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

Author(s):  
Matthias Kirschner ◽  
André Schmidt ◽  
Benazir Hodzic-Santor ◽  
Achim Burrer ◽  
Andrei Manoliu ◽  
...  

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.

Author(s):  
Matthias Kirschner ◽  
André Schmidt ◽  
Benazir Hodzic-Santor ◽  
Achim Burrer ◽  
Andrei Manoliu ◽  
...  

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.


2020 ◽  
Author(s):  
Avyarthana Dey ◽  
Kara Dempster ◽  
Michael Mackinley ◽  
Peter Jeon ◽  
Tushar Das ◽  
...  

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.


2014 ◽  
Vol 29 (3) ◽  
pp. 153-159 ◽  
Author(s):  
J. Lyne ◽  
L. Renwick ◽  
K. Madigan ◽  
B. O’Donoghue ◽  
M. Bonar ◽  
...  

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.


2010 ◽  
Vol 25 ◽  
pp. 1178
Author(s):  
J. García ◽  
R. Segarra ◽  
P. Sánchez ◽  
N. Ojeda ◽  
J. Peña ◽  
...  

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Avyarthana Dey ◽  
Kara Dempster ◽  
Michael MacKinley ◽  
Peter Jeon ◽  
Tushar Das ◽  
...  

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.


2001 ◽  
Vol 178 (6) ◽  
pp. 518-523 ◽  
Author(s):  
Attila Sipos ◽  
Glynn Harrison ◽  
David Gunnell ◽  
Shazad Amin ◽  
Swaran P. Singh

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.


2021 ◽  
Author(s):  
Shaunagh O'Sullivan ◽  
Lianne Schmaal ◽  
Simon D'Alfonso ◽  
Yara J Toenders ◽  
Lee Valentine ◽  
...  

BACKGROUND Multicomponent digital interventions offer the potential for tailored and flexible interventions that aim to address high attrition rates and increase engagement, an area of concern in digital mental health. However, increased flexibility in usage makes it difficult to determine which components lead to improved treatment outcomes. OBJECTIVE This study aimed to identify user profiles on Horyzons, an 18-month digital relapse prevention intervention that incorporates therapeutic content and social networking, along with clinical, vocational and peer support, and to examine the predictive value of these user profiles for treatment outcomes. A secondary objective was to compare each user profile with young people receiving treatment as usual (TAU). METHODS Participants comprised 82 young people (16-27 years of age) with access to Horyzons and 84 receiving TAU, recovering from first-episode psychosis. Six-month usage data from the therapy and social networking components of Horyzons were used as features for K-means clustering for joint trajectories to identify user profiles. Social functioning, psychotic symptoms, depression and anxiety were assessed at baseline and six-month follow-up. General linear mixed models were used to examine the predictive value of user profiles for treatment outcomes, and between each user profile with TAU. RESULTS Three user profiles were identified based on system usage metrics including: (a) low usage; (b) maintained usage of social components; and (c) maintained usage of both therapy and social components. The maintained therapy and social group showed improvements in social functioning (F (2, 51) = 3.58; P = .04), negative symptoms (F (2, 51) = 4.45; P = .02) and overall psychiatric symptom severity (F (2, 50) = 3.23; P = .048) compared to the other user profiles. This group also showed improvements in social functioning (F (1, 62) = 4.68; P = .03), negative symptoms (F (1, 62) = 14.61; P = <.001) and overall psychiatric symptom severity (F (1, 63) = 5.66; P = .02) compared to TAU. Conversely, the maintained social group showed increases in anxiety compared to TAU (F (1, 57) = 7.65; P = .01). No differences were found between the low usage group and TAU on treatment outcomes. CONCLUSIONS Continued engagement with both therapy and social components might be key in achieving long-term recovery. Maintained social usage and low usage outcomes were broadly comparable to TAU, emphasizing the importance of maintaining engagement for improved treatment outcomes. Although the social network may be a key ingredient to increase sustained engagement, as users engaged with this more consistently, it should be leveraged as a tool to engage young people with therapeutic content to bring about social and clinical benefits.


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