Context-specific abnormalities of the central executive network in first-episode psychosis: relationship with cognition

2020 ◽  
pp. 1-10
Author(s):  
Deepak K. Sarpal ◽  
Goda Tarcijonas ◽  
Finnegan J. Calabro ◽  
William Foran ◽  
Gretchen L. Haas ◽  
...  

Abstract Background Cognitive impairments, which contribute to the profound functional deficits observed in psychotic disorders, have found to be associated with abnormalities in trial-level cognitive control. However, neural tasks operate within the context of sustained cognitive states, which can be assessed with ‘background connectivity’ following the removal of task effects. To date, little is known about the integrity of brain processes supporting the maintenance of a cognitive state in individuals with psychotic disorders. Thus, here we examine background connectivity during executive processing in a cohort of participants with first-episode psychosis (FEP). Methods The following fMRI study examined background connectivity of the dorsolateral prefrontal cortex (DLPFC), during working memory engagement in a group of 43 patients with FEP, relative to 35 healthy controls (HC). Findings were also examined in relation to measures of executive function. Results The FEP group relative to HC showed significantly lower background DLPFC connectivity with bilateral superior parietal lobule (SPL) and left inferior parietal lobule. Background connectivity between DLPFC and SPL was also positively associated with overall cognition across all subjects and in our FEP group. In comparison, resting-state frontoparietal connectivity did not differ between groups and was not significantly associated with overall cognition, suggesting that psychosis-related alterations in executive networks only emerged during states of goal-oriented behavior. Conclusions These results provide novel evidence indicating while frontoparietal connectivity at rest appears intact in psychosis, when engaged during a cognitive state, it is impaired possibly undermining cognitive control capacities in FEP.

2020 ◽  
Author(s):  
Emmanuel Kiiza Mwesiga ◽  
Noeline Nakasujja ◽  
Lawrence Nankaba ◽  
Juliet Nakku ◽  
Seggane Musisi

Introduction: Individual and group level interventions have the largest effect on outcomes in patients with the first episode of psychosis. The quality of these individual and group level interventions provided to first-episode psychosis patients in Uganda is unclear.Methods: The study was performed at Butabika National Psychiatric Teaching and referral hospital in Uganda. A retrospective chart review of recently discharged adult in-patients with the first episode of psychosis was first performed to determine the proportion of participants who received the different essential components for individual and group level interventions. From the different proportions, the quality of the services across the individual and group interventions was determined using the first-Episode Psychosis Services Fidelity Scale (FEPS-FS). The FEPS-FS assigns a grade of 1-5 on a Likert scale depending on the proportion of patients received the different components of the intervention. Results: The final sample included 156 first-episode psychosis patients. The median age was 27 years [IOR (24-36)] with 55% of participants of the female gender. 13 essential components across the individual and group interventions were assessed and their quality quantified. All 13 essential components had poor quality with the range of scores on the FEPS-FS of 1-3. Only one essential component assessed (use of single antipsychotics) had moderate quality.Discussion: Among current services at the National psychiatric hospital of Uganda, the essential for individual and group level interventions for psychotic disorders are of low quality. Further studies are required on how the quality of these interventions can be improved.


Author(s):  
Meike Heurich ◽  
Melanie Föcking ◽  
David Mongan ◽  
Gerard Cagney ◽  
David R. Cotter

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.


2019 ◽  
Vol 50 (13) ◽  
pp. 2182-2193 ◽  
Author(s):  
Kirsten B. Bojesen ◽  
Bjørn H. Ebdrup ◽  
Kasper Jessen ◽  
Anne Sigvard ◽  
Karen Tangmose ◽  
...  

AbstractBackgroundPoor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).MethodsThirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.ResultsBefore treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.ConclusionGlutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S93-S93
Author(s):  
Irina Falkenberg ◽  
Huai-Hsuan Tseng ◽  
Gemma Modinos ◽  
Barbara Wild ◽  
Philip McGuire ◽  
...  

Abstract Background Studies indicate that people with schizophrenia and first-episode psychosis experience deficits in their ability to accurately detect and display emotions through facial expressions, and that functioning and symptoms are associated with these deficits. This study aims to examine how emotion recognition and facial emotion expression are related to functioning and symptoms in a sample of individuals at ultra-high risk, first-episode psychosis and healthy controls. Methods During fMRI, we combined the presentation of emotional faces with the instruction to react with facial movements predetermined and assigned. 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs) were examined while viewing happy, sad, or neutral faces and were instructed to simultaneously move the corners of their mouths either (a). upwards or (b). downwards, or (c). to refrain from movement. The subjects’ facial movements were recorded with an MR-compatible video camera. Results Neurofunctional and behavioral response to emotional faces were measured. Analyses have only recently commenced and are ongoing. Full results of the clinical and functional impact of behavioral and neuroimaging results will be presented at the meeting. Discussion Increased knowledge about abnormalities in emotion recognition and behaviour as well as their neural correlates and their impact on clinical measures and functional outcome can inform the development of novel treatment approaches to improve social skills early in the course of schizophrenia and psychotic disorders.


2020 ◽  
Author(s):  
Santosh Lamichhane ◽  
Alex M. Dickens ◽  
Partho Sen ◽  
Heikki Laurikainen ◽  
Jaana Suvisaari ◽  
...  

AbstractPatients with schizophrenia have a lower than average life span, largely due to the increased prevalence of cardiometabolic co-morbidities. Identification of individuals with psychotic disorders with a high risk of rapid weight gain, and the associated development of metabolic complications, is an unmet need as regards public health. Here, we applied mass spectrometry-based lipidomics in a prospective study comprising 48 controls (CTR), 44 first-episode psychosis (FEP) patients and 22 individuals at clinical-high-risk (CHR) for psychosis, from two study centers (Turku/Finland and London/UK). Baseline serum samples were analyzed by lipidomics, while body mass index (BMI) was assessed at baseline and after 12 months. We found that baseline triacylglycerols with low double bond counts and carbon numbers were positively associated with the change in BMI at follow-up. In addition, a molecular signature comprised of two triacylglycerols (TG(48:0) and TG(45:0)), was predictive of weight gain in individuals with a psychotic disorder, with an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI: 0.60–0.85). When independently tested in the CHR group, this molecular signature predicted said weight change with AUROC = 0.73 (95% CI: 0.61–0.83). We conclude that molecular lipids may serve as a predictor of weight gain in psychotic disorders in at-risk individuals, and may thus provide a useful marker for identifying individuals who are most prone to developing cardiometabolic co-morbidities.


2007 ◽  
Vol 13 (3) ◽  
pp. 4 ◽  
Author(s):  
S Mashaphu ◽  
D L Mkize

<p><strong>Background.</strong> In order to gauge the impact of the HIV epidemic on psychotic disorders, the magnitude and causal direction of the association between HIV infection and psychosis need to be examined closely.</p><p><strong>Objective.</strong> To determine the HIV seropositivity rate among adult patients presenting with first-episode psychosis (FEP) to Town Hill Hospital in Pietermaritzburg, KwaZulu-Natal.</p><p><strong>Design.</strong> A cross-sectional, point-prevalence study was done over a 6-month period.</p><p><strong>Results.</strong> Of the 63 FEP patients in the study, 48 tested HIV- negative and 15 tested positive, giving a seroprevalence rate of 23.8%.</p><p><strong>Conclusion.</strong> The prevalence of HIV seropositivity is high among patients with FEP.</p>


1996 ◽  
Vol 30 (4) ◽  
pp. 498-504 ◽  
Author(s):  
Henry J. Jackson ◽  
Patrick D. McGorry ◽  
Susan Harrigan ◽  
Jenepher Dakis ◽  
Lisa Henry ◽  
...  

Objective: As part of the DSM-IV field trial for psychotic disorders, the authors endeavoured to determine the reliability of the DSM-IV prodromal features for schizophrenia in a first-episode sample. Method: Fifty first-episode psychotic patients were assessed using a semi-structured instrument to determine the presence/absence of nine prodromal symptoms. Inter-rater reliability data were calculated for 25 of the patients, and test-retest data were calculated for the remaining 25 patients. Results: Levels of reliability were poor. Conclusions: The results lend some support to American Psychiatric Association and World Health Organization decisions to omit specific criteria for prodromal features from their respective nosologies.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Martino Belvederi Murri ◽  
Flaminia Fanelli ◽  
Uberto Pagotto ◽  
Elena Bonora ◽  
Federico Triolo ◽  
...  

Neuroactive steroids may play a role in the pathophysiology of psychotic disorders, but few studies examined this issue. We compared serum levels of cortisol, testosterone, dehydroepiandrosterone, and progesterone between a representative sample of first-episode psychosis (FEP) patients and age- and gender-matched healthy subjects. Furthermore, we analyzed the associations between neuroactive steroids levels and the severity of psychotic symptom dimensions. Male patients had lower levels of progesterone than controls (p=0.03). Progesterone levels were inversely associated with the severity of positive symptoms (p=0.007). Consistent with preclinical findings, results suggest that progesterone might have a role in the pathophysiology of psychotic disorders.


2017 ◽  
Vol 41 (S1) ◽  
pp. S276-S276
Author(s):  
E. Pereira ◽  
M. Mota Oliveira ◽  
R. Guedes ◽  
M.J. Peixoto ◽  
I. Ferraz ◽  
...  

IntroductionRelapse after first-episode psychosis (FEP) is a frequent problem, which can lead to patients’ poorer functioning and response to treatment. Its prevention is one of the most important and challenging targets in the treatment of psychotic disorders.ObjectivesTo characterize and evaluate relapse rates after FEP, during the course of 3 years, of a group of patients admitted at a psychiatry department.MethodsA retrospective observational study was conducted. Patients with a FEP between ages 18 to 40, admitted at the Clinic of Psychiatry and Mental Health at São João Hospital Centre between January 1, 2007 and September 30, 2013. Only patients with, at least, 3 years of follow-up at the clinic were included.ResultsFinal sample of 58 patients, 39 of which were male (mean age = 26.4 years). Forty patients were excluded by not completing the 3 years follow-up at our department. The cumulative relapse rates were 32.8% at 12 months, 53.4% at 24 months and 63.8% at 36 months. Patients with at least one relapse were younger (25.78 years vs. 27.52 years) and had shorter periods of first hospitalization (19.25 days vs. 23.52 days). These data did not reach statistical significance. Non-adherence to prescribed medication was described in 73.0% (n = 27) of patients at the time of relapse. Eight of them (21.6%) presented with cannabis use.ConclusionsAlthough no statistical significance was reached, our findings are consistent with other studies. A future study with a bigger sample would be important in achieving statistical significant results.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2006 ◽  
Vol 36 (10) ◽  
pp. 1349-1362 ◽  
Author(s):  
N. M. MENEZES ◽  
T. ARENOVICH ◽  
R. B. ZIPURSKY

Background. Existing outcome literature has had an over-representation of chronic patients and suggested a progressive course and poor outcome for schizophrenia. The current study aimed to recombine data of samples from longitudinal studies of first-episode psychosis (FEP) to describe outcome and its predictors.Method. A literature search (1966–2003) was conducted for prospective studies examining outcome in first-episode non-affective psychosis using the following key words: early, first, incident, episode, admission, contact, psychosis, schizophrenia, psychotic disorders, course, outcome, follow-up, longitudinal, cohort. These were pooled and analyzed using descriptive and regression analyses.Results. Thirty-seven studies met the inclusion criteria, representing 4100 patients with a mean follow-up of 35·1±6·0 months. Studies varied in the categories of outcome used, the most common being ‘good’ (54% of studies) and ‘poor’ (34% of studies), variably defined. In studies reporting these categories, good outcomes were reported in 42·2% (3·5%) and poor outcomes in 27·1% (2·8%) of cases. Predictors associated with better outcome domains were: combination of pharmacotherapy and psychosocial therapy, lack of epidemiologic representativeness of the sample, and a developing country of origin. Use of typical neuroleptics was associated with worse outcome. Stratification analyses suggested that populations with schizophrenia only, and those with prospective design, were associated with worse outcome domains.Conclusions. Outcome from FEP may be more favorable than previously reported, and treatment and methodological variables may be important contributors to outcome. Significant heterogeneity in definitions and methodology limited the comparison and pooling of data. A multi-dimensional, globally used definition of outcome is required for future research.


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