Tag Archives: #think

Potential Means of Improving Learning and Memory in People With Mental Illnesses (Psychiatry)

More than a dozen drugs are known to treat symptoms such as hallucinations, erratic behaviors, disordered thinking and emotional extremes associated with schizophrenia, bipolar disorder and other severe mental illnesses. But, drug treatments specifically able to target the learning, memory and concentration problems that may accompany such disorders remain elusive.

Average brain activity during a working memory task in a group of healthy subjects as measured by fMRI. The colors represent higher brain activity in the carriers of the G version of the GCPII enzyme, where brains are less efficient at performing the task, compared with those carriers with the A version of the enzyme. ©Bigos laboratory

In an effort to find such treatments, Johns Hopkins Medicine researchers report they have identified a genetic variation in the brain tissue of a subset of deceased people — some with typical mental health and some with schizophrenia or other psychoses — that may influence cognition and IQ. In the process, they unearthed biochemical details about how the gene operates.

Results of their work, described in the Dec. 1 issue of the American Journal of Psychiatry, could advance the development of drugs that target the enzyme made by this gene, and thus improve cognition in some people with serious mental illnesses or other conditions that cause reduced capacity in learning and memory.

Typical antipsychotic medications that treat schizophrenia symptoms regulate the brain chemical dopamine, a transmitter of nerve impulses associated with the ability to feel pleasure, think and plan, which malfunctions in patients with the disorder. However, previous genetic studies have also shown that another brain chemical signal transmitter, glutamate, a so-called “excitatory” chemical associated with learning and memory, plays a role as well. Another so-called neurotransmitter in this process, N-acetyl-aspartyl-glutamate (NAAG), specifically binds to a protein receptor found on brain cells that has been linked to schizophrenia, but how it impacts this disorder is unknown.

The research of clinical pharmacologist Kristin Bigos, Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine, sought to explore more deeply the role of NAAG in cognitive impairment with the goal of eventually developing therapies for treating these learning, memory or concentration problems.

Using tissues gathered from a repository of brains from deceased donors belonging to the Lieber Institute for Brain Development, Bigos and her team measured and compared levels of certain genetic products in the brains of 175 people who had schizophrenia and the brains of 237 typical controls.

Bigos and her colleagues specifically looked at the gene that makes an enzyme known as glutamate carboxypeptidase II (GCPII), which breaks down NAAG into its component parts ? NAA and glutamate. In the brains of people with schizophrenia and in the typical controls, they found that carriers of this genetic variant (having one or two copies of the gene variation) had higher levels of the genetic product that makes the GCPII enzyme.

In the gene for the enzyme, the only difference in the versions was a single letter of the genetic code, either G or A (for the nucleotide bases guanine and adenine). If people had the version of the gene with one copy of G, then the tissue at the front of their brain ? the seat of cognition ? had 10.8% higher levels of the enzyme than those who had the version of the gene with A, and if people had two copies, they had 21% higher levels of the enzyme.

To see if this genetic variation in GCPII controlled the levels of NAAG in the brains of living people, the researchers measured levels of NAAG in the brain using magnetic resonance spectroscopy, which uses a combination of strong magnetic field and radio waves to measure the quantity of a chemical in a tissue or organ.

In this experiment, they focused on 65 people without psychosis and 57 patients diagnosed with recent onset of psychosis, meaning many of them were likely to eventually be diagnosed with schizophrenia, at the Johns Hopkins Schizophrenia Center. Participants averaged 24 years of age, and 59% were men. About 64% of participants identified as African American, and the remaining 36% were white.

The researchers found 20% lower levels of NAAG in the left centrum semiovale — a region of the brain found deep inside the upper left side of the head — in the white participants both with and without psychosis who had two copies of the G version of the enzyme compared with other white people who had the A version.

To see if having the G or A version of the gene plays a role in cognition, the researchers tested IQ and visual memory in the healthy participants and those with psychosis, both white and African American. They found that people with the most NAAG in their brain (in the top 25%) scored 10% higher on the visual memory test than those in the bottom 25%. They also found that people with two copies of the G version of the GCPII sequence scored 10 points lower on their IQ test on average than the people with the A version of the gene, which the researchers say is a meaningful difference in IQ.

Finally, they showed that healthy carriers of the G version of the GCPII sequence had less efficient brain activity during a working memory task, as measured by functional MRI, by at least 20% compared with those people with the A version of the gene.

“Our results suggest that higher levels of the NAAG are associated with better visual and working memory, and that may eventually lead us to develop therapies that specifically raise these levels in people with mental illness and other disorders related to poor memory to see if that can improve cognition,” says Bigos.

Additional authors on the study include Caroline Zink, Peter Barker, Akira Sawa, Min Wang, Andrew Jaffe, Joel Kleinman, Thomas Hyde, Kayla Carta and Marcus van Ginkel of Johns Hopkins Medicine, and Daniel Weinberger, Henry Quillian, William Ulrich, Qiang Chen, Greer Prettyman and Mellissa Giegerich of the Lieber Institute for Brain Development.

This work was supported by the Lieber Institute for Brain Development, the National Institutes of Mental Health (MH092443, MH094268, MH105660 and MH107730) and the National Institute on Drug Abuse (DA040127).

Some patient or volunteer recruitment costs were supported by the Mitsubishi Tanabe Pharma Corporation.

Provided by Johns Hopkins Medicine

The High Place Phenomenon Is A Strange Urge To Jump Off A Bridge (Psychology)

If you’ve ever sat atop a steep cliff, or on the observation deck of a skyscraper, and looked straight down, you probably remember thinking about how easy it would be to jump. If you’re reading this now, we can safely assume you didn’t — but where does this irrational, obviously suicidal urge come from? Psychologists call it the “high place phenomenon,” and they say it may even be a sign of a healthy mind.

Psychology researchers have found that the urge to jump off a bridge or veer off a cliff is actually surprisingly common. A 2012 study found that it occurs both to people who report having suicidal thoughts and to people who have never shown suicidal tendencies whatsoever. Roughly 50 percent of the non-suicidal study respondents reported having an inexplicable urge to jump from a dangerously high place.

The study’s authors think that the high place phenomenon is a matter of your brain playing a trick on you. Although you weren’t actually going to jump off of the cliff, simply seeing the edge triggers a subconscious fear response that the conscious mind attempts to rationalize. Conscious thought works more slowly than emotional response and the rest of the human brain’s auto-pilot circuitry, which is why you pull your hand away from a hot stove before even thinking about it. In this case, there is no stove, so the conscious mind looks for a rationalization of its fear and says to itself, “Oh no, I must have wanted to jump!”

Another theory suggests that the phenomenon comes from the human tendency to gamble when faced with great risk. It may be that a fear of heights and a fear of death aren’t completely connected in our minds, so while looking down off of a precipice sets off alarm bells, your mind may hold onto an irrational belief that if you could only get to the ground somehow, you’d be safe. So you might as well take the risk and jump.

Scientists and philosophers are just beginning to scratch the surface of the way experiences like the high place phenomenon work. Both fear response and gambit theories rely on the idea that human beings are largely unaware of their own thoughts, motives, and judgments. In 2017, Peter Carruthers published a compelling argument for the idea that we’re all fundamentally unaware of our own thoughts and that the idea that we know them is a convenient illusion — our brains playing another trick on us. This theory explains how the high place phenomenon (and many other irrational behaviors) can take place in our minds, even though everyone likes to think they act in a more-or-less rational way.