Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings

Misiak, Błażej; Krefft, Maja; Bielawski, Tomasz; Moustafa, Ahmed A.; Sąsiadek, Maria M.; Frydecka, Dorota

doi:10.1016/j.neubiorev.2017.02.015

Cited by 179 publications

(115 citation statements)

References 192 publications

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“…Our findings suggest, tentatively, that a putative cognitive pathway between early childhood maltreatment and later psychosis risk could be contingent on the development of EMS. Indeed, some argue that exposure to early trauma may not be sufficient to trigger the onset of psychosis (Misiak et al, ). Therefore, our findings support the need for systematic investigation of not only the occurrence of child maltreatment, but the potential presentation of EMSs since both may synergistically combine to index risk for later onset of a psychotic disorder.…”

Section: Resultsmentioning

confidence: 99%

Childhood maltreatment and psychotic experiences: Exploring the specificity of early maladaptive schemas

et al. 2018

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Results indicated specificity effects in that specific types of maltreatment are associated with specific maladaptive schemas. From a practitioner's perspective, these findings offer credence to cognitive theories of psychopathology, and support the validity of EMS identification and modification among clients with psychotic symptomology both as a fundamental component of traditional CBT and within specialized schema-focused therapy.

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Section: Resultsmentioning

confidence: 99%

Childhood maltreatment and psychotic experiences: Exploring the specificity of early maladaptive schemas

et al. 2018

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“…Adverse experiences can have long-lasting transgenerational effects on mental and physical health, and often increase disease risk 4,5 . Traumatic stress in early life in particular, can induce pathologies like psychosis, depression and metabolic dysfunctions in adulthood across generations 6 . To examine the biological factors involved, we recapitulated heritable behavioural and metabolic effects of postnatal trauma across several generations using a previously established model of unpredictable maternal separation combined with unpredictable maternal stress (MSUS) in the mouse, that shows symptoms through up to three generations (Fig.…”

Section: Introductionmentioning

confidence: 99%

Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma

Gapp

Steenwyk

Germain

et al. 2018

Preprint

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30Psychiatric diseases have a strong heritable component known to not be restricted to 31 DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in 32 germ cells 1,2 . Initial evidence suggested that sperm RNA is causally linked 2,3 to the 33 transmission of symptoms induced by traumatic experiences. Here we show that 34 alterations in long RNA in sperm contribute to the inheritance of specific trauma 35 symptoms. Injection of long RNA fraction from sperm of males exposed to postnatal 36 trauma recapitulates the effects on food intake, glucose response to insulin and risk-37 taking in adulthood whereas the small RNA fraction alters body weight and behavioral 38 despair. Alterations in long RNA are maintained after fertilization, suggesting a direct 39 link between sperm and embryo RNA. 40 41 42 43 Adverse experiences can have long-lasting transgenerational effects on mental and 46 physical health, and often increase disease risk 4,5 . Traumatic stress in early life in 47 particular, can induce pathologies like psychosis, depression and metabolic 48 dysfunctions in adulthood across generations 6 . To examine the biological factors 49 involved, we recapitulated heritable behavioural and metabolic effects of postnatal 50 trauma across several generations using a previously established model of 51 unpredictable maternal separation combined with unpredictable maternal stress 52(MSUS) in the mouse, that shows symptoms through up to three generations ( Fig.1) 2,7-53 13 . We have shown that such postnatal trauma alters small RNA in sperm and that 54 injection of total sperm RNA from exposed male mice into naïve fertilized oocytes elicits 55 symptoms reminiscent of those observed in natural offspring of exposed fathers 2 . Other 56 studies have demonstrated that adult stress 14,15 and environmental insults like altered 57 diet or vinclozolin exposure, or positive factors such as exercise or environmental 58 enrichment can affect small RNA in sperm 16-21 and somatic tissues 22 in the offspring.59Recently, tRNA fragments and their modifications were also found to be affected by 60 nutritional insult, and unmodified or modified sperm small RNA injected into fertilized 61 oocytes could mimic metabolic changes resulting from altered parental diet in the 62 progeny 18,23,24 . These studies therefore suggest that small RNA in sperm can be 63 carrier of heritable information. Here we sought to determine whether long RNA in 64 sperm also contributes to the transmission of the effects of previous exposure. 66 Materials and Methods 68Mice. C57BL/6J mice were housed in a temperature and humidity-controlled facility 69 under a reverse light-dark cycle, and food and water were provided ad libitum. 70 Experimental procedures were performed during the animals' active cycle. All71 experiments were approved by the cantonal veterinary office, Zurich (license 55/12 then 72 57/15).73 74 MSUS paradigm. C57BL/6J primiparous females and males were mated at 2.5-3 75 months of age. Randomly selected dams and litt...

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“…Therefore, investigating the effects of childhood trauma on the AL index serves as one of directions for future studies. Given that early-life stress is neither necessary nor sufficient to trigger the onset of psychosis as approximately one third of patients with psychosis report this type of experiences, insights into potential mediators and moderators should be taken into account (4,6). Indeed, a number of psychological phenomena have been found to mediate the effects of traumatic events on psychosis risk, including cognitive biases and self disturbances (51,52).…”

Section: Summary Of Evidence and Future Directionsmentioning

confidence: 99%

“…Approximately one third of patients with psychosis report a history of childhood trauma and this type of stressful experiences is a well-established risk factor of psychosis development (4,5). Although exposure to early-life stress is neither necessary nor sufficient to cause psychosis, several studies indicate that a history of childhood adversities is related to a number of biological alterations observed in this group of patients [for review see (6)]. These alterations are represented by the hypothalamic-pituitary-adrenal (HPA) axis dysregulation, manifesting in elevated morning (7) and diurnal cortisol (8) levels, blunted cortisol awakening response (9), and attenuated cortisol response to stress (10).…”

Section: Introductionmentioning

confidence: 99%

Stress, Allostatic Load, and Psychosis: One Step Forward in Research But Where to Go Next?

Misiak

2020

Front. Psychiatry

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Stress exposure leads to the activation of several biological mechanisms that have been termed allostasis. These processes enable adaptation to novel situations; however; their prolonged activation exerts systemic and detrimental effects called the allostatic load (AL). The AL concept represents one of useful paradigms to describe biological consequences of chronic stress that might lead to a number of disease outcomes. The AL index, which is a collective measure of cardiovascular, metabolic, neuroendocrine, and immune dysregulations associated with stress exposure, has been found to predict morbidity and mortality in non-clinical populations. Consequently, it has been proposed that the AL concept might be a useful framework to describe biological consequences of chronic stress exposure in patients with psychotic disorders. This perspective article is an overview of studies investigating the AL index and its clinical correlates in patients with psychotic disorders. These studies have consistently reported elevated AL index in patients at the early and chronic course of psychosis. In addition, the AL index has been associated with a higher severity of positive and depressive symptoms, working memory impairments, and lower general functioning. The article provides some critical appraisal of studies in this field and indicates several future directions for investigating the AL concept in psychosis.

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Toward a unified theory of childhood trauma and psychosis: A comprehensive review of epidemiological, clinical, neuropsychological and biological findings

Cited by 179 publications

References 192 publications

Childhood maltreatment and psychotic experiences: Exploring the specificity of early maladaptive schemas

Childhood maltreatment and psychotic experiences: Exploring the specificity of early maladaptive schemas

Alterations in sperm long RNA contribute to the epigenetic inheritance of the effects of postnatal trauma

Stress, Allostatic Load, and Psychosis: One Step Forward in Research But Where to Go Next?

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