Perinatal Risks and Childhood Premorbid Indicators of Later Psychosis: Next Steps for Early Psychosocial Interventions

Liu, Cindy H.; Keshavan, Matcheri S.; Tronick, Ed; Seidman, Larry J.

doi:10.1093/schbul/sbv047

Cited by 99 publications

(79 citation statements)

References 252 publications

(275 reference statements)

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“…Such interventions to potentially reduce the risk of non-communicable disorders including schizophrenia in vulnerable persons at risk may range from the care of pregnant patients with psychoses who may benefit from prenatal care and social support and family centered programs, to preemptive cognitive remediation and early intervention for children at risk. (Liu et al, 2015). Additionally, having a systemic approach which allows for multiple referral sources being established through networking with general practitioners, community mental health workers and school officials allows for the earlier recognition and referral of persons within the early phase of a psychotic disorder (Ho et al, 2005).…”

Section: Prevention Strategiesmentioning

confidence: 99%

A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis

Davis

Eyre

Jacka

et al. 2016

Neuroscience & Biobehavioral Reviews

288

209

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Schizophrenia risk has often been conceptualized using a model which requires two hits in order to generate the clinical phenotype—the first as an early priming in a genetically predisposed individual and the second a likely environmental insult. The aim of this paper was to review the literature and reformulate this binary risk-vulnerability model. We sourced the data for this narrative review from the electronic database PUBMED. Our search terms were not limited by language or date of publication. The development of schizophrenia may be driven by genetic vulnerability interacting with multiple vulnerability factors including lowered prenatal vitamin D exposure, viral infections, smoking intelligence quotient, social cognition cannabis use, social defeat, nutrition and childhood trauma. It is likely that these genetic risks, environmental risks and vulnerability factors are cumulative and interactive with each other and with critical periods of neurodevelopmental vulnerability. The development of schizophrenia is likely to be more complex and nuanced than the binary two hit model originally proposed nearly thirty years ago. Risk appears influenced by a more complex process involving genetic risk interfacing with multiple potentially interacting hits and vulnerability factors occurring at key periods of neurodevelopmental activity, which culminate in the expression of disease state. These risks are common across a number of neuropsychiatric and medical disorders, which might inform common preventive and intervention strategies across non-communicable disorders.

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Section: Prevention Strategiesmentioning

confidence: 99%

A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis

Davis

Eyre

Jacka

et al. 2016

Neuroscience & Biobehavioral Reviews

288

209

View full text Add to dashboard Cite

show abstract

“…(pp. 801, Liu et al, 2015). The evidence indicates that cognitive abnormalities often precede the onset of psychosis by many years , and premorbid cognitive deficits are more closely linked to schizophrenia than to affective psychosis (Agnew-Blais et al, 2017).…”

Section: Schizophrenia As a Neurodevelopmental Disordermentioning

confidence: 99%

Evolving Notions of Schizophrenia as a Developmental Neurocognitive Disorder

Seidman

Mirsky

2017

J Int Neuropsychol Soc

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We review the changing conceptions of schizophrenia over the past 50 years as it became understood as a disorder of brain function and structure in which neurocognitive dysfunction was identified at different illness phases. The centrality of neurocognition has been recognized, especially because neurocognitive deficits are strongly related to social and role functioning in the illness, and as a result neurocognitive measures are used routinely in clinical assessment of individuals with schizophrenia. From the original definitions of the syndrome of schizophrenia in the early 20th century, impaired cognition, especially attention, was considered to be important. Neurocognitive impairments are found in the vast majority of individuals with schizophrenia, and they vary from mild, relatively restricted deficits, to dementia-like syndromes, as early as the first psychotic episode. Neurocognitive deficits are found in the premorbid phase in a substantial minority of pre-teenage youth who later develop schizophrenia, and they apparently worsen by the prodromal, high-risk phase in a majority of those who develop the illness. While there is limited evidence for reversibility of impairments from pharmacological interventions in schizophrenia, promising results have emerged from cognitive remediation studies. Thus, we expect cognitive interventions to play a larger role in schizophrenia in the coming years. Moreover, because youth at risk for schizophrenia can be identified by an emergent high-risk syndrome, earlier interventions might be applied in a preemptive way to reduce disability and improve adaptation. The notion of schizophrenia as a developmental neurocognitive disorder with stages opens up a window of possibilities for earlier interventions. (JINS, 2017, 23, 881-892)

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“…There is ample evidence of significant but milder impairments during the premorbid phase 10–12 , greater deficits during the prodromal or clinical high risk (CHR) period, 13–15 culminating in relatively severe deficits in the first episode 16 and chronic phases 17 . This suggests an evolution of neurocognitive dysfunction in individuals developing psychosis, especially schizophrenia 10,14,18,19 . The CHR 20 period is of considerable interest because it offers a temporal window into the changes occurring during the “near-psychotic” state, before confounders such as chronicity and long-term medication use cloud the picture.…”

Section: Introductionmentioning

confidence: 99%

Association of Neurocognition With Transition to Psychosis

et al. 2016

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Importance Neurocognition is a central characteristic of schizophrenia and other psychotic disorders. Identifying the pattern and severity of neurocognitive functioning during the “near-psychotic”, prodromal, clinical high-risk (CHR) state is necessary to develop accurate predictors of psychosis and more effective and potentially preventative treatments. Objective Identify core neurocognitive dysfunctions associated with the CHR phase, and measure the ability of neurocognitive tests to predict the transition to psychosis. Determine if the neurocognitive deficits are robust or explained by potential confounders. Design Case control study. Baseline neurocognitive functioning collected from 2008–2012 in the second phase of the North American Prodrome Longitudinal Study (NAPLS-2). Setting A consortium of eight university-based, outpatient programs studying the psychosis prodrome in North America. Participants CHR individuals (n=689) and healthy controls (HCs, n=264) consisting of 137 male and 127 female HC and 398 male and 291 female CHR individuals ages 12–35. Interventions or Exposures A naturalistic, observational study. Main Outcome and Measure(s) Neurocognitive differences between those who did and did not transition to psychosis, differences between medicated and unmedicated groups, and time to conversion. Nineteen neuropsychological tests and four factors derived from factor analysis. Results The factors were Executive Function/Visual-Spatial, Verbal, Attention/Working Memory, and Declarative Memory. Amongst widespread mild to moderate impairments, CHR individuals were significantly impaired compared to HCs on Attention/Working Memory and Declarative Memory. CHR converters had large Declarative Memory and Attention/Working Memory deficits (Cohen’s d = ~0.8, p <.001) compared with controls and were significantly worse on these dimensions than non-converters. In Cox regression, impaired Declarative Memory and high Verbal (premorbid) ability in addition to age, site and positive psychotic symptoms, significantly predicted time to conversion in those who later transitioned to psychosis. The pattern of impairments could not be accounted for by premorbid or current general cognitive ability, medications, current depression, alcohol or cannabis abuse. Conclusions and Relevance Neurocognitive impairment is a robust characteristic of CHR individuals, especially those who later develop psychosis. Tests tapping verbal and visual declarative memory and attention/working memory were most sensitive to imminent psychosis amongst those at CHR. Interventions targeting the enhancement of neurocognitive functioning are warranted in this population.

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Perinatal Risks and Childhood Premorbid Indicators of Later Psychosis: Next Steps for Early Psychosocial Interventions

Cited by 99 publications

References 252 publications

A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis

A review of vulnerability and risks for schizophrenia: Beyond the two hit hypothesis

Evolving Notions of Schizophrenia as a Developmental Neurocognitive Disorder

Association of Neurocognition With Transition to Psychosis

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