Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis.

In multiple sclerosis, microstructural damage of normal-appearing brain tissue is an important feature of its pathology. Understanding these mechanisms is vital to help develop neuroprotective strategies. The visual pathway is a key model to study mechanisms of damage and recovery in demyelination. Anterograde trans-synaptic degeneration across the lateral geniculate nuclei has been suggested as a mechanism of tissue damage to explain optic radiation abnormalities seen in association with demyelinating disease and optic neuritis, although evidence for this has relied solely on cross-sectional studies. We therefore aimed to assess: (i) longitudinal changes in the diffusion properties of optic radiations after optic neuritis suggesting trans-synaptic degeneration; (ii) the predictive value of early optic nerve magnetic resonance imaging measures for late optic radiations changes; and (iii) the impact on visual outcome of both optic nerve and brain post-optic neuritis changes. Twenty-eight consecutive patients with acute optic neuritis and eight healthy controls were assessed visually (logMAR, colour vision, and Sloan 1.25%, 5%, 25%) and by magnetic resonance imaging, at baseline, 3, 6, and 12 months. Magnetic resonance imaging sequences performed (and metrics obtained) were: (i) optic nerve fluid-attenuated inversion-recovery (optic nerve cross-sectional area); (ii) optic nerve proton density fast spin-echo (optic nerve proton density-lesion length); (iii) optic nerve post-gadolinium T1-weighted (Gd-enhanced lesion length); and (iv) brain diffusion-weighted imaging (to derive optic radiation fractional anisotropy, radial diffusivity, and axial diffusivity). Mixed-effects and multivariate regression models were performed, adjusting for age, gender, and optic radiation lesion load. These identified changes over time and associations between early optic nerve measures and 1-year global optic radiation/clinical measures. The fractional anisotropy in patients' optic radiations decreased (P = 0.018) and radial diffusivity increased (P = 0.002) over 1 year following optic neuritis, whereas optic radiation measures were unchanged in controls. Also, smaller cross-sectional areas of affected optic nerves at 3 months post-optic neuritis predicted lower fractional anisotropy and higher radial diffusivity at 1 year (P = 0.007) in the optic radiations, whereas none of the inflammatory measures of the optic nerve predicted changes in optic radiations. Finally, greater Gd-enhanced lesion length at baseline and greater optic nerve proton density-lesion length at 1 year were associated with worse visual function at 1 year (P = 0.034 for both). Neither the cross-sectional area of the affected optic nerve after optic neuritis nor the damage in optic radiations was associated with 1-year visual outcome. Our longitudinal study shows that, after optic neuritis, there is progressive damage to the optic radiations, greater in patients with early residual optic nerve atrophy, even after adjusting for optic radiation lesions. These findings provide evidence for trans-synaptic degeneration.

Schizotypy and personality profiles of Cluster A in a group of schizophrenic patients and their siblings.

BACKGROUND: Schizotypy, or the set of personality traits related to schizophrenia, is considered an endophenotypic manifestation that is more represented in first-degree relatives of patients with schizophrenia than in the general population. The assessment of schizotypy is primarily based on self-reports, and for this reason it presents several limitations. In order to assess schizotypy, this study proposes a diagnostic instrument based on clinical reports. METHODS: A sample of 66 subjects, composed of 25 outpatients with schizophrenia, 18 siblings of these patients and 23 healthy controls, was subjected to the personality assessment test SWAP-200 by trained clinical interviewers. To test the hypothesis of the difference between the profiles of the Personality Disorders within the schizophrenia spectrum, a Multivariate Analysis of Variance and subsequent planned comparisons were conducted. RESULTS: Patients with schizophrenia scored higher than both their siblings and the controls on all SWAP-200 scales; their siblings, compared to the healthy controls, showed significant statistical differences, with higher mean scores for paranoid (F(1,63) = 7.02; p = 0.01), schizoid (F(1,63) = 6.56; p = 0.013) and schizotypal (F(1,63) = 6.47; p = 0.013) traits (PD T scores of Cluster A and Q-factor scores for the schizoid scale [F(1,63) = 6.47; p = 0.013]). CONCLUSIONS: Consistent with previous data, first-degree relatives of patients with schizophrenia scored higher on schizophrenia-related personality traits than a general population comparison sample. SWAP-200, as an alternative diagnostic instrument to self-report measures, is able to reveal the higher prevalence of schizotypal traits in siblings of patients with schizophrenia, suggesting its possible use as a complementary instrument for the assessment of schizophrenia.

The relationship between alexithymia and circulating cytokine levels in subjects undergoing upper endoscopy.

OBJECTIVE: Despite emerging evidence suggesting a link between alexithymia and immune function, previous studies yielded contrasting results. The proposed link between alexithymia and immune function remains controversial as does the role, in this relationship, of anxiety, depression and subjective stress. The aim of the study is to investigate the possible association between alexithymia and circulating levels of cytokines in subjects awaiting an upper endoscopy, a stressful procedure, controlling for anxiety levels, depression and subjective stress. METHODS: Participants were recruited from among consecutive patients referred for routine diagnostic upper endoscopy. All participants completed the Toronto Alexithymia Scale (TAS-20), the Hospital Anxiety and Depression Scale, and the Stress-related Vulnerability Scale. Serum levels of IL-1ß, IL-4, IL-6, IL-10, TNF-α and IFN-γ were measured by ELISA. RESULTS: Of the 90 subjects initially approached, 68 completed the study. The TAS-20 identified 22 alexithymic and 36 non-alexithymic patients. ELISA detected significantly lower IL-4 and IL-6 concentrations in alexithymic than in non-alexithymic patients. According to multiple linear regression analysis, alexithymia predicted low IL-4 and IL-6 levels in the sample overall, independently of stress, anxiety, depression and other possible confounders. No between-group differences were found in serum levels of IFN-γ, IL-1ß, and TNF-α. CONCLUSION: These findings argue against an isolated shift towards pro-inflammatory or anti-inflammatory mediators and suggest that circulating cytokine profiles differ in alexithymic and non-alexithymic subjects.

[Personality disorders self-inflicted woundings in detention]. / Disturbi di personalità e autolesionismo in ambito penitenziario.

Personality disorders, especially borderline and antisocial, are pre-eminent in a penitentiary. Under detention, among 100 patients valuated, 75% have a personality disorder; the 55% of these is diagnosed with borderline personality, while the 20% have a diagnosis of antisocial personality. Borderline disorder is often unnoticed instead of antisocial that is emphasized by self-inflicted wounding and behavioural disorders. The most frequent self-damaging behaviours are, first of all, slashes, then ingestion of foreign bodies and finally burnings and using sharp objects. Environment associated with narrowness, overcrowding, low drugs effects, heighten self-inflicted wounding. Psychiatrists, psychologists and prison guards must consider this manipulative, recriminating, self-therapeutic behavioural way aimed just by obtaining benefits.

Negative functional brain networks.

The anticorrelations in fMRI measurements are still not well characterized, but some new evidences point to a possible physiological role. We explored the topology of functional brain networks characterized by negative edgess and their possible alterations in schizophrenia, using functional images of 8 healthy subjects and 8 schizophrenic patients in a resting state condition. In order to minimize the insertion of artifactual negative correlations, the preprocessing of images was carried out by the CompCorr procedure, and the results compared with the Global Signal Regression (GSR) procedure. The degree distribution, the centrality, the efficiency and the rich-club behavior were used to characterize the functional brain network with negative links of healthy controls in comparison with schizophrenic patients. The results show that functional brain networks with both positive and negative values have a truncated power-law degree distribution. Moreover, although functional brain networks characterized by negative values have not small-world topology, they show a specific disassortative configuration: the more connected nodes tend to have fewer connections between them. This feature is lost using the GSR procedure. Finally, the comparison with schizophrenic patients showed a decreased (local and global) efficiency associated to a decreased connectivity among central nodes. As a conclusion, functional brain networks characterized by negative values, despite lacking a well defined topology, show specific features, different from random, and indicate an implication in the alterations associated to schizophrenia.

[Functional magnetic resonance imaging in subjects at high risk for schizophrenia: a review]. / La risonanza magnetica funzionale nei soggetti ad alto rischio per la schizofrenia.

Functional magnetic resonance (fMRI) has an important role in the study of the vulnerability to psychosis: it is an essential tool to search for endophenotypes that can let us to understand the pathophysiological mechanisms of schizophrenia and increase the ability to predict the onset of the illness. In this review are summarized results of the fMRI studies conducted on individuals at enhanced risk for developing psychosis, for clinical or genetic reasons. The cerebral activity in this kind of subjects appear in most cases more similar to that of individuals affected than to that of normal controls; this increases the possibility, in the future, for a diagnostic role of the cerebral activation. Nevertheless the technology is too young and the studies are too heterogeneous to reach conclusive results.

Medial frontal gyrus alterations in schizophrenia: relationship with duration of illness and executive dysfunction.

Executive functioning is consistently impaired in schizophrenia, and it has been associated with reduced gray matter volume in prefrontal areas. Abnormalities in prefrontal brain regions have also been related to the illness duration. The aim of the study was to investigate the effect of executive functioning decline and chronicity in prefrontal regions of patients with schizophrenia. Participants comprised 33 schizophrenic patients, 18 with duration of illness (DoI) shorter than 10 years and 15 with duration of illness longer than 10 years. In addition, 24 healthy controls served as a comparison group. Participants performed the Wisconsin Card Sorting Test (WCST) and underwent structural magnetic resonance imaging. Patients with longer DoI showed significant reduction of gray matter volume in the left medial frontal gyrus compared with healthy controls. Moreover, there was a trend for greater gray matter volume decrease in patients with a longer illness duration compared with patients with shorter illness duration. There was no interaction between the volume of the left medial frontal gyrus performance on the WCST. The present study supports the hypothesis that medial frontal gyrus alterations in schizophrenia are sensitive to duration of illness. These alterations were not associated with executive functioning.