Early striatal hypertrophy in first-episode psychosis within 3 weeks of initiating antipsychotic drug treatment

2008 ◽  
Vol 39 (5) ◽  
pp. 793-800 ◽  
Author(s):  
S. E. Chua ◽  
Y. Deng ◽  
E. Y. H. Chen ◽  
C. W. Law ◽  
C. P. Y. Chiu ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Grey Matter ◽  
Economic Status ◽  
Region Of Interest ◽  
Brain Morphology ◽  
Group Differences ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Caudate Nuclei ◽  
The Right

BackgroundWe and others have reported that patients experiencing their first episode of psychosis already have significant structural brain abnormalities. Antipsychotics seem to reverse subcortical volume deficits after months of treatment. However, the early impact of medication on brain morphology is not known.MethodForty-eight individuals in their first episode of psychosis underwent magnetic resonance imaging (MRI) brain scanning. Twenty-six were antipsychotic naive and 22 were newly treated with antipsychotic medication for a median period of 3 weeks. In each group, 80% of subjects received a diagnosis of schizophrenia. The two groups were balanced for age, sex, handedness, ethnicity, height, years of education, paternal socio-economic status (SES) and Positive and Negative Syndrome Scale (PANSS) score. Group differences in whole-brain grey matter were compared voxel by voxel, using Brain Activation and Morphological Mapping (BAMM) software. We also conducted testing of group differences with region-of-interest (ROI) measurements of the caudate nucleus.ResultsRelative to the untreated group, those receiving antipsychotic medication for 3–4 weeks had significantly greater grey-matter volumes in the bilateral caudate and cingulate gyri, extending to the left medial frontal gyrus. ROI analysis confirmed that, in treated patients, the right and left caudate nuclei were significantly larger by 10% (p<0.039, two-tailed) and 9% (p<0.048, two-tailed) respectively.ConclusionsEarly striatal grey-matter enlargement may occur within the first 3–4 weeks of antipsychotic treatment. Possible reasons for putative striatal hypertrophy and its implications are discussed.

Changes in the cytokine profile in first episode, drug-naïve patients with psychosis after short-term antipsychotic treatment

2017 ◽  
Vol 41 (S1) ◽  
pp. S371-S371
Author(s):  
P. Petrikis ◽  
P. Voulgari ◽  
V. Boumba ◽  
D. Archimandriti ◽  
P. Skapinakis ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antipsychotic Treatment ◽  
Before And After ◽  
Drug Naïve ◽  
Competing Interest

IntroductionAn increasing body of evidence suggests that antipsychotic medication can cause immunological changes that could be attributed to the amelioration of psychotic symptoms or the metabolic side effects of the drugs. So far, the results of the studies remain controversial.ObjectiveOur aim was to compare the levels of interleukin (IL) IL-2, IL-6 and transforming growth factor-β2 (TGF-β2) in drug-naïve, first-episode patients with psychosis before and after six weeks of antipsychotic medication.MethodsThirty-nine first episode patients with psychosis were enrolled in the study. Serum levels of IL-2, IL-6 and TGF-β2 were measured by enzyme linked immunosorbent assay (ELISA) before and six weeks after the initiation of antipsychotic medication. In addition, clinical psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS) before and after treatment.ResultsSerum levels of IL-2 were significantly higher in the study group six weeks after the initiation of antipsychotic treatment (P < 0.001) while TGF-β2 levels were decreased (P < 0.001) and IL-6 levels were slightly reduced (P < 0.004).ConclusionThe changes in cytokine levels may be attributed to the action of antipsychotic medication and the remission of psychopathology. The reduction in TGF-β2 levels is observed in all patients and with all antipsychotic medications used. TGF-β2 may be a marker of clinical efficacy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals A Multimodal Fusion Analysis of Pretreatment Anatomical and Functional Cortical Abnormalities in Responsive and Non-responsive Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenyang Yao ◽  
Na Hu ◽  
Hengyi Cao ◽  
Biqiu Tang ◽  
Wenjing Zhang ◽  
...  
Keyword(s):  
Multimodal Fusion ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Pathophysiological Mechanism ◽  
Multimodal Features ◽  
Significant Difference ◽  
Postcentral Gyrus ◽  
Functional Features ◽  
Fusion Analysis ◽  
The Right

Background: Antipsychotic medications provide limited long-term benefit to ~30% of schizophrenia patients. Multimodal magnetic resonance imaging (MRI) data have been used to investigate brain features between responders and nonresponders to antipsychotic treatment; however, these analytical techniques are unable to weigh the interrelationships between modalities. Here, we used multiset canonical correlation and joint independent component analysis (mCCA + jICA) to fuse MRI data to examine the shared and specific multimodal features between the patients and healthy controls (HCs) and between the responders and non-responders.Method: Resting-state functional and structural MRI data were collected from 55 patients with drug-naïve first-episode schizophrenia (FES) and demographically matched HCs. Based on the decrease in Positive and Negative Syndrome Scale scores from baseline to the 1-year follow-up, FES patients were divided into a responder group (RG) and a non-responder group (NRG). Gray matter volume (GMV), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) maps were used as features in mCCA + jICA.Results: Between FES patients and HCs, there were three modality-specific discriminative independent components (ICs) showing the difference in mixing coefficients (GMV-IC7, GMV-IC8, and fALFF-IC5). The fusion analysis indicated one modality-shared IC (GMV-IC2 and ReHo-IC2) and three modality-specific ICs (GMV-IC1, GMV-IC3, and GMV-IC6) between the RG and NRG. The right postcentral gyrus showed a significant difference in GMV features between FES patients and HCs and modality-shared features (GMV and ReHo) between responders and nonresponders. The modality-shared component findings were highlighted by GMV, mainly in the bilateral temporal gyrus and the right cerebellum associated with ReHo in the right postcentral gyrus.Conclusions: This study suggests that joint anatomical and functional features of the cortices may reflect an early pathophysiological mechanism that is related to a 1-year treatment response.

scholarly journals Patients with Poor Response to Antipsychotics Have a More Severe Pattern of Frontal Atrophy: A Voxel-Based Morphometry Study of Treatment Resistance in Schizophrenia

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mario Quarantelli ◽  
Olga Palladino ◽  
Anna Prinster ◽  
Vittorio Schiavone ◽  
Barbara Carotenuto ◽  
...  
Keyword(s):  
Grey Matter ◽  
Temporal Cortex ◽  
Region Of Interest ◽  
Treatment Resistance ◽  
Poor Response ◽  
Mr Studies ◽  
Normal Volunteers ◽  
Significant Difference ◽  
The Right ◽  
Post Hoc

Approximately 30% of schizophrenia patients do not respond adequately to the therapy. Previous MRI studies have suggested that drug treatment resistance is associated with brain morphological abnormalities, although region-of-interest analysis of MR studies from nonresponder and responder patients failed to demonstrate a statistically significant difference between these two schizophrenia subgroups. We have used a voxel-based analysis of segmented MR studies to assess structural cerebral differences in 20 nonresponder and 15 responder patients and 16 age-matched normal volunteers. Differences between the three groups emerged bilaterally mainly at the level of the superior and middle frontal gyri, primarily due to reduced grey matter volumes in nonresponders, as compared to both normal volunteers and responder patients. Post hoc direct comparison between the two schizophrenia subgroups demonstrated significantly reduced grey matter volumes in middle frontal gyrus bilaterally, in the dorsolateral aspects of left superior frontal gyrus extending into postcentral gyrus and in the right medial temporal cortex. Our results extend and integrate previous findings suggesting a more severe atrophy in nonresponder schizophrenia patients, compared to responder patients, mainly at the level of the superior and middle frontal gyri. Longitudinal studies in drug-naïve patients are needed to assess the role of these associations.

What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis?

2014 ◽  
Vol 45 (4) ◽  
pp. 817-828 ◽  
Author(s):  
P. G. P. Rosa ◽  
M. V. Zanetti ◽  
F. L. S. Duran ◽  
L. C. Santos ◽  
P. R. Menezes ◽  
...  
Keyword(s):  
Grey Matter ◽  
Superior Temporal Gyrus ◽  
Structural Mri ◽  
Population Based ◽  
First Episode ◽  
Schizophrenia Spectrum Disorders ◽  
Brain Abnormalities ◽  
Dorsolateral Prefrontal ◽  
The Right ◽  
First Episode Schizophrenia

Background.Magnetic resonance imaging (MRI) studies have shown that brain abnormalities in psychosis might be progressive during the first years of illness. We sought to determine whether first-episode psychosis (FEP) subjects show progressive regional grey matter (GM) changes compared with controls, and whether those changes are associated with diagnosis, illness course or antipsychotic (AP) use.Method.Thirty-two subjects with first-episode schizophrenia-spectrum disorders (FESZ), 24 patients with first-episode affective psychoses (FEAP) and 34 controls recruited using a population-based design underwent structural MRI scanning at baseline and at a 5-year follow-up. Regional GM volumes were assessed with voxel-based morphometry (VBM). Patients were treated at community settings, and about half of them remained mainly untreated.Results.No significant progressive changes in GM regional volumes were observed in either the FESZ or FEAP group overall. However, FESZ subjects with a non-remitting course showed GM decrements in the left superior temporal gyrus (STG) and insula relative to remitted FESZ subjects. Non-remitted FEAP subjects exhibited a GM decrease in the dorsolateral prefrontal cortex (DLPFC) bilaterally in comparison to remitted FEAP subjects. Among FESZ subjects, AP use was associated with regional GM decrements in the right insula and increments in the cerebellum.Conclusions.Our results suggest that the progression of brain abnormalities in FEP subjects is restricted to those with a poor outcome and differs between diagnosis subgroups. AP intake is associated with a different pattern of GM reductions over time.

scholarly journals Changes in Brain Structure, Function, and Network Properties in Patients With First-Episode Schizophrenia Treated With Antipsychotics

2021 ◽  
Vol 12 ◽  
Author(s):  
Ping Yin ◽  
Chao Zhao ◽  
Yang Li ◽  
Xiaoyi Liu ◽  
Lei Chen ◽  
...  
Keyword(s):  
Structure Function ◽  
Clinical Symptoms ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Precentral Gyrus ◽  
Inferior Parietal Lobule ◽  
Network Properties ◽  
Parietal Lobule ◽  
The Right ◽  
First Episode Schizophrenia

Purpose: Comprehensive and longitudinal brain analysis is of great significance for understanding the pathological changes of antipsychotic drug treatment in patients with schizophrenia. This study aimed to investigate the changes of structure, function, and network properties in patients with first-episode schizophrenia (FES) after antipsychotic therapy and their relationship with clinical symptoms.Materials and Methods: A total of 30 patients diagnosed with FES and 30 healthy subjects matched for sex and age were enrolled in our study. Patients at baseline were labeled as antipsychotic-naive first-episode schizophrenia (AN-FES), and patients after antipsychotic treatment were labeled as antipsychotic treatment first-episode schizophrenia (AT-FES). The severity of illness was measured by using the PANSS and CGI score. Structural and functional MRI data were also performed. Differences in GMV, ALFF, and ReHo between the FES group and healthy control group were tested using a voxel-wise two-sample t-test, and the comparison of AN-FES group and AT-FES group was evaluated by paired-sample t-test.Results: After the 1-year follow-up, the FES patients showed increased GMV in the right cerebellum, right inferior temporal gyrus, left middle frontal gyrus, parahippocampal gyrus, bilateral inferior parietal lobule, and reduced GMV in the left occipital lobe, gyrus rectus, right orbital frontal cortex. The patients also showed increased ALFF in the medial superior frontal gyrus and right precentral gyrus. For network properties, the patients showed reduced characteristic path length and increased global efficiency. The GMV of the right inferior parietal lobule was negatively correlated with the clinical symptoms.Conclusions: Our study showed that the antipsychotic treatment contributed to the structural alteration and functional improvement, and the GMV alteration may be associated with the improvement of clinical symptoms.

scholarly journals Psychosocial Intervention With or Without Antipsychotic Medication for First-Episode Psychosis: A Randomized Noninferiority Clinical Trial

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Shona M Francey ◽  
Brian O’Donoghue ◽  
Barnaby Nelson ◽  
Jessica Graham ◽  
Lara Baldwin ◽  
...  
Keyword(s):  
Early Intervention ◽  
Antipsychotic Medication ◽  
Psychosocial Intervention ◽  
First Episode Psychosis ◽  
Functional Improvement ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Free Treatment ◽  
Intervention Service ◽  
Episode Psychosis

Abstract This triple-blind (participants, clinicians, and researchers) randomized controlled noninferiority trial examined whether intensive psychosocial intervention (cognitive-behavioral case management, CBCM) for first-episode psychosis (FEP) in 15–25 year-olds managed in a specialized early intervention for psychosis service was noninferior to usual treatment of antipsychotic medication plus CBCM delivered during the first 6 months of treatment. To maximize safety, participants were required to have low levels of suicidality and aggression, a duration of untreated psychosis (DUP) of less than 6 months, and be living in stable accommodation with social support. The primary outcome was level of functioning as assessed by the Social and Occupational Functioning Scale (SOFAS) at 6 months. Ninety young people were randomized by computer, 46 to placebo, and 44 antipsychotic medication and 33% of those who commenced trial medication completed the entire 6-month trial period. On the SOFAS, both groups improved, and group differences were small and clinically trivial, indicating that treatment with placebo medication was no less effective than conventional antipsychotic treatment (mean difference = −0.2, 2-sided 95% confidence interval = −7.5 to 7.0, t = 0.060, P = .95). Within the context of a specialized early intervention service, and with a short DUP, the immediate introduction of antipsychotic medication may not be required for all cases of FEP in order to see functional improvement. However, this finding can only be generalized to a very small proportion of FEP cases at this stage, and a larger trial is required to clarify whether antipsychotic-free treatment can be recommended for specific subgroups of those with FEP. Trial Registration: ACTRN12607000608460 (www.anzctr.org.au).

scholarly journals Are we getting any better at staying better? The long view on relapse and recovery in first episode nonaffective psychosis and schizophrenia

2019 ◽  
Vol 9 ◽  
pp. 204512531987003 ◽  
Author(s):  
Mark Taylor ◽  
Sameer Jauhar
Keyword(s):  
Systematic Reviews ◽  
Antipsychotic Medication ◽  
Maintenance Treatment ◽  
Relevant Literature ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Long Term Outcomes ◽  
Medication Discontinuation ◽  
Recent Debate

Relapse in, and recovery from, schizophrenia has been acknowledged since the disease was first described. In this review the authors summarize the long-term (>100 years) data on relapse and recovery in schizophrenia by reviewing the extant older and modern relevant literature. The authors systematically question the utility of pharmacological and nonpharmacological interventions, with an emphasis on first episode nonaffective psychosis. The method used is a narrative review of earlier meta-analytic and systematic reviews. Antipsychotic medication discontinuation studies suggest a role for prophylactic maintenance treatment in the majority of people with schizophrenia, despite recent debate on this subject. The authors conclude that long-term outcomes, including relapse and recovery rates, have improved in the last 100 years, though prospectively identifying those people who do not require long-term antipsychotic treatment has not yet been possible. Data also suggests that interventions and outcomes during the first 5 years of the disease can influence the long-term schizophrenia trajectory.

scholarly journals The Role of Untreated Psychosis in Neurodegeneration: A Review of Hypothesized Mechanisms of Neurotoxicity in First-Episode Psychosis

2014 ◽  
Vol 59 (10) ◽  
pp. 513-517 ◽  
Author(s):  
Kelly K Anderson ◽  
Aristotle Voineskos ◽  
Benoit H Mulsant ◽  
Tony P George ◽  
Kwame J McKenzie
Keyword(s):  
Systematic Review ◽  
Structural Changes ◽  
First Episode Psychosis ◽  
Brain Morphology ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Persistent Activity ◽  
Duration Of Untreated Psychosis ◽  
Episode Psychosis

For over 20 years, studies have tried to measure the association between the duration of untreated psychosis (DUP) and changes in brain morphology. A hypothesis that untreated psychosis is neurotoxic has been postulated, but the mechanisms of that toxicity have not been described. We re-analyzed papers collected for a systematic review to extract data on the hypotheses that have been generated on the potential mechanisms by which DUP could impact brain morphology in first-episode psychosis. Dopaminergic hyperactivity, prolonged hypothalamic–pituitary–adrenal activation, and persistent activity of catecholamines have been hypothesized as mechanisms to explain these associations. However, the question remains as to whether the observed structural changes are permanent or may be reversed via antipsychotic treatment.

Dysfunction of a distributed neural circuitry in schizophrenia patients during a working-memory performance

2005 ◽  
Vol 35 (2) ◽  
pp. 187-196 ◽  
Author(s):  
A. MENDREK ◽  
K. A. KIEHL ◽  
A. M. SMITH ◽  
D. IRWIN ◽  
B. B. FORSTER ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Performance ◽  
Memory Task ◽  
Anterior Cingulate ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Compensatory Mechanism ◽  
Control Subjects ◽  
Left Dlpfc ◽  
The Right

Background. In a recent longitudinal study of first-episode schizophrenia patients, we found that while dysfunction of the right dorsolateral prefrontal cortex (DLPFC), right thalamus, left cerebellum and cingulate gyrus normalized with antipsychotic treatment and significant reduction in symptomatology, the left DLPFC, left thalamus, and right cerebellum remained disturbed. In the present study we investigated whether these abnormalities are also present in clinically stable, relatively well-functioning schizophrenia patients in comparison to control subjects during performance of the N-back working-memory task.Method. Twelve schizophrenia and 12 control subjects completed the study. The functional images collected during scanning were analyzed using a random-effects model in a restricted set of six regions of interest (ROIs). In addition, the exploratory search in the entire brain volume was performed.Results. The ROI analyses revealed relative underactivation in the region of the left DLPFC and the right cerebellum, as well as overactivation in the left cerebellum. The exploratory whole-brain search exposed additional overactivation in the medial frontal, anterior cingulate, and left parietal cortices.Conclusions. The present study provides evidence of significant underactivations in stable schizophrenia patients in regions that we have previously observed to be dysfunctional in acutely psychotic and partially remitted patients, together with extensive overactivations in several regions that potentially reflect some compensatory mechanism or increased effort on the working-memory task.

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