Longitudinal Changes in Functional Connectivity in Antipsychotic-treated and Antipsychotic-naive Patients with First Episode Psychosis

AbstractBackgroundAltered functional connectivity (FC) is a common finding in resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotics may influence the temporal evolution of these disturbances, remains unclear. Here, we scanned first episode psychosis (FEP) patients who were and were not exposed to antipsychotic medication during the first six months of illness at baseline, three months, and 12 months, to characterize how FC changes over time and in relation to medication use.MethodsSixty-two antipsychotic-naïve patients with FEP received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. A total of 202 rs-fMRI scans were obtained across three timepoints: baseline, 3-months and 12-months. Our primary aim was to differentiate patterns of FC in antipsychotic-treated and antipsychotic-naive patients within the first 3 months of treatment, and to examine associations with clinical and functional outcomes. A secondary aim was to investigate long-term effects at the 12-month timepoint.ResultsAt baseline, FEP patients showed widespread functional dysconnectivity in comparison to controls, with reductions predominantly affecting interactions between the default mode network (DMN), limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems, and some of these changes correlated with improved clinical outcomes. Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. At the 12-month follow-up, antipsychotic treatment was associated with a prolonged increase of FC primarily in the DMN and limbic systems.Conclusions and RelevanceAntipsychotic-naïve FEP patients show widespread functional dysconnectivity at baseline, followed by an early normalization of DMN and paralimbic dysfunction in patients receiving a psychosocial intervention only. Antipsychotic exposure is associated with distinct FC changes, principally concentrated on thalamo-cortical and limbic networks.

Download Full-text

Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study

Neuropsychopharmacology ◽

10.1038/s41386-021-00980-0 ◽

2021 ◽

Author(s):

Sidhant Chopra ◽

Alex Fornito ◽

Shona M. Francey ◽

Brian O’Donoghue ◽

Vanessa Cropley ◽

...

Keyword(s):

Antipsychotic Medication ◽

Brain Volume ◽

First Episode Psychosis ◽

Common Finding ◽

First Episode ◽

Control Group ◽

Grey Matter Volume ◽

Long Term Effects ◽

Significant Group ◽

Episode Psychosis

AbstractChanges in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.

Download Full-text

Anterior Hippocampal–Cortical Functional Connectivity Distinguishes Antipsychotic Naïve First-Episode Psychosis Patients From Controls and May Predict Response to Second-Generation Antipsychotic Treatment

Schizophrenia Bulletin ◽

10.1093/schbul/sbz076 ◽

2019 ◽

Vol 46 (3) ◽

pp. 680-689 ◽

Cited By ~ 3

Author(s):

Esther M Blessing ◽

Vishnu P Murty ◽

Botao Zeng ◽

Jijun Wang ◽

Lila Davachi ◽

...

Keyword(s):

Functional Connectivity ◽

Random Forest ◽

Treatment Response ◽

Second Generation ◽

First Episode Psychosis ◽

First Episode ◽

Antipsychotic Treatment ◽

Episode Psychosis ◽

Second Generation Antipsychotic ◽

Cortical Regions

Abstract Background Converging evidence implicates the anterior hippocampus in the proximal pathophysiology of schizophrenia. Although resting state functional connectivity (FC) holds promise for characterizing anterior hippocampal circuit abnormalities and their relationship to treatment response, this technique has not yet been used in first-episode psychosis (FEP) patients in a manner that distinguishes the anterior from posterior hippocampus. Methods We used masked-hippocampal-group-independent component analysis with dual regression to contrast subregional hippocampal–whole brain FC between healthy controls (HCs) and antipsychotic naïve FEP patients (N = 61, 36 female). In a subsample of FEP patients (N = 27, 15 female), we repeated this analysis following 8 weeks of second-generation antipsychotic treatment and explored whether baseline FC predicted treatment response using random forest. Results Relative to HC, untreated FEP subjects displayed reproducibly lower FC between the left anteromedial hippocampus and cortical regions including the anterior cingulate and insular cortex (P < .05, corrected). Anteromedial hippocampal FC increased in FEP patients following treatment (P < .005), and no longer differed from HC. Random forest analysis showed baseline anteromedial hippocampal FC with four brain regions, namely the insular–opercular cortex, superior frontal gyrus, precentral gyrus, and postcentral gyrus predicted treatment response (area under the curve = 0.95). Conclusions Antipsychotic naïve FEP is associated with lower FC between the anterior hippocampus and cortical regions previously implicated in schizophrenia. Preliminary analysis suggests that random forest models based on hippocampal FC may predict treatment response in FEP patients, and hence could be a useful biomarker for treatment development.

Download Full-text

Maintenance antipsychotic treatment versus discontinuation strategies following remission from first episode psychosis: systematic review

BJPsych Open ◽

10.1192/bjo.2018.17 ◽

2018 ◽

Vol 4 (4) ◽

pp. 215-225 ◽

Cited By ~ 11

Author(s):

Andrew Thompson ◽

Catherine Winsper ◽

Steven Marwaha ◽

Jon Haynes ◽

Mario Alvarez-Jimenez ◽

...

Keyword(s):

Systematic Review ◽

Maintenance Treatment ◽

Meta Analysis ◽

First Episode Psychosis ◽

Risk Difference ◽

First Episode ◽

Control Group ◽

Antipsychotic Treatment ◽

Medication Discontinuation ◽

Episode Psychosis

BackgroundUnderstanding the relative risks of maintenance treatment versus discontinuation of antipsychotics following remission in first episode psychosis (FEP) is an important area of practice.MethodA systematic review and meta-analysis. Prospective experimental studies including a parallel control group were identified to compare maintenance antipsychotic treatment with total discontinuation or medication discontinuation strategies following remission in FEP.ResultsSeven studies were included. Relapse rates were higher in the discontinuation group (53%; 95% CIs: 39%, 68%; N = 290) compared with maintenance treatment group (19%; 95% CIs: 0.05%, 37%; N = 230). In subgroup analyses, risk difference of relapse was lower in studies with a longer follow-up period, a targeted discontinuation strategy, a higher relapse threshold, a larger sample size, and samples with patients excluded for drug or alcohol dependency. Insufficient studies included psychosocial functioning outcomes for a meta-analysis.ConclusionsThere is a higher risk of relapse for those who undergo total or targeted discontinuation strategies compared with maintenance antipsychotics in FEP samples. The effect size is moderate and the risk difference is lower in trials of targeted discontinuation strategies.Declaration of interestA.T. has received honoraria and support from Janssen-Cilag and Otsuka Pharmaceuticals for meetings and has been has been an investigator on unrestricted investigator-initiated trials funded by AstraZeneca and Janssen-Cilag. He has also previously held a Pfizer Neurosciences Research Grant. S.M. has received sponsorship from Otsuka and Lundbeck to attend an academic congress and owns shares in GlaxoSmithKline and AstraZeneca. J.H. has attended meetings supported by Sunovion Pharmaceuticals.

Download Full-text

Brief psycho-education for caregivers of persons with first episode psychosis

Indian Journal of Positive Psychology ◽

10.15614/ijpp.v9i01.11741 ◽

2018 ◽

Vol 9 (01) ◽

Author(s):

Praful Prabhuappa Kapse ◽

Manisha Kiran

Keyword(s):

First Episode Psychosis ◽

First Episode ◽

Control Group ◽

Episode Psychosis ◽

Study Results ◽

Before And After ◽

Quasi Experimental ◽

Expressed Emotions ◽

Experimental Group ◽

Group Family

Caring for the persons with first episode psychosis is challenging and demanding. It may lead to the increased burden, expressed emotions among the caregivers. The numerous studies have shown that high burden and negative expressed emotions among caregivers can lead to early relapse in the patients with first episode psychosis. To evaluate the effects of the brief psychoeducation on the caregivers burden and expressed emotions. A quasi experimental - before and after with control group research design was adopted for the study. A total of 60 caregivers have participated in the study, of which 30 caregivers in experimental group and 30 caregivers in the control group. Family Burden Interview Schedule (Pai and Kapoor, 1981) and Attitude Questionnaire (Sethi et al., 1981) was used to assess caregiver's burden and expressed emotions. At end of the psychoeducation intervention, burden among caregivers and negative expressed emotions of the caregivers have significantly reduced. The positive expressed emotions have been increased. Study results demonstrates the importance of psychoeducation intervention in reducing the burden and negative expressed emotions.

Download Full-text

Implementation of NAVIGATE Coordinated Specialty Care for First Episode Psychosis: the Michigan Experience

CNS Spectrums ◽

10.1017/s1092852920002928 ◽

2021 ◽

Vol 26 (2) ◽

pp. 177-178

Author(s):

Eric D. Achtyes ◽

Kari Kempema ◽

Zhehui Luo ◽

Katharine N. Thakkar ◽

Catherine Adams ◽

...

Keyword(s):

Mental Health ◽

Clinical Symptoms ◽

The United States ◽

First Episode Psychosis ◽

Specialty Care ◽

First Episode ◽

Control Group ◽

Evidence Based ◽

Block Grant ◽

Episode Psychosis

AbstractStudy ObjectivesCoordinated specialty care (CSC) is widely accepted as an evidence-based treatment for first episode psychosis (FEP). The NAVIGATE intervention from the Recovery After an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study is a CSC intervention which offers a suite of evidence-based treatments shown to improve engagement and clinical outcomes, especially in those with shorter duration of untreated psychosis (DUP). Coincident with the publication of this study, legislation was passed by the United States Congress in 2014–15 to fund CSC for FEP via a Substance Abuse and Mental Health Services Administration (SAMHSA) block grant set-aside for each state. In Michigan (MI) the management of this grant was delegated to Network180, the community mental health authority in Kent County, with the goal of making CSC more widely available to the 10 million people in MI. Limited research describes the outcomes of implementation of CSC into community practices with no published accounts evaluating the use of the NAVIGATE intervention in a naturalistic setting. We describe the outcomes of NAVIGATE implementation in the state of MI.MethodsIn 2014, 3 centers in MI were selected and trained to provide NAVIGATE CSC for FEP. In 2016 a 4th center was added, and 2 existing centers were expanded to provide additional access to NAVIGATE. Inclusion: age 18–31, served in 1 of 4 FEP centers in MI. Data collection began in 2015 for basic demographics, global illness (CGI q3 mo), hospital/ED use and work/school (SURF q3 mo) and was expanded in 2016 to include further demographics, diagnosis, DUP, vital signs; and in 2018 for clinical symptoms with the modified Colorado Symptom Inventory (mCSI q6 mo), reported via an online portal. This analysis used data until 12/31/19. Mixed effects models adjusted by age, sex and race were used to account for correlated data within patients.ResultsN=283 had useable demographic information and were included in the analysis. Age at enrollment was 21.6 ± 3.0 yrs; 74.2% male; 53.4% Caucasian, 34.6% African American; 12.9 ± 1.7 yrs of education (N=195). 18 mo retention was 67% with no difference by sex or race. CGI scores decreased 20% from baseline (BL) to 18 mo (BL=3.5, N=134; 15–18 mo=2.8, N=60). Service utilization via the SURF was measured at BL (N=172) and 18 mo (N=72): psychiatric hospitalizations occurred in 37% at BL and 6% at 18 mo (p<0.01); ER visits occurred in 40% at BL and 13% at 18 mo (p<0.01). 44% were working or in school at BL and 68% at 18 mo (p<0.01). 21% were on antipsychotics (AP) at BL (N=178) and 85% at 18 mo (N=13) with 8% and 54% on long acting injectable-AP at BL and 18 mo, respectively. Limitations include missing data and lack of a control group.ConclusionThe implementation of the NAVIGATE CSC program for FEP in MI resulted in meaningful clinical improvement for enrollees. Further support could make this evidence-based intervention available to more people with FEP.FundingSupported by funds from the SAMHSA Medicaid State Block Grant set-aside awarded to Network180 (Achtyes, Kempema). The funders had no role in the design of the study, the analysis or the decision to publish the results.

Download Full-text

Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

Psychological Medicine ◽

10.1017/s0033291719002277 ◽

2019 ◽

Vol 50 (13) ◽

pp. 2182-2193 ◽

Cited By ~ 11

Author(s):

Kirsten B. Bojesen ◽

Bjørn H. Ebdrup ◽

Kasper Jessen ◽

Anne Sigvard ◽

Karen Tangmose ◽

...

Keyword(s):

Psychotic Disorders ◽

Poor Response ◽

First Episode Psychosis ◽

Anterior Cingulate ◽

First Episode ◽

Antipsychotic Treatment ◽

Resonance Spectroscopy ◽

Reference Levels ◽

Clinical Prognosis ◽

Episode Psychosis

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.

Download Full-text

Association of cannabis use with hospital admission and antipsychotic treatment failure in first episode psychosis: an observational study

BMJ Open ◽

10.1136/bmjopen-2015-009888 ◽

2016 ◽

Vol 6 (3) ◽

pp. e009888 ◽

Cited By ~ 56

Author(s):

Rashmi Patel ◽

Robin Wilson ◽

Richard Jackson ◽

Michael Ball ◽

Hitesh Shetty ◽

...

Keyword(s):

Observational Study ◽

Hospital Admission ◽

Treatment Failure ◽

First Episode Psychosis ◽

Cannabis Use ◽

First Episode ◽

Antipsychotic Treatment ◽

Episode Psychosis

Download Full-text

Does food responsiveness change in people with first episode psychosis (FEP) over a period of 6 months after commencing antipsychotics? Preliminary results

BJPsych Open ◽

10.1192/bjo.2021.682 ◽

2021 ◽

Vol 7 (S1) ◽

pp. S255-S255

Author(s):

Adrian Heald ◽

Mark Shakespeare ◽

Kevin Williamson ◽

Adrianne Close ◽

Adrian Phillipson ◽

...

Keyword(s):

Rating Scales ◽

Eating Behaviour ◽

First Episode Psychosis ◽

Intuitive Eating ◽

First Episode ◽

Antipsychotic Treatment ◽

Loss Of Control ◽

Convenience Sample ◽

Preliminary Results ◽

Episode Psychosis

AimsWe here present preliminary results from our study to understand better the changes in people’ s experience of food in the months after diagnosis with first episode psychosis (FEP). Weight gain often occurs in the weeks/months after diagnosis and is related to an increase in appetite and food intake. Many drugs that are effective in treating psychosis are associated with changes in the way that people experience reward when they eat.The aim of this project is to increase our understanding of exactly why this happens in terms of an individual's experience of food reward and reduced satiety – and therefore how we can help people with FEP to keep their weight down. At this stage we are looking at the feasibility of applying currently available evaluation tools to people in this situation.MethodA convenience sample was used to recruit 10 service users from RDaSH NHS FT Early Intervention Services. This is a feasibility study which will provide data to underpin a fully powered, larger trial.Rating scales applied were:Power of food questionnaire: measures responsiveness to the food environment.Intuitive Eating Scale: measures an individual's tendency to follow their physical hunger and satiety cues.The loss of control over eating scale (LOCES): measures a global sense of whether individuals experience LOC over eating.Dutch Eating Behaviour Questionnaire (DEBQ): measures restrained eating, emotional eating and external eating.ResultThe ages of the participants ranged from 17-26 years. All were started on Olanzapine at the dose of 5 or 10 mg daily.Baseline total scores for the Power of Food (2.47-3.80)/5 (higher score = more responsiveness) and Intuitive Eating scales (2.10-2.62)/5 (higher score = greater tendency to follow hunger and satiety cues) were in the mid-range, while the LOCES scores varied widely from 1.50-2.38/5.The DEBQ restrained subscale score range was 2.40-2.80/5 (higher indicates greater restraint with food) while the DEBQ external subscale ranged from 2.70—3.00/5 (higher = greater tendency to overeat) and the DEBQ emotional subtotal score was 1.92-1.94/5, in keeping with a relatively low emotional drive to eat.ConclusionOur preliminary results reveal at the beginning of antipsychotic treatment a moderate responsiveness to food and tendency to follow hunger/ satiety cues, with scores for Loss of Control of eating in the low to moderate range and a low emotional drive to eat. The difference between these and the follow-up eating behaviour scores will provide important clues as to the precise changes in eating behaviour with anti-psychotic treatment in FEP.

Download Full-text