“The Therapist's Voice” The life force

Three-hundred-and-fifty-nine Chinese pregnant women were surveyed to determine prevalence and psychosocial correlates of eating disturbance in pregnancy. About 9.8% of participants reported disordered eating symptoms. Prevalence of these symptoms was related to general factors of drive for thinness, body image dissatisfaction, and traditional gender role attitudes. These general factors were, in turn, associated with factors specific to pregnant women. In particular, drive for thinness was related to poor spousal support; body image dissatisfaction was related to poor maternal-fetal attachment; and traditional gender role attitudes were related to strong maternal-fetal attachment and spousal support. Limitations and implications of these findings are discussed.     

Letter From The Editors-In-Chief

Dear Colleagues,Despite 2021 is a year full of challenges and continued to be so,it has been a busy and encouraging year for Neural Regeneration Research(NRR)!Since 2020 with the new impact factor reached 3.171.NRR became top 50%of neuroscience journals(JCR Q2,among 271 journals under the specialty"Neurosciences").In the past year,NRR has made great progress,especially in internationalization and the scientific level,and has the strength to compete with recognized journals in the same field.     

The opsoclonus–myoclonus syndrome

The opsoclonus–myoclonus syndrome is a rare and distinct neurological disorder characterised by rapid multidirectional conjugate eye movements (opsoclonus), myoclonus and ataxia, along with behavioural changes in adults and irritability in children. Sometimes it is due to a self-limiting presumed para-infectious brainstem encephalitis but it may also represent a non-metastatic manifestation of neuroblastoma in children and small cell carcinoma of the lung in adults. In this article, we will describe the clinical features, diagnosis, pathogenesis and management.     

The Dopamine Hypothesis of Schizophrenia: Version III��The Final Common Pathway

The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia—version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.     

The β-secretase, BACE

Evidence suggests that the β-amyloid peptide (Aβ) is central to the pathophysiology of Alzheimer’s disease (AD). Amyloid plaques, primarily composed of Aβ, progressively develop in the brains of AD patients, and mutations in three genes (APP, PS1, and PS2) cause early onset familial AD (FAD) by directly increasing synthesis of the toxic, plaque-promoting Aβ42 peptide. Given the strong association between Aβ and AD, therapeutic strategies to lower the concentration of Aβ in the brain should prove beneficial for the treatment of AD. One such strategy would involve inhibiting the enzymes that generate Aβ. Aβ is a product of catabolism of the large TypeI membrane protein, amyloid precursor protein (APP). Two proteases, called β- and γ-secretase, mediate the endoproteolysis of APP to liberate the Aβ peptide. For over a decade, the molecular identities of these proteases were unknown. Recently, the γ-secretase has been tentatively identified as the presenilin proteins, PS1 and PS2, and the identity of the β-secretase has been shown to be the novel transmembrane aspartic protease, β-site APP cleaving enzyme 1 (BACE1; also called Asp2 and memapsin2). BACE2, a novel protease homologous to BACE1, was also identified, and together the two enzymes define a new family of transmembrane aspartic proteases. BACE1 exhibits all the properties of the β-secretase, and as the key rate-limiting enzyme that initiates the formation of Aβ, BACE1 is an attractive drug target for AD. Here, I review the identification and initial characterization of BACE1 and BACE2, and summarize our current understanding of BACE1 post-translational processing and intracellular trafficking. In addition, I discuss recent studies of BACE1 knockout mice and the BACE1 X-ray structure, and relate implications for BACE1 drug development.     

Serotonin: The Anti-SuddenDeathAmine?

Sudden unexpected death in epilepsy (SUDEP) is an exceptionally difficult condition to study in humans. Therefore, translational research in animal models has been very important in defining pathophysiological mechanisms of death and identifying potential treatments. These models are helping define whether the primary mechanism of death is cardiac or respiratory. They have also identified a link to the serotonergic system of the brainstem; this, in turn, led to recognition that SUDEP and sudden infant death syndrome (SIDS) may share a common final pathway in the sequence of events that lead to death.SUDEP is responsible for 10 to 50 percent of deaths in those with chronic refractory epilepsy (1–4), but its sporadic occurrence is infrequent enough that it is hard to capture cardiovascular, respiratory, EEG, and other physiological data during actual SUDEP events. Our understanding of mechanisms in humans comes in part from those rare patients who died—or came close—while in epilepsy monitoring units (EMUs) (3, 5). It is not known if the small number of reported cases is representative of the rest of SUDEP deaths. Another clue to the mechanisms comes from human data showing that it is common for seizures to induce cardiovascular (1) and respiratory dysfunction (6–8), but these events are very common but rarely fatal. There is no evidence that having severe cardiovascular and respiratory changes with seizures predisposes a patient to SUDEP, but it seems likely to be the case. The human data are valuable and important, but with rare exceptions they are from epilepsy patients who did not die, so it is unclear whether the data are relevant to actual SUDEP.     

Professionals’ Attitudes Toward Reducing Restraint: The Case of Seclusion in The Netherlands

Introduction

Despite public opinion and policy interventions, restraint remains a common practice. This is also the case in the Netherlands, where projects aimed to reduce seclusion, have not lead to a decreased use of restraint. Is this lack of effectiveness related to attitudes of the professionals? The aim of this study was to explore the attitudes of professionals working in mental health care toward restraint.

Method

A questionnaire with eight scales was constructed for measuring attitudes of professionals. Scores of 540 professionals were studied, using analysis of variance and cluster analysis and related to several personnel and organizational characteristics.

Results

The more professionals were personally involved in seclusion, the more they believed in it. Three types of professionals were identified: Transformers, Doubters and Maintainers. More than half of the psychiatrists (56%) belonged to the type of maintainers. Nurses were more divided.

Conclusion

Professionals working in clinical settings are not really opposed to restraint. This could explain the limited effects of innovation projects.     

The best medicine? The influence of physical activity and inactivity on Parkinson's disease

The incidence of Parkinson's disease (PD) is expected to increase as our population ages and will likely strain the projected capacity of our health care system. Despite being the most common movement disorder, there have been few noninvasive therapeutic advances for people with PD since the first levodopa clinical trial in 1961. The study of PD pathogenesis, combined with an appreciation for the biochemical mechanisms by which physical activity and exercise may impact physiology, has resulted in emerging hypotheses for new modifiable risk factors for PD. Physical activity and exercise as a means of preventing PD, or maintaining the functionality of people with PD, are a promising area of investigation. Conversely, physical inactivity is implicated in many disease states, some of which are also correlated with the development of PD, such as metabolic syndrome. The primary relationship between these diseases is likely rooted in heightened inflammation and oxidative stress at the cellular level. Physical activity and exercise as a means of attenuating inflammation have led to increased interest in related potential therapeutic targets for PD. Ultimately, these findings may translate into low‐cost, universally available therapies for PD disease modification or prevention. © 2016 International Parkinson and Movement Disorder Society     

The Structure of The Extended Psychosis Phenotype in Early Adolescence—A Cross-sample Replication

The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and structure of the extended psychosis phenotype was investigated. Positive psychotic experiences, broadly defined, were reported by the majority of adolescents. Exploratory analysis with Structural Equation Modelling (Exploratory Factor Analysis followed by Confirmatory Factor Analysis [CFA]) in sample 1 suggested that psychotic experiences were best represented by 5 underlying dimensions; CFA in sample 2 provided a replication of this model. Dimensions were labeled Hallucinations, Delusions, Paranoia, Grandiosity, and Paranormal beliefs. Prevalences differed strongly, Hallucinations having the lowest and Paranoia having the highest rates. Girls reported more experiences on all dimensions, except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations, Delusions, and Paranoia, but not Grandiosity and Paranormal beliefs, were associated with distress and general measures of psychopathology. Thus, only some of the dimensions of the extended psychosis phenotype in young people may represent a continuum with more severe psychopathology and predict later psychiatric disorder.     

The tip of the iceberg?The underestimated potential of non-canonical beta-amyloids for Alzheimer's disease

<正>Formation and deposition of amyloid-beta(Aβ) are considered one of the main drivers of Alzheimer’s disease(AD). For more than 30 years, Aβ has challenged researchers through its complex physicochemical properties and multiple peptide processing steps that involve several proteases(Andreasson et al., 2007),     

The immunobiology of Guillain-Barré syndromes

This presentation highlights aspects of the immunobiology of the Guillain-Barré syndromes (GBS), the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the key pathophysiological pathways of GBS and developing rational, specific immunotherapies are essential steps towards improving the clinical outcome of this devastating disorder. Much of the research into GBS over the last decade has focused on the forms mediated by anti-ganglioside antibodies, and we have made substantial progress in our understanding in several related areas. Particular highlights include (a) the emerging correlations between anti-ganglioside antibodies and specific clinical phenotypes, notably between anti-GM1/anti-GD1a antibodies and the acute motor axonal variant and anti-GQ1b/anti-GT1a antibodies and the Miller Fisher syndrome; (b) the identification of molecular mimicry between GBS-associated Campylobacter jejuni oligosaccharides and GM1, GD1a, and GT1a gangliosides as a mechanism for anti-ganglioside antibody induction; (c) the development of rodent models of GBS with sensory ataxic or motor phenotypes induced by immunisation with GD1b or GM1 gangliosides, respectively. Our work has particularly studied the motor nerve terminal as a model site of injury, and through combined active and passive immunisation paradigms, we have developed murine neuropathy phenotypes mediated by anti-ganglioside antibodies. This has been achieved through use of glycosyltransferase and complement regulator knock-out mice, both for cloning anti-ganglioside antibodies and inducing disease. Through such studies, we have proven a neuropathogenic role for murine anti-ganglioside antibodies and human GBS-associated antisera and identified several determinants that influence disease expression including (a) the level of immunological tolerance to microbial glycans that mimic self-gangliosides; (b) the ganglioside density in target tissue; (c) the level of complement activation and the neuroprotective effects of endogenous complement regulators; and (d) the role of calcium influx through complement pores in mediating axonal injury. Such studies provide us with clear information on an antibody-mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in humans.     

Excerpts from “The Organism”

In this article, I contend that John Macmurray's philosophy of community provides a perspective that can add to our understanding of parent–infant interactions, omnipotence, transference, and psychoanalytic goals. In brief, Macmurray defines community as mutual/personal forms of associations wherein persons recognize and treat each other as persons—unique, responsive, agentic, centers of subjectivity. From a developmental view, for Macmurray, it is the parent's intentional recognition and omnipotent construction of the baby as a person that shape and govern the infant's impulse to communicate. Initially, the infant's impulse to communicate involves omnipotent impersonal recognition of objects—whereby the objects are recognized primarily in terms of utility, benefit, and function. The parent's personalization enables the child, in time, to subordinate impersonal recognition to personal recognition. Transference, from this standpoint, is understood as a confluence of past forms of impersonal associations and the wish for mutual/personal associations. The psychoanalytic relationship, while a contractual association, instantiates mutual/personal associations. Thus, an aim of psychoanalytic psychotherapy is community, which for Macmurray is the crucible where persons experience freedom, as well as being alive and real.