The effect of lifetime adversities on resistance to antipsychotic treatment in schizophrenia patients

Hassan, Ahmed; Luca, Vincenzo De

doi:10.1016/j.schres.2014.10.048

Cited by 103 publications

(63 citation statements)

References 34 publications

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“…Future longitudinal work geared toward establishing whether the detected features are a primary component of a treatmentresistant illness subtype or a secondary feature of long-term illness or ineffective pharmacologic treatment is warranted. The current study provides evidence of physiologic substrates related to treatment resistance in schizophrenia; however, although it is likely that both genetic (Frank et al, 2015) and environmental (Hassan and De Luca, 2015) factors underlie treatment resistance and its associated mechanisms, the causative factors remain inadequately explained. Characterizing the treatment-resistance phenotype in terms of clinical and cognitive features has the potential to improve our understanding of the key etiological determinants (Gonzalez-Rodriguez et al, 2014).…”

Section: Discussionmentioning

confidence: 94%

Dysfunctional Striatal Systems in Treatment-Resistant Schizophrenia

White

Wigton

Joyce³

et al. 2015

Neuropsychopharmacol

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The prevalence of treatment-resistant schizophrenia points to a discrete illness subtype, but to date its pathophysiologic characteristics are undetermined. Information transfer from ventral to dorsal striatum depends on both striato-cortico-striatal and striato-nigro-striatal subcircuits, yet although the functional integrity of the former appears to track improvement of positive symptoms of schizophrenia, the latter have received little experimental attention in relation to the illness. Here, in a sample of individuals with schizophrenia stratified by treatment resistance and matched controls, functional pathways involving four foci along the striatal axis were assessed to test the hypothesis that treatment-resistant and non-refractory patients would exhibit contrasting patterns of resting striatal connectivity. Compared with non-refractory patients, treatment-resistant individuals exhibited reduced connectivity between ventral striatum and substantia nigra. Furthermore, disturbance to corticostriatal connectivity was more pervasive in treatment-resistant individuals. The occurrence of a more distributed pattern of abnormality may contribute to the failure of medication to treat symptoms in these individuals. This work strongly supports the notion of pathophysiologic divergence between individuals with schizophrenia classified by treatmentresistance criteria.

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Section: Discussionmentioning

confidence: 94%

Dysfunctional Striatal Systems in Treatment-Resistant Schizophrenia

White

Wigton

Joyce³

et al. 2015

Neuropsychopharmacol

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“…TRS is commonly defined as insufficient treatment response despite at least two different antipsychotic treatment courses of adequate dose and duration. [1][2][3] It has been shown, that individuals with a family history of psychosis are more likely to poorly respond to antipsychotic drugs, [4][5][6] suggesting a genetic influence in the development of TRS. This is supported by previous research indicating that variants in the gene coding for the Dopamine D2 receptor (DRD2) may be predictive of response to antipsychotic drugs in first-episode schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Polygenic Risk Score for Schizophrenia and Treatment-Resistant Schizophrenia

Wimberley

Gasse

Meier

et al. 2017

Schizophrenia Bulletin

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Treatment-resistant schizophrenia (TRS) affects around one third of individuals with schizophrenia.Although a number of socio-demographic and clinical predictors of TRS have been identified, data on the genetic risk of TRS are sparse. We aimed to investigate the association between the polygenic risk score for schizophrenia and treatment resistance in patients with schizophrenia. We conducted a nationwide, population-based follow-up study among all Danish individuals born after 1981 and with an incident diagnosis of schizophrenia between 1999 and 2007. Based on genome-wide data polygenic risk scores for schizophrenia were calculated in 862 individuals with schizophrenia. TRS was defined as either clozapine initiation or at least two periods of different antipsychotic monotherapies and still being hospitalized. We estimated hazard rate ratios (HRs) for TRS in relation to the polygenic risk score while adjusting for population stratification, age, sex, geographical area at birth, clinical treatment setting, psychiatric comorbidity, and calendar year. Among the 862 individuals with schizophrenia, 181 (21.0%) met criteria for TRS during 4,674 person-years of follow-up. We found no significant association between the polygenic risk score and TRS, adjusted HR = 1.13 (95% CI: 0.95-1.35). Based on these results, the use of the polygenic risk score for schizophrenia to identify individuals with TRS is at present inadequate to be of clinical utility at the individual patient level. Future research should include larger genetic samples in combination with nongenetic markers. Moreover, a TRS-specific developed polygenic risk score would be of great interest towards early prediction of TRS.

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“…These events were independent from the behaviour of the patients, thereby minimising the potential effect of illness processes (Docherty, St-Hilaire, Aakre, & Seghers, 2009). Tentative evidence also suggests that cumulative life events are associated with resistance to antipsychotic medication in schizophrenia patients (Hassan & De Luca, 2015). Also, suicide in schizophrenia patients seems to be preceded by stressful life events (Tousignant et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

The effect of childhood trauma and Five-Factor Model personality traits on exposure to adult life events in patients with psychotic disorders

Pos¹,

Boyette

Meijer³

et al. 2016

Cognitive Neuropsychiatry

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Introduction: Recent life events are associated with transition to and outcome in psychosis. Childhood trauma and personality characteristics play a role in proneness to adult life events. However, little is known about the relative contribution and interrelatedness of these characteristics in psychotic disorders. Therefore, we investigated whether Five-Factor Model (FFM) personality traits and childhood trauma (abuse and neglect) predict adult life events, and whether the effect of childhood trauma on life events is mediated by personality traits. Method: One hundred and sixty-three patients with psychotic disorders were assessed at baseline on history of childhood maltreatment and FFM personality traits, and on recent life events at 3-year follow-up. Results: Childhood abuse is associated with negative life events, and part of the effect of childhood abuse on negative life events is mediated by openness to experience. Openness to experience and extraversion are associated with more positive and negative life events. Childhood neglect and lower extraversion are related to experiencing less positive events. Conclusion: The association between childhood trauma and recent life events is partly mediated by personality. Future research could focus on mechanisms leading to positive life events, as positive life events may buffer against development of mental health problems.

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The effect of lifetime adversities on resistance to antipsychotic treatment in schizophrenia patients

Cited by 103 publications

References 34 publications

Dysfunctional Striatal Systems in Treatment-Resistant Schizophrenia

Dysfunctional Striatal Systems in Treatment-Resistant Schizophrenia

Polygenic Risk Score for Schizophrenia and Treatment-Resistant Schizophrenia

The effect of childhood trauma and Five-Factor Model personality traits on exposure to adult life events in patients with psychotic disorders

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