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

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.

Download Full-text

Family history of psychosis negatively impacts age at onset, negative symptoms, and duration of untreated illness and psychosis in first-episode psychosis patients

Psychiatry Research ◽

10.1016/j.psychres.2012.03.001 ◽

2012 ◽

Vol 197 (1-2) ◽

pp. 23-28 ◽

Cited By ~ 20

Author(s):

Michelle Esterberg ◽

Michael Compton

Keyword(s):

Family History ◽

Negative Symptoms ◽

Age At Onset ◽

First Episode Psychosis ◽

First Episode ◽

Duration Of Untreated Illness ◽

Episode Psychosis ◽

History Of

Download Full-text

Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

Psychological Medicine ◽

10.1017/s0033291717000435 ◽

2017 ◽

Vol 47 (11) ◽

pp. 1981-1989 ◽

Cited By ~ 78

Author(s):

A. Demjaha ◽

J. M. Lappin ◽

D. Stahl ◽

M. X. Patel ◽

J. H. MacCabe ◽

...

Keyword(s):

Negative Symptoms ◽

Age At Onset ◽

Treatment Resistance ◽

First Episode Psychosis ◽

First Episode ◽

Antipsychotic Treatment ◽

Treatment Resistant ◽

Illness Onset ◽

Episode Psychosis

BackgroundWe examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.MethodThe study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.ResultsFrom the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.ConclusionsThe striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Download Full-text

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

Psychological Medicine ◽

10.1017/s0033291719003568 ◽

2019 ◽

pp. 1-11 ◽

Cited By ~ 5

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.

Download Full-text

Longitudinal assessment of negative symptoms in early onset first episode psychosis

10.26226/morressier.5b681763b56e9b005965c031 ◽

2018 ◽

Author(s):

Maria Garcia Traverso

Keyword(s):

Early Onset ◽

Negative Symptoms ◽

First Episode Psychosis ◽

First Episode ◽

Longitudinal Assessment ◽

Episode Psychosis

Download Full-text

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

10.31234/osf.io/rzvby ◽

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.

Download Full-text

P.553 Negative symptoms correlate with social functioning in first-episode psychosis: results from a cross-sectional study

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2020.09.405 ◽

2020 ◽

Vol 40 ◽

pp. S313-S314

Author(s):

L.A. Fernandes ◽

F. Ferreira ◽

I. Figueiredo ◽

R. Gasparinho ◽

F. Viegas ◽

...

Keyword(s):

Social Functioning ◽

Negative Symptoms ◽

Cross Sectional Study ◽

First Episode Psychosis ◽

First Episode ◽

Sectional Study ◽

Cross Sectional ◽

Episode Psychosis

Download Full-text

Patterns and predictors of hospitalisation in first-episode psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.178.6.518 ◽

2001 ◽

Vol 178 (6) ◽

pp. 518-523 ◽

Cited By ~ 47

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.

Download Full-text

Exploring the relationship between recency and frequency of cannabis use and diminished expression and apathy as two dimensions of negative symptoms in first episode psychosis. A one-year follow-up study

Schizophrenia Research ◽

10.1016/j.schres.2021.08.004 ◽

2021 ◽

Vol 236 ◽

pp. 89-96

Author(s):

Henrik Myhre Ihler ◽

Trine Vik Lagerberg ◽

Siv Hege Lyngstad ◽

Ingrid Melle ◽

Kristin Lie Romm

Keyword(s):

Negative Symptoms ◽

First Episode Psychosis ◽

Two Dimensions ◽

Cannabis Use ◽

First Episode ◽

Follow Up Study ◽

Episode Psychosis ◽

One Year ◽

The Relationship

Download Full-text

Characterising Usage of a Multicomponent Digital Intervention to Predict Treatment Outcomes in First-Episode Psychosis: A Cluster Analysis (Preprint)

10.2196/preprints.29211 ◽

2021 ◽

Author(s):

Shaunagh O'Sullivan ◽

Lianne Schmaal ◽

Simon D'Alfonso ◽

Yara J Toenders ◽

Lee Valentine ◽

...

Keyword(s):

Young People ◽

Treatment Outcomes ◽

Social Functioning ◽

Negative Symptoms ◽

User Profile ◽

First Episode Psychosis ◽

First Episode ◽

User Profiles ◽

Episode Psychosis ◽

Social Components

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.

Download Full-text