Yoshinori Mizokami

Low risk of male suicide and lithium in drinking water.

OBJECTIVE Recently, several epidemiologic studies reported that lithium in drinking water may be associated with lower rates of suicide mortality at the population level, but other studies failed to confirm the association. The objective of the present study is to determine whether lithium in drinking water is associated with lower suicide rate after adjustment of potential confounding factors. METHOD From 2010 to 2013, 274 mean lithium levels of 434 lithium samples in drinking water were examined in relation to suicide standardized mortality ratios (SMRs) in 274 municipalities of Kyushu Island in Japan. Weighted least squares regression analysis adjusted for the size of each population was used to investigate the association of lithium levels with suicide SMRs. The associations of lithium levels in drinking water with suicide SMRs (total, male, and female) were investigated adjusting for proportion of elderly people, proportion of 1-person households, proportion of people with college education or more, and proportion of people engaging in primary industry (adjusted model 1), and further adjustment was performed with overall unemployment rate, annual marriage rate, annual mean temperature, and annual postal savings per person (adjusted model 2). RESULTS Lithium levels in drinking water were significantly (β = -.169, P = .019) and inversely associated with male suicide SMRs but not total or female SMRs in the adjusted model 2. CONCLUSIONS The present findings suggest that lithium in drinking water may be associated with the low risk of male suicide in the general population. Further studies are required to confirm these findings and investigate gender differences.

Trace lithium is inversely associated with male suicide after adjustment of climatic factors.

BACKGROUND Previously, we showed the inverse association between lithium in drinking water and male suicide in Kyushu Island. The narrow variation in meteorological factors of Kyushu Island and a considerable amount of evidence regarding the role of the factors on suicide provoked the necessities of adjusting the association by the wide variation in sunshine, temperature, rain fall, and snow fall. METHODS To keep the wide variation in meteorological factors, we combined the data of Kyushu (the southernmost city is Itoman, 26°) and Hokkaido (the northernmost city is Wakkanai, 45°). Multiple regression analyses were used to predict suicide SMRs (total, male and female) by lithium levels in drinking water and meteorological factors. RESULTS After adjustment of meteorological factors, lithium levels were significantly and inversely associated with male suicide SMRs, but not with total or female suicide SMRs, across the 153 cities of Hokkaido and Kyushu Islands. Moreover, annual total sunshine and annual mean temperature were significantly and inversely associated with male suicide SMRs whereas annual total rainfall was significantly and directly associated with male suicide SMRs. LIMITATIONS The limitations of the present study include the lack of data relevant to lithium levels in food and the proportion of the population who drank tap water and their consumption habits. CONCLUSIONS The present findings suggest that trace lithium is inversely associated with male but not female suicide after adjustment of meteorological factors.

Hyperthymic temperament and brightness judgment in healthy subjects: Involvement of left inferior orbitofrontal cortex

BACKGROUND Hyperthymic temperament has been generally accepted as one of premorbid temperament of bipolar disorders. Since recent several studies indicate an association between illuminance and hyperthymic temperament, it can be hypothesized that more hyperthymic temperament subjects have a different threshold of brightness or darkness perception in comparison with less hyperthymic temperament subjects. METHODS We compared the threshold of brightness and darkness judgment between more and less hyperthymic subjects, and by simultaneously using fMRI we compared activations of whole brain between these subjects by two sample t-test. Furthermore, the association between the activations and hyperthymic temperament scores was analyzed. RESULTS Although there was no significant difference in the threshold of brightness or darkness judgment between more and less hyperthymic subjects, there was a significant difference in activations of the regions including left superior temporal gyrus, left inferior orbitofrontal cortex, left triangular inferior frontal gyrus and left insula between these subjects. Moreover, there was a significantly positive association between a cluster containing left inferior orbitofrontal cortex and hyperthymic temperament scores. The common activated region of these two analyses (categorical and continuous ones) was determined as left inferior orbitofrontal cortex. LIMITATIONS Limitation of the present study is a lack of brightness and darkness preference experiment between more and less hyperthymic subjects. CONCLUSIONS The present findings suggest that the threshold of brightness and darkness judgment is not different between more and less hyperthymic subjects, and that hyperthymic temperament may be associated with left inferior orbitofrontal cortex, which has been reported to be associated with bipolar disorder.

Difference in brain activations during appreciating paintings and photographic analogs

Several studies have investigated neural correlates of aesthetic appreciation for paintings but to date the findings have been heterogeneous. This heterogeneity may be attributed to previous studies’ measurement of aesthetic appreciation of not only the beauty of paintings but also the beauty of motifs of the paintings. In order to better elucidate the beauty of paintings, it seems necessary to compare aesthetic appreciation of paintings and photographic analogs which included corresponding real images. We prepared for famous painters’ pictures and their photographic analogs which were set up to resemble each painting in order to investigate the hypothesis that there exist specific neural correlates associated with the aesthetic appreciation for paintings. Forty-four subjects participated in functional magnetic resonance study which required comparisons of aesthetic appreciation of paintings of still life and landscape versus photographic analogs including corresponding real images of still life and landscape. Bilateral cuneus and the left lingual gyrus were activated in the comparison of aesthetic appreciation of paintings versus photographic analogs. In conclusion, the present findings suggest a possibility of the existence of specific neural correlates associated with the aesthetic appreciation for paintings and that bilateral cuneus and the left lingual gyrus may be involved.

Therapeutic Window of Lamotrigine for Mood Disorders: A Naturalistic Retrospective Study

INTRODUCTION Lamotrigine is widely used for mood disorders including bipolar disorder and major depression, but its therapeutic levels have yet to be determined. This study was conducted to investigate the hypothesis that lamotrigine may have a therapeutic window for mood disorders. METHODS 25 patients with mood disorders received lamotrigine for more than one year during which time plasma lamotrigine levels were measured at least once. Their mental state was retrospectively and regularly but blindly assessed using the Clinical Global Impression-Severity (CGI-S) scale. In order to investigate our hypothesis, we depicted the relationship between the last lamotrigine levels and the last CGI scores in 25 patients. If any, the potential therapeutic window was further investigated. RESULTS The relationship between the last lamotrigine levels and the last CGI scores in the 25 patients indicated the presence of a therapeutic window of lamotrigine from 5 to 11 μg/mL. The repeated measures of ANOVA reached a significant tendency of the effects of lamotrigine levels within 5-11 μg/mL on better CGI-S scores, and the CGI-S scores at the last observation of the 15 patients whose lamotrigine levels were within 5-11 μg/mL were significantly better than those of 10 patients whose lamotrigine levels were not within 5-11 μg/mL. CONCLUSION These findings suggest that lamotrigine may have a therapeutic window for patients with mood disorder from 5 to 11 μg/mL.

Risk factors for suicide in Japan: A model of predicting suicide in 2008 by risk factors of 2007

BACKGROUND This study aims to comprehensively investigate the causal relationship between suicide and its risk factors in a longitudinal design. METHODS A model was derived in which suicide rate in 2008 was longitudinally and comprehensively predicted by potential risk factors recorded one year before (2007) which included personal and interpersonal factors, medical factors, economic factors, climate factors, alcoholic factors, and ω-3 fatty-acid factors. RESULTS In males, elderly population rate and complete unemployment rate predicted SMR of suicide significantly and positively whereas marriage rate and annual postal savings per person predicted SMR of suicide significantly and negatively. Also in females, complete unemployment rate predicted SMR of suicide significantly and positively whereas annual mean temperature predicted SMR of suicide significantly and negatively. LIMITATIONS The limitations of this study are that predictions are based on the data of only the recent two years, that these epidemiological data cannot be always extrapolated to individuals, and that other factors should be taken into consideration to female suicide. CONCLUSIONS The present findings suggest that male suicide may be accounted for by older age, more complete employment rate, less marriage rate and less annual postal savings whereas female suicide may be accounted for by more complete employment rate and lower annual mean temperature.

Association between affective temperaments and regional gray matter volume in healthy subjects.

BACKGROUND Affective temperaments such as cyclothymic and hyperthymic temperaments have been regarded as potential antecedents of bipolar disorder but the neural substrates underlying these temperaments have not been identified. The aim of this study is to determine whether these temperaments are associated with specific neural substrates in regional brain morphology in healthy subjects. METHODS We conducted a cross-sectional neuroimaging study of 60 healthy subjects (30 males and 30 females) with affective temperaments. All participants underwent the Mini-International Neuropsychiatric Interview (MINI) to screen for the past and present psychiatric disorder. The scores of cyclothymic and hyperthymic temperaments were measured by the Temperament Scale of Memphis, Pisa, Paris and San Diego-Autoquestionnaire. We analyzed the association between voxel-based morphometry of the brain and these affective temperaments. RESULTS Subjects classified as having high cyclothymic scores had a significantly larger gray matter volume of the left medial frontal gyrus (MFG) than low cyclothymic subjects. High hyperthymic males also had significantly larger gray matter volume of the left MFG than low hyperthymic males, but there was no difference in females. Subjects with both high cyclothymic and high hyperthymic temperaments demonstrated significantly larger gray matter volume of the left MFG than their counterparts. Region of interest analysis revealed that peaks of these clusters showed a significant positive correlation of the regional volume with temperament scores. LIMITATIONS The subjects were relatively young and the number was relatively small. Due to the nature of a cross-sectional research design, we could not determine the causal relationship between temperament and the volume changes. CONCLUSIONS These findings suggest that cyclothymic and hyperthymic temperaments in healthy subjects may have their morphological basis in the left MFG.

Type A behavior pattern: Bortner scale vs. Japanese-original questionnaires

BACKGROUND Type A behavior pattern (TABP) has been regarded as a putative risk factor for coronary heart disease and recent studies from our group suggest that TABP individuals, identified via the Bortner scale whose validity had been confirmed by structured interviews, may have a greater tendency towards hyperthymic temperament, shorter sleep time and shorter snooze time. Since the Bortner scale was developed in USA and may reflect western culture, it is necessary to reconfirm our findings using a Japanese questionnaire such as Coronary-prone Type Scale for Japanese (CTS) and Kwansei Gakuins daily life questionnaire (KG questionnaire). METHODS Fifty healthy subjects were assessed for TABP using the Bortner scale, as well as the CTS and KG questionnaires. Hyperthymic temperament was assessed via the Japanese standardized version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire (TEMPS-A), while sleep time and snooze time were measured by actigraphy. RESULTS Both CTS and KG questionnaire scores were significantly and positively associated with the Bortner scale scores. Although CTS and KG scores were significantly and positively associated with hyperthymic temperament scores, none were associated with sleep time or snooze time. LIMITATIONS The number of subjects was relatively small. CONCLUSIONS The findings suggest that Japanese questionnaires such as CTS and KG questionnaires are valid as measures of TABP. Moreover, the association between TABP and hyperthymic temperament was reconfirmed by both CTS and KG questionnaires, whereas the association between TABP and sleep pattern was not. As such, the present findings provide supportive evidence about the usefulness of CTS and KG questionnaires.

Hyperthymic temperament and brightness preference in healthy subjects: Further evidence for involvement of left inferior orbitofrontal cortex in hyperthymic temperament

BACKGROUND Hyperthymic temperament has been generally accepted as one of premorbid temperament of bipolar disorders. Although several studies indicate that subjects with hyperthymic temperament receive more illuminance, our recent study suggests that the threshold of brightness and darkness judgment is not different between more and less hyperthymic subjects, and that hyperthymic temperament may be associated with left inferior orbitofrontal cortex, which has been reported to be associated with bipolar disorder. Therefore, at the next stage, it can be hypothesized that hyperthymic subjects may prefer brightness (i.e., heliotropism) and thereby seek illuminance, and that percent signal changes of left inferior orbitofrontal cortex during the preference task may be associated with hyperthymic temperament scores. METHODS We compared brightness preference and un-preference between more and less hyperthymic subjects, and investigated percent signal changes of left inferior orbitofrontal cortex during brightness preference judgment, brightness un-preference judgment, and control task by using functional Magnetic Resonance Imaging (fMRI). RESULTS There were significant differences in brightness preference judgment and un-preference judgment, showing that more hyperthymic subjects preferred brighter illuminace levels and un-preferred darker illuminance levels than less hyperthymic subjects. Moreover, fMRI signal changes of left inferior orbitofrontal cortex was significantly and negatively associated with hyperthymic temperament scores. LIMITATIONS It is unknown why left but not right inferior orbitofrontal cortex was associated with hyperthymic temperament scores. CONCLUSIONS The present findings suggest that more hyperthymic subjects may prefer brightness and un-prefer darkness than less hyperthymic subjects (i.e., heliotropism), and reconfirm that hyperthymic temperament may be associated with left inferior orbitofrontal cortex, which have been reported to be associated with bipolar disorders.

Postcomparison of [18F]-fluorodeoxyglucose uptake in the brain after short-term bright light exposure and no intervention

Bright light therapy is widely used as the treatment of choice for seasonal affective disorder. Nonetheless, our understanding of the mechanisms of bright light is limited and it is important to investigate the mechanisms. The purpose of this study is to examine the hypothesis that bright light exposure may increase [18F]‐fluorodeoxyglucose (FDG) uptake in olfactory bulb and/or hippocampus which may be associated neurogenesis in the human brain.