Differential clinical, structural and P300 parameters in schizophrenia patients resistant to conventional neuroleptics

Molina, Vicente; Reig, Santiago; Sanz, Javier; Palomo, Tomás; Benito, Carlos; Sarramea, Fernando; Pascau, Javier; Sánchez, J.; Martı́n-Loeches, Manuel; Muñoz, Francisco; Desco, Manuel

doi:10.1016/j.pnpbp.2007.08.017

Cited by 36 publications

(44 citation statements)

References 59 publications

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“…The effect of different treatment should be taken into account as in our case the two SC subgroups were under different therapeutic regimens, which may partly explain discrepancies with previous results of ROI-based analysis of baseline studies in patients treated with haloperidol only, which highlighted differences in occipital GM, beside frontal cortex [20], while in our case the presence of a substantial proportion of NonResp-SC undergoing clozapine treatment may have hindered parietal and occipital differences with the Resp-SC subgroup.…”

Section: Discussionmentioning

confidence: 74%

“…More recently a study, directly assessing structural parameters in patients resistant to conventional antipsychotics using Region of Interest (ROI) analysis of segmented MRI [20], has shown that NonResp-SC patients have significantly lower gray matter (GM) volumes in the frontal and occipital regions and significantly more white matter (WM) in the frontal, parietal, and occipital regions as compared to the controls, while these alterations are less prominent in Resp-SC patients, although in that case the direct comparison between NonResp-SC and Resp-SC patients failed to reach statistical significance.…”

Section: Discussionmentioning

confidence: 99%

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

Quarantelli

Palladino

Prinster

et al. 2014

BioMed Research International

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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.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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

Quarantelli

Palladino

Prinster

et al. 2014

BioMed Research International

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“…All the treatment-resistant patients were prescribed clozapine, while the majority of treatment-responsive patients were prescribed olanzapine or risperidone. In Molina et al, 49 Spanish patients (30 resistant, 19 responsive) were studied [29]; no patients had taken clozapine prior to baseline assessments, and all patients were trialled on haloperidol to confirm resistance or responsiveness. They report that discriminant analysis demonstrated hypertrophy in occipital white matter to be the best predictor of treatment-resistance, and that significant decreases in frontal and occipital grey matter of treatment-resistant patients compared to healthy volunteers were not evident in treatment-responsive patients.…”

Section: Resultsmentioning

confidence: 99%

“…In the same study, Molina et al also investigated P300 parameters - the late component of the event-related potential - with EEG but found no differences between responsive and resistant patients [29]. …”

Section: Resultsmentioning

confidence: 99%

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

et al. 2017

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BackgroundSchizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes.MethodA systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics).ResultsNineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons.ConclusionsTentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-016-1177-y) contains supplementary material, which is available to authorized users.

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“…Increasing task difficulty and using multi-modal techniques (Bender et al, 2007;Molina et al, 2007;Price et al, 2006;Sponheim et al, 2006) should increase our ability to detect subtle cognitive changes in the prodrome of psychosis.…”

Section: Discussionmentioning

confidence: 99%

Abnormal P300 in people with high risk of developing psychosis

et al. 2008

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Background: Individuals with an "At Risk Mental State" (or "prodromal" symptoms) have a 20-40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable.Method: 35 cases meeting PACE criteria for the At Risk Mental State (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression.Results: The P300 amplitude was significantly reduced in the ARMS group [8.6 ±6.4 microvolt] compared to controls [12.7 ±5.8 microvolt] (p<0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis. Please find attached a fully revised manuscript titled "Abnormal P300 in people with high risk of developing psychosis". We also enclose a letter with the comments from the reviewers and our detailed answers on how we have done all the changes requested. (t-test; p=0.93). Those making a transition to psychosis were marginally more educated but this was only at trend level with a 3 year average difference in the age at which they completed their studies (t-test; p=0.07).Similarly, logistic regression analyses showed that compared to those who remained at risk, the seven cases who made a transition to psychosis had no significant differences in P300 amplitude/latency or N100 amplitude/latency (p values ranging from 0.30 to 0.63 for all four analyses). We have reported these comparisons very concisely and cautiously because referee #2 said that these analyses with only 7 individual making a transition were preliminary and power is limited. Please see results section paragraph 2. RESPONSE TO REVIEWER #2:Thank you for your suggestions, which have improved the paper. Below are your comments in blue-italics and how we have amended the manuscript accordingly in black with cross-references to the revised manuscript.This paper addresses an important and timely topic, namely, whether auditory P300 is reduced in subjects with at risk mental states and whether the P300 predicts subsequent conversion to psychosis. The study finds a significant deficit in P300 in ARMS subjects, relative to controls, replicating a previously a previously published report. The study had the potential to incrementally * 2. Response to Reviews 2 contribute to the literature by examining the utility of baseline P300 deficits as a predictor of subsequent conversion to psychosis; however, the negative finding coupled with the lack of power for this analysis (only 7 converters) make this aspect of the study inconclusive. More detailed comments are provided below:We have added a paragraph in the discussion to acknowledge the limitation of our small group of converters and how we have low statistical power to compa...

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Differential clinical, structural and P300 parameters in schizophrenia patients resistant to conventional neuroleptics

Cited by 36 publications

References 59 publications

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

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

Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review

Abnormal P300 in people with high risk of developing psychosis

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