Altering the course of schizophrenia: progress and perspectives

Millan, Mark J.; Andrieux, Annie; Bartzokis, George; Cadenhead, Kristin S.; Dazzan, Paola; Fusar‐Poli, Paolo; Gallinat, Jürgen; Giedd, Jay N.; Grayson, Dennis R.; Heinrichs, Markus; Kahn, Rene M.; Krebs, Marie‐Odile; Leboyer, Marion; Lewis, David A.; Marı́n, Oscar; Marin, Philippe; Meyer‐Lindenberg, Andreas; McGorry, Patrick D.; McGuire, Philip; Owen, Michael John; Patterson, Paul; Sawa, Akira; Spedding, Michael; Uhlhaas, Peter J.; Vaccarino, Flora M.; Wahlestedt, Claes; Weinberger, Daniel R.

doi:10.1038/nrd.2016.28

Cited by 444 publications

(393 citation statements)

References 309 publications

(503 reference statements)

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“…This study has several conceptual implications. On an etiopathological level, our findings corroborate the notion that psychotic disorders can be related to adversities in an individual's social milieu, whereby environmental exposures during critical developmental periods impact brain, neurocognition, affect, and social cognition 13,138 . It is also apparent that most of these factors are likely not specific to psychosis, but also associated with other mental disorders 139 .…”

Section: Discussionsupporting

confidence: 76%

What causes psychosis? An umbrella review of risk and protective factors

et al. 2018

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Psychosis is a heterogeneous psychiatric condition for which a multitude of risk and protective factors have been suggested. This umbrella review aimed to classify the strength of evidence for the associations between each factor and psychotic disorders whilst controlling for several biases. The Web of Knowledge database was searched to identify systematic reviews and meta-analyses of observational studies which examined associations between socio-demographic, parental, perinatal, later factors or antecedents and psychotic disorders, and which included a comparison group of healthy controls, published from 1965 to January 31, 2017. The literature search and data extraction followed PRISMA and MOOSE guidelines. The association between each factor and ICD or DSM diagnoses of non-organic psychotic disorders was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of psychotic cases, random-effects p value, largest study 95% confidence interval, heterogeneity between studies, 95% prediction interval, small study effect, and excess significance bias. In order to assess evidence for temporality of association, we also conducted sensitivity analyses restricted to data from prospective studies. Fifty-five meta-analyses or systematic reviews were included in the umbrella review, corresponding to 683 individual studies and 170 putative risk or protective factors for psychotic disorders. Only the ultra-high-risk state for psychosis (odds ratio, OR59.32, 95% CI: 4.91-17.72) and Black-Caribbean ethnicity in England (OR54.87, 95% CI: 3.96-6.00) showed convincing evidence of association. Six factors were highly suggestive (ethnic minority in low ethnic density area, second generation immigrants, trait anhedonia, premorbid IQ, minor physical anomalies, and olfactory identification ability), and nine were suggestive (urbanicity, ethnic minority in high ethnic density area, first generation immigrants, North-African immigrants in Europe, winter/spring season of birth in Northern hemisphere, childhood social withdrawal, childhood trauma, Toxoplasma gondii IgG, and non-right handedness). When only prospective studies were considered, the evidence was convincing for ultra-high-risk state and suggestive for urbanicity only. In summary, this umbrella review found several factors to be associated with psychotic disorders with different levels of evidence. These risk or protective factors represent a starting point for further etiopathological research and for the improvement of the prediction of psychosis.

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Section: Discussionsupporting

confidence: 76%

What causes psychosis? An umbrella review of risk and protective factors

et al. 2018

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“…However, benefits have generally not extended to broader aspects of cognition [212,215]. If impaired synaptic plasticity disrupts the optimal tuning of local and long-range circuits, targeting plasticity deficits with pharmacological interventions and/or behavioral interventions intended to strengthen adaptive synapses earlier in development (e.g., support for school/extracurricular involvement, cognitive enhancement training, cognitive behavioral therapy) may provide more effective options for ameliorating the emergence of subsequent cognitive and/or psychotic symptoms [216–219]. Indeed, meta-analyses suggest that behavioral interventions can delay or prevent conversion to psychosis among some clinical high risk individuals [220,221], although sample sizes have been modest, effects on cognitive and neural functioning have been rarely investigated, and the neural mechanisms of treatment efficacy are unclear.…”

Section: Discussionmentioning

confidence: 99%

Mapping the Consequences of Impaired Synaptic Plasticity in Schizophrenia through Development: An Integrative Model for Diverse Clinical Features

Forsyth

Lewis

2017

Trends in Cognitive Sciences

122

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Schizophrenia is associated with alterations in sensory, motor, and cognitive functions that emerge prior to psychosis-onset; identifying pathogenic processes that can account for this multi-faceted phenotype remains a challenge. Accumulating evidence suggests that synaptic plasticity is impaired in schizophrenia. Given the role of synaptic plasticity in learning, memory, and neural circuit maturation, impaired plasticity may underlie many features of the schizophrenia syndrome. Here, we summarize the neurobiology of synaptic plasticity, review evidence that plasticity is impaired in schizophrenia, and explore a framework in which impaired synaptic plasticity interacts with brain maturation to yield the emergence of sensory, motor, cognitive, and psychotic features at different times during development in schizophrenia. Key gaps in the literature and future directions for testing this framework are discussed.

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“…Given that, currently, no universal genetic biomarker of the risk of transition into psychosis is available (Millan et al, 2016) and the fact that the opportunity for intervention on environmental factors is clearly easier than on genes, the focus of this review will be on environmental risk factors. Among them, stress sensitivity and exposure to drugs of abuse (such as cannabis) are linked to the later transition into psychosis (Kahn et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Adolescence as a period of vulnerability and intervention in schizophrenia: Insights from the MAM model

Gomes¹,

Rincón-Cortés²,

Grace³

2016

Neuroscience & Biobehavioral Reviews

108

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Adolescence is a time of extensive neuroanatomical, functional and chemical reorganization of the brain, which parallels substantial maturational changes in behavior and cognition. Environmental factors that impinge on the timing of these developmental factors, including stress and drug exposure, increase the risk for psychiatric disorders. Indeed, antecedents to affective and psychotic disorders, which have clinical and pathophysiological overlap, are commonly associated with risk factors during adolescence that predispose to these disorders. In the context of schizophrenia, psychosis typically begins in late adolescence/early adulthood, which has been replicated by animal models. Rats exposed during gestational day (GD) 17 to the mitotoxin methylazoxymethanol acetate (MAM) exhibit behavioral, pharmacological, and anatomical characteristics consistent with an animal model of schizophrenia. Here we provide an overview of adolescent changes within the dopamine system and the PFC and review recent findings regarding the effects of stress and cannabis exposure during the peripubertal period as risk factors for the emergence of schizophrenia-like deficits. Finally, we discuss peripubertal interventions appearing to circumvent the emergence of adult schizophrenia-like deficits.

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Altering the course of schizophrenia: progress and perspectives

Cited by 444 publications

References 309 publications

What causes psychosis? An umbrella review of risk and protective factors

What causes psychosis? An umbrella review of risk and protective factors

Mapping the Consequences of Impaired Synaptic Plasticity in Schizophrenia through Development: An Integrative Model for Diverse Clinical Features

Adolescence as a period of vulnerability and intervention in schizophrenia: Insights from the MAM model

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