Researchers discover gene variant associated with cocaine dependence, cocaine induced paranoia

March 2, 2009

Researchers from Boston University School of Medicine (BUSM) and Yale University School of Medicine and the University of Connecticut School of Medicine, have discovered that variants in the α-endomannosidase (MANEA) gene are associated with cocaine addiction and cocaine-induced paranoia in European American and African American populations. These findings appear in the March issue of the Archives of General Psychiatry.

Cocaine is widely abused in the United States. The 2002 National Survey on Drug Use and Health revealed that nearly six million Americans age 12 or older used the drug during the preceding year. Compulsive use of cocaine is also common with more than one million individuals considered dependent on the drug. Several studies have suggested a substantial genetic contribution to cocaine dependence and related behaviors.

The researchers took a total of 3,992 individuals from two family-based samples (European American and African American) and two case-control samples (European American and African American) enrolled in studies of drug addiction and classified them as either cocaine dependent, suffering from cocaine-induced paranoia or controls. They were then genotyped for 11 markers spanning the MANEA gene. MANEA encodes an enzyme (a-endomannosidase) that metabolizes complex carbohydrates. MANEA was chosen for further study based on evidence from a low-resolution scan of the entire genome the researchers performed previously to search for genes associated with substance dependence.

The researchers found cocaine induced paranoia was associated with six of the 11 markers in the European American family sample. They also found these six markers and three other markers were significant in the African American sample. The strongest evidence for association in either population and in the total sample was observed for marker rs9387522, which is located in the 3' untranslated region of the gene. The A allele for this marker was associated with increased risk of cocaine induced paranoia in all four data sets.

"Our findings suggest that cocaine dependence and associated behaviors may involve biological pathways not typically thought to be associated with brain metabolism and now opens a new pathway to understanding these highly prevalent disorders and their psychopathological manifestations," said lead author Lindsay A. Farrer, PhD, chief of the Genetics Program and professor of medicine, neurology, genetics & genomics epidemiology and biostatistics at BUSM.

According to the researchers, given MANEA's role in carbohydrate metabolism and relatively minor expression in brain, it would not appear initially to be a good biological candidate to modulate susceptibility to cocaine dependence or its associated psychotic complications. "However, insight into the relationship between MANEA, paranoia, and cocaine dependence can be gleaned from studies of mannosidase and other glycoproteins," notes Farrer.

MANEA is one of several glycosidic enzymes that remove oligosaccharide chains of dopamine β-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine. Low levels of DBH in plasma or cerebrospinal fluid and genetic variants in DBH have been associated with greater vulnerability to psychotic symptoms in several psychiatric disorders including cocaine dependence, schizophrenia, and major depression. MANEA may also influence susceptibility to cocaine dependence by modifying the function of liver carboxylesterase, a glycoprotein of the high mannose type, two forms of which hydrolyze cocaine and other drugs.

"This finding suggests that drug dependence and associated behaviors may involve biological pathways not typically associated with brain metabolism, and opens a new pathway to understanding these highly prevalent disorders and their psychopathological manifestations," added Farrer.

Source: Boston University

Explore further: Opioid abuse leads to heroin use and a hepatitis C epidemic, researcher says

Related Stories

Opioid abuse leads to heroin use and a hepatitis C epidemic, researcher says

February 22, 2018
Heroin is worse than other drugs because people inject it much sooner, potentially resulting in increased risk of injection-related epidemics such as hepatitis C and HIV, a Keck School of Medicine of USC study shows.

Study finds neurotransmitter may play a role in alcohol relapse, addiction

February 12, 2018
A study led by Indiana University on neurochemical changes associated with alcohol addiction found that the neurotransmitter glutamate plays a role in some alcohol cravings.

The link between drugs and music explained by science

January 25, 2018
For centuries, musicians have used drugs to enhance creativity and listeners have used drugs to heighten the pleasure created by music. And the two riff off each other, endlessly. The relationship between drugs and music ...

Researchers discover key link between mitochondria and cocaine addiction

December 20, 2017
For years, scientists have known that mitochondria in brain cells play a role in brain disorders such as depression, bipolar disorder, anxiety and stress responses. But recently, scientists at the University of Maryland School ...

Potency, purity of drugs reaching even higher levels

December 8, 2017
Ten years ago, the average gram of meth available in the U.S. was 39 percent pure. Today, it is being sold in a nearly pure state, manufactured in Mexican "superlabs" and smuggled across the border to feed an epidemic of ...

Opioid crisis strains foster system as kids pried from homes

December 12, 2017
The case arrives with all the routine of a traffic citation: A baby boy, just 4 days old and exposed to heroin in his mother's womb, is shuddering through withdrawal in intensive care, his fate now here in a shabby courthouse ...

Recommended for you

Young children use physics, not previous rewards, to learn about tools

February 23, 2018
Children as young as seven apply basic laws of physics to problem-solving, rather than learning from what has previously been rewarded, suggests new research from the University of Cambridge.

Study: Tinder loving cheaters—dating app facilitates infidelity

February 23, 2018
The popular dating app Tinder is all about helping people form new relationships. But for many college-aged people, it's also helping those in relationships cheat on their romantic partners.

Looking for the origins of schizophrenia

February 23, 2018
Schizophrenia may be related to neurodevelopmental changes, including brain's inability to generate an appropriate vascular system, according to new study resulted from a partnership between the D"Or Institute for Research ...

Color of judo uniform has no effect on winning

February 22, 2018
New research on competitive judo data finds a winning bias for the athlete who is first called, regardless of the colour of their uniform. This unique study, published in Frontiers in Psychology, puts to rest the debate on ...

Antidepressants are more effective than placebo at treating acute depression in adults, concludes study

February 22, 2018
Meta-analysis of 522 trials includes the largest amount of unpublished data to date, and finds that antidepressants are more effective than placebo for short-term treatment of acute depression in adults.

Infants are able to learn abstract rules visually

February 22, 2018
Three-month-old babies cannot sit up or roll over, yet they are already capable of learning patterns from simply looking at the world around them, according to a recent Northwestern University study published in PLOS One.

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.