Mihoko Nakamura

Increased Frontal Gyrification Negatively Correlates with Executive Function in Patients with First-Episode Schizophrenia

Abstract Previous neuroimaging studies of gyrification, a possible marker of early neurodevelopment, in schizophrenia patients have reported inconsistent results. In addition, it remains unclear whether aberrant gyrification in schizophrenia patients, if present, is associated with cognitive impairment, which is one of the core features of schizophrenia. Magnetic resonance images were obtained from 62 patients with first‐episode schizophrenia and 57 healthy control subjects. Using FreeSurfer software, local gyrification index (LGI) of the entire cortex was compared between the groups. The relationship between LGI and performance in the Wisconsin Card Sorting Test (WCST) was also examined in a subgroup of patients (n= 28). Compared with the controls, the patients showed a significantly higher LGI in a wide range of bilateral frontal regions as well as in the right inferior parietal and bilateral occipital regions. The number of WCST categories archived in patients was negatively correlated with the LGI mainly in the rostral middle frontal and anterior cingulate regions in the right hemisphere. Our findings suggested a widespread hypergyrification pattern in schizophrenia patients, which supported early neurodevelopmental abnormalities. Our results also suggested that executive dysfunction in schizophrenia patients may be at least partly related to aberrant neurodevelopment, especially in the right frontal regions.

Possible relation between olfaction and anxiety in healthy subjects

While olfaction is a sense closely associated with the limbic system and emotions, the relation between emotional status and olfactory functioning has not been well documented. This study aimed to examine the possible effect of anxiety on olfaction in healthy subjects.

The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain neurodevelopmental markers in schizophrenia and healthy subjects

Increasing evidence has implicated the role of Disrupted-in-Schizophrenia-1 (DISC1), a potential susceptibility gene for schizophrenia, in early neurodevelopmental processes. However, the effect of its genotype variation on brain morphologic changes related to neurodevelopmental abnormalities in schizophrenia remains largely unknown. This magnetic resonance imaging study examined the association between DISC1 Ser704Cys polymorphism and a range of brain neurodevelopmental markers [cavum septi pellucidi (CSP), adhesio interthalamica (AI), olfactory sulcus depth, and sulcogyral pattern (Types I, II, III, and IV) in the orbitofrontal cortex (OFC)] in an all Japanese sample of 75 schizophrenia patients and 87 healthy controls. The Cys carriers had significantly larger CSP than the Ser homozygotes for both schizophrenia patients and healthy controls. The Cys carriers also exhibited a reduction in the Type I pattern of the right OFC in the healthy controls, but not in the schizophrenia patients. The DISC1 Ser704Cys polymorphism did not affect the AI and olfactory sulcus depth in either group. These results suggested a possible role of the DISC1 genotype in the early neurodevelopment of human brains, but failed to show its specific role in the neurodevelopmental pathology of schizophrenia.

Reduced Thickness of the Anterior Cingulate Cortex in Individuals With an At-Risk Mental State Who Later Develop Psychosis

BACKGROUND Despite the fact that only a part of the individuals with at-risk mental state (ARMS) for psychosis do develop psychosis, biological markers of future transition to psychosis have not been well documented. Structural abnormality of the anterior cingulate gyrus (ACG), which probably exists prior to the onset of psychosis, could be such a risk marker. METHODS We conducted a multicenter magnetic resonance imaging (MRI) study of 3 scanning sites in Japan. 1.5-T 3D MRI scans were obtained from 73 ARMS subjects and 74 age- and gender-matched healthy controls. We measured thickness, volume, and surface area of the ACG using labeled cortical distance mapping and compared these measures among healthy controls, ARMS subjects who later converted to overt psychosis (ARMS-C), and those who did not (ARMS-NC). RESULTS Seventeen of 73 (23%) ARMS subjects developed overt psychosis within the follow-up period. The thickness of the left ACG was significantly reduced in ARMS-C relative to healthy subjects (P = .026) while both ARMS-C (P = .001) and ARMS-NC (P = .01) had larger surface areas of the left ACG compared with healthy controls. CONCLUSION Further studies will be needed to identify potential markers of future transition to psychosis though cortical thinning of the ACG might be one of the candidates.

Decreased number of orbital sulci in schizophrenia spectrum disorders.

An altered orbitofrontal sulcogyral pattern has been reported in the schizophrenia-spectrum, but it remains unknown whether they also have differences in the number of intermediate and posterior orbital sulci compared with healthy subjects. This magnetic resonance imaging study investigated the number of these sulci in 102 schizophrenia patients, 47 schizotypal disorder patients, and 84 controls. Both patient groups had a significantly lower number of both sulci bilaterally compared with controls, which was weakly associated with the severity of negative symptoms. Our results may reflect the neurodevelopmental pathology related to vulnerability to psychosis.

Brain neurodevelopmental markers related to the deficit subtype of schizophrenia

Deficit schizophrenia is a homogeneous subtype characterized by a trait-like feature of primary and prominent negative symptoms, but the etiologic factors related to this specific subtype remain largely unknown. This magnetic resonance imaging study aimed to examine gross brain morphology that probably reflects early neurodevelopment in 38 patients with deficit schizophrenia, 37 patients with non-deficit schizophrenia, and 59 healthy controls. Potential brain neurodevelopmental markers investigated in this study were the adhesio interthalamica (AI), cavum septi pellucidi (CSP), and surface morphology (i.e., olfactory sulcus depth, sulcogyral pattern, and number of orbital sulci) of the orbitofrontal cortex (OFC). The subtype classification of schizophrenia patients was based on the score of Proxy for the Deficit Syndrome. The deficit schizophrenia group had a significantly shorter AI compared with the non-deficit group and controls. The deficit group, but not the non-deficit group, was also characterized by an altered distribution of the OFC sulcogyral pattern, as well as fewer posterior orbital sulcus compared with controls. Other neurodevelopmental markers did not differentiate the deficit and non-deficit subgroups. These results suggest that the deficit subtype of schizophrenia and its clinical manifestation may be at least partly related to prominent neurodevelopmental pathology.

Surface morphology of the orbitofrontal cortex in individuals at risk of psychosis: a multicenter study

Changes in the surface morphology of the orbitofrontal cortex (OFC), such as a fewer orbital sulci and altered sulcogyral pattern of the ‘H-shaped’ orbital sulcus, have been reported in schizophrenia, possibly reflecting abnormal neurodevelopment during gestation. However, whether high-risk subjects for developing psychosis also exhibit these gross morphologic anomalies is not well documented. This multicenter MRI study from four scanning sites in Japan investigated the distribution of the number of intermediate and posterior orbital sulci, as well as the OFC sulcogyral pattern, in 125 individuals with an at-risk mental state (ARMS) [of whom 22 later developed psychosis (ARMS-P) and 89 did not (ARMS-NP)] and 110 healthy controls. The ARMS group as a whole had a significantly lower number of intermediate and posterior orbital sulci compared with the controls, which was associated with prodromal symptomatology. However, there was no group difference in OFC pattern distribution. The ARMS-P and -NP groups did not differ in OFC surface morphology. These results suggest that gross morphology of the OFC in high-risk subjects may at least partly reflect neurodevelopmental pathology related to vulnerability to psychosis.

Quality of life in individuals with attenuated psychotic symptoms: Possible role of anxiety, depressive symptoms, and socio-cognitive impairments

Individuals with Clinical High-Risk state for Psychosis (CHR-P) are reported to exhibit impaired quality of life (QOL) similar to that observed in schizophrenia, but its determinants remain unclear. We investigated the QOL of 33 subjects with CHR-P, 45 patients with schizophrenia, and 63 healthy subjects using the Quality of Life Scale (QLS). The CHR-P and schizophrenia groups were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) for socio-cognitive functions; and the Positive and Negative Syndrome Scale (PANSS) and the State-Trait Anxiety Inventory for clinical symptoms. The CHR-P group was also assessed using the Beck Depression Inventory. The CHR-P and schizophrenia groups had a significantly lower QLS score to the same degree compared with controls, which was predominantly associated with the SOFAS, SCoRS, and PANSS negative/general scores. For the CHR-P, the severity of anxiety and depressive symptoms was also correlated with a lower QLS score. Regression analyses demonstrated that the QLS score was predicted by SOFAS (for both groups) and SCoRS (for CHR-P) scores. Our findings suggest the importance of addressing socio-cognitive dysfunctions as well as anxiety and depressive symptoms for better QOL in CHR-P.

S178. ALTERED GYRIFICATION IN THE SCHIZOPHRENIA SPECTRUM

Abstract Background Increased gyrification in diverse cortical areas has been reported in patients with schizophrenia, which is considered to reflect deviations in early neurodevelopment. Schizotypal personality disorder (SPD) is thought to be a prototypic disorder within the schizophrenia spectrum, which shares biological and psychological commonalities with schizophrenia as a neurobiological basis for vulnerability factors. However, to the best of our knowledge, no magnetic resonance imaging (MRI) studies have investigated the gyrification pattern in SPD. Methods T1-weighted structural MRI scans were obtained by 1.5-T scanner from 101 patients with schizophrenia, 46 patients with SPD, and 77 age- and gender- matched healthy control subjects. Using FreeSurfer software (version 5.3.), the local gyrification indices (LGIs) of entire cortex were obtained with the method of Schaer and colleagues. Clinical symptoms of the patients were rated with the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) at the time of scanning. A general linear model controlling for age, gender, medication dose, and duration of medication was used to compare the LGIs across the groups and to conduct vertex-by-vertex whole brain LGI correlation analyses with clinical variables. This study was approved by the Committee on the Medical Ethics of Toyama University based on the declaration of Helsinki. After a complete description of the study was provided, written informed consent was obtained from all subjects. Results Compared with the controls, the patients with schizophrenia showed significantly higher LGI in widespread cortical areas including the bilateral frontal, parietal, and occipital regions. The patients with SPD demonstrated significantly higher LGI in the bilateral frontal and left parietal regions compared with the controls. Compared with the patients with SPD, the patients with schizophrenia showed significantly higher LGI in the left occipital and right frontal regions. Both SAPS and SANS total scores were positively correlated with LGI in the bilateral temporal regions in patients with schizophrenia, and were negatively correlated with LGI in the bilateral occipital regions in patients with SPD. Discussion Increased LGI in the bilateral frontal regions may be the common morphological substrates for the schizophrenia spectrum, possibly representing vulnerability to schizophrenia. In addition, increased LGI in the left occipital and right frontal regions preferentially observed in schizophrenia may have a critical role in manifestation of florid psychotic symptoms.

Olfactory deficits in individuals at risk for psychosis and patients with schizophrenia: relationship with socio-cognitive functions and symptom severity

Odor identification deficits are well documented in patients with schizophrenia, but it remains unclear whether individuals at clinical high-risk for psychosis exhibit similar changes and whether their olfactory function is related to social/cognitive functions and symptomatology. In this study, we investigated odor detection sensitivity and identification ability in 32 individuals with at-risk mental state (ARMS), 59 schizophrenia patients, and 169 healthy controls using a T&T olfactometer. The ARMS and schizophrenia subjects were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) to assess their cognitive and social functions, and the Positive and Negative Syndrome Scale (PANSS) for clinical symptoms. Both the ARMS and schizophrenia subjects had lower odor identification ability when compared with healthy controls, while no significant difference was found in the odor detection sensitivity. The lower odor identification ability in the ARMS group correlated with the severity of negative symptoms and weakly correlated with lower performance on the BACS verbal fluency test. The olfactory measures of schizophrenia patients did not correlate with illness duration, medication, symptom severity, and social and cognitive functions. For the ARMS and schizophrenia groups, the olfactory measures did not correlate with the SOFAS and SCoRS scores. These findings suggest that high-risk subjects for psychosis already show odor identification deficits similar to those observed in schizophrenia patients, which probably reflect a biological trait related to vulnerability to psychosis.