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July 1998

Markku Linnoila, MD, PhD, 1947-1998

Arch Gen Psychiatry. 1998;55(7):659-660. doi:10.1001/archpsyc.55.7.659

Markku Linnoila, MD, PhD, was born Veli Markku Ilari Linnoila in Helsinki, Finland, on June 10, 1947. On February 25, 1998, he died in Bethesda, Md, following a brief but courageous struggle with cancer, thus cutting short a lifetime of outstanding achievement in biological psychiatry. He is survived by his wife, Ilona Linnoila, PhD, his 4 children, Juuso, Jenny, William, and Robert, and his mother, Hilkka-Liisa Linnoila of Helsinki.

Markku Linnoila, MD, PhD

Markku Linnoila, MD, PhD

Dr Linnoila was educated at the University of Helsinki, receiving degrees in biochemistry and pharmaceutical chemistry, a PhD in pharmacology, and a doctor of medicine. He came to the United States after working for a brief period in the Finnish Academy, Helsinki, and the University of Helsinki in the areas of clinical psychopharmacology and forensic toxicology, joining Duke University Medical Center, Durham, NC, in 1974. Although he never returned to his homeland on any continuous basis, he remained affiliated with the University of Helsinki until his death. As both a mentor to many junior scientists and a colleague, he was a powerful advocate for research in Finland.

In 1975, he was appointed assistant professor of psychiatry, and in 1979, he was appointed associate professor at Duke University Medical Center. In 1980, he became a staff psychiatrist at the National Institute of Mental Health, Bethesda. In this position, he developed methods for quantifying neurotransmitters and their metabolites. These methods provided the foundation for studies of the role of neurotransmitters in behavior and for the mechanisms of action of antidepressant and antipsychotic drugs. He also developed the first gas chromatographic method for quantifying tricyclic antidepressants and their metabolites and was among the first to relate drug concentrations to pharmacodynamics. In 1983, after Congress authorized the clinical program for the National Institute on Alcohol Abuse and Alcoholism, Dr Linnoila became the first clinical director of that program and founded the Laboratory of Clinical Studies at the Clinical Center, National Institutes of Health, Bethesda.

Dr Linnoila's commitment to science emerged in the context of the value of the individual and from being a practicing physician. He experienced the pathos of psychiatric illness through his patients, their families, and, occasionally, his colleagues. Although a deep humanitarian impulse drove him, the direction of his research was steered by a deep understanding of the common threads of human experience. This realization led him to reject the analysis of experience on an anecdote-by-anecdote basis, which is paradoxical in that Dr Linnoila himself fit in none of the usual categories. Finally, he maintained an unwavering commitment to the disease concept for the psychiatric disorders that most closely drew his attention: alcoholism, suicide, and depression.

Dr Linnoila believed that a characteristic ingredient of outstanding clinical investigations was close coupling of science at the laboratory bench with research at the bedside. At the National Institutes of Health, he developed his model of science into reality by creating the Laboratory of Clinical Studies. Under his guidance, this laboratory became a unique and enormously powerful clinical research environment in which the biological characteristics of alcoholism could be explored in definitive ways and the incisive tools that were becoming available could be used. Tools that he helped to introduce to alcoholism research included new methods for assessment of psychiatric diagnosis, cognitive performance, neuropsychological functions, brain metabolic activity, neurotransmitter function, and genotype. Using these approaches and carefully assembling teams of researchers, he amassed an extraordinary record of scientific productivity, publishing more than 400 research reports in peer-reviewed journals and more than 100 book chapters. He is among the most cited psychiatric researchers in the world. He was always in demand in all the places around the world where biological psychiatry was discussed and advanced. However, his last days were spent in a hospital across the road from the National Institutes of Health, the site of so many of his achievements.

In his earliest publications and his second publication in 1973, Dr Linnoila's efforts were singularly directed toward alcoholism and 2 related issues: suicide and depression. He recognized that these 3 diseases are not only frequently seen in combination, but also, because of an underlying level of causation, they are interrelated through the action of the neurotransmitter serotonin. He elucidated many of the dimensions of this relationship by direct measures of neurotransmitter metabolites in the cerebrospinal fluid of humans and nonhuman primates, by creation of a Macaca mulatta model of alcoholism and aggression and by pharmacological and neuroimaging studies. The neurotransmitter serotonin will always owe him a debt of gratitude. Because of his contributions, as well as the pioneering efforts of others including Marie Asberg, the relationship of serotonin to impulsive behavior is the single most widely accepted connection of neurochemistry to behavior.

Recently, Dr Linnoila and his colleagues turned their attention to the genetic underpinnings of alcoholism and other behaviors. He was the driving force behind genetic studies establishing that differences in brain serotonin function in nonhuman primates were highly heritable and, furthermore, that those differences were closely related to alcohol preference and aggression. Translating scientific vision into reality, Dr Linnoila and his colleagues were among the first to explore the effect of the interaction between genes and the environment on behavior in a meaningful way. He and his colleagues found an interacting role for stress and genetic background in alcohol self-administration among M mulatta monkeys.

Dr Linnoila also correctly interpreted the alcoholism heritability studies for what they are: proof that there are vulnerability genes in humans to be identified. He was a champion of genetic studies of complex behavioral diseases before it was fashionable to be one. He was also one of the first to realize the unique advantages of population isolates for complex diseases. He alternately led and encouraged the first large-scale molecular genetic studies on alcoholism in 2 human isolates in his native Finland and Native Americans. He survived to see the first whole-genome linkage scan in Native Americans completed by Long et al (Am J Med Genet. 1998;81:216-221) and the whole genome scan of the large Finnish genetic sample he developed near its completion. He also had the satisfaction of being proved correct by seeing the vulnerability genes for the behaviors that most interested him actually identified; the identification of the vulnerability genes emerged both from his program and independently from others. For example, the link between aldehyde dehydrogenase 2 and alcoholism was confirmed, and the link between tryptophan hydroxylase and suicide was partially replicated in a study by Nielsen et al in this issue of the ARCHIVES (1998;55:593-602).

Dr Linnoila will be missed both as a tenacious advocate of excellence in psychiatric research and for his extraordinary level of integrity and commitment. Unapologetically forthright and outspoken, he demanded of others the same high level of integrity, scholarship, and rigor. Those who were fortunate to know him well appreciated this quality of honesty because we knew its motives. Although strange, it is true that in many ancient cultures it was the practice to sacrifice kings at their full height of vitality so that their power did not slowly ebb (Frazer J. The Golden Bough. London, England: Oxford University Press; 1994). A brilliant life has been cut short. We hope that we can continue to learn and share the strength of individuals such as Markku Linnoila by reflecting on their lives and that portion of our common experience.