Obstetric Complications and Brain Imaging in Schizophrenia: A Systematic Review

Costas-Carrera, Ana; García-Rizo, Clemente; Bitanihirwe, Byron K.Y.; Penadés, Rafael

doi:10.1016/j.bpsc.2020.07.018

Cited by 8 publications

(9 citation statements)

References 78 publications

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“…As expected, abnormalities during gestation will promote two main effects: on one side, metabolic changes intra uterus will promote a risk of morbidity and early mortality (over time and in combination with resource-plentiful environment, antipsychotic side-effects, and unhealthy lifestyle), and on the other side, they will interfere in the normal neuronal maturation and migration, increasing the risk of developing psychosis ( 12 ). Indeed, previous obstetric complications have been described as affecting not only metabolism but also brain structure ( 43 ), cognition ( 44 ), and psychopathology ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

The effect of early life events on glucose levels in first-episode psychosis

García-Rizo

Cabrera²,

Bioque³

et al. 2022

Front. Endocrinol.

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First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients’ increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients.

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Section: Discussionmentioning

confidence: 99%

The effect of early life events on glucose levels in first-episode psychosis

García-Rizo

Cabrera²,

Bioque³

et al. 2022

Front. Endocrinol.

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“…In SZ patients, prenatal hypoxia correlated also with ventricular enlargement (Cannon et al 2002). Obstetric complications induce brain abnormalities ranging from decreased grey matter volume and increased ventricles up to reduced hippocampus volume (Costas-Carrera et al 2020). A reduced hippocampus volume has been reported in SZ patients and controls with obstetric complications (Haukvik et al 2010).…”

Section: Impact Of Neurodevelopmental Disturbances On Brain Connectiv...mentioning

confidence: 95%

Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors

2022

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Since more than 3 decades, schizophrenia (SZ) has been regarded as a neurodevelopmental disorder. The neurodevelopmental hypothesis proposes that SZ is associated with genetic and environmental risk factors, which influence connectivity in neuronal circuits during vulnerable developmental periods. We carried out a non-systematic review of genetic/environmental factors that increase SZ risk in light of its neurodevelopmental hypothesis. We also reviewed the potential impact of SZ-related environmental and genetic risk factors on grey and white matter pathology and brain function based on magnetic resonance imaging and post-mortem studies. Finally, we reviewed studies that have used patient-derived neuronal models to gain knowledge of the role of genetic and environmental factors in early developmental stages. Taken together, these studies indicate that a variety of environmental factors may interact with genetic risk factors during the pre- or postnatal period and/or during adolescence to induce symptoms of SZ in early adulthood. These risk factors induce disturbances of macro- and microconnectivity in brain regions involving the prefrontal, temporal and parietal cortices and the hippocampus. On the molecular and cellular level, a disturbed synaptic plasticity, loss of oligodendrocytes and impaired myelination have been shown in brain regions of SZ patients. These cellular/histological phenotypes are related to environmental risk factors such as obstetric complications, maternal infections and childhood trauma and genetic risk factors identified in recent genome-wide association studies. SZ-related genetic risk may contribute to active processes interfering with synaptic plasticity in the adult brain. Advances in stem cell technologies are providing promising mechanistic insights into how SZ risk factors impact the developing brain. Further research is needed to understand the timing of the different complex biological processes taking place as a result of the interplay between genetic and environmental factors.

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“… 4 , 32 – 34 Obstetric complications, lower premorbid social adjustment, a history of suicide attempts, extended hospitalization, impaired illness insight, and comorbid personality disorders have also been associated with an increased risk for TRS. 32 , 34 – 36 …”

Section: The Neurobiology Of Treatment Resistancementioning

confidence: 99%

“…These include male sex, living in a less urban area, younger age, family history of psychosis, a high load of schizophrenia risk genes, longer duration of untreated psychosis, substance abuse, and a higher number of relapses due to non-adherence 4,[32][33][34] . Obstetric complications, lower premorbid social adjustment, a history of suicide attempts, extended hospitalization, impaired illness insight and comorbid personality disorders have also been associated with an increased risk for TRS 32,[34][35][36] .…”

Section: The Neurobiology Of Treatment Resistancementioning

confidence: 99%

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

Qubad

Bittner

2023

Therapeutic Advances in Psychopharmacology

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Despite its enduring relevance as the single most effective and important evidence-based treatment for schizophrenia, underutilization of clozapine remains considerable. To a substantial degree, this is attributable to a reluctance of psychiatrists to offer clozapine due to its relatively large side-effect burden and the complexity of its use. This underscores the necessity for continued education regarding both the vital nature and the intricacies of clozapine treatment. This narrative review summarizes all clinically relevant areas of evidence, which support clozapine’s wide-ranging superior efficacy – for treatment-resistant schizophrenia (TRS) and beyond – and make its safe use eminently feasible. Converging evidence indicates that TRS constitutes a distinct albeit heterogeneous subgroup of schizophrenias primarily responsive to clozapine. Most importantly, the predominantly early onset of treatment resistance and the considerable decline in response rates associated with its delayed initiation make clozapine an essential treatment option throughout the course of illness, beginning with the first psychotic episode. To maximize patients’ benefits, systematic early recognition efforts based on stringent use of TRS criteria, a timely offer of clozapine, thorough side-effect screening and management as well as consistent use of therapeutic drug monitoring and established augmentation strategies for suboptimal responders are crucial. To minimize permanent all-cause discontinuation, re-challenges after neutropenia or myocarditis should be considered. Owing to clozapine’s unique efficacy, comorbid conditions including substance use and most somatic disorders should not dissuade but rather encourage clinicians to consider clozapine. Moreover, treatment decisions need to be informed by the late onset of clozapine’s full effects, which for reduced suicidality and mortality rates may not even be readily apparent. Overall, the singular extent of its efficacy combined with the high level of patient satisfaction continues to distinguish clozapine from all other available antipsychotics.

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Obstetric Complications and Brain Imaging in Schizophrenia: A Systematic Review

Cited by 8 publications

References 78 publications

The effect of early life events on glucose levels in first-episode psychosis

The effect of early life events on glucose levels in first-episode psychosis

Neurodevelopmental disturbances in schizophrenia: evidence from genetic and environmental factors

Second to none: rationale, timing, and clinical management of clozapine use in schizophrenia

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