Volume reduction and altered sulco-gyral pattern of the orbitofrontal cortex in first-episode schizophrenia

Takayanagi, Yoichiro; Takahashi, Tsutomu; Orikabe, Lina; Masuda, Norimichi; Mozue, Yuriko; Nakamura, Kazue; Kawasaki, Yasuhiro; Itokawa, Masanari; Sato, Yoko; Yamasue, Hidenori; Kasai, Kiyoto; Okazaki, Yuji; Suzuki, Michio

doi:10.1016/j.schres.2010.05.006

Cited by 70 publications

(63 citation statements)

References 84 publications

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“…Decreased orbitofrontal cortex volume has also been reported in patients with schizophrenia [58,59,60]. GM volume in this region has been found to be associated with illness duration [61], theory of mind deficits [62] and formal thought disorder severity [53]. Together with previous findings, our results suggest that abnormalities in these regions may underlie a common brain pathophysiology in patients with LOS and EOS.…”

Section: Discussionsupporting

confidence: 84%

Different and Shared Brain Volume Abnormalities in Late- and Early-Onset Schizophrenia

Egashira

Matsuo²,

Mihara³

et al. 2014

Neuropsychobiology

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The differences in clinical characteristics between late- (LOS) and early-onset schizophrenia (EOS) are well documented. However, very little is known about the neural mechanisms underlying these differences. Here, we compared morphometric abnormalities between patients with EOS and those with LOS. A total of 22 patients with LOS, 24 patients with EOS and 41 healthy control subjects were included in this magnetic resonance imaging study. Brain images were analyzed using DARTEL preprocessing for voxel-based morphometry in SPM8. We tested a main effect of diagnosis in the whole-brain analysis and compared the results among the three groups. We also carried out correlation analyses between regional volumes and clinical variables. Patients with LOS showed larger gray matter (GM) volume of the left precuneus compared with healthy subjects and patients with EOS. Patients with LOS and EOS showed decreased GM volumes in the right insula, left superior temporal gyrus and left orbitofrontal gyrus compared with healthy subjects. A longer duration of illness was associated with reduced GM volume in the temporal pole in patients with EOS. Our findings may help improve our understanding of schizophrenia pathophysiology and shed light on the different and shared neurobiological underpinnings of LOS and EOS.

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Section: Discussionsupporting

confidence: 84%

Different and Shared Brain Volume Abnormalities in Late- and Early-Onset Schizophrenia

Egashira

Matsuo²,

Mihara³

et al. 2014

Neuropsychobiology

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“…Thalamo-OFC connectivity was also highly correlated with the GAF score in CHR patients. Interestingly, the thalamo-PC connectivity presented the opposite trend of change, with the connection Along with the previously reported structural abnormalities including volume, cortical thickness and sulcogyral pattern of the OFC, [48][49][50] the anomaly in the white matter connection between thalamus and OFC might have a significant impact on schizophrenia pathophysiology. OFC is involved in emotion processing and in various higher-order cognitive functions such as social cognition and decision making.…”

Section: Discussionsupporting

confidence: 63%

Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis

Cho

Shenton

Kubicki

et al. 2015

SCHBUL

106

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Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F = 5.65, P < .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofrontal cortex was significantly reduced compared to both healthy controls (F = 11.86, P < .005) and CHR (F = 6.63, P < .05). Interestingly, CHR exhibited a similar pattern as FEP, albeit with slightly reduced magnitude. Compared to healthy controls, there was a significant decrease (F = 4.16, P < .05) in CHR thalamo-orbitofrontal connectivity. Also, the strength of the thalamo-orbitofrontal connectivity was correlated with the Global Assessment of Functioning score in CHR (r = .35, P < .05). This observed pattern of white matter connectivity disruptions in FEP and in CHR suggests that this pattern of disconnectivity not only highlights the involvement of thalamus but also might be useful as an early biomarker for psychosis.

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“…This is consistent with the well-established finding of dorsolateral PFC hypofunction in patients (42). In contrast, deficits in reversal learning have been observed regardless of the current intellectual function of patients (2) and may arise from OFC dysfunctions (43, 44). In a study by Heerey and Gold, patients with schizophrenia self-reported similar depths of emotion to positive, neutral and negative stimuli than control subjects but failed at coupling their behavior to the motivational properties of a stimulus (45).…”

Section: Discussionmentioning

confidence: 99%

Mediodorsal Thalamus Hypofunction Impairs Flexible Goal-Directed Behavior

Parnaudeau

Taylor

Bolkan

et al. 2015

Biological Psychiatry

142

119

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Background Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit. Methods Using the ‘Designer Receptors Exclusively Activated by Designer Drugs’ (DREADD) system we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors including extinction, contingency degradation, outcome devaluation and Pavlovian-to-instrumental transfer (n=134 mice). Results While MD hypofunction impaired reversal learning, it did not affect the ability to learn about non-rewarded cues nor the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior. Conclusion MD hypofunction causes cognitive inflexibility reflected by an inability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility.

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Volume reduction and altered sulco-gyral pattern of the orbitofrontal cortex in first-episode schizophrenia

Cited by 70 publications

References 84 publications

Different and Shared Brain Volume Abnormalities in Late- and Early-Onset Schizophrenia

Different and Shared Brain Volume Abnormalities in Late- and Early-Onset Schizophrenia

Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis

Mediodorsal Thalamus Hypofunction Impairs Flexible Goal-Directed Behavior

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