Loneliness is associated with mentalizing and emotion recognition abilities in schizophrenia, but only in a cluster of patients with social cognitive deficits.

OBJECTIVE: Loneliness is a concern for patients with schizophrenia. However, the correlates of loneliness in patients with schizophrenia are unclear; thus, the aim of the study is to investigate neuro- and social cognitive mechanisms associated with loneliness in individuals with schizophrenia. METHOD: Data from clinical, neurocognitive, and social cognitive assessments were pooled from two cross-national samples (Poland/USA) to examine potential predictors of loneliness in 147 patients with schizophrenia and 103 healthy controls overall. Furthermore, the relationship between social cognition and loneliness was explored in clusters of patients with schizophrenia differing in social cognitive capacity. RESULTS: Patients reported higher levels of loneliness than healthy controls. Loneliness was linked to increased negative and affective symptoms in patients. A negative association between loneliness and mentalizing and emotion recognition abilities was found in the patients with social-cognitive impairments, but not in those who performed at normative levels. CONCLUSIONS: We have elucidated a novel mechanism which may explain previous inconsistent findings regarding the correlates of loneliness in individuals with schizophrenia.

Social cognitive bias increases loneliness both directly and by decreasing social connection in patients with schizophrenia.

While considerable emphasis has been put on investigating the mechanisms that drive reduced social connection in patients with schizophrenia (SCZ), recent studies have increasingly focused on the issue of loneliness in SCZ. As both social cognitive bias and self-reported empathy predict loneliness in non-clinical populations, the current study aims to examine the relationship between loneliness, reduced social connection and social cognitive biases, and self-reported empathy in SCZ. Ninety-three adult SCZ and sixty-six matched healthy individuals completed a battery of questionnaires measuring loneliness and social connection (Revised-UCLA Loneliness Scale, Lubben-Social Network Scale, Social Disconnectedness Scale), cognitive biases (Ambiguous Intentions Hostility Questionnaire, Davos Assessment of Cognitive Biases Scale, Cognitive Biases Questionnaire for psychosis) and self-reported empathy (Interpersonal Reactivity Index). Significant predictors of loneliness in SCZ were entered into two latent variables ("Social Threat Bias", "Social Connection"), and structural equation modeling was used to explore the direct and indirect relationships between Social Threat Bias, symptoms. and loneliness in SCZ. Patients reported higher levels of loneliness, cognitive biases and personal distress compared to controls. Furthermore, SCZ reported less social connection and perspective taking compared to controls. Structural equation modeling revealed that Social Threat Bias was linked to increased loneliness in SCZ both directly and indirectly via decreased social connection. Negative symptoms were directly linked with loneliness, while the association between affective symptoms and loneliness was mediated via Social Threat Bias. The results of the current study suggest that social threat bias should be considered while planning the interventions aimed to reduce loneliness in schizophrenia.

Mentalizing abilities mediate the impact of the basic social perception on negative symptoms in patients with schizophrenia.

Social cognitive deficits are currently considered as one of the main predictors of clinical symptoms and functional outcome in patients with schizophrenia. Multiple studies have suggested that a two-factor solution (low-level vs. high-level) best describes the structure of social cognitive processes in patients. While higher-order processes have been repeatedly linked to negative symptoms, no such association was found for lower-level processes. Thus, the aim of the current study is to examine whether the association between basic social perception processes and symptoms in patients with schizophrenia is mediated by mentalizing abilities. One hundred thirty-nine patients have completed basic social perception (Communicative Interactions Database task CID-12) and mentalizing (Reading the Mind in the Eyes task) tasks. In line with our hypothesis, we have observed full mediation of the effects of basic social perception abilities on negative symptoms via mentalizing abilities in patients. This effect suggests that, similarly as in the case of positive symptoms, a hierarchical nature of social cognitive processes should be considered while investigating negative symptoms of schizophrenia.

Social and nonsocial affective processing in schizophrenia - An ERP study.

BACKGROUND: Despite social cognitive dysfunction that may be observed in patients with schizophrenia, the knowledge about social and nonsocial affective processing in schizophrenia is scant. The aim of this study was to examine neurophysiological and behavioural responses to neutral and negative stimuli with (faces, people) and without (animals, objects) social content in schizophrenia. METHODS: Twenty-six patients with schizophrenia (SCZ) and 21 healthy controls (HC) completed a visual oddball paradigm with either negative or neutral pictures from the Nencki Affective Picture System (NAPS) as targets while EEG was recorded. Half of the stimuli within each category presented social content (faces, people). RESULTS: Negative stimuli with social content produced lower N2 amplitude and higher mean LPP than any other type of stimuli in both groups. Despite differences in behavioural ratings and alterations in ERP processing of affective stimuli (lack of EPN differentiation, decreased P3 to neutral stimuli) SCZ were still able to respond to specific categories of stimuli similarly to HC. CONCLUSIONS: The pattern of results suggests that with no additional emotion-related task demands patients with schizophrenia may present similar attentional engagement with negative social stimuli as healthy controls.

Discovery of new human beta-defensins using a genomics-based approach.

Epithelial beta-defensins are broad-spectrum cationic antimicrobial peptides that also act as chemokines for adaptive immune cells. In the human genome, all known defensin genes cluster to a <1 Mb region of chromosome 8p22-p23. To identify new defensin genes, the DNA sequence from a contig of large-insert genomic clones from the region containing human beta-defensin-2 (HBD-2) was analyzed for the presence of defensin genes. This sequence survey identified a novel beta-defensin, termed HBD-3. The HBD-3 gene contains two exons, is located 13 kb upstream from the HBD-2 gene, and it is transcribed in the same direction. A partial HBD-3 cDNA clone was amplified from cDNA derived from IL-1beta induced fetal lung tissue. The cDNA sequence encodes for a 67 amino acid peptide that is approximately 43% identical to HBD-2 and shares the beta-defensin six cysteine motif. By PCR analysis of two commercial cDNA panels, HBD-3 expression was detected in adult heart, skeletal muscle, placenta and in fetal thymus. From RT-PCR experiments, HBD-3 expression was observed in skin, esophagus, gingival keratinocytes, placenta and trachea. Furthermore, in fetal lung explants and gingival keratinocytes, HBD-3 mRNA expression was induced by IL-1beta. Additional sequence analysis identified the HE2 (human epididymis secretory protein) gene 17 kb upstream from the HBD-3 gene. One splice variant of this gene (HE2beta1) encodes a beta-defensin consensus cysteine motif, suggesting it represents a defensin gene product. HE2beta1 mRNA expression was detected in gingival keratinocytes and bronchial epithelia using RT-PCR analysis. The discovery of these novel beta-defensin genes may allow further understanding of the role of defensins in host immunity at mucosal surfaces.

The DNA sequence of human chromosome 21.

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Higher frequency of DPC4/Smad4 alterations in pancreatic cancer cell lines than in primary pancreatic adenocarcinomas.

The tumor suppressor gene DPC4/Smad4 at 18q21.1 is inactive in about 50% of pancreatic carcinoma xenografts and cell lines. However, the role of DPC4 in the multistep carcinogenesis of primary pancreatic adenocarcinomas remains uncertain. Therefore, we examined 45 primary human pancreatic adenocarcinomas and 12 pancreatic cancer cell lines for DPC4 alterations by single-strand conformational variant (SSCV) analysis and a PCR-based deletion assay. DPC4 was inactivated by either homozygous deletion or point mutation in 6 of 12 cell lines (50%). None of the primary pancreatic carcinomas carried a DPC4 mutation, although 66% revealed LOH of 18q21 sequences. These findings suggest that inactivation of DPC4 occurs more frequently in tumor-derived cell lines than in primary pancreatic adenocarcinomas. In addition, another, yet unidentified, tumor suppressor gene(s) may be linked with the frequent LOH of 18q21 in primary pancreatic adenocarcinomas.

MEN1 gene mutations in 12 MEN1 families and their associated tumors.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumor syndrome characterized by the development of multiple endocrine tumors. The gene responsible for the disease, termed MEN1 gene. has recently been isolated and germline mutations have been described in affected MEN1 individuals. Twelve unrelated (German MEN1 families and their associated tumors (5 parathyroid tumors, 1 vipoma, 1 gastrinoma, 1 insulinoma) were characterized for MEN1 gene mutations by single-strand conformational variant (SSCV) analysis and DNA sequence analysis as well as for loss of heterozygosity on chromosome 11q13. We identified nine different heterozygous germline mutations (6 frameshift, 2 missense, 1 nonsense), eight of them were novel. Four of five informative MEN1-associated tumors revealed deletion of the second MEN1 allele, supporting the concept of a tumor suppressor gene. Furthermore. SSCV analysis proved an effective and sensitive method for the detection of menin mutations providing a reliable genetic screening approach supporting genetic counseling and clinical management of MEN1 family members.

K-ras oncogene mutations indicate malignancy in cystic tumors of the pancreas.

OBJECTIVE: To evaluate clinical parameters, presurgical diagnostic tests, histologic findings, and the presence of K-ras oncogene mutations in cystic tumors of the pancreas to determine which best predict malignancy. SUMMARY BACKGROUND DATA: Because presurgical, intraoperative, and final pathologic differentiation is difficult in cystic tumors of the pancreas, it would be a major benefit to identify markers that accurately predict malignancy in these rare tumors. The role of K-ras oncogene mutations as an indicator of malignancy has not been determined in these tumors. METHODS: Nineteen patients with cystic tumors of the pancreas were evaluated, including K-ras mutation analysis based on polymerase chain reaction and restriction digestion assays and direct DNA sequencing, to screen for parameters that accurately predict malignancy. RESULTS: All malignant cystic pancreatic tumors (five cystadenocarcinomas and three mucin-producing adenocarcinomas) harbored K-ras mutations at codon 12 or 13. K-ras mutations were also detected in the percutaneous fine-needle aspirates of two of these patients. In contrast, none of nine benign cystadenomas or the solid-papillary neoplasm had K-ras mutations. None of the patients with a benign tumor carrying K-ras wild-type sequences developed recurrent disease after a mean follow-up of 50 months. Seven of the 8 malignant cystic pancreatic tumors, but none of the 11 benign tumors, showed dilatation of the main pancreatic duct on computed tomography or endoscopic retrograde cholangiopancreatography. CONCLUSIONS: K-ras mutation analysis seems to be a powerful tool to determine the malignant potential of cystic pancreatic tumors before and after surgery. Dilatation of the main pancreatic duct on computed tomography or endoscopic retrograde cholangiopancreatography is highly suggestive for malignancy in these rare tumors.

Organization of the 5'-End of the porcine gamma-glutamyl transpeptidase gene and identification of three different mRNAs in the kidney.

Three different mRNAs coding for the porcine gamma-glutamyl transpeptidase (GGT) in the kidney were identified by 5'-RACE-PCR. These differ in their 5'-noncoding region. Genomic Southern blot analysis has demonstrated the existence of a single GGT gene in the porcine genome. Thus, the existence of multiple mRNAs can only be explained by the use of different promoters or alternative splicing. Four GGT-specific genomic clones containing the complete 5'-end of the gene were isolated and characterized, revealing six exons common to all three mRNAs. Four of these exons were located in the coding region comprising the codons for amino acids 1 to 138. Two exons and an intervening sequence were identified upstream from these six common exons representing the unique 5'-ends of the three mRNAs. The coding exons show a significant sequence homology to mouse, rat, and human GGT cDNA, whereas exons 1 and 3 display no homology.