Dataset Information

Hippocampus and cognitive domain deficits in treatment-resistant schizophrenia: A comparison with matched treatment-responsive patients and healthy controls✰,✰✰,★,★★.

ABSTRACT: Some patients with schizophrenia do not respond to pharmacotherapy. More severe cognitive dysfunctions have been associated with treatment-resistant schizophrenia (TRS). This study examines cognitive functions and hippocampal volumes in 43 patients with TRS and compared them to 43 treatment-responsive patients (NTRS), matched on age, sex and education, as well as 53 healthy controls (HC). The results showed that there were significant deficits in all domains of cognition and hippocampal volumes in TRS as compared to HC group. However, TRS specific deficits, as indicated by comparisons with matched NTRS, were limited to poorer performance in working memory (p = 0.003) and smaller total hippocampal volume (p = 0.01). Logistic regression analysis showed that working memory deficits [OR 0.94 (95% CI 0.89-0.98), p = 0.005] and smaller hippocampal volume [OR 0.89 (95% CI 0.81-0.97), p = 0.01], but not their interactions (p = 0.68), contributed to higher risk of treatment resistance. The findings suggest that treatment-resistance to currently available antipsychotic medications may not be due to global cognitive deficits in these patients, but be associated with specific deficits in working memory and hippocampus deficits in the subgroup of schizophrenia.

SUBMITTER: Huang J

PROVIDER: S-EPMC7490244 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Hippocampus and cognitive domain deficits in treatment-resistant schizophrenia: A comparison with matched treatment-responsive patients and healthy controls<sup>✰,✰✰,★,★★</sup>.

Huang Junchao J Zhu Yu Y Fan Fengmei F Chen Song S Hong Yuan Y Cui Yimin Y Luo Xingguang X Tan Shuping S Wang Zhiren Z Shang Lan L Yuan Ying Y Zhang Jianxin J Yang Fude F Li Chiang-Shan R CR Rowland Laura M LM Kochunov Peter P Zhang Fengyu F Hong L Elliot LE Tan Yunlong Y

Psychiatry research. Neuroimaging 20200204

Some patients with schizophrenia do not respond to pharmacotherapy. More severe cognitive dysfunctions have been associated with treatment-resistant schizophrenia (TRS). This study examines cognitive functions and hippocampal volumes in 43 patients with TRS and compared them to 43 treatment-responsive patients (NTRS), matched on age, sex and education, as well as 53 healthy controls (HC). The results showed that there were significant deficits in all domains of cognition and hippocampal volumes ...[more]

PMID: 32062167

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Project description:BackgroundThe relationship between brain structural changes and cognitive dysfunction in schizophrenia is strong. However, few studies have investigated both neuroanatomical abnormalities and cognitive dysfunction in treatment-resistant schizophrenia (TRS). We examined neuroanatomical markers and cognitive function between patients with TRS or early-stage schizophrenia (ES-S) and healthy controls (HCs). Relationships between neuroanatomical markers and cognitive function in the patient groups were also investigated.MethodsA total of 46 and 45 patients with TRS and ES-S and 61 HCs underwent structural magnetic resonance imaging (MRI) brain scanning and comprehensive cognitive tests. MRI scans were analyzed using the FreeSurfer to investigate differences in cortical surface area (CSA), cortical thickness (CT), cortical volume (CV), and subcortical volume (SCV) among the groups. Four cognitive domains (attention, verbal memory, executive function, and language) were assessed. Comparisons of neuroanatomical and cognitive function results among the three groups were performed.ResultsA widespread reduction in CT was observed in patients with TRS compared to HCs, but differences in cortical thinning between TRS and ES-S patients were mainly limited to the inferior frontal gyrus and insula. Several subcortical structures (accumbens, amygdala, hippocampus, putamen, thalamus and ventricles) were significantly altered in TRS patients compared to both ES-S patients and HCs. Performance in the verbal memory domain was significantly worse in TRS patients compared to ES-S patients. A positive relationship between the thickness of the left middle temporal gyrus and the composite score for language was identified in patients with ES-S.ConclusionsOur findings suggest significant cognitive impairment and reductions in CT and SCV in individuals with TRS compared to those with ES-S and HCs. These abnormalities could act as biomarkers for earlier identification of TRS.

Project description:BackgroundThe significant proportion of schizophrenia patients refractory to treatment, primarily directed at the dopamine system, suggests that multiple mechanisms may underlie psychotic symptoms. Reinforcement learning tasks have been employed in schizophrenia to assess dopaminergic functioning and reward processing, but these have not directly compared groups of treatment-refractory and non-refractory patients.MethodsIn the current functional magnetic resonance imaging study, 21 patients with treatment-resistant schizophrenia (TRS), 21 patients with non-treatment-resistant schizophrenia (NTR), and 24 healthy controls (HC) performed a probabilistic reinforcement learning task, utilizing emotionally valenced face stimuli which elicit a social bias toward happy faces. Behavior was characterized with a reinforcement learning model. Trial-wise reward prediction error (RPE)-related neural activation and the differential impact of emotional bias on these reward signals were compared between groups.ResultsPatients showed impaired reinforcement learning relative to controls, while all groups demonstrated an emotional bias favoring happy faces. The pattern of RPE signaling was similar in the HC and TRS groups, whereas NTR patients showed significant attenuation of RPE-related activation in striatal, thalamic, precentral, parietal, and cerebellar regions. TRS patients, but not NTR patients, showed a positive relationship between emotional bias and RPE signal during negative feedback in bilateral thalamus and caudate.ConclusionTRS can be dissociated from NTR on the basis of a different neural mechanism underlying reinforcement learning. The data support the hypothesis that a favorable response to antipsychotic treatment is contingent on dopaminergic dysfunction, characterized by aberrant RPE signaling, whereas treatment resistance may be characterized by an abnormality of a non-dopaminergic mechanism - a glutamatergic mechanism would be a possible candidate.

Dataset Information

Hippocampus and cognitive domain deficits in treatment-resistant schizophrenia: A comparison with matched treatment-responsive patients and healthy controls✰,✰✰,★,★★.

Publications

Hippocampus and cognitive domain deficits in treatment-resistant schizophrenia: A comparison with matched treatment-responsive patients and healthy controls<sup>✰,✰✰,★,★★</sup>.

Similar Datasets

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