Katsuya Ohta

Diurnal fluctuation of sleep propensity and hormonal secretion across the menstrual cycle

BACKGROUND The fact that most women experience sleep changes across the menstrual cycle is thought to be associated with changes in circadian rhythms; however, few studies have investigated this relationship. METHODS We applied an ultrashort sleep-wake schedule to eight healthy women and studied diurnal fluctuations in sleep propensity, sleepiness, rectal temperature, and serum concentrations of melatonin, thyroid-stimulating hormone, and cortisol in the follicular and luteal phases. RESULTS In the luteal phase, amplitude of core body temperature, total melatonin secretions, and amplitudes of TSH and cortisol rhythms were significantly decreased, whereas sleepiness and occurrence of slow-wave sleep during the daytime were significantly increased. Differences in the amount of daytime slow-wave sleep across the menstrual cycle were positively correlated with differences in the daily mean rectal temperature. CONCLUSIONS The findings suggest that the amplitude of circadian oscillation may be dampened in the luteal phase. Increased daytime sleepiness in the luteal phase may be associated with increased daytime slow-wave sleep, due possibly to changes in thermoregulation in the luteal phase.

Stability of exploratory eye movements as a marker of schizophrenia-A WHO multi-center study

The exploratory eye movements of patients with schizophrenia reportedly differ from those of patients without schizophrenia and healthy controls. In an attempt to determine whether exploratory eye movements provide valid markers for schizophrenia, the present collaborative study was conducted in six countries to analyze the stability of and variation in the following parameters of exploratory eye movements: the number of eye fixations (NEFs) and mean eye scanning length (MESL) in a retention task; the cognitive search score (CSS) that indicates how frequently the eye focused on each important area of a figure in order to recognize it in a comparison task; and the responsive search score (RSS), which reflects the frequency of eye fixations on each section of a figure in response to questioning in a comparison task. In addition, we investigated the validity of the currently employed discriminant function to extract a common feature of schizophrenia by applying it to the findings of the present study. The exploratory eye movements of 145 patients with schizophrenia, 116 depressed patients and 124 healthy controls at seven WHO collaborative centers in six countries were measured using eye mark recorders during viewing of stationary S-shaped figures in two sequential tasks. The RSSs of patients with schizophrenia were found to be significantly lower than those of depressed patients or healthy controls irrespective of geographical location, with no significant difference existing between the RSSs for depressed patients and those for healthy controls. By inserting the RSS and NEF data for each subject into the formula used to calculate discriminant function, patients with schizophrenia could be discriminated from depressed patients and healthy controls with a sensitivity of 89.0% and a specificity of 86.7%. The RSS is an exploratory eye movement parameter that detected schizophrenia irrespective of culture, race and various other subject variables. Furthermore, it is indicative of the stable, significant difference that exists between subjects with and without schizophrenia. The results of discriminant analysis confirm the previously reported validity of discriminant function.

Cognitive dysfunction in systemic lupus erythematosus

Abstract  Systemic lupus erythematosus (SLE) is an autoimmune‐mediated collagen disease that results in multiorgan failure. It is the collagen disease most frequently associated with neuropsychiatric symptoms, which have been hypothesized to stem from certain types of cognitive dysfunction. Subjects were 21 patients with SLE (one man, 20 women; aged 16–55 years; mean age, 35.1 ± 10.7 years) who were undergoing treatment in the rheumatology unit of a general hospital, and 17 healthy control subjects matched to the patient group with respect to age and gender (two men, 15 women; mean age, 35.9 ± 6.3 years). They were administered various tests of cognitive function including verbal reasoning, non‐verbal reasoning, verbal memory, non‐verbal memory, attention and mental flexibility, psychomotor speed and frontal lobe function. In addition, the SLE patients were tested for antiphospholipid antibodies. The SLE patients performed worse than the control group on immediate, delayed and interference of the Rey verbal test and paired associate tests of Wechsler Memory Scale, and their reaction time was slower in Trail A and Trail B tests. Moreover, these findings were more pronounced in the group with major neuropsychiatric symptoms. However, no relationship was apparent between these deficits in cognitive function and the presence or absence of antiphospholipid antibodies. The results suggest that verbal memory and psychomotor speed underlie the neuropsychiatric symptoms seen in SLE patients.

Regional cerebral blood flow in depressed patients with white matter magnetic resonance hyperintensity

BACKGROUND Functional neuroimaging studies have consistently demonstrated decreased regional cerebral blood flow (rCBF) or metabolism in the frontal lobe, temporal lobe, or anterior cingulate gyrus of depressed patients. On the other hand, white matter hyperintensity as defined by magnetic resonance imaging (MRI) has been the most consistently replicated finding in structural neuroimaging studies on depression; however, these functional and structural neuroimaging findings of depression have not been well integrated. We aimed to clarify the possible associations of MRI-defined subcortical hyperintensities with rCBF changes in depressed patients. METHODS Twelve depressed patients with subcortical hyperintensities defined by MRI, 11 depressed patients without MRI hyperintensities, and 25 healthy volunteers underwent 99mTc ECD SPECT. Group comparisons of their rCBF and correlation analysis between MRI hyperintensity and rCBF in patients were performed with a voxel-based analysis using statistical parametric mapping (SPM) software. RESULTS Depressed patients showed decreased rCBF compared with control subjects in the frontal lobe, temporal lobe, and anterior cingulate gyrus whether subcortical hyperintensity existed or not; however, the patients with MRI hyperintensity showed decreased rCBF in the thalamus, basal ganglia, and brainstem in addition to cortical areas. Further, the score for white matter hyperintensity correlated negatively with rCBF in subcortical brain structures, including the thalamus and right basal ganglia. CONCLUSION Our study indicates that depressed patients with MRI hyperintensities may have dysfunction in subcortical brain structures in addition to dysfunction in the fronto-temporal cortical structures.

An event-related potential study in schizophrenia using Japanese sentences

To examine the neurophysiological and cognitive characteristics of language disorder in schizophrenia, the N400 component and late positive component (LPC) of event-related potentials (ERPs) were investigated in medicated schizophrenic patients and health comparison subjects. The subjects were required to indicate whether Japanese sentence completions were semantically congruous or incongruous. The ERPs for the range of 300-500 ms to the incongruous completions contained a more negative component (N400), followed by LPC, which was inversely more positive for the incongruous than congruous condition. The N400 effect and the mean amplitude of the LPC were reduced in the patients. The attenuated N400 effect in schizophrenics mainly originated from an enhanced negativity for the congruous completions, suggesting that the use of context is poor in schizophrenia.

Exploratory eye movement dysfunctions in patients with schizophrenia: possibility as a discriminator for schizophrenia

In our previous studies patients with schizophrenia and their parents had less frequent eye fixations and a more limited area of inspection than normal controls while freely viewing stationary S-shaped figures. The present study attempted to discriminate schizophrenics from non-schizophrenics using exploratory eye movements. Two groups (A and B) were formed, each comprising 30 schizophrenic and 70 non-schizophrenic subjects (10 each of patients with depression, methamphetamine psychosis, alcohol psychosis, anxiety disorder, temporal lobe epilepsy, frontal lobe lesions and healthy normal controls). Discriminant analysis was performed on group A to obtain a discriminant. The validity of applying this discriminant to group B was investigated. By focussing on exploratory eye movements, schizophrenics could be discriminated from non-schizophrenics with a sensitivity of 76.7% and a specificity of 81.4%. These results show that exploratory eye movements are a useful discriminator for schizophrenia.

Attentional processing of emotional information in obsessive-compulsive disorder

In order to investigate attentional processing of emotional information in obsessive–compulsive disorder (OCD), 14 patients with OCD and 28 normal control (NC) subjects were asked to name the background colors of anxiety‐relevant, compulsion‐relevant, positive and neutral words (an emotional Stroop color‐naming test). The stimulus words were presented subliminally, and supraliminally. The time of subliminal presentation for each subject was determined in advance by the lexical decision task. In the subliminal condition, the delay for anxiety‐ and compulsion‐relevant words, when compared with neutral words, was greater in OCD patients, while no difference was found in NC subjects. In the supraliminal condition, no delay was found for both OCD patients and NC subjects. In other words, OCD patients were more sensitive to threat information when it could not be identified with consciousness. Moreover, the present study compared checking OCD with cleaning OCD in the attentional processing of emotional information. As a result, it was found that checking OCD patients responded more slowly in naming the background color of subliminal emotional words than cleaning OCD patients. The results indicate that OCD patients, especially with checking compulsion, may have a deficit in automatic processing of threat information.

Association of an orexin 1 receptor 408Val variant with polydipsia-hyponatremia in schizophrenic subjects.

BACKGROUND Primary polydipsia is a common complication in patients with chronic psychoses, particularly schizophrenia. Disease pathogenesis is poorly understood, but one contributory factor is thought to be dopamine dysregulation caused by prolonged treatment with neuroleptics. Both angiotensin-converting enzyme (ACE) and orexin (hypocretin) signaling can modulate drinking behavior through interactions with the dopaminergic system. METHODS We performed association studies on the insertion/deletion (I/D) sequence polymorphism of ACE and single nucleotide polymorphisms within the prepro-orexin (HCRT), orexin receptor 1 (HCRTR1), and orexin receptor 2 (HCRTR2) genes. Genotypes were determined by polymerase chain reaction amplification, followed by either electrophoretic separation or direct sequencing. RESULTS The ACE I/D polymorphism showed no association with polydipsic schizophrenia. Screening of the orexin signaling system detected a 408 isoleucine to valine mutation in HCRTR1 that showed significant genotypic association with polydipsic-hyponatremic schizophrenia (p = .012). The accumulation of this mutation was most pronounced in polydipsic versus nonpolydipsic schizophrenia (p = .0002 and p = .008, for the respective genotypic and allelic associations). The calcium mobilization properties and the protein localization of mutant HCRTR1 seem to be unaltered. CONCLUSION Our preliminary data suggest that mutation carriers might have an increased susceptibility to polydipsia through an undetermined mechanism.

Epileptic Seizure Prediction Based on Multivariate Statistical Process Control of Heart Rate Variability Features

Objective: The present study proposes a new epileptic seizure prediction method through integrating heart rate variability (HRV) analysis and an anomaly monitoring technique. Methods: Because excessive neuronal activities in the preictal period of epilepsy affect the autonomic nervous systems and autonomic nervous function affects HRV, it is assumed that a seizure can be predicted through monitoring HRV. In the proposed method, eight HRV features are monitored for predicting seizures by using multivariate statistical process control, which is a well-known anomaly monitoring method. Results: We applied the proposed method to the clinical data collected from 14 patients. In the collected data, 8 patients had a total of 11 awakening preictal episodes and the total length of interictal episodes was about 57 h. The application results of the proposed method demonstrated that seizures in ten out of eleven awakening preictal episodes could be predicted prior to the seizure onset, that is, its sensitivity was 91%, and its false positive rate was about 0.7 times per hour. Conclusion: This study proposed a new HRV-based epileptic seizure prediction method, and the possibility of realizing an HRV-based epileptic seizure prediction system was shown. Significance: The proposed method can be used in daily life, because the heart rate can be measured easily by using a wearable sensor.

Attention disorders in schizophrenia

Abstract  In order to clarify the feature of attention disorders in schizophrenia, two tasks (X and AX) of the Continuous Performance Test (CPT) were given to 36 schizophrenic patients and 25 healthy controls. The schizophrenic patients performed considerably less well than normal controls. Performances were expressed in indices such as omission and commission errors, reaction time and discriminability. Among errors, omission in both the X and AX tasks was found to be an index that varied in reaction time, indicating difficulty in sustaining attention. Omission was found to act as a state‐dependent index of schizophrenia in relation to inattentiveness in clinical settings and emotional disturbance in interpersonal situations. Commission, in contrast, differed between the two tasks, acting as an index of disinhibition of reaction in the X task, and of disturbance of the capacity and allocation of attention in the AX task. Commission was also thought to be an index related to thought disorder during episodes of acute schizophrenia, that is, it reflects an essential pathology in schizophrenia.