Structural and Functional Neuroimaging Biomarkers of Antipsychotic Treatment Response in Early-Course and Chronic Schizophrenia

Abstract Background The corpus callosum (CC) deficits have been well documented in chronic schizophrenia. However, the long-term impacts of antipsychotic monotherapies on callosal anatomy remain unclear. This cross-sectional study sought to explore micro- and macro-structural characteristics of the CC in never-treated patients and those with long-term mono-antipsychotic treatment. Methods The study included 23 clozapine-treated schizophrenia patients (CT-SCZ), 19 risperidone-treated schizophrenia patients (RT-SCZ), 23 never-treated schizophrenia patients (NT-SCZ), and 35 healthy controls (HCs). High resolution structural images and diffusion tensor imaging (DTI) data for each participant were obtained via a 3.0 T MR scanner. FreeSurfer was used to examine the volumes and fractional anisotropy (FA) values of the CC for each participant. Results There were significant deficits in the total and sub-regional CC volume and white matter integrity in NT-SCZ in comparison with healthy subjects. Compared with NT-SCZ, both CT-SCZ and RT-SCZ showed significantly increased FA values in the anterior CC region, while only RT-SCZ showed significantly increased volume in the mid-anterior CC region. Moreover, the volume of the mid-anterior CC region was significantly smaller in CT-SCZ compared to HCs. No correlations of clinical symptoms with callosal metrics were observed in schizophrenia patients. Conclusions Our findings provide insight into micro- and macro-structural characteristics of the CC in chronic schizophrenia patients with or without antipsychotics. These results suggest that the pathology itself is responsible for cerebral abnormalities in schizophrenia and that chronic exposure to antipsychotics may have an impact on white matter structure of schizophrenia patients, especially in those with risperidone treatment.

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

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgaa014 ◽

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.

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Association study between COMT, DRD2, and DRD3 gene variants and antipsychotic treatment response in Mexican patients with schizophrenia

Neuropsychiatric Disease and Treatment ◽

10.2147/ndt.s176455 ◽

2018 ◽

Vol Volume 14 ◽

pp. 2981-2987 ◽

Cited By ~ 9

Author(s):

Raul Escamilla ◽

Beatriz Camarena ◽

Ricardo Saracco ◽

Ana Fresán ◽

Sandra Hernández ◽

...

Keyword(s):

Association Study ◽

Treatment Response ◽

Antipsychotic Treatment ◽

Gene Variants ◽

Em Gene ◽

Mexican Patients

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The Potential Role of Regulatory Genes (DNMT3A, HDAC5, and HDAC9) in Antipsychotic Treatment Response in South African Schizophrenia Patients

Frontiers in Genetics ◽

10.3389/fgene.2019.00641 ◽

2019 ◽

Vol 10 ◽

Author(s):

Kevin Sean O’Connell ◽

Nathaniel Wade McGregor ◽

Robin Emsley ◽

Soraya Seedat ◽

Louise Warnich

Keyword(s):

Treatment Response ◽

South African ◽

Potential Role ◽

Regulatory Genes ◽

Antipsychotic Treatment

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Should antipsychotic medications for schizophrenia be given for a lifetime? Replication of a naturalistic, long-term, follow-up study of antipsychotic treatment

CNS Spectrums ◽

10.1017/s109285291800144x ◽

2019 ◽

Vol 24 (5) ◽

pp. 557-563 ◽

Cited By ~ 1

Author(s):

Ira D. Glick ◽

Daisy Zamora ◽

Danielle Kamis ◽

John M. Davis

Keyword(s):

Life Satisfaction ◽

Medication Adherence ◽

Past History ◽

Chronic Schizophrenia ◽

Antipsychotic Treatment ◽

Consecutive Series ◽

Linear Regression Models ◽

Long Term Treatment

ObjectiveBecause ethically and practically a randomized control trial of antipsychotics will never be done, we recently conducted and reported a 8- to 50-year, naturalistic follow-up from an academic clinic of patients with chronic schizophrenia on antipsychotic medication. We found that better medication adherence was a statistically significant predictor of better long-term global outcome and life satisfaction. Because there were important limitations on our findings, we now in this communication, using similar methodology, detail outcomes for a very different sample—inner city patients with chronic schizophrenia with a long past history of antipsychotic treatment, who were enrolled in clinical trials for new medications for schizophrenia.MethodsThis is a retrospective, naturalistic, longitudinal 6- to 49-years antipsychotic treatment (mean average, 20) follow-up of a consecutive series of patients volunteering for screening for studies with schizophrenia. Lifetime data were collected on (1) their medication adherence, (2) long-term global outcome, and (3) life satisfaction. Outcomes were rated by 2 different clinicians, 1 with information on medication adherence (nonblind rater) and 1 without (blind rater). We used linear regression models adjusted for age, family support, substance use disorder, race, marital status, and number of years in treatment to estimate the association between adherence and each outcome.ResultsA total of 34 patients were assessed. Medication adherence was positively associated with the blind clinician’s rating of global outcome (P value=0.03) and the global assessment of functioning (P value=0.05). In the nonblinded clinician rating, medication adherence was unrelated to global outcome (P value=0.26) and to patients’ report of life satisfaction (P value=0.54).ConclusionThis replication study, like our previous study, is not inconsistent with the recommendation for continuous, long-term treatment for chronic schizophrenia unless medically contraindicated.

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