A Multimodal Analysis of Antipsychotic Effects on Brain Structure and Function in First-Episode Schizophrenia

Lesh, Tyler A.; Tanase, Costin; Geib, Benjamin R.; Niendam, Tara A.; Yoon, Jangho; Minzenberg, Michael; Ragland, J. Daniel; Solomon, Marjorie; Carter, Cameron S.

doi:10.1001/jamapsychiatry.2014.2178

Cited by 151 publications

(117 citation statements)

References 51 publications

(62 reference statements)

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“…Indeed, several other investigators using cognitive control (Lesh et al, 2015) and WM (Johnson et al, 2006;Walter et al, 2007) tasks have also reported no significant difference in dlPFC activation during correct trials between medicated first-episode schizophrenia patients and healthy individuals. Further, in our study, although positive symptoms negatively correlated with activation in FPCN (echoing previous results from Menon et al, 2001), patients still showed normal activation of the network during correct trials.…”

Section: Fpcn Function and Its Relation To Performance In Schizophreniamentioning

confidence: 95%

“…Notably, despite equivalent performance compared with controls, unmedicated individuals with high genetic loading for schizophrenia exhibit abnormal FPCN activation (Seidman et al, 2006) and medial prefrontal deactivation (Landin-Romero et al, 2014) during WM. A recent multimodal study on first-episode psychosis also showed that medicated patients and healthy controls do not differ significantly in dlPFC activation during a cognitive control task (Lesh et al, 2015). It is therefore possible that the lack of difference in dlPFC activation between patients and controls during correct performance partially reflects the medication effects.…”

Section: Thalamus-fpcn Disconnection In Schizophrenia During Task Permentioning

confidence: 99%

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Disrupted Working Memory Circuitry in Schizophrenia: Disentangling fMRI Markers of Core Pathology vs Other Aspects of Impaired Performance

Eryilmaz

Tanner

et al. 2016

Neuropsychopharmacol

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Working memory (WM) impairment, a core feature of schizophrenia, is often associated with aberrant dorsolateral prefrontal cortex (dlPFC) activation. Reduced resting-state connectivity within the frontoparietal control network (FPCN) has also been reported in schizophrenia. However, interpretation of WM-related dlPFC dysfunction has been limited by performance differences between patients and controls, and by uncertainty over the relevance of resting-state connectivity to network engagement during task. We contrasted brain activation in 40 schizophrenia patients and 40 controls during verbal WM performance, and evaluated underlying functional connectivity during rest and task. During correct trials, patients demonstrated normal FPCN activation, despite an inverse relationship between positive symptoms and activation. FPCN activation differed between the groups only during error trials (controls4patients). In contrast, controls demonstrated stronger deactivation of the ventromedial prefrontal cortex (vmPFC) during correct and error trials. Functional connectivity analysis indicated impaired resting-state FPCN connectivity in patients, but normal connectivity during task. However, patients showed abnormal connectivity among regions such as vmPFC, lateral orbitofrontal cortex, and parahippocampal gyrus (PHG) during both rest and task. During task, patients also exhibited altered thalamic connectivity to PHG and FPCN. Activation and connectivity patterns that were more characteristic of controls generally correlated with better performance. In summary, patients demonstrated normal FPCN activation when they remained on-task, and exhibited normal FPCN connectivity during WM, whereas vmPFC deactivation differences persisted regardless of WM performance. Our findings suggest that altered FPCN activation in patients reflects performance difference, and that limbic and thalamic dysfunction is critically involved in WM deficits in schizophrenia.

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Section: Fpcn Function and Its Relation To Performance In Schizophreniamentioning

confidence: 95%

Section: Thalamus-fpcn Disconnection In Schizophrenia During Task Permentioning

confidence: 99%

Disrupted Working Memory Circuitry in Schizophrenia: Disentangling fMRI Markers of Core Pathology vs Other Aspects of Impaired Performance

Eryilmaz

Tanner

et al. 2016

Neuropsychopharmacol

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“…Notably, when we used current medication in CPZ equivalent units as a quantitative measures of antipsychotic medication (at the cost of a reduced sample size), an effect on MOFC thickness was not observed. While past studies predominantly reported volume and thickness deficits in frontal brain regions in patients treated with typical compared with those treated with atypical antipsychotics or unmedicated patients (van Haren et al 2011;Lesh et al 2015;Vita et al 2015), there have also been many conflicting findings (Cahn et al 2002;Ho et al 2011). Attempting to reconcile previous reports, it has been suggested that antipsychotic medication effects on brain structure might be substance specific (Xiao et al 2008) and might also depend on illness chronicity and the duration of untreated psychosis.…”

Section: Antipsychotic Medicationmentioning

confidence: 99%

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

et al. 2017

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Background. Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. Results. Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.Conclusions. Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

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“…They were part of an ongoing longitudinal study of early psychosis (Lesh et al 2015), although none of these memory results have been published. Clinical participants were recruited from the Early Diagnosis and Preventive Treatment (EDAPT) clinic at UC Davis Medical Center.…”

Section: Methodsmentioning

confidence: 99%

Episodic memory functions in first episode psychosis and clinical high risk individuals

Greenland-White

Ragland

Niendam

et al. 2017

Schizophrenia Research

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Objective Individuals with schizophrenia have disproportionate memory impairments when encoding relational versus item-specific information, and when using recollection versus familiarity during retrieval. It is unclear whether this pattern is unique to people with chronic schizophrenia, or if it occurs in individuals after a first episode of psychosis (FE), or when at clinical high-risk for psychosis (CHR). Methods We administered the Relational and Item-Specific Memory task (RiSE) to 22 CHR, 101 FE, and 58 typically developing (TD) participants. We examined group differences in item and relational encoding, and familiarity-based and recollection-based retrieval using parametric analysis and structural equation modeling (SEM). Longitudinal data allowed us to examine relations between baseline RiSE performance and change in clinical symptoms at 1-year follow-up in the FE group. Results Groups did not differ on familiarity. FE and CHR groups were equally impaired on overall recognition accuracy. Although recollection was impaired in both FE and CHR groups following relational encoding, only the FE group had impaired recollection following item encoding. SEM showed atypical relationships between familiarity and recollection, as well as familiarity and item recognition for both the FE and CHR groups. For FE individuals, better baseline recognition accuracy predicted less severe negative symptoms at 1-year follow-up. Conclusions Impaired relational and recollective memory may reflect neurodevelopmental abnormalities predating conversion to psychosis. These memory deficits appear related to negative symptom changes. In contrast, item specific recollection deficits appear to occur after the development of full psychosis. Familiarity appears to be a relatively preserved memory function across the psychosis spectrum.

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A Multimodal Analysis of Antipsychotic Effects on Brain Structure and Function in First-Episode Schizophrenia

Cited by 151 publications

References 51 publications

Disrupted Working Memory Circuitry in Schizophrenia: Disentangling fMRI Markers of Core Pathology vs Other Aspects of Impaired Performance

Disrupted Working Memory Circuitry in Schizophrenia: Disentangling fMRI Markers of Core Pathology vs Other Aspects of Impaired Performance

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

Episodic memory functions in first episode psychosis and clinical high risk individuals

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