Thomas R Insel

U.S. Department of Health and Human Services | HHS · National Institutes of Health (NIH)

Mental disorders represent a public health challenge of staggering proportions. In the most recent Global Burden of Disease study, mental and substance abuse disorders constitute the leading source of years lost to disability from all medical causes ( 1 ). The World Health Organization estimates over 800,000 suicides each year globally, nearly all...

As directors of two NIH institutes supporting neuroscience research, we explore the gap between 25 years of stunning progress in fundamental neuroscience and the persistent needs of those with brain disorders. We conclude that closing this gap will require a more detailed comprehension of brain function, a rethinking of how we approach translationa...

The brain is now commonly viewed as a complex information-processing system whose major circuits interact to implement effective behavior in motivational, cognitive, and regulatory domains. In turn, mental disorders are increasingly understood in terms of malfunctions in these systemsthat result from various combinations of genetic and environmenta...

Background Current diagnostic systems for mental disorders rely upon presenting signs and symptoms, with the result that current definitions do not adequately reflect relevant neurobiological and behavioral systems - impeding not only research on etiology and pathophysiology but also the development of new treatments. Discussion The National Insti...

On 2 April 2013, President Barack Obama announced the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. In front of some 200 scientists in the East Room of the White House, the President declared, “…there is this enormous mystery waiting to be unlocked, and the BRAIN Initiative will change that by giving scientists t...

In the first article of a five-part series providing a global perspective on integrating mental health, Pamela Collins and colleagues set the scene for why mental health care should be combined with priority programs on maternal and child health, non-communicable diseases, and HIV, and how this might be done.

Despite the need for more effective treatments for psychiatric disorders, development of new medications has stalled. Here we discuss the promise of personalized medicine in developing more efficacious and individualized pharmacotherapies that take into account genetic variation and target groups of patients who share biology, not just symptoms.

Thomas R. Insel and Barbara J. Sahakian describe what the next decade of mental-health drug development should look like.

Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology, publishing the highest quality original research and advancing our understanding of the brain and behavior.

A consortium of researchers, advocates and clinicians announces here research priorities for improving the lives of people with mental illness around the world, and calls for urgent action and investment.

Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology, publishing the highest quality original research and advancing our understanding of the brain and behavior.

How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world's population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a cen...

For more than a century, clinical investigators have focused on early life as a source of adult psychopathology. Early theories about psychic conflict and toxic parenting have been replaced by more recent formulations of complex interactions of genes and environment. Although the hypothesized mechanisms have evolved, a central notion remains: early...

Current versions of the DSM and ICD have facilitated reliable clinical diagnosis and research. However, problems have increasingly been documented over the past several years, both in clinical and research arenas (e.g., 1, 2). Diagnostic categories based on clinical consensus fail to align with findings emerging from clinical neuroscience and genet...

In the first 2010 issue of Nature, the editor, Philip Campbell,1 suggested that the next 10-year period is likely to be the “decade for psychiatric disorders.” This was not a prediction of an epidemic, although mental illnesses are highly prevalent, nor a suggestion that new illnesses would emerge. The key point was that research on mental illness...

Neuroscience is revealing the malfunctioning connections underlying psychological disorders and forcing psychiatrists to rethink the causes of mental illness

Social neuroscience is rapidly exploring the complex territory between perception and action where recognition, value, and meaning are instantiated. This review follows the trail of research on oxytocin and vasopressin as an exemplar of one path for exploring the "dark matter" of social neuroscience. Studies across vertebrate species suggest that t...

STAR*D (Sequenced Treatment Alternatives to Relieve Depression) continues to stimulate debate. The landmark trial demonstrated the feasibility of large-scale, community-based studies conducted without pharmaceutical company support. The results provided insight into nonresponse to initial treatment with selective serotonin reuptake inhibitors and a...

Mental disorders such as schizophrenia, bipolar illness, and depression have become the predominant chronic diseases of young people, accounting for approximately 40% of the medical burden for people aged 15-44 in the United States and Canada. Research is transforming our understanding of these disorders, as exemplified in the articles in this Revi...

Research has transformed many areas of medicine, with profound effects on morbidity and mortality. Exciting advances in neuroscience and genomics have transformed research but have not yet been translated to public health impact in psychiatry. Current treatments are necessary but not sufficient for most patients. To improve outcomes we will need to...

Mental disorders impose considerable socioeconomic costs due to their episodic/chronic nature, their relatively early ages at onset, and the highly disabling nature of inadequately treated mental illness. Despite substantial increases in the volume of mental health treatment for disorders in the past two decades, particularly pharmacotherapies, the...

This issue of Science features a special section (see page [891][1]) that focuses on an emerging area of neurogenetics--the effort to link genomics and behavior. We are all intrigued by the notion that genomics may yield "simple" explanations for complex behaviors, including our own. The power of genomics has already revealed new insights into huma...

Wayne Fenton dedicated his career to addressing the unmet needs of people with mental illness. His commitment to a public health approach was made clear by his actions: he left behind a leadership role in Chestnut Lodge, an institution dedicated to treating individual patients, to accept a position at the National Institute of Mental Health (NIMH)...

Real-time, high-speed optical imaging is a promising approach for elucidating networks of brain activity associated with depression.

Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology, publishing the highest quality original research and advancing our understanding of the brain and behavior.

The mission of the National Institute of Mental Health (NIMH) is to reduce the burden of mental and behavioral disorders through research, and eating disorders embody an important fraction of this burden. Although past and current research has provided important knowledge regarding the etiology, classification, pathophysiology, and treatment of the...

The completion of the Allen Brain Atlas generated a great deal of press interest and enthusiasm from the research community. What does it do, and what other complementary resources increase its functionality?

A conservative estimate indicates that almost 30% of the U.S. population will be afflicted with an anxiety disorder at some point in their lives, and preliminary data suggest that this risk is increasing (Kessler et al 2005a). A significant proportion of people diagnosed with an anxiety disorder will experience severe and chronic symptoms that can...

We, the directors of the 27 NIH institutes and centers, wanted to respond to the points made by Andrew Marks in his recent editorial. While we appreciate that the scientific community has concerns, the current initiatives and directions of the NIH have been developed through planning processes that reflect openness and continued constituency input,...

The involvement of dopamine within the nucleus accumbens in the formation and maintenance of pair bonds was assessed in a series of experiments using the monogamous prairie vole. We show that dopamine transmission that promotes pair bond formation occurs within the rostral shell of the nucleus accumbens, but not in its core or caudal shell. Within...

Genomics and neuroscience, 2 areas of science fundamental to psychiatry, have undergone revolutionary changes in the past 20 years. Yet methods of diagnosis and treatment for patients with mental disorders have remained relatively unchanged. Indeed, during the same time, the public health burden of mental disorders has grown alarmingly. Mental diso...

Over the past 2 decades, the National Institute of Mental Health supported ambitious population-based efforts in psychiatric epidemiology. The landmark 5-site Epidemiological Catchment Area (ECA) study of the 1980s provided the first comprehensive picture of the prevalence of DSM-III mental disorders in the United States.1 A decade later, the Natio...

The Molecular Libraries Initiative (MLI) of the NIH Roadmap for Medical Research is a bold set of programs to facilitate the use of small molecules in the public sector and expand the reach of small-molecule technologies to define gene, cell, and organism function in health and disease. The initiative described in this [Policy Forum][1] has three c...

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they ha...

Studies conducted in the past two years have yielded several new insights about neuroendocrine regulation of social recognition. The social recognition deficits seen in oxytocin knockout mice have now been demonstrated in both males and females, as well as in female estrogen receptor knockout mice. The male vasopressin V1A receptor knockout mouse (...

Because information about gender, kin, and social status are essential for reproduction and survival, it seems likely that specialized neural mechanisms have evolved to process social information. This review describes recent studies of four aspects of social information processing: (a) perception of social signals via the vomeronasal system, (b) f...

To study the brain from molecules to behaviour, neuroscientists face the challenge of communicating an emerging wealth of information in coherent accessible forms.

There is a considerable literature on the neurobiology of reward, based largely on studies of addiction or substance abuse. This review considers the possibility that the neural circuits that mediate reward evolved for ethologically relevant cues, such as social attachment. Specifically, mesocorticolimbic dopamine appears important for maternal beh...

Depression is an illness that frequently starts early in life, tends to run a chronic course, and produces substantial disability. According to the World Health Organization, depression is the leading global cause of years of life lived with disability and the fourth leading cause of disability-adjusted life-years, a measure that takes premature mo...

Mother-reared (MR) and nursery-reared (NR) male rhesus monkeys exhibit profound and persistent differences in social and emotional behavior. Compared to MR animals, NR monkeys show reduced reciprocal social behaviors and increased agonistic behavior and high levels of stereotypy. Cerebrospinal fluid oxytocin (CSF OT) in NR monkeys was significantly...

Inbred mouse strains are classically used to search for the genes associated with behavioral traits, including emotionality. To distinguish genetic and environmental contributions to the expression of adult behavior in mice, we investigated the effects of prenatal (embryo transfer) and postnatal (cross-fostering) environments in two strains of inbr...

A full understanding of the biology and behavior of humans cannot be complete without the collective contributions of the social sciences, cognitive sciences, and neurosciences. This book collects eighty-two of the foundational articles in the emerging discipline of social neuroscience. The book addresses five main areas of research: multilevel int...

A full understanding of the biology and behavior of humans cannot be complete without the collective contributions of the social sciences, cognitive sciences, and neurosciences. This book collects eighty-two of the foundational articles in the emerging discipline of social neuroscience. The book addresses five main areas of research: multilevel int...

Vaginocervical stimulation (VS) significantly elevated the concentration of oxytocin (OT) in spinal cord superfusates of 8 intact urethane-anesthetized rats measured 10-15 min after VS (median [interquartile range]: 1.7 [1.00-3.37] pg/ml) compared to that measured 10-15 min before VS (1.1 [1.01-1.40] pg/ml). When VS was administered once (n = 8), i...

All social relationships are dependent on an organism's ability to remember conspecifics. Social memory may be a unique form of memory, critical for reproduction, territorial defense, and the establishment of dominance hierarchies in a natural context. In the laboratory, social memory can be assessed reliably by measuring the reduction in investiga...

Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after repeated social exposures, despite normal olfactory and spatial learning abilities. OT treatment fully restores social recognition. Here we demonstrate that OT acts in the medial amygdala during the initial exposure to facilitate social recognition. OT given before, but not...

Brain-derived neurotrophic factor (BDNF) has been linked to the development, differentiation, and plasticity of the central nervous system. In the present study, we first used a highly specific affinity-purified antibody and a cRNA probe to generate a detailed mapping of BDNF immunoreactive (BDNF-ir) staining and mRNA labeling throughout the forebr...

The neuropeptide oxytocin has been implicated in the initiation of maternal behavior, based on studies in rats and sheep. Females in both of these species naturally avoid infants until parturition when they begin to show an intense interest in maternal care. Oxytocin pathways in the brain appear to be important for this transition from avoidance to...

Oxytocin (OT) and arginine vasopressin (AVP) were among the first peptide hormones to be isolated and sequenced (1). Both OT and AVP consist of nine amino acids that form a ring structure from disulfide bonds, bridging two cysteine residues. Although the two hormones are similar in structure, differing at only two positions, their functions appear...

A number of studies have implicated the neurohypophyseal peptides oxytocin and vasopressin in the central mediation of complex social behaviors, including affiliation, parental care and territorial aggression. Research on a monogamous rodent, the prairie vole (Microtus ochrogaster), suggests that these neuropeptides are also involved in the control...

Several lines of evidence have implicated the neurohypophyseal peptide, vasopressin (VP), in the mediation of complex social behaviors including affiliation, aggression, juvenile recognition and parental behavior. Recent studies in microtine rodents using cellular, molecular and behavioral approaches provide additional evidence suggesting a role fo...

Changes in brain oxytocin receptor (OTR) binding sites during the course of pregnancy may influence the sudden onset of maternal behavior in female rats at parturition. In situ hybridization was used to identify changes in OTR messenger ribonucleic acid (mRNA) expression during pregnancy and parturition. Two patterns of mRNA regulation were observe...

Monogamous prairie voles (Microtus ochrogaster) show mating-induced aggression towards conspecific strangers. This behavior is both selective and enduring. The present study was designed to investigate the behavioral conditions for the emergence of selective aggression (by varying prior experience with a female and identity of intruders) and the li...

Transgenic technology affords exciting new opportunities in the field of behavioral neuroendocrinology. We have extended our research into the behavioral function of oxytocin in maternal and social behavior using two transgenic approaches: (i) targeted deletion of the oxytocin gene in mice and (ii) augmented oxytocin receptor expression in the brai...

Arginine vasopressin modulates a number of species-typical social behaviors, including social memory in rats, scent marking and aggressive behavior in hamsters, and partner preference formation and paternal behavior in monogamous rodents. The distribution of V₁a receptor binding sites in the brain varies greatly among species. Using in situ hybridi...

This chapter summarizes the available literature on parental behavior in voles. An attempt is also made to examine the interactions of the environment with the behavior, as well as to explore the possible neural mechanisms underlying parental care in voles. The chapter focuses on monogamous prairie (Microtus ochrogaster), pine (M. pinetorum) voles,...

The distribution of oxytocin binding sites in the brain is highly variable among mammals. Using two species of microtine rodents (voles) with strikingly different patterns of oxytocin binding sites in the brain, we demonstrate that these differences are due to differences in region specific gene expression and not post-translational processing. The...

Previous studies have demonstrated that central administration of vasopressin but not oxytocin facilitates pair bonding in the monogamous male prairie vole. This study tested vasopressin and oxytocin in the formation of the female vole's preference for a particular male partner. Initial studies showed that in monogamous female prairie voles (but no...

Prairie voles (Microtus ochrogaster) are monogamous mammals that form male-female pair bonds. Partner preference formation, one component of the pair bond in prairie voles, occurs following male-female cohabitation and is facilitated by mating. The peptide hormone oxytocin is released during physical contact and particularly following vaginal stimu...

The neural basis of affiliative behavior was examined in the prairie vole, a rodent that exhibits high levels of social contact and paternal behavior. In the first study, the axon-sparing excitotoxin N-methyl-D,L-aspartic acid (NMA) produced lesions in the basolateral nucleus of the amygdala or the corticomedial amygdala. Males with corticomedial l...

The prairie vole is an excellent model for examining the neurobiology of social attachment, and in particular of pair-bond formation. In female prairie voles either sexual interactions or oxytocin infusions can hasten the formation of a partner preference. These results implicate oxytocin in the formation of adult heterosexual social bonds. In conj...