Appetite-regulating Peptide Leptin Influences Alcohol Craving For Some Alcoholics

Key findings: 

• Craving is an important contributor to the development and maintenance of alcoholism.
• New findings show that appetite-regulating peptides leptin and ghrelin influence alcohol craving.
• Leptin's influence on craving is especially notable among patients of Lesch's Type 1 and 2.

"We chose to examine leptin and ghrelin because both peptides are of high importance in appetite regulation and both have already been subject to former investigations," said Thomas Hillemacher, assistant professor in the department of psychiatry and psychotherapy at the University Hospital of Erlangen, Germany. "However, these former investigations have shown contradictory results which may have been due to their use of samples of alcoholics without specifying subgroups. This raised the idea of investigating these peptides in specific subtypes of alcohol dependence." Hillemacher is also the corresponding author for the study.

"There exist four different mechanisms of craving, which can lead to relapse," explained Otto Lesch, professor of psychiatry at the University of Vienna. "We know that these four different mechanisms are caused by different biological mechanisms. They have different long-term courses and they profit significantly differently from different pharmaceutical compounds. Therefore, it is very important to define basic workings of these different craving mechanisms in order to develop better models to proof new medications."

These four mechanisms of craving correspond to Lesch's typology of alcoholics according to different psychological, social and somatic characteristics. Type 1 refers to patients with heavy alcohol withdrawals who tend to use alcohol to weaken withdrawal symptoms. Type 2 patients use alcohol as self-medication because of its anxiolytic effects. In patients of Type 3, the main characteristic is an affective disorder as origin for alcohol abuse. Type 4 patients show pre-morbid cerebral defects, behavioral disorders and a high social burden.

Researchers analyzed data gathered as part of a larger examination of different neurobiological aspects of alcohol dependence. Of the original sample of 200 patients, 188 (155 males, 33 females) provided leptin serum levels, and 117 (96 males, 21 females) provided ghrelin serum levels. Study authors measured craving through use of the Obsessive Compulsive Drinking Scale, and further classified patients according to Lesch's typology of alcohol dependence, as well as their preferred type of alcoholic beverage.

"The study showed that the involvement of appetite-regulating peptides in the neurobiology of alcohol craving is of different importance in specific subgroups," said Hillemacher. More specifically, results showed a positive association between leptin and craving among patients of Lesch's Type 1 and 2, and between leptin and craving among patients consuming beer or wine; but a negative trend between ghrelin and craving among patients of Lesch's Type 1.

"In alcohol dependence," added Lesch, "88 different methods are used to decrease relapse rates. Most of them are not effective, some of them increase relapse rates, some of them are really effective in subgroups of alcohol-dependent patients, but there is no one method which has only positive results." This study's results, he said, are of great importance to alcohol research because they help to clarify that other studies' results may be due to different selection criteria leading to different rates among subgroups.

Both Hillemacher and Lesch said that recognizing subgroups of alcoholics is imperative for future research as well as clinical applications.

"Our findings show that there exist important differences between alcohol-dependent patients, not only regarding psychosocial but also regarding neurobiological influences," said Hillemacher.

"Transmitter systems interact with peptides, and genetic research has to be aware that this interaction influences brain activities and therefore different mechanisms of craving," added Lesch. "To explain addiction, we need mechanisms of different types of craving. Addiction is not caused by the drug, but is caused by biological and psychological vulnerabilities leading to different types of craving."

Results are published in the June issue of Alcoholism: Clinical & Experimental Research.