Serum Oxytocin Levels and Logical Memory in Older People in Rural Japan.

OBJECTIVE: The present study aimed to investigate the relationship between serum oxytocin (OT) and logical memory among older people in rural Japan. METHODS: This was a cross-sectional study using a survey conducted from October 2009 through March 2011. Most of the study was conducted as part of a national prevalence survey of dementia in Japan. The final sample comprised 385 community-dwelling people aged 65 years or older living in rural Japan. The mean age and standard deviation were 75.7 ± 6.76 years (144 men, mean age 75.0 ± 6.48 years; 241 women, mean age 76.2 ± 6.91 years). The participants underwent screening examinations for a prevalence survey of dementia. The screening examinations were the Mini-Mental State Examination, Clinical Dementia Rating, and "logical memory A" from the Wechsler Memory Scale-Revised (WMSR). We used the WMSR Logical Memory II delayed recall score (LM II-DR) to assess logical memory. Levels of serum OT were obtained using the enzyme immunoassay method. RESULTS: Serum OT levels were significantly higher among women than men. The present study revealed that serum OT levels were positively associated with LM II-DR in older women living in rural Japan in multiple linear regression analyses. CONCLUSIONS: The present results suggested a positive correlation between OT and logical memory in older women living in rural Japan.

Progressive symptom-associated prefrontal volume loss occurs in first-episode schizophrenia but not in affective psychosis.

Although smaller gray matter volumes (GMV) in the prefrontal cortex (PFC) in schizophrenia and bipolar disorder have been reported cross-sectionally, there are, to our knowledge, no reports of longitudinal comparisons using manually drawn, gyrally based ROI, and their associations with symptoms. The object of this study was to determine whether first-episode schizophrenia (FESZ) and first-episode affective psychosis (FEAFF) patients show initial and progressive PFC GMV reduction in bilateral frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and examine their symptom associations. Twenty-one FESZ, 24 FEAFF and 23 healthy control subjects (HC) underwent 1.5T MRI with follow-up imaging on the same scanner ~ 1.5 years later. Groups were strikingly different in progressive GMV loss. FESZ showed significant progressive GMV loss in the left SFG, bilateral MFG, and bilateral IFG. In addition, left MFG and/or IFG GMV loss was associated with worsening of withdrawal-retardation and total BPRS symptoms scores. In contrast, FEAFF showed no significant difference in GMV compared with HC, either cross-sectionally or longitudinally. Of note, FreeSurfer run on the same images showed no significant changes longitudinally.

Effect of Excessive Coffee Consumption on the Clinical Course of a Patient With Bipolar Disorder: A Case Report and Literature Review.

OBJECTIVE: The aim of this study was to examine the impact of excessive caffeine consumption on therapeutic outcomes in bipolar disorder. METHODS AND RESULTS: We report on a case of a patient with bipolar disorder whose psychiatric symptoms were ameliorated with the elevation of lithium concentrations after the reduction of excessive daily coffee consumption, and we review the relevant literatures. CONCLUSIONS: Excessive coffee consumption may exacerbate the therapeutic course of bipolar disorder through its effects on the mechanisms underlying bipolar disorder itself, as well as by affecting the blood concentration of lithium.

An association between belief in life after death and serum oxytocin in older people in rural Japan.

OBJECTIVE: Previous research suggests that spirituality/religiosity has benefits for both mental and physical health, measured using biological indices such as cortisol and IL-6. However, there have been few studies concerning the association of religious beliefs with oxytocin, a neuropeptide hormone secreted by the pituitary. Levels of peripheral oxytocin are thought to reflect the strength of bonding and stress regulation in social relationships. As such, the oxytocin system may underpin the biological mechanisms by which belief in life after death is associated with good mental and physical health. Here, we examine associations between oxytocin and belief in life after death. METHODS: We recruited 317 community-dwelling people, aged 65 or older, without cognitive or mental deficits, and living in rural Japan. We recorded demographics, belief in life after death, and logical memory using the Wechsler Memory Scale. Levels of serum oxytocin were obtained using an enzyme immunoassay method. RESULTS: Serum oxytocin levels were higher among women than men and were negatively associated with strength of belief in life after death. CONCLUSIONS: Our findings could be interpreted differently depending on whether the anxiogenic or anxiolytic function of the oxytocin system is considered. Greater endorsement of afterlife beliefs may reduce secure attachment. Alternatively, based on the literature suggesting that basal levels of oxytocin are lower in those with reduced relational distress or anxiety, afterlife beliefs may play a role in these reductions. Copyright © 2016 John Wiley & Sons, Ltd.

Safety of Long-term Use of Lamotrigine for the Treatment of Psychiatric Disorders.

OBJECTIVES: Lamotrigine (LTG) is a drug commonly used to treat epilepsy and can also be used to manage mood disorders, such as bipolar disorder. One of the most dangerous adverse effects of LTG is skin rash, which can make early cessation necessary. Here, we examine the adverse effects associated with long-term use of LTG for the treatment of mood disorders. METHODS: Data were obtained from the medical records of 101 psychiatric patients who were prescribed long-term treatment with LTG. Patients were retrospectively divided into those who discontinued treatment within 6 months and those who continued for longer, and the groups were compared for adverse effects. We also compared the incidence of adverse effects in high and low doses. RESULTS: Fifty-four patients continued LTG treatment for 6 months or longer; 47 discontinued within 6 months. A history of allergy was more prevalent among the patients who discontinued treatment early than in those who continued. Of the patients who continued treatment for 6 months or longer, only 2 later discontinued treatment because of adverse effects. Lamotrigine monotherapy showed no difference in the incidence of adverse effects for different doses of LTG (>200 mg = 4.8% vs >100 mg, ≤200 mg = 7.7%; P = 1, vs >50 mg, ≤100 mg = 0%; P = 1 vs ≤50 mg = 0%; P = 1). CONCLUSIONS: Clinicians must be mindful of the adverse effects occurring early during the titration phase. However, long-term use of LTG was very well tolerated, even at high maintenance doses.

Aripiprazole-Associated Hypoprolactinemia in the Clinical Setting.

BACKGROUND: The increase in prolactin (PRL) levels is a common adverse effect that occurs when using conventional and atypical antipsychotic drugs. Aripiprazole (ARI) is beneficial for antipsychotic-associated hyperprolactinemia but has been reported to decrease PRL secretion. Therefore, we investigated blood levels of PRL in patients who had taken ARI alone or in combination with other antipsychotics. METHODS: Retrospective information was obtained from 25 psychiatric patients who were prescribed ARI, and the blood levels of PRL were measured. RESULTS: The incidence of hypoprolactinemia in the current study was 44.0% (11/25). Eighteen patients were treated with ARI alone and 7 received ARI in combination with other antipsychotics. The PRL value of patients who took ARI alone was significantly lower than those who were also taking other antipsychotics (5.45 ± 3.93 vs 10.85 ± 5.53, P = 0.02; mean ± SD). There was no significant correlation of the PRL levels and dose of ARI used in the 18 patients who had taken ARI alone. LIMITATIONS: This was a retrospective study, and the data were obtained from a small number of psychiatric patients treated with ARI. CONCLUSIONS: Monitoring of PRL levels in patients treated with ARI may be useful in minimizing hypoprolactinemia, which has the potential to negatively impact patients. In particular, hypoprolactinemia as a consequence of taking ARI should be discussed with patients of childbearing age and those with immune deficiencies.

A patient with Alzheimer's disease complicated by elderly-onset Cushing's syndrome who had undergone surgical treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia.

Cushing's syndrome (CS) is a rare disorder, especially in older people. Loss of brain volume and neurocognitive impairment of varying degrees has been demonstrated in patients with CS. However, there is a large difference between the median age of presentation of CS and that of Alzheimer's disease. We herein report a case of a patient with Alzheimer's disease complicated by elderly-onset CS who had undergone surgical treatment for adrenal hyperplasia. Surgical correction of hypercortisolism seems to have slowed the progression of brain volume loss and cognitive dysfunction and improved psychiatric symptoms such as visual hallucination, restlessness, and psychomotor excitement. These improvements have remarkably reduced the burden on the patient's caregivers. The present case suggests that subclinical CS may be present, particularly in rapidly progressive dementia, and that surgical treatment of CS for neuropsychiatric symptoms is useful.

Abnormal behaviours during pramipexole treatment for Cotard's syndrome: a case report.

Cotard's syndrome is a relatively rare condition that involves a delusion of negation in which an individual believes he or she has lost his or her soul, is dead, or is without functional body systems. This syndrome is observed in various neuropsychiatric disorders but most commonly in mood disorders. Pramipexole has often been used in the adjunctive treatment of both bipolar and unipolar depression, and it is known to cause rare but serious adverse effects such as compulsive behaviours in the treatment of Parkinson's disease. Here we report a case of Cotard's syndrome in treatment-resistant major depression associated with abnormal behaviours that might be caused by pramipexole. In the present case, the patient's abnormal behaviours gradually disappeared about 2 months after the discontinuation of pramipexole. The hypoperfusion in the bilateral parieto-occipital lobe found on single-photon emission computed tomography suggests the presence of Lewy body disease pathology. Nonetheless, the patient's abnormal behaviours disappeared after the discontinuation of pramipexole, indicating that they are mainly attributable to pramipexole treatment. However, the possible existence of Lewy body pathology could facilitate the emergence of abnormal behaviours after treatment with pramipexole. The patient's abnormal behaviours, such as eating other patients' food and taking her medicine before the scheduled time, might differ from typical compulsive behaviours induced by pramipexole (such as pathological gambling and hypersexuality), but they could be regarded as disinhibition. Therefore, we should follow up on the clinical course of this case carefully through neuroimaging investigation and neurocognitive assessment.

Association of inflammatory biomarkers with depressive symptoms and cognitive decline in a community-dwelling healthy older sample: a 3-year follow-up study.

BACKGROUND: The relationship between the pathophysiology of dementia and neuroinflammation is well-known. The number of reports stating that depression is a risk factor for dementia has recently been increasing. These epidemiological findings suggest the possibility that both depression and dementia have common pathophysiological backgrounds of neuroinflammation. METHODS: The sample consists of 64 non-demented community-dwelling older participants aged 65 years or over. Participants were assessed at baseline (2004-2006) and 3 years later (2007-2009). Plasma concentration of markers of inflammation (interleukins (IL)-1ß, IL-2, IL-6, soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), high sensitivity C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α) were measured at baseline. Depression symptoms were assessed with the Beck Depression Inventory (BDI) and cognitive decline was assessed with the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Clock Drawing Test (CDT) at baseline and follow-up. All analyses were adjusted for age, gender and years of education. RESULTS: In the cross-sectional analysis, the present study found soluble IL-2 receptor (sIL-2R) to be associated only with the MMSE score at baseline in men. In the longitudinal analysis, none of our inflammatory biomarkers were associated with either depressive symptoms or cognitive decline. LIMITATIONS: The present study consists of small number of participants and body mass index (BMI) scores were not obtained. CONCLUSIONS: Our findings suggest that sIL-2R is associated with current cognitive function in men. None of our inflammatory markers predicted future depressive state or cognitive decline in our community-dwelling healthy older sample.

Belief in life after death, salivary 3-methoxy-4-hydroxyphenylglycol, and well-being among older people without cognitive impairment dwelling in rural Japan.

OBJECTIVES: Research has found that spirituality/religiosity has a salutary association with mental/physical health. However, the association of belief in life after death with well-being has rarely been studied, and the same is true of its association with biological indices, such as monoamine transmitters. Therefore, we examined the associations between well-being and religiosity, salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), and demographic characteristics. METHODS: The participants were 346 community-dwelling people, aged 65 years or older, without cognitive or mental deficits, in rural Japan. Measures of religiosity consisted of belief in life after death, attachment to life, and experiences related to death and religion. The measures were assessed by scales specifically suited for Japanese religious orientations. Participants' well-being was assessed by a life satisfaction scale containing two subscales. We also measured sMHPG, a major metabolite of noradrenaline that is thought to reflect certain psychological states, such as psychomotor retardation and effortful attention. RESULTS: One subscale of life satisfaction was positively associated with belief in life after death and sMHPG, and the other life satisfaction subscale was positively associated with education and death/religion-related experiences (e.g., visiting family graves or loss of a friend). Gender differences were found in afterlife beliefs and each life satisfaction subscale. CONCLUSIONS: These results suggest that religiosity, including belief in life after death and death/religion-related experiences, is salubriously associated with mental health among older people, especially women, living in rural Japan. The basal level of sMHPG was positively associated with life satisfaction, but not with belief in life after death.

Association of salivary cortisol levels and later depressive state in elderly people living in a rural community: a 3-year follow-up study.

BACKGROUND: Late-life depressive disorder is becoming an important issue in health economics in the world, as it has been reported to be one of major risk factors for incidence of dementia. Identification of predictive markers associated with depression in later life is therefore of high priority in public health. The aim of the study was to examine the association of salivary cortisol levels with a later depressive state in elderly healthy people living in a rural Japan community. METHODS: Salivary cortisol levels were measured in 68 elderly healthy people (24 men; 44 women) followed by completion of the BDI, MMSE, and FAB from 2004 to 2006. The same cohort underwent BDI again from 2007 to 2009. RESULTS: In healthy elderly women subject, a significant positive correlation was found between salivary cortisol levels at baseline and BDI scores at follow-up, but not at baseline. Salivary cortisol levels at baseline were not correlated with the score of either MMSE or FAB. When the cut-off point of BDI scores were set at 20/21, logistic regression analyses revealed that salivary cortisol levels at baseline had a significant positive relationship with a later depressive state. Age and gender were also significantly related with a later depressive state. LIMITATIONS: The present study involves small number of participants. CONCLUSIONS: Higher salivary cortisol levels were associated with a later depressive state in elderly healthy women living in rural community. Salivary cortisol might be a predictive marker for a later depressive state in elderly women.

Prefrontal cortex volume deficit in schizophrenia: a new look using 3T MRI with manual parcellation.

In this study we use high resolution Magnetic Resonance imaging (MRI) and apply rigorous manual tracing criteria in order to assess volumetrically the prefrontal cortex (PFC) in schizophrenia. Previous MRI studies suggested PFC is included in neural systems necessary for emotional processing and cognition, and regional PFC abnormalities might, thus, lead to specific negative symptoms, as well as a frequent association of poorer performance in category switching. The aim of this study was to use 3T imaging and reliable manual parcellation to determine if, as hypothesized, this higher precision would reveal additional MRI abnormalities in PFC in schizophrenia, and an association between PFC abnormalities and specific negative symptoms, as well as in category switching. Using 3-T MRI, 27 schizophrenia patients and 27 healthy controls were examined. PFC was manually parcellated into frontal pole, superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Left SFG (p=0.004), bilateral MFG (left: p=0.007; right: p=0.007), and bilateral IFG (left: p<0.001; right: p=0.002) showed volume reduction. There were symptom associations between smaller left MFG volumes and more affective flattening (R=-0.465, p=0.015), and smaller left IFG volumes and poorer performance on the alternating semantic category test (R=0.440, p=0.025). In summary, 3-T imaging revealed widespread gyral volume deficits in PFC gyri, and specific associations with selective negative symptoms, such as affective flattening, and with deficits in cognitive switching.

Disruption of function-structure coupling in brain regions sub-serving self monitoring in schizophrenia.

Deficits in self monitoring are a core feature of cognitive dysfunction in schizophrenia, and may be the basis for disturbances of self and lack of insight, ultimately impacting social functioning. However, the functional and structural neural correlates of such deficits in self monitoring are not well understood. We investigated this issue using measurements of neurophysiological and structural brain indices, i.e., error-related and correct-response negativity (ERN & CRN) of event-related potentials, and gray matter volume of the anterior cingulate cortex (ACC), and tested whether the association between these indices is altered in patients with schizophrenia. Participants consisted of 18 male patients with chronic schizophrenia and 18 healthy male controls. The 2 groups did not differ in ERN amplitude. In contrast, schizophrenia patients showed significantly larger CRN amplitudes than did healthy subjects. Although the 2 groups did not significantly differ in gray matter volume of the ACC subregions, a significant negative correlation was found between ERN amplitudes at the frontocentral electrodes and absolute gray matter volumes of the left cognitive region of ACC only in healthy controls. These results suggest a disruption of function-structure coupling of the brain regions sub-serving self monitoring in schizophrenia.

Alzheimer's disease: diagnosis by different methods of voxel-based morphometry.

PURPOSE: The purpose of this study was to determine the optimal computational options in voxel-based morphometry (VBM) for discrimination between Alzheimer's disease (AD) patients and healthy control (HC) subjects. MATERIALS AND METHODS: Structural magnetic resonance images of 24 AD patients and 26 HC subjects were analyzed using VBM to determine brain regions with significant gray matter (GM) loss due to AD. The VBM analyses were performed with 4 different computational options: gray matter concentration (GMC) analysis with and without global normalization, and gray matter volume (GMV) analysis, with and without global normalization. Statistical maps calculated with the 4 computational options were obtained at 3 different P-value thresholds (P < 0.001, P < 0.0005, and P < 0.0001, uncorrected for multiple comparisons), yielding a total of 12 sets of maps, from which regions-of-interest (ROI) were generated for subsequent analyses of performance in terms of discrimination between AD patients and HC subjects as based on the mean value of either the GMC or GMV within the ROI for each of the 12 maps. Discrimination performance was evaluated by means of comparing the area-under-the-curve derived from the receiver-operating characteristic analysis as well as on the accuracy of the discrimination. RESULTS: Discrimination based on GMC analysis resulted in better performance than that based on GMV analysis. The best discrimination performance was achieved with GMC analysis either with or without proportional global normalization. CONCLUSION: The findings suggested that GMC-based VBM is better suited than GMV-based VBM for discrimination between AD patients and HC subjects.

Simultaneous arterial spin labeling cerebral blood flow and morphological assessments for detection of Alzheimer's disease.

RATIONALE AND OBJECTIVES: The relative roles of arterial spin-labeling (ASL) perfusion imaging and magnetic resonance morphological assessment in diagnosing Alzheimer's disease (AD) have not been established. Our purposes were to directly compare the diagnostic performance of ASL regional cerebral blood flow (rCBF) measurement and that of morphological assessment, and to determine whether or not the combination of the two methods improves diagnostic performance. MATERIALS AND METHODS: We analyzed 23 consecutive, retrospectively identified AD patients and 23 healthy control subjects. For each subject, both high-resolution T1-weighted images and ASL perfusion images were obtained. A linear discriminant analysis was performed to distinguish the AD patients from the control subjects based on the three imaging parameters: 1) globally normalized gray matter (GM) density determined by voxel-based morphometry (VBM) procedures, 2) normalized rCBF calculated from ASL data, and 3) the combination of the two. The discriminative abilities of these methods were evaluated by the area under the curve (AUC) derived from receiver-operating characteristics analysis. RESULTS: The morphological assessment based on the globally normalized GM density resulted in an AUC of 0.779, whereas ASL-normalized rCBF analysis achieved better performance (AUC = 0.893). The combination of the two methods performed better (AUC = 0.919) than either method alone. CONCLUSION: Normalized rCBF measurement by ASL may perform better than morphological analysis based on the VBM procedure in discriminating AD patients from healthy control subjects. The combination of the two approaches was more effective than either method alone.

Deterioration of abstract reasoning ability in mild cognitive impairment and Alzheimer's disease: correlation with regional grey matter volume loss revealed by diffeomorphic anatomical registration through exponentiated lie algebra analysis.

OBJECTIVE: To determine which brain regions are relevant to deterioration in abstract reasoning as measured by Raven's Colored Progressive Matrices (CPM) in the context of dementia. METHODS: MR images of 37 consecutive patients including 19 with Alzheimer's disease (AD) and 18 with amnestic mild cognitive impairment (aMCI) were retrospectively analyzed. All patients were administered the CPM. Regional grey matter (GM) volume was evaluated according to the regimens of voxel-based morphometry, during which a non-linear registration algorithm called Diffeomorphic Anatomical Registration Through Exponentiated Lie algebra was employed. Multiple regression analyses were used to map the regions where GM volumes were correlated with CPM scores. RESULTS: The strongest correlation with CPM scores was seen in the left middle frontal gyrus while a region with the largest volume was identified in the left superior temporal gyrus. Significant correlations were seen in 14 additional regions in the bilateral cerebral hemispheres and right cerebellum. CONCLUSION: Deterioration of abstract reasoning ability in AD and aMCI measured by CPM is related to GM loss in multiple regions, which is in close agreement with the results of previous activation studies.

Uncinate fasciculus abnormalities in recent onset schizophrenia and affective psychosis: a diffusion tensor imaging study.

Two of the most frequently investigated regions in diffusion tensor imaging studies in chronic schizophrenia are the uncinate fasciculus (UF) and cingulum bundle (CB). The purpose of the present study was to determine whether UF and CB white matter integrity were altered at the early stage of illness and specific to schizophrenia. Fifteen schizophrenia subjects and 15 affective psychosis within 4 years of first hospitalization (12 patients with schizophrenia and 12 patients with affective psychosis during their first hospitalization), and 15 psychiatrically healthy controls underwent line-scan diffusion tensor imaging. Fractional anisotropy (FA) and mean diffusivity (D(m)) were used to quantify water diffusion, and cross-sectional area was defined with a directional threshold method. Bilaterally reduced FA, but not D(m), was present in the UF of schizophrenia compared with healthy controls. Affective psychosis was intermediate between schizophrenia subjects and healthy controls, but not significantly different from either. For CB, there was no significant group difference for FA or D(m). These findings suggest that UF, but not CB, white matter integrity is altered at the early stage of illness in schizophrenia although it may not be specific to schizophrenia. The CB abnormalities reported in chronic schizophrenia may develop during the later course of the disease.

Relationship between saliva level of 3-methoxy-4-hydroxyphenylglycol and mental health in the elderly general population.

AIMS: A large number of studies on the monoamine systems in Alzheimer's disease (AD) have found abnormalities of the noradrenergic system in the brain, but there has been no report concerning the relationship between noradrenergic activity and cognitive function in elderly living in a community. The aim of the present study was to explore the relationship between saliva level of 3-methoxy-4-hydroxyphenylglycol (sMHPG) and mental health in this population. METHODS: The study was to examine the relationship between sMHPG and performance on the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Beck Depression Inventory (BDI) in 213 elderly people living in the local community. RESULTS: sMHPG in female subjects was positively correlated with age (r = 0.24, P = 0.003) and negatively correlated with scores on the MMSE (r = -0.26, P = 0.0016) and FAB (r = -0.19, P = 0.024), even after controlling for the effect of age (MMSE r = -0.20, P = 0.013). Notably, sMHPG was correlated with the pentagon drawing score (P = 0.0008) of MMSE. sMHPG was significantly correlated with BDI score in male subjects, but negatively correlated in female subjects. A gender difference was found in the relationship between the sMHPG and BDI score. CONCLUSION: The measurement of sMHPG may be a useful marker of mental health in elderly community-dwelling subjects.

Orbitofrontal volume deficit in schizophrenia and thought disorder.

Orbitofrontal Cortex (OFC) structural abnormality in schizophrenia has not been well characterized, probably due to marked anatomical variability and lack of consistent definitions. We previously reported OFC sulcogyral pattern alteration and its associations with social disturbance in schizophrenia, but OFC volume associations with psychopathology and cognition have not been investigated. We compared chronically treated schizophrenia patients with healthy control (HC) subjects, using a novel, reliable parcellation of OFC subregions and their association with cognition, especially the Iowa Gambling Task (IGT), and with schizophrenic psychopathology including thought disorder. Twenty-four patients with schizophrenia and 25 age-matched HC subjects underwent MRI. OFC Regions of Interest (ROI) were manually delineated according to anatomical boundaries: Gyrus Rectus (GR); Middle Orbital Gyrus (MiOG); and Lateral Orbital Gyrus (LOG). The OFC sulcogyral pattern was also classified. Additionally, MiOG probability maps were created and compared between groups in a voxel-wise manner. Both groups underwent cognitive evaluations using the IGT, Wisconsin Card Sorting Test, and Trail Making Test (TMT). An 11% bilaterally smaller MiOG volume was observed in schizophrenia, compared with HC (F(1,47) = 17.4, P = 0.0001). GR and LOG did not differ, although GR showed a rightward asymmetry in both groups (F(1,47) = 19.2, P < 0.0001). The smaller MiOG volume was independent of the OFC sulcogyral pattern, which differed in schizophrenia and HC (chi2 = 12.49, P = 0.002). A comparison of MiOG probability maps suggested that the anterior heteromodal region was more affected in the schizophrenia group than the posterior paralimbic region. In the schizophrenia group, a smaller left MiOG was strongly associated with worse 'positive formal thought disorder' (r = -0.638, P = 0.001), and a smaller right MiOG with a longer duration of the illness (r = -0.618, P = 0.002). While schizophrenics showed poorer performance than HC in the IGT, performance was not correlated with OFC volume. However, within the HC group, the larger the right hemisphere MiOG volume, the better the performance in the IGT (r = 0.541, P = 0.005), and the larger the left hemisphere volume, the faster the switching attention performance for the TMT, Trails B (r = -0.608, P = 0.003). The present study, applying a new anatomical parcellation method, demonstrated a subregion-specific OFC grey matter volume deficit in patients with schizophrenia, which was independent of OFC sulcogyral pattern. This volume deficit was associated with a longer duration of illness and greater formal thought disorder. In HC the finding of a quantitative association between OFC volume and IGT performance constitutes, to our knowledge, the first report of this association.