Impaired Performance on the Reading the Mind in the Eyes Test in First-Episode Psychosis and Clinical High Risk for Psychosis

Objective Although previous studies have reported impaired performance in the reading the mind in the eyes test (RMET), which measures complex emotion recognition abilities, in patients with schizophrenia, reports regarding individuals at clinical high risk (CHR) for psychosis have been inconsistent, mainly due to the interacting confounding effects of general cognitive abilities and age. We compared RMET performances across first-episode psychosis (FEP) patients, CHR individuals, and healthy controls (HCs) while controlling for the effects of both general cognitive abilities and age.Methods A total of 25 FEP, 41 CHR, and 44 HC subjects matched for age participated in this study. RMET performance scores were compared across the groups using analysis of variance with sex and intelligence quotient as covariates. Exploratory Pearson’s correlation analyses were performed to reveal the potential relationships of RMET scores with clinical symptom severity in the FEP and CHR groups.Results RMET performance scores were significantly lower among FEP and CHR participants than among HCs. FEP patients and CHR subjects showed comparable RMET performance scores. RMET scores were negatively correlated with Positive and Negative Syndrome Scale (PANSS) positive symptom subscale scores in the FEP patients. No significant correlation was identified between RMET scores and other clinical scale scores.Conclusion Impaired RMET performance is present from the risk stage of psychosis, which might be related to positive symptom severity in early psychosis. Longitudinal studies are necessary to confirm the stability of complex emotion recognition impairments and their relationship with social functioning in early psychosis patients.

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Developmental influences on symptom expression in antipsychotic-naïve first-episode psychosis

Psychological Medicine ◽

10.1017/s0033291720003463 ◽

2020 ◽

pp. 1-12

Author(s):

Miranda Bridgwater ◽

Peter Bachman ◽

Brenden Tervo-Clemmens ◽

Gretchen Haas ◽

Rebecca Hayes ◽

...

Keyword(s):

Negative Symptom ◽

Symptom Severity ◽

Negative Symptoms ◽

First Episode Psychosis ◽

Positive Symptom ◽

First Episode ◽

Positive Symptoms ◽

Symptom Expression ◽

Age Related ◽

Episode Psychosis

Abstract Background The neurodevelopmental model of psychosis was established over 30 years ago; however, the developmental influence on psychotic symptom expression – how age affects clinical presentation in first-episode psychosis – has not been thoroughly investigated. Methods Using generalized additive modeling, which allows for linear and non-linear functional forms of age-related change, we leveraged symptom data from a large sample of antipsychotic-naïve individuals with first-episode psychosis (N = 340, 12–40 years, 1–12 visits), collected at the University of Pittsburgh from 1990 to 2017. We examined relationships between age and severity of perceptual and non-perceptual positive symptoms and negative symptoms. We tested for age-associated effects on change in positive or negative symptom severity following baseline assessment and explored the time-varying relationship between perceptual and non-perceptual positive symptoms across adolescent development. Results Perceptual positive symptom severity significantly decreased with increasing age (F = 7.0, p = 0.0007; q = 0.003) while non-perceptual positive symptom severity increased with age (F = 4.1, p = 0.01, q = 0.02). Anhedonia severity increased with increasing age (F = 6.7, p = 0.00035; q = 0.0003), while flat affect decreased in severity with increased age (F = 9.8, p = 0.002; q = 0.006). Findings remained significant when parental SES, IQ, and illness duration were included as covariates. There were no developmental effects on change in positive or negative symptom severity (all p > 0.25). Beginning at age 18, there was a statistically significant association between severity of non-perceptual and perceptual symptoms. This relationship increased in strength throughout adulthood. Conclusions These findings suggest that as maturation proceeds, perceptual symptoms attenuate while non-perceptual symptoms are enhanced. Findings underscore how pathological brain–behavior relationships vary as a function of development.

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Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy Controls

10.1101/2021.03.11.21253426 ◽

2021 ◽

Author(s):

Kristina Sabaroedin ◽

Adeel Razi ◽

Sidhant Chopra ◽

Nancy Tran ◽

Andrii Pozaruk ◽

...

Keyword(s):

Symptom Severity ◽

Effective Connectivity ◽

First Episode Psychosis ◽

Striatal Dopamine ◽

Positive Symptom ◽

Dopamine Synthesis ◽

First Episode ◽

Positron Emission ◽

Episode Psychosis ◽

Patient Groups

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naive first-episode psychosis (FEP) patients and 23 controls and an independent sample of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent sample of 33 healthy individuals who underwent concurrent fMRI and [18F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.

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Learning to trust: social feedback normalizes trust behavior in first-episode psychosis and clinical high risk

Psychological Medicine ◽

10.1017/s003329171800140x ◽

2018 ◽

Vol 49 (5) ◽

pp. 780-790 ◽

Cited By ~ 4

Author(s):

Imke L. J. Lemmers-Jansen ◽

Anne-Kathrin J. Fett ◽

Esther Hanssen ◽

Dick J. Veltman ◽

Lydia Krabbendam

Keyword(s):

High Risk ◽

Symptom Severity ◽

Brain Activation ◽

First Episode Psychosis ◽

First Episode ◽

Healthy Controls ◽

Clinical High Risk ◽

Social Feedback ◽

Chronic Patients ◽

Episode Psychosis

AbstractBackgroundPsychosis is characterized by problems in social functioning that exist well before illness onset, and in individuals at clinical high risk (CHR) for psychosis. Trust is an essential element for social interactions that is impaired in psychosis. In the trust game, chronic patients showed reduced baseline trust, impaired response to positive social feedback, and attenuated brain activation in reward and mentalizing areas. We investigated whether first-episode psychosis patients (FEP) and CHR show similar abnormalities in the neural and behavioral mechanisms underlying trust.MethodsTwenty-two FEP, 17 CHR, and 43 healthy controls performed two trust games, with a cooperative and an unfair partner in the fMRI scanner. Region of interest analyses were performed on mentalizing and reward processing areas, during the investment and outcome phases of the games.ResultsCompared with healthy controls, FEP and CHR showed reduced baseline trust, but like controls, learned to trust in response to cooperative and unfair feedback. Symptom severity was not associated with baseline trust, however in FEP associated with reduced response to feedback. The only group differences in brain activation were that CHR recruited the temporo-parietal junction (TPJ) more than FEP and controls during investment in the unfair condition. This hyper-activation in CHR was associated with greater symptom severity.ConclusionsReduced baseline trust may be associated with risk for psychotic illness, or generally with poor mental health. Feedback learning is still intact in CHR and FEP, as opposed to chronic patients. CHR however show distinct neural activation patterns of hyper-activation of the TPJ.

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Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis

Molecular Psychiatry ◽

10.1038/s41380-021-01197-9 ◽

2021 ◽

Author(s):

Meike Heurich ◽

Melanie Föcking ◽

David Mongan ◽

Gerard Cagney ◽

David R. Cotter

Keyword(s):

High Risk ◽

Psychotic Disorder ◽

Psychotic Disorders ◽

Clinical Symptoms ◽

First Episode Psychosis ◽

Specific Protein ◽

First Episode ◽

Clinical High Risk ◽

Blood Proteins ◽

Episode Psychosis

AbstractEarly identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies.

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The Implementation and Review of Cognitive Remediation Training for First Episode Psychosis in Singapore

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.784935 ◽

2021 ◽

Vol 12 ◽

Author(s):

Nigel Ian Ming Chong ◽

Yogeswary Maniam ◽

Yi Chian Chua ◽

Charmaine Tang

Keyword(s):

Verbal Memory ◽

Cognitive Abilities ◽

Statistical Significance ◽

Real Life ◽

Cognitive Remediation ◽

First Episode Psychosis ◽

Early Psychosis ◽

First Episode ◽

Educational Approach ◽

Episode Psychosis

Objective: Early intervention in patients with first episode psychosis (FEP) can improve cognitive abilities, with both short- and long-term benefits. In this paper, we describe the implementation and review of cognitive remediation training (CRT) in an Asian FEP population. The outcomes of the training are also evaluated and discussed.Methods: This naturalistic paper describes in detail the real-life implementation and conduct of CRT in an early psychosis intervention service. One hundred and nine patients with FEP underwent a 24-session CRT programme, using Cogpack and Neuropsychological Educational Approach to Remediation. The program is evaluated with pre- and post-CRT assessment scores which included Montreal Cognitive Assessment and Brief Assessment of Cognition in Schizophrenia. The rates of improvement on these cognitive assessments were evaluated using paired t-tests, with statistical significance set at p ≤ 0.05.Results: Of the 109 patients who underwent CRT, a total of 92 (84.4%) completed all 24 sessions. Paired t-tests between pre- and post-CRT assessments scores revealed that participants significantly improved on majority of the measures, including verbal memory, digit sequencing, and symbol coding.Conclusion: As with other cognitive remediation programmes, CRT has shown to improve cognitive functioning in patients with FEP. The results support the use of CRT in an Asian context and may serve as guidance for the implementation of similar training programmes in other Asian early psychosis intervention services.

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