scholarly journals Striatal functional connectivity in psychosis relapse: A comparison between antipsychotic adherent and non-adherent patients at the time of relapse

2020 ◽  
Author(s):  
Jose M Rubio ◽  
Todd Lencz ◽  
Anita Barber ◽  
Franchesica Bassaw ◽  
Gabriela Ventura ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Treatment Response ◽  
Psychotic Disorders ◽  
Prognostic Biomarker ◽  
Dorsal Striatum ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Course Of Illness ◽  
Striatal Function ◽  
Group Comparisons

Most individuals with psychotic disorders relapse over their course of illness. Relapse pathophysiology is generally not well captured in studies that do not account for antipsychotic non-adherence, which is common and often unnoticed in schizophrenia. This study was explicitly designed to understand relapse in patients with guaranteed antipsychotic delivery. We compared individuals with psychosis breakthrough on antipsychotic maintenance medication (BAMM, n=23), for whom antipsychotic adherence prior to relapse was confirmed by using long acting injectable antipsychotics, and individuals who at the time of relapse were antipsychotic free (APF, n=27), as they had declared treatment non-adherence. Resting state functional MRI was acquired to conduct a region of interest (ROI) analyses. We generated functional connectivity maps to calculate striatal connectivity index (SCI) values, a prognostic biomarker of treatment response in first episode schizophrenia. Group differences in SCI values (BAMM vs APF) were compared in a linear regression model. We hypothesized that individuals in the BAMM group would have greater aberrant striatal function, thus lower SCI values, than in individuals in the APF group. Furthermore, we conducted exploratory group comparisons at the ROI level. As predicted, the BAMM group had significantly lower SCI values (β=0.95, standard error=0.378, p=0.013). Group comparisons at the ROI level indicate differences in functional connectivity of dorsal striatum, and greater decoupling in striato-cerebellar connections among the BAMM group. A prognostic biomarker of treatment response in first episode psychosis showed differences by antipsychotic exposure upon relapse, suggesting that relapse during continued antipsychotic treatment may be characterized by aberrant striatal function.

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

2019 ◽  
Vol 46 (3) ◽  
pp. 680-689 ◽  
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.

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

2019 ◽  
Vol 50 (13) ◽  
pp. 2182-2193 ◽  
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.

scholarly journals Interaction of Cannabis Use Disorder and Striatal Connectivity in Antipsychotic Treatment Response

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Melanie Blair Thies ◽  
Pamela DeRosse ◽  
Deepak K Sarpal ◽  
Miklos Argyelan ◽  
Christina L Fales ◽  
...  
Keyword(s):  
Treatment Response ◽  
Reward Processing ◽  
Cannabis Use ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Cannabis Use Disorder ◽  
Schizophrenia Spectrum Disorders ◽  
Double Blind ◽  
History Of ◽  
The Relationship

Abstract Antipsychotic (AP) medications are the mainstay for the treatment of schizophrenia spectrum disorders (SSD), but their efficacy is unpredictable and widely variable. Substantial efforts have been made to identify prognostic biomarkers that can be used to guide optimal prescription strategies for individual patients. Striatal regions involved in salience and reward processing are disrupted as a result of both SSD and cannabis use, and research demonstrates that striatal circuitry may be integral to response to AP drugs. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between a history of cannabis use disorder (CUD) and a striatal connectivity index (SCI), a previously developed neural biomarker for AP treatment response in SSD. Patients were part of a 12-week randomized, double-blind controlled treatment study of AP drugs. A sample of 48 first-episode SSD patients with no more than 2 weeks of lifetime exposure to AP medications, underwent a resting-state fMRI scan pretreatment. Treatment response was defined a priori as a binary (response/nonresponse) variable, and a SCI was calculated in each patient. We examined whether there was an interaction between lifetime CUD history and the SCI in relation to treatment response. We found that CUD history moderated the relationship between SCI and treatment response, such that it had little predictive value in SSD patients with a CUD history. In sum, our findings highlight that biomarker development can be critically impacted by patient behaviors that influence neurobiology, such as a history of CUD.

scholarly journals Familial and socioeconomic contributions to premorbid functioning in psychosis: Impact on age at onset and treatment response

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Alex Hatzimanolis ◽  
Pentagiotissa Stefanatou ◽  
Emmanouil Kattoulas ◽  
Irene Ralli ◽  
Stefanos Dimitrakopoulos ◽  
...  
Keyword(s):  
Treatment Response ◽  
Social Functioning ◽  
Early Adolescence ◽  
Psychotic Disorders ◽  
Age At Onset ◽  
Familial Risk ◽  
Treatment Resistance ◽  
Joint Effect ◽  
First Episode ◽  
Environment Interaction

Abstract Background. Premorbid adjustment (PA) abnormalities in psychotic disorders are associated with an earlier age at onset (AAO) and unfavorable clinical outcomes, including treatment resistance. Prior family studies suggest that familial liability, likely reflecting increased genetic risk, and socioeconomic status (SES) contribute to premorbid maladjustment. However, their joint effect possibly indicating gene–environment interaction has not been evaluated. Methods. We examined whether family history of psychosis (FHP) and parental SES may predict PA and AAO in unrelated cases with first-episode psychosis (n = 108) and schizophrenia (n = 104). Premorbid academic and social functioning domains during childhood and early adolescence were retrospectively assessed. Regression analyses were performed to investigate main effects of FHP and parental SES, as well as their interaction. The relationships between PA, AAO, and response to antipsychotic medication were also explored. Results. Positive FHP associated with academic PA difficulties and importantly interacted with parental SES to moderate social PA during childhood (interaction p = 0.024). Positive FHP and parental SES did not predict differences in AAO. Nevertheless, an earlier AAO was observed among cases with worse social PA in childhood (β = −0.20; p = 0.005) and early adolescence (β = −0.19; p = 0.007). Further, confirming evidence emerged for an association between deficient childhood social PA and poor treatment response (p = 0.04). Conclusions. Familial risk for psychosis may interact with parental socioeconomic position influencing social PA in childhood. In addition, this study supports the link between social PA deviations, early psychosis onset, and treatment resistance, which highlights premorbid social functioning as a promising clinical indicator.

scholarly journals T119. NO DIFFERENCE BETWEEN VOLITIVE AND EXPRESSIVE NEGATIVE SYMPTOMS FOR EARLY TREATMENT RESPONSE IN FIRST EPISODE OF PSYCHOSIS ANTIPSYCHOTIC NAïVE PATIENTS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S276-S276
Author(s):  
Bernardo Haguiara ◽  
Gabriela Koga Tonsig ◽  
Simão Kagan ◽  
Daniel Cavalcante ◽  
Cristiano Noto ◽  
...  
Keyword(s):  
Treatment Response ◽  
Negative Symptoms ◽  
Real Life ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Social Avoidance ◽  
F Test ◽  
The Social ◽  
Highly Correlated

Abstract Background Negative symptoms are associated with a range of poor clinical and real-life functioning outcomes in people with schizophrenia. The division of negative symptoms into two separate factors, named “expressive deficits” and “social amotivation” could enable more accurate analysis and the development of new therapeutic tools. We aim to investigate whether the different symptoms that make up the negative dimension at baseline differently predict treatment response in first episode psychosis (FEP) antipsychotic naïve patients. Methods Patients with FEP (n=80), without previous use of antipsychotics, were recruited at an emergency service in São Paulo, Brazil, between 2014 and 2019. Individuals were assessed at admission and after 10 weeks of follow-up. Patients with schizophrenia, schizoaffective disorder and schizophreniform disorder were included. The diagnosis was confirmed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I). Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at the baseline and after 10 weeks of treatment. The “expressive deficits” factor was defined as the sum of the six following items of the PANSS: N1 (blunted affect), N3 (poor rapport), N6 (lack of spontaneity and flow of conversation), G5 (mannerisms and posturing), G7 (motor retardation), G13 (disturbance of volition). The “social amotivation” factor was defined as the sum of N2 (emotional withdrawal), N4 (passive/apathetic social withdrawal) and G16 (active social avoidance). To evaluate treatment response, we used the difference between the PANSS score at baseline and after ten weeks of follow-up (delta-PANSS). We performed three linear regressions, one using the “expressive deficits” factor, one using the “social amotivation” factor and another using the total negative symptom score at baseline. Results The mean age was 26.01 years old (SD ± 7.2), and the majority was male (58.75%). “Expressive deficits” (p=0.005, R-squared=0.084, F-test=8.28, β=8.24, df=78), “social amotivation” (p=0.009, R-squared=0,072, F-test=7.14, β=5.59, df=78); and negative symptoms (p=0.002, R-squared=0.105, F-test=10.23, β=9.08, df=78) at baseline behaved similarly in relation to delta-PANSS. All measures of negative symptoms are highly correlated to PANSS total at both time points. Discussion The results were different from our initial hypothesis of worse outcome for patients with higher expressive negative symptoms. We found that negative symptoms overall and both subdomains are highly correlated to PANSS total in acute phase in early stages, what can explain the association to better outcomes with antipsychotic treatment. Longer follow-up can help us to investigate whether differences between the subdomains of negative symptoms can be observed in more stable patients.

scholarly journals Association of a Schizophrenia Risk Variant at theDRD2Locus With Antipsychotic Treatment Response in First-Episode Psychosis

2015 ◽  
Vol 41 (6) ◽  
pp. 1248-1255 ◽  
Author(s):  
Jian-Ping Zhang ◽  
Delbert G. Robinson ◽  
Juan A. Gallego ◽  
Majnu John ◽  
Jin Yu ◽  
...  
Keyword(s):  
Treatment Response ◽  
First Episode Psychosis ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Risk Variant ◽  
Episode Psychosis

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

2021 ◽  
Author(s):  
Sidhant Chopra ◽  
Shona M. Francey ◽  
Brian O’Donoghue ◽  
Kristina Sabaroedin ◽  
Aurina Arnatkeviciute ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
First Episode Psychosis ◽  
Common Finding ◽  
First Episode ◽  
Control Group ◽  
Antipsychotic Treatment ◽  
Long Term Effects ◽  
Limbic Systems ◽  
Episode Psychosis ◽  
The Brain

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.

scholarly journals O2.1. LOCAL AND LONG-RANGE CONNECTIVITY PATTERNS OF AUDITORY PERCEPTUAL DISTURBANCE IN SCHIZOPHRENIA

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S3-S4
Author(s):  
Stephanie Hare ◽  
Bhim Adhikari ◽  
Joshua Chiappelli ◽  
Xiaoming Du ◽  
Shuo Chen ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Subscale Score ◽  
Small Sample ◽  
Fmri Data ◽  
First Episode ◽  
Functional Communication ◽  
Resting State Functional Connectivity ◽  
Course Of Illness ◽  
Temporoparietal Junction ◽  
Local Functional

Abstract Background Auditory hallucinations are a prevalent, debilitating symptom of schizophrenia (Sz). Lack of detailed phenomenological assessments of perceptual disturbances in large psychiatric imaging datasets limits our ability to disentangle the underlying neural mechanisms of hallucinations. Our study investigates how changes in local functional communication dynamics may be associated with wide-ranging auditory disturbances in Sz. Methods Local functional connectivity was estimated using regional homogeneity (ReHo) analysis of resting fMRI data, which quantifies synchronization of fMRI activity of a voxel to its neighboring voxels. Resting fMRI data of 99 Sz patients was analyzed (mean age=36.2±13.3 y, sex=71/28 m/f); Auditory perceptual disturbance in the past week was estimated using the auditory perception state (APS) subscale score of the recently validated Auditory Perceptual Trait and State Scale (http://www.mdbrain.org/APTS.pdf). Voxelwise regression analysis of ReHo was performed including APS score as a regressor of interest. Significant results were thresholded using AFNI’s 3dClustSim with autocorrelation function option to yield corrected p<0.05, corresponding to cluster-size threshold of 49 voxels at voxelwise p=0.001. Results Higher APS scores were associated with reduced ReHo in clusters in left putamen, right putamen, left temporoparietal junction, and right hippocampus. In a follow-up analysis using these clusters as seeds in whole-brain resting-state functional connectivity analysis (rsFC) analysis, higher APS scores were significantly associated with reduced rsFC between the right putamen seed and clusters in the contralateral putamen and auditory cortex. Discussion Our findings are consistent with those of a prior study that reported abnormal ReHo in left and right putamen of a unmedicated first-episode Sz patients (Cui et al. 2016). However, in that small sample (n=32), striatal ReHo was elevated relative to controls, and AH severity was not significantly correlated with striatal ReHo measures. Our study investigated ReHo in a large sample of chronic, medicated patients (all except 4 were taking antipsychotic medication at time of study). While it is widely accepted that striatal signaling is disrupted in Sz, future work is needed to better understand how striatal signaling deficits may change over the course of illness and how this relates to particular symptoms such as hallucinations. Implications for development of novel therapies that account for these nuanced findings will be discussed.

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