Treatment resistant schizophrenia and neurological soft signs may converge on the same pathology: Evidence from explanatory analysis on clinical, psychopathological, and cognitive variables

Bartolomeis, Andrea de; Prinzivalli, Emiliano; Callovini, Gemma; D’Ambrosio, Luigi; Altavilla, Benedetta; Avagliano, Camilla; Iasevoli, Felice

doi:10.1016/j.pnpbp.2017.09.002

Cited by 27 publications

(23 citation statements)

References 76 publications

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“…In our study, both male and female patients with TRS had significantly higher PANSS total, positive, negative, and general psychopathology scores, as well as higher chlorpromazine equivalent doses in comparison to male and female patients in non-TRS group. This is in agreement with previous studies reporting that patients with TRS had more severe symptomatology as measured by PANSS ( Moretti et al, 2018 ) and received higher total antipsychotic dose presented as chlorpromazine equivalents, compared to patients with non-TRS ( Hotta et al, 2011 ; de Bartolomeis et al, 2018 ; Moretti et al, 2018 ). In the present study, the concentration of antipsychotics in plasma was not measured.…”

Section: Discussionsupporting

confidence: 93%

Haplotypic and Genotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia

et al. 2018

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Treatment-resistant schizophrenia (TRS) continues to be a challenge. It was related to different factors, including alterations in the activity of brain dopaminergic system, which could be influenced by the dopamine-degrading enzyme, catechol-O-methyltransferase (COMT). Variants of the COMT gene have been extensively studied as risk factors for schizophrenia; however, their association with TRS has been poorly investigated. The aim of the present study was to determine the haplotypic and genotypic association of COMT rs4680 and rs4818 polymorphisms with the presence of TRS. Overall, 931 Caucasian patients diagnosed with schizophrenia (386 females and 545 males) were included, while 270 participants met the criteria for TRS. In males, no significant haplotypic and genotypic associations between COMT rs4680 and rs4818 polymorphisms and TRS were detected. However, genotypic analyses demonstrated higher frequency of COMT rs4680 AA genotype carriers compared to G-allele carriers (p = 0.033) and higher frequency of COMT rs4818 CC genotype carriers than G-allele carriers (p = 0.014) in females with TRS. Haplotype analyses confirmed that the presence of the G allele in females was associated with lower risk of TRS. In women with TRS, the high activity G-G/G-G haplotype was rare, while carriers of other haplotypes were overrepresented (p = 0.009). Such associations of COMT rs4680 and rs4818 high-activity (G variants), as well as G-G/G-G haplotype, with the lower risk of TRS in females, but not in males, suggest significant, but sex-specific influence of COMT variants on the development of treatment-resistance in patients with schizophrenia. However, due to relatively low number of females, those findings require replication in a larger sample.

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Section: Discussionsupporting

confidence: 93%

Haplotypic and Genotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia

et al. 2018

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“…The neurodevelopmental theory of schizophrenia proposes that disrupted normal development, in utero or early infancy, leads to deficits in psychophysiological and neurological functioning in childhood or early adolescence, and eventually to prodromal or diagnostic symptoms of schizophrenia (Jablensky et al, 2017;Murray et al, 2017). Previous research has linked characteristics of abnormal development with TRS; higher rates of minor physical anomalies (Lin et al, 2015), more neurological soft signs (de Bartolomeis et al, 2018), poor verbal intelligence and fluency (Kravariti et al, 2018), and poor verbal memory (Joober et al, 2002;de Bartolomeis et al, 2013). None of the studies in this review included variables measuring physiology during development or cognition at the first episode.…”

Section: Discussionmentioning

confidence: 99%

Predictors of treatment resistant schizophrenia: a systematic review of prospective observational studies

et al. 2019

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Treatment-resistant schizophrenia, affecting approximately 20–30% of patients with schizophrenia, has a high burden both for patients and healthcare services. There is a need to identify treatment resistance earlier in the course of the illness, in order that effective treatment, such as clozapine, can be offered promptly. We conducted a systemic literature review of prospective longitudinal studies with the aim of identifying predictors of treatment-resistant schizophrenia from the first episode. From the 545 results screened, we identified 12 published studies where data at the first episode was used to predict treatment resistance. Younger age of onset was the most consistent predictor of treatment resistance. We discuss the gaps in the literature and how future prediction models can identify predictors of treatment response more robustly.

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“…Approximately 30% of schizophrenia patients do not respond or respond poorly to antipsychotics treatment ( 36 ), treatment resistant schizophrenia is defined as lack of response to at least two different antipsychotics at 600 mg chlorpromazine equivalent and for the duration of treatment of at least 6 weeks. These patients show reduction in milestone acquisition ( 37 ), more cognitive impairment ( 38 ), and functioning deficits as well as higher incidence of neurological soft signs ( 39 ) compared to patients who respond to antipsychotic treatment.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Management of Patients With Dual Disorder (Psychosis) in Italy: A Survey of Psychiatrists and Other Physicians Focusing on Clinical Practice

Clerici

Bartolomeis

Filippis³

et al. 2018

Front. Psychiatry

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Patients with severe psychotic disorders such as schizophrenia, schizoaffective, and bipolar disorders frequently suffer from concomitant substance use disorders (SUDs)–Dual Disorder (DD) patients. In order to better understand current practices for management of patients with psychotic episodes and concomitant SUD in Italy, we carried out a survey of psychiatrists on current routine practice among prescribers. These aspects can help to identify at-risk patients, improve current prescribing practices, and favor early intervention. An ad hoc survey of 17 questions was administered to psychiatrists via electronic polling and on-line distribution; 448 completed questionnaires were collected. Comorbid substance abuse was most frequently diagnosed within the context of anxiety disorder (46%), followed by bipolar disorder (25%), and schizophrenia/schizoaffective disorder (12%). The vast majority of respondents felt that patient management was becoming more complex due to substance abuse. The areas reported to be most affected in patients with SUD were functioning, interpersonal relations, and impulsivity, while sensory perception disorders, ideation, agitation, and impulsivity were the most frequently reported symptoms. In the acute setting, haloperidol was used as the first-line agent of choice followed by aripiprazole and olanzapine. In the maintenance phase, aripiprazole was the dominantly used first-line agent, followed by olanzapine. Almost half of respondents used long-acting agents, while about one-third did not. Among those prescribing long-acting agents, efficacy, control of impulsivity, and control of specific symptoms were cited as motivators, while in the maintenance phase, better adherence, and tolerability were mainly cited. From the responses to the present survey, it is clear that the respondents are aware of the problem of SUD in psychotic patients. While treatment be optimized in terms of the choice and formulation of antipsychotics, greater emphasis should be placed on efficacy, tolerability, and the negative metabolic consequences of some antipsychotics. When considering the ideal antipsychotic, long-acting agents were considered to be superior in reducing relapse, even if current treatment guidelines often give preference to oral formulations.

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Treatment resistant schizophrenia and neurological soft signs may converge on the same pathology: Evidence from explanatory analysis on clinical, psychopathological, and cognitive variables

Cited by 27 publications

References 76 publications

Haplotypic and Genotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia

Haplotypic and Genotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Polymorphisms and Treatment Resistance in Schizophrenia

Predictors of treatment resistant schizophrenia: a systematic review of prospective observational studies

Patterns of Management of Patients With Dual Disorder (Psychosis) in Italy: A Survey of Psychiatrists and Other Physicians Focusing on Clinical Practice

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