Tetsuya Shiga

Mismatch negativity (MMN) deficiency: A break-through biomarker in predicting psychosis onset

Currently, the mismatch negativity (MMN) deficit is one of the most robust and replicable findings in schizophrenia, reflecting cognitive and functional decline, psychosocial and socio-occupational impairment, and executive dysfunction in these patients. An important break-through has very recently taken place here in the prediction of conversion to psychosis when the MMN in particular to change in tone duration was recorded in clinically at risk-mental state (ARMS) individuals. Attenuations in the MMN in these patients may be very useful in helping clinicians determine who are most likely to develop a psychotic disorder, as we will review in the present article.

Severe Psychological Distress of Evacuees in Evacuation Zone Caused by the Fukushima Daiichi Nuclear Power Plant Accident: The Fukushima Health Management Survey

Background Following the Great East Japan Earthquake on March 11, 2011, the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant has continued to affect the mental health status of residents in the evacuation zone. To examine the mental health status of evacuee after the nuclear accident, we conducted the Mental Health and Lifestyle Survey as part of the ongoing Fukushima Health Management Survey. Methods We measured mental health status using the Kessler 6-item psychological distress scale (K6) in a total of 73,569 (response rate: 40.7%) evacuees aged 15 and over who lived in the evacuation zone in Fukushima Prefecture. We then dichotomized responders using a 12/13 cutoff on the K6, and compared the proportion of K6 scores ≥13 and ≤12 in each risk factor including demographic information, socioeconomic variables, and disaster-related variables. We also performed bivariate analyses between mental health status and possible risk factors using the chi-square test. Furthermore, we performed multivariate regression analysis using modified Poisson regression models. Results The median K6 score was 5 (interquartile range: 1–10). The number of psychological distress was 8,717 (14.6%). We found that significant differences in the prevalence of psychological distress by almost all survey items, including disaster-related risk factors, most of which were also associated with increased Prevalence ratios (PRs). Additionally, we found that psychological distress in each evacuation zone was significantly positively associated with the radiation levels in their environment (r = 0.768, p = 0.002). Conclusion The earthquake, tsunami and subsequent nuclear accident likely caused severe psychological distress among residents in the evacuation zone in Fukushima Prefecture. The close association between psychological distress and the radiation levels shows that the nuclear accident seriously influenced the mental health of the residents, which might be exacerbated by increased risk perception. To provide prompt and appropriate support, continued psychosocial intervention for evacuees is strongly recommended.

Psychometric Evaluation of the Japanese Version of the Posttraumatic Stress Disorder Checklist in Community Dwellers Following the Fukushima Daiichi Nuclear Power Plant Incident

We investigated the psychometric properties of the Japanese version of the Posttraumatic Stress Disorder Checklist–Stressor Specific Version (PCL-S) using baseline data from the Fukushima Health Management Survey. A total of 26,332 men and 33,516 women aged 16 and above participated in this study. Participants lived in the Fukushima evacuation zone in Japan and experienced the Great East Japan Earthquake and nuclear power plant (NPP) incident. The PCL-S was used to assess participants’ posttraumatic stress disorder (PTSD) symptoms. In addition, we described participants and tested the validity of the PCL-S by administering the Kessler Six-item Screening Scale for Psychological Distress (K6) and assessing education; employment; self-rated health; sleep satisfaction; experiencing the earthquake, tsunami, and NPP incident; and bereavement as a result of the disaster. PCL-S scores exhibited a positively skewed, slightly leptokurtic distribution. Confirmatory factor analysis revealed that the five-factor model was a better fit than were the three- or four-factor models. The PCL-S and its subscales had high Cronbach’s alpha coefficients. The PCL-S scores had weak-to-moderate correlations with history of mental illness, bereavement, experiencing the tsunami, experiencing the NPP incident, self-rated health, and sleep satisfaction, as well as a strong correlation with psychological distress. There were significant gender and age differences in PCL-S scores. Overall, this study confirmed the psychometric properties of the PCL-S, including the score distribution, factor structure, reliability, validity, and gender and age differences. Thus, the Japanese version of the PCL-S would be a useful instrument for assessing the PTSD symptoms of community dwellers who have experienced traumatic events.

Deviance-Related Responses along the Auditory Hierarchy: Combined FFR, MLR and MMN Evidence.

The mismatch negativity (MMN) provides a correlate of automatic auditory discrimination in human auditory cortex that is elicited in response to violation of any acoustic regularity. Recently, deviance-related responses were found at much earlier cortical processing stages as reflected by the middle latency response (MLR) of the auditory evoked potential, and even at the level of the auditory brainstem as reflected by the frequency following response (FFR). However, no study has reported deviance-related responses in the FFR, MLR and long latency response (LLR) concurrently in a single recording protocol. Amplitude-modulated (AM) sounds were presented to healthy human participants in a frequency oddball paradigm to investigate deviance-related responses along the auditory hierarchy in the ranges of FFR, MLR and LLR. AM frequency deviants modulated the FFR, the Na and Nb components of the MLR, and the LLR eliciting the MMN. These findings demonstrate that it is possible to elicit deviance-related responses at three different levels (FFR, MLR and LLR) in one single recording protocol, highlight the involvement of the whole auditory hierarchy in deviance detection and have implications for cognitive and clinical auditory neuroscience. Moreover, the present protocol provides a new research tool into clinical neuroscience so that the functional integrity of the auditory novelty system can now be tested as a whole in a range of clinical populations where the MMN was previously shown to be defective.

Effective surgical intervention for schizophrenia-like symptoms and low event-related potentials caused by arachnoid cyst.

quine 200 mg/day and had remission of symptoms. She had had one major depressive episode at the age of 43 and a manic episode at 51, which had subsided under psychotropic treatment within 1 month. She was admitted to our psychiatric ward due to persecutory delusion, auditory and visual hallucination, and labile mood for 1 week. As the patient had normal serological data, no systemic lupus signs, and no abnormality on brain computed tomography (CT), both the rheumatologist and psychiatrist favored the diagnosis of bipolar I disorder with psychotic features. To control her psychotic symptoms, we first prescribed aripiprazole 15 mg/day. However, her visual and tactile hallucinations were aggravated. She often witnessed and felt water dripping on her face from the dry ceiling. Two weeks later, we switched to amisulpride 800 mg/day but there was still no improvement. Meanwhile, another major depressive episode developed, which did not respond to lamotrigine 150 mg/day and bupropion 300 mg/day augmentation. The rheumatologist still favored primary psychosis because the autoimmune profiles (anticardiolipin antibodies [IgG and IgM], C3, C4 complements, antinuclear antibody, anti-Ro, anti-La, D-D dimmer) were still within normal limits. Nevertheless, her erythrocyte sedimentation rate (ESR) was 62 mm/h. On the third rheumatologic consultation, brain magnetic resonance imaging (MRI) revealed a 0.8-cm old infarction in the left thalamus and old leukoaraiosis in periventricular white matter. Tc-ECD brain single-photon emission computed tomography (SPECT) showed bilateral ventricle dilatation, and moderate to severe hypoperfusion in bilateral frontal and parietal cerebrum. The diagnosis was modified to NPSLE. On the 90th day of admission, she was transferred to the rheumatologic ward for immunosuppressant therapy. After a 3-day course of cyclophosphamide pulse therapy, she was discharged with dramatic improvement. Although her lupus activity seemed in the remitted phase, NPSLE was most likely due to persistently vivid tactile and visual hallucination, the changeable and treatment-refractory course of psychosis and depression, abnormally high level of ESR as well as brain hypoperfusion on SPECT. The dramatic improvement under a 3-day course of cyclophosphamide pulse therapy supported our rationale. The moderate-tosevere hypoperfusion in bilateral frontal and parietal lobes could explain her psychotic and depressive symptoms. Patchy hypoperfusion in the parietal lobes and frontal lobes occurs in up to 80% and 65%, respectively, in SPECT in patients with NPSLE. The infarct and periventricular white matter changes are also common findings. Though her presentations did not fulfill the usual diagnostic criteria of SLE, the evidences strongly suggested NPSLE. Although there is still no single neurodiagnostic tool proven to be definitive in diagnosing NPSLE, we suggest that, for a patient in the remitted phase of SLE showing psychosis, the brain MRI and SPECT could be beneficial in making the differential diagnosis and further management.

Temporal integration of deviant sound in automatic detection reflected by mismatch negativity

Mismatch negativity (MMN) is an event-related potential that is elicited by deviant sounds that are presented along with frequent sounds in the absence of attention. Auditory MMN is generated by the comparison process between sensory memory trace of a frequent auditory event and a deviant event. It is well known that frequent sounds are encoded in memory trace and processed as a single unit within 160–170 ms. This study examined whether deviant sound would be similarly processed as a temporal unit. Twelve healthy men were presented with relatively short standard sounds and relatively long deviant sounds that contained an omitted (i.e. silent) part. Three types of deviant sounds were designed to vary in duration. The MMN amplitude was gradually enhanced from the short to long duration deviant events that contained an omitted part. In contrast, MMN latency showed no significant differences among the deviants. These findings show that deviant sounds are also processed as a unitary event.

Alteration of Duration Mismatch Negativity Induced by Transcranial Magnetic Stimulation Over the Left Parietal Lobe

Mismatch negativity (MMN) is generated by a comparison between an incoming sound and the memory trace of preceding sounds stored in sensory memory without any attention to the sound. N100 (N1) is associated with the afferent response to sound onset and reflects early analysis of stimulus characteristics. MMN generators are present in the temporal and frontal lobe, and N1 generators are present in the temporal lobe. The parietal lobe is involved in MMN generation elicited by a change in duration. The anatomical network connecting these areas, lateralization, and the effect of the side of ear stimulation on MMN remain unknown. Thus, we studied the effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the left parietal lobe on MMN and N1 in 10 healthy subjects. Low-frequency rTMS over the left parietal lobe decreased the amplitude of MMN following right ear sound stimulation, but the amplitude was unaffected with left ear sound stimulation. We observed no significant changes in the amplitude of N1 or the latency of MMN or N1. These results suggest that low-frequency rTMS over the left parietal lobe modulates the detection of early auditory changes in duration in healthy subjects. Stimulation that is contralateral to the side of the ear experiencing sound may affect the generation of duration MMN more than ipsilateral stimulation.

Switching antipsychotics to aripiprazole or blonanserin and plasma monoamine metabolites levels in patients with schizophrenia

Blonanserin is a novel atypical antipsychotic drug that has efficacy equal to risperidone. We investigated the effects of aripiprazole and blonanserin on clinical symptoms and plasma levels of homovanillic acid (pHVA) and 3‐methoxy‐4hydroxyphenylglycol in the switching strategy of schizophrenia.

Mental Health Status of Children After the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant Accident

The disaster at the Fukushima Daiichi Nuclear Power Plant after the Great East Japan Earthquake on March 11, 2011, might have affected the mental health status of children. To assess the mental health status, we measured the Strengths and Difficulties Questionnaire (SDQ) in 15 274 children (aged 4-15 years). The proportions of those who scored above the cutoff (≥16) of SDQ, reflecting the clinical range of the mental health status, were 25.0% (aged 4-6 years), 22.0% (aged 7-12 years, and 16.3% (aged 13-15 years), which were higher than that in the usual state (9.5%). We also explored the possibility that the distribution on the Fukushima prefectural map of the proportions of those who scored above the cutoff (≥16) of SDQ might correspond with the environmental radiation levels, but there was no significant correlation.

Temporal integration of segmented-speech sounds probed with mismatch negativity.

Deviant sounds occurring in a sequence of standard sounds, in the absence of attention, elicit an event-related potential known as mismatch negativity (MMN). Standard sounds are encoded in auditory sensory memory trace and processed as a single unit within 160–170 ms, where each unitary event stored is closely related to the temporal window of integration. The temporal window of integration of pure tone sound has already been reported. However, there are no reported correlations between segmented-speech sounds and a temporal unit. It is well known that pure tone sounds are predominantly recognized in the right hemisphere, whereas speech sounds are recognized in the left hemisphere. The aim of this study was to examine whether segmented-speech sounds were processed as a temporal unit like pure tone sounds and whether there were differences between right and left ear stimuli. Twenty-five right-handed healthy Japanese men participated in this study. Stimuli consisted of the vowel /a/ spoken by a Japanese female and the stimuli sequences were randomized from short standard sounds and three types of long deviant sounds. The stimuli were presented to both ears separately. All bilateral stimuli induced definite MMN with similar peak latencies. The MMN amplitude gradually enhanced from the short to the long duration deviant. There were no differences in MMN between the right and the left ear stimuli. These findings perhaps show that bilateral deviant segmented-speech sounds were processed equally as a temporal unit.