Abstract A large array of studies has investigated peripheral oxytocin (OT) and vasopressin (ADH) as potential biomarkers of psychiatric disorders, with highly conflicting and heterogenous findings. ...We searched Web of KnowledgeSM and Scopus® for English original articles investigating OT and/or ADH levels in different biological fluids (plasma/serum, saliva, urine and cerebrospinal fluid) across several psychiatric disorders. Sixty-four studies were included. We conducted 19 preliminary meta-analyses addressing OT alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 7 psychiatric disorders and ADH alterations in plasma/serum, saliva, urine and cerebrospinal fluid of 6 psychiatric disorders compared to controls. Hedge's g was used as effect size measure, together with heterogeneity analyses, test of publication biases and quality control. None of them (except serum OT in anorexia nervosa) revealed significant differences. There is no convincing evidence that peripheral ADH or OT might be reliable biomarkers in psychiatric disorders. However, the lack of significant results was associated with high methodological heterogeneity, low quality of the studies, small sample size, and scarce reliability of the methods used in previous studies, which need to be validated and standardized.
Lack of insight or unawareness of illness are the hallmarks of many psychiatric disorders, especially schizophrenia (SCZ) and other psychoses and could be conceived of as a failure in metacognition. ...Research in this area in the mental health field h as burgeoned with the development and widespread use of standard assessment instruments and the mapping out of the clinical and neuropsychological correlates of insight and its loss. There has been a growing appreciation of the multi-faceted nature of the concept and of the different ‘objects’ of insight, such as the general awareness that one is ill, to more specific metacognitive awareness of individual symptoms, impairments and performance. This in turn has led to the notion that insight may show modularity and may fractionate across different domains and disorders, supported by work that directly compares metacognition of memory deficits and illness awareness in patients with SCZ, Alzheimer's disease and brain injury. The focus of this paper will be on the varieties of metacognitive failure in psychiatry, particularly the psychoses. We explore cognitive models based on self-reflectiveness and their possible social and neurological bases, including data from structural and functional MRI. The medial frontal cortex appears to play an important role in self-appraisal in health and disease.
The coronavirus disease 2019 (COVID-19) pandemic has had a significant psychological impact on healthcare workers (HCWs).
There is an urgent need to understand the risk and protective factors ...associated with poor mental well-being of UK HCWs working during the COVID-19 pandemic.
Shortly after the April 2020 UK COVID-19 peak 2773 HCWs completed a survey containing measures of anxiety, depression, post-traumatic stress disorder and stress, as well as questions around potential predictors such as roles, COVID-19 risk perception and workplace-related factors. Respondents were classified as high or low symptomatic on each scale and logistic regression revealed factors associated with severe psychiatric symptoms. Change in well-being from pre- to during COVID-19 was also quantified.
Nearlya third of HCWs reported moderate to severe levels of anxiety and depression, and the number reporting very high symptoms was more than quadruple that pre-COVID-19. Several controllable factors were associated with the most severe level of psychiatric symptoms: insufficient personal protective equipment availability, workplace preparation, training and communication, and higher workload. Being female, 'front line', previous psychiatric diagnoses, traumatic events, and being an allied HCW or manager were also significantly associated with severe psychiatric symptoms. Sharing stress, resilience and ethical support for treatment decisions were significantly associated with low psychiatric symptoms. Front-line workers showed greater worsening of mental health compared with non-front-line HCWs.
Poor mental well-being was prevalent during the COVID-19 response, however, controllable factors associated with severe psychiatric symptoms are available to be targeted to reduce the detrimental impact of COVID-19 and other pandemics on HCW mental health.
Subjects with a diagnosis of schizophrenia (Scz) overweight unexpected evidence in probabilistic inference: such evidence becomes "aberrantly salient." A neurobiological explanation for this effect ...is that diminished synaptic gain (e.g., hypofunction of cortical NMDARs) in Scz destabilizes quasi-stable neuronal network states (or "attractors"). This attractor instability account predicts that (1) Scz would overweight unexpected evidence but underweight consistent evidence, (2) belief updating would be more vulnerable to stochastic fluctuations in neural activity, and (3) these effects would correlate. Hierarchical Bayesian belief updating models were tested in two independent datasets (
= 80 male and
= 167 female) comprising human subjects with Scz, and both clinical and nonclinical controls (some tested when unwell and on recovery) performing the "probability estimates" version of the beads task (a probabilistic inference task). Models with a standard learning rate, or including a parameter increasing updating to "disconfirmatory evidence," or a parameter encoding belief instability were formally compared. The "belief instability" model (based on the principles of attractor dynamics) had most evidence in all groups in both datasets. Two of four parameters differed between Scz and nonclinical controls in each dataset: belief instability and response stochasticity. These parameters correlated in both datasets. Furthermore, the clinical controls showed similar parameter distributions to Scz when unwell, but were no different from controls once recovered. These findings are consistent with the hypothesis that attractor network instability contributes to belief updating abnormalities in Scz, and suggest that similar changes may exist during acute illness in other psychiatric conditions.
Subjects with a diagnosis of schizophrenia (Scz) make large adjustments to their beliefs following unexpected evidence, but also smaller adjustments than controls following consistent evidence. This has previously been construed as a bias toward "disconfirmatory" information, but a more mechanistic explanation may be that in Scz, neural firing patterns ("attractor states") are less stable and hence easily altered in response to both new evidence and stochastic neural firing. We model belief updating in Scz and controls in two independent datasets using a hierarchical Bayesian model, and show that all subjects are best fit by a model containing a belief instability parameter. Both this and a response stochasticity parameter are consistently altered in Scz, as the unstable attractor hypothesis predicts.
Effective estimation of the salience of environmental stimuli underlies adaptive behavior, while related aberrance is believed to undermine rational thought processes in schizophrenia. A network ...including bilateral frontoinsular cortex (FIC) and dorsal anterior cingulate cortex (dACC) has been observed to respond to salient stimuli using functional magnetic resonance imaging (fMRI). To test the hypothesis that activity in this salience network (SN) is less discriminately modulated by contextually-relevant stimuli in schizophrenia than in healthy individuals, fMRI data were collected in 20 individuals with schizophrenia and 13 matched controls during performance of a modified monetary incentive delay (MID) task. After quantitatively identifying spatial components representative of the FIC and dACC features of the SN, two principal analyses were conducted. In the first, modulation of SN activity by salience was assessed by measuring response to trial outcome. First-level general linear models were applied to individual-specific time-courses of SN activity identified using spatial independent component analysis (ICA). This analysis revealed a significant salience-by-performance-by-group interaction on the best-fit FIC component's activity at trial outcome, whereby healthy individuals but not individuals with schizophrenia exhibited greater distinction between the response to hits and misses in high salience trials than in low salience trials. The second analysis aimed to ascertain whether SN component amplitude differed between the study groups over the duration of the experiment. Independent-samples T-tests on back-projected, percent-signal-change scaled SN component images importantly showed that the groups did not differ in the overall amplitude of SN expression over the entire dataset. These findings of dysregulated but not decreased SN activity in schizophrenia provide physiological support for mechanistic conceptual frameworks of delusional thought formation.
Clinical high-risk (CHR) individuals have been increasingly utilized to investigate the prodromal phases of psychosis and progression to illness. Research has identified medial and lateral temporal ...lobe abnormalities in CHR individuals. Dysfunction in the medial temporal lobe, particularly the hippocampus, is linked to dysregulation of glutamate and dopamine
a hippocampal-striatal-midbrain network that may lead to aberrant signaling of salience underpinning the
. Similarly, lateral temporal dysfunction may be linked to the
observed in the CHR stage. Here, we summarize the significance of these neurobiological findings in terms of emergent psychotic symptoms and conversion to psychosis in CHR populations. We propose key questions for future work with the aim to identify the neural mechanisms that underlie the development of psychosis.
•Controlled experiment on functional connectivity-based real-time fMRI neurofeedback.•Reduced anxiety levels in the experimental group after neurofeedback training.•Altered activity and connectivity ...in neurofeedback ROIs in the experimental group.•Increased resting state functional connectivity in the PCC in the experimental group.
High levels of trait anxiety are associated with impaired attentional control, changes in brain activity during attentional control tasks and altered network resting state functional connectivity (RSFC). Specifically, dorsolateral prefrontal cortex to anterior cingulate cortex (DLPFC – ACC) functional connectivity, thought to be crucial for effective and efficient attentional control, is reduced in high trait anxious individuals. The current study examined the potential of connectivity-based real-time functional magnetic imaging neurofeedback (rt-fMRI-nf) for enhancing DLPFC – ACC functional connectivity in trait anxious individuals. We specifically tested if changes in DLPFC - ACC connectivity were associated with reduced anxiety levels and improved attentional control. Thirty-two high trait anxious participants were assigned to either an experimental group (EG), undergoing veridical rt-fMRI-nf, or a control group (CG) that received sham (yoked) feedback. RSFC (using resting state fMRI), anxiety levels and Stroop task performance were assessed pre- and post-rt-fMRI-nf training. Post-rt-fMRI-nf training, relative to the CG, the EG showed reduced anxiety levels and increased DLPFC-ACC functional connectivity as well as increased RSFC in the posterior default mode network. Moreover, in the EG, changes in DLPFC – ACC functional connectivity during rt-fMRI-nf training were associated with reduced anxiety levels. However, there were no group differences in Stroop task performance. We conclude that rt-fMRI-nf targeting DLPFC – ACC functional connectivity can alter network connectivity and interactions and is a feasible method for reducing trait anxiety.
Abstract
Background
Paranoid thinking, a common symptom of psychosis and schizophrenia, manifests as a sense of threat and may also be indexed by a lack of trust. Stress, in turn, exacerbates ...psychosis and paranoia, and is a well-established risk factor for schizophrenia as well as a component in several models of psychosis. The present study aimed to determine the impact that acute stress has on paranoid thinking during social interaction in vivo in high (HSZ) vs low (LSZ) schizotypy using an iterated social reciprocity game. The main hypothesis was that HSZ would anticipate grerater social threat and paranoia at baseline compared to LSZ, and moreover that experimentally-induced stress would exacerbate those differences, and thus show that stress differentially modulates how HSZ model the intentions of others.
Methods
Matched healthy participants were stratified into HSZ (N=17) and LSZ (N=17) groups and were administered a non-financial, social-reciprocity game against benevolent and malevolent opponents under both stress and no-stress conditions. Stress was manipulated using the MIST (Dedovic et al., 2005) stress paradigm. Cortisol was measured from saliva samples acquired before and after the MIST stress task. Anticipation of threat and trust scores were derived from the social interaction task.
Results
At baseline, cortisol levels were not significantly different between HSZ and LSZ but were significantly raised by the stressor task in HSZ (p<.05) but not in LSZ. Higher cortisol at baseline (pre-stress) predicted greater initial and average anticipation of threat (both r=.5, p<.05) (no-stress) to other players; and lower initial trust ratings of malevolent, but not benevolent, players. The MIST task significantly elevated stress ratings compared to baseline (p<.001) and following stress, greater change in cortisol from baseline to post-MIST was associated with lower trust ratings (r=.51, p<.05). In HSZ greater stressor-related cortisol levels correlated with greater anticipation of threat (r=.58, p<.05) and lower trust levels (r=.57, p<.05) which was not apparent in low schizotypes.
Discussion
Acute stress elevates cortisol and paranoia in HSZ – in the form of greater anticipation of threat, and lower trust compared to LSZ. The study adds evidence to the role of stress in exacerbating schizophrenia-like experiences in those who are sub-threshold for schizophrenia and psychosis.
Abstract Several efforts to develop pharmacological treatments with a beneficial effect on cognition in schizophrenia are underway, while cognitive remediation has shown modest effects on cognitive ...performance. Our goal was to test if pharmacological augmentation of cognitive training would result in enhancement of training-induced learning. We chose modafinil as the pharmacological augmenting agent, as it is known to have beneficial effects on learning and cognition. 49 participants with chronic schizophrenia were enroled in a double-blind, placebo-controlled study across two sites and were randomised to either modafinil (200 mg/day) or placebo. All participants engaged in a cognitive training program for 10 consecutive weekdays. The primary outcome measure was the performance on the trained tasks and secondary outcome measures included MATRICS cognitive battery, proxy measures of everyday functioning and symptom measures. 84% of the participants completed all study visits. Both groups showed significant improvement in the performance of the trained tasks suggesting potential for further learning. Modafinil did not induce differential enhancement on the performance of the trained tasks or any differential enhancement of the neuropsychological and functional measures compared to placebo. Modafinil showed no significant effects on symptom severity. Our study demonstrated that combining pharmacological compounds with cognitive training is acceptable to patients and can be implemented in large double-blind randomised controlled trials. The lack of differential enhancement of training-induced learning raises questions, such as choice and optimal dose of drug, cognitive domains to be trained, type of cognitive training, intervention duration and chronicity of illness that require systematic investigation in future studies.
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