How Depression Affects the Brain
December 16, 2025Transcript
- 00:08The current standard of care
- 00:10for the treatment of depression
- 00:13is based on what we
- 00:14call the monoamine
- 00:15deficiency hypothesis.
- 00:17Essentially presuming
- 00:19that one of three neurotransmitters
- 00:21in the brain is deficient
- 00:23or under active. Neurotransmitters can
- 00:25be thought of as the
- 00:26chemical messengers within the brain.
- 00:28It's what helps one cell
- 00:29in the brain communicate with
- 00:30another to pass that message
- 00:32along. But the reality is
- 00:33there are more than a
- 00:34hundred neurotransmitters
- 00:35in the brain and billions
- 00:37of connections between neurons.
- 00:39So we know that that's
- 00:41a limited hypothesis.
- 00:48For decades,
- 00:49we thought that the primary
- 00:52pathology, the primary cause of
- 00:53depression was some abnormality in
- 00:55these neurotransmitters,
- 00:56specifically serotonin or norepinephrine.
- 00:59However, norepinephrine
- 01:01and serotonin
- 01:02did not seem to be
- 01:03able to account for the
- 01:05symptoms of depression in people
- 01:07who had major depression.
- 01:09Instead,
- 01:10the chemical messengers
- 01:12between the nerve cells in
- 01:14the higher centers of the
- 01:15brain involved in
- 01:17regulating mood and emotion, which
- 01:20include glutamate and GABA,
- 01:22were
- 01:23possibilities
- 01:24as alternative causes
- 01:26for the symptoms of depression.
- 01:28We know that these two,
- 01:30which are the most ubiquitous
- 01:31and abundant
- 01:33neurotransmitters in the brain,
- 01:35actually regulate
- 01:36how the brain is
- 01:38changing over time and adapting.
- 01:40When you are exposed to
- 01:42severe and chronic stress, like
- 01:43people experience when they have
- 01:45depression,
- 01:46you lose some of the
- 01:48connections between the nerve cells.
- 01:50And the communication in these
- 01:52circuits
- 01:53becomes inefficient
- 01:55and noisy.
- 01:57Because of the
- 01:58noisy communication
- 02:00in the circuits involved
- 02:02in regulating mood and emotion.
- 02:05We think that the loss
- 02:07of these synaptic connections
- 02:11contributes to the biology of
- 02:12depression.
- 02:19It's critical to understand the
- 02:21neurobiology
- 02:22of depression and how the
- 02:24brain plays a role in
- 02:25that for two main reasons.
- 02:27One, it helps us understand
- 02:29how the disease
- 02:30develops and progresses
- 02:32and we can start to
- 02:33target treatments based on that.
- 02:35There are clear differences between
- 02:37a healthy brain and a
- 02:38depressed brain. And the exciting
- 02:40thing is when you treat
- 02:41that depression
- 02:44effectively,
- 02:45the brain goes back to
- 02:46looking like a healthy brain.
- 02:47We recognize that the treatment
- 02:49for depression is a long
- 02:50term process because for many
- 02:52people depression is a long
- 02:54term disorder.
- 02:56So we need new treatments.
- 02:59We've needed new ways to
- 03:01approach depression
- 03:02for people that haven't responded
- 03:04well to their prior treatments.
- 03:06We are
- 03:07in a new era of
- 03:09psychiatry. Psychiatry. This is a
- 03:11paradigm shift
- 03:12away from
- 03:15a model of monoamaminergic
- 03:18deficiency
- 03:19to
- 03:20a fuller understanding
- 03:22of the brain as a
- 03:23complex
- 03:25neurochemical
- 03:29organ.