Abnormal niacin response may be a marker for schizophrenia

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - An abnormal response to niacin may help doctors differentiate between schizophrenia and bipolar disorder, new research suggests.

"In our study of niacin response characteristics among 216 volunteers - the largest study of its kind - we demonstrated that the presence of an abnormal niacin response is specific to schizophrenia, not bipolar disorder, and that the presence of an abnormal niacin response can distinguish between schizophrenia and bipolar disorder with 97% specificity," lead study author Dr. Jeffrey K. Yao of the University of Pittsburgh, Pennsylvania, told Reuters Health by email.

"In patients with schizophrenia, we repeatedly observed an abnormally low sensitivity to the skin flush effect of niacin. We also showed that the abnormality is only present in a subset of schizophrenia patients we believe are physiologically distinct from others. These patients are likely to have abnormal functioning of arachidonic acid-derived chemical messengers," he said.

"We provide evidence that not all schizophrenias are physiologically similar - that some schizophrenias are characterized by an abnormal niacin response, and we show that niacin subsensitivity rarely occurs in bipolar disorder," Dr. Yao said.

Dr. Yao and colleagues used a laser Doppler flowmeter to estimate the prevalence of the niacin response abnormality (NRA) and its specificity in voluntary participants, ages 18 to 65, from the Veterans Affairs Pittsburgh Healthcare System. They recruited 70 patients with schizophrenia, 59 with bipolar disorder, and 87 healthy controls.

From the dose-response curves, the researchers calculated the concentration of methylnicotinate required to elicit a half-maximal blood flow response - i.e., the effective concentration (EC) 50 value - and maximal blood-flow value for each participant. The median log10EC50 of the schizophrenia group was above the third quartile of log10EC50 of either the healthy control or bipolar groups, while the maximal blood flow was significantly lower in the schizophrenia group than in the other two groups.

The authors defined NRA as having both EC50 above the 90th percentile of the control samples and maximal blood flow response below the 60th percentile for the control range. The NRA predicted schizophrenia with 31% sensitivity and 97% specificity.

Age, gender, race, or cigarette smoking did not influence the NRA, the authors reported online September 14 in Schizophrenia Bulletin.

"It is extremely unlikely that schizophrenia arises from a single cause. In fact, the variable therapeutic response to antipsychotic medication provides strong evidence against a unitary cause of schizophrenia. It is important to discover physiologically distinct subtypes of schizophrenia. Niacin sensitivity may be a viable method to subtype the schizophrenias," Dr. Yao said.

"The niacin skin flush response is mediated by chemical messengers derived from arachidonic acid stored in the phospholipids of cellular membranes," he said. "Therefore, an abnormal niacin response suggests that arachidonic acid-derived signals are disrupted in the niacin-subsensitive subtype of schizophrenia."

"Quantitative measuring (of) niacin-induced skin flush by a laser Doppler flowmeter is noninvasive, which could lead to improved diagnosis for early detection of the illness. The identified schizophrenia-subtype may also be valuable in early specific treatment," he added.

Dr. Yao explained that these findings, if validated, may lead to a lab test to help discern between schizophrenia and bipolar disorder, may help identify people at risk of developing psychosis, and may result in new treatments.

"We do not believe that all patients have phospholipid metabolism abnormalities, but understanding pathogenesis in even a subgroup of patients will be an important advance. A physiological abnormality that is present in one-third of patients - and is virtually absent in other psychiatric illnesses - is worthy of better understanding," he added.

Dr. William Hoffman, associate professor in the Departments of Psychiatry and Behavioral Neuroscience at Oregon Health and Science University (OHSU) in Portland told Reuters Health by email, "Other purported endophenotypes, such as deficient prepulse inhibition, decreased brain volume, or genetic associations, may statistically separate patients and controls, but none can claim the status of pathognomonic biomarker."

"The promise of this, and other, investigations of endophenotypes is that patients could be matched to specific pharmacological and non-pharmacological treatments," he added.

Dr. Demian Rose, assistant professor in the Department of Psychiatry of the University of California, San Francisco, told Reuters Health by email, "The niacin response could add novel information and enhance a clinical assessment's predictive value. With further study, it also opens up the possibility of new treatments for a defined subpopulation of patients with schizophrenia, most of whom currently receive a one-size-fits-all treatment regimen, due to our inability to discriminate clinical subtypes."

"The trick is to find biological indicators for quantifiable subtypes of schizophrenia and use those indicators to guide treatment choices," said Dr. Aaron Janowsky, professor in the Departments of Psychiatry and Behavioral Neuroscience of OHSU, in an email. "Those kinds of studies are ongoing."

Drs. Hoffman, Janowsky, and Rose were not involved in the study.

The Department of Veterans Affairs partially supported this research.

SOURCE: http://bit.ly/1R7oZKg

Schizophr Bull 2015.

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