Research

The diagnostic concept of “schizophrenia” is over 100 years old. It was developed at a time when medical laboratory testing barely existed. The concept of schizophrenia was based on behavioral observations interpreted in the light of the dominant theories of the day. Those theories were based on the concepts of Freudian psychodynamics, germ theories of infection, and nerve degeneration. Those theories of causation have been almost entirely discredited as causes of schizophrenia.

The modern definition of schizophrenia has retained many of the original ideas, diverse as they are. The modern definition of schizophrenia undoubtedly captures a population of individuals who are similar only on a superficial level. Though outward behavioral symptoms may look similar, the underlying disease processes are numerous and distinctly different. This underlying diversity of biological cause is the best explanation for why some with schizophrenia derive rapid robust benefit from medication while others with similar outward symptoms are not helped by the same medication.

My major current research interest is the unusually sluggish response to niacin often seen in schizophrenia. Pharmacological doses of niacin cause most people to have a skin flush response. A similar skin flush response occurs when a sufficiently high concentration of methyl-niacin is applied to the skin. Many people with schizophrenia do not have a skin flush response to niacin.

The blunted skin flush response to niacin is interesting for several reasons:

• The niacin response abnormality is selectively associated with schizophrenia; it has not been found to any significant extent in bipolar disorder, depression, or other psychiatric illnesses.
• The niacin response abnormality is not an anomaly caused by psychotropic medications.
• The niacin response abnormality appears to be a heritable trait the occurs within schizophrenia-affected families
• Although we know relatively little about the biochemical pathways responsible for schizophrenia symptoms, the biochemistry and physiology of the niacin skin flush response is well understood.
• The chemical messengers responsible for niacin-induced skin flushing are the therapeutic targets of existing schizophrenia treatments.

Potential applications of the niacin skin test

• Understanding the biochemical cause of the abnormal niacin response is likely expand our understanding of the biochemistry of schizophrenia.
• The heritable nature of the niacin response abnormality within schizophrenia-affected families means that the skin test could be used as a tool to discover a schizophrenia risk gene.
• Because the niacin test in abnormal in only a portion of schizophrenia-affected people, the test may be a way to subtype the schizophrenias according to underlying differences in biochemistry.
• If those with an abnormal test have a better response to a particular form of treatment, then testing for niacin response might prove useful as a tool for a personalized medicine approach to schizophrenia treatment.