To support the free and open dissemination of research findings and information on alcoholism and alcohol-related problems. To encourage open access to peer-reviewed articles free for all to view.

For full versions of posted research articles readers are encouraged to email requests for "electronic reprints" (text file, PDF files, FAX copies) to the corresponding or lead author, who is highlighted in the posting.


Saturday, November 24, 2012

Issue Paper: Stakeholder Feedback Department of Alcohol and Drug Programs Transfer of Functions October 10, 2012

Senate Bill (SB) 1014 (regular session 2011-2012) authorized Department of Alcohol and Drug Programs’ (ADP) functions to be transferred to other state departments within the California Health and Human Services Agency (CHHS), effective July 1, 2013. The passage of SB 1014 requires CHHS to develop and implement a plan reflective of the following goals:

Improving access to alcohol and drug treatment services for consumers, including a focus on recovery and rehabilitative services.

Effectively integrating the implementation and financing of services.

Ensuring appropriate state and county accountability through oversight and outcome measurement strategies.

Providing focused high-level leadership within state government for alcohol and drug treatment services.

In developing the plan, SB 1014 requires the consultation of stakeholders who would be affected by the transfer of functions. Specifically, consumers, family members, service providers, counties, and legislative staff have been invited to provide input for the plan through two rigorous stakeholder meetings, to date.

Ultimately, stakeholders have been tasked with assessing current system needs and making key recommendations for the future state administration that supports the goals of SB 1014. The recommendations generated by this diverse stakeholder community offer an alternative approach to the existing proposal, the details of which are described in this paper. > > > >   Read More

Thursday, November 22, 2012

Current Issue: September–October 2012

Interventions and Assessments

Health Outcomes


Ethical Conduct of Alcohol and Other Drug Research: Feature Article

Slide Presentations

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Update on the Genetics of Alcoholism

266 Overview: Assessing the Genetic Risk for Alcohol Use Disorders [PDF]
Tatiana Foroud, Ph.D., and Tamara J. Phillips, Ph.D.

274 Identifying Genetic Variation for Alcohol Dependence [PDF]
Arpana Agrawal, Ph.D., and Laura J. Bierut, M.D.

282 Using Genetically Engineered Animal Models in the Postgenomic Era to Understand Gene Function in Alcoholism [PDF]
Matthew T. Reilly, Ph.D.; R. Adron Harris, Ph.D.; and Antonio Noronha, Ph.D.

293 Epigenetics—Beyond the Genome in Alcoholism [PDF]
Bela G. Starkman; Amul J. Sakharkar, Ph.D.; and Subhash C. Pandey, Ph.D.
306 Identifying Gene Networks Underlying the Neurobiology of Ethanol and Alcoholism [PDF]
Aaron R. Wolen, Ph.D., and Michael F. Miles, M.D., Ph.D.
318 The Impact of Gene–Environment Interaction on Alcohol Use Disorders [PDF]
Danielle M. Dick, Ph.D., and Kenneth S. Kendler, M.D.
325 Bridging Animal and Human Models: Translating From (and to) Animal Genetics[PDF]
Amanda M. Barkley-Levenson and John C. Crabbe, Ph.D.

339 Genes Encoding Enzymes Involved in Ethanol Metabolism[PDF]
Thomas D. Hurley, Ph.D., and Howard J. Edenberg, Ph.D.

362 Circadian Genes, the Stress Axis, and Alcoholism [PDF]
Dipak K. Sarkar, Ph.D., D.Phil.

367 Discovering Genes Involved in Alcohol Dependence and Other Alcohol Responses: Role of Animal Models [PDF]
Kari J. Buck, Ph.D.; Lauren C. Milner, Ph.D.; Deaunne L. Denmark, M.D., Ph.D.; Seth G.N. Grant, Ph.D.; and Laura B. Kozell, Ph.D.

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Alcohol Alert No. 84 - The Genetics of Alcoholism

Why can some people have a glass of wine or beer with their meal without feeling compelled to drink more, whereas others can’t seem to stop drinking? Can some people “hold” their liquor better than others? Does alcoholism tend to run in families? Does genetics hold the key to developing medications to treat alcoholism and its effects on the body? Researchers have been trying to find answers to questions such as these for several decades, seeking to identify the factors that influence a person’s risk of becoming alcohol dependent. Research, to date, indicates that both your genetic makeup (i.e., the information stored in the DNA that you inherited from your parents) and your environment (i.e., how you live) influence your risk for alcohol abuse and alcoholism.1 Your genes certainly play an important role, influencing how your body responds to alcohol, how sensitive you are to its effects, and how likely you are to have a problem with alcohol. However, environmental factors—such as being surrounded by people who are heavy drinkers and who encourage you to drink—also can raise your risk for drinking too much.

The next question then becomes just how much of this risk is determined by our genes—that is, how much can be attributed to factors beyond our control. By studying large families with alcoholic and nonalcoholic members, comparing identical and fraternal twins, and studying adopted children and their biological and adoptive families, researchers found that about half of our risk for alcoholism is influenced by genetics.2,3 The remaining risk is related to the influence of environment—where and how we live. The two factors also work together in complex ways.

Understanding how genetics influences alcoholism also is important for another reason. Knowing the genes involved in this disease could help researchers and clinicians identify those who are most at risk of becoming alcoholic and understand how alcohol affects the body. These individuals then could be targeted more effectively for prevention and treatment efforts.1

This Alcohol Alert describes how research is helping to identify the genes involved in alcoholism. In examining this research, one thing becomes clear: Unlike for some other diseases, there is no single gene that determines whether you will develop a problem with alcohol; instead, many genes influence your risk for developing alcoholism, each of which only has a small impact. Further, environmental influences may override or blunt the effects of the genes that increase risk. This overview describes how researchers are trying to tease apart which of the thousands of genes and millions of gene variants that make up your DNA play a role in alcoholism, how some of these genes act, and how these genes interact with your environment to determine how you and your body respond to alcohol.

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Monday, November 19, 2012

Alcohol and acetaldehyde in African fermented milk mursik - A possible etiological factor for high incidence of esophageal cancer in western Kenya

Esophageal cancer is unusually frequent in western Kenya, despite the low prevalence of classical risk factors such as heavy drinking and tobacco smoking. Among Kenyans consumption of fermented milk is an old tradition. 

Our hypothesis is that alcohol and acetaldehyde are produced during the fermentation process and that their carcinogenic potential contributes to the high incidence of esophageal cancer.

Eight samples of mursik milk starter cultures were collected from different Kalenjin families in the Rift Valley province, Western Kenya. A protocol provided by the families was used for milk fermentation. Ethanol and acetaldehyde levels were measured by gas chromatography. The microbial flora in starter cultures was identified by 16S and 18S sequencing.

7/8 starter cultures produced mutagenic (>100 µM) levels of acetaldehyde and 4/8 starter cultures produced >1000 µM of acetaldehyde. The highest alcohol levels (mean 79.4 mM) were detected in the four fermented milks with highest acetaldehyde production. The mean number of microbial species in the starter cultures was 5 (range 2-8). Yeasts were identified in all starter cultures (mean 1.5 species/milk) but their proportion of the total microbial count varied markedly (mean 35%, range 7-90%). A combination of yeast and lactobacilli, especially Candida krusei with Lactobacillus kefiri, with the exclusion of other species, seemed to correlate with higher acetaldehyde and ethanol levels. 

Significant levels of ethanol and acetaldehyde were produced during mursik fermentation. Impact: When ingested several times daily the repeated exposure to carcinogenic levels of acetaldehyde may contribute to esophageal carcinogenesis.

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Effects of alcohol dependence on cortical thickness

Alterations of brain structures have been seen in patients suffering from drug abuse or mental disorders like schizophrenia. Similar changes in volume of brain structures have been observed in both alcoholic men and women. 

We examined the thickness of gray matter in the cerebral cortex in control men and women (n=69, 47 men) and alcohol dependent subjects (n=130, 83 men) to test the hypothesis that alcoholic inpatients would have more cortical damage than controls. 

We also hypothesized that alcoholic women would be more affected than alcoholic men. Alcoholic participants with a history of schizophrenia, psychotic, or bipolar disorder were excluded from the study. Volumetric structural magnetic resonance images were collected, 3D surfaces were created using Freesurfer, and statistical testing for cortical thickness differences was carried out using AFNI/SUMA. 

Covarying for age and years of education, we confirmed significant differences between alcoholics and healthy controls in cortical thickness in both the left and right hemispheres. 

Significant differences in cortical thickness between control men and women were also observed. These differences may reflect sexual dimorphisms in the human brain, a genetic predisposition to alcoholism and comorbid drug use, and the extent of gray matter damage in alcoholism and substance use.

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Recent binge drinking predicts smaller cerebellar volumes in adolescents

The current study examined the effects of recent binge drinking on cerebellar morphometry in a sample of healthy adolescents.

Participants were 106 teenagers (46 bingers and 60 controls) aged 16–19 who received a high-resolution magnetic resonance imaging (MRI) scan. FreeSurfer segmented and quantified the volume of each cerebellum. Maximum drinks during a binge in the past 3 months and duration since last binge were examined as predictors of cerebellar volume, after controlling for potentially confounding variables.

In the 106 teens, higher peak drinks predicted smaller left hemisphere cerebellar gray (f2=0.06, p=0.02) and white matter (f2=0.08, p=0.02) and right hemisphere cerebellar gray matter (f2=0.08, p=0.006), and marginally predicted smaller right hemisphere cerebellar white matter (f2=0.05, p=0.09). Gender did not moderate these effects.

More intense adolescent binge drinking is linked to smaller cerebellar volumes even in healthy teens, above and beyond variability attributable to risk factors for binge drinking. 

Longitudinal research is needed to see if cerebellar volumes worsen with protracted drinking and recover with abstinence. 

Interventions aimed at improving brain structure in adolescent binge drinkers are necessary given the high prevalence of risky drinking in youth.

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Neurometabolite concentration and clinical features of chronic alcohol use: A proton magnetic resonance spectroscopy study

Chronic, heavy alcohol consumption may affect the concentration of neurometabolites assessed with proton magnetic resonance spectroscopy (1H-MRS). 

We investigated the largest sample reported to date (N=213) with the primary goal of determining how specific clinical features impact neurometabolite concentrations in an anterior cingulate gray matter voxel. This community dwelling sample included both treatment seeking and non-treatment seeking individuals. A healthy control group (N=66) was matched for age and education. 

In multivariate analyses predicting neurometabolite concentrations, the heavy drinking group had greater concentrations overall. An age by group interaction was noted, as group difference across neurometabolites increased with age. More years drinking, but not more drinks per drinking day (DPDD), predicted greater concentrations of choline-containing compounds (Cho), creatine-phosphocreatine (Cre), glutamate–glutamine (Glx), and n-acetyl-aspartate (NAA). 

The effects of other clinical variables (depression, cigarette smoking, marijuana use) were negligible. After controlling for DPDD and years drinking, treatment-seeking status had no impact on neurometabolites. In the very oldest portion of the sample (mean age=50), however, a negative relationship was seen between NAA and years drinking. 

These results suggest that the nature of neurometabolite abnormalities in chronic heavy drinkers may vary as a function of duration of abuse.

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Alcohol News - 47/2012

Baltic Course (Latvia) - Two truckloads bootleg alcohol sold in Latvia daily
The black market for alcoholic beverages in Latvia is about five million liters annually or 2,200 cases of half-liter bottles (40% strong) daily, as Valters Kaze, Latvian Alcoholic Beverage Producers and Distributors Association board member, informed the portal.
Latvijas Saeima (Latvia) - Defence Committee supports amendments to decrease alcohol consumption among youths
On Tuesday, 13 November, the Defence, Internal Affairs and Corruption Prevention Committee of the Saeima supported in principle amendments to several laws which aim to decrease alcohol consumption among children and youths; amendments also state that individuals purchasing alcohol for youths, as well as sellers of illegal alcohol, will be held accountable.
YLE (Finland) - Dentists: Cut alcohol for healthy mouth
Drinking more than recommended daily levels significantly raises the risk of developing oral cancer, says the Finnish Dental Association.
YLE (Finland) - Fewer drunken drivers on Finnish roads
The daily Helsingin Sanomat reported on Saturday that a fresh police study shows that 11 in every 10,000 drivers on the road in Finland are over the legal limit, less than half the number seen in some past years.
BBC News (Wales) - Alcohol Concern Cymru claims white collar workers at risk
Professional people may be up to four times more likely to develop drink problems than the unemployed or blue-collar workers, campaigners claim.
Chicago Tribune - Even moderate drinking in pregnancy may affect child's IQ
Women who drink even moderate amounts of alcohol while pregnant may risk lowering child's intelligence levels, according to a study by British scientists. (UK) - Alcohol pricing should be set at minimum of 50p per unit
A group of leading medical bodies has called on the Government to set a minimum alcohol price of 50p per unit to tackle ''head on'' the problems caused by cheap drink and protect the next generation.
ABC Online (Australia) - Indigenous alcohol abuse hits 'crisis point'
A forum has been told that alcohol abuse among Indigenous Territorians has hit a crisis point. Stakeholders have met to discuss alcohol policy and its impact on Aboriginal communities.
Food Consumer - Alcoholic beverage consumption may boost recurrence of breast cancer
Alcoholic beverage consumption increases risk of developing breast cancer, which is a fact. Now a study in Cancer Epidemiologgy, Biomarkers & Prevention suggests that drinking some alcohol daily after diagnosis of breast cancer did not seem to increase risk of death from the disease, but may increase recurrence risk, particularly in postmenopausal women.
Scottish Daily Record (Scotland) - Fire figures show alcohol more likely factor than smoking
DRUGS and alcohol were thought to be a factor in twice as many house fires as smoking last year, figures show. The Scottish Government and fire service chiefs have warned people not to cook while inebriated amid figures showing that alcohol and drugs were a factor in one in six house fires.
Medical Xpress - Effects of alcohol on lymphoma, leukemia, and other types of hematological cancers
Many observational epidemiologic studies have found an inverse association between alcohol consumption and hematological cancers (such as lymphoma and leukemia). This study, based on the Million Women's Study in the UK, is large enough to permit an evaluation of associations with various types of such cancers. - Why having that one relaxed drink could lead to alcohol problems
People who have a drink to cope with stress could face to potential future drinking problems, a study has suggested. (Zambia) - Minister Raises Red Flag On Alcohol Abuse
Health Minister Joseph Kasonde has urged Zambians to reduce on consumption of alcohol and instead ensure a balanced diet to reduce the risk of contracting non-communicable diseases such as diabetes.
South African Broadcasting Corporation (South Africa) - Anti-alcohol ads campaign still on the cards: Motsoaledi
Health Minister Aaron Motsoaledi has reiterated that a campaign against the advertisement of alcohol in public spaces is still very much on the cards. He was addressing delegates at the 3rd All Africa Environmental Health Congress in Durban.
Metro (UK) - Medical leaders call for alcohol price hike as UK's under 13s hit the bottle
Health chiefs are calling for a minimum alcohol price of 50p per unit to combat the medical problems linked to binge drinking, while a survey has found that the UK's young people are among the most likely to get drunk by 13 years old.
AFP (UK) - Cheap alcohol drives young Britons to drink – report
Young Britons are more likely to have been drunk by the time they reach their teens than their European peers and are spurred on by cheap alcohol promotions, a study says. (new Zealand) - Police get tough on drink-drivers
Invercargill police have issued a stern warning, after a number of alcohol-related arrests during the weekend. Senior sergeant Maggie Windle said this morning there had been 22 arrests between Friday evening and this morning, including 11 on Saturday night. (canada) - Should warning labels be required on products other than cigarettes?
The Canadian Cancer Society says that Canada's cigarette package warnings, now covering 75 per cent of the package, rank fourth in the world behind Australia and other countries that prohibit company colours and logos. (Russia) - Russia cracks down on drunk air passengers
Russia is cracking down on drunken air passengers by forcing travellers to hand over duty free alcohol for the duration of their flight.

A Longitudinal Study of the Long-Term Consequences of Drinking during Pregnancy: Heavy In Utero Alcohol Exposure Disrupts the Normal Processes of Brain Development bstract

Exposure to alcohol in utero can cause birth defects, including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. 

Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group.

This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering “experience” over time may improve brain trajectories in individuals with heavy PAE and possibly other neurodevelopmental disorders.

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Decision making in the pathway from genes to psychiatric and substance use disorders

In influencing risk for psychiatric and substance use disorders, genes are typically conceptualized as working in silent physiological pathways in the bowels of our biology, far from the influences of human desires.

I here argue that this model of gene action is too restricted. At the individual, family and societal level, humans can, through their decision-making capacity, intervene in causal pathways from genes to behavior.

At the individual level, I present four paradigmatic cases involving alcohol dependence, major depression, general externalizing behaviors and animal phobia showing how human decisions can inhibit the expression of risk genes. 

I review the literatures demonstrating that parental behaviors can suppress or augment the heritability of traits in their children, and social attitudes can alter and even create causal pathways from genes to phenotypes. We evolved from organisms whose nervous systems were networks of reflexes that then developed simple cognitive systems and finally self-reflection. Just as our cognitions have gone ‘meta,’ we are now nearing a time when we can go ‘meta’ about our genetic risk. 

For many psychiatric disorders, our risk genes are not entirely cordoned off in our silent, purposeless biological substrate. Rather, we are able to make decisions that impact on the expression of our own genomes, those of our loved ones and those of our friends and neighbors. Our actions and our genes are often weaved together, integrated into the fabric of our lives.

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The α5 Neuronal Nicotinic Acetylcholine Receptor Subunit Plays an Important Role in the Sedative Effects of Ethanol But Does Not Modulate Consumption in Mice

Alcohol use disorders (AUDs) are a major public health problem, and the few treatment options available to those seeking treatment offer only modest success rates. There remains a need to identify novel targets for the treatment of AUDs. The neuronal nicotinic acetylcholine receptors (nAChRs) represent a potential therapeutic target in the brain, as recent human genetic studies have implicated gene variants in the α5 nAChR subunit as high risk factors for developing alcohol dependence.

Here, we evaluate the role of the α5* nAChR for ethanol (EtOH)-mediated behaviors using male α5+/+ and α5−/− transgenic mice. We characterized the effect of hypnotic doses of EtOH and investigated drinking behavior using an adapted drinking-in-the-dark (DID) paradigm that has been shown to induce high EtOH consumption in mice.

We found the α5 subunit to be important in mediating the sedative effects of EtOH. The α5−/− mice showed slower recovery from EtOH-induced sleep, as measured by loss of righting reflex. Additionally, the α5−/− mice showed enhanced impairment to EtOH-induced ataxia. We found the initial sensitivity to EtOH and EtOH metabolism to be similar in both α5+/+ and α5−/− mice. Hence, the enhanced sedation is likely due to a difference in the acute tolerance of EtOH in α5−/− mice. However, the α5 subunit did not play a role in EtOH consumption for EtOH concentrations ranging from 5 to 30% using the DID paradigm. Additionally, varenicline was effective in reducing EtOH intake in α5−/− mice.

Together, our data suggest that the α5 nAChR subunit is important for the sedative effects of EtOH but does not play a role in EtOH consumption in male mice. Varenicline can be a treatment option even when there is loss of function of the α5 nAChR subunit.

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Alcohol Awareness Week 2012 kicks off with 'time to talk about drinking' theme

The week of 19-25 November has been designated Alcohol Awareness Week (AAW) 2012 by Alcohol Concern.

The theme of "It’s time to talk about drinking" is intended to stimulate discussion and local activity to promote understanding of the risks and problems associated with alcohol misuse.  > > > >  Read More

Sunday, November 18, 2012

Media Release - Alcohol accounts for almost half of drug treatment episodes

Nearly half of government-funded drug treatment episodes in 2010-11 were for alcohol use, according to a report released today by the Australian Institute of Health and Welfare (AIHW).

The report Alcohol and other drug treatment services in Australia 2010-11: report on the National Minimum Data Set shows that alcohol was the principal drug of concern in 47% of treatment episodes, and in 62% of all treatment episodes it was listed as a drug of concern.

'The number of treatment episodes for alcohol use has remained relatively stable since 2009-10 when it was 48%, however it is still more than in 2001-02, when it was 37%,' said AIHW spokesperson Justin Harvey.  > > > >  Read More

Prefrontal correlates of approach preferences for alcohol stimuli in alcohol dependence

An approach bias for alcohol stimuli (i.e. faster approach than avoidance reactions) might facilitate relapses in alcohol dependence. Neurobiological models suggest hypersensitivity in the reward system [inter alia nucleus accumbens and orbitofrontal cortex (OFC)] to cause pathologically enhanced approach impulses towards alcohol stimuli. At the same time, in alcohol dependence, these structures are only insufficiently controlled by a hypoactive dorsolateral prefrontal cortex (DLPFC). 

The present study investigated the cortical aspects of this model with functional near-infrared spectroscopy in 21 alcohol-dependent in-patients and 21 healthy controls (HC; comparable in age, gender and education) during performance of the Approach-Avoidance Task (AAT) for the first time. 

Complementing previous findings, in reaction times (RTs), patients showed stronger approach preferences for alcohol than non-alcohol stimuli. For non-alcohol stimuli, patients even displayed avoidance preferences. The reversed pattern was found in HC. Group differences in activity of the OFC were identical to those in RTs, revealing patients to assign higher subjective value to approaching alcohol stimuli. In both groups, regulatory activity in the right DLPFC was stronger during avoiding than approaching alcohol pictures. Probable awareness of the behavioural hypotheses due to explicit task instructions and patients' deficient prefrontal function might account for this equally aligned pattern.

Results are discussed with regard to recent findings revealing a reduced behavioural approach bias and risk for relapse by applying a retraining version of the AAT. Functional measurements might serve as a method for monitoring the corresponding neurobiological changes and—possibly—predicting the success of such a training.

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5-HTTLPR genotype and daily negative mood moderate the effects of sertraline on drinking intensity

We previously reported moderating effects of age of onset of alcohol dependence (AD) and a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter protein in a sample of 134 individuals participating in a 12-week, placebo-controlled trial of sertraline. 

To understand more fully the effects seen in that study, we examined moderation by negative moods reported each evening, with nighttime drinking intensity (i.e. the number of standard drinks consumed at night) as the dependent variable. 

We found a daily anxiety × age of onset × 5-HTTLPR polymorphism × medication interaction, which reflected a daily anxiety × medication group effect for early-onset individuals homozygous for the high-expression (L′) allele, but not others. Specifically, on days characterized by relatively high levels of anxiety, early-onset L′ homozygotes receiving placebo reduced their drinking intensity significantly. In contrast, early-onset L′ homozygotes treated with sertraline non-significantly increased their drinking intensity. 

These findings implicate anxiety as a key moderator of the observed pharmacogenetic effects. These findings have important implications because of the high prevalence of AD and the frequency with which SSRIs are prescribed to treat the disorders.

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