Incidence and risk factors of mental disorders in the elderly: The European MentDis_ICF65+ study.

OBJECTIVE: While incidence rates of depression and anxiety disorders in the elderly have been comprehensively investigated, the incidence rates of other mental disorders have rarely been researched. The incidence rate and predictors of various mental disorders in the elderly were evaluated in different European and associated countries. METHODS: A cross-sectional and longitudinal multi-centre survey of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnoses was conducted in different European and associated countries (Germany, Italy, Spain, Switzerland, the United Kingdom and Israel) to collect data on the prevalence and incidence of mental disorders in the elderly. The sample size of the longitudinal wave was N = 2592 elderly. RESULTS: The overall 1-year incidence rate for any mental disorder in the elderly is 8.65%. At 5.18%, any anxiety disorder had the highest incidence rate across all diagnostic groups. The incidence rate for any affective disorder was 2.97%. The lowest incidence rates were found for agoraphobia (1.37%) and panic disorder (1.30%). Risk factors for the development of any mental disorder were never having been married, no religious affiliation, a higher number of physical illnesses and a lower quality of life. CONCLUSION: In comparison to other studies, lower incidence rates for any affective disorder and middle-range incidence for any anxiety disorder were found. To the authors' knowledge, no prior studies have reported 1-year incidence rates for somatoform disorder, bipolar disorder and substance misuse in community-dwelling elderly. These findings indicate the need to raise awareness of psychosocial problems in the elderly and to ensure adequate availability of mental health services.

The factor structure of the Zanarini Rating Scale for Borderline Personality Disorder: Exploratory Structural Equation Modelling and measurement invariance over time.

OBJECTIVES: There is a lack of independent longitudinal evidence on the factor structure and validity of the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). This study aimed to investigate the dimensionality of ZAN-BPD and its conceptual consistency over time. METHODS: Adult BPD participants (n = 276) were recruited for a multicentre, two-arm randomised clinical trial with ZAN-BPD measured at baseline and follow up at 12, 24 and 52 weeks. The construct and stability of the ZAN-BPD across 52 weeks was examined through a measurement equivalence/invariance procedure via Exploratory Structural Equation Modelling. RESULTS: Factor analysis results showed that the ZAN-BPD had a bi-2 factor structure that was stable over 52 weeks with a general factor and two specific factors. Factor loadings for eight of the nine items were greater for the general factor than the two specific factors. Factor 1 contrasts externalising distress with internalising distress. Factor 2 contrasts depression and self-destruction with interpersonal anxiety and conflict. CONCLUSION: ZAN-BPD is a conceptually and empirically valid measure of total BPD symptom severity in BPD patients over time suitable for use in clinical trials. Two factors related to the expression of distress and self-harm may be utilised as possible predictors of outcome.

Regeneration and development. An amphibian call to arms.

BACKGROUND: Unlike axolotls, the urodele Notophthalmus viridescens completes two metamorphoses and emerges from its aquatic environment to mate as a fully terrestrial adult. Larval and adult limb regeneration are commonly treated as roughly equivalent processes and, at least in part, as a recapitulation of embryonic development. RESULTS: We compared larval limb development to regeneration of both larval and adult forelimbs and found that there are substantial differences in developmental pattern among larvae and adults. The larval pattern of preaxial dominance is absent in adult regenerates: adult regenerates instead develop digits synchronously, and they do so before proximal autopodial elements have formed discrete aggregation zones. By contrast, larval regenerates follow a pattern of sequential digit formation from anterior to posterior, like their embryonic limb buds. CONCLUSIONS: Based upon these morphological clues, we conclude that larval regenerates are unlikely to exhibit features of epimorphic regeneration seen in adults, but are more likely to represent a form of developmental regulation. Furthermore, we confirm that post-metamorphic limb regeneration is not a simple recapitulation of ontology at the morphological level. These distinctions may help to explain and interpret some experiments and observations of regeneration in neotenic or paedomorphic urodeles.

Switching antipsychotic medication to reduce sexual dysfunction in people with psychosis: the REMEDY RCT.

BACKGROUND: Sexual dysfunction is common among people who are prescribed antipsychotic medication for psychosis. Sexual dysfunction can impair quality of life and reduce treatment adherence. Switching antipsychotic medication may help, but the clinical effectiveness and cost-effectiveness of this approach is unclear. OBJECTIVE: To examine whether or not switching antipsychotic medication provides a clinically effective and cost-effective method to reduce sexual dysfunction in people with psychosis. DESIGN: A two-arm, researcher-blind, pilot randomised trial with a parallel qualitative study and an internal pilot phase. Study participants were randomised to enhanced standard care plus a switch of antipsychotic medication or enhanced standard care alone in a 1 : 1 ratio. Randomisation was via an independent and remote web-based service using dynamic adaptive allocation, stratified by age, gender, Trust and relationship status. SETTING: NHS secondary care mental health services in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, have schizophrenia or related psychoses and experience sexual dysfunction associated with the use of antipsychotic medication. We recruited only people for whom reduction in medication dosage was ineffective or inappropriate. We excluded those who were acutely unwell, had had a change in antipsychotic medication in the last 6 weeks, were currently prescribed clozapine or whose sexual dysfunction was believed to be due to a coexisting physical or mental disorder. INTERVENTIONS: Switching to an equivalent dose of one of three antipsychotic medications that are considered to have a relatively low propensity for sexual side effects (i.e. quetiapine, aripiprazole or olanzapine). All participants were offered brief psychoeducation and support to discuss their sexual health and functioning. MAIN OUTCOME MEASURES: The primary outcome was patient-reported sexual dysfunction, measured using the Arizona Sexual Experience Scale. Secondary outcomes were researcher-rated sexual functioning, mental health, side effects of medication, health-related quality of life and service utilisation. Outcomes were assessed 3 and 6 months after randomisation. Qualitative data were collected from a purposive sample of patients and clinicians to explore barriers to recruitment. SAMPLE SIZE: Allowing for a 20% loss to follow-up, we needed to recruit 216 participants to have 90% power to detect a 3-point difference in total Arizona Sexual Experience Scale score (standard deviation 6.0 points) using a 0.05 significance level. RESULTS: The internal pilot was discontinued after 12 months because of low recruitment. Ninety-eight patients were referred to the study between 1 July 2018 and 30 June 2019, of whom 10 were randomised. Eight (80%) participants were followed up 3 months later. Barriers to referral and recruitment included staff apprehensions about discussing side effects, reluctance among patients to switch medication and reticence of both staff and patients to talk about sex. LIMITATIONS: Insufficient numbers of participants were recruited to examine the study hypotheses. CONCLUSIONS: It may not be possible to conduct a successful randomised trial of switching antipsychotic medication for sexual functioning in people with psychosis in the NHS at this time. FUTURE WORK: Research examining the acceptability and effectiveness of adjuvant phosphodiesterase inhibitors should be considered. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12307891. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 44. See the NIHR Journals Library website for further project information.

Antipsychotic medications can improve the mental health of people with psychosis but may also cause side effects. These include sexual side effects, such as reduced desire for sex or less pleasure from having sex. One way to try to tackle this problem is to switch the medicine people take to one that is thought less likely to cause these problems. However, it is unclear if this helps, and switching medication could potentially harm mental health or cause new side effects. We conducted a study to compare the effect of switching with not switching the medication of people with psychosis experiencing sexual side effects. We collected information about sexual functioning, mental health, quality of life and use of services at the start of the study and 6 months later. We also interviewed nurses, doctors and patients to get their views about the study. We recruited 10 patients over a 12-month period and conducted interviews with 51 clinicians and four patients. Many clinicians said that they found it difficult to talk to their patients about sex. Some thought that these problems occurred rarely and that other side effects mattered more to patients. Many patients were concerned about switching their medication, especially when it had improved their mental health. Others felt that these side effects were not very important, and some were not prepared to take part in a trial that could delay a change being made to their medication. We did not collect enough information to be able to find out if switching medication helps people who experience sexual side effects of antipsychotic drugs. It is important that clinicians ask about sexual side effects of antipsychotic medication and that further efforts are made to find ways to help patients who experience them.

Process evaluation of a randomised controlled trial of PBS-based staff training for challenging behaviour in adults with intellectual disability.

BACKGROUND: Positive Behaviour Support (PBS) for challenging behaviour is a complex intervention. Process evaluation is pivotal in fully understanding the mechanisms and contextual factors that impact on participant outcomes. AIMS: To conduct a process evaluation of a national clinical trial investigating the impact of PBS-based staff training on the level of challenging behaviour in adults with intellectual disability. METHOD: The Medical Research Council guidance for process evaluation of complex interventions was followed. Semi-structured interviews with 62 stakeholders from the intervention arm (service users, family and paid carers, service managers, staff who delivered the intervention and PBS trainers), quantitative data from the study database and an external evaluation of the quality of the PBS plans were used. RESULTS: Twenty-one health staff volunteered to be trained in delivering PBS. Available log data from 17 therapists revealed that they worked with 63 participants a median of 11.50 hours (IQR 8-32). Only 33 out of 108 reports had included all elements of the intervention. Another 47 reports had some elements of the intervention. All PBS plans were rated weak, indicating insufficient quality to impact challenging behaviour. Stakeholders reported an appreciation of PBS and its potential to impact quality of care and engagement with the participant. However, they also identified important challenges including managing PBS-related caseloads, paid carer turnover and service commitment to the delivery of PBS. CONCLUSIONS: PBS-based staff training was well received, but therapists found it difficult to undertake all the elements of the intervention in routine care. Implementing a workforce training strategy is important to better define the active components of PBS, and resource implications if the intervention is no better than usual care.

Clinical outcomes of staff training in positive behaviour support to reduce challenging behaviour in adults with intellectual disability: cluster randomised controlled trial.

BACKGROUND: Staff training in positive behaviour support (PBS) is a widespread treatment approach for challenging behaviour in adults with intellectual disability. Aims To evaluate whether such training is clinically effective in reducing challenging behaviour during routine care (trial registration: NCT01680276). METHOD: We carried out a multicentre, cluster randomised controlled trial involving 23 community intellectual disability services in England, randomly allocated to manual-assisted staff training in PBS (n = 11) or treatment as usual (TAU, n = 12). Data were collected from 246 adult participants. RESULTS: No treatment effects were found for the primary outcome (challenging behaviour over 12 months, adjusted mean difference = -2.14, 95% CI: -8.79, 4.51) or secondary outcomes. CONCLUSIONS: Staff training in PBS, as applied in this study, did not reduce challenging behaviour. Further research should tackle implementation issues and endeavour to identify other interventions that can reduce challenging behaviour. Declaration of interest None.

Cognitive-behaviour therapy for health anxiety in medical patients (CHAMP): a randomised controlled trial with outcomes to 5 years.

BACKGROUND: Health anxiety is an under-recognised but frequent cause of distress that is potentially treatable, but there are few studies in secondary care. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of a modified form of cognitive-behaviour therapy (CBT) for health anxiety (CBT-HA) compared with standard care in medical outpatients. DESIGN: Randomised controlled trial. SETTING: Five general hospitals in London, Middlesex and Nottinghamshire. PARTICIPANTS: A total of 444 patients aged 16-75 years seen in cardiology, endocrinology, gastroenterology, neurology and respiratory medicine clinics who scored ≥ 20 points on the Health Anxiety Inventory (HAI) and satisfied diagnostic requirements for hypochondriasis. Those with current psychiatric disorders were excluded, but those with concurrent medical illnesses were not. INTERVENTIONS: Cognitive-behaviour therapy for health anxiety - between 4 and 10 1-hour sessions of CBT-HA from a health professional or psychologist trained in the treatment. Standard care was normal practice in primary and secondary care. MAIN OUTCOME MEASURES: Primary - researchers masked to allocation assessed patients at baseline, 3, 6, 12, 24 months and 5 years. The primary outcome was change in the HAI score between baseline and 12 months. Main secondary outcomes - costs of care in the two groups after 24 and 60 months, change in health anxiety (HAI), generalised anxiety and depression [Hospital Anxiety and Depression Scale (HADS)] scores, social functioning using the Social Functioning Questionnaire and quality of life using the EuroQol-5 Dimensions (EQ-5D), at 6, 12, 24 and 60 months, and deaths over 5 years. RESULTS: Of the 28,991 patients screened over 21 months, 5769 had HAI scores of ≥ 20 points. Improvement in HAI scores at 3 months was significantly greater in the CBT-HA group (mean number of sessions = 6) than in the standard care, and this was maintained over the 5-year period (overall p < 0.0001), with no loss of efficacy between 2 and 5 years. Differences in the generalised anxiety (p = 0.0018) and depression scores (p = 0.0065) on the HADS were similar in both groups over the 5-year period. Gastroenterology and cardiology patients showed the greatest CBT gains. The outcomes for nurses were superior to those of other therapists. Deaths (n = 24) were similar in both groups; those in standard care died earlier than those in CBT-HA. Patients with mild personality disturbance and higher dependence levels had the best outcome with CBT-HA. Total costs were similar in both groups over the 5-year period (£12,590.58 for CBT-HA; £13,334.94 for standard care). CBT-HA was not cost-effective in terms of quality-adjusted life-years, as measured using the EQ-5D, but was cost-effective in terms of HAI outcomes, and offset the cost of treatment. LIMITATIONS: Many eligible patients were not randomised and the population treated may not be representative. CONCLUSIONS: CBT-HA is a highly effective treatment for pathological health anxiety with lasting benefit over 5 years. It also improves generalised anxiety and depressive symptoms more than standard care. The presence of personality abnormality is not a bar to successful outcome. CBT-HA may also be cost-effective, but the high costs of concurrent medical illnesses obscure potential savings. This treatment deserves further research in medical settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14565822. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 50. See the NIHR Journals Library website for further project information.

A prospective, quantitative study of mental health act assessments in England following the 2007 amendments to the 1983 act: did the changes fulfill their promise?

BACKGROUND: In 2008, the Mental Health Act (MHA) 2007 amendments to the MHA 1983 were implemented in England and Wales. The amendments were intended to remove perceived obstacles to the detention of high risk patients with personality disorders (PDs), sexual deviance and learning disabilities (LDs). The AMEND study aimed to test the hypothesis that the implementation of these changes would lead to an increase in numbers or proportions of patients with these conditions who would be assessed and detained under the MHA 2007. METHOD: A prospective, quantitative study of MHA assessments undertaken between July-October 2008-11 at three English sites. Data were collected from local forms used for MHA assessment documentation and patient electronic databases. RESULTS: The total number of assessments in each four month period of data collection varied: 1034 in 2008, 1042 in 2009, 1242 in 2010 and 1010 in 2011 (n = 4415). Of the assessments 65.6% resulted in detention in 2008, 71.3% in 2009, 64.7% in 2010 and 63.5% in 2011. There was no significant change in the odds ratio of detention when comparing the 2008 assessments against the combined 2009, 2010 and 2011 data (OR = 1.025, Fisher's exact Χ 2 p = 0.735). Only patients with LD and 'any other disorder or disability of the mind' were significantly more likely to be assessed under the MHA post implementation (Χ2 = 5.485, P = 0.018; Χ2 = 24.962, P > 0.001 respectively). There was no significant change post implementation in terms of the diagnostic category of detained patients. CONCLUSIONS: In the first three years post implementation, the 2007 Act did not facilitate the compulsory care of patients with PDs, sexual deviance and LDs.

Xenopus pitx3 target genes lhx1 and xnr5 are identified using a novel three-fluor flow cytometry-based analysis of promoter activation and repression.

BACKGROUND: Pitx3 plays a well understood role in directing development of lens, muscle fiber, and dopaminergic neurons; however, in Xenopus laevis, it may also play a role in early gastrulation and somitogenesis. Potential downstream targets of pitx3 possess multiple binding motifs that would not be readily accessible by conventional promoter analysis. RESULTS: We isolated and characterized pitx3 target genes lhx1 and xnr5 using a novel three-fluor flow cytometry tool that was designed to dissect promoters with multiple binding sites for the same transcription factor. This approach was calibrated using a known pitx3 target gene, Tyrosine hydroxylase. CONCLUSIONS: We demonstrate how flow cytometry can be used to detect gene regulatory changes with exquisite precision on a cell-by-cell basis, and establish that in HEK293 cells, pitx3 directly activates lhx1 and represses xnr5. Developmental Dynamics 246:657-669, 2017. © 2017 Wiley Periodicals, Inc.

An audit of the quality of inpatient care for adults with learning disability in the UK.

OBJECTIVES: To audit patient hospital records to evaluate the performance of acute general and mental health services in delivering inpatient care to people with learning disability and explore the influence of organisational factors on the quality of care they deliver. SETTING: Nine acute general hospital Trusts and six mental health services. PARTICIPANTS: Adults with learning disability who received inpatient hospital care between May 2013 and April 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: Data on seven key indicators of high-quality care were collected from 176 patients. These covered physical health/monitoring, communication and meeting needs, capacity and decision-making, discharge planning and carer involvement. The impact of services having an electronic system for flagging patients with learning disability and employing a learning disability liaison nurse was assessed. RESULTS: Indicators of physical healthcare (body mass index, swallowing assessment, epilepsy risk assessment) were poorly recorded in acute general and mental health inpatient settings. Overall, only 34 (19.3%) patients received any assessment of swallowing and 12 of the 57 with epilepsy (21.1%) had an epilepsy risk assessment. For most quality indicators, there was a non-statistically significant trend for improved performance in services with a learning disability liaison nurse. The presence of an electronic flagging system showed less evidence of benefit. CONCLUSIONS: Inpatient care for people with learning disability needs to be improved. The work gives tentative support to the role of a learning disability liaison nurse in acute general and mental health services, but further work is needed to confirm these benefits and to trial other interventions that might improve the quality and safety of care for this high-need group.

The use of psychotropic medication in patients with emotionally unstable personality disorder under the care of UK mental health services.

BACKGROUND: Guideline recommendations for the pharmacologic treatment of personality disorder lack consensus, particularly for emotionally unstable personality disorder (EUPD), and there is limited information on current prescribing practice in the United Kingdom. OBJECTIVE: To characterize the nature and quality of current prescribing practice for personality disorder across the United Kingdom, as part of a quality improvement program. METHOD: A cross-sectional survey of self-selected psychiatric services providing care for adults with personality disorder (ICD-10 criteria) was conducted. Data were collected during May 2012. RESULTS: Of 2,600 patients with a diagnosis of personality disorder, more than two-thirds (68%) had a diagnosis of EUPD. Almost all (92%) patients in the EUPD subgroup were prescribed psychotropic medication, most commonly an antidepressant or antipsychotic, principally for symptoms and behaviors that characterize EUPD, particularly affective dysregulation. Prescribing patterns were similar between those who had a diagnosed comorbid mental illness and those who had EUPD alone, but the latter group was less likely to have had their medication reviewed over the previous year, particularly with respect to tolerability (53% vs 43%). CONCLUSIONS: The use of psychotropic medication in EUPD in the United Kingdom is largely outside the licensed indications. Whether the treatment target is identified as intrinsic symptoms of EUPD or comorbid mental illness may depend on the diagnostic threshold of individual clinicians. Compared with prescribing for EUPD where there is judged to be a comorbid mental illness, the use of off-label medication for EUPD alone is less systematically reviewed and monitored, so opportunities for learning may be lost. Treatment may be continued long term by default.

Therapist differences in a randomised trial of the outcome of cognitive behaviour therapy for health anxiety in medical patients.

BACKGROUND: Health anxiety is common in medical settings and can be treated successfully by cognitive behaviour therapy. However it is not clear who might be best placed to deliver this therapy. OBJECTIVES: In a planned secondary analysis of data from a randomised trial of adapted cognitive behaviour therapy for health anxiety we compared outcomes of therapy delivered by nurses and other professional groups. DESIGN: A randomised controlled trial with two treatment arms, 5-10 sessions of cognitive behaviour therapy adapted health anxiety or standard care. SETTING: Cardiology, endocrine, gastroenterology, neurological and respiratory clinics in six general hospitals in the UK covering urban, suburban and rural areas. PARTICIPANTS: Medical patients attending the clinics who had pathological health anxiety and also scored for a diagnosis of hypochondriasis. METHODS: Patients were randomised to one of two treatment arms, 5-10 sessions of cognitive behaviour therapy adapted health anxiety or standard care delivered by naive therapists (not randomised) who were trained in advance before delivering the treatment. Independent assessment of outcomes by researchers masked to allocation status at 3m, 6m, 12m and 24m. RESULTS: 444 patients were randomised in the trial, 219 to cognitive behaviour therapy adapted health anxiety and 225 to standard care. 373 (84%) completed assessments after two years. Those treated by nurses (n=66) had improvement in health anxiety, generalised anxiety and depression outcomes that were significantly better and twice as great as those of the professional groups of assistant psychologists (n=87) and graduate workers (n=66) (P<0.01 over all time points). The number needed to treat to show superiority of nurse-delivered treatment over other treatment delivery was 4 at 6 months and 6 at one year. CONCLUSION: General nurses, after suitable training, are very effective therapists for patients with health anxiety in medical clinics and should be the therapists of choice for patients in these settings.

Microinjection manipulations in the elucidation of Xenopus brain development.

Microinjection has a long and distinguished history in Xenopus and has been used to introduce a surprisingly diverse array of agents into embryos by both intra- and intercellular means. In addition to nuclei, investigators have variously injected peptides, antibodies, biologically active chemicals, lineage markers, mRNA, DNA, morpholinos, and enzymes. While enumerating many of the different microinjection approaches that can be taken, we will focus upon the mechanical operations and options available to introduce mRNA, DNA, and morpholinos intracellularly into early stage embryos for the study of neurogenesis.

Microarray-based identification of Pitx3 targets during Xenopus embryogenesis.

BACKGROUND: Unexpected phenotypes resulting from morpholino-mediated translational knockdown of Pitx3 in Xenopus laevis required further investigation regarding the genetic networks in which the gene might play a role. Microarray analysis was, therefore, used to assess global transcriptional changes downstream of Pitx3. RESULTS: From the large data set generated, selected candidate genes were confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization. CONCLUSIONS: We have identified four genes as likely direct targets of Pitx3 action: Pax6, ß Crystallin-b1 (Crybb1), Hes7.1, and Hes4. Four others show equivocal promise worthy of consideration: Vent2, and Ripply2 (aka Ledgerline or Stripy), eFGF and RXRα. We also describe the expression pattern of additional and novel genes that are Pitx3-sensitive but that are unlikely to be direct targets.

Classifying personality disorder according to severity.

Current systems for classifying personality disorder according to specific categories are unsatisfactory because they do not take account of wide variations in levels of personality disturbance and associated impairment. We review previous attempts to classify personality disorder according to severity and place these findings in the context of work exploring the severity of other mental disorders. On the basis of these findings, we propose a new system for classifying personality-related problems based on severity defined by the extent of personality disturbance, the level of social dysfunctioning, and the impact of the disorder for individuals and society. We recognize that studies using these definitions will need piloting and testing in field trials, but believe that this simplified approach to classifying personality disorder would encourage greater use by clinicians and assist those involved in planning services for people with personality disorder.

The central domains of personality pathology in psychiatric patients.

There is general agreement that the classification of personality disorders in DSM-IV is unsatisfactory. We systematically reviewed all studies that have analyzed patterns of personality disorder symptoms and signs in psychiatric patients; twenty-two papers were included in the final synthesis. There is reasonable consistency over the number and type of personality pathology traits reported despite differing samples, varying assessment methods, and different statistical manipulations. There are three or four high order traits; an externalizing factor incorporating borderline, narcissistic, histrionic, and antisocial traits (the latter is sometimes recorded as a separate trait); an internalizing factor incorporating avoidant and dependent traits; a schizoid factor; and often a compulsive factor. Using these domains of personality pathology would simplify classification, have higher clinical utility, and allow relatively easy translation of current research.

Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice.

A central hypothesis for the limited capacity for adult central nervous system (CNS) axons to regenerate is the presence of myelin-derived axon growth inhibitors, the role of which, however, remains poorly understood. We have conducted a comprehensive genetic analysis of the three major myelin inhibitors, Nogo, MAG, and OMgp, in injury-induced axonal growth, including compensatory sprouting of uninjured axons and regeneration of injured axons. While deleting any one inhibitor in mice enhanced sprouting of corticospinal or raphespinal serotonergic axons, there was neither associated behavioral improvement nor a synergistic effect of deleting all three inhibitors. Furthermore, triple-mutant mice failed to exhibit enhanced regeneration of either axonal tract after spinal cord injury. Our data indicate that while Nogo, MAG, and OMgp may modulate axon sprouting, they do not play a central role in CNS axon regeneration failure.

Expression of CAP2 during early Xenopus embryogenesis.

We have cloned and characterized a second member of the Xenopus CAP (cyclase associated protein) gene family. xCAP2 demonstrates greater restriction of expression than its homolog, xCAP1, and is differentially expressed throughout early embryogenesis. Although present as a maternal transcript, CAP2 comes to be expressed in the anterior-most mesoderm/endoderm during late gastrulation, in paraxial mesoderm during late neurula stages, and later expresses in lens, cardiac primordia, somites, otic vesicles, retina, and in the optic and craniofacial musculature. The gene is also expressed in the leading edge of myotome.