A unifying hypothesis of schizophrenia: Abnormal immune system development may help explain roles of prenatal hazards, post-pubertal onset, stress, genes, climate, infections, and brain dysfunction

Kinney, Dennis K.; Hintz, Kathryn; Shearer, Erika M.; Daniel, Hannelore; Riffin, Catherine; Whitley, Katherine; Butler, Robert W.

doi:10.1016/j.mehy.2009.09.040

Cited by 91 publications

(66 citation statements)

References 127 publications

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“…61,63,94 ) together with development of disease-modifying therapies 95 and special regards to sex-differences 96 have been repeatedly suggested. Further, the current scientific literature has suggested the validation of existing animal models and the development of newer models to better reflect psychiatric diseases 97,98 . Furthermore, the possible gender differences in clinical findings (suggesting women with schizophrenia/de-pression are more vulnerable to MetS development) are not yet assessed in animal studies.…”

Section: Resultsmentioning

confidence: 99%

The common pathophysiology underlying the metabolic syndrome, schizophrenia and depression. A review

Kučerová

Babinská

Horská

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. There is a growing interest in metabolic alterations in patients with psychiatric disorders due to their increased risk for metabolic syndrome (MetS) development. Inflammation is known to underlie the pathophysiology of schizophrenia and depression as well as MetS. Vulnerability factors for schizophrenia/depression and MetS hence appear to be shared. Methods and Results. Based on a Web of Science search, this review examines current evidence for MetS pathophysiology involving dysregulation of adipose tissue signaling -adipokines and pro-inflammatory cytokine, both also known to be aberrant in schizophrenia/depression. Further, gender differences in the incidence and course of schizophrenia/ depression were reported. The disturbances linked to the MetS are also described. Therefore, this review further maps the gender differences in the psychiatric-metabolic comorbidities. Conclusion. There is evidence supporting a pathological predisposition to MetS in both schizophrenia and depression in both humans and animal models. This predisposition is dramatically enhanced by antipsychotic medication. Further, there are gender differences from clinical findings suggesting women with schizophrenia/depression are more vulnerable to MetS development. This has not yet been assessed in animal studies. We suggest further validation of existing schizophrenia and depression animal models for the assessment of metabolic disturbances to provide tools for developing new antipsychotics and antidepressants with "metabolically inert" profile or improving the metabolic status in schizophrenic/depressed patients.

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Section: Resultsmentioning

confidence: 99%

The common pathophysiology underlying the metabolic syndrome, schizophrenia and depression. A review

Kučerová

Babinská

Horská

et al. 2015

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…Reference [25] found that elevated stress was a significant predictor of high IL-6 to IL-10 ratios in the 1 st trimester and elevated C Reactive Protein, which is a marker of systemic inflammation, in the 2 nd trimester. Individuals exposed to severe maternal stress prenatally often have robust cytokine and inflammatory responses as adults, resembling those of chronically stressed individuals even if the individual is not under stress at the time [3].…”

Section: The Stress Responsementioning

confidence: 99%

“…Injection of pregnant monkeys with adrenalcorticotropic hormone can alter the physiology and immune system of offspring. Also, monkeys exposed to synthetic corticosteroids in utero had altered thymus structure, indicating that prenatal stress altered the course of immune system development [3]. Therefore, stress can bolster the effects of early cytokine exposure.…”

Section: The Stress Responsementioning

confidence: 99%

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The cytokine hypothesis: A neurodevelopmental explanation for the emergence of schizophrenia later in life

Howard¹

2013

ABB

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There is increasing evidence for the cytokine hypothesis, which states that exposure to elevated cytokines in utero due to maternal immune activation is a major risk factor for the development of schizophrenia later in life. This is supported by numerous epidemicologic studies that connect multiple infections with schizophrenia emergence. Furthermore, cytokines are critically involved in early neurodevelopment and deviations from the norm can result in abnormal neuroanatomy and brain chemistry. Animal models of schizophrenia also support the critical role of developmental neuroinflammation in predisposing the brain to anatomical and behavioral abnormalities. Although there is strong evidence for the critical role of cytokines, they most likely work with other contributing risk factors such as genetic predisposition. New evidence indicates that cytokine exposure in utero may prime the brain and that a second stressor during adolescence, referred to as a second hit, may activate existing developmental vulnerabilities resulting in the emergence of clinical schizophrenia. Further knowledge of these pathogenic processes and risk factors could be very instrumental in reducing risk and slowing emergence of schizophrenia.

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“…It is associated with raised neonatal mortality and morbidity and with an increased incidence of diabetes, hypertension, ischemic heart disease, and metabolic syndrome in adulthood (2). Fetal inflammation is associated with increased schizophrenia, autism, cognitive impairment, and neurologic diseases in later life (5,6).…”

Section: To the Editormentioning

confidence: 99%

The Potential for Low-Dose Functional Studies in Maternal–Fetal Medicine Using PET/MR Imaging

Jones¹,

Budinger²

2013

J Nucl Med

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A unifying hypothesis of schizophrenia: Abnormal immune system development may help explain roles of prenatal hazards, post-pubertal onset, stress, genes, climate, infections, and brain dysfunction

Cited by 91 publications

References 127 publications

The common pathophysiology underlying the metabolic syndrome, schizophrenia and depression. A review

The common pathophysiology underlying the metabolic syndrome, schizophrenia and depression. A review

The cytokine hypothesis: A neurodevelopmental explanation for the emergence of schizophrenia later in life

The Potential for Low-Dose Functional Studies in Maternal–Fetal Medicine Using PET/MR Imaging

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