Individual differences in borderline personality traits: A genetic perspective

Boomsma, D.I. [Promotor]Willemsen, A.H.M. [Copromotor]Trull, T.J. [Copromotor

Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10−5 and c.2702T > G [p.V901G], MAF 2.51 × 10−3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05–13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10−8), viability (P = 8.9 × 10−7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10−4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10−5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia

Nederlandse vertaling van de Personality Assessment Inventory - Borderline kenmerken schaal (PAI-BOR): normgegevens, factorstructuur en betrouwbaarheid

Borderline personality disorder (BPD) is a severe personality disorder whose main features include affective instability, identity problems, negative relationships and self-harm. The Personality Assessment Borderline- features (PAI-BOR) scale developed by Morey (1991) assesses these features on a continuous scale. In 2004, the PAI-BOR was translated into Dutch and completed by 8511 men and women aged 18 to 90 years. The internal consistency (Crohnbach's α) of the Dutch PAI-BOR is good (α = 0.81). Six-month test-retest correlation is 0.78. Thus, BPD features in the general population can reliably be assessed by the Dutch version of the PAI-BOR. The four domains as proposed by Morey (1991) are also found in the Dutch data. The effects of sex, age and educational level on BPD features are discussed and means and standard deviations for twelve sex (3287 men, 5224 women) by age (18 - 35, 36 - 90 years) by level of education (low, middle, high) groups are presented. © 2009 Bohn Stafleu van Loghum