Redox proteomic profiling of neuroketal-adducted proteins in human brain: Regional vulnerability at middle age increases in the elderly.

Protein lipoxidation was assessed in the parietal cortex (PC), frontal cortex (FC), and cingulate gyrus (CG) in middle-aged and old-aged individuals with no clinical manifestations of cognitive impairment, in order to increase understanding of regional brain vulnerability to oxidative damage during aging. Twenty-five lipoxidized proteins were identified in all the three regions although with regional specificities, by using redox proteomics to detect target proteins of neuroketals (NKT) adduction. The number of cases with NKT-adducted proteins was higher in old-aged individuals but most oxidized proteins were already present in middle-aged individuals. Differences in vulnerability to oxidation were dependent on the sub-cellular localization, secondary structure, and external exposition of certain amino acids. Lipoxidized proteins included those involved in energy metabolism, cytoskeleton, proteostasis, neurotransmission and O2/CO2, and heme metabolism. Total NKT and soluble oligomer levels were estimated employing slot-blot, and these were compared between age groups. Oligomers increased with age in PC and FC; NKT significantly increased with age in FC, whereas total NKT and oligomer levels were not modified in CG, thus highlighting differences in brain regional vulnerability with age. Oligomers significantly correlated with NKT levels in the three cortical regions, suggesting that protein NKT adduction parallels soluble oligomer formation.

Depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia (CDSS): genetic vulnerability and sex effects.

The present study compares the occurrence of depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia (CDSS) in patients of Multiplex (MS) and Simplex Schizophrenia families (SS). The Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychopathology. A total of 206 paranoid schizophrenia patients were studied according DSM-IV criteria. The Family Interview for Genetic Studies (FIGS) was used to study the families. A result in the FIGS for a positive family history of schizophrenia was referred as MS (patients); its lack as SS (patients). CDSS scores were compared among MS and SS patients and possible sex differences intra- and inter-groups were explored. In the analysis of our sample (30) 19% of the total persons with schizophrenia group was depressed. The depressive symptoms measured by the CDSS were higher in females and the MS males group. Males from MS group showed more depressive symptoms than males from SS group. No differences with females from both groups were found. Findings in this study underscore the importance of gender and family history in understanding the heterogeneity of schizophrenia. This study suggests that sex and familiar history are important to consider in studying depressive symptoms.

Impairment of emotional expression recognition in schizophrenia: a Cuban familial association study.

It is well established that schizophrenia is associated with difficulties in recognizing facial emotional expressions, but few studies have reported the presence of this deficit among their unaffected relatives. This study attempts to add new evidence of familial association on an emotional expression processing test. The study evaluated the performance of 93 paranoid schizophrenia patients, 110 first-degree relatives of probands from multiplex schizophrenia families, and 109 nonpsychiatric controls on a facial emotional recognition test using a computer morphing technique to present the dynamic expressions. The task entailed the recognition of a set of facial expressions depicting the six basic emotions presented in 21 successive frames of increasing intensity. The findings indicated that schizophrenia patients were consistently impaired for the recognition of the six basic facial expressions. In contrast, their unaffected relatives showed a selective impairment for the recognition of disgust and fearful expressions. Familial association of selective facial emotional expressions processing deficit may further implicate promising new endophenotypes that can advance the understanding of affective deficits in schizophrenia.

Heritability of Trail Making Test performance in multiplex schizophrenia families: implications for the search for an endophenotype.

The impairment of the Trail Making Test (TMT) performance as a measure of executive function deficits has been found both in patients with schizophrenia and in their unaffected first-degree relatives, suggesting that it might be considered as a familial vulnerability marker, but its heritability estimates are not well known. This study investigated the genetic heritability of impairments in TMT performance using a sample of 80 schizophrenia patients, 145 unaffected first-degree relatives and 127 healthy controls from families with multiple members with schizophrenia. Consistent with previous reports in the literature, relatives performed in between healthy controls and schizophrenia patients. Based on these results, a variance component-analysis provided small, but significant additive heritability estimates for performance indices relating performance in TMT-version A to TMT-version B. These results showed that this significant but small evidence of heritability on the one hand suggests an association with genetic predisposition to schizophrenia, but that TMT performance is also associated with epigenetic or environmental factors.

N400 deficits from semantic matching of pictures in probands and first-degree relatives from multiplex schizophrenia families.

Endophenotypes is one emerging strategy in schizophrenia research that is being used to identify the functional importance of genetically transmitted, brain-based deficits present in this disease. Currently, event-related potentials (ERPs) are timely used in this search. Several ERPs, including N400, present deficits in relation to schizophrenia. In order to assess the genetic liability of N400 as a possible endophenotype, a picture semantic matching task (congruent and incongruent pairs of pictures) was performed by 21 unaffected first-degree relatives of patients with schizophrenia, 21 DSM-IV diagnosed schizophrenia probands, and 21 control subjects, matched by age, gender and educational level. Probands and relatives were selected form Multiplex schizophrenia families. Significantly reduced N400 amplitude for congruent categories in N400 was found in probands and relatives in relation to controls. The latency onset and the maximum peak latency of N400 were delayed in both, relatives and probands groups compared to control. The voltage maps of incongruous-minus-congruous difference indicate a more reduced right restricted negativity in probands and relatives, when compared to a widely extended bilateral negativity in controls. No general differences were found between patients and relatives. These results demonstrate an electrophysiological deficit in semantic match processing in clinically unaffected first-degree relatives of patients with schizophrenia, suggesting a possible use of this marker as endophenotype.