S81. METAMEMORY IMPAIRMENT ACROSS THE PSYCHOSIS TRAJECTORY: ASSOCIATIONS WITH SYMPTOM SEVERITY

Abstract Background Schizophrenia is a psychiatric disorder characterized by a deficit in reality testing, most often manifest in the form of delusions and hallucinations. Because differentiating real from imagined experiences is critically dependent on episodic and associative memory, deficits in mnemonic processes could be involved in the genesis of impaired reality testing. Prior work has shown that individuals with psychosis exhibit impairment in metamemory, or, awareness and knowledge of one’s own memory and memory processes, and that these impairments may be relevant to the emergence and/or maintenance of psychotic symptoms. Methods In the present study, we used a verbal associative memory paradigm incorporating subject confidence ratings to examine differences in metamemory processes in three separate samples: patients with chronic schizophrenia (CHR; n = 34), patients with recent-onset (first-episode) psychosis (n = 49), and individuals at clinical high risk for psychosis (n = 29) compared to control groups (n = 24, n = 26, and n = 22, respectively). We used an analysis of variance design to examine group differences in confidence gap and knowledge corruption between patients and controls. We further assessed the association of both of these metrics to symptom severity in each patient sample. Results We found that both chronic and first-episode patients displayed significantly decreased confidence gap compared to healthy controls, with patients being more confident in incorrect memory retrievals and less confident in correct memory retrievals as compared to healthy controls. Additionally, compared to healthy controls, chronic patients and first-episode patients showed significantly increased knowledge corruption (the proportion of confident incorrect memory retrievals compared to all confident retrievals). While there were no group differences in confidence gap and knowledge corruption between CHR subjects and healthy controls, decreased confidence gap was significantly correlated with positive symptom severity in CHR subjects, as well as in first-episode subjects. Discussion These findings suggest that underlying deficits in metamemory processes may possibly reflect mechanisms involved in the development and/or maintenance of disrupted reality testing in those with and at risk for psychosis.

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Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

10.21203/rs.3.rs-929283/v1 ◽

2021 ◽

Author(s):

Haidong Yang ◽

Wen Pan ◽

Wenhuan Xiao ◽

Man Yang ◽

Jianchun Xu ◽

...

Keyword(s):

Antipsychotic Drugs ◽

Chronic Schizophrenia ◽

Serum Levels ◽

Psychotic Symptoms ◽

First Episode ◽

Antipsychotic Treatment ◽

Therapeutic Effects ◽

Pathophysiological Mechanism ◽

Healthy Controls ◽

Drug Naïve

Abstract Background: Neuregulin1 (NRG1) plays a role in neuronal migration, regulation of synaptic plasticity, and neural survival, and has been considered to be among the candidate genes for schizophrenia. This study focused on the variations in serum NRG1b1 levels following antipsychotic treatment and the relationship between NRG1b1 level and improvements in psychotic symptoms in first-episode drug-naïve (FEDN) patients and chronic schizophrenia.Methods: A total of 100 patients with schizophrenia were recruited and compared with 79 matched healthy controls. All patients had been drug-naïve for at least four weeks. Serum NRG1b1 levels and positive and negative syndrome scale (PANSS) scores were measured at the baseline and after four weeks. Serum NRG1b1 levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA).Results: Baseline NRG1b1 levels were significantly lower in the patients with schizophrenia compared with the healthy controls. NRG1b1 levels increased significantly following antipsychotic treatment. NRG1b1 levels gradually increased with declining PANSS scores and its three subscales during antipsychotic therapy. The levels of NRG1b1 increased significantly in responders after four weeks of treatment, although non-responders showed no such effect. Correlation analyses showed that the levels of NRG1b1 were negatively correlated with the duration of illness and positively correlated with improvement in symptoms.Conclusion: The levels of serum NRG1b1 and the therapeutic effects gradually increased following treatment, indicating that NRG1b1 may be an indicator of therapy, and that it may also be associated with the pathophysiological mechanism causing schizophrenia, although this possible pathway requires further investigation. Antipsychotic drugs increase Neuregulin1b1 serum levels in first-episode drug-naïve patients and chronic schizophrenia with suggestions for improving the treatment of psychotic symptoms

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Precuneus functioning differentiates first-episode psychosis patients during the fantasy movie Alice in Wonderland

Psychological Medicine ◽

10.1017/s0033291716002609 ◽

2016 ◽

Vol 47 (3) ◽

pp. 495-506 ◽

Cited By ~ 12

Author(s):

E. Rikandi ◽

S. Pamilo ◽

T. Mäntylä ◽

J. Suvisaari ◽

T. Kieseppä ◽

...

Keyword(s):

Machine Learning ◽

Brain Regions ◽

First Episode Psychosis ◽

Positive Symptom ◽

Psychotic Symptoms ◽

First Episode ◽

Chronic Patients ◽

Control Subjects ◽

Alice In Wonderland ◽

Episode Psychosis

BackgroundWhile group-level functional alterations have been identified in many brain regions of psychotic patients, multivariate machine-learning methods provide a tool to test whether some of such alterations could be used to differentiate an individual patient. Earlier machine-learning studies have focused on data collected from chronic patients during rest or simple tasks. We set out to unravel brain activation patterns during naturalistic stimulation in first-episode psychosis (FEP).MethodWe recorded brain activity from 46 FEP patients and 32 control subjects viewing scenes from the fantasy film Alice in Wonderland. Scenes with varying degrees of fantasy were selected based on the distortion of the ‘sense of reality’ in psychosis. After cleaning the data with a novel maxCorr method, we used machine learning to classify patients and healthy control subjects on the basis of voxel- and time-point patterns.ResultsMost (136/194) of the voxels that best classified the groups were clustered in a bilateral region of the precuneus. Classification accuracies were up to 79.5% (p = 5.69 × 10−8), and correct classification was more likely the higher the patient's positive-symptom score. Precuneus functioning was related to the fantasy content of the movie, and the relationship was stronger in control subjects than patients.ConclusionsThese findings are the first to show abnormalities in precuneus functioning during naturalistic information processing in FEP patients. Correlational findings suggest that these alterations are associated with positive psychotic symptoms and processing of fantasy. The results may provide new insights into the neuronal basis of reality distortion in psychosis.

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Cigarette smoking, psychopathology and cognitive function in first-episode drug-naive patients with schizophrenia: a case-control study

Psychological Medicine ◽

10.1017/s0033291712002590 ◽

2012 ◽

Vol 43 (8) ◽

pp. 1651-1660 ◽

Cited By ~ 20

Author(s):

X. Y. Zhang ◽

D. C. Chen ◽

M. H. Xiu ◽

C. N. Haile ◽

S. C. He ◽

...

Keyword(s):

Cognitive Function ◽

General Population ◽

Psychotic Disorders ◽

Chronic Schizophrenia ◽

Case Control ◽

Mental Illnesses ◽

Positive Symptom ◽

First Episode ◽

Healthy Controls ◽

Drug Naïve

BackgroundAlthough patients with chronic schizophrenia have substantially higher smoking rates than either the general population or patients with other mental illnesses, drug-naive patients with a first episode of schizophrenia have received little systemic study. This study examined smoking rates, the association between smoking and symptom severity and cognitive function in Chinese first-episode schizophrenia (FES) patients using cross-sectional and case-control designs.MethodTwo hundred and forty-four drug-naive FES patients and 256 healthy controls matched for gender, age and education completed the Fagerström Test for Nicotine Dependence (FTND) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients were also rated on the Positive and Negative Symptom Scale (PANSS).ResultsThe rate and quantity of smoking were not significantly higher among FES patients compared to the general population. Among patients, smokers scored higher than non-smokers on the total PANSS and the positive symptom subscale scores. There were no significant associations between cognitive function and smoking in either FES patients or healthy controls.ConclusionsIn contrast to studies in patients with chronic schizophrenia, drug-naive FES patients did not smoke more frequently than the general population. Furthermore, patients with psychotic disorders who smoked did not exhibit significant cognitive differences compared with those who did not smoke. However, smoking may have other detrimental effects on physical and mental health, for example on positive symptoms.

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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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Relationship between TNF-α levels and psychiatric symptoms in first-episode drug-naïve patients with schizophrenia before and after risperidone treatment and in chronic patients

BMC Psychiatry ◽

10.1186/s12888-021-03569-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chen Lin ◽

Ke Chen ◽

Jianjin Yu ◽

Wei Feng ◽

Weihong Fu ◽

...

Keyword(s):

Negative Symptoms ◽

Psychiatric Symptoms ◽

Psychotic Symptoms ◽

First Episode ◽

Healthy Controls ◽

Chronic Patients ◽

Tnf Α ◽

Before And After ◽

Drug Naïve ◽

Factor Α

Abstract Background The influence of antipsychotic drugs on tumor necrosis factor-α (TNF-α) levels is unclear, and there is no consensus on the association between TNF-α and psychotic symptoms. This study aimed to investigate the differences in TNF-α levels and clinical correlations in first-episode drug-naïve (FEDN) patients with schizophrenia before and after treatment and in chronic patients. Methods A total of 103 (51 FEDN and 52 chronic) patients and 114 healthy controls were recruited. Demographic and clinical data, including TNF-α levels, were recorded. We used the Positive and Negative Syndrome Scale (PANSS) to measure the psychopathology of all patients. Results TNF-α levels before treatment were significantly higher in FEDN patients than in chronic patients and healthy controls. No significant sex differences were found in the TNF-α levels of patients with schizophrenia. The TNF-α levels before treatment were significantly positively related to changes in PANSS negative symptoms in FEDN patients. The TNF-α levels in chronic patients were significantly negatively correlated with the general psychopathology subscales and PANSS total scores. Conclusions Increased TNF-α levels in FEDN patients and their correlation with psychopathology indicate that inflammatory cytokines may play a crucial role in the etiopathogenesis of schizophrenia, and inflammation-directed therapy may, therefore, improve negative symptoms.

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Failure to use corollary discharge to remap visual target locations is associated with psychotic symptom severity in schizophrenia

Journal of Neurophysiology ◽

10.1152/jn.00155.2015 ◽

2015 ◽

Vol 114 (2) ◽

pp. 1129-1136 ◽

Cited By ~ 18

Author(s):

Lara Rösler ◽

Martin Rolfs ◽

Stefan van der Stigchel ◽

Sebastiaan F. W. Neggers ◽

Wiepke Cahn ◽

...

Keyword(s):

Symptom Severity ◽

Target Location ◽

Visual Target ◽

Saccadic Eye Movements ◽

Landing Site ◽

Corollary Discharge ◽

Psychotic Symptoms ◽

Healthy Controls ◽

Visual Stability ◽

Target Locations

Corollary discharge (CD) refers to “copies” of motor signals sent to sensory areas, allowing prediction of future sensory states. They enable the putative mechanisms supporting the distinction between self-generated and externally generated sensations. Accordingly, many authors have suggested that disturbed CD engenders psychotic symptoms of schizophrenia, which are characterized by agency distortions. CD also supports perceived visual stability across saccadic eye movements and is used to predict the postsaccadic retinal coordinates of visual stimuli, a process called remapping. We tested whether schizophrenia patients (SZP) show remapping disturbances as evidenced by systematic transsaccadic mislocalizations of visual targets. SZP and healthy controls (HC) performed a task in which a saccadic target disappeared upon saccade initiation and, after a brief delay, reappeared at a horizontally displaced position. HC judged the direction of this displacement accurately, despite spatial errors in saccade landing site, indicating that their comparison of the actual to predicted postsaccadic target location relied on accurate CD. SZP performed worse and relied more on saccade landing site as a proxy for the presaccadic target, consistent with disturbed CD. This remapping failure was strongest in patients with more severe psychotic symptoms, consistent with the theoretical link between disturbed CD and phenomenological experiences in schizophrenia.

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Theory of mind in the early course of schizophrenia: stability, symptom and neurocognitive correlates, and relationship with functioning

Psychological Medicine ◽

10.1017/s0033291714003171 ◽

2015 ◽

Vol 45 (10) ◽

pp. 2031-2043 ◽

Cited By ~ 38

Author(s):

J. Ventura ◽

A. Ered ◽

D. Gretchen-Doorly ◽

K. L. Subotnik ◽

W. P. Horan ◽

...

Keyword(s):

Theory Of Mind ◽

Negative Symptoms ◽

Chronic Schizophrenia ◽

First Episode ◽

Positive Symptoms ◽

Healthy Controls ◽

Role Functioning ◽

Recent Onset ◽

Early Course ◽

The Relationship

BackgroundNumerous studies have reported links between theory of mind (ToM) deficits, neurocognition and negative symptoms with functional outcome in chronic schizophrenia patients. Although the ToM deficit has been observed in first-episode patients, fewer studies have addressed ToM as a possible trait marker, neurocognitive and symptom correlations longitudinally, and associations with later functioning.MethodRecent-onset schizophrenia patients (n = 77) were assessed at baseline after reaching medication stabilization, and again at 6 months (n = 48). Healthy controls (n = 21) were screened, and demographically comparable with the patients. ToM was assessed with a Social Animations Task (SAT), in which the participants’ descriptions of scenes depicting abstract visual stimuli ‘interacting’ in three conditions (ToM, goal directed and random) were rated for degree of intentionality attributed to the figures and for appropriateness. Neurocognition, symptoms and role functioning were also assessed.ResultsOn the SAT, patients had lower scores than controls for both intentionality (p < 0.01) and appropriateness (p < 0.01) during the ToM condition, at baseline and 6 months. The ToM deficit was stable and present even in remitted patients. Analyses at baseline and 6 months indicated that for patients, ToM intentionality and appropriateness were significantly correlated with neurocognition, negative symptoms and role functioning. The relationship between ToM and role functioning was mediated by negative symptoms.ConclusionsThe ToM deficit was found in recent-onset schizophrenia patients and appears to be moderately trait-like. ToM is also moderately correlated with neurocognition, negative and positive symptoms, and role functioning. ToM appears to influence negative symptoms which in turn makes an impact on role functioning.

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Computational Modeling of Contrast Sensitivity and Orientation Tuning in First-Episode and Chronic Schizophrenia

Computational Psychiatry ◽

10.1162/cpsy_a_00005 ◽

2017 ◽

Vol 1 ◽

pp. 102-131 ◽

Cited By ~ 10

Author(s):

Steven M. Silverstein ◽

Docia L. Demmin ◽

James A. Bednar

Keyword(s):

Computational Modeling ◽

Contrast Sensitivity ◽

Visual Processing ◽

Hebbian Learning ◽

Gain Control ◽

Chronic Schizophrenia ◽

Orientation Tuning ◽

Psychotic Symptoms ◽

First Episode ◽

Psychotic Episode

Computational modeling is a useful method for generating hypotheses about the contributions of impaired neurobiological mechanisms, and their interactions, to psychopathology. Modeling is being increasingly used to further our understanding of schizophrenia, but to date, it has not been applied to questions regarding the common perceptual disturbances in the disorder. In this article, we model aspects of low-level visual processing and demonstrate how this can lead to testable hypotheses about both the nature of visual abnormalities in schizophrenia and the relationships between the mechanisms underlying these disturbances and psychotic symptoms. Using a model that incorporates retinal, lateral geniculate nucleus (LGN), and V1 activity, as well as gain control in the LGN, homeostatic adaptation in V1, lateral excitation and inhibition in V1, and self-organization of synaptic weights based on Hebbian learning and divisive normalization, we show that (a) prior data indicating increased contrast sensitivity for low-spatial-frequency stimuli in first-episode schizophrenia can be successfully modeled as a function of reduced retinal and LGN efferent activity, leading to overamplification at the cortical level, and (b) prior data on reduced contrast sensitivity and broadened orientation tuning in chronic schizophrenia can be successfully modeled by a combination of reduced V1 lateral inhibition and an increase in the Hebbian learning rate at V1 synapses for LGN input. These models are consistent with many current findings, and they predict several relationships that have not yet been demonstrated. They also have implications for understanding changes in brain and visual function from the first psychotic episode to the chronic stage of illness.

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0321 MISMATCH NEGATIVITY (MMN), EXECUTIVE FUNCTION AND SYMPTOM SEVERITY IN FIRST-EPISODE AND CHRONIC SCHIZOPHRENIA

Schizophrenia Research ◽

10.1016/s0920-9964(06)70215-8 ◽

2006 ◽

Vol 86 ◽

pp. S72

Author(s):

P.B. Ward ◽

E. Stone ◽

L. Meyer ◽

E. Connaughton ◽

K. Metcalf ◽

...

Keyword(s):

Executive Function ◽

Symptom Severity ◽

Mismatch Negativity ◽

Chronic Schizophrenia ◽

First Episode

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Tolerability and treatment response in patients with recently diagnosed vs. chronic schizophrenia treated with paliperidone ER

European Psychiatry ◽

10.1016/s0924-9338(11)73206-0 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1502-1502

Author(s):

A. Schreiner ◽

D. Hoeben ◽

C. Tessier ◽

M. Lahaye ◽

J. Turczynski ◽

...

Keyword(s):

Treatment Response ◽

Chronic Schizophrenia ◽

Psychotic Symptoms ◽

Chronic Patients ◽

Open Label ◽

Patient Functioning ◽

Syndrome Scale ◽

Negative Syndrome ◽

Mean Time ◽

Time Since Diagnosis

ObjectiveTo explore tolerability and treatment response in adult patients with recently diagnosed (<5 years) and chronic (>5 years) schizophrenia treated with flexible doses of paliperidone ER.MethodsInternational prospective open-label 6-month study. Endpoints were the Positive and Negative Syndrome Scale (PANSS), patient functioning and treatment-emergent adverse events (TEAEs).ResultsOf 713 recently diagnosed patients, most were male (60.9%), mean age was 33.6 ± 11.2 years and mean time since diagnosis was 2.3 ± 1.7 years. Chronic patients (n = 1003) were predominantly male (59.2%) with a mean age of 43.8 ± 11.4 and mean time since diagnosis of 15.6 ± 9.2 years. 70.4% and 71.7% of patients completed the study, respectively. Mean mode doses of paliperidone ER were similar between recently diagnosed and chronic patients (7.0 ± 2.9 mg/day and 7.2 ± 2.9 mg/day). 63.1% of recently diagnosed and 60.8% of chronic patients switching due to lack of efficacy with their previous antipsychotic had a >20% improvement in PANSS total score at endpoint, and improvement with other switching reasons was consistently numerically higher in recently diagnosed patients. The rate of patients with mild or no functional impairment increased from 17.7% to 39.8% in recently diagnosed and from 14.4% to 32.9% in chronic patients. TEAEs reported in >5% were insomnia (10.7% and 8.1%), anxiety (8.6% and 6.0%) and somnolence (5.8% and 3.4%), respectively.ConclusionThese data suggest that both recently diagnosed and chronic patients previously unsuccessfully treated with other oral antipsychotics may benefit from paliperidone ER, with a tendency for recently diagnosed patients showing some higher treatment response in psychotic symptoms and patient functioning.

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