Publications by authors named "John L Waddington"

Article Synopsis
  • Scientists studied how a type of receptor in the brain called kappa (κ) opioid receptors affects eating and sugar levels in the body.
  • They found that a drug called nalfurafine increased how much food animals ate, but only when they weren't hungry.
  • This study suggests that nalfurafine might help people with a loss of appetite caused by cancer treatment.
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A wide array of biological abnormalities in psychotic illness appear to reflect non-cerebral involvement. This review first outlines the evidence for such a whole-body concept of schizophrenia pathobiology, focusing particularly on cardiovascular disease, metabolic syndrome and diabetes, immunity and inflammation, cancer, and the gut-brain axis. It then considers the roles of miRNAs in general and of miRNA-143 in particular as they relate to the epidemiology, pathobiology, and treatment of schizophrenia.

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Development of the craniofacies occurs in embryological intimacy with development of the brain and both show normal left-right asymmetries. While facial dysmorphology occurs to excess in psychotic illness, facial asymmetry has yet to be investigated as a putative index of brain asymmetry. Ninety-three subjects (49 controls, 22 schizophrenia, 22 bipolar disorder) received 3D laser surface imaging of the face.

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Background And Purpose: Diabetic patients have an increased risk of psychiatric disorders. Because hyperglycaemia increases L-lactate in the brain and L-lactate inhibits AMP-activated protein kinase (AMPK), this study investigated the role of L-lactate and AMPK in strengthened fear memory, a model for human psychiatric disorders, in diabetic mice.

Experimental Approach: The diabetic model was mice injected with streptozotocin.

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Article Synopsis
  • Lipopolysaccharide (LPS) from Gram-negative bacteria activates Toll-like receptors (TLRs) and may affect locomotion in mice when exposed to new environments, with Porphyromonas gingivalis (Pg) LPS's influence being previously unknown.
  • In this study, researchers compared the effects of Pg-LPS and Escherichia coli (Ec-LPS) on mouse locomotion and blood levels of inflammatory markers IL-6, TNF-alpha, and IL-10, using a TLR4 antagonist (TAK-242) to assess TLR4's role.
  • Results showed that while Ec-LPS inhibited locomotion and increased IL-6 and IL-10 levels, Pg-LPS did not produce
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Aberrant attentional salience has been implicated in the cannabis-psychosis association. Here, history and frequency of cannabis use were examined against changes in overshadowing (OS), a cue competition paradigm that involves salience processing. Additionally, we examined the association between OS and alternative measures of aberrant salience, as well as schizotypy, in a non-clinical adult sample.

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SCH23390 is a widely used D dopamine receptor (DR) antagonist that also elicits some DR-independent effects. We previously found that the benzazepine, SKF83959, an analog of SCH23390, produces positive allosteric modulation of the Sigma-1 receptor (Sig1R). SCH23390 does not bind to the orthodoxic site of Sig1R but enhances the binding of H (+)-pentazocine to Sig1R.

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Article Synopsis
  • Patients with cancer are more likely to have psychiatric disorders, but the reason behind this is not well understood.
  • A study using tumor-bearing mice revealed that they have difficulties in overcoming conditioned fear due to changes in certain cytokines, particularly IL-1β and KC, which interact with brain regions involved in fear memory.
  • The findings suggest that increased levels of specific cytokines may disrupt fear memory extinction by affecting microglia in the hippocampus, highlighting a potential link between cancer and psychological changes.
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While duration of the psychosis prodrome (DPP) attracts attention in relation to the developmental trajectory of psychotic illness and service models, fundamental issues endure in the context of dimensional-spectrum models of psychosis. Among 205 epidemiologically representative subjects in the Cavan-Monaghan First Episode Psychosis Study, DPP was systematically quantified and compared, for the first time, across all 12 DSM-IV psychotic diagnoses. DPP was also compared with duration of untreated psychosis (DUP) and each was then analysed in relation to premorbid features across three age ranges: <12, 12-15 and 16-18 years.

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Substance use disorder remains a major challenge, with an enduring need to identify and evaluate new, translational targets for effective treatment. Here, we report the upregulation of Hypoxia-inducible factor-1α (HIF-1α) expression by roxadustat (Rox), a drug developed for renal anemia that inhibits HIF prolyl hydroxylase to prevent degradation of HIF-1α, administered either systemically or locally into selected brain regions, suppressed morphine (Mor)-induced conditioned place preference (CPP). A similar effect was observed with methamphetamine (METH).

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Glucose metabolism is reported to be regulated by the central nervous system, but it is unclear whether this regulation is altered in diabetes. We investigated whether regulation of glucose metabolism by central dopamine D receptors is altered in type 1 and type 2 diabetic models. Intracerebroventricular injections of both the dopamine D receptor agonist quinpirole and the antagonist l-sulpiride induced hyperglycemia in control mice, but not in streptozotocin (STZ)-induced diabetic mice, a type 1 diabetic model.

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Nandrolone, an anabolic androgenic steroid, is included in the prohibited list of the World Anti-Doping Agency. Drugs of abuse activate brain dopamine neurons and nandrolone has been suspected of inducing dependence. Accordingly, possible critical periods for the effects of nandrolone on muscular strength and dopaminergic activity have been investigated, including the effects of chronically administered nandrolone alone and on morphine-induced increases in dopamine efflux in the nucleus accumbens.

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Psychiatry is currently negotiating several challenges that are typified by (but are not unique to) schizophrenia: do periodic refinements in operational diagnostic algorithms (a) resolve intricacies and subtleties within and between psychotic and non-psychotic disorders that are authentic and impactful, or (b) constitute arbitrary and porous boundaries that should be complemented, or even replaced, by dimensional-continuum concepts of abnormality and dysfunction. Critically, these issues relate not only to apparent boundaries between diagnoses but also to those between 'health' and 'illness'. This article considers catatonia within evolving dimensional-continuum approaches to the description of impairment and dysfunction among psychotic and non-psychotic disorders.

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In the first half of the 20th century, well before the antipsychotic era, paratonia, Gegenhalten and psychomotor hypertonia were described as new forms of hypertonia intrinsic to particular psychoses and catatonic disorders. A series of astute clinical observations and experiments supported their independence from rigidity seen in Parkinson's disease. After World War II, motor disorders went out of fashion in psychiatry, with drug-induced parkinsonism becoming the prevailing explanation for all involuntary resistance to passive motion.

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While associations between duration of untreated psychosis (DUP) and outcome have been widely reported, how long these relationships endure following initiation of treatment and how such associations are distributed across the range of DUP values encountered remain unclear. This study investigates prospectively (i) whether prediction of outcome by DUP and by duration of untreated illness (DUI) diminishes, remains stable or increases in the long term after initiating treatment, and (ii) whether these relationships for differing indices of outcome vary across gradations of DUP-DUI values. Sixty-two subjects were evaluated prospectively for DUP, DUI, premorbid features, psychopathology and quality of life at both first episode psychosis (FEP) and at 7-year follow-up; functionality and service engagement were assessed at follow-up.

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The mechanisms underlying the dichotomic cortical/basal ganglia dopaminergic abnormalities in schizophrenia are unclear. Astrocytes are important non-neuronal modulators of brain circuits, but their role in dopaminergic system remains poorly explored. Microarray analyses, immunohistochemistry, and two-photon laser scanning microscopy revealed that Dys1 hypofunction increases the reactivity of astrocytes, which express only the Dys1A isoform.

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Objective: Determining the extent to which relationships between duration of untreated psychosis (DUP) and outcome endure longitudinally across the lifetime course of psychotic illness requires prospective, systematic studies of epidemiologically representative incidence cohorts across decades. Transience, persistence, or heterogeneity in associations between DUP and distinct outcome domains are yet to be investigated over such time frames.

Methods: Prospective, sequential follow-up studies of an epidemiologically representative first-episode psychosis incidence cohort in Ireland were conducted at 6 months and 4, 8, 12, and 20 years (N=171).

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Rationale: Clinical studies have revealed that methamphetamine abuse increases risk for developing Parkinson's diseases. It is thus important to elucidate the mechanisms by which methamphetamine damages dopaminergic neurons.

Objectives: The present study was designed to elucidate the role of the dopamine D1 receptor in methamphetamine-mediated dopaminergic neuronal damage and its underlying mechanisms.

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Aberrant salience processing may underlie the link between cannabis and psychosis, as posited in individuals with schizophrenia or high schizotypy. We investigated the relative effects of cannabis use, schizotypy status, and self-reported aberrant salience experiences on salience processing, measured using a latent inhibition (LI) task (Granger et al., 2016), in a non-clinical population.

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The nucleus accumbens contain orexinergic neural inputs and orexin OX - and OX -receptors. Behavioural studies suggest that accumbal orexin receptors modulate accumbal dopaminergic activity-dependent locomotion in rats. We studied the effects of intra-accumbal injection of orexin receptor ligands on accumbal extracellular dopamine levels in freely moving rats, using in vivo microdialysis and analysed the roles of OX - and OX -receptors in the regulation of basal accumbal dopamine efflux.

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Current classification systems use the terms "catatonia" and "psychomotor phenomena" as mere a-theoretical descriptors, forgetting about their theoretical embedment. This was the source of misunderstandings among clinicians and researchers of the European collaboration on movement and sensorimotor/psychomotor functioning in schizophrenia and other psychoses or ECSP. Here, we review the different perspectives, their historical roots and highlight discrepancies.

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