Psychometric Evaluation of the Polish adaptation of a Self-Report Form of the DSM-5 Level of Personality Functioning Scale (LPFS-SR)

Objectives: This study examined psychometric properties of the Polish adaptation of a Self-Report Form of the DSM-5 Level of Personality Functioning Scale (LPFS-SR). It is a scale designed to measure general impairment, jointly with a detailed assessment of distinguished components of personality functioning characterized in terms of disturbances in self (identity and self-direction) and interpersonal (empathy and intimacy) functioning – Criterion A in the DSM-5 Alternative Model for Personality Disorders (AMPD). Methods: The study involved a non-clinical sample of N = 242 adults (52.9% female; Mage = 30.63 years, SDage = 11.81 years). To provide an evaluation of the criterion validity, Personality Inventory for DSM-5 (PID-5), Personality Inventory for ICD-11 (PiCD), Level of Personality Functioning Scale-Brief Form 2.0 (LPFS-BF 2.0), and Big Five Inventory-2 (BFI-2) were administered. Results: Our data supported that identity, self-direction, intimacy, and empathy components of the LPFS-SR can be characterized by a single, global dimension of personality dysfunction, consistent with the assumption that DSM-5 Criterion A is a relatively homogeneous construct. The LPFS-SR showed good reliability estimates and demonstrated conceptually sound associations with the PD severity index and related measures of personality functioning. Moreover, all the LPFS-SR components manifested at least partial distinction from maladaptive personality traits (i.e., Criterion B in the DSM-5 AMPD). Conclusions: These findings provide support for the validity of the Polish adaptation of the LPFS-SR as an operationalization of impairment in the core and common features of personality pathology described in the DSM-5 alternative model

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors