'Whole-Body' Perspectives of Schizophrenia and Related Psychotic Illness: miRNA-143 as an Exemplary Molecule Implicated across Multi-System Dysfunctions.

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.

Loss of normal facial asymmetry in schizophrenia and bipolar disorder: Implications for development of brain asymmetry in psychotic illness.

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.

AMP-activated protein kinase in the amygdala and hippocampus contributes to enhanced fear memory in diabetic mice.

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.

Overshadowing and salience attribution in relation to cannabis use.

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.

The classical D1 dopamine receptor antagonist SCH23390 is a functional sigma-1 receptor allosteric modulator.

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.

Bedrock morphology influences rock barrens turtle nesting habitat energy dynamics.

Energy absorption and flow through a nest is an important aspect of embryonic development in many reptile species including turtles. To date, few studies have explicitly attempted to quantify the energy flow through turtle nests, opting instead for the simplified approach offered by temperature index models. However, the quantification of the energy can provide an explicit abiotic link that can link biological models to biometeorological and ecohydrological processes and models.

Duration of the psychosis prodrome and its relationship to duration of untreated psychosis across all 12 DSM-IV psychotic diagnoses: Evidence for a trans-diagnostic process associated with resilience.

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.

Hypoxia-inducible factor upregulation by roxadustat attenuates drug reward by altering brain iron homoeostasis.

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).

Regulation of plasma glucose levels by central dopamine D receptors is impaired in type 1 but not type 2 diabetic mouse models.

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.

From one to many: Hypertonia in schizophrenia spectrum psychosis an integrative review and adversarial collaboration report.

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics.

Activation of Human CD8+ T Cells with Nitroso Dapsone-Modified HLA-B*13:01-Binding Peptides.

Previous studies have shown that cysteine-reactive drug metabolites bind covalently with protein to activate patient T cells. However, the nature of the antigenic determinants that interact with HLA and whether T cell stimulatory peptides contain the bound drug metabolite has not been defined. Because susceptibility to dapsone hypersensitivity is associated with the expression of HLA-B*13:01, we have designed and synthesized nitroso dapsone-modified, HLA-B*13:01 binding peptides and explored their immunogenicity using T cells from hypersensitive human patients.

Identification of flucloxacillin-modified hepatocellular proteins: implications in flucloxacillin-induced liver injury.

Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver injury. Although expression of HLA-B*57:01 is associated with increased susceptibility, little is known of the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the provision of flucloxacillin-modified peptides that are presented to T-cells by the protein encoded by the risk allele.

Adolescence as a critical period for nandrolone-induced muscular strength in relation to abuse liability, alone and in conjunction with morphine, using accumbal dopamine efflux in freely moving rats.

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.

Omics and Multi-Omics Analysis for the Early Identification and Improved Outcome of Patients with Psoriatic Arthritis.

The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent.

From operational diagnostic to dimensional-continuum concepts of psychotic and non-psychotic illness: Embracing catatonia across psychopathology and intrinsic movement disorder in neural network dysfunction.

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.

Paratonia, Gegenhalten and psychomotor hypertonia Back to the roots.

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.

Mixed-effects models reveal prediction of long-term outcome by duration of untreated psychosis (DUP) and illness (DUI) varies with quantile gradation but is invariant with time across 7 years in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS).

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.