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Myron A. Hofer is a psychiatrist and research scientist who is best known for his pioneering work in devising laboratory animal models to gain a new understanding of the basic developmental processes at work within the mother infant relationship(1). Through experimental analysis of the behavioral and neurobiological interactions that enmesh the infant rat and its mother, Dr. Hofer and his colleagues discovered hidden regulatory processes that have become the basis for a new understanding of the early origins of the attachment bond, the dynamics of the maternal separation response and the shaping of postnatal development through the first relationship.(2)

Education and Career Path- Hofer is currently Sackler Institute Professor Emeritus in the Department of Psychiatry at Columbia University College of Physicians & Surgeons and founding director of the Sackler Institute for Developmental Psychobiology at Columbia, established in December of 2000. He and his research group moved to Columbia / NY State Psychiatric Institute from the department of psychiatry at Albert Einstein College of Medicine in July of 1984, founding the first department of Developmental Psychobiology at a Medical School in this country. Hofer began his developmental animal model research at Albert Einstein, in the department of psychiatry at Montefiore Hospital in 1966, and with a fellowship in the Department of Animal Behavior at the American Museum of Natural History. During these years, he worked closely with a senior mentor, Herbert Weiner, and began his long association with a group of younger colleagues: Harry Shair, Michael Myers, Susan Brunelli, and Bill Fifer, who have continued their own research at Columbia to this day.

After graduating from Harvard College and Medical School in 1954 and 1958, Hofer received his clinical training in medicine at Massachusetts General Hospital, and in psychiatry at New York State Psychiatric Institute at Columbia University Medical Center. He was a Research Fellow in the Human Ecology Study Program at Cornell University Medical School with Harold Wolff and Lawrence Hinkle in 1960 –1962, and at the Adult Psychiatry Branch of the National Institutes of Mental Health, for the next two years, with Carl Wolff and John Mason.

Narrative Summary of Research Findings- Inspired by his experience in medicine, Dr. Hofer's first research, begun in 1960, was aimed at discovering the pathways by which mental processes can affect physiological systems of the body so as to influence the course of medical illness, a connection that was widely disputed at that time. While at Cornell, he was able to show that human anti-diuretic hormone, (known to be important for controlling water balance in diabetic patients), could be made to respond to a learning process, classical ‘Pavlovian’ conditioning. Once the respose was conditioned, he discovered that its intensity could become greatly increased by relatively minor changes in the subject’s emotional arousal (Hofer and Hinkle). Subsequently, he joined Carl Wolff and John Mason at the National Institute of Mental health in a landmark study showing that the effectiveness of the psychological defenses of each of the parents of children with leukemia (assessed by structured interviews without knowledge of the endocrine data) was related to their 24-hour level of adrenocortical hormone output: the more effective their defenses, the lower their corticoid levels ( Wolff et al 19??). This study revealed, for the first time, the capacity of psychological processes to modify the neuroendocrine effects of stress in humans. Hofer went on to study the parents at 6 and at 12 months after their child’s death, finding that their corticoid levels changed markedly, the ‘highs’ decreasing and the ‘lows’ increasing. Their levels now correlated with the degree to which they were immersed in their grief (using criteria that were replicated by an outside rater) ( P.M. ). Following his psychiatric residency in 1966, Hofer began his innovative research creating novel laboratory animal models to enable an experimental analysis of the biological and behavioral processes underlying early postnatal development and their first environmental influences within the parent-infant interaction. His initial studies on early maternal separation in rat pups, showed a sequence of effects on their exploratory, ingestive and vocal behavior, autonomic physiology, thermoregulation and sleep-wake state organization. Surprisingly, he found that this response pattern was not a typical emotional stress response as expected, but the result of the abrupt withdrawal of a number of discrete and independent components of the mother infant interaction, such as the mother’s licking, warmth, odor, contact, milk delivery, and the timing or rhythm with which these regulatory interactions had occurred.. For each of the pup’s responses to separation could be individually prevented by supplying one or another artificial substitute or reenactment of these events to the pups during the separation period. . Hofer called these "hidden maternal regulators" because they were not apparent when simply observing the mother with her litter ( Hofer- Acta?                  ). The discovery of these novel behavioral and biological processes within the separation experience has had implications for understanding the psychological and physiological disorganization of human grief as a loss of regulatory functions within social relationships, and for our understanding of the formation of mental representations (Hofer, 1984, Shear and Shair, 2005).

The discovery of hidden maternal regulators immediately suggested their possible role in shaping development over extended periods of time, linking different patterns or ‘qualities’ of parenting  to particular  long term  developmental outcomes. This implication was first borne out in studies by Michael Myers and Hofer showing major adult effects of normal variation  in  patterns of  maternal behavior  within the laboratory colony (Myers, Brunelli and Hofer (198?). These studies have led to the extensive recent work of  Michael Meaney and others, demonstrating novel ‘epigenetic’ mechanisms for  the  shaping of  adult behavioral, physiological and molecular/genetic  functions  by differences in early parenting patterns       Another form of long term developmental effect, discovered by Sigurd Ackerman and Herbert Weiner in Hofer’s group, resulted from the permanent loss of all maternal regulators through early weaning. They soon found that the whole life course trajectory of susceptibility to stress ulcer in the rat is radically altered by this early experience, resulting in a very high incidence of severe gastric ulcers in adolescence, and a significantly reduced vulnerability in late adulthood, with little or no effect of early weaning at midlife. In a series of subsequent studies, the mechanism of this vulnerability was found to involve alterations in thermoregulation and a reduction in gastric cellular defense properties during the prolonged alteration in sleep wake patterns of early weaned adolescents during immobilization stress. In the subsequent generation, their normally weaned offspring showed a transgenerational effect of their mother’s early weaning experience, becoming abnormally susceptible to stress ulcer as adolescents. Cross fostering studies showed this susceptibility to be transmitted prenatally, rather than being due to their changed maternal behavior, possibly as a result of a germ cell epigenetic or trans-placental mechanisms.

Next, Hofer's lab turned to the question of the pup’s ‘attachment bond’, then assumed to be absent in such a primitive organism. Regina Sullivan, as a post-doctoral fellow in Hofer’s lab, discovered an associative learning process that for the first time established a mammalian form of avian ‘imprinting’ and a postnatal period during which attachment can be formed to cues associated with clearly aversive levels of stimulation. Sullivan has gone on to independent work that explores the developmental timing, underlying neural mechanisms, and lasting effects of these early memories on adult maternal behavior, and attachment to abusive mothers in particular.in particular. . More recently, Jonathan Polan and Hofer described in detail the ‘maternally directed orienting behaviors’ with which pups first initiate, then maintain contact with their mother, and position themselves for nursing. Using high-speed video analysis and experimental modification of sensory cues, they discovered how maternal contours, scent, textures, thermal gradients and movements are used by newborn pups to knit together their simple fetal behaviors to form the flexibly organized and highly motivated behavioral system of mammalian  (refs in vol 47 of DPB )

In a far ranging series of studies beginning in the 1970s, Hofer first showed that the bursts of ultrasound known at the time to be emitted by infant rodents in response to rough handling and cold, were also regulated by their social interactions with littermates and dam. He used the pups’ ultrasonic vocalization (USV) as an experimental model to gain a deeper understanding of the ‘separation cry’, viewed at the time as the first expression of a ‘rupture of the attachment bond’ in primates and humans. But he and his group found regulatory processes, underlying these psychological constructs, that mediated the USV response to separation from social companions through the loss of contact with specific olfactory, tactile and thermal sources of stimulation they provided, and through which the ‘contact comfort’ responses of isolated pups were elicited when they were re-united with littermates or a lactating female. Subsequent psychopharmacologic studies by Carden, Brunelli and Hofer, as well as many others, showed that the neural modulatory systems mediating these USV responses were the same as those known to be involved in the treatment of anxiety in humans, and in the experimental elicitation and/or reduction of anxiety-like responses in animals. This has resulted in the widespread use of these USV isolation responses in basic developmental neuroscience research on anxiety, facilitated by the publication of a detailed guide to the use of these measures by Hofer’s group in “Protocols in Neuroscience”.

Hofer and Harry Shair went on to discover another more complex form of USV response to separation: a two- to three- fold increase in the isolation response rate following a brief maternal interaction. This ‘potentiation’	 develops a week later than the isolation response itself, is not elicited by handling, novelty, brief exposure to littermates or to a virgin female, and represents maturation of the pup’s capacity to regulate USV in response to a  past experience, rather than simply to its immediate environment. It appears to represent a violation of expectancy, resembling a toddler’s vocal outburst when his mother leaves the day care center unexpectedly after returning to retrieve something she had left behind. The USV findings described above, and others on the physiological effects of USV, were synthesized by Hofer within an evolutionary theoretical framework. This concept was based on the likely trade-offs in selection pressures for USV between its role as a directional signal for maternal retrieval, as opposed to the likelihood of its attracting predators ( Ch. In Brud. Ed. Handbook on mammal. vocs.) Continuing their interest in evolution, Hofer and Brunelli carried out the first experimental study exploring the effects of testing the long-held evolutionary principle that selection can act at any point in development (DPB paper) They selectively bred adult rats to form two lines on the basis of their emitting the lowest, or the highest, USV isolation response rates in their litters as 10 day old infants; and compared them to randomly bred controls. After 15 generations, the USV rates of high and low lines were markedly different at all ages between birth and 16 days when the isolation response is no longer present. After 25 generations, life long differences were created in a number of behaviors that followed patterns typical of the development of temperament in humans: juvenile play and adult impulsivity, aggression, anxiety, sexual check this and maternal behaviors. This study is the first known experiment in selective breeding for an infantile trait. It has established a new way to study the roles of possible epigenetic, as well as genetic and behavioral transgenerational processes in a laboratory model of the evolution of developmental processes (2008 paper).

Conceptual Contributions Hofer has had a long-standing interest in the nature and evolution of development. In 1981, he wrote the first book introducing the new field of developmental psychobiology, bringing animal and human research together within a unified conceptual framework. . By 1990, he began to write about the place of development in evolution and its possible role in creating some of the vast variation that selection may act upon. More recently, stimulated by the emerging field of evolutionary developmental biology (‘Evo Devo’), Hofer has proposed a useful conceptual framework for studying development ( ISDP”framework” ref.) “Developmental selection”, like kin selection or sexual selection, is viewed as an integral part of the evolutionary process. It consists of four evolutionary ‘functions’ through which development has facilitated and shaped the evolution of multicellular life over the past 500 million years, going well beyond its traditional function of constructing larger and more complex organisms capable of exploiting new ecological niches. The other three are: new mechanisms of variation, of trans-generational inheritance, and novel adaptations for immature forms to survive the unique environments of early development ( Hand bk. Behav. Neuro). In attempting to understand the bewildering stages of growth and the transformations of physiology and behavior during development, as well as the seemingly unresolvable questions of the relationship between nature and nurture, these four evolved functions of development can provide a guide for asking new questions about how development works and a better understanding of its ultimate function within the evolutionary process.

Research-Related Activities, Awards and Honors Throughout his career, Hofer served on numerous national scientific advisory committees, private foundation review panels and governmental research grant review committees. He served on the editorial board of the journals, Psychosomatic Medicine, the Journal of Psychosomatic Research, Behavioral Neuroscience, and Developmental Psychobiology. He was elected president of the International Society for Developmental Psychobiology in 1980, and of the American Psychosomatic Society in 1982. He held an NIMH Research Scientist Development Award from 1968-2003 and a project grant MERIT award from 1986-1996. .          In 1996, Hofer was selected to give the 64th annual Thomas William Salmon Lectures, and in 2008, the 51st Sandor Rado Lecture at the New York Academy of Medicine. In 2009, he received the Senior Investigator Award from the International Society for Developmental Psychobiology.

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