Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Brain scans reveal how gene may boost schizophrenia risk

22.04.2005


Clues about how a suspect version of a gene may slightly increase risk for schizophrenia are emerging from a brain imaging study by the National Institutes of Health’s (NIH) National Institute of Mental Health (NIMH). The gene variant produced a telltale pattern of activity linked to production of a key brain messenger chemical.


Areas in prefrontal cortex where blood flow (yellow) was linked to midbrain dopamine synthesis, in opposite directions in subjects with val and met COMT gene type. PET data is superimposed on 3-D MRI view of brain. Source: NIMH Clinical Brain Disorders Branch


An inverted "U" models the relationship between COMT gene type, prefrontal cortex activity, and prefrontal dopamine levels. The cortex functions optimally when dopamine activity is neither too low nor too high, corresponding to the top of the curve. Dopamine is thought to "tune" prefrontal neurons by regulating signal-to-noise ratios - but in opposite directions, depending on whether an individual has inherited the val or met COMT gene type. Source: NIMH Clinical Brain Disorders Branch



The study found that increased activity in the front of the brain predicted increases in the neurotransmitter dopamine in the middle of the brain in subjects with the suspected schizophrenia-related version of the gene. Yet, the opposite relationship held for subjects with the other of two common versions of the gene.

"A tiny variation in the gene that makes the enzyme that breaks down dopamine causes a complete flipflop – not a mere difference in degree – in dopamine activity in these two brain areas," explained NIMH’s Dr. Andreas Meyer-Lindenberg, who, along with Dr. Karen Berman and colleagues, reported their findings in the April 10, 2005 online edition of Nature Neuroscience.


The NIMH study also for the first time confirms in living humans that activity of the front brain area, the prefrontal cortex, is regulated by dopamine production in the midbrain, which, in turn, is regulated by these two common gene variants.

Schizophrenia, a severe mental illness marked by hallucinations and delusions, affects one percent of the population and is treated with antipsychotic drugs that block dopamine. The prefrontal cortex is critical for motivation, learning in response to reward, and working memory – functions impaired in schizophrenia, which is thought to involve a dopamine imbalance.

Individuals inherit two copies (one from each parent) of the gene for the enzyme catecho-O-methyltransferase (COMT), which chemically breaks down dopamine. It comes in two versions, val and met, so a person can have two of the same version or one of each. Since it results in considerably weaker enzyme action, people with the met version are thought have more dopamine in their prefrontal cortex and perform better on tasks involving that part of the brain. Schizophrenia patients typically perform poorly on such tasks. Earlier studies had shown that inheriting two copies of the more common val version leads to a slightly higher risk for schizophrenia and a signature pattern of midbrain dopamine activity.

To see how the two gene versions affect the living human brain, the NIMH researchers scanned 24 healthy young adults twice using PET (positron emission tomography), which uses radioactive tracers to visualize brain function. The first scan measured subjects’ overall brain activity while they performed working memory tasks. The second scan used a dopamine tracer to reveal the synthesis of the neurotransmitter in the midbrain.

Frontal cortex activity increased as midbrain dopamine activity increased in subjects with val, but decreased in those who had inherited two copies of the met COMT gene.

This "trait-like characteristic" of COMT gene type fits a model in which the prefrontal cortex functions optimally when dopamine activity is neither too low nor too high, corresponding to the top of an upside-down "U" (see diagram below). In this model, people with val fall on the left (rising) slope, with lower dopamine levels, while those with met fall on the right (falling) slope, with higher dopamine levels.

The findings suggest that dopamine "tunes" prefrontal neurons (brain cells) to achieve an optimal signal-to-noise ratio, much like a fine-tuning dial on a radio. For the clearest signal, the "dial" must be turned in opposite directions, depending on which version of the COMT gene one inherits: up with val, down with met. In people with val and schizophrenia, which is marked by too little prefrontal and too much midbrain dopamine, the dial is turned "way up," the NIMH researchers speculate.

"We expected that there would be different regulatory mechanisms between the two gene types, but it’s amazing how well the data support this tuning model," said Berman. "The study is important for our understanding of schizophrenia because it clarifies the neural mechanism for a well-established risk gene."

Also participating in the NIMH brain imaging study were: Dr. Daniel Weinberger, Philip Kohn, Dr. Bhaskar Kolachana, Shane Kippenhan, NIMH; Dr. Aideen McInerney-Leo, Dr. Robert Nussbaum, National Human Genome Research Institute (NHGRI).

Jules Asher | EurekAlert!
Further information:
http://www.nih.gov

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
21.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
21.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>