Huda Akil, Ph.D.

Dr. Akil is the Gardner Quarton Distinguished University Professor of Neuroscience and Psychiatry and co-director of the Molecular & Behavioral Neuroscience Institute, Univesity of Michigan.  Dr. Akil has made seminal contributions to the understanding of the brain biology of emotions, including pain, anxiety, depression and substance abuse. She and her colleagues provided the first physiological evidence for a role of endorphins in the brain; and showed that endorphins are activated by stress and cause pain inhibition. Dr. Akil’s current research investigates the genetic, molecular and neural mechanisms underlying stress, addiction and mood disorders.
She is a former president of the Society for Neuroscience (2002-2003) and an elected member of the National Academy of Sciences. Professor Akil‘s scientific contributions have been recognized with numerous honors and awards. ... more.

Molecules of Temperament, Mood and Emotion: Animal Models and Human Studies

Elizabeth H. Blackburn, Ph.D.

Dr. Blackburn, awarded the Nobel Prize in Physiology or Medicine (2009), is the Morris Herzstein Professor in Biology and Physiology at the University of California, San Francisco. She discovered the molecular nature of telomeres - the ends of eukaryotic chromosomes that serve as protective caps essential for preserving the genetic information - and the ribonucleoprotein enzyme, telomerase. ...more

Telomeres And Telomerase: Their Relation to Stress and Human Disease

Telomeres are the protective tips that stabilize the ends of chromosomes. Telomeres contain specialized, simple repetitive DNA sequences that, together with their specifically-bound proteins, protect chromosome ends from damage and thus stabilize the genetic information. As cells divide, unless a process of telomere elongation intervenes, telomeres suffer progressive attrition, causing the cells eventually to die or malfunction. This telomere shortening process can be counteracted by the ribonucleoprotein enzyme telomerase in eukaryotic cells. Telomerase is a unique reverse transcriptase found at highly regulated levels in various human cell types. Telomerase replenishes telomeres by adding telomeric DNA to them, thereby slowing, preventing or even reversing telomere shortening. In humans, in normal cells throughout human life, telomerase generally appears to be insufficient, because telomeres often erode down, even in some stem cell types. Increased telomere shortness has been linked to chronic psychological stress and to the major diseases that increase with aging. Through many clinical studies, telomere shortness has emerged as a potential marker for stress and its effects, which include the biological aging that limits human "healthspan". An important challenge is applying the growing knowledge of telomeres and telomerase to improvements in health and clinically.

Daniel Geschwind, M.D.

Dr. Daniel Geschwind is the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics and is a professor of neurology and psychiatry at the UCLA School of Medicine. He is director of the Neurogenetics Program and the Center for Autism Research and Treatment and co-director of the Center for Neurobehavioral Genetics at UCLA. Dr. Geschwind is active on the scientific advisory boards of the March of Dimes (Committee C), Cure Autism Now Foundation (now Autism Speaks), Faculty of 1000 Medicine, the NIMH Scientific Advisory Council. He received the Derek Denny-Brown Neurological Scholar Award from the American Neurological Association, the Scientific Service Award from Autism Speaks, and was inducted into the Institute of Medicine of the National Academies.

Advances in Autism: From Genes to Therapy

Autism is a common, complex neurodevelopmental syndrome that causes significant morbidity because few effective treatments are available. Since there is a significant genetic component to autism, we and others have used modern genetic methods, including whole-exome sequencing to identify genetic causes of autism, as a first step in defining its etiology, Many genes have been identified, but none account for more than 1% of ASD, which has led us to conceive of autism more as "the autisms" than as a unitary disease. From this perspective, autism is best conceived as a group of disorders caused by developmental disconnection of specific brain circuits involving the frontal lobes and other interconnected regions. Recent translational advances based on these genetic findings have begun to expose potential mechanisms of the autisms, and harbor great potential for development of new treatments. This includes valid mouse models and in vitro models based on human neural stem cells, which provide exciting possibilities for drug development and screening. One of the big challenges now is to understand how specific genetic perturbations effect brain development and function, leading to the specific clinical features of ASD.

Baroness Susan Greenfield

Susan Greenfield is Professor of Pharmacology at Oxford University and a neuroscientist, writer, and broadcaster. She has been awarded over 30 Honorary Degrees from British and foreign universities and heads a multi-disciplinary research group exploring novel brain mechanisms linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s. In addition, she has published a neuroscientific theory of consciousness: The Private Life of the Brain (2003) and developed an interest in the impact of 21st Century technologies on how young people think and feel, as discussed in her book ID: The Quest for Identity in the 21st Century (2008). She received the Michael Faraday Medal from the Royal Society, was awarded a CBE in the Millennium New Year’s Honours List, and granted a non-political Life Peerage in 2001.  She is an Honorary Fellow of the Royal College of Physicians and the Royal Society of Edinburgh. She was appointed Chancellor of Heriot Watt University in 2005. Further recognition of her work includes L’Ordre National de la Légion d’Honneur from the French Government and the American Academy of Achievement Golden Plate Award as well as the Australian Medical Research Society Medal. ... more.

Are Digital Technologies Impacting on Wellness of the Young Mind?

A recent survey of US teenagers showed that over half those aged 13 to 17 spend more than 30 hours a week, outside school, using screen technologies. Given the plasticity of the human brain, not surprisingly, adaption to a cyber-environment will lead to positives in enhanced performance in a variety of skills continuously rehearsed. However, we need urgently to gain a much fuller picture. Time spent in front of a screen is time not spent doing other things. We need to understand the full impact of the current cyber culture on the emotional and cognitive profile of the 21st century mind. We can look at three broad areas. First, what is the impact of social networking sites on interpersonal skills and personal identity? If a young brain with the evolutionary mandate to adapt to the environment is establishing relationships through the more sanitized medium of a screen, the skills that are so essential for empathy may not be acquired as naturally, as well or as quickly as in the past. Secondly, on video games, neuropsychological studies suggest that frequent and continued playing might lead to enhanced recklessness and low-grade aggression. In addition, data indicate reduced attention spans and even possible addiction. Moreover, significant chemical and even structural changes are being reported in the brains of obsessional gamers. Thirdly, on search engines, can the internet actually improve or impair cognitive skills and learning? We need to understand much more about the impact of search engines on comprehension skills and need to differentiate information from knowledge. Like Climate Change, this transformational scenario of 'Mind Change' is complex, unprecedented and controversial. However, unlike climate change, the end point is not one of just damage limitation but rather of ensuring that we deliver to the next generation an environment that can for the first time enable the realization en masse of each individual's full potential.

Jan-Åke Gustafsson, M.D., Ph.D.

Dr. Gustafsson is THE Robert A. Welch Professor in the Department of Biology and Biochemistry and Director of the new Center of Nuclear Receptors and Cell Signaling at the University of Houston. His early focus on the biochemistry of steroid receptors led to his discovery of the three domain structure of the glucocorticoid receptor, its specific DNA binding and its cloning. Dr Gustafsson determined the first structure of the DNA-binding domain of a steroid receptor and furthermore discovered two novel receptors, liver X receptor beta (LXRβ), and the second estrogen receptor ERβ. ... more.


LRB and LXRB are later discovered members of the nuclear receptor gene family. Both were discovered in 1995 and both are important in the development of the CNS and in the maintenance of specific populations of neurons in adults. ERbeta is involved in the survival of GABAergic interneurons, serotonergic neurons of the Dorsal Raphe (DR) and the activity of microglia, while the motor neurons of the spinal cord, the dopaminergic neurons of the Substantia Nigra (SN) and the neurons of the prefrontal cortex depend on the presence of the LXRbeta. Thus ERB is involved in depression, anxiety and neuroinflammation while LXRbetais involved in Amyotrophic lateral sclerosis and Parkinson's disease. The functions of ERB have been revealed with the use of knockout mice and the use of selective ERB agonist (LY3201) provided by Lilly. At present there is no specific a LXRbeta agonist available so we have worked with LXRbeta-1-mice and an agonist which acts on both LXRbeta and LXRbeta. Male but not female LXRbeta-1-mice develop motor neuron disease as they age. The first symptoms occur when mice are 6 months of age and begin to perform poorly on the rotor rod. The disease progresses to paralysis when mice are one year old and is accompanied by loss of motor neurons in the spinal cord and loss of dopaminergic neurons in the SN. Administration of the LXR agonist, GW3965, protected mice against the MPTP-induced loss of dopaminergic neurons in WT mice. ERbeta but not ERa is the ER in the serotonergic neurons of the DR. These are the neurons involved in fear, anxiety and depression. In overiectomized WT mice and in ERbeta-1-mice, there is a marked reduction in the number of tryptophan hydroxylase-positive neurons and this decrease in WT mice can be prevented by administration of LY3201. Thus LXR agonists may have beneficial effects in treatment to PD and ERbeta agonists in treatment of depression. Both receptors may be targets for treatment of neurodegeneration by modulating the cytotoxic functions of microglia.

Jeremy A. Lazarus, M.D.

Psychiatry, the AMA and Medicine: The Next Chapter

As physicians, psychiatrists are constantly learning and striving for more – better outcomes, better tools, improved systems, and more focused frameworks. With more integration into primary care, psychiatrists can learn from each other and other physicians. Psychiatrists are also sensitive to their patients overall health and wellness and need tools and guidance to help patients improve their physical wellness and reduce the life expectancy disparities between the general patient population and the psychiatric patient population. The AMA is working to improve outcomes and set the standards for the next generation of team approaches to care as part of its new strategic focus and Dr. Lazarus will discuss this, as well as the impact of the Affordable Care Act on psychiatrists and physicians in general and the AMA's efforts to shape health system reform going forward.

Robert H. Lenox, M.D.

CNS Drug Discovery & Development 2013: Problems, Promises and Partnering

The discovery and clinical development of new drugs for the treatment of both psychiatric and neurological disorders has been struggling over the past 50 years since the major breakthroughs in the last century that resulted in the introduction of the first anxiolytics, antidepressants, neuroleptics, and treatments for Parkinson's disease. The pharmaceutical industry has been facing significant challenges in productivity and cost within their drug discovery and clinical development paradigms due to the lack of understanding of the pathophysiology of many of the diseases, especially in psychiatry, and the relative lack of clinically-validated preclinical animal models; despite the remarkable advances that are being made in both the basic and clinical neurosciences. Discovery of pathways modulating the neuronal biology of survival/differentiation, inflammation, protein processing, axonal repair, and synaptogenesis are defining novel approaches to neurodegenerative diseases including Alzheimer's and MS.
   Progress in functional brain imaging is providing new insights into neuropsychiatric disorders including pain, and recent studies in autism are offering the promise of modifying the disease process and phenotype of developmental brain disorders in childhood, and may augur similar opportunities for altering disease progression in schizophrenia. New strategies for drug discovery and clinical development are shifting risk of failure to earlier phases of the drug development process with the incorporation of novel translational biomarkers. Public-private partnering ventures by Pharma including universities, the NIH and MRC, promise more efficient screening for clinical proof of concept using repurposing strategies, as well as designing new 'crowdsourcing' approaches for more rapid and novel drug development in an open-access environment; addressing the thorny issues directly related to cost, proprietary, and regulatory constraints within the standard pharmaceutical drug discovery paradigms.

Eric J. Nestler, M.D., Ph.D.

New Insight Into the Neurobiology of Depression

Depression is a common, chronic, and debilitating syndrome. Only about half of depressed patients show a complete remission to available treatments, which underscores the need for more effective agents. The mechanisms that precipitate depression, such as stress in some patients, are incompletely understood. Unraveling the pathophysiology of depression represents a unique challenge. In addition to the heterogeneity of depressive syndromes and their diverse etiologies, symptoms like guilt and suicidality are impossible to recapitulate in animal models. Nevertheless, other symptoms can be accurately modeled, which, along with growing clinical data, are beginning to provide new insight into the neurobiology of depression. Recent studies, which combine behavioral, molecular, and electrophysiological techniques, reveal that certain aspects of depression result from maladaptive stress-induced changes in reward circuits of the brain. We are currently investigating the detailed molecular mechanisms underlying these changes. One major focus is stress-induced changes in gene expression, which are mediated via epigenetic mechanisms, that is, changes at the level of chromatin remodeling. We have identified such mechanisms that mediate susceptibility to stress in some individual animals and other mechanisms that instead mediate resilience to stress in other individuals. This work provides new insight into the molecular mechanisms by which chronic stress produces lasting changes in brain to cause depression-like symptoms. The findings also suggest novel leads for the development of new antidepressant treatments, including mimicking coping mechanisms mounted by resilient individuals.

Maria A. Oquendo, M.D.

Dr. Oquendo is Professor of Clinical Psychiatry and Vice-Chair for Education in Psychiatry at Columbia University and the New York State Psychiatric Institute, with expertise is in diagnosis, pharmacologic treatment, and neurobiology of bipolar disorder and major depression with an emphasis on suicidal behavior. She has received many awards including the APA Simon Bolivar Award (2010) and twice NAMI's Exemplary Psychiatrist Award. She was recently awarded a T32 grant to implement a research fellowship program in Global Mental Health.   ...more

Suicidal Behavior: Should It Be a Separate Diagnosis?

Although there are about 1 million suicides a year and anywhere between 25 and 50 suicide attempts for each suicide death, preventive strategies have so far done little to decrease the morbidity and mortality associated with suicidal behavior. Further, suicidal behavior is associated or comorbid with a wide range of psychiatric diagnoses. A pragmatic problem has been the ease with which crucial information about history of suicidal behavior is lost in medical communications. Often times, discharge summaries lack information about this key element and there is no way for clinicians to code it in diagnostic summaries of the case. Interestingly, suicidal behavior meets the criteria for diagnostic validity set forth by Robins and Guze, and it does so as well as most conditions we treat. It is clinically well described; research has identified postmortem and in vivo laboratory biomarkers; it can be subjected to a strict differential diagnosis; follow-up studies confirm its presence at higher rates in those with a past diagnosis; and it is familial. From both theoretical and practical perspectives, making such a diagnosis available to clinicians makes sense and more importantly, has the potential to save lives.

Stanley B. Prusiner, M.D.

Dr. Prusiner is an American neurologist and biochemist, and founder and director of the Institute for Neurodegenerative Diseases at University of California, San Francisco. In the early 1970s, he discovered the cause of a sudden and mysterious form of brain disease called Creutzfeldt-Jakob disease (CJD). He found that harmful proteins (called “prions”) were forcing the normal proteins around them to misfold, sparking a chain reaction that ravaged the brain. His work helped authorities respond to the threat of mad cow disease and was recognized with the Albert Lasker Award for Basic Medical Research in 1994 and  a Nobel prize in 1997. Now the prion disorders are better understood than most brain diseases and may pave the way for better treatments for diseases like Alzheimer’s and Parkinson’s.  ... more

Prion Biology: New Interface Between Psychiatry and Neurology

Over the past three decades, there has been a steady accumulation of evidence that each neurodegenerative disease is caused by a particular protein that becomes a prion. As with the prion diseases caused by the aberrant prion protein (PrPSc), amyloid deposits in other neurodegenerative disorders were found to have the same protein as that identified by molecular genetic studies of patients with inherited neurodegeneration. Mammalian prions composed of PrP, Aβ, tau, α-synuclein, SOD1 or huntingtin proteins all cause distinct neurodegenerative diseases. In each of these disorders, the respective mammalian proteins adopt a β-sheet–rich conformation that readily oligomerizes and becomes self-propagating. The oligomeric states of mammalian prions are thought to be the toxic forms, and assembly into larger polymers such as amyloid fibrils seems to be a common mechanism for minimizing toxicity. The role of the tau protein in the pathogenesis of AD was resolved when mutations in the tau gene were found to cause heritable tauopathies including familial frontotemporal dementia (FTD), inherited progressive supranuclear palsy (PSP) and Pick's disease but not familial AD. Aggregates formed from truncated recombinant tau were shown to enter cells and seed the polymerization of endogenous tau into additional aggregates. Such self-propagating tau aggregates were also detected in the brains of Tg mice expressing wild-type human tau that were inoculated with brain homogenates prepared from Tg mice expressing mutant tau. Tau prions are likely to cause all the tauopathies including the sporadic and familial FTDs, PSP, Pick's disease and chronic traumatic encephalopathy (CTE). Some athletes participating in contact sports develop FTD after repeated traumatic brain injury (TBI). In boxers, this illness has been called punch-drunk syndrome as well as dementia pugilistica; in football players, a similar progressive neuropsychiatric disorder with numerous neurofibrillary tangles in the frontal lobes is called CTE. Recent reports of military personnel, who were diagnosed with posttraumatic stress disorder (PTSD) and committed suicide, argue that concussions from shock waves from roadside bombs can initiate a tau prion–mediated process indistinguishable from that in football players with CTE. To date, there is not a single medication that halts or even slows a neurodegenerative disease caused by prions. This may indicate that unique pathogenic mechanisms feature in each of the prion diseases.

Andrew V. Schally, Ph.D., M.D. h.c.

Dr. Schally, awarded the Nobel Prize in Physiology and Medicine (1977), is internationally renowned for his research in the hypothalamic hormones and has authored or co-authored more than 2,300 scientific publications in the field of endocrinology and oncology. He is currently Distinguished Leonard M. Miller Professor of Pathology, Professor in the Division of Hematology/Oncology, Department of Medicine and Director of the Endocrine, Polypeptide and Cancer Institute, University of Miami Miller School of Medicine.

Beneficial Effects of Novel Antagonists of GHRH in Different Models of Alzheimer 's Disease

Alzheimer's disease is the most frequent debilitating disorder of the central nervous system, afflicting millions of people all over the world. Neuroendocrine mechanisms appear to play an important role in this insidiously developing degenerative disease. In the present study, the effects of a recently developed growth hormone releasing hormone (GHRH) antagonist (MIA-690) were evaluated in vivo observing the behavior of genetically modified 5XFAD strain, "Alzheimer's" mice in Morris water maze (MWM). The effects of the antagonist were also evaluated in vitro using cell cultures of HCN-2 human cortical cell lines treated with amyloidbeta (1-42). In vivo, the indices of cognitive performance (latency, cumulative index etc.) were followed up for 6 months. In vitro, the formation of reactive oxygen species, markers of inflanlmatory and neurohormonal signaling were measured by fluorescent detection, PCRs, and ELISAs in tissue culture supernatants. Accumulation of amyloid-beta rafts and tau-filaments in necropsied brain samples was verified with the help of ELISA. In the MWM experiments, MIA-690 attenuated the progress of cognitive decline, prolonged survival and inhibited the aggregation of pathologic proteins. In cell cultures, the analog showed strong anti-oxidative and neuro-protective properties and inhibited the GHRH-growth hormone (GH)-insulin like growth factor (IGF) axis. The beneficial in vivo and proteomic findings were supported by concordant PCR results. Our data strongly suggest the merit of further studies with GHRH analogs in the models of Alzheimer's and elementary clinical trials.

Gary W. Small, M.D.

Brain Health and Alzheimer’s Prevention

Age is the greatest single risk factor for developing Alzheimer's disease, and more than five million Americans and 34 million people worldwide suffer from this condition, which impairs an individual's ability to live independently. Genetics account for only part of the risk for developing Alzheimer's disease; thus, non-genetic factors likely contribute to disease risk. A recent NIH consensus panel couldn't draw firm conclusions between decreasing risk factors for Alzheimer's disease and slowing cognitive decline. However, the panel did conclude that many studies of healthy lifestyle habits – including diet, physical activity, and cognitive engagement – are providing new insights into the prevention of cognitive decline and Alzheimer' disease. Additional studies to supplement these findings are needed, but since these lifestyle choices help us feel better right away and appear to help prevent several diseases that increase Alzheimer's risk, the question is: Why wait years for results of definitive studies? Moreover, physical exercise and healthy diet, two of the key strategies of an Alzheimer's prevention program, are proven ways to prevent diabetes. Since diabetes is a major risk factor for developing Alzheimer's disease, anything that prevents diabetes should also prevent Alzheimer's disease. The goal of Alzheimer's prevention strategies is to help people stave off the onset of dementia symptoms for as long as possible. A 25% reduction in modifiable risk factors could potentially prevent as many as 500,000 cases of Alzheimer's disease in the United States and three million cases worldwide. This lecture will review the scientific evidence suggesting that healthy lifestyle habits can improve and maintain brain health and possibly forestall symptoms of Alzheimer's disease. It also will provide practical strategies to help people begin to develop brain healthy habits for preventing cognitive decline.

Stephen M. Stahl, M.D., Ph.D.

What Is a 21st Century Neurobiologically Empowered Psychiatrist? Lessons From Crime Scene Investigators

Classically, a psychiatrist makes a diagnosis from an interview alone without diagnostic tests, and then chooses a treatment from published guidelines derived from evidence-based medicine from studies of populations of patients. Currently, treatments are linked to a specific diagnosis but not to the unique characteristics of the individual patient. Now all of this is changing. Increasingly available are genomic tests which promise to link specific patients to markers that suggest greater or lesser likelihood of responding to or tolerating a given drug. Thus," population based medicine" defining the median patient dictating treatment for all, is giving way to personalized medicine and customization of both symptom profiles and treatments to the individual. Also, translational neuroscientists are rapidly making available results from structural and functional neuroimaging techniques that correlate with symptom endophenotypes but not necessarily with DSM diagnoses. Endophenotypes are symptoms linked to inefficient information processing in specific brain circuits that are present transdiagnostically as a dimension of psychopathology that cut across many psychiatric disorders. Examples include impulsivity, compulsivity, mood, anxiety, motivation and many more. Thus, the 21st century neurobiologically empowered psychiatrist is poised to become a "disease scene investigator" analogous to crime scene investigators celebrated in the popular media and who investigate individual unique crimes and not the median crime. That is, practicing psychiatrists may soon be investigating the "scene of the disease," namely, the brain, with neuroimaging and pharmacogenomics, to determine the linkage of specific symptoms to specific malfunctioning brain circuits regulated by unique genes and neurotransmitters that predict what treatments to select for best results for that individual. Sherlock Holmes, watch out.

Nora Volkow, M.D.

Substance Use Disorders: New Scientific Findings and Therapeutic Opportunities

Recent scientific advances have increased our understanding of the biological (genetic and epigenetic), developmental and environmental factors and their interactions that are involved in drug abuse and addiction. This presentation will highlight recent findings on the consequences of acute and chronic drug exposure on epigenetic modifications, gene expression and cell function; brain circuit disruption in addiction; and factors involved in genetic vulnerability and resilience for drug abuse. In the coming years key addiction research challenges and opportunities will include discovery of genes that are involved in vulnerability and resilience for drug abuse, genes that affect brain development and function and how they interact with the environment to either protect or increase drug abuse vulnerability. Emphasis will also be placed on translational research employing state-of-the-art imaging tools as biomarkers to predict effectiveness of drug abuse prevention interventions and to assess and monitor promising addiction treatment strategies. Progress in the development of targeted pharmacotherapies, medication combinations, and immunotherapeutic approaches for addiction treatment will also be summarized.

Irvin D. Yalom, M.D.

Emeritus professor of psychiatry at Stanford University and a psychiatrist in private practice in San Francisco. He is the author of many books, including Love's Executioner, Theory and Practice in Group Psychotherapy, and When Nietzsche Wept.            

The Teaching Novel: The Spinoza Problem

For decades I have used narrative as a tool for teaching psychotherapy. My textbooks on group therapy and existential therapy are full of short narratives that teach some aspect of therapy theory or technique. Following that I've written four novels meant to teach important therapy ideas and techniques. I'll review the therapy ideas in each of these and concentrate on my most recent novel: The Spinoza Problem.