What Has Neuroscience Done for Psychiatry Lately?
Psychiatry: Clinical Relevance of Neuroscientific Advances
Posted Aug 01, 2011
We have argued that psychiatry's clinical future is increasingly tied to an understanding of basic neurosciences. Some have challenged this notion and ask for examples of clinically relevant advances that have resulted from neuroscience research.
We acknowledge that clinical advances in psychiatry based on neuroscience research have not been rapid. However, it is often hard to predict if and when findings from basic science will have clinical applicability. This is true of all fields of medicine. Nonetheless, we believe that the field of neuroscience has strong potential to increase our understanding of psychiatric diagnoses and treatments. Because of this, we argue that training in psychiatry must include a solid foundation in modern neuroscience.
To support the contention that neuroscience is relevant to clinical psychiatry, we will discuss a few examples of neuroscience research that are significantly impacting psychiatry.
- Progress in understanding Alzheimer's disease (AD) and diagnosing this illness before clinical symptoms become apparent is perhaps the most dramatic example. Advances in molecular genetics together with research using genetically modified mice led to the identification of beta-amyloid, an endogenous chemical that is likely involved in the development of this illness. A research team led by William Klunk, a psychiatrist, and Chester Mathis, a chemist, from the University of Pittsburgh, spent years in the lab developing an agent that allows the visualization of beta-amyloid in the living human brain using positron emission tomography (PET), a type of brain scan. Research using this compound has shown that beta-amyloid accumulates in the brain several years before even subtle clinical symptoms of AD can be detected. This raises the distinct possibility that clinicians soon will be able to use neuroimaging procedures to confirm a diagnosis of AD in someone with very mild symptoms or to determine which individuals are at very high risk of developing the clinical illness even before symptoms appear. In addition, researchers are busy trying to develop interventions to stop beta-amyloid accumulation in people who are not yet symptomatic. This is an example of basic science research that is leading to a marked improvement in the ability to diagnose (and hopefully treat) this common and destructive illness. This work would not have been possible without the tools of neuroscience, chemistry, and advanced imaging techniques. Other recent research suggests that neuronal death is a relatively late event in the disease process and that dysfunction in the connections between neurons (called synapses) may be the driver of the earliest manifestations of AD. This provides yet another avenue for therapeutic intervention in an illness that heretofore has been considered hopeless. Related to this we are also beginning to understand that a specific neural system (called the default mode network) is likely the earliest target of damage in AD and that the default network is particularly vulnerable because of its high degree of activity and energy use. Again, this raises interesting possibilities for novel therapeutic strategies.
- Over the last decade, significant advances have been made in understanding the brain circuitry that underlies major depression. The development of deep brain stimulation (DBS) techniques by Helen Mayberg and colleagues to treat major depression has taken advantage of this new knowledge. We know that some patients suffering from chronic and severe depression can be helped by available treatments, but others are unresponsive to all current treatments. Some of these patients with refractory illness are participating in experiments that involve the implantation and stimulation of electrodes in areas of the brain involved in depression circuits. Early results from such brain stimulation studies are encouraging. This work is modeled after work that has demonstrated the success of DBS for treating Parkinson's disease and has been extended to trials in refractory obsessive compulsive disorder. To our knowledge, DBS is the first example where advances in neuroimaging have led to a specific therapeutic intervention in a primary psychiatric disorder.
- Research involving the influence of magnetic fields on brain circuitry has been instrumental in the development of repetitive transmagnetic stimulation (rTMS) for the treatment of depression and other neuropsychiatric disorders. Again, this treatment is in its early days, but studies using TMS in cognitive neuroscience are now commonplace and are helping to elucidate how brain connectivity networks process information in normal individuals and persons with neuropsychiatric illnesses.
- Recent brain imaging research is demonstrating that it may be possible to determine whether neural connections in a child's brain are developing in a normal-for-age pattern or in a pattern suggestive of dysfunction. In our opinion, it is likely that simple imaging procedures will soon become available that will help identify illnesses such as autism in very young children. This will provide opportunities for early interventions. Changes in the developmental trajectories of specific brain networks may also be critical for understanding the earliest manifestations of other major illness including schizophrenia and mood disorders.
- Advances in understanding the processes involved in learning and memory at the level of specific transmitter and brain systems are leading to provocative new treatment approaches. For example, if a behavioral therapy is coupled with a single dose of a medication that enhances learning and memory (D-cycloserine), the behavioral treatment may be more rapid in onset and more effective. One potential application of this research involves the treatment of fear of heights.
- Glutamate is the major fast excitatory neurotransmitter in the mammalian brain and is involved in learning and memory. Basic neuroscience research has shown that glutamate may also be involved in the biology of depression. These findings have prompted trials of ketamine, a drug that interferes with a specific type of glutamate receptor (the NMDA receptor), for the treatment of severe refractory depressions. Based on early work, it appears that a single infusion of ketamine produces a substantial antidepressant effect in severely depressed individuals within a few hours. The antidepressant effect lasts for days. Thus, initial studies suggest that ketamine may not only be effective for refractory depression, but may also act more rapidly than conventional antidepressant treatments. Unfortunately, ketamine can also produce psychotic-like side effects, and safer approaches are now being investigated. The early success of ketamine in refractory depression is a clear example where basic science research has led to a proof of concept trial that is already influencing research and clinical thinking.
These are only a few examples where neuroscience is providing new ideas about psychiatric diagnosis and treatment. Importantly, each of these examples has clear implications for future studies and clinical practice. We predict that the number of such advances will continue to increase. We want to emphasize, however, that we are not saying that psychiatrists should abandon their expertise in communication skills and psychotherapy. Rather, we are encouraging psychiatrists to add a more sophisticated understanding of neuroscience to their skill set. We believe strongly that nihilism about the possible contributions of genetics and neuroscience to psychiatry is inappropriate and misguided. This science is the ticket out of the current state in which serious psychiatric disorders result in way too much disability and death.
This column was written by Eugene Rubin MD, PhD and Charles Zorumski MD.