CAMHS Clinician Attitudes to Borderline Personality Disorder in Adolescence Across Scotland.

ABSTRACT: Child and Adolescent Mental Health Service (CAMHS) clinicians have been reported to hold negative views toward the diagnosis of borderline personality disorder (BPD) in adolescence. We aimed to reevaluate with the expectation that recent advances have nurtured more positive attitudes. One hundred ninety clinicians working across CAMHS in Scotland completed a 16-item electronic survey of attitudes to BPD, derived from the Attitudes and Skills Questionnaire. Eighty-three percent of psychiatrists, 72% of nurses, and 37% of psychologists surveyed agreed that BPD is a valid diagnosis in adolescence, and 92%, 74%, and 44%, respectively, were willing to make this diagnosis. CAMHS clinicians were more optimistic compared with clinicians working in adult mental health services. CAMHS clinicians' responses may indicate increased acceptance of BPD in the adolescent population. There is a thirst for workforce education and training. Consideration should be taken to actively move the focus of identification and diagnosis of BPD into CAMHS rather than the current culture of late diagnosis.

Parents in Control: Parental perceptions of problem behaviors before and after attending an ADHD-specific parent-training program.

PROBLEM: There is scant evidence to support the efficacy of attention deficit hyperactivity disorder (ADHD)-specific parent-training programs in the treatment of preadolescent children with ADHD. This study explores the effectiveness of the Parents in Control (PINC) parent-training program, designed specifically for children with ADHD. METHODS: In this pragmatic uncontrolled pre-poststudy parents of preadolescent children with a diagnosis of ADHD were invited to attend the 6-week PINC course. Fifty-seven parent-report pre/postprogram questionnaires were completed. FINDINGS: Parental ratings of the intensity and frequency of problem behaviors after completing PINC showed a significant reduction (p < .001) with a moderate effect size (0.6-0.7). CONCLUSIONS: Our findings demonstrate the efficacy of PINC in reducing the parental perception of problem behaviors and support a need for further rigorous randomised controlled trial (RCT) evaluation of this ADHD-specific intervention.

Alignment of corneal and lens epithelial cells by co-operative effects of substratum topography and DC electric fields.

Corneal and lens epithelial cells (CECs and LECs) in the eye encounter precisely ordered fibre arrays on the nanoscale in tandem with an endogenous electric field (EF). Prosthetic biomaterials often incorporate topographical features intended to mimic those in situ. However, the cellular basis for control of cell morphology by nanotopography or by an EF is not clear. We examined cell axis alignment in response to substratum nanotopography and a physiological EF separately and in combination. Bovine CECs aligned parallel to substratum nanogrooves (NGs) as shallow as 14 nm but LECs were less sensitive. Actin filaments of both cell types concentrated at substratum ridges so we tested the mechanistic roles of rho, rac and cdc42, molecules that control cytoskeletal organization. CEC alignment to 130 nm deep NGs was prevented by the inhibition of rho, but not by the inhibition of cdc42, rac, or the rho effectors myosin light chain kinase or rho kinase. Conversely, CEC alignment was enhanced by the activation of rho. CECs on planar quartz substrata aligned orthogonal to an EF of 150 mV/mm. Alignment required signalling by cdc42 and rho but not rac, and was accompanied by lamellipodial reorganisation and cell migration toward the cathode. When CECs on vertically oriented NGs were exposed simultaneously to a horizontal EF, they aligned more robustly than to either cue alone and the enhanced alignment required rho signalling. Therefore, nanoscale substratum features and EFs co-operate to control cell axis alignment via rho, and cdc42-mediated intracellular signals, which can be exploited in tissue engineering.

Prioritising guidance cues: directional migration induced by substratum contours and electrical gradients is controlled by a rho/cdc42 switch.

Coordinated cell migration is a fundamental feature of embryogenesis but the intracellular mechanism by which cells integrate co-existing extracellular cues to yield appropriate vectoral migration is unknown. Cells in the cornea are guided by a naturally occurring DC electric field (EF) (electrotaxis) as they navigate non-planar substrata but the relative potencies of electrotaxis and guidance by substratum shape (contact guidance) have never been determined. We tested the hypothesis that vectoral migration was controlled by selective activation of rac, cdc42 or rho in response to a 150 mV/mm EF or to a series of parallel substratum nanogrooves (NGs) 130 nm deep. EFs and NGs were presented singly or in combination. Electrotaxis of dissociated bovine corneal epithelial cells (CECs) on planar quartz required signalling by cdc42 and rho but not rac. Contact guidance by substratum NGs required rho but not cdc42 or rac activities. When an EF and NGs were superimposed in parallel, cathodal electrotaxis along NGs was enhanced compared to that on planar quartz but when they were superimposed orthogonally (vertical NGs with horizontal EF) cells were recruited from contact guidance to electrotaxis, suggesting that the EF was more potent. However, increasing the EF to 250 mV/mm was insufficient to recruit the majority to electrotaxis. Consistent for the cues in isolation, when an EF (150 mV/mm) and NGs were superimposed orthogonally, rac activity was not essential for either contact guidance or electrotaxis. However, attenuation of cdc42 signalling abolished electrotaxis and enhanced contact guidance relative to controls (no drug), whereas inhibiting rho signalling enhanced electrotaxis and rho stimulation enhanced contact guidance. Our data are consistent with the idea that migrating CECs use a cdc42/rho "switch" to sort vectoral cues, with cdc42 controlling electrotaxis and rho controlling contact guidance.

Growth cone steering by a physiological electric field requires dynamic microtubules, microfilaments and Rac-mediated filopodial asymmetry.

Electric fields (EFs) resembling those in the developing and regenerating nervous systems steer growth cones towards the cathode. Requirements for actin microfilaments, microtubules and their interactions during EF growth cone steering have been presumed, but remain unproven. Here, we demonstrate essential roles for dynamic microfilaments and microtubules in cathode-directed migration. Cathodal turning of growth cones on cultured Xenopus embryonic spinal neurons was attenuated significantly by nanomolar concentrations of the microfilament inhibitor latrunculin, the microtubule-stabilising drug taxol, or the microtubule-destabilising drugs vinblastine or nocodazole. Dynamically, the cathodal bias of filopodia preceded cathodal turning of the growth cone, suggesting an instructive role in EF-induced steering. Lamellipodial asymmetry accompanied turning. Filopodia and lamellipodia are regulated by the GTPases Cdc42 and Rac, respectively, and, as shown in the companion paper in this issue, peptides that selectively prevented effector binding to the CRIB domains of Cdc42 or Rac abolished cathodal growth cone turning during 3 hours of EF exposure. Here, the Rac peptide suppressed lamellipodium formation, increased the number of filopodia, abolished cathodal filopodial orientation, and prevented cathodal steering. The Cdc42 peptide suppressed filopodium formation, increased lamellipodial area and prevented cathodal steering. The cathodal bias of lamellipodia was independent of Cdc42 CRIB activity and was not sufficient for cathodal steering in the absence of filopodia, but the cathodal bias of filopodia through Rac CRIB activity was necessary for cathodal turning. Understanding the mechanism for cathodal growth cone guidance will enhance the emerging clinical effort to stimulate human spinal cord regeneration through EF application.

Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their effectors in growth cone guidance by a physiological electric field.

Although it is known that neuronal growth cones migrate towards the cathode of an applied direct current (DC) electric field (EF), resembling the EF present in the developing nervous system, the underlying mechanism remains unclear. Here, we demonstrate temporally and spatially coordinated roles for the GTPases Rac, Cdc42 and Rho and their effectors. Growth cones of cultured Xenopus embryonic spinal neurons turned towards the cathode but collective inhibition of Rho, Rac and Cdc42 attenuated turning. Selective inhibition of Rho, Cdc42 or Rac signalling revealed temporally distinct roles in steering by an electrical gradient. Rho, Rac and Cdc42 are each essential for turning within the initial 2 hours (early phase). Later, Rho and Cdc42 signals remain important but Rac signalling dominates. The EF increased Rho immunofluorescence anodally. This correlated spatially with collapsed growth cone morphology and reduced anodal migration rates, which were restored by Rho inhibition. These data suggest that anodally increased Rho activity induces local cytoskeletal collapse, biasing growth cone advance cathodally. Collapse might be mediated by the Rho effectors p160 Rho kinase and myosin light chain kinase since their inhibition attenuated early turning. Inhibitors of phosphoinositide 3-kinase, MEK1/2 or p38 mitogen-activated protein kinase (MAPK) did not affect turning behaviour, eliminating them mechanistically. We propose a mechanism whereby Rac and Cdc42 activities dominate cathodally and Rho activity dominates anodally to steer growth cones towards the cathode. The interaction between Rho GTPases, the cytoskeleton and growth cone dynamics is explored in the companion paper published in this issue. Our results complement studies of growth cone guidance by diffusible chemical gradients and suggest that growth cones might interpret these co-existing guidance cues selectively.