Schizophrenia Bulletin Open

Treatment-resistant schizophrenia (TRS) affects around 30% of patients with schizophrenia (SZ) resulting in poor functioning, relapses, and reduced quality of life. Convergent findings show that inflammation could contribute to resistance. We thus search for immune signatures of patients with TRS/ultra TRS (UTRS) in a sample of community-dwelling outpatients with SZ. In total, 195 stabilized SZ patients (mean age = 31.2 years, 73% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia in France and received a thorough clinical assessment. At inclusion, psychotic symptomatology was evaluated by the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Circulating serum/plasma levels of a large panel of markers reflecting the main inflammatory pathways were evaluated. TRS was defined by current treatment by clozapine (CLZ) and UTRS by current CLZ treatment + PANSS total score ≥ 70. The frequency of TRS and UTRS patients was, respectively, 20% and 7.7% and was defined using multivariable analysis elevated by high levels of interleukin (IL)-12/IL-23p40, IL-17A, IL-10, and beta 2 microglobulin (B2M) and IL-12/IL-23p40, IL-17A, IL-6, IL-10, IFNγ, and B2M, respectively. These observations suggest that resistance and ultra resistance to CLZ treatment are underpinned by pro-inflammatory molecules mainly belonging to the T helper 17 pathway, a finding making sense given the interplay between inflammation and antipsychotic treatment responses. If confirmed, our findings may allow us to consider IL-23/IL-17 pathway as a therapeutic target for patients with resistance to antipsychotics.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

Extramammary Paget's Disease of the Scrotum Associated with Hepatocellular Carcinoma

Extramammary Paget's disease (EMPD) is a rare cutaneous carcinoma of epidermal origin. The diagnosis is frequently delayed, and the disease tends to be associated with an underlying adnexal or internal malignancy. There have been several reports of EMPD associated with carcinoma of the bladder, prostate, kidney, and colon. The association of hepato-cellular carcinoma (HCC) with EMPD appears to be exceedingly rare; to our knowledge, it has been reported only once in the English literature. Herein, we report an unusual case of EMPD of the scrotum associated with HCC. EMPD was diagnosed 1 year after the appearance of an erythematous plaque, and HCC was noted 19 months after the diagnosis of EMPD. From our experience and literature review, in patients with nonspecific skin lesions that are unresponsive to conventional treatment, EMPD should be considered and skin biopsy performed. Long-term follow-up is needed to watch for the appearance of adnexal carcinoma or internal malignancy. [J Chin Med Assoc 2009;72(10):542–546

Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis

Human endogenous retroviruses (HERVs) are remnants of infections that took place several million years ago and represent around 8% of the human genome. Despite evidence implicating increased expression of HERV type W envelope (HERV-W ENV) in schizophrenia and bipolar disorder, it remains unknown whether such expression is associated with distinct clinical or biological characteristics and symptoms. Accordingly, we performed unsupervised two-step clustering of a multivariate data set that included HERV-W ENV protein antigenemia, serum cytokine levels, childhood trauma scores, and clinical data of cohorts of patients with schizophrenia (n = 29), bipolar disorder (n = 43) and healthy controls (n = 32). We found that subsets of patients with schizophrenia (~41%) and bipolar disorder (~28%) show positive antigenemia for HERV-W ENV protein, whereas the large majority (96%) of controls was found to be negative for ENV protein. Unsupervised cluster analysis identified the presence of two main clusters of patients, which were best predicted by the presence or absence of HERV-W ENV protein. HERV-W expression was associated with increased serum levels of inflammatory cytokines and higher childhood maltreatment scores. Furthermore, patients with schizophrenia who were positive for HERV-W ENV protein showed more manic symptoms and higher daily chlorpromazine (CPZ) equivalents, whereas HERV-W ENV positive patients with bipolar disorder were found to have an earlier disease onset than those who were negative for HERV-W ENV protein. Taken together, our study suggest that HERV-W ENV protein antigenemia and cytokines can be used to stratify patients with major mood and psychotic disorders into subgroups with differing inflammatory and clinical profiles.ISSN:2158-318

Immune signatures of treatment resistant schizophrenia: a FACE-SZ study

International audienc