The Chemical Factory Inside Your Head

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Most neuromodulators bind to more than one receptor, and different receptors predominate in different parts of the brain. This makes the whole biochemical brain map even more complex and intriguing. Some of the neuroimaging tools of modern neuroscience, for example, positron emission tomography (PET) and magnetic resonance spectroscopy (MRS), help elucidate the anatomical distribution of neurotransmitter and neuromodulator pathways and their receptors both in the normal brain and in brain disease. These techniques also help clarify the mode of action of various pharmaceuticals designed to treat neurological and psychiatric disorders.

Expanding our knowledge of brain biochemistry has been essential for the development of treatments for a wide range of brain disorders under the broad term of “psychopharmacology.”

Several approaches are used, some of which act by modifying the synthesis of the neurotransmitter or neuromodulator by using various methods, such as providing extra supplies of “precursor” chemicals, and others by modifying the rate at which these substances are broken down in the synapse, or by blocking the receptors to which they bind.

Through such methods, different neurotransmitters and neuromodulators are targeted to treat different disorders. The last few decades have witnessed a growing sophistication and precision of these approaches:

  • Stimulants used to treat attention deficit hyperactivity disorder (ADHD) and related conditions act on norepinephrine and dopamine. Pharmacological treatment of Parkinson’s disease targets one of several dopamine systems in the brain by increasing its activity.
  • Treatments of schizophrenia target a different dopamine system by “down-regulating” it — that is, by making it less active.
  • The most common treatments for depression target the serotonergic system by “up-regulating” it — that is, by making it more active.
  • Most pharmacological interventions aimed at reducing memory impairments and other cognitive symptoms of Alzheimer’s disease, and of certain other dementias (for example, Lewy body disease) target the cholinergic system by interfering with the breakdown of acetylcholine in the synapse and thus prolonging its action. More recently, glutamate has also been targeted as a way of alleviating the cognitive symptoms of Alzheimer’s disease.

The Future of Pharmacology

There is an ever-growing pharmacological arsenal for the treatment of seizure disorders, obsessive-compulsive disorder, Tourette’s syndrome and other conditions. Further advances in our understanding of brain biochemistry will translate into the design of novel, effective, and increasingly more precise pharmacologies to treat a wide range of brain disorders.

There is also growing evidence, albeit still preliminary, that various nonpharmacological interventions — such as cognitive exercise and psychotherapy — may impact brain biochemistry in positive ways by impacting the number of certain neurotransmitter receptor sites and possibly through other mechanisms as well. These findings lead to a tantalizing conclusion, which until relatively recently would have been rejected by most scientists as highly implausible: namely, that a two-way relationship exists between brain biochemistry and brain activities. Not only does brain biochemistry affect mental processes, but mental processes affect brain biochemistry.

Traditionally, psychopharmacology has been used to treat various neurological and psychiatric conditions. More recently, the idea of expanding the use of psychopharmacology to enhance normal cognition has been attracting increasing attention and interest.

The application of psychopharmacology as a cognitive-performance enhancer, and not just as a tool of psychiatry and neurology, remains controversial and is mired in a whole array of ethical and practical issues. Supporters argue that if certain innovative ways of expanding the limits of our cognition exist then it is self-defeating for society not to use them in our increasingly information-processing-dependent world, while the detractors are concerned about the unknown long-term effects of psychopharmacology in healthy individuals, and raise the “even playing field” argument to prevent its use.

For now, the use of pharmacology as the enhancer of normal cognition is a matter of a somewhat futuristic debate rather than of imminent reality, but society evolves rapidly these days and the future may be upon us before we know it.

Through the convergence of efforts by several disciplines — neuroscience, neuropsychology, pharmacology, neuroimaging, and others — science is gaining an ever-deeper understanding of the brain’s chemical factory, and in so doing is discovering innovative ways of applying this knowledge to solving a wide range of practical challenges facing society.

Elkhonon Goldberg, Ph.D., is a scientist, clinician, educator, and author. He conducts cognitive neuroscience research at New York University School of Medicine, has an active practice in clinical neuropsychology in Manhattan, and lectures worldwide. Goldberg’s books, which have been translated into many languages, include “The New Executive Brain: Frontal Lobes in a Complex World.”

This article was first published in Brain World Magazine’s Fall 2010 issue.

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