Familial Aggregation in Skin Flush Response to Niacin Patch Among Schizophrenic Patients and Their Nonpsychotic Relatives

Abstract

Though a reduced flush response to niacin has been found in schizophrenic patients, whether it is a vulnerability indicator to schizophrenia remains little known. We aimed to examine the familial aggregation in niacin flush response among schizophrenic patients and their nonpsychotic relatives. In a sample of 153 schizophrenia probands, 217 parents, 70 siblings, and 94 normal subjects, 3 concentrations (0.001 M, 0.01 M, and 0.1 M) of niacin were applied to the forearm skin and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. Both the heritability for continuous flush scores and the recurrence risk ratios for binary non-flush response in the nonpsychotic relatives of schizophrenic patients were estimated, and ordinal logistic regression analyses of relatives' niacin response on probands' were further conducted to adjust for potential confounders. The greatest heritabilities ranged from 47% (0.01 M at 10 minutes) to 54% (0.1 M at 5 minutes). The risk ratios of 0.01 M at 10 minutes (ranging from 2.60 for using score 1 or less to 5.06 for using score 0 as non-flush) and 5 minutes (1.66 for using score 0 as non-flush) were significantly greater than one. Multiple ordinal logistic regression analyses further revealed that the association between probands and relatives in niacin flush response remained after adjustment for potential confounders, including age, sex, allergy, tobacco smoking, and coffee drinking. These findings provide support for the potential of niacin flush response as a vulnerability indicator to schizophrenia.

Comparison of Niacin Skin Flush Response in Patients with Schizophrenia and Bipolar Disorder

“…Lin et al demonstrated impaired flush response to niacin in patients' relatives (31). These investigators further found more impairment in families with more than one sibling with schizophrenia (multiplex families) compared to those families with one 6…”

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

“…If such drugs do tend to normalize niacin sensitivity, then the potential bias in patient sample would be to underestimate the prevalence or magnitude of the niacin response abnormality in SZ. Taken together, comparing the niacin-induced flushing between medicated and unmedicated SZ patients, or unmedicated, non-psychotic relatives, suggests that the niacin response abnormality in SZ is not an artifact of antipsychotic medications (Chang et al, 2009;Lin et al, 2007;Maclean et al, 2003;Shah et al, 2000).…”

A Genome-wide Quantitative Linkage Scan of Niacin Skin Flush Response in Families With Schizophrenia

“…2 Depending on the criteria to define nonresponse, the prevalence estimates of impaired flush response to the niacin skin patch in schizophrenia patients ranged from 49% to 90%, whereas those in healthy controls ranged from 8% to 64%. [8][9][10] The impaired niacin flush response was specific to schizophrenia and not observed in depression, 11 bipolar disorder, [12][13][14] or autism. 15 One study in healthy subjects showed that age and gender might be associated with the niacin flush response.…”

“…16 The impaired niacin flush response in schizophrenia patients was not influenced by medication status, 17,18 antipsychotic drug doses, 14,19 or substance use such as tobacco smoking, 13,14,17 coffee drinking, 14 or alcohol consumption. 14,17 Attenuated niacin flush response has also been demonstrated in nonpsychotic first-degree relatives of patients with schizophrenia, 9,17,20 with a heritability of 47% to 54%. 9 Greater familial loading for schizophrenia was associated with more impairment in flush response to niacin.…”

“…14,17 Attenuated niacin flush response has also been demonstrated in nonpsychotic first-degree relatives of patients with schizophrenia, 9,17,20 with a heritability of 47% to 54%. 9 Greater familial loading for schizophrenia was associated with more impairment in flush response to niacin. 21 Those clues implied that the niacin flush response may be a useful trait for QTL genome-wide linkage scans for schizophrenia.…”