Linking novelty seeking and harm avoidance personality traits to cerebellar volumes

Personality traits are multidimensional traits comprising cognitive, emotional, and behavioral characteristics, and a wide array of cerebral structures mediate individual variability. Differences in personality traits covary with brain morphometry in specific brain regions, and neuroimaging studies showed structural or functional abnormalities of cerebellum in subjects with personality disorders, suggesting a cerebellar role in affective processing and an effect on personality characteristics. To test the hypothesis that cerebellar [white matter (WM) and cortex] volumes are correlated with scores obtained in the four temperamental scales of the Temperament and Character Inventory (TCI) by Cloninger, a total of 125 healthy participants aged 18–67 years of both genders (males = 52) completed the TCI and underwent magnetic resonance imaging. The scores obtained in each temperamental scale were associated with the volumes of cerebellar WM and cortex of right and left hemispheres separately by using linear regression analyses. In line with our hypothesis, novelty seeking (NS) scores were positively associated with WM and cortex cerebellar volumes. Harm avoidance (HA) scores were negatively associated with WM and cortex cerebellar volumes. The range of individual differences in NS and HA scores reflects the range of variances of cerebellar volumes. The present data indicating a cerebellar substrate for some personality traits extend the relationship between personality and brain areas to a structure up to now thought to be involved mainly in motor and cognitive functions, much less in emotional processes and even less in personality individual differences. Hum Brain Mapp 35:285–296, 2014. © 2012 Wiley Periodicals, Inc.     

A new mutation in GJC2 associated with subclinical leukodystrophy

Recessive mutations in GJC2, the gene-encoding connexin 47 (Cx47), cause Pelizaeus–Merzbacher-like disease type 1, a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype––hereditary spastic paraplegia type 44. Here, we present evidence that a novel Arg98Leu mutation causes an even milder phenotype––a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady-state junctional conductance–junctional voltage (G _j–V _j) relations differed only slightly from those for wild-type Cx47. Our data suggest that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes.     

Biologic agents for rheumatoid arthritis: Can we hypothesize new strategies of treatment?

Rheumatoid arthritis is a complex multifactorial disease, whose pathogenesis has not been fully elucidated. Biologic agents have revolutionized RA treatment, but a significant percentage of patients does not obtain an adequate response to the therapy. Most of the biologic agents do better if combined with conventional immunosuppressive DMARDs and they show a similar efficacy profile: most of the responders achieve the minimum desirable level of response (ACR20) and only few patients obtain a worthwhile clinical improvement (ACR70 or better). We need to identify new strategies of treatment, able to comply the non satisfied needs of RA patients. Taking inspiration from other medical fields, we could hypothesize a combined regimen in which biologic agents are administered simultaneously at a low or ultra-low dosage, targeting several pathogenetic mechanisms but avoiding important side effects. Alternatively it should be useful to identify rapid succession regimens in which biologic drugs are taken according to an established sequence. Research in this field is obviously not encouraged by pharmaceutical industries, but our efforts should be driven in this direction. According to these observations, adequate clinical trials should be designed to search for appropriate drugs associations and dosages.     

ICON: The Early Diagnosis of Congenital Immunodeficiencies

Primary immunodeficiencies are intrinsic defects in the immune system that result in a predisposition to infection and are frequently accompanied by a propensity to autoimmunity and/or immunedysregulation. Primary immunodeficiencies can be divided into innate immunodeficiencies, phagocytic deficiencies, complement deficiencies, disorders of T cells and B cells (combined immunodeficiencies), antibody deficiencies and immunodeficiencies associated with syndromes. Diseases of immune dysregulation and autoinflammatory disorder are many times also included although the immunodeficiency in these disorders are often secondary to the autoimmunity or immune dysregulation and/or secondary immunosuppression used to control these disorders. Congenital primary immunodeficiencies typically manifest early in life although delayed onset are increasingly recognized. The early diagnosis of congenital immunodeficiencies is essential for optimal management and improved outcomes. In this International Consensus (ICON) document, we provide the salient features of the most common congenital immunodeficiencies.     

Linking novelty seeking and harm avoidance personality traits to basal ganglia: volumetry and mean diffusivity

Novelty Seeking (NS) and Harm Avoidance (HA) temperamental traits are related to approaching or avoiding motivational circuits relying on the integrity and functionality of distributed brain areas implicated in arousal and action. The present study verified whether and how macro- and micro-structural variations of basal ganglia are correlated with scores obtained in the NS and HA temperamental scales of the Temperament and Character Inventory by Cloninger. To this aim, 125 healthy adults aged 18–67 years of both sexes completed the Temperament and Character Inventory and underwent a high-resolution T1-weighted magnetic resonance imaging and a diffusion tensor imaging using a 3T scanner. The scores obtained in the temperamental scales were associated with volumes, mean diffusivity and fractional anisotropy measures of basal ganglia of both hemispheres separately, by using linear regression analyses. We found increased bilateral caudate and pallidum volumes associated with higher NS scores, as well as increased mean diffusivity in the bilateral putamen associated with higher HA scores. Macro- and micro-structural variations of basal ganglia regions contribute to explain the biological variance associated with NS or HA personality phenotype. The present findings evidencing some brain-temperament relationships highlight the importance of obtaining macro- and micro-structural measures in relation to individual differences.     

Interleukin-4 down-regulates MHC class II antigens on cultured rat astrocytes

Mammalian cerebral astrocytes can be brought to express major histocompatibility complex (MHC) class II molecules upon appropriate stimulation. It is well established that this expression is subject to modulation by several neurotransmitters and cytokines. We show that the low, basal expression of MHC class II antigens on cultured rat astrocytes is concentration-dependently down-regulated by low concentrations of interleukin-4 (IL-4), reaching maximal inhibition at 10 U/ml. The higher, γ-IFN-induced, expression of class II molecules is also decreased by increasing concentrations of IL-4, significant effects being already observed at 5 U/ml. Since the cAMP as well as the nitric oxide dependent cGMP pathway have previously been shown to mediate an inhibition on astroglial MHC class II expression, we measured the intra-cellular content of cyclic nucleotides after stimulation with IL-4. No rise in cAMP or cGMP is detected. Similarly, IL-4 does not affect the induced synthesis of nitric oxide radicals. Since MHC class II expression is a critical step in many regulatory processes of the cellular immune reaction, IL-4, via its activity on astroglial cells, emerges as an important modulator of immunological activities in the central nervous system. © 1996 Wiley-Liss, Inc.