Aberrant salience relationship with first rank symptoms.

BACKGROUND: Aberrant salience is the incorrect assignment of salience, significance, or value to different innocuous stimuli that might precede the onset of psychotic symptoms. The present study aimed to perform a preliminary evaluation of potentially different correlations between the Aberrant Salience Inventory (ASI) score and dimensional or categorical diagnostic approaches. METHODS: 168 adult outpatients with a current psychiatric diagnosis were consecutively enrolled. Patients were evaluated using different psychometric scales. ASI was used to evaluate aberrant salience, and to evaluate the association between ASI scores and first rank symptoms (FRS), and/or with a psychiatric diagnosis. Principal dichotomic clusters of ASI were identified using the Chi-square automatic interaction detection (CHAID) method. RESULTS: Current (16.76 ± 6.02 vs 13.37 ± 5.76; p = 0.001), lifetime (15.74 ± 6.08 vs 13.16 ± 5.74; p = 0.005) and past (15.75 ± 6.01 vs 13.33 ± 5.80; p = 0.009) FRS were the main clusters dichotomizing ASI. The average ASI score did not significantly differ among patients with different diagnoses. CONCLUSIONS: ASI could be used as a tool to identify psychopathological dimensions, rather than the categorical diagnoses, in the schizophrenic spectrum.

Immune environment of the brain in schizophrenia and during the psychotic episode: A human post-mortem study.

A causal relationship between immune dysregulation and schizophrenia has been supported by genome-wide association studies and epidemiological evidence. It remains unclear to what extent the brain immune environment is implicated in this hypothesis. We investigated the immunophenotype of microglia and the presence of perivascular macrophages and T lymphocytes in post-mortem brain tissue. Dorsal prefrontal cortex of 40 controls (22F:18M) and 37 (10F:27M) schizophrenia cases, of whom 16 had active psychotic symptoms at the time of death, was immunostained for seven markers of microglia (CD16, CD32a, CD64, CD68, HLA-DR, Iba1 and P2RY12), two markers for perivascular macrophages (CD163 and CD206) and T-lymphocytes (CD3). Automated quantification was blinded to the case designation and performed separately on the grey and white matter. 3D reconstruction of Iba1-positive microglia was performed in selected cases. An increased cortical expression of microglial Fcγ receptors (CD64 F = 7.92, p = 0.007; CD64/HLA-DR ratio F = 5.02, p = 0.029) highlights the importance of communication between the central and peripheral immune systems in schizophrenia. Patients in whom psychotic symptoms were present at death demonstrated an age-dependent increase of Iba1 and increased CD64/HLA-DR ratios relative to patients without psychotic symptoms. Microglia in schizophrenia demonstrated a primed/reactive morphology. A potential role for T-lymphocytes was observed, but we did not confirm the presence of recruited macrophages in the brains of schizophrenia patients. Taking in account the limitations of a post-mortem study, our findings support the hypothesis of an alteration of the brain immune environment in schizophrenia, with symptomatic state- and age-dependent effects.

BDNF and Artemin are increased in drug-naïve non-depressed GAD patients: preliminary data.

OBJECTIVE: While the role of neuronal and glial plasticity are well established in the pathophysiology of mood disorders, the pattern and measures of neuronal and glial cell line-derived neurotrophic factors are unknown in generalized anxiety disorder (GAD). The present study evaluates brain-derived neurotrophic factor (BDNF) and Artemin (ARTN) plasma levels in GAD patients. METHODS: Fourteen drug-naïve GAD patients without major depression were enrolled and plasmatic levels of BDNF and ARTN mRNA were measured by RT-PCR, and compared to matched healthy controls. RESULTS: The results showed an unexpected increase in mRNA levels of both BDNF and ARTN in patients with GAD, that appeared almost doubled when compared to healthy controls. In comparison, both BDNF and ARTN are reduced in patients with major depressive disorder. Further, the results are intriguing and might involve distinguishing pathophysiological pathways. CONCLUSIONS: This is the first report of increased levels of a neurotrophic factor and of a glial cell line-derived neurotrophic factor family member in GAD patients. While further studies to confirm these results and the functional meaning in terms of pathophysiology of GAD are needed, the potential conceptual and clinical meanings are discussed.