Nobuhiko Hoaki

Cyclothymic and hyperthymic temperaments may predict bipolarity in major depressive disorder: A supportive evidence for bipolar II1/2 and IV

BACKGROUND The concept of soft bipolar spectrum has not been fully confirmed. The aim of the present study is to investigate the validity of bipolar II1/2 and IV concept. METHODS The subjects were 46 consecutive outpatients. The individual temperament of each patient was recorded using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A). The operational definition of bipolar II1/2 was those who had depression with cyclothymic temperament and that of bipolar IV was those who had depression with hyperthymic temperament. Finally, drug responses were investigated. RESULTS DSM-IV-TR diagnoses were bipolar I (N=1), bipolar II (N=9), major depressive disorder (N=34) and depressive disorder not otherwise specified (N=2). Excluding one bipolar I patient, who had both cyclothymic and hyperthymic temperaments, patients with bipolar II1/2 (N=32) and IV (N=13) as well as bipolar II (N=9) were classified into the soft bipolar spectrum, although there was considerable overlap. The categorization of soft bipolar spectrum and unipolar depression significantly predicted depressive, cyclothymic, irritable, and anxious temperaments. Moreover, soft bipolar spectrum patients with lithium treatment were significantly more in remission than those without lithium treatment. In addition, more of those with selective serotonin reuptake inhibitors (SSRIs) had a significant tendency to lower remission than those without SSRIs. LIMITATIONS This is a cross-sectional study with a relatively small number of subjects. CONCLUSIONS The present findings suggest that cyclothymic and hyperthymic temperaments may predict bipolarity, and the validity of bipolar II1/2 and IV concept is supported.

Biological aspect of hyperthymic temperament: light, sleep, and serotonin

RationaleHyperthymic temperament is one of several premorbid temperaments putatively associated with bipolar disorder. Several reports suggest that depressive patients with hyperthymic temperament may belong to the proposed soft bipolar spectrum.ObjectivesTo investigate biological aspects of hyperthymic temperament, the present study examined daily activity, sleep time, central serotonergic function, and other relevant variables in relation to hyperthymic temperament in healthy subjects.MethodsFifty six healthy subjects were monitored via the actigraphy system to measure daily total activity, sleep time, and illuminance. A neuroendocrine challenge test was performed to estimate central serotonergic function.ResultsMultiple regression analysis revealed that higher illuminance of daytime, greater fluctuation in sleep time, and lower central serotonergic function significantly and independently predicted hyperthymic temperament scores.ConclusionsThe present findings suggest that light, sleep, and serotonin are crucial factors in understanding hyperthymic temperament, which may be common to bipolar disorder.

Type A behavior pattern and hyperthymic temperament: possible association with bipolar IV disorder.

BACKGROUND Type A behavior pattern (TABP) has traditionally been reported to be associated with coronary heart disease and, more recently, several researchers have examined its association with depression and bipolar disorder. According to Akiskal and Pinto (1999), there are 2 subtypes of bipolar spectrum which are not associated with manic or hypomanic state. These are bipolar II1/2 (depression in those who have cyclothymic temperament) and bipolar IV (depression in those who have hyperthymic temperament). Our hypothesis is that individuals with hyperthymic temperament may have a tendency towards TABP. OBJECTIVES The purposes of the present study are to investigate the association between TABP and hyperthymic temperament and to determine other biological factors associated with TABP. METHODS Fifty healthy subjects were assessed for TABP and hyperthymic temperament by self-rating scales, daily activity, sleep time and illuminance by actigraphy, and central serotonergic function via the neuroendocrine challenge test. Serum brain-derived neurotrophic factor (BDNF) levels were also measured. RESULTS Stepwise regression analysis indicated that hyperthymic temperament score was positively associated with TABP scores and both sleep time and snooze time were negatively associated with TABP scores. BDNF levels were not associated with TABP scores. CONCLUSIONS These findings suggest that individuals with hyperthymic temperament may have a tendency towards TABP, and TABP persons may have short sleep time and short snooze time. Although further studies are required to investigate the association between TABP and affective disorders, the present findings clearly indicate the association between TABP and hyperthymic temperament, which may be associated with bipolar IV disorder. Taking TABP as a risk factor of cardiovascular events into consideration, this association between TABP and bipolar IV disorder may account for the well-known cardiovascular mortality in bipolar disorder.

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.

Latitude effect on bipolar temperaments.

BACKGROUND Growing evidence points to an association of daily light exposure and both mood and mood disorders. In recent studies, we demonstrated that higher illuminance of daytime may be positively associated with hyperthymic temperament while lower illuminance of daytime may be positively associated with cyclothymic temperament. However, it is not possible to determine whether hyperthymic or cyclothymic temperament induces higher or lower illuminance via heliotropism or non-heliotropism or whether higher or lower illuminance induces hyperthymic or cyclothymic temperament via light effects. METHODS In order to elucidate these questions, we sought to compare bipolar temperaments between residents who live in regions with varying levels of sunshine. Japan has 4 large islands -Hokkaido, Honshu, Shikoku, and Kyushu. Sapporo in Hokkaido and Oita in Kyushu located at 43° and 33° of latitude differ significantly in mean yearly sunshine. We investigated the data of 189 subjects (94 from Sapporo and 95 from Oita) including their data of Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire version (TEMPS-A). RESULTS Multiple regression analyses revealed that latitude (Sapporo or Oita) effect predicted significant variance of hyperthymic temperament, but not of the other temperaments. LIMITATIONS The limitation of the present study was that there was a small but significant difference in age between the subjects of Sapporo and those of Oita. Therefore, we included age in the multiple regression analysis. Second, there were several climate factors other than sunshine which were significantly different between Sapporo and Oita. We cannot exclude these effects completely. Finally, we did not consider other factors such as psychosocial factors which might have affected bipolar temperaments. CONCLUSIONS The present findings suggest that relatively lower latitude (potentially via more sunshine) may induce hyperthymic temperament.

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.

Light can ameliorate low mood in healthy people

We greatly appreciate Emeritus Professor Kripke for his interest in our recent article (Hoaki et al. 2010) where it was revealed that higher illuminance of daytime, greater fluctuation in sleep time, and lower central serotonergic function significantly and independently predicted hyperthymic tendency. In response to the inquiry from Emeritus Professor Kripke, we investigated the association between illuminance of daytime and Hamilton depression rating scale (HAM-D) scores and that between illuminance of daytime and Young mania rating scale (YMRS) scores. As a result, there was a significantly negative association between illuminance of daytime and Hamilton depression rating scale scores (rho=−0.23, p=0.035), but no significant association between illuminance of daytime and YMRS. It should be noted that our subjects were healthy volunteers, and their range of HAM-D and YMRS was 0–6 and 0–4, respectively. Therefore, these scores were within normal limits. Nonetheless, the significantly negative association between illuminance of daytime and HAM-D scores indicate that light can ameliorate low mood in healthy people. These findings are in accordance with the report from Kripke’s group (Espiritu et al. 1994). Further studies are required to prospectively investigate whether light can prevent the occurrence of depression in healthy people.

Association between affective temperaments and brain-derived neurotrophic factor, Glycogen synthase kinase 3β and Wnt signaling pathway gene polymorphisms in healthy subjects

BACKGROUND There is increased attention towards elucidating genetic factors that underlie both psychiatric diseases as well as healthy psychological phenomena. Recent evidence suggests that temperamental traits, including affective temperaments, are heritable and associated with genetic polymorphisms. Genetic research examining affective temperaments using the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) may therefore elucidate the concept of a spectrum of mood disorders and the genetic relationship between affective temperaments and mood disorders. The purpose of this study was to examine the association between brain-derived neurotrophic factor (BDNF), glycogen synthase kinase 3β(GSK3β) and Wnt signaling pathway (Wnt) gene polymorphisms and affective temperaments in non-clinical Japanese subjects, as measured by TEMPS-A. METHODS 44 healthy Japanese subjects were recruited through our university hospital and completed the TEMPS-A. We genotyped three SNPs (single nucleotide polymorphisms) from the BDNF, GSK3βand Wnt genes in order to test the relationship between these gene variants and five affective temperaments measured by the TEMPS-A. RESULTS No significant difference in the frequency of alleles between affective temperaments (depressive, cyclothymic, hyperthymic, irritable and anxious temperament) and non affective temperaments was shown. One-way analysis of variance (ANOVA) revealed no significant differences among 5 groups (depressive, cyclothymic, hyperthymic, irritable and anxious temperament) in healthy subjects for all the scores of affective temperaments by TEMPS-A. LIMITATIONS The number of subjects was relatively small. CONCLUSIONS The variant of BDNF, GSK3β and Wnt gene polymorphism might not be related to the five temperaments of TEMPS-A and TEMPS-A score in healthy Japanese subjects. The present results suggest that BDNF, GSK3βand Wnt genes, might not have a major role in the development of personality traits. Further studies with larger sample size are warranted to evaluate the association of affective temperament and gene polymorphisms.

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.

Triiodothyronine may be possibly associated with better cognitive function and less extrapyramidal symptoms in chronic schizophrenia.

OBJECTIVE Many chronic inpatients with schizophrenia demonstrate enduring psychiatric symptoms and various side effects of antipsychotic drugs. Several biological markers such as prolactin, thyroid hormones and brain-derived neurotrophic factor (BDNF) are reportedly associated with psychiatric symptoms and/or antipsychotic side effects in patients with schizophrenia but to date findings are inconsistent. The objective of the present study was to comprehensively investigate the association of psychiatric and extrapyramidal symptoms with hormones and BDNF in chronic schizophrenia. METHODS In this study, 93 chronic inpatients with schizophrenia were comprehensively investigated in order to examine the association of psychiatric and extrapyramidal symptoms with prolactin, thyroid hormones (free triiodothyronine (T₃), free thyroxine (T₄), thyroid stimulating hormone), cortisol and BDNF. Symptoms were assessed via the Positive and Negative Syndrome Scale (PANSS), Mini-Mental State Examination (MMSE), and drug-induced extrapyramidal symptoms scale (DIEPSS). RESULTS Multiple regression analyses revealed that antipsychotic dose was the only variable that predicted significant variance in PANSS positive subscale scores, that BDNF and free T₃ predicted significant variance in MMSE scores, and that prolactin and free T₃ predicted significant variance in DIEPSS scores. CONCLUSION These findings suggest that BDNF, free T₃, and prolactin may be associated with cognitive function and/or extrapyramidal symptoms in patients with chronic schizophrenia. Notably, free T₃ may be possibly associated with better cognitive function and less extrapyramidal symptoms, although our cross-sectional study could not reveal a causal relationship.