Impaired Flush Response to Niacin Skin Patch Among Schizophrenia Patients and Their Nonpsychotic Relatives: The Effect of Genetic Loading

Abstract

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia.

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

“…The data indicate that genetic background affects the flush response to niacin (14). In contrast to these studies, and consistent with our findings, the study by Smesny et al found no impaired niacin skin response in relatives of schizophrenic patients (16).…”

“…In the study by Liu et al, also the greatest degree of differentiation occurred at the 0.01 M concentration, but with the rating time point of 10 minutes (18). However, in the study by Change et al, the differentiation was better using 0.1 M compared to 0.01 M or 0.001 M concentrations of niacin (14). The skin flush response evaluation method also can affect the test properties and the optimal solution concentration and evaluation time point (29).…”

“…This inflammatory response can cause skin vasodilatation and redor (flushing) which is about four times greater in healthy control subjects compared with schizophrenic patients (10)(11)(12)(13). Some studies also showed that skin flush response to niacin is more impaired in the relatives of schizophrenic patients indicating the genetic aspect of schizophrenia (14,15). However, there have been controversies in this regard (16) and it is not known whether this phenomenon can be generalized to other psychiatric disorders.…”

Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

“…Similarly, it appears that nicotine use has no effect on the niacin-induced flushing response (Chang et al, 2009;Liu et al, 2007;Messamore, 2003Messamore, , 2010Ross et al, 2004;Shah et al, 2000;Smesny et al, 2003). Our recent findings (Yao et al, 2015) also support the notion that niacin sensitivity is not significantly affected by smoking.…”

“…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).…”