Diffusion tensor imaging in borderline personality disorder showing prefrontal white matter alterations.

Borderline personality disorder (BPD) has repeatedly been linked to alterations in fronto-limbic dysfunction. In this study, we tested the hypothesis of disturbed structural connectivity in underlying fibre tracts and their relation to symptom profiles. We analysed diffusion tensor imaging (DTI) data from 18 female BPD patients and 38 female healthy controls. Group comparisons showed significant (p < .05, FDR adjusted) increase of radial diffusivity (RD) in the right frontal lobe, including the uncinate fasciculus, anterior thalamic radiation, and inferior fronto-occipital fasciculus, as well as overall apparent diffusion coefficient (ADC) increases in the anterior and posterior internal capsule. Symptom correlations, based on the BSL-95 questionnaires, within the BPD sample showed significant negative correlations of dysphoria with ADC the left and right anterior thalamic radiation, and positive correlations of fractional anisotropy with self-perception scores in the right superior corona radiata. While our findings add to the fronto-limbic dysfunction model of BPD, they provide additional evidence of links to its affective core pathology, particularly frontotemporal and fronto-thalamic systems.

Targeting RNA With Antisense Oligonucleotides and Small Interfering RNA: JACC State-of-the-Art Review.

There is an unmet clinical need to reduce residual cardiovascular risk attributable to apolipoprotein B-containing lipoproteins, particularly low-density lipoprotein and remnant particles. Pharmacological targeting of messenger RNA represents an emerging, innovative approach. Two major classes of agents have been developed-antisense oligonucleotides and small interfering RNA. Early problems with their use have been overcome by conjugation with N-acetylgalactosamine, an adduct that targets their delivery to the primary site of action in the liver. Using these agents to inhibit the translation of key regulatory proteins such as PCSK9, apolipoprotein CIII, apolipoprotein(a), and angiopoietin-like 3 has been shown to be effective in attenuating dyslipidemic states. Cardiovascular outcome trials with N-acetylgalactosamine-conjugated RNA-targeting drugs are ongoing. The advantages of these agents include long dosing intervals of up to 6 months and the potential to regulate the abundance of any disease-related protein. Long-term safety has yet to be demonstrated in large-scale clinical trials.