Depression, Anxiety and Heart Disease Risk All Linked To A Single Brain Region

Depression, Anxiety and Heart Disease Risk All Linked To A Single Brain Region
Over-activity in the brain’s subgenual anterior cingulate cortex is likely to be one cause of depression and anxiety.
ESB Professional/ Shutterstock

Although depression and anxiety affect millions of people worldwide, there’s still much we don’t know about them. In fact, we still don’t fully understand which brain regions are involved in depression and anxiety, and how they differ between people with varying symptoms. Understanding how or why these differences occur is fundamental to developing better treatments.

So far, we know that part of the brain’s frontal lobe, the prefrontal cortex, often shows activity changes in people with depression and anxiety. Parts involved in cognition and regulating emotions are underactive, whereas other parts involved in emotion generation and internal bodily functions are over-active.

One key region shown to be over-active in people with depression and anxiety is the subgenual anterior cingulate cortex (sgACC), thought to be involved in emotional responses. However, neuroimaging studies only show correlation and don’t tell us that the over-activity causes any of the symptoms. But our new research has found over-activating the sgACC induces symptoms of depression and anxiety, highlighting causality.

For our study, we used marmosets (a type of primate) because their brain closely resembles a human’s brain. We found over-activity in this region causes several key features of mood and anxiety disorders, particularly how reactive they are to threat. Their reaction to threat is important, as patients with depression and anxiety tend to perceive and react to situations more negatively.

To over-activate sgACC, we implanted tiny hollow tubes – called cannulae – into the marmosets’ brains. We then infused small amounts of a drug into sgACC to increase excitability without damaging or disrupting function in other brain regions. We also implanted a small wireless device into an artery to measure blood pressure and heart rate.

But before over-activating sgACC, we trained the marmosets to associate a specific tone with the presence of a rubber snake, which marmosets find threatening. After learning this association, the marmosets exhibited fear and had higher blood pressure when hearing the tone. We then presented the tone without the snake to break this association. This allowed us to measure how quickly the marmosets could dampen their fear response with and without sgACC over-activation.

Without over-activation, marmosets gradually regulated their threat response within minutes when hearing the tone without the snake. But after over-activating sgACC, marmosets exhibited fearful behaviour and higher blood pressure for much longer. They also remained anxious around other types of threat (in the form of an unfamiliar human). This reaction showed they could no longer dampen down their threat responses. Being unable to regulate emotions is also seen in many patients with anxiety and depression.

These findings build on our earlier work that showed over-activity of sgACC reduces anticipation and motivation for rewards, mirroring the anhedonia (inability to feel pleasure) seen in depression. This suggests sgACC over-activity can cause two of the core symptoms seen in depression – negative emotions (including anxiety) and lack of pleasure.

Heart disease and depression

Another outstanding question is why people with depression also have increased risk of heart disease. While there’s undoubtedly lifestyle and socioeconomic factors linking heart disease and depression, we wanted to test whether sgACC over-activity itself could disrupt cardiovascular function. We thought this region might be important because it’s connected to the brainstem, which regulates our heart rate and blood pressure.

We found that sgACC over-activity not only exaggerated marmosets’ blood pressure response to threat, it also increased heart rate and reduce heart rate variability even at rest. Heart rate variability is an important measure of how rapidly the heart can adapt to changes in the environment, especially cues which predict reward or punishment.

These changes mirror some of the cardiac dysfunction seen in depression and anxiety. The elevated heart rate and reduced heart rate variability suggests that over-activity in sgACC promotes the body’s “fight-or-flight” response, which – if lasting over long periods of time – puts the heart under extra strain and might explain the increased incidence of heart disease.

Treatment response

We also used brain imaging to investigate the other regions affected by sgACC over-activity in threatening situations. We saw increased activity in two key parts of the brain’s stress network, the amygdala and hypothalamus. By contrast, reduced activity was seen in parts of the lateral prefrontal cortex, which regulates emotional responses and is underactive in depression. These changes were very different to those seen following over-activation during a rewarding situation.

Knowing these differences may be key to us understanding which treatments will be most effective depending on the symptoms exhibited by a patient. This then led us to investigate why some people respond to antidepressants while others don’t. The most common type of antidepressants are selective serotonin re-uptake inhibitors (SSRIs). But up to one-third of people who take antidepressants are treatment resistant – meaning they don’t respond to them. New treatments are urgently needed for these people.

Ketamine has shown some promise in successfully treating people with treatment resistant depression – and acts within hours to relieve symptoms. Previously, we had shown ketamine effectively treated anhedonia after sgACC had been over-activated.

But in our recent study, we found that ketamine could not improve the elevated anxiety-like responses the marmosets displayed towards the unfamiliar human. This shows us different depression and anxiety symptoms react differently to different types of antidepressants or treatments. On one hand, anhedonia was reversed by ketamine, while anxiety was not.

But over-activation of sgACC is likely to be just one underlying cause of depression and anxiety. Others may have altered activity in different regions of the prefrontal cortex, which are also linked to anxiety. There’s still a long way to go before we have identified the different causes of depression and anxiety and which treatments can improve them. But our research shows that for some, targeting sgACC over-activity may be key in treating their symptoms.

About the AuthorsThe Conversation

Laith Alexander, Academic Foundation Doctor, University of Cambridge; Angela Charlotte Roberts, Professor of Behavioural Neuroscience, University of Cambridge, and Christian Wood, Postdoctoral Research Associate, Physiology and Pharmacology, University of Cambridge

This article is republished from The Conversation under a Creative Commons license. Read the original article.

You May Also Like

AVAILABLE LANGUAGES

enafarzh-CNzh-TWdanltlfifrdeeliwhihuiditjakomsnofaplptroruesswsvthtrukurvi

INNERSELF VOICES

happy woman 's face
How To Experience A Mystical State of Consciousness
by Ora Nadrich
Whatever it is we seek pleasure from, relying on external things to give us the high or a feeling…
a blurred clock expanding over a starry background
Horoscope Current Week: December 6 - 12, 2021
by Pam Younghans
This weekly astrological journal is based on planetary influences, and offers perspectives and…
12 05 from rigidity to change 647528 complete
From Rigidity to Change
by Marie T. Russell, InnerSelf.com
In order for things, or people, to change they need to be flexible. A willow tree bends in the wind…
man and dog in front of giant sequoia trees in California
The Art of Constant Wonder: Thank you, Life, for this day
by Pierre Pradervand
One of the greatest secrets of life is to know how to constantly marvel at existence and at the…
Photo: Total Solar Eclipse on August 21, 2017.
Horoscope: Week of November 29 - December 5, 2021
by Pam Younghans
This weekly astrological journal is based on planetary influences, and offers perspectives and…
young boy looking through binoculars
The Power of Five: Five Weeks, Five Months, Five Years
by Shelly Tygielski
At times, we have to let go of what is to make room for what will be. Of course, the very idea of…
man eating fast food
It's Not About the Food: Overeating, Addictions, and Emotions
by Jude Bijou
What if I told you a new diet called the "It's Not About the Food" is gaining popularity and…
woman dancing in the middle of an empty highway with a city skyline in the background
Having the Courage to Be True to Ourselves
by Marie T. Russell, InnerSelf.com
Each one of us is a unique individual, and thus it seems to follow that each one of us has a…
Lavender Uses
The Benefits of Lavender: Growing, Harvesting and Using This Medicinal Plant
by Michelle Schoffro Cook, PhD, DNM, ROHP
It’s easier than you think to experience the beauty and healing properties of lavender by growing…
No More Saviours: Reclaiming Our Mind from The Tyranny of Fear
No More Saviours: Reclaiming Our Mind from The Tyranny of Fear
by Sarah Varcas
A lunar eclipse in Sagittarius on 26th May begins a sequence of key astrological events, making…
The Dilemma of The Freedom to Choose
The Dilemma of The Freedom to Choose
by Lisette Schuitemaker
Across the globe, the freedom to choose what will define our lives is vastly different. We who have…

Selected for InnerSelf Magazine

MOST READ

How Living On The Coast Is Linked To Poor Health
How Living On The Coast Is Linked To Poor Health
by Jackie Cassell, Professor of Primary Care Epidemiology, Honorary Consultant in Public Health, Brighton and Sussex Medical School
The precarious economies of many traditional seaside towns have declined still further since the…
The Most Common Issues for Earth Angels: Love, Fear, and Trust
The Most Common Issues for Earth Angels: Love, Fear, and Trust
by Sonja Grace
As you experience being an earth angel, you will discover that the path of service is riddled with…
How Can I Know What's Best For Me?
How Can I Know What's Best For Me?
by Barbara Berger
One of the biggest things I've discovered working with clients everyday is how extremely difficult…
Honesty: The Only Hope for New Relationships
Honesty: The Only Hope for New Relationships
by Susan Campbell, Ph.D.
According to most of the singles I have met in my travels, the typical dating situation is fraught…
An Astrologer introduces the Nine Dangers of Astrology
An Astrologer introduces the Nine Dangers of Astrology
by Tracy Marks
Astrology is a powerful art, capable of enhancing our lives by enabling us to understand our own…
Giving Up All Hope Could Be Beneficial For You
Giving Up All Hope Could Be Beneficial For You
by Jude Bijou, M.A., M.F.T.
If you're waiting for a change and frustrated it's not happening, maybe it would be beneficial to…
Chakra Healing Therapy: Dancing toward the Inner Champion
Chakra Healing Therapy: Dancing toward the Inner Champion
by Glen Park
Flamenco dancing is a delight to watch. A good flamenco dancer exudes an exuberant self-confidence…
Taking A Step Toward Peace by Changing Our Relationship With Thought
Stepping Toward Peace by Changing Our Relationship With Thought
by John Ptacek
We spend our lives immersed in a flood of thoughts, unaware that another dimension of consciousness…

New Attitudes - New Possibilities

InnerSelf.comClimateImpactNews.com | InnerPower.net
MightyNatural.com | WholisticPolitics.com | InnerSelf Market
Copyright ©1985 - 2021 InnerSelf Publications. All Rights Reserved.