A Systematic Review of Cognitive Function in First-Episode Psychosis, Including a Discussion on Childhood Trauma, Stress, and Inflammation

Aas, Monica; Dazzan, Paola; Mondelli, Valeria; Melle, Ingrid; Murray, Robin M.; Pariante, Carmine M.

doi:10.3389/fpsyt.2013.00182

Cited by 193 publications

(148 citation statements)

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“…Because deletion or overexpression of Hdac1 in all neurons of the mouse brain from prenatal stages did not cause any behavioral changes (23), we speculated that elevated HDAC1 levels in patients with schizophrenia may be due to environmental risk factors that drive Hdac1 expression in the postnatal brain, thereby limiting the effect of compensatory processes. One environmental risk factor that has repeatedly, although not exclusively, been linked to the pathogenesis of schizophrenia is ELS (25,26), which can be modeled in rodents (27). Thus, we hypothesized that ELS might increase Hdac1 expression.…”

Section: Resultsmentioning

confidence: 99%

HDAC1 links early life stress to schizophrenia-like phenotypes

Bahari‐Javan

Varbanov

Halder

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate with a widespread increase of histone-deacetylase 1 (Hdac1) expression that is linked to altered DNA methylation. Hdac1 overexpression in neurons of the medial prefrontal cortex, but not in the dorsal or ventral hippocampus, mimics schizophrenia-like phenotypes induced by ELS. Systemic administration of an HDAC inhibitor rescues the detrimental effects of ELS when applied after the manifestation of disease phenotypes. In addition to the hippocampus and prefrontal cortex, mice subjected to ELS exhibit increased Hdac1 expression in blood. Moreover, Hdac1 levels are increased in blood samples from patients with schizophrenia who had encountered ELS, compared with patients without ELS experience. Our data suggest that HDAC1 inhibition should be considered as a therapeutic approach to treat schizophrenia.

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Section: Resultsmentioning

confidence: 99%

HDAC1 links early life stress to schizophrenia-like phenotypes

Bahari‐Javan

Varbanov

Halder

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Exposure to childhood trauma is common among UHR individuals (Kraan et al, 2015a), although evidence linking it to increased risk of transition to psychotic disorder in this group remains inconclusive (Thompson et al, 2014;Kraan et al, 2015b;Stowkowy et al, 2016). Poor engagement with clinical services, more severe psychiatric symptoms and cognitive impairment have all been linked to childhood trauma in patients with psychosis (Aas et al, 2014;Gumley et al, 2014). Post-traumatic stress disorder (PTSD) may also be a comorbid problem among those individuals exposed to trauma, which in turn is associated with poorer employment outcomes even among individuals with serious mental illness (Mueser et al, 2004a;2004b).…”

Section: Discussionmentioning

confidence: 99%

Long-term employment among people at ultra-high risk for psychosis

Cotter

Lin

Drake

et al. 2017

Schizophrenia Research

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Word count abstract: 250Word count paper: 2,894 Number of tables: 2Supplementary data: Supplementary Table 1 2 Abstract BackgroundPsychotic disorders are associated with high rates of sustained unemployment, however, little is known about the long-term employment outcome of people at ultrahigh risk (UHR) of developing psychosis. We sought to investigate the long-term unemployment rate and baseline predictors of employment status at follow-up in a large UHR cohort. Method UHR patients recruited from the Personal Assessment and Crisis Evaluationclinic in Melbourne, Australia were followed-up over 2-14 years after initial presentation to the service. Individuals in no form of employment or education were classed as unemployed. Logistic regression analyses were used to examine predictors of employment outcome. ResultsA high rate of unemployment was present at follow-up in this UHR sample (23%). At baseline, those who were unemployed at follow-up had a longer duration of untreated illness, more severe negative symptoms, lower IQ, poorer social and occupational functioning and reported more childhood trauma than the employed group. At follow-up, unemployed individuals exhibited significantly more severe symptoms on all measures and were more likely to have been diagnosed with a mood, anxiety, psychotic or substance use disorder. Childhood trauma and the duration of untreated illness at baseline were significant independent predictors of employment status at follow-up in the multivariate analyses.3 ConclusionsNearly a quarter of this UHR sample were unemployed at long-term follow-up. The duration of untreated illness and the effects of childhood trauma are potentially modifiable risk factors for long-term employment outcome in this group. Vocational support may be beneficial for many UHR patients presenting to services.

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“…17 The negative association between age and years of education on TMT-A scores is in accordance with the decreased attention and processing speed 17 observed with age and lower general intelligence in patients with first-episode psychosis. 28,56 Our study focused on patients with first-episode schizophrenia to exclude effects due to chronic evolution of the disease. In the present study, patients were untreated or treated for only a few days, thus limiting the possible effects of medication.…”

Section: Discussionmentioning

confidence: 99%

“…28 The TMT offers the advantage of assessing in a single test several cognitive processes: TMT-A evaluates basic processes (attention and processing speed), while TMT-B evaluates executive functions (working memory, cognitive flexibility and control inhibition). The difference score (TMT-B -TMT-A) controls for the processing speed 17 and is more specific for assessing executive functioning than TMT-B alone.…”

Section: Discussionmentioning

confidence: 99%