New findings linking abnormalities in circadian rhythms to neurochemical to changes in specific neurotransmitters

May 31, 2016, McLean Hospital

Results of the first study of its kind to link abnormalities in circadian rhythms to changes in specific neurotransmitters in people with bipolar disorder will be published this week in the journal Biological Psychiatry.

The three-year study conducted by McLean researchers points to specific neuroanatomical changes in human subjects with these illnesses, and specifically to neurons that regulate anxiety and stress response, according to Harry Pantazopoulos, PhD, assistant neuroscientist at McLean's Translational Neuroscience Laboratory and instructor in psychiatry at Harvard Medical School.

"For more than 50 years, there's been evidence that there's something wrong with in people with , but there has been a huge gap in terms of what we understand about their brains and how altered circadian rhythms are contributing to their symptoms," noted Pantazopoulos, lead author of the study.

"Growing evidence points to a key role for somatostatin, a neurotransmitter in schizophrenia and bipolar disorder," he said. "In the amygdala, a part of the brain involved in anxiety and stress, somatostatin plays an important role in the regulation of anxiety and depression, often co-occurring in these disorders."

The paper provides three main, previously unreported findings:

  • Somatostatin immunoreactive neurons are decreased in the amygdala in schizophrenia and in bipolar disorder.
  • The expression of somatostatin in the human amygdala displays a healthy circadian rhythm of expression.
  • This circadian somatostatin expression is altered in subjects with bipolar disorder.

This altered circadian function of somatostatin in subjects with bipolar disorder consists of a sharp decrease in somatostatin expression by neurons in the early morning, in comparison to a rise in the same neurons during this time interval in healthy control subjects, according to Pantazopoulos.

"We eventually saw that people with bipolar disorder have a very strong decrease of this protein in the beginning of the day while people without a psychiatric disorder normally have an increase in this protein," he said. "The decrease of the protein correlates very strongly with the established severity of depression and anxiety symptoms in people with mood disorders, in the morning. Therefore, our findings point to potential neural correlates of circadian rhythm abnormalities associated with specific symptoms in bipolar disorder."

The study was conducted using postmortem brains from the Harvard Brain Tissue Resource Center, in which 15 brains were used from healthy controls, 15 with bipolar disorder, and 12 with schizophrenia.

"Brain imaging technology doesn't have the resolution at the moment to allow us to examine these neurons in the brain in people with bipolar disorder because the changes are in very specific neurocircuits that we can't visualize very well," said Pantazopoulos. "With post mortem brain studies, we are able to look at changes microscopically."

While the study validates what many researchers have long suspected, Pantazopoulos is cautious about drawing conclusions. "We're only scratching the surface of learning what the rhythmic expression of these proteins does biologically and how this goes awry in psychiatric disorders. We have a long way to go, as this is just one brain region and one specific protein."

Pantazopoulos recently launched a new study that looks at neurotransmitters as well as the clock genes within the suprachiasmatic nucleus of people with bipolar disorder and those without psychotic disorders—to characterize how the proteins' rhythm of expression change.

"From studies on animals, we know we can treat the circadian rhythm of the suprachiasmatic nucleus non-pharmacologically by using . We could potentially correct the abnormalities in circadian rhythms in some areas, such as the amygdala—by resetting the circadian rhythm with bright light therapy," said Pantazopoulos. "The goal is to not only understand the pathology of these disorders, but to develop new diagnostic methods and treatments down the line, possibly patient-specific bright light therapy."

Explore further: Study lays groundwork for potential bipolar disorder therapies

Related Stories

Study lays groundwork for potential bipolar disorder therapies

March 9, 2016
Bipolar disorder, which affects nearly eight million Americans, takes a toll not only on patients, but also on their families and communities.

Adults with bipolar disorder at equal risk for anxiety or depression following mania

May 3, 2016
Adults with bipolar disorder are just as likely to develop anxiety as depression following an episode of mania, according to data from a national survey of more than 34,000 adults. This finding, published today in Molecular ...

Neurosurgeon studying if deep brain stimulation can help with bipolar disorder

May 26, 2016
Jennifer Sweet, MD, a neurosurgeon at University Hospitals Case Medical Center, recently opened a clinical research study to learn if there is a structural target in the brain for patients suffering from bipolar disorder ...

Ras protein regulates circadian rhythm

March 18, 2015
Biochemists at the Ruhr-Universität Bochum have gained new insights into the generation and maintenance of circadian rhythms. They demonstrated that the Ras protein is important for setting the phase of such a circadian ...

Adolescent brain develops differently in bipolar disorder

June 1, 2015
In adolescents with bipolar disorder, key areas of the brain that help regulate emotions develop differently, a new study by Yale School of Medicine researchers shows.

Recommended for you

Psychiatric disorders share an underlying genetic basis

June 21, 2018
Psychiatric disorders such as schizophrenia and bipolar disorder often run in families. In a new international collaboration, researchers explored the genetic connections between these and other disorders of the brain at ...

One year of school comes with an IQ bump, meta-analysis shows

June 21, 2018
A year of schooling leaves students with new knowledge, and it also equates with a small but noticeable increase to students' IQ, according to a systematic meta-analysis published in Psychological Science, a journal of the ...

Ketamine acts fast to treat depression and its effects last—but how?

June 21, 2018
In contrast to most antidepressant medications, which can take several weeks to reduce depressive symptoms, ketamine—a commonly used veterinary anesthetic—can lift a person out of a deep depression within minutes of its ...

Mindful movement may help lower stress, anxiety

June 21, 2018
Taking a walk may be a good opportunity to mentally review your to-do list, but using the time to instead be more mindful of your breathing and surroundings may help boost your wellbeing, according to researchers.

Brain tingles—first study of its kind reveals physiological benefits of ASMR

June 21, 2018
Autonomous sensory meridian response (ASMR) – the relaxing 'brain tingles' experienced by some people in response to specific triggers, such as whispering, tapping and slow hand movements – may have benefits for both ...

New study debunks Dale Carnegie advice to 'put yourself in their shoes'

June 21, 2018
Putting yourself in someone else's shoes and relying on intuition or "gut instinct" isn't an accurate way to determine what they're thinking or feeling," say researchers from Ben-Gurion University of the Negev (BGU), the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.