December 17, 2010 was a special day in the history of psychiatric diagnosis. Bob Spitzer retired after a remarkable 52 year career. The event was celebrated in a warm and wonderful conference held in his honor at Columbia University– where Bob has worked for the past 52 years. Dozens of Bob’s colleagues and students gave speeches describing his powerful influence on our field and his personal impact on our lives.

Source: Psychiatric Times

The journal Nature began the year by declaring that this decade would be “the decade for psychiatric disorders,” in that the field is “ripe for a revolution.” In this opening year of the decade, the revolution seems well underway. Here are 10 breakthroughs and events of 2010 that are changing the way we approach mental disorders.

1. HIV/AIDS: treatment as prevention. Treatment for HIV/AIDS has improved markedly in the last decade, but HIV infection rates continue to be unacceptably high. Globally, treatment cannot keep pace with new infections; in Sub-Saharan Africa, it is estimated that seven are infected for every one person who starts treatment. Behavioral prevention via education about safer sex, male circumcision, and microbicides for women all have an impact in research studies, but barriers to implementation limit population-level impact. This year we discovered that doses of HIV-treatment among HIV-negative persons is the best prevention to date. Pre-exposure prophylaxis (PrEP) reduced infection by nearly 50 percent in the most conservative estimate and, when combined with behavioral interventions to ensure adherence, reduced infection by a stunning 97 percent. For the first time, we have an effective prevention strategy that may be readily taken to scale.¹
2. The human connectome. Functional magnetic resonance imaging (fMRI) of the brain when it is at rest (sometimes called resting state fMRI) has emerged as a powerful approach for detecting correlations of large, infrequent fluctuations in activity levels across functionally related brain areas. A collaboration across 35 laboratories in 10 countries compared patterns of brain-function connection (called connectomes) in 1,414 volunteers, yielding harmonized brain maps based on age and gender.² As with the human genome, this functional connectome is important not only for providing a reference wiring map of the human brain, but also demonstrating intriguing, stable individual differences. New projects on the human connectome, supported via the NIH Blueprint for Neuroscience Research, will be exploring individual differences and developing more precise tools for measuring connections in the human brain. http://www.humanconnectome.org/consortia/
3. DNA sequencing. The cost of DNA sequencing has dropped by a factor of 10 every year for the past few years. This new capacity to sequence rapidly and inexpensively the full genome (or candidate gene regions) is transforming psychiatric genetics. In previous years, costs have constrained full genome sequencing efforts, and investigators have compensated by using strategies to search for hints of variation in certain regions of the genome. This year, however, whole genome sequencing in multiple individuals finally became a reality. The result was the discovery of enormous genomic variation across healthy subjects, with hundreds of thousands of rare gene variants identified and, on average, each child showing 50 – 100 new mutations not present in his or her parents.³ We have also learned that autism, schizophrenia, and other neurodevelopmental disorders are associated with rare “structural” variations in the genome, sometimes involving millions of bases of DNA.⁴ Only through full genome sequencing efforts will we be able to understand the scope of these rare variations and their contribution to the causes of mental disorders.
4. Parental imprinting. We have long known that certain diseases and disorders can be inherited via genetic mutation. For certain genes, it makes a big difference whether you inherit a copy from your mother or your father. For instance, inheriting a mutation on maternal chromosome 15 confers a disorder called Angelman’s syndrome. The same mutation inherited from the father results in a completely different disorder, Prader-Willi syndrome. This phenomenon is known as “parental imprinting,” a process through which the gene inherited from one parent is either always silenced or always expressed. Parental imprinting was once thought to be a rare event, influencing only a few genes. This year, however, Dulac and colleagues discovered that in the mouse, parent of origin matters for over 1300 genes involved in shaping the brain’s structure and function.⁵ Paternally-inherited genes were most evident in the hypothalamus, while maternally-inherited genes exerted their effects on the brain’s cortex. While these findings have yet to be demonstrated in humans, observations from these studies in mice suggest that the rules for gene expression in the brain may be far more complex than we ever considered.
5. The human epigenome. Although every cell in your body has identical DNA, different parts of the code are expressed in neurons, blood cells, and muscle cells. The epigenome describes all of the proteins that bind to DNA that lead to different patterns of gene expression – accounting for differences in cell type, differences in identical twins, and presumably how experience influences development or, fundamentally, how nurture affects nature. In this year, epigenomics became a discovery science, as new techniques allowed the interrogation of epigenetic marks across the entire human genome. ⁶ Stable, individual differences in the human epigenome suggest a powerful new approach to study the long-term effects of early experience.
6. Next Gen antidepressants. Antidepressant medications or cognitive behavioral therapy generally require six to eight weeks to have an effect. In the past five years, ketamine and scopolamine have been shown to reduce depression experimentally, including thoughts of suicide, within six hours. This year saw the first identification of biological indicators of how the brain responds to ketamine⁷ and the first demonstration of the molecular mechanism for this rapid response—the rapid activation of an enzyme, mTOR, which regulates cell growth, proliferation, and survival.⁸ In addition, new targets for intervention have emerged, including MKP-1, a protein involved in the resiliency of brain cells to stress.⁹ While several pharmaceutical companies moved away from psychiatric medication development this year, the scientific opportunities for new targets and new approaches have never been better.
7. The autistic brain. Autism spectrum disorder (ASD) has been recognized as a disorder of brain development, but there have been few clues to what is different in the brain of someone with ASD. Several papers this year described differences in structure of brain regions; patterns and strength of connections between brain regions; and function of brain circuits.^10-13 One intriguing brain imaging study looked at brain activity in response to social information in children with ASD, their unaffected siblings, and controls. Compared to controls, both children with ASD and their unaffected siblings showed different brain activity patterns in some regions. Remarkably, the brains of unaffected siblings appeared to compensate for the difference with additional brain activity in other regions.¹⁴
8. Disease-in-a-dish. History may judge one of the most important discoveries in the past decade to be the creation of induced pluripotent stem cells (iPSCs): cells taken from adults, de-differentiated into a pluripotent state (in which they have the potential of becoming any cell type), and then differentiated into a mature cell type. For example, a skin cell taken from an adult can be made pluripotent and then differentiated into a neuron. This year, we saw this revolutionary technology begin to shed light on Rett Syndrome, a genetic disorder that causes autism. Marchetto et al. (Cell, Nov, 2010) derived iPSCs from patients with Rett Syndrome and then differentiated them into neurons in vitro (e.g. “in-a-dish”), with a range of abnormalities corresponding to observed neuronal abnormalities seen in Rett Syndrome patients.¹⁵ These cells were useful not only for identifying the process of developing Rett pathology but also allowed testing of potential treatments.
9. High throughput screening. High throughput screening of small molecules, previously the domain of pharmaceutical companies, has been developed as a tool for academic scientists with the Molecular Libraries Program, an NIH Common Fund effort led by NIMH and the National Human Genome Research Institute. The Molecular Libraries Program Comprehensive Screening Centers provide academic scientists with the means of quickly screening over 350,000 small molecules to identify those that interact with biological targets. Using this technology, researchers have identified over 120 molecules with biological activity that may one day lead to the development of new medications. In one extraordinary effort, independent of the Screening Centers, Andrew Pieper and his colleagues at University of Texas Southwestern Medical Center identified a series of novel molecules with antidepressant and neuroprotective effects.¹⁶
10. Nature focuses on schizophrenia. Nature, regarded by many as the world’s premier science journal, rarely features a disease as a special topic. In November, Nature dedicated a special issue to schizophrenia, with articles spanning the biology, psychology, and social implications of the disorder.¹⁷

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via Blog Post » NIMH’s Top 10 Research Events and Advances of 2010. (References link to external website)