Pellagra is a photosensitivity syndrome characterized by three “D's”: diarrhea, dermatitis, and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis, the hallmark abnormality of this syndrome, remain unclear. We prepared niacin deficient mice in order to develop a murine model of pellagra. Niacin deficiency induced photosensitivity and severe diarrhea with weight loss. In addition, niacin deficient mice exhibited elevated expressions of COX-2 and PGE syntheses (Ptges) mRNA. Consistently, photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. Moreover, enhanced PGE₂ production in niacin deficiency was mediated via ROS production in keratinocytes. In line with the above murine findings, human skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Niacin deficiency-induced photosensitivity was mediated through EP4 signaling in response to increased PGE₂ production via induction of ROS formation.

Continuous decrease in serum brain-derived neurotrophic factor (BDNF) levels in a neuropsychiatric syndrome of systemic lupus erythematosus patient with organic brain changes Atsuko Ikenouchi-Sugita, Reiji Yoshimura, Nobuhisa Ueda, Yuki Kodama, Wakako Umene-Nakano, Jun NakamuraDepartment of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, Japan In the present study, the authors reported on a case in neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) with irreversible organic brain changes. The authors also longitudinally investigated serum brain-derived neurotrophic factor (BDNF) levels in the patient. We found that serum BDNF levels in the NPSLE patient with irreversible organic brain change were consistently low, independent of the severity of psychiatric symptoms. Thus, the longitudinal measurement of serum BDNF levels might be useful in predicting the prognosis of NPSLE.Keywords: brain-derived neurotrophic factor; neuropsychiatric syndrome of systemic lupus erythematosus; organic brain change

Higher cortisol levels due to a hyperactive hypothalamic–pituitary–adrenal axis have been reported in patients with major depressive disorder (MDD). Increased cortisol levels change both the brain morphology and function in MDD patients. The multivariate source-based morphometry (SBM) technique has been applied to investigate neuroanatomical changes in some neuropsychiatric diseases, but not MDD. We aimed to examine the alterations in gray matter (GM) networks and their relationship with serum cortisol levels in first-episode, drug-naïve MDD patients using SBM. Forty-two patients with MDD and 39 controls were recruited via interviews. Morning serum cortisol levels were measured, and high-resolution T1-weighted imaging followed by SBM analysis was performed in all participants. The patients had significantly higher serum cortisol levels than the controls. We found two GM sources, which were significantly different between patients with MDD and controls (prefrontal network, p < .01; insula-temporal network, p < .01). Serum cortisol levels showed a statistically significant negative correlation with the loading coefficients of the prefrontal network (r = − 0.354, p = 0.02). In conclusion, increased serum cortisol levels were associated with reductions in the prefrontal network in the early stage of MDD, and SBM may be a useful approach for analyzing structural MRI data.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious but potentially treatable disease. However, biological markers such as IgG index or IL-6 do not always reflect the severity of the psychotic symptoms of NPSLE. We hypothesized that serum BDNF levels may be a biological marker for reflecting the severity of the psychiatric symptoms of NPSLE. The participants enrolled in this study were 28 healthy volunteers and 54 Japanese SLE inpatients at the University Hospital of Occupational and Environmental Health, all of whom fulfilled the criteria for the classification of SLE. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms including an acute confusional state, anxiety disorder, cognitive dysfunction, mood disorder, and psychosis (NP group); NPSLE without psychiatric symptoms (NN group); and SLE without neuropsychiatric symptoms (S group). The serum BDNF levels were measured by ELISA. Serum BDNF levels were significantly increased in the NP group (mean +/- SE = 37.0 +/- 5.46 ng/ml) compared with those in the other three groups (NN group; mean +/- SE = 9.1 +/- 2.44 ng/ml, P < 0.0001, S group; mean +/- SE = 10.4 +/- 2.51 ng/ml, P < 0.0001, healthy control; mean +/- SE = 11.44 +/- 0.69, P < 0.0001). Subsequently, serum BDNF levels were decreased in parallel with the improvement of psychiatric symptoms in the NP group. These results suggest that serum BDNF is a biological marker for the severity of psychiatric symptoms in NPSLE patients.