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Critical Age Windows for Neurodevelopmental Psychiatric Disorders: Evidence from Animal Models
Abstract
A disruption in normal brain development has been hypothesized to contribute to the aetiology of major psychiatric disorders. According to the 'double-hit' hypothesis, mutant genes-based deviations, associated with specific environmental insults during brain development, may result in neurobehavioural disturbances. The existence of age windows of vulnerability to environmental conditions during brain maturation will be discussed, using as examples a series of studies we have performed during the last years. Major deviations from normative neurobehavioural trajectories have been reported in animal models following exposure to severe stress (either episodes of maternal separation, deprivation or corticosterone supplementation) early in infancy. Rodent models of difficult and/or stressful pregnancies, including obstetric complications (e.g. prenatal restrain stress or neonatal hypoxia) and gestational exposure to infection (e.g prenatal immune challenge), have been associated with profound long-lasting deficits in the offspring's emotional and social behaviour, and with immune and endocrine changes. More recently, adolescence, characterized by elevated rates of brain plasticity, has emerged as an additional period during which sensitivity to environmental influence (either adverse or stimulatory) is maximal. We have reported that both pharmacological (methylphenidate) and environmental (physical or social enrichment) interventions can be used to counteract the detrimental effects of earlier-origin developmental insults. Present findings indicate that these age periods (i.e. prenatal stage, early infancy and adolescence) do represent critical windows open to plastic changes and might be susceptible to both adverse and supportive shaping environmental forces. Taken together, age-related neuroplasticity might be considered not only as a risk factor for psychopathology but also as a potent mechanism for compensation. A better understanding of these critical periods of brain development is a concern for public health and may provide new insights into prevention strategies and into novel therapeutic approaches in neuropsychiatry.
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“Indeed, adolescence is a critical period for not only social interaction (Larsen and Luna, 2018; ) but also the emergence of psychiatric diseases (Orben et al., 2020; Marco et al., 2011), and social isolation during adolescence can exacerbate mental health problems (Larsen and Luna, 2018; Almeida et al., 2021; ; Graf et al., 2021; Andersen, 2021).”
From Oxytocin neurons mediate the effect of social isolation via the VTA circuits (2022) · cites this paper as Marco et al., 2011
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Metadata
- Authors
- Marco, E. M., Macrì, S., & Laviola, G.
- Affiliations
- Istituto Superiore di Sanità (IT)
- ORCID
- Marco, Eva M.
- Venue
- Neurotoxicity Research
- Published
- 2010-07-07
- Volume
- 19
- Issue
- 2
- Pages
- 286-307
- ISSN
- 1029-8428 (ISSN-L)
- 1476-3524
- OpenAlex
- W2111063637
- Cited by
- 144
- References
- 260
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 15 · 2015: 9 · 2014: 7 · 2013: 10 · 2012: 13
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurotoxicity Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- double-hit hypothesis, prenatal stress, maternal separation, corticosterone, prenatal hypoxia, prenatal immune challenge, pregnancy complications, methylphenidate, social enrichment, neuroplasticity
- MeSH terms
- Age Factors, Animals, Mental Disorders, Critical Period, Psychological, Disease Models, Animal, Female, Humans, Pregnancy, Prenatal Exposure Delayed Effects, Risk Factors, Stress, Psychological, Evidence-Based Medicine
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