Mie Matsui

The effect of tandospirone, a serotonin1A agonist, on memory function in schizophrenia

BACKGROUND The purpose of this study was to test the hypothesis that the addition of tandospirone, a 5-HT(1A) partial agonist, to ongoing treatment with typical antipsychotic drugs, would improve memory function in patients with schizophrenia. METHODS Eleven outpatients (male/female = 7/4) with schizophrenia who had been on stable doses of haloperidol and biperiden were given tandospirone, 30 mg/day, for 4 weeks. The Wechsler Memory Scale-Revised (WMS-R) was administered at baseline and 4 weeks after the addition of tandospirone. The Brief Psychiatric Rating Scale (BPRS; Total, Positive, and Negative subscale scores) and the Simpson-Angus Scale for Extrapyramidal Symptoms (SAS) were also completed on the two occasions. To exclude the possibility of a practice effect on the WMS-R test, 11 age-matched patients with schizophrenia (M/F = 7/4) were tested at baseline and after a 4-week interval. RESULTS Repeated measures analysis of variance revealed a significant time by group (patients with or without tandospirone) effect for the Verbal-, but not the Visual Memory composite scores of the WMS-R test; no significant change was observed in patients without tandospirone, whereas improvement in the Verbal Memory score was noted in patients receiving tandospirone. Moreover, there was improvement in the Inclusion score, an index of memory organization as measured by the Logical Memory subtest of WMS-R, only in patients with tandospirone. Scores on the BPRS and SAS were improved during treatment with tandospirone, but the effects did not reach statistical significance. CONCLUSIONS The results suggest that adjunctive treatment with 5-HT(1A) agonists may improve some types of memory function in schizophrenia.

Lack of normal structural asymmetry of the anterior cingulate gyrus in female patients with schizophrenia: a volumetric magnetic resonance imaging study

We investigated anterior cingulate gyrus (ACG) volume in 40 patients with schizophrenia (20 males, 20 females) and 40 age-and sex-matched normal controls using three-dimensional magnetic resonance imaging (MRI). Volumes of the whole brain and both the gray and white matter of the ACG were measured on consecutive coronal 1-mm slices. There was no significant difference between the patients with schizophrenia and the normal controls in the whole brain volume. Right ACG gray matter volume was significantly reduced in the female patients with schizophrenia as compared with the female controls. Furthermore.in the female controls, ACG gray matter volume was significantly larger on the right than on the left, while this asymmetry was not significant in the female patients. ACG white matter findings were similar to those of the ACG gray matter in that the volume was significantly larger on the right in the female controls, and this normal structural asymmetry was reduced in the female patients. These results suggest that gender may play an important role in the structural asymmetry anomalies in schizophrenia.

Neural correlates of memory organization deficits in schizophrenia A single photon emission computed tomography study with 99mTc-ethyl-cysteinate dimer during a verbal learning task

Abstract Regional cerebral blood flow (rCBF) during a verbal learning task was measured using 99m Tc-ethyl-cysteinate dimer and single photon emission computed tomography in 10 patients with schizophrenia and nine normal controls. Verbal repetition was used as a control task. The schizophrenic patients showed failure to spontaneously utilize implicit category information to learn the word lists. In the normal controls, rCBF in the left inferior frontal and left anterior cingulate regions was significantly increased during the verbal learning task, compared with the verbal repetition task. In contrast, there was no significant frontal lobe activation by the verbal learning in the schizophrenic patients. The patients had lower rCBF during the verbal learning task than the controls in the bilateral inferior frontal, left anterior cingulate, right superior frontal, and bilateral middle frontal regions. Activation in the left inferior frontal region was significantly positively correlated with categorical clustering in the task in the controls, but no such correlation was found in the patients. These results indicate that memory organization deficits in schizophrenia may be related to dysfunction in the prefrontal areas, especially in the left inferior frontal region.

Quantification of lateral ventricular subdivisions in schizophrenia by high-resolution three-dimensional magnetic resonance imaging.

In vivo brain imaging and postmortem investigations have demonstrated ventricular enlargement in the brains of schizophrenic patients. However, the extent of changes in the volume of discrete ventricle subdivisions has not been clearly established. We conducted high-resolution three-dimensional magnetic resonance imaging in 40 schizophrenic patients (20 males and 20 females) and 40 healthy volunteers (20 males and 20 females). The lateral ventricle in each hemisphere was divided into the anterior horn, body, posterior horn and temporal horn. The volumes of the hemispheres, four subdivisions of the lateral ventricles and the third ventricle were measured. Compared to the control subjects, the bilateral hemisphere volumes were significantly lower in the patients than in the control subjects. In the lateral ventricular subdivisions of the male patients, the most substantial volume increase was in the left temporal horn, and volume increases were also observed in the bilateral anterior horns and the right body. The male patients also had a significantly increased volume of the third ventricle. The female patients showed similar patterns with less statistical significance. Thus, the schizophrenia patients showed ventricular enlargement, particularly in the left temporal horn, being more severely affected in the male than in the female.

Minnesota Multiphasic Personality Inventory profile characteristics of schizotypal personality disorder

Abstract The goal of the present study was to determine whether precursors for psychopathology can be found in personality dimensions of the general population. Two hundred and 62 university students were compared with 41 schizophrenic patients and 18 patients with schizotypal personality disorder (SPD) on the Minnesota Multiphasic Personality Inventory (MMPI). Schizotypal personality disorder patients showed significantly elevated Pt and Si scales compared with the schizophrenic patients. Schizophrenia and SPD groups generally produced two‐point codetypes of 6–8/8–6, 2–6/6–2, 7–8/8–7, and 7–8/8–7, 2–7/7–2, 6–8/8–6. A total of 77.5% of students had no codetype with a T‐value of ≥ 70, although the frequency of codetypes of spike 5, spike 0 and 2–7/7–2 was relatively high in the student group compared with the general population. Discriminant function analysis of the MMPI profiles revealed significant variance among the three groups. The overall rate of correct classification of the subjects into schizophrenia, SPD or university students was 90.3%. The first coefficient, mainly defined by a negative weight on the Sc scale, best distinguished the patients with either schizophrenia or SPD from the students. The second coefficient, defined by negative weights on the Sc and Si scales, and positive weights on the F and Ma scales identified patients with schizophrenia and SPD patients. The Harris‐Lingoes subscales, which are supposed to provide the profile patterns characteristic of schizotypy, well discriminated the three groups. These results suggest the usefulness of the MMPI subscales for the detection of subjects with the SPD trait.

Elucidation of developmental patterns of marmoset corpus callosum through a comparative MRI in marmosets, chimpanzees, and humans

The corpus callosum (CC) is present in all primate brains and is the major white matter tract connecting the cerebral hemispheres for integration of sensory, motor and higher-order cognitive information. The midsagittal area of the CC has frequently been used as a sensitive biomarker of brain development. Although the marmoset has been considered as an alternative non-human primate model for neuroscience research, the developmental patterns of the CC have not been explored. The present longitudinal study of magnetic resonance imaging demonstrated that marmosets show a rapid increase of CC during infancy, followed by a slow increase during the juvenile stage, as observed in chimpanzees and humans. Marmosets also show a tendency toward a greater increase in CC during late infancy and the juvenile stage, as observed in humans, but not in chimpanzees. However, several differences between marmosets and humans were identified. There was a tendency toward a greater maturation of the human CC during early infancy. Furthermore, there was a tendency toward a greater increase during late infancy and the juvenile stage in marmosets, compared to that observed in chimpanzees and humans. These differences in the developmental trajectories of the CC may be related to evolutional changes in social behavior.

Developmental trajectory of the corpus callosum from infancy to the juvenile stage: Comparative MRI between chimpanzees and humans

How brains develop during early life is one of the most important topics in neuroscience because it underpins the neuronal functions that mature during this period. A comparison of the neurodevelopmental patterns among humans and nonhuman primates is essential to infer evolutional changes in neuroanatomy that account for higher-order brain functions, especially those specific to humans. The corpus callosum (CC) is the major white matter bundle that connects the cerebral hemispheres, and therefore, relates to a wide variety of neuronal functions. In humans, the CC area rapidly expands during infancy, followed by relatively slow changes. In chimpanzees, based on a cross-sectional study, slow changes in the CC area during the juvenile stage and later have also been reported. However, little is known about the developmental changes during infancy. A longitudinal study is also required to validate the previous cross-sectional observations about the chimpanzee CC. The present longitudinal study of magnetic resonance imaging scans demonstrates that the CC development in chimpanzees and humans is characterized by a rapid increase during infancy, followed by gradual increase during the juvenile stage. Several differences between the two species were also identified. First, there was a tendency toward a greater increase in the CC areas during infancy in humans. Second, there was a tendency toward a greater increase in the rostrum during the juvenile stage in chimpanzees. The rostral body is known to carry fibers between the bilateral prefrontal and premotor cortices, and is involved in behavior planning and control, verbal working memory, and number conception. The rostrum is known to carry fibers between the prefrontal cortices, and is involved in attention control. The interspecies differences in the developmental trajectories of the rostral body and the rostrum might be related to evolutional changes in the brain systems.

Macroanatomical Landmarks Featuring Junctions of Major Sulci and Fissures and Scalp Landmarks Based on the International 10–10 System for Analyzing Lateral Cortical Development of Infants

The topographic relationships between the macroanatomical structure of the lateral cortex, including sulci and fissures, and anatomical landmarks on the external surface of the head are known to be consistent. This allows the coregistration of EEG electrodes or functional near-infrared spectroscopy over the scalp with underlying cortical regions. However, limited information is available as to whether the topographic relationships are maintained in rapidly developing infants, whose brains and heads exhibit drastic growth. We used MRIs of infants ranging in age from 3 to 22 months old, and identified 20 macroanatomical landmarks, featuring the junctions of major sulci and fissures, as well as cranial landmarks and virtually determined positions of the international 10-20 and 10-10 systems. A Procrustes analysis revealed developmental trends in changes of shape in both the cortex and head. An analysis of Euclidian distances between selected pairs of cortical landmarks at standard stereotactic coordinates showed anterior shifts of the relative positions of the premotor and parietal cortices with age. Finally, cortical landmark positions and their spatial variability were compared with 10-10 landmark positions. The results indicate that variability in the distribution of each macroanatomical landmark was much smaller than the pitch of the 10-10 landmarks. This study demonstrates that the scalp-based 10-10 system serves as a good frame of reference in infants not only for assessing the development of the macroanatomy of the lateral cortical structure, but also for functional studies of cortical development using transcranial modalities such as EEG and fNIRS.

Diosgenin-Rich Yam Extract Enhances Cognitive Function: A Placebo-Controlled, Randomized, Double-Blind, Crossover Study of Healthy Adults

Diosgenin, a yam-derived compound, was found to facilitate the repair of axonal atrophy and synaptic degeneration and improve memory dysfunction in a transgenic mouse model of Alzheimer’s disease (AD). It was also found to enhance neuronal excitation and memory function even in normal mice. We hypothesized that diosgenin, either isolated or in an extract, may represent a new category of cognitive enhancers with essential activities that morphologically and functionally reinforce neuronal networks. This study aimed to investigate the effects of a diosgenin-rich yam extract on cognitive enhancement in healthy volunteers. For this placebo-controlled, randomized, double-blind, crossover study, 28 healthy volunteers (age: 20–81 years) were recruited from Toyama Prefecture, Japan, and was randomly assigned to receive either a yam extract or placebo. Preliminary functional animal experiments indicated that an oil solvent mediated the most efficient distribution of diosgenin into the blood and brain after oral administration, and was a critical factor in the cognitive benefits. Therefore, test samples (placebo and yam extract) were prepared with olive oil and formulated as soft capsules. The intake period was 12 weeks, and a 6-week washout period separated the two crossover intake periods. The Japanese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was used for neurocognitive assessment, and the adverse effects were monitored through blood testing. Diosgenin-rich yam extract consumption for 12 weeks yielded significant increases in total RBANS score. Among the 12 individual standard cognitive subtests, diosgenin-rich yam extract use significantly improved the semantic fluency. No adverse effects were reported. The diosgenin-rich yam extract treatment appeared to safely enhance cognitive function in healthy adults.

Inflammatory markers and their possible effects on cognitive function in women with posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) has been associated with increased inflammation, albeit with some controversy. Another key feature of PTSD is compromised function in wide-ranging cognitive domains. Increased peripheral inflammation can contribute to cognitive dysfunction, although this relationship has not been studied in patients with PTSD. Here, we examined blood inflammatory markers in adult patients with PTSD compared to healthy controls taking account of potentially confounding effects of childhood maltreatment and comorbid major depressive disorder (MDD), and explored the association between inflammation and cognition. We enrolled 40 women with PTSD, most of whom developed the disorder after interpersonal violence during adulthood, and 65 healthy control women. Diagnoses were made based on DSM-IV. History of childhood maltreatment was assessed using the Childhood Trauma Questionnaire (CTQ). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Blood samples were collected for the measurement of 5 inflammatory markers including interleukin-6 (IL-6), soluble IL-6 receptor, interleukin-1β, high-sensitivity tumor necrosis factor-α, and high-sensitivity C-reactive protein. Compared to controls, patients with PTSD showed significantly higher IL-6 levels (p = 0.009) and lower scores on all RBANS domains (all p < 0.01). IL-6 levels in patients were not significantly associated with the presence/absence of comorbid MDD or CTQ scores. IL-6 levels in patients were significantly negatively correlated with RBANS visuospatial construction (p = 0.046), language (p = 0.008), attention (p = 0.036) and total score (p = 0.008). These results suggest that elevated IL-6 is associated with PTSD and that the lower cognitive function in PTSD may be due at least partly to increased inflammation.