Major
depressive disorder (MDD) is a debilitating psychiatric condition characterized
by a persistently low mood, a lack of motivation, feelings of hopelessness,
altered sleeping and/or eating patterns, and a reduced interest in everyday
activities.
All these symptoms typically make it very difficult
for affected individuals to complete daily tasks, connect with others and
engage in other activities that would normally contribute to their well-being.
Past studies estimate that about half of patients
diagnosed with MDD experience the first symptoms of the disorder during
adolescence, the critical stage of development between childhood and adulthood.
Adolescence can be a very confusing and challenging time for many humans, as it
is a period marked by rapid and yet profound changes affecting both the brain
and body.
While the incidence of early depressive episodes
during teenage years is now well-documented, diagnosing the disorder is not
always easy. Currently, psychiatrists, psychologists and general health
practitioners predominantly diagnose MDD via clinical interviews or
self-reported questionnaires, rather than biological or medical tests.
Researchers at the Psychiatric Center of Chongqing
Medical University and other institutes in China have identified new biomarkers
of MDD in adolescence, by specifically looking at the microorganisms and
bacteria within the digestive system.
Their paper, published in Translational Psychiatry, offers new insight into the gut microbiota that are more prevalent in teenagers diagnosed with depression than in adolescents with no mental health disorders.
"Despite its high prevalence and impact, objective diagnostic
biomarkers for adolescent MDD remain limited, particularly those related to gut
microbiota," write Xueer Liu, Aoyi Geng and their colleagues. "Our
study examined potential co-diagnostic biomarkers from peripheral blood and
fecal samples in adolescents with MDD."
Probing the link between mind and gut
To carry out the study, the researchers recruited 46 adolescents who were
experiencing their first episode of MDD and were less than 19 years old, along
with 44 teenagers in the same age group who were not diagnosed with any mental
health disorders. They collected both blood and stool samples from all these
participants and analyzed them via standard laboratory procedures.
The blood samples were spun in a centrifuge to separate plasma (i.e.,
liquid part of blood) from cells, then analyzed to derive gut barrier proteins
present in the samples and identify any markers of inflammation. The stool
samples, on the other hand, were analyzed using genetics and microbiome
analysis tools, to identify the DNA in gut bacteria, as well as the abundance
of different microorganisms and overall microbiome diversity.
"We enrolled drug-naive adolescents with first-episode MDD and
age-/sex-matched healthy controls," write the authors.
"The levels of tight junction proteins (Claudin-5, Zonulin,
FABP) and inflammatory biomarkers (IL-6, IL-8, TNF-α, and CRP)
were markedly elevated in the plasma of adolescents with MDD, indicating gut
barrier dysfunction and systemic inflammation. The microbiome in MDD patients
exhibited a lower Firmicutes-to-Bacteroidetes ratio.
At the genus level, Intestinimonas and Barnesiella were significantly enriched,
while Dialister and Collinsella were considerably reduced."
The researchers analyzed all the data they collected using statistical
methods and were able to identify common patterns in the gut microbiome of
healthy participants and those diagnosed with MDD. Firstly, they observed that
adolescents with depression exhibited signs of weakened gut barriers and
greater inflammation in their blood.
The composition of their gut bacteria was also different compared to that
of teens with no psychiatric disorders. The team observed a lower balance of
bacteria in the gut of teens with MDD, as well as a prevalence of a bacterium
known as Collinsella, which was linked to inflammation and changes in the gut's
barrier.
Informing the future diagnosis and treatment of
depression
As part of their study, the researchers also explored the possibility of
diagnosing MDD using the blood and stool markers they identified. They found
that looking at a combination of inflammation-related biomarkers and the
abundance of the bacterium Collinsella allowed them to diagnose MDD with good
accuracy.
"Integrating Collinsella abundance with tight junction proteins and
inflammatory markers significantly improved diagnostic performance, achieving
an area under the curve (AUC) of 0.964," write Liu, Geng and their
colleagues.
"Moreover, Collinsella negatively correlated with sex, Claudin-5, and
TNF-α. Claudin-5 was strongly associated with short-chain fatty acids
(SCFAs)-related pathways, including alanine, aspartate, glutamate metabolism,
D-glutamine and D-glutamate metabolism, and autophagy regulation. Treatment of
Caco-2 cells with propionate and butyrate confirmed the regulatory effects of
SCFAs on tight junction biomarkers."
Overall, the team's research suggests that changes in gut bacteria
influence the production of SCFAs, small molecules that are produced when gut
bacteria break down dietary fiber. These changes in turn impact the function of
the gut barrier, potentially contributing to inflammation and to the emergence
of depressive symptoms.
In the future, the inflammation and gut-related biomarkers identified by
Liu, Geng and their colleagues could serve as more effective targets for the
reliable diagnosis of MDD in adolescents. In addition, their work could
potentially contribute to the identification of new strategies aimed at
reducing the intensity of depressive symptoms by altering the gut microbiome.
"These findings suggest the interplay between gut dysbiosis, barrier dysfunction, and inflammation in adolescent MDD and support microbiota-host biomarkers as a promising strategy for improving MDD diagnostic precision," write the authors.
Source: How gut bacteria could help to diagnose teen depression
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