The cumulative incidence of and risk factors for morphometric severe vertebral fractures in Japanese men and women: the ROAD study third and fourth surveys.

This population-based cohort study with a 3-year follow-up revealed that the annual incidence rates of vertebral fracture (VF) and severe VF (sVF) were 5.9%/year and 1.7%/year, respectively. The presence of mild VF at the baseline was a significant risk factor for incident sVF in participants without prevalent sVF. INTRODUCTION: This study aimed to estimate the incidence of morphometric vertebral fracture (VF) and severe VF (sVF) in men and women and clarify whether the presence of a mild VF (mVF) increases the risk of incident sVF. METHODS: Data from the population-based cohort study, entitled the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study, were analyzed. In total, 1190 participants aged ≥ 40 years (mean age, 65.0 ± 11.2) years completed whole-spine lateral radiography both at the third (2012-2013, baseline) and fourth surveys performed 3 years later (2015-2016, follow-up). VF was defined using Genant's semi-quantitative (SQ) method: VF as SQ ≥ 1, mVF as SQ = 1, and sVF as SQ ≥ 2. Cumulative incidence of VF and sVF was estimated. Multivariate logistic regression analyses were performed to evaluate risk factors for incident sVF. RESULTS: The baseline prevalence of mVF and sVF were 16.8% and 6.0%, respectively. The annual incidence rates of VF and sVF were 5.9%/year and 1.7%/year, respectively. The annual incidence rates of sVF in participants without prevalent VF, with prevalent mVF, and with prevalent sVF were 0.6%/year, 3.8%/year, and 11.7%/year (p < 0.001), respectively. Multivariate logistic regression analyses in participants without prevalent sVF showed that the adjusted odds ratios for incident sVF were 4.12 [95% confident interval 1.85-9.16] and 4.53 [1.49-13.77] if the number of prevalent mVF at the baseline was 1 and ≥ 2, respectively. CONCLUSIONS: The annual incidence rates of VF and sVF were 5.9%/year and 1.7%/year, respectively. The presence of prevalent mVF was an independent risk factor for incident sVF.

Incidence rate and risk factors for radiographic hip osteoarthritis in Japanese men and women: a 10-year follow-up of the ROAD study.

OBJECTIVE: To investigate the incidence and progression rate of radiographic hip osteoarthritis (OA) and its risk factors in Japanese men and women using a large-scale population of a nationwide cohort study, Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: From the baseline survey of the ROAD study, 2,975 participants (1,043 men and 1,932 women) aged 23-94 years (mean, 70.2 years) living in urban, mountainous, and coastal communities were followed up with hip radiography at 3, 7, and 10 years (mean follow-up, 7.1 years). Radiographs were scored using the Kellgren/Lawrence (K/L) grading system, and radiographic hip OA was defined as K/L ≥ 2. The incidence and progression rate of hip OA were examined. Acetabular dysplasia was defined as a central-edge angle <20°. Cox's proportional hazard model was used to assess risk factors for incident and progressive radiographic hip OA. RESULTS: The incidence rate of radiographic hip OA was 5.6/1,000 person-years and 8.4/1,000 person-years in men and women, respectively. The progression rate of hip OA was 2.2/1,000 person-years and 6.0/1,000 person-years in men and women, respectively. The significant risk factors for incident hip OA were age, obesity, and acetabular dysplasia at baseline (hazard risk [HR] 1.05, 95% confidence interval [CI] 1.03-1.08; 1.78, 1.10-2.75; 2.06, 1.30-3.17, respectively). The significant risk factors for progressive hip OA were baseline hip pain and acetabular dysplasia (HR 5.68, 95%CI 1.07-22.61; 14.78, 3.66-56.06, respectively). CONCLUSION: Continued longitudinal surveys of the ROAD study will contribute to knowledge about and potential prevention of incident and progressive hip OA.

Do sarcopenia and/or osteoporosis increase the risk of frailty? A 4-year observation of the second and third ROAD study surveys.

In this 4-year follow-up study including 1083 subjects (≥ 60 years), the prevalence of frailty was estimated to be 5.6%; osteoporosis was found to be significantly associated with frailty. Moreover, the presence of both osteoporosis and sarcopenia increased the risk of frailty compared to the presence of osteoporosis or sarcopenia alone. INTRODUCTION: This study aims to examine the contribution of sarcopenia and osteoporosis to the occurrence of frailty using 4-year follow-up information of a population-based cohort study. METHODS: The second survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study was conducted between 2008 and 2010; 1083 subjects (aged ≥ 60 years, 372 men, 711 women) completed all examinations on frailty, sarcopenia, and osteoporosis, which were defined using Fried's definition, Asian Working Group for Sarcopenia criteria, and WHO criteria, respectively. The third survey was conducted between 2012 and 2013; 749 of 1083 individuals enrolled from the second survey (69.2%, 248 men, 501 women) completed assessments identical to those in the second survey. RESULTS: The prevalence of frailty in the second survey was 5.6% (men, 3.8%; women, 6.6%). The cumulative incidence of frailty was 1.2%/year (men, 0.8%/year; women, 1.3%/year). After adjustment for confounding factors, logistic regression analysis indicated that osteoporosis was significantly associated with the occurrence of frailty (odds ratio, 3.07; 95% confidence interval, 1.26-7.36; p = 0.012). Moreover, the occurrence of frailty significantly increased according to the presence of osteoporosis and sarcopenia (odds ratio vs. neither osteoporosis nor sarcopenia: osteoporosis alone, 2.50; osteoporosis and sarcopenia, 5.80). CONCLUSIONS: Preventing osteoporosis and coexistence of osteoporosis and sarcopenia may help reduce the risk of frailty.

High-resolution copy number variation analysis of schizophrenia in Japan.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (<100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio=3.04, P=9.3 × 10-9, 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e.g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio=2.79, P=0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e.g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

Radiographic measurements of the hip joint and their associations with hip pain in Japanese men and women: the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study.

OBJECTIVE: To investigate radiographic measurements of the hip joint and their associations with hip pain, and the prevalence of acetabular dysplasia defined by radiographic measurements of the hip joint in Japanese men and women using the large-scale population-based cohort of the Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study. METHODS: From the baseline survey of the ROAD study (cross-sectional study), 2963 participants (1040 men, 1923 women; mean age, 70.2 years) were analyzed. All participants underwent radiographic examinations of both hips using an anteroposterior view under weight-bearing. Minimum joint space width (mJSW), central-edge (CE) angle, acetabular depth-to-width ratio (ADR), and acetabular head index (AHI) were measured. Associations between these radiographic measurements and hip pain were assessed by calculating odds ratios (ORs) using multivariable logistic-regression analysis. Acetabular dysplasia was defined as a CE angle <20°. RESULTS: Mean radiographic measurements of the hip joint for men were: mJSW, 3.8 mm; CE angle, 30.6°; ADR, 262.1 per 1000; and AHI, 81.4%. For women, these values were: mJSW, 3.4 mm; CE angle, 29.9°; ADR, 262.7 per 1000; and AHI, 81.2%. Associations were seen between hip pain and each of mJSW, CE angle, ADR, and AHI (OR 4.52, 95% confidence interval 3.45-5.97; 1.14, 1.11-1.18; 1.31, 1.24-1.40; and 1.15, 1.12-1.18, respectively). Acetabular dysplasia showed an overall prevalence of 13.9%, and was significantly more prevalent in women than in men (P = 0.012). CONCLUSION: The present study of radiographic measurements of the hip joint showed that mJSW, CE angle, ADR, and AHI were associated with hip pain.

Is osteoporosis a predictor for future sarcopenia or vice versa? Four-year observations between the second and third ROAD study surveys.

In a 4-year follow-up study that enrolled 1099 subjects aged ≥60 years, sarcopenia prevalence was estimated at 8.2%. Moreover, the presence of osteoporosis was significantly associated with short-term sarcopenia occurrence, but the reciprocal relationship was not observed, suggesting that osteoporosis would increase the risk of osteoporotic fracture and sarcopenia occurrence. INTRODUCTION: The present 4-year follow-up study was performed to clarify the prevalence, incidence, and relationships between sarcopenia (SP) and osteoporosis (OP) in older Japanese men and women. METHODS: We enrolled 1099 participants (aged, ≥60 years; 377 men) from the second survey of the Research on Osteoarthritis/Osteoporosis against Disability (ROAD) study (2008-2010) and followed them up for 4 years. Handgrip strength, gait speed, skeletal muscle mass, and bone mineral density were assessed. SP was defined according to the Asian Working Group for Sarcopenia. OP was defined based on the World Health Organization criteria. RESULTS: SP prevalence was 8.2% (men, 8.5%; women, 8.0%) in the second survey. In those with SP, 57.8% (21.9%; 77.6%) had OP at the lumbar spine L2-4 and/or femoral neck. SP cumulative incidence was 2.0%/year (2.2%/year; 1.9%/year). Multivariate regression analysis revealed that OP was significantly associated with SP occurrence within 4 years (odds ratio, 2.99; 95% confidence interval, 1.46-6.12; p < 0.01), but the reciprocal relationship was not significantly observed (2.11; 0.59-7.59; p = 0.25). CONCLUSIONS: OP might raise the short-term risk of SP incidence. Therefore, OP would not only increase the risk for osteoporotic fracture but may also increase the risk for SP occurrence.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Prevalence of radiographic hip osteoarthritis and its association with hip pain in Japanese men and women: the ROAD study.

OBJECTIVE: Although hip osteoarthritis (OA) is a major cause of hip pain and disability in elderly people, few epidemiologic studies have been performed. We investigated the prevalence of radiographic hip OA and its association with hip pain in Japanese men and women using a large-scale population of a nationwide cohort study, Research on Osteoarthritis/osteoporosis Against Disability (ROAD). METHODS: From the baseline survey of the ROAD study, 2975 participants (1043 men and 1932 women), aged 23-94 years (mean 70.2 years), living in urban, mountainous, and coastal communities were analyzed. The radiographic severity at both hips was determined by the Kellgren/Lawrence (K/L) grading system. Radiographic hip OA was defined as K/L ≥ 2, and severe radiographic hip OA as K/L ≥ 3. RESULTS: The crude prevalence of radiographic hip OA was 18.2% and 14.3% in men and women, respectively, that of severe radiographic hip OA was 1.34% and 2.54%, and that of symptomatic K/L ≥ 2 OA was 0.29% and 0.99%, respectively. The crude prevalence of hip OA, including severe OA, was not age-dependent in men or women. Male sex was a risk factor for radiographic hip OA, whereas female sex was a risk factor for severe radiographic hip OA and hip pain. Compared with K/L = 0/1, hip pain was significantly associated with K/L ≥ 3, but not with K/L = 2. CONCLUSION: The present cross-sectional study revealed the prevalence of radiographic hip OA and severe hip OA in Japanese men and women. Hip pain was strongly associated with K/L ≥ 3.

Double seismic zone for deep earthquakes in the izu-bonin subduction zone.

A double seismic zone for deep earthquakes was found in the Izu-Bonin region. An analysis of SP-converted phases confirms that the deep seismic zone consists of two layers separated by approximately 20 kilometers. Numerical modeling of the thermal structure implies that the hypocenters are located along isotherms of 500 degrees to 550 degrees C, which is consistent with the hypothesis that deep earthquakes result from the phase transition of metastable olivine to a high-pressure phase in the subducting slab.

Differential amygdala response during facial recognition in patients with schizophrenia: an fMRI study.

Human lesion or neuroimaging studies suggest that amygdala is involved in facial emotion recognition. Although impairments in recognition of facial and/or emotional expression have been reported in schizophrenia, there are few neuroimaging studies that have examined differential brain activation during facial recognition between patients with schizophrenia and normal controls. To investigate amygdala responses during facial recognition in schizophrenia, we conducted a functional magnetic resonance imaging (fMRI) study with 12 right-handed medicated patients with schizophrenia and 12 age- and sex-matched healthy controls. The experiment task was a type of emotional intensity judgment task. During the task period, subjects were asked to view happy (or angry/disgusting/sad) and neutral faces simultaneously presented every 3 s and to judge which face was more emotional (positive or negative face discrimination). Imaging data were investigated in voxel-by-voxel basis for single-group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM). No significant difference in task accuracy was found between the schizophrenic and control groups. Positive face discrimination activated the bilateral amygdalae of both controls and schizophrenics, with more prominent activation of the right amygdala shown in the schizophrenic group. Negative face discrimination activated the bilateral amygdalae in the schizophrenic group whereas the right amygdala alone in the control group, although no significant group difference was found. Exaggerated amygdala activation during emotional intensity judgment found in the schizophrenic patients may reflect impaired gating of sensory input containing emotion.

Functional asymmetry of human prefrontal cortex in verbal and non-verbal episodic memory as revealed by fMRI.

Functional neuroimaging studies have demonstrated preferential involvement of bilateral prefrontal cortex during episodic memory encoding and retrieval. The aim of the present study is to address the question whether left prefrontal model for encoding holds when highly non-verbal material is used, and which region of the brain is critically related to successful retrieval. To do this, seven normal subjects were investigated using functional magnetic resonance imaging (fMRI) during encoding and retrieval of word and checkerboard pattern. Our results revealed that word encoding activated the left prefrontal cortices and right cerebellum, whereas pattern encoding activated the bilateral middle frontal gyrus, superior parietal lobule, premotor area, and occipital visual cortex. Word-specific activation was found in the ventral prefrontal cortices, and pattern-specific activation located in the right dorsal prefrontal cortex. Conjunction analysis during encoding of word and pattern showed that activity in the left dorsal prefrontal cortex and the right cerebellum might relate to common neural network for encoding regardless of the type of material. Finally, the present study demonstrates strong association between the left ventral prefrontal cortex and retrieval success for word. The evidence, that both encoding and retrieval of words activated the left ventral prefrontal cortex, indicates that this area is involved in active and strategic operation of the mnemonic representation. A lack of the right prefrontal activation during retrieval was interpreted as that activity in this region might relate to retrieval effort rather than success.

An fMRI study of the functional neuroanatomy of picture encoding in younger and older adults.

Age-related changes in the neural mechanisms of picture encoding were investigated using functional magnetic resonance imaging (fMRI). Seven younger and seven older adults were studied while they were encoding pairs of concrete-related, concrete-unrelated, and abstract pictures. Functional (T2*-weighted) and anatomical (T1-weighted) images of the brain were obtained using a 1.5 T MRI scanner. The results in the younger adults showed that the left dorsal prefrontal cortex (PFC) was activated during associative learning of the concrete-unrelated or abstract pictures. The results also suggest that both ventral and dorsal visual pathways are involved in the encoding of abstract pictures, and that the right superior parietal lobule likely mediates spatial information of the abstract pictures. The older adults showed significant activation in the left dorsal PFC under concrete-unrelated and abstract conditions. However, the older adults failed to activate either the left ventral and right dorsal PFC under the concrete-unrelated condition, or the parietal areas under abstract condition. A direct comparison between the two age groups demonstrates that the older adults had a reduced activation in the bilateral parieto-temporo-occipital areas under abstract condition, and in the right temporo-occipital area extending to the fusiform gyrus under the concrete-unrelated condition. Finally, age difference was found in correlation between memory performance and amplitude of signal change in the parahippocampal gyrus and fusiform gyrus under the concrete-unrelated and abstract conditions. These changes in neural response likely underlie the age-related memory decline in relation to pictorial information.

Brain regions involved in verbal or non-verbal aspects of facial emotion recognition.

To depict the neural substrates for facial emotion recognition and to determine whether their activation is confounded by a verbal factor, we studied eight normal volunteers with functional magnetic resonance imaging (fMRI). Verbal and non-verbal sample stimuli were used in a facial emotion matching task and a gender matching task (control condition). Compared with the gender tasks, the emotion tasks significantly activated the right ventral prefrontal cortex, the right lingual cortex, and the left lateral fusiform cortex, irrespective of sample stimuli. The visual association cortices showed a significant interaction between the task and the material presented, as the activation for verbal materials was higher than for non-verbal materials during the emotion matching tasks. By contrast, no significant interaction was found in the right ventral prefrontal cortex. These results suggest that the verbal factor has a different effect on the neural networks for facial emotion, processing.

Quantitative regional cerebral flow measured by Tc-99M HMPAO SPECT in mood disorder.

Depressed (n = 14) and remitted (n = 9) patients with mood disorder, patients with depressive disorder not otherwise specified (NOS; n = 10) and normal subjects (n = 8) underwent non-invasive and quantitative measurement of cerebral blood flow using HMPAO and SPECT in a resting state. The mean and regional cerebral blood flow (CBF) in twelve ROIs were compared among the four groups and correlations between CBF and the depressive symptoms were studies. The CBF was computed using graphical analysis on the SPECT console after a bolus injection of Tc-99m HMPAO and radionuclide angiography. The depressed group had significantly lower mCBF in the bilateral hemisphere and rCBF in all except one of the ROIs than the NOS and normal group. Significant negative correlations were found between the Hamilton scale for depression and rCBF in the bilateral lower frontal cortex after correcting for age in the mood disorder. Parallel analysis using both the quantitative and semiquantitative methods revealed that the former provided more global reduction of CBF in mood disorder. These results indicate that mean and regional CBF measured by this non-invasive method contributes to the objective evaluation of depressive symptoms. Negative correlations between HRSD and rCBF in the frontal regions indicate that frontal hypoactivity is closely related to depressive symptoms.

Proliferative activity of canine mast cell tumours evaluated by bromodeoxyuridine incorporation and Ki-67 expression.

The proliferative activity of 91 canine mast cell tumours was assessed on the basis of the Ki-67 positive index (Ki-67 PI) and mitotic index (MI) and, in 15 cases, also by the labelling index of bromodeoxyuridine (BrdU; an analogue of tritiated thymidine) incorporated in vivo into S-phase cells. BrdU and Ki-67 were detected immunohistochemically. The tumours were graded histologically (I, II or III). The BrdU labelling index (BrdU LI) tended to increase as the grade became higher. In terms of the mean values of Ki-67 PI, significant differences were found between histological tumour grades I and II (P < 0.01) and between grades II and III (P < 0.01). In terms of mean MI, grades I and II were found to differ significantly (P < 0.05). With Spearman rank correlation coefficient and linear regression analysis, the BrdU LI and Ki-67 PI showed a highly significant correlation. This strong correlation indicated that Ki-67 was, like BrdU, a useful marker for proliferative potential in canine mast cell tumours; moreover, its use did not require the prior administration of any reagent to the live animal.

[Brain MRI hyperintense lesions and cerebrovascular risk factors in the elderly].

It is known that asymptomatic MRI lesions of the brain are found in elderly subjects, but the significance of the lesions has not been determined. In previous reports, the prevalence of MRI lesions varied from 11% to 59%, but many of the authors indicated a close relationship with cerebrovascular risk factors. We evaluated 76 elderly subjects (over 60 years old, average age +/- SD was 66.7 +/- 4.5) without a history of cerebrovascular disease and dementia, and determined the prevalence of periventricular (PVH), white matter (WMH) and pontine (PH) hyperintensity and risk factors. The severity of MRI lesion was evaluated in T2-weighted images by Fazekas' scoring method of MRI hyperintense lesions. PVH, WMH and PH were graded visually from 0 to 3 by the author and these points are added to the MRI score. In T1-weighted images, we also measured the diameter of the third ventricle, frontal horn and body of the lateral ventricle. Our results were that 62% of subjects had PVH, 64% had WMH and 8% had PH. In regard to risk factors, 38% of subjects had hypertension, 17% had diabetes mellitus, 8% had ischemic heart disease. The PVH (+) group was significantly older (p<0.01) and had larger lateral ventricles (p<0.05) than the PVH (-) group. The WMH (+) group was significantly older (p<0.05) and had higher risk of cerebrovascular disease (p<0.05) than the WMH (-) group. The MRI score was related, but not significantly, to a history of hypertension, diabetes mellitus and ischemic heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Common variants at 1p36 are associated with superior frontal gyrus volume.

The superior frontal gyrus (SFG), an area of the brain frequently found to have reduced gray matter in patients with schizophrenia, is involved in self-awareness and emotion, which are impaired in schizophrenia. However, no genome-wide association studies of SFG volume have investigated in patients with schizophrenia. To identify single-nucleotide polymorphisms (SNPs) associated with SFG volumes, we demonstrated a genome-wide association study (GWAS) of gray matter volumes in the right or left SFG of 158 patients with schizophrenia and 378 healthy subjects. We attempted to bioinformatically ascertain the potential effects of the top hit polymorphism on the expression levels of genes at the genome-wide region. We found associations between five variants on 1p36.12 and the right SFG volume at a widely used benchmark for genome-wide significance (P<5.0 × 10(-8)). The strongest association was observed at rs4654899, an intronic SNP in the eukaryotic translation initiation factor 4 gamma, 3 (EIF4G3) gene on 1p36.12 (P=7.5 × 10(-9)). No SNP with genome-wide significance was found in the volume of the left SFG (P>5.0 × 10(-8)); however, the rs4654899 polymorphism was identified as the locus with the second strongest association with the volume of the left SFG (P=1.5 × 10(-6)). In silico analyses revealed a proxy SNP of rs4654899 had effect on gene expression of two genes, HP1BP3 lying 3' to EIF4G3 (P=7.8 × 10(-6)) and CAPN14 at 2p (P=6.3 × 10(-6)), which are expressed in moderate-to-high levels throughout the adult human SFG. These results contribute to understand genetic architecture of a brain structure possibly linked to the pathophysiology of schizophrenia.

Signal hyperintensities on brain magnetic resonance imaging in elderly depressed patients.

In a retrospective brain magnetic resonance imaging study, we evaluated the prevalence and severity of signal hyperintensities in 30 elderly depressed patients and 30 controls matched for age, sex and cerebrovascular risk factors. A semiquantitative scoring method was used to grade findings in T2-weighted and proton density images. The elderly depressed patients had more extended periventricular hyperintensities, especially in the frontal region (depressed vs. control, 87 vs. 57%, p < 0.05), pons (33 vs. 7%, p < 0.05) as well as hyperintensities in the putamen and globus pallidus (57 vs. 27%, p < 0.05). The third ventricle was more dilated in depressed patients than controls after adjustment for age and cerebrovascular risk factors. The global index for ventricular enlargement was correlated significantly (r = 0.36, p < 0.05) with the severity of the hyperintensity in depressed patients. Our results indicate that these hyperintensities, especially in the frontal region, pons and lenticular nuclei, and the dilatation of the third ventricle play an important role, through the frontal-subcortical circuits, in mood regulation of elderly depressed patients.

The effect of divided attention on encoding and retrieval in episodic memory revealed by positron emission tomography.

The effects of divided attention (DA) on episodic memory encoding and retrieval were investigated in 12 normal young subjects by positron emission tomography (PET). Cerebral blood flow was measured while subjects were concurrently performing a memory task (encoding and retrieval of visually presented word pairs) and an auditory tone-discrimination task. The PET data were analyzed using multivariate Partial Least Squares (PLS), and the results revealed three sets of neural correlates related to specific task contrasts. Brain activity, relatively greater under conditions of full attention (FA) than DA, was identified in the occipital-temporal, medial, and ventral-frontal areas, whereas areas showing relatively more activity under DA than FA were found in the cerebellum, temporo-parietal, left anterior-cingulate gyrus, and bilateral dorsolateral-prefrontal areas. Regions more active during encoding than during retrieval were located in the hippocampus, temporal and the prefrontal cortex of the left hemisphere, and regions more active during retrieval than during encoding included areas in the medial and right-prefrontal cortex, basal ganglia, thalamus, and cuneus. DA at encoding was associated with specific decreases in rCBF in the left-prefrontal areas, whereas DA at retrieval was associated with decreased rCBF in a relatively small region in the right-prefrontal cortex. These different patterns of activity are related to the behavioral results, which showed a substantial decrease in memory performance when the DA task was performed at encoding, but no change in memory levels when the DA task was performed at retrieval.