author Carol Marchetto and colleagues, developed a

strategy to more easily study the early development of human neurons

compared with the neurons of nonhuman primates. The research offers

scientists a novel tool to construct an evolutionary tree of multiple

primate species to better understand the evolution of the human brain.

UNCOVERING THE

EVOLUTION OF THE BRAIN

DISCOVERIES

In two recent editions of

Molecular Psychiatry

, Gage,

first author Krishna Vadodaria and collaborators

showed why selective serotonin reuptake inhibitors

(SSRIs), a common treatment for major depressive

disorder that increases the neurotransmitter serotonin,

do not work in some patients. The discoveries could help

lead to more personalized treatments for depression

as well as other psychiatric conditions, such as bipolar

disorder and schizophrenia.

In the first study, published in January, the researchers

created neurons from skin cells from patients whose

depression did not show signs of improving with SSRIs.

The team discovered that these patient-derived neurons

became hyperactive when serotonin levels increased,

compared with cells derived from healthy individuals or

those who respond to SSRIs.

InMarch, a second paper by the group demonstrated that

neurons from SSRI-resistant patients had longer neuron

projections than did neurons from SSRI-responders,

along with low levels of key genes involved in forming

brain circuits.

WHY

ANTIDEPRESSANTS

DO NOT WORK FOR

EVERYONE

A stylized microscopy image of forebrain neural

progenitor cells from chimpanzees.The image

represents the work’s potential for offering insights

into the evolution of the primate tree of life.

Image credit: Salk Institute/Carol Marchetto/

Ana P.D. Mendes

From left: Amy Le, Kelly Heard, Rusty Gage,

Krishna Vadodaria and Carol Marchetto.

MOLECULAR

PSYCHIATRY

1/30/2019,

3/22/2019

eLIFE

02/2019

10 INSIDE SALK

FALL 2019

WWW.SALK.EDU

NEUROSCIENCE