Ann Manzardo

Assistant Professor, Department of Psychiatry and Behavioral Sciences
Primary office:


Dr. Manzardo is a Behavioral Pharmacologist who specializes in the field of addiction research with advanced training in biostatistics and expertise in the epidemiology of alcoholism. She has established a translational research program in the Department of Psychiatry and Behavioral Sciences at the University of Kansas Medical Center through which she has directed funded research projects on alcoholism spanning multiple scientific disciplines: clinical, epidemiological and genetic. Her interests include gender disparate effects of genetic, biological and neurodevelopmental risk factors for the development of alcoholism; the influence of psychiatric co-morbidity; and the role of thiamine deficiency in alcohol abuse behaviors.

Dr. Manzardo is part of a 30 year international research collaboration with Danish investigators utilizing the Danish Perinatal Cohort to examine antecedents of alcoholism including perinatal neurodevelopmental influences, and genetics. The Danish Study of Perinatal Neurodevelopmental Contributions to Adult Alcoholism examined neurodevelopmental factors such as low birth weight, delayed motor development and gender influences on the development of alcohol dependence in males and females in the entire 9,125 subjects of the perinatal cohort. The Danish Longitudinal Study on Alcoholism (DLSA) is a prospective examination of premorbid antecedents of alcoholism in a well-characterized subset of 329 men recruited at 19 years of age, before drinking problems began, and followed up into adulthood. Two-thirds of the DLSA study subjects are considered “high risk” sons of fathers treated for alcoholism (N=173) while one-third reflect a matched group of sons of non-alcoholic fathers (N=87). Seventy of these subjects were recorded as alcohol dependent in follow-up studies at age 30 and 40 years. A history of conduct problems including diagnosis and treatment of Childhood Conduct Disorder were identified as powerful antecedent predictors of alcoholism in this sample. A recent grant from the Danish Council for Strategic Research Program Commission on Individuals, Disease and Society has been secured to support recruitment and clinical assessment for a 50 year follow-up study of this cohort which is currently underway. This extension study is designed to determine antecedents of male alcoholism, death, and remission from alcoholism and includes the collection of saliva for DNA isolation and study.

Many of the physical and neurological complications associated with alcoholism arise from deficiency of a specific vitamin, vitamin B1 (thiamine). Thiamine is an essential co-factor for several important enzymes required for cellular energy production and thiamine deficiency is known to selectively damage heart muscle and nervous tissues. Dr. Manzardo has studied the effects of high-dose thiamine intervention on drinking patterns and psychiatric symptoms and traits using the vitamin analogue, benfotiamine, in a group of men and women alcoholics from the Kansas City area. Follow-up studies evaluated cytokine disturbances and a common polymorphism in the androgen receptor gene involving CAG repeats in males and females in this cohort and considered their impact on psychiatric symptoms and traits such as anxiety and impulsiveness. 

Her expanded research interests include bioinformatics as it is applied to the genetics of alcoholism. She has applied state-of-the-art genetics technology to the study of gene-specific and DNA global methylation patterns, coding and non-coding RNA expression, and RNA sequencing in alcoholism utilizing brain tissue samples of alcoholics, schizophrenia and controls and utilizing samples from the New South Wales Tissue Resource Center. Integration of these advanced techniques with historical epidemiological databases such as the DLSA will help advance scientific understanding of the genetic underpinnings of complex behaviors.

Publications

  1. Manzardo AM, Penick EC, Knop J, Nickels EJ, Hall S, Jensen P, Gabrielli WF (2005) Developmental differences in childhood motor coordination predict adult alcohol dependence: Proposed role for the cerebellum in alcoholism. Alcoholism: Clinical and Experimental Research 29(3):353-357, PMID: 15770110
  2. Manzardo AM, Penick EC, Knop J, Nickels EJ, Hall S, Miller C, Jensen P, Gabrielli WF (2005) Neonatal vitamin K might reduce vulnerability to alcohol dependence in Danish men. Journal on Studies of Alcohol 66:586-592, PMID: 16331844.
  3. Manzardo AM, Penick EC (2006) A theoretical argument for inherited thiamine insensitivity as one possible biological cause of familial alcoholism. Alcoholism: Clinical and Experimental Research 30(9):1545-1550, PMID: 16930217.
  4. O'Dell LE, Manzardo AM, Polis I, Stouffer DG, Parsons LH (2006) Biphasic alterations in serotonin-1B (5-HT1B) receptor function during abstinence from extended cocaine self-administration. Journal of Neurochemistry 99(5): 1363-1376, PMID: 17074068.
  5. Knop J, Penick EC, Nickels EJ, Mednick SA, Jensen P, Manzardo AM, Gabrielli WF (2007) Paternal alcoholism predicts the occurrence but not the remission of alcoholic drinking: a forty-year follow-up. Acta Psychiatrica Scandinavia 116(5): 386-393, PMID: 17919158.
  6. Knop J, Penick EC, Nickels EJ, Mortensen EL, Mednick SA, Jensen P, Manzardo AM, Gabrielli WF (2009) Childhood ADHD and conduct disorder as independent predictors of male alcohol dependence at age 40. Journal of Studies on Alcohol and Drugs Mar; 70(2):169-77, PMCID: PMC2653603
  7. Penick EC, Knop J, Nickels EJ, Jensen P, Manzardo AM, Mortensen EL, Gabrielli WF (2010) Do premorbid predictors of alcohol dependence also predict the failure to recover from alcoholism? Journal of Studies on Alcohol and Drugs Sep; 71(5):685-95, PMCID: PMC2930498.
  8. Manzardo AM, Madarasz W, Penick EC, Knop J, Mortensen EL, Sorensen HJ, Mahnken J, Becker U, Nickels EJ, Gabrielli WF (2011) Effects of premature birth on the risk for alcoholism appear to be greater in males than females. Journal of Studies on Alcohol and Drugs May; 72(3):390-98, PMCID: PMC3084356.
  9. Sorensen HJ,  Manzardo AM, Knop J, Penick EC, Madarasz W, Nickels EJ, Gabrielli WF, Becker U, Mortensen EL (2011) The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring.  Alcoholism Clinical and Experimental Research Jul; 35(7):1315-1320, PMCID: PMC3653408.
  10. Manzardo AM, Henkhaus R, Butler MG (2012) Genome-wide promoter methylation in frontal cortex of alcoholics and controls. Gene Apr, 498(1): 5-12, PMCID: PMC3653411.
  11. Manzardo AM, Henkhaus R, Hidakka B, Penick EC, Poje A, Butler MG (2012) X Chromosome Inactivation in Blood from Women with Alcoholism. Alcoholism Clinical and Experimental Research Aug, 36(8): 1325-9, PMCID: PMC3371305.
  12. Madarasz W, Manzardo AM, Mortensen EL,  Penick EC,  Knop J, Sorensen HJ, Becker U, Nickels EJ, Gabrielli WF (2012) 45-year mortality rate as a function of the number and type of psychiatric diagnosis found in a large Danish birth cohort, Canadian Journal of Psychiatry, Aug, 57(8):505-511, PMID: 22854033
  13. Manzardo AM, Gunewardena S, Butler MG (2013) Over-expression of miRNA cluster at 14q32 in the alcoholic brain correlates with suppression of mRNA activated in oligodendrocyte proliferation, Gene, 526 (2): 356-63, PMID: 23747354.
  14. Manzardo AM, Poje A, He J, Penick EC, Butler MG, Campbell J (2013) Double-blind, randomized placebo-controlled clinical trial of benfotiamine for severe alcohol dependence, Drug and Alcohol Dependence, 133(2): 562-570.
  15. Mettman DJ, Butler MG, Poje AB, Penick EC, Manzardo AM: Androgen receptor gene polymorphism: an association with impulsivity in women with alcoholism. Advances in Genomics and Genetics, in press
  16. Manzardo AM, Gunewardena S, Wang K, Butler MG, Exon Microarray Analysis of Human Dorsolateral Prefrontal Cortex in Alcoholism, Alcoholism Clinical and Experimental Research, in review, 2014.


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