The Neurodevelopmental Hypothesis of Schizophrenia

Piper, Michael; Beneyto, Manuel Gómez; Burne, Thomas H. J.; Eyles, Darryl W.; Lewis, David A.; McGrath, John J.

doi:10.1016/j.psc.2012.06.002

Cited by 77 publications

(24 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pathogeneses of schizophrenia and other complex neuropsychiatric disorders are likely rooted in aberrant neurodevelopment (Lewis and Levitt, 2002; Piper et al, 2012; Rapoport et al, 2012). Environmental disturbances during pregnancy may interact adversely in genetically predisposed offspring to compromise neuronal circuitry.…”

Section: Introductionmentioning

confidence: 99%

Maternal complement C1q and increased odds for psychosis in adult offspring

Severance

Gressitt

Buka

et al. 2014

Schizophrenia Research

View full text Add to dashboard Cite

The presence of maternal antibodies to food and infectious antigens may confer an increased risk of developing schizophrenia and psychosis in adult offspring. Complement factor C1q is an immune molecule with multiple functions including clearance of antigen-antibody complexes from circulation and mediation of synaptic pruning during fetal brain development. To determine if maternal C1q was associated with offspring schizophrenia and psychosis, we evaluated 55 matched case-control maternal serum pairs from the National Collaborative Perinatal Project. Sample pairs were composed of mothers whose offspring developed psychoses as adults and those whose offspring were free from psychiatric disease. Matching criteria for offspring included birth date, delivery hospital, race and gender, with further matching based on mother’s age. IgG markers of C1q, bovine milk casein, egg ovalbumin and wheat gluten were measured with enzyme-linked immunosorbent assays. C1q levels were compared to food antigen IgG and to previously generated data for C-reactive protein, adenovirus, herpes simplex viruses, influenza viruses, measles virus and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p≤0.008–0.05). In case mothers only, C1q was significantly correlated with antibodies to both food and infectious antigens: gluten (R2=0.26, p≤0.004), herpes simplex virus type 2 (R2=0.21, p≤0.02), adenovirus (R2=0.25, p≤0.006). In conclusion, exposure to maternal C1q activity during pregnancy may be a risk factor for the development of schizophrenia and psychosis in offspring. Prenatal measurement of maternal C1q may be an important and convergent screening tool to identify potentially deleterious immune activation from multiple sources.

show abstract

Section: Introductionmentioning

confidence: 99%

Maternal complement C1q and increased odds for psychosis in adult offspring

Severance

Gressitt

Buka

et al. 2014

Schizophrenia Research

View full text Add to dashboard Cite

show abstract

“…One of the most explored aspects on the environment-gene interaction prompting schizophrenic phenotype is the impact of harsh early life conditions, leading to the neurodevelopmental hypothesis of schizophrenia (Fatemi and Folsom, 2009; Piper et al, 2012), which postulates that neurochemical disturbances induced by adverse early life events could permanently affect brain function, producing abnormalities that would ultimately underlie the emergence of the disorder. The early stages of life are characterized by an intense neural development, in which there is a dynamic process of synaptic shaping and pruning, making this period highly vulnerable to damaging disturbances (Martínez-Téllez et al, 2009; Stolp et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Neonatal stress-induced affective changes in adolescent Wistar rats: early signs of schizophrenia-like behavior

Girardi

Zanta

Suchecki

2014

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Psychiatric disorders are multifactorial diseases with etiology that may involve genetic factors, early life environment and stressful life events. The neurodevelopmental hypothesis of schizophrenia is based on a wealth of data on increased vulnerability in individuals exposed to insults during the perinatal period. Maternal deprivation (MD) disinhibits the adrenocortical response to stress in neonatal rats and has been used as an animal model of schizophrenia. To test if long-term affective consequences of early life stress were influenced by maternal presence, we submitted 10-day old rats, either deprived (for 22 h) or not from their dams, to a stress challenge (i.p. saline injection). Corticosterone plasma levels were measured 2 h after the challenge, whereas another subgroup was assessed for behavior in the open field, elevated plus maze (EPM), social investigation and the negative contrast sucrose consumption test in adolescence (postnatal day 45). Maternally deprived rats exhibited increased plasma corticosterone (CORT) levels which were higher in maternally deprived and stress challenged pups. Social investigation was impaired in maternally deprived rats only, while saline injection, independently of MD, was associated with increased anxiety-like behavior in the EPM and an impaired intake decrement in the negative sucrose contrast. In the open field, center exploration was reduced in all maternally-deprived adolescents and in control rats challenged with saline injection. The most striking finding was that exposure to a stressful stimulus per se, regardless of MD, was linked to differential emotional consequences. We therefore propose that besides being a well-known and validated model of schizophrenia in adult rats, the MD paradigm could be extended to model early signs of psychiatric dysfunction, and would particularly be a useful tool to detect early signs that resemble schizophrenia.

show abstract

“…Many SCZ putative risk genes are expressed prenatally or early in pluripotent stem cell (PSC) differentiation [26–28], highlighting the importance of studying developmental process to clarify the etiology of SCZ. Many genetic as well as environmental models of SCZ show more pronounced SCZ-like behavioral and morphological changes with perturbations during early development, indicating the significance of developmental disturbance in generating SCZ-like abnormalities [29–32]. However, the ability to study these critical pathologic events in the developing human nervous system once seemed unimaginable since after symptom onset in young adulthood, it is not possible to go back in time to study what happened during fetal brain development (Fig.…”

Section: Developmental Model For Schizophreniamentioning

confidence: 99%

“…Srikanth et al [32] reported that DISC1 NPCs show an abnormal forebrain specification and high levels of Wnt signaling accompanied by increased neural proliferation, which could be reversed by early inhibition of Wnt. Wen et al [41] examined the mature neuronal phenotype and observed a synaptic release deficit using 90% homogeneous glutamatergic neuronal population, which was reversed by isogenic correction of DISC1 mutation.…”

Section: Recent Ipsc-based Cellular Models Of Sczmentioning

confidence: 99%

Modeling schizophrenia pathogenesis using patient-derived induced pluripotent stem cells (iPSCs)

Noh

Shao

Coyle

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Schizophrenia is a chronic disabling mental disorder that affects about 1% population world-wide, for which there is a desperate need to develop more effective treatments. In this minireview, we summarize the findings from recent studies using induced pluripotent stem cells to model the developmental pathogenesis of schizophrenia and discuss what we have learned from these studies. We also discuss what are the important next steps and key issues to be addressed to move the field forward.

show abstract

The Neurodevelopmental Hypothesis of Schizophrenia

Cited by 77 publications

References 124 publications

Maternal complement C1q and increased odds for psychosis in adult offspring

Maternal complement C1q and increased odds for psychosis in adult offspring

Neonatal stress-induced affective changes in adolescent Wistar rats: early signs of schizophrenia-like behavior

Modeling schizophrenia pathogenesis using patient-derived induced pluripotent stem cells (iPSCs)

Contact Info

Product

Resources

About