scholarly journals Orbitofrontal-Striatal Structural Alterations Linked to Negative Symptoms at Different Stages of the Schizophrenia Spectrum

2020 ◽  
Author(s):  
Matthias Kirschner ◽  
André Schmidt ◽  
Benazir Hodzic-Santor ◽  
Achim Burrer ◽  
Andrei Manoliu ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Disease Onset ◽  
Brain Regions ◽  
First Episode ◽  
Phenotypic Trait ◽  
Imaging Data ◽  
Magnetic Resonance Imaging Data ◽  
Imaging Studies ◽  
Schizophrenia Spectrum ◽  
Episode Psychosis

Abstract Negative symptoms such as anhedonia and apathy are among the most debilitating manifestations of schizophrenia (SZ). Imaging studies have linked these symptoms to morphometric abnormalities in 2 brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and striatum. Higher negative symptoms are generally associated with reduced OFC thickness, while higher apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment or an underlying phenotypic trait. Here, we use multicentre magnetic resonance imaging data to investigate orbitofrontal-striatal abnormalities across the SZ spectrum from healthy populations with high schizotypy to unmedicated and medicated first-episode psychosis (FEP), and patients with chronic SZ. Putamen, caudate, accumbens volume, and OFC thickness were estimated from T1-weighted images acquired in all 3 diagnostic groups and controls from 4 sites (n = 337). Results were first established in 1 discovery dataset and replicated in 3 independent samples. There was a negative correlation between apathy and putamen/accumbens volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger putamen volume, which appears to be a consequence of antipsychotic medications. The negative association between reduced OFC thickness and total negative symptoms also appeared to vary along the SZ spectrum, being significant only in FEP patients. In schizotypy, there was increased OFC thickness relative to controls. Our findings suggest that negative symptoms are associated with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of SZ. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to the disease onset.

scholarly journals Orbitofrontal-striatal structural alterations linked to negative symptoms at different stages of the schizophrenia spectrum

2020 ◽  
Author(s):  
Matthias Kirschner ◽  
André Schmidt ◽  
Benazir Hodzic-Santor ◽  
Achim Burrer ◽  
Andrei Manoliu ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Ventral Striatum ◽  
Disease Onset ◽  
Chronic Schizophrenia ◽  
Brain Regions ◽  
First Episode Psychosis ◽  
First Episode ◽  
Phenotypic Trait ◽  
Schizophrenia Spectrum ◽  
Episode Psychosis

AbstractAmong the most debilitating manifestations of schizophrenia are negative symptoms such as anhedonia and apathy. Imaging studies have linked these symptoms to morphometric abnormalities in two brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and ventral striatum. Negative symptoms generally are associated with reduced OFC thickness, while apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment, or an underlying phenotypic trait. Here we use multicentre MRI data to investigate orbitofrontal-striatal abnormalities across the schizophrenia-spectrum from healthy populations with schizotypy, to unmedicated and medicated first-episode psychosis patients, and patients with chronic schizophrenia. Striatal volumes and OFC thickness were estimated from T1-weighted images acquired in all three diagnostic groups and controls from four sites (n=337). Results were first established in one test cohort (“Zurich sample”) and replicated in three independent samples. There was a correlation between apathy and striatal volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger striatal volumes, which appears to be a consequence of antipsychotic medications. The association between reduced OFC thickness and negative symptoms generally also appeared to vary along the disease course, being significant only in first-episode psychosis patients. In schizotypy there was increased OFC relative to controls. Our findings suggest that negative symptoms associate with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of schizophrenia. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to disease-onset.

Conceptual disorganization and redistribution of resting state cortical hubs in untreated first episode psychosis: A 7T MRI study

2020 ◽  
Author(s):  
Avyarthana Dey ◽  
Kara Dempster ◽  
Michael Mackinley ◽  
Peter Jeon ◽  
Tushar Das ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Superior Temporal Gyrus ◽  
Brain Regions ◽  
First Episode Psychosis ◽  
Cortical Reorganization ◽  
First Episode ◽  
Formal Thought Disorder ◽  
Whole Brain ◽  
Episode Psychosis ◽  
Positive And Negative Symptoms

Background:Network level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype which predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs).Methods:We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs and characterized the patterns of network connectivity in the two groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity.Results:Compared to HCs, reduced hubness of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased hubness of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. These two regions were strongly correlated with CD scores but not with other symptom scores.Discussion:Our observations are congruent with previous findings of reduced but not increased hubness. We observed increased hubness of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer.Conclusion:These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. A longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.

scholarly journals A multimodal study of a first episode psychosis cohort: potential markers of antipsychotic treatment resistance

2021 ◽  
Author(s):  
Kun Yang ◽  
Luisa Longo ◽  
Zui Narita ◽  
Nicola Cascella ◽  
Frederick C. Nucifora ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Biological Markers ◽  
Negative Symptoms ◽  
Age At Onset ◽  
First Episode Psychosis ◽  
First Episode ◽  
Imaging Data ◽  
Episode Psychosis ◽  
And Biological Markers ◽  
Brain Imaging Data

Treatment resistant (TR) psychosis is considered to be a significant cause of disability and functional impairment. Numerous efforts have been made to identify the clinical predictors of TR. However, the exploration of molecular and biological markers is still at an early stage. To understand the TR condition and identify potential molecular and biological markers, we analyzed demographic information, clinical data, structural brain imaging data, and molecular brain imaging data in 7 Tesla magnetic resonance spectroscopy, from a first episode psychosis cohort that includes 138 patients. Age, gender, race, smoking status, duration of illness, and antipsychotic dosages were controlled in the analyses. We found that TR patients had a younger age at onset, more hospitalizations, more severe negative symptoms, a significant reduction in the volumes of the hippocampus (HP) and superior frontal gyrus (SFG), and a significant reduction in glutathione (GSH) levels in the anterior cingulate cortex (ACC), when compared to non-TR patients. The combination of multiple markers provided a better classification between TR and non-TR patients compared to any individual marker. Our study shows that ACC GSH, HP and SFG volumes, and age at onset could potentially be trait biomarkers for TR diagnosis, while hospitalization and negative symptoms could be used to evaluate the progression of the disease. Multimodal cohorts are essential in obtaining a comprehensive understanding of brain disorders.

Do psychosis prodrome onset negative symptoms predict first presentation negative symptoms?

2014 ◽  
Vol 29 (3) ◽  
pp. 153-159 ◽  
Author(s):  
J. Lyne ◽  
L. Renwick ◽  
K. Madigan ◽  
B. O’Donoghue ◽  
M. Bonar ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Treatment Phase ◽  
First Episode Psychosis ◽  
Diagnostic Group ◽  
First Episode ◽  
Regression Analyses ◽  
Schizophrenia Spectrum ◽  
Episode Psychosis ◽  
Psychosis Prodrome ◽  
The Relationship

AbstractBackground:Negative symptoms have been previously reported during the psychosis prodrome, however our understanding of their relationship with treatment-phase negative symptoms remains unclear.Objectives:We report the prevalence of psychosis prodrome onset negative symptoms (PONS) and ascertain whether these predict negative symptoms at first presentation for treatment.Methods:Presence of expressivity or experiential negative symptom domains was established at first presentation for treatment using the Scale for Assessment of Negative Symptoms (SANS) in 373 individuals with a first episode psychosis. PONS were established using the Beiser Scale. The relationship between PONS and negative symptoms at first presentation was ascertained and regression analyses determined the relationship independent of confounding.Results:PONS prevalence was 50.3% in the schizophrenia spectrum group (n = 155) and 31.2% in the non-schizophrenia spectrum group (n = 218). In the schizophrenia spectrum group, PONS had a significant unadjusted (χ2 = 10.41, P < 0.001) and adjusted (OR = 2.40, 95% CI = 1.11–5.22, P = 0.027) association with first presentation experiential symptoms, however this relationship was not evident in the non-schizophrenia spectrum group. PONS did not predict expressivity symptoms in either diagnostic group.Conclusion:PONS are common in schizophrenia spectrum diagnoses, and predict experiential symptoms at first presentation. Further prospective research is needed to examine whether negative symptoms commence during the psychosis prodrome.

scholarly journals Neuroanatomical abnormalities in first-episode psychosis across independent samples: a multi-centre mega-analysis

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Sandra Vieira ◽  
Qiyong Gong ◽  
Cristina Scarpazza ◽  
Su Lui ◽  
Xiaoqi Huang ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
First Episode Psychosis ◽  
Small Samples ◽  
First Episode ◽  
Grey Matter Volume ◽  
Anti Psychotic ◽  
Imaging Data ◽  
Duration Of Illness ◽  
Episode Psychosis ◽  
And Gender

Abstract Background Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples. Methods Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons. Results FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease – gyrus rectus – was negatively correlated with the severity of positive and negative symptoms. Conclusions This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.

scholarly journals Conceptual disorganization and redistribution of resting-state cortical hubs in untreated first-episode psychosis: A 7T study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Avyarthana Dey ◽  
Kara Dempster ◽  
Michael MacKinley ◽  
Peter Jeon ◽  
Tushar Das ◽  
...  
Keyword(s):  
Information Transfer ◽  
Negative Symptoms ◽  
Network Connectivity ◽  
Brain Regions ◽  
First Episode Psychosis ◽  
Cortical Reorganization ◽  
First Episode ◽  
Whole Brain ◽  
Episode Psychosis ◽  
Positive And Negative Symptoms

AbstractNetwork-level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype that predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs). We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs, and characterized the patterns of network connectivity in the 2 groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity. Compared to HCs, reduced centrality of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased centrality of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. This cluster was strongly correlated with CD scores but not with other symptom scores. Our observations are congruent with previous findings of reduced but not increased centrality. We observed increased centrality of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer. These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. Longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.

scholarly journals Patterns and predictors of hospitalisation in first-episode psychosis

2001 ◽  
Vol 178 (6) ◽  
pp. 518-523 ◽  
Author(s):  
Attila Sipos ◽  
Glynn Harrison ◽  
David Gunnell ◽  
Shazad Amin ◽  
Swaran P. Singh
Keyword(s):  
Negative Symptoms ◽  
First Episode Psychosis ◽  
Psychiatric Services ◽  
First Episode ◽  
Psychotic Episode ◽  
Duration Of Untreated Illness ◽  
Specialist Services ◽  
Increased Risk ◽  
Episode Psychosis

BackgroundLittle is known about predictors of hospitalisation in patients with first-episode psychosis.AimsTo identify the pattern and predictors of hospitalisation of patients with a first psychotic episode making their first contact with specialist services.MethodThree-year follow-up of a cohort of 166 patients with a first episode of psychosis making contact with psychiatric services in Nottingham between June 1992 and May 1994.ResultsEighty-eight (53.0%) patients were admitted within 1 week of presentation; 32 (19.3%) were never admitted during the 3 years of follow-up. Manic symptoms at presentation were associated with an increased risk of rapid admission and an increased overall risk of admission; negative symptoms and a longer duration of untreated illness had an increased risk of late admission.ConclusionsCommunity-oriented psychiatric services might only delay, rather than prevent, admission of patients with predominantly negative symptoms and a longer duration of untreated illness. First-episode studies based upon first admissions are likely to be subject to selection biases, which may limit their representativeness.

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