Clinical phenotypes of Behçet's syndrome in a large cohort of Italian patients: focus on gender differences.

Objective: The aim of this study was to investigate the clinical phenotypes of Italian patients with Behçet's syndrome (BS) according to gender. BS is a rare chronic multisystemic disorder with a wide spectrum of clinical manifestations. Human leucocyte antigen (HLA)-B51, gender, and ethnicity have been suggested as factors that could influence the clinical manifestations in BS patients. To date, few data assessing gender differences in Italian BS patients are available in the literature.Method: We retrospectively evaluated a group of Italian patients seen consecutively at our dedicated tertiary centre from 1 January 2000 to 31 May 2018. Demographics, clinical features during follow-up, and HLA status were obtained from a review of medical records and analysed in male and female groups.Results: In total, 285 [168 male (M) and 117 female (F)] patients were eligible for the study. Males had papulopustolar lesions, posterior uveitis, and deep venous thrombosis more often than females (83.3% M vs 46.2% F, 36.9% M vs 18.8% F, and 8.3% M vs 0.9% F, respectively; p < 0.01). Erythema nodosum (59.0% F vs 41.1% M; p < 0.01) and arthralgia (52.1% F vs 31.6% M; p < 0.01) were more frequent in females. No differences were found in HLA-B51 status (59.2% M vs 59.0% F).Conclusion: In our Italian cohort, BS was slightly more prevalent in males. Some gender-related differences were observed when comparing male and female cohorts. The data also confirmed that BS tends to be less aggressive in Italian female patients.

ERAP1 molecular characterization: Identification of a de novo allelic variant.

The novel ERAP1 allelic variant is a missense polymorphism leading to the Arg53Pro substitution.

Adolescence is the starting point of sex-dichotomous COMT genetic effects.

The catechol-o-methyltransferase (COMT) genetic variations produce pleiotropic behavioral/neuroanatomical effects. Some of these effects may vary among sexes. However, the developmental trajectories of COMT-by-sex interactions are unclear. Here we found that extreme COMT reduction, in both humans (22q11.2 deletion syndrome COMT Met) and mice (COMT-/-), was associated to cortical thinning only after puberty and only in females. Molecular biomarkers, such as tyrosine hydroxylase, Akt and neuronal/cellular counting, confirmed that COMT-by-sex divergent effects started to appear at the cortical level during puberty. These biochemical differences were absent in infancy. Finally, developmental cognitive assessment in 22q11DS and COMT knockout mice established that COMT-by-sex-dichotomous effects in executive functions were already apparent in adolescence. These findings uncover that genetic variations severely reducing COMT result in detrimental cortical and cognitive development selectively in females after their sexual maturity. This highlights the importance of taking into account the combined effect of genetics, sex and developmental stage.

Implication of reward alterations in the expression of negative symptoms in 22q11.2 deletion syndrome: a behavioural and DTI study.

BACKGROUND: Alterations of the reward system have been proposed as one of the core mechanisms underlying the expression of negative symptoms in schizophrenia. Specifically, deficits in specific reward components and white matter (WM) integrity of the reward system have been highlighted. The putative link between negative symptoms and the hedonic experience, or structural connectivity of the reward system has never been examined in the 22q11.2 deletion syndrome (22q11DS), a condition with increased risk for psychosis. METHOD: Anticipatory and consummatory dimensions of pleasure were assessed in participants with 22q11DS (N = 54) and healthy controls (N = 55). In patients with 22q11DS, the association between pleasure scores and positive or negative symptoms was investigated. Furthermore, WM integrity of the accumbofrontal tract was quantified using diffusion tensor imaging (DTI). Associations between DTI measures, pleasure dimensions and negative symptoms were examined. RESULTS: Patients with 22q11DS showed reduced anticipatory and consummatory pleasure compared to controls. Furthermore, anticipatory pleasure scores were negatively correlated to negative and positive symptoms in 22q11DS. WM microstructural changes of the accumbofrontal tract in terms of increased fractional anisotropy and reduced radial anisotropy were also identified in patients. However, no significant correlation between the DTI measures and pleasure dimensions or psychotic symptoms was observed. CONCLUSIONS: This study revealed that participants with 22q11DS differed in their experience of pleasure compared to controls. The anticipatory pleasure component appears to be related to negative and positive symptom severity in patients. Alterations of WM integrity of the accumbofrontal tract seem to be related to myelination abnormalities in 22q11DS patients.

Long-range dysconnectivity in frontal and midline structures is associated to psychosis in 22q11.2 deletion syndrome.

Patients affected by 22q11.2 deletion syndrome (22q11DS) present a characteristic cognitive and psychiatric profile and have a genetic predisposition to develop schizophrenia. Although brain morphological alterations have been shown in the syndrome, they do not entirely account for the complex clinical picture of the patients with 22q11DS and for their high risk of psychotic symptoms. Since Friston proposed the "disconnection hypothesis" in 1998, schizophrenia is commonly considered as a disorder of brain connectivity. In this study, we review existing evidence pointing to altered brain structural and functional connectivity in 22q11DS, with a specific focus on the role of dysconnectivity in the emergence of psychotic symptoms. We show that widespread alterations of structural and functional connectivity have been described in association with 22q11DS. Moreover, alterations involving long-range association tracts as well as midline structures, such as the corpus callosum and the cingulate gyrus, have been associated with psychotic symptoms in this population. These results suggest common mechanisms for schizophrenia in syndromic and non-syndromic populations. Future directions for investigations are also discussed.

Vibrotactile forward masking as a function of age.

Thresholds for the detection of a 50-ms test stimulus delivered to the thenar eminence were measured as a function of the time interval between the offset of a 500-ms masking stimulus and the onset of the test stimulus (delta t). The frequency of the masker and the test stimulus was the same during a particular testing session and was either 25 or 250 Hz. At all values of delta t, older subjects exhibited significantly more masking than did young subjects. The effects of age were greater for stimuli that primarily affect the Pacinian system (250 Hz) than those that primarily affect non-Pacinian systems (25 Hz). Psychophysical measurements of the apparent duration of tactile sensations suggest that both sensory persistence and adaptation are affected by aging. Since adaptation seemed to be the more dominant factor for stimuli with durations as long as 500 ms, it was concluded that the effects of aging on forward masking seen in our study were due mainly to increased amounts of adaptation produced by the masker.