Gray Matter Alterations in Schizophrenia High-Risk Youth and Early-Onset Schizophrenia

Brent, Benjamin K.; Thermenos, Heidi W.; Keshavan, Matcheri S.; Seidman, Larry J.

doi:10.1016/j.chc.2013.06.003

Cited by 98 publications

(71 citation statements)

References 168 publications

(219 reference statements)

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“…Converging evidence points to both structural, functional and/or neurochemical abnormalities in these three regions in CHR. In the frontal cortex, CHR exhibit both structural alterations (e.g., gray matter, cortical surface, integrity)(Bloemen et al, 2010; Fusar-Poli et al, 2011a; Iwashiro et al, 2012; Jung et al, 2012; Kambeitz-Ilankovic et al, 2015; Mechelli et al, 2011; Nenadic et al, 2015; Pantelis et al, 2009) (reviewed in (Brent et al, 2013; Smieskova et al, 2013) and functional changes in response to WM and other cognitive tasks (Allen et al, 2011; Dutt et al, 2015; Fusar-Poli et al, 2011b; Natsubori et al, 2014). In the PHP and medial temporal lobe (MTL, including the hippocampus, amygdala and surrounding entorhinal and perirhinal cortices), CHR most reliably demonstrate structural alterations (e.g., reduced gray matter, cortical thinning)(Buehlmann et al, 2010; Jung et al, 2011; Mechelli et al, 2011; Mittal et al, 2011; Pantelis et al, 2003; Tognin et al, 2013), with one previous study demonstrating task-induced functional alterations in antipsychotic naïve CHR (Allen et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis

Thermenos

Juelich

DiChiara

et al. 2016

Schizophrenia Research

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BACKGROUND Deficits in working memory (WM) are a core feature of schizophrenia (SZ) and other psychotic disorders. We examined brain activity during WM in persons at clinical high risk (CHR) for psychosis. METHODS Thirty-seven CHR and 34 healthy control participants underwent functional MRI (fMRI) on a 3.0 T scanner while performing an N-back WM task. The sample included a sub-sample of CHR participants who had no lifetime history of treatment with psychotropic medications (n=11). Data were analyzed using SPM8 (2-back > 0-back contrast). Pearson correlations between brain activity, symptoms, and WM performance were examined. RESULTS The total CHR group and medication-naive CHR sub-sample were comparable to controls in most demographic features and in N-back WM performance, but had significantly lower IQ. Relative to controls, medication-naïve CHR showed hyperactivity in the left parahippocampus (PHP) and the left caudate during performance of the N-back WM task. Relative to medication-exposed CHR, medication naïve CHR exhibited hyperactivity in the left caudate and the right dorsolateral prefrontal cortex (DLPFC). DLPFC activity was significantly negatively correlated with WM performance. PHP, caudate and DLPFC activity correlated strongly with symptoms, but results did not withstand FDR-correction for multiple comparisons. When all CHR participants were combined (regardless of medication status), only trend-level PHP hyperactivity was observed in CHR relative to controls. CONCLUSIONS Medication-naïve CHR exhibit hyperactivity in regions that subserve WM. These regions are implicated in studies of schizophrenia and risk for psychosis. Results emphasize the importance of medication status in the interpretation of task induced brain activity.

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Section: Discussionmentioning

confidence: 99%

Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis

Thermenos

Juelich

DiChiara

et al. 2016

Schizophrenia Research

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“…Although links to both the immediate mechanical shearing injury as well as brain atrophy and ventricular enlargement after brain trauma have been reported, 1,16 the exact pathomechanism of the development or enlargement of a CSP after brain trauma remains unknown. While CSP is also seen in patients with neurodevelopmental disorders, [20][21][22][23] and is therefore not specific to CTE, we believe that in those who experience repetitive head impacts, CSP is likely the result of trauma, which is also thought to be one of the risk factors for development of CTE or other possible neurodegenerative disorders.…”

mentioning

confidence: 99%

“…The overall prevalence of CSP in the population varies greatly in the literature, depending on the cohort and technique used. 18,19 Moreover, a higher prevalence of CSP has been linked to neurodevelopmental diseases such as schizophrenia [20][21][22][23] as well as to genetic conditions. 24 Increased rates of CSP have also been reported among boxers and participants of other contact-sports exposed to repetitive head impacts.…”

Section: Introductionmentioning

confidence: 99%

Cavum Septi Pellucidi in Symptomatic Former Professional Football Players

Koerte

Hufschmidt

Muehlmann

et al. 2016

Journal of Neurotrauma

112

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Post-mortem studies reveal a high rate of cavum septi pellucidi (CSP) in chronic traumatic encephalopathy (CTE). It remains, however, to be determined whether or not the presence of CSP may be a potential in vivo imaging marker in populations at high risk to develop CTE. The aim of this study was to evaluate CSP in former professional American football players presenting with cognitive and behavioral symptoms compared with noncontact sports athletes. Seventytwo symptomatic former professional football players (mean age 54.53 years, standard deviation [SD] 7.97) as well as 14 former professional noncontact sports athletes (mean age 57.14 years, SD 7.35) underwent high-resolution structural 3T magnetic resonance imaging. Two raters independently evaluated the CSP, and interrater reliability was calculated. Within National Football League players, an association of CSP measures with cognitive and behavioral functioning was evaluated using a multivariate mixed effects model. The measurements of the two raters were highly correlated (CSP length: rho = 0.98; Intraclass Correlation Coefficient [ICC] 0.99; p < 0.0001; septum length: rho = 0.93; ICC 0.96; p < 0.0001). For presence versus absence of CSP, there was high agreement (Cohen kappa = 0.83, p < 0.0001). A higher rate of CSP, a greater length of CSP, as well as a greater ratio of CSP length to septum length was found in symptomatic former professional football players compared with athlete controls. In addition, a greater length of CSP was associated with decreased performance on a list learning task (Neuropsychological Assessment Battery List A Immediate Recall, p = 0.04) and decreased test scores on a measure of estimate verbal intelligence (Wide Range Achievement Test Fourth Edition Reading Test, p = 0.02). Given the high prevalence of CSP in neuropathologically confirmed CTE in addition to the results of this study, CSP may serve as a potential early in vivo imaging marker to identify those at high risk for CTE. Future research is needed to investigate the pathomechanism underlying the development of CSP after repetitive head impacts, and its potential association with neuropathologically confirmed CTE.

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“…73,74 FHR youth ages 8 to 30 have substantial GM volume abnormalities compared to controls, with an accelerated volume reduction over time in association with psychotic-like symptoms and cognitive deficits. Prefrontal cortex (PFC) alterations are the most consistently reported, followed by smaller hippocampal volume.…”

Section: Characteristics and Correlates Of Psychosis Riskmentioning

confidence: 99%

“…73 Compared with controls, PR groups show both smaller GM volume and cortical thinning in PFC, lateral temporal cortex (particularly superior temporal gyrus [STG]), and, to a lesser extent, parietal cortex. Less PFC GM has been associated with impaired executive function and greater severity of symptoms in CHR whereas smaller STG GM has been linked with deficits involving semantic fluency.…”

Section: Characteristics and Correlates Of Psychosis Riskmentioning

confidence: 99%

Progress and Future Directions in Research on the Psychosis Prodrome

Woodberry¹,

Shapiro²,

Bryant³

et al. 2016

Harvard Review of Psychiatry

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The psychosis prodrome, or period of clinical and functional decline leading up to acute psychosis, offers a unique opportunity for identifying mechanisms of psychosis onset and testing early intervention strategies. We summarize major findings and emerging directions in prodromal research and provide recommendations for clinicians working with individuals suspected to be at high risk for psychosis. The past two decades of research have led to three major advances. First, tools and criteria have been developed that can reliably identify imminent risk for a psychotic disorder. Second, longitudinal clinical and psychobiological data from large multisite studies are strengthening individual risk assessment and offering insights into potential mechanisms of illness onset. Third, psychosocial and pharmacological interventions are demonstrating promise for delaying or preventing the onset of psychosis in help-seeking, high-risk individuals. The dynamic psychobiological processes implicated in both risk and onset of psychosis, including altered gene expression, cognitive dysfunction, inflammation, gray and white matter brain changes, and vulnerability-stress interactions suggest a wide range of potential treatment targets and strategies. The expansion of resources devoted to early intervention and prodromal research worldwide raises hope for investigating them. Future directions include identifying psychosis-specific risk and resilience factors in children, adolescents, and non-help-seeking community samples, improving study designs to test hypothesized mechanisms of change, and intervening with strategies that better engage youth, their environmental contexts, and neurodevelopmental targets to improve functional outcomes. Prospective research on putatively prodromal samples has the potential to substantially reshape our understanding of mental illness and our efforts to combat it.

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Gray Matter Alterations in Schizophrenia High-Risk Youth and Early-Onset Schizophrenia

Cited by 98 publications

References 168 publications

Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis

Hyperactivity of caudate, parahippocampal, and prefrontal regions during working memory in never-medicated persons at clinical high-risk for psychosis

Cavum Septi Pellucidi in Symptomatic Former Professional Football Players

Progress and Future Directions in Research on the Psychosis Prodrome

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