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Biomedical subjects

Richard J Brown

Publications and source records attributed to Richard J Brown.

12 recordsLinked to original sources

Different types of "dissociation" have different psychological mechanisms.

The term "dissociation" has been used to describe a wide range of psychological and psychiatric phenomena. The popular conception of dissociation describes it as a unitary phenomenon, with only quantitative differences in severity between the various dissociative conditions. More recently, it has been argued that the available evidence is more consistent with a model that identifies at least two distinct categories of dissociative phenomena-"detachment" and "compartmentalization"- that have different definitions, mechanisms and treatment implications (Holmes, Brown, Mansell, Fearon, Hunter, Frasquilho & Oakley 2005). This paper presents evidence for this bipartite model of dissociation, followed by definitions and descriptions of detachment and compartmentalization. Possible psychological mechanisms underlying these phenomena are then discussed, with particular emphasis on the nature of compartmentalization in conversion disorder, hypnosis, dissociative amnesia and dissociative identity disorder.

Amnesia↗

Model for growth hormone receptor activation based on subunit rotation within a receptor dimer.

Growth hormone is believed to activate the growth hormone receptor (GHR) by dimerizing two identical receptor subunits, leading to activation of JAK2 kinase associated with the cytoplasmic domain. However, we have reported previously that dimerization alone is insufficient to activate full-length GHR. By comparing the crystal structure of the liganded and unliganded human GHR extracellular domain, we show here that there is no substantial change in its conformation on ligand binding. However, the receptor can be activated by rotation without ligand by inserting a defined number of alanine residues within the transmembrane domain. Fluorescence resonance energy transfer (FRET), bioluminescence resonance energy transfer (BRET) and coimmunoprecipitation studies suggest that receptor subunits undergo specific transmembrane interactions independent of hormone binding. We propose an activation mechanism involving a relative rotation of subunits within a dimeric receptor as a result of asymmetric placement of the receptor-binding sites on the ligand.

Amino Acid Sequence↗

Are there two qualitatively distinct forms of dissociation? A review and some clinical implications.

This review aims to clarify the use of the term 'dissociation' in theory, research and clinical practice. Current psychiatric definitions of dissociation are contrasted with recent conceptualizations that have converged on a dichotomy between two qualitatively different phenomena: 'detachment' and 'compartmentalization'. We review some evidence for this distinction within the domains of phenomenology, factor analysis of self-report scales and experimental research. Available evidence supports the distinction but more controlled evaluations are needed. We conclude with recommendations for future research and clinical practice, proposing that using this dichotomy can lead to clearer case formulation and an improved choice of treatment strategy. Examples are provided within Depersonalization Disorder, Conversion Disorder and Posttraumatic Stress Disorder (PTSD).

Consciousness↗

Pediatric upper extremity replantation.

The evolution of microsurgical technique has led to increasing success with pediatric replantation. The broader inclusion criteria for pediatric replantation, together with the greater technical demands of repair and the less favorable mechanism of pediatric amputations (crush-avulsion), yield a slightly lower overall survival rate than in adults. The superior nerve and soft tissue regenerative capacity of children appears to produce better functional outcomes. Nonetheless, the issue of cosmesis and developing self-image in a child may have ramifications beyond a simple calculus of range of motion and strength variables--hence the imperative that microsurgical salvage be attempted in pediatric upper-extremity amputations.

Amputation, Traumatic↗

Dissociation, childhood interpersonal trauma, and family functioning in patients with somatization disorder.

OBJECTIVE: The goals of this study were to determine 1) the occurrence of various dissociative phenomena in patients with somatization disorder, 2) the occurrence of six different types of childhood interpersonal trauma in these patients, and 3) the nature of these patients' early family environment. METHOD: Twenty-two patients with somatization disorder and 19 medical comparison subjects completed the Structured Clinical Interview for DSM-IV Dissociative Disorders, the Childhood Trauma Interview, and the Family Functioning Scale. RESULTS: The somatization disorder patients reported significantly higher level of dissociative amnesia than the comparison subjects. The two groups reported similar levels of depersonalization, derealization, identity confusion, and identity alteration. Somatization disorder patients reported significantly greater childhood emotional abuse and more severe forms of physical abuse, relative to the comparison subjects, with chronic emotional abuse being the best predictor of unexplained symptoms. Childhood sexual abuse, separation/loss, and witnessing violence were equally common in the two groups. The somatization disorder group reported significantly more family conflict and less family cohesion. CONCLUSIONS: Only some types of dissociation are more severe in patients with somatization disorder, relative to medical comparison subjects. Many patients with somatization disorder are raised in an emotionally cold, distant, and unsupportive family environment characterized by chronic emotional and physical abuse. Sexual abuse is not a necessary prerequisite for the disorder.

Adult↗

Crystallization and preliminary X-ray diffraction analysis of the unliganded human growth hormone receptor.

The crystal structure of the extracellular domain of growth hormone receptor complexed to its ligand, growth hormone, has been known since 1992. However, no information exists for the unliganded form of the receptor. The human growth hormone receptor's extracellular ligand-binding domain, encompassing amino-acid residues 1-238, has been expressed in Escherichia coli, purified by anion ion-exchange chromatography and crystallized in its unliganded state by the hanging-drop vapour-diffusion method in 100 mM HEPES pH 7.0 containing 27.5%(w/v) PEG 5000 monomethyl ether and 200 mM ammonium sulfate as the co-precipitants. The crystals belong to the othorhombic space group C222(1), have unit-cell parameters a = 99.7, b = 112.2, c = 93.2 A and diffract to 2.5 A resolution using synchrotron radiation. The crystal structure will shed light on the nature of any conformation changes that occur upon ligand binding and will provide information to develop potential low-molecular-weight agonists/antagonists to treat clinical diseases in which the growth hormone receptor is implicated.

Chromatography, Ion Exchange↗

Psychological mechanisms of medically unexplained symptoms: an integrative conceptual model.

Theories of medically unexplained illness based on the concepts of dissociation, conversion, and somatization are summarized. Evidence cited in support of these theories is described and the conceptual strengths and shortcomings of each approach are considered. It is argued that each of these approaches adds to the understanding of unexplained illness but that none is able to provide a comprehensive explanation of the phenomenon. An integrative conceptual model of unexplained illness based on cognitive psychological principles is then presented. This model attempts to combine existing theoretical approaches within a single explanatory framework, extending previous theory by explaining how compelling symptoms can exist in the absence of organic pathology. The clinical and empirical implications of the model are then considered.

Diagnosis, Differential↗

The impact of different directed forgetting instructions on implicit and explicit memory: new evidence from a modified process dissociation procedure.

In contrast to previous research on directed forgetting, the present studies adopted a recent modification of the process dissociation procedure (Jacoby, 1991; Richardson-Klavehn & Gardiner, 1995) to accommodate the cross-contamination of memory test performance by implicit and explicit memorial factors. In Experiment 1, 120 subjects were compared in global directed forgetting, item-by-item directed forgetting, and control conditions on estimates of voluntary conscious memory, involuntary conscious memory, and involuntary unconscious memory performance. In Experiment 2, 80 subjects were compared in specific directed forgetting and control conditions on estimates of voluntary conscious memory, involuntary conscious memory, and involuntary unconscious memory performance. Subjects showed significant decrements in voluntary and involuntary conscious memory performance following instructions for directed forgetting in all conditions. None of the directed forgetting conditions showed a decrement in involuntary unconscious memory performance. Results suggest that, regardless of instruction type, directed forgetting prevents the conscious expression of memorial information (both voluntary and involuntary) while leaving unconscious memory intact.

Adult↗

Genes induced by growth hormone in a model of adipogenic differentiation.

A substantial number of GH regulated genes have been reported in mature hepatocytes, but genes involved in GH-initiated cell differentiation have not yet been identified. Here we have studied a well-characterised model of GH-dependent differentiation, adipogenesis of 3T3-F442A preadipocytes, to identify genes rapidly induced by GH. Using the suppression subtractive hybridisation technique, we have identified eight genes induced within 60 min of GH treatment, and verified these by northern analysis. Six were identifiable as Stat 2, Stat 3, thrombospondin-1, oncostatin M receptor beta chain, a DEAD box RNA helicase, and muscleblind, a developmental transcription factor. Bioinformatic approaches assigned one of the two remaining unknown genes as a novel 436 residue serine/threonine kinase. As each of the identified genes have important developmental roles, they may be important in initiating GH-induced adipogenesis.

Adipocytes↗

Suggestibility and negative priming: two replication studies.

Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

Adult↗

The cognitive psychology of dissociative states.

INTRODUCTION: A number of theoretical models have identified dissociation as a possible cognitive mechanism underlying medically unexplained symptoms (''hysteria''). A review of research and theory in this area indicates that the dissociation concept is a useful explanation of this phenomenon. However, existing models of dissociation have a number of explanatory shortcomings. METHODS: This article describes a recent model of unexplained illness that aims to extend the dissociation concept by reference to research and theory from contemporary cognitive psychology. RESULTS: According to this view, unexplained symptoms should be regarded as disturbances of consciousness and behavioural control, resulting from the chronic activation of stored symptom representations within memory. This process is driven by the repeated reallocation of high-level attention on to symptom representations. CONCLUSIONS: The model offers a fresh perspective on the nature of unexplained symptoms, providing an explicit account of the factors involved in the creation and maintenance of this phenomenon.

Journal Article↗