Aberrant thalamocortical connectivity and shifts between the resting state and task state in patients with schizophrenia.

Prominent pathological hypotheses for schizophrenia include auditory processing deficits and dysconnectivity within cerebral networks. However, most neuroimaging studies have focused on impairments in either resting-state or task-related functional connectivity in patients with schizophrenia. The aims of our study were to examine (1) blood oxygen level-dependent (BOLD) signals during auditory steady-state response (ASSR) tasks, (2) functional connectivity during the resting-state and ASSR tasks and (3) state shifts between the resting-state and ASSR tasks in patients with schizophrenia. To reduce the functional consequences of scanner noise, we employed resting-state and sparse sampling auditory fMRI paradigms in 25 schizophrenia patients and 25 healthy controls. Auditory stimuli were binaural click trains at frequencies of 20, 30, 40 and 80 Hz. Based on the detected ASSR-evoked BOLD signals, we examined the functional connectivity between the thalamus and bilateral auditory cortex during both the resting state and ASSR task state, as well as their alterations. The schizophrenia group exhibited significantly diminished BOLD signals in the bilateral auditory cortex and thalamus during the 80 Hz ASSR task (corrected p < 0.05). We observed a significant inverse relationship between the resting state and ASSR task state in altered functional connectivity within the thalamo-auditory network in schizophrenia patients. Specifically, our findings demonstrated stronger functional connectivity in the resting state (p < 0.004) and reduced functional connectivity during the ASSR task (p = 0.048), which was mediated by abnormal state shifts, within the schizophrenia group. These results highlight the presence of abnormal thalamocortical connectivity associated with deficits in the shift between resting and task states in patients with schizophrenia.

Multi-modal imaging of the auditory-larynx motor network for voicing perception.

Voicing is one of the most important characteristics of phonetic speech sounds. Despite its importance, voicing perception mechanisms remain largely unknown. To explore auditory-motor networks associated with voicing perception, we firstly examined the brain regions that showed common activities for voicing production and perception using functional magnetic resonance imaging. Results indicated that the auditory and speech motor areas were activated with the operculum parietale 4 (OP4) during both voicing production and perception. Secondly, we used a magnetoencephalography and examined the dynamical functional connectivity of the auditory-motor networks during a perceptual categorization task of /da/-/ta/ continuum stimuli varying in voice onset time (VOT) from 0 to 40 ms in 10 ms steps. Significant functional connectivities from the auditory cortical regions to the larynx motor area via OP4 were observed only when perceiving the stimulus with VOT 30 ms. In addition, regional activity analysis showed that the neural representation of VOT in the auditory cortical regions was mostly correlated with categorical perception of voicing but did not reflect the perception of stimulus with VOT 30 ms. We suggest that the larynx motor area, which is considered to play a crucial role in voicing production, contributes to categorical perception of voicing by complementing the temporal processing in the auditory cortical regions.

Anxious temperament as a risk factor of suicide attempt.

OBJECTIVE: Suicide has been reported to be associated with cyclothymic, irritable, depressive and anxious temperaments. In contrast, hyperthymic temperament has been reported to be protective against suicide. In the present study, we hypothesized that Japanese patients with suicide attempt may have higher scores of cyclothymic, irritable, depressive, and anxious temperaments but lower scores of hyperthymic temperament than non-suicidal patients. In order to examine this hypothesis, we investigated Japanese patients of a university emergency center. METHODS: The association of temperament and suicide attempt was investigated in 116 patients referred to a university emergency center for intoxication or injury. Of them, 35 patients of suspected suicide attempt were categorized as 18 patients who intended to die with attempted suicide and suffered from self-inflicted but not fatal injury (Suicide Attempt II), 4 patients whose intention to die were undetermined although they suffered from self-inflicted injury (Undetermined Suicide-Related Behavior II), and 13 patients who had no intention to die although they suffered from self-inflicted injury (Self-Harm II). Logistic regression analyses and multiple regression analyses were used to identify factors associated with the present suicide attempt and the number of suicide attempts, respectively. RESULTS: Anxious temperament scores were significantly and directly associated with Suicide Attempt II group whereas irritable temperament scores were associated with Self-Harm II group. CONCLUSION: The present findings suggest that those with anxious temperament may have more suicide attempts than those with other temperaments, indicating anxious temperament as a risk factor of suicide attempt.

Effect of temperaments on quality of life and social adaptation in depressive patients with mood disorder.

AIMS: The aim of this study was to investigate the effects of temperament on quality of life and social adaptation in depressive patients with mood disorder. METHODS: Forty-six consecutive depressive outpatients were investigated by using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire version, the Munich Personality Test, the World Health Organization Quality of Life 26 (WHO QOL 26), and the Social Adaptation Self-evaluation Scale (SASS). The unpaired t-test, Pearson's r and multiple regression analysis were used to assess three variables (age, the number of temperaments and/or personality types, and Hamilton Depression Rating Scale scores) as independent variables with the scores of WHO QOL 26 and SASS as the dependent variables. RESULTS: The number of temperaments and/or personalities and Hamilton Depression Rating Scale scores were significantly and negatively associated with WHO QOL 26 scores while only the number of temperaments and/or personalities was significantly and negatively associated with SASS scores. CONCLUSIONS: The findings suggest that the combination of temperaments and/or personality types assessed with the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire version and the Munich Personality Test may worsen both quality of life and social adaptation and that some temperaments and/or personality types in combination may be subclinical manifestations of mood disorders.

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.

Identification of the neural correlates of cyclothymic temperament using an esthetic judgment for paintings task in fMRI.

BACKGROUND: There is a well-known association between artistic creativity and cyclothymic temperament but the neural correlates of cyclothymic temperament have not yet been fully identified. Recently, we showed that the left lingual gyrus and bilateral cuneus may be associated with esthetic judgment of representational paintings, we therefore sought to investigate brain activity during esthetic judgment of paintings in relation to measures of cyclothymic temperament. METHODS: Regions of interest (ROI) were set at the left lingual gyrus and bilateral cuneus using automated anatomical labeling, and percent signal changes of the ROIs were measured by marsbar toolbox. The associations between percent signal changes of the ROIs during esthetic judgments of paintings and cyclothymic temperament scores were investigated by Pearson׳s coefficient. Moreover, the associations were further analyzed using multiple regression analysis whereby cyclothymic temperament scores were a dependent factor and percent signal changes of the 3 ROIs and the other 4 temperament scores were independent factors. RESULTS: There was a significantly negative association of cyclothymic temperament scores with the percent signal changes of the left lingual gyrus during esthetic judgments of paintings, but not with those of bilateral cuneus. Even after adjustment using multiple regression analysis, this finding remained unchanged. LIMITATIONS: The number of subjects was relatively small and the task was limited to appreciation of paintings. CONCLUSIONS: The present findings suggest that cyclothymic temperament may be associated with the left lingual gyrus.

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.

Relationship between hostility and subjective sleep quality.

While hostility and sleep disturbance are the potential risk factors for health problems and disease, few studies have examined the relationship between the two factors. The present study was performed to investigate the relationship between hostility and sleep problems assessed both subjectively and objectively in a nonclinical sample. Sixty-one healthy subjects were enrolled in this study. Hostility was measured according to the Cook-Medley hostility scale. Subjective sleep quality was evaluated according to the global score of the Pittsburgh Sleep Quality Index. Objective sleep was evaluated using actigraphy. A multiple regression analysis revealed that a higher level of hostility was significantly associated with the global score of the Pittsburgh Sleep Quality Index and that a higher level of depression was not associated with the global score of the Pittsburgh Sleep Quality Index. Objective sleep measures were not found to be associated with hostility. Confirming the robust relationship between poor sleep and hostility would have several important treatment implications for preventing health problems.

Affective temperaments and psychotropic adherence.

BACKGROUND: It is generally accepted that a range of factors affect adherence to psychotropic medications. In the present study, we focused on the influence of affective temperaments (i.e., depressive, hyperthymic, cyclothymic, irritable, and anxious temperaments) on treatment adherence. METHODS: Thirty-eight psychiatric consecutive inpatients were instructed to perform Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire version (TEMPS-A) for affective temperaments, Drug attitude inventory-10 (DAI-10) for concordance and persistence, and Visual Analogue Scale (VAS) for compliance. RESULTS: VAS scores for dose compliance were significantly and negatively associated with irritable temperament scores whereas DAI-10 scores were significantly and positively associated with male gender, depressive temperament scores and hyperthymic temperament scores. LIMITATIONS: The main limitations of the study were the relatively small number of subjects and the lack of objective method of adherence. CONCLUSIONS: These findings suggest that patients with irritable temperament may be poor in their compliance with treatment, and that more education may be required for patients with irritable temperament in order to maintain good compliance. In contrast, men and patients with depressive or hyperthymic temperament have a relatively positive attitude towards medication.

Hyperthymic temperament and rapid reaction time in brightness preference.

BACKGROUND: It is well-known that Type A behavior pattern is characterized by hard-driving, competitive behavior and time urgency. Also, people with hyperthymic temperament are known to have high energy levels and are full of plans. It is therefore hypothesized that hyperthymic temperament is associated with rapid processing and fast reaction time in making decisions. METHODS: Using data from our previous experimental studies (N=58) examining brightness judgment and brightness preference, reaction time (RT) was investigated in relation to hyperthymic temperament scores and fMRI signal changes of the left inferior orbitofrontal cortex during brightness judgment. RESULTS: RT for brightness judgment was significantly shorter than RT for brightness preference. Significant associations were found between RT for brightness preference and hyperthymic temperament scores, and RT for brightness preference and fMRI signal changes of the left inferior orbitofrontal cortex whilst performing brightness preference task. Multiple regression analysis revealed that RT for brightness preference task was significantly and negatively associated with hyperthymic temperament scores, and significantly and positively associated with fMRI signal changes of the left inferior orbitofrontal cortex. LIMITATIONS: It is uncertain whether the findings of RT (around 1s) can be extrapolated to routine life (around 24h) and whether RT for brightness preference can be generalized to a variety of daily activities. CONCLUSIONS: The present findings suggest that hyperthymic temperament is associated with rapid processing. Further studies are required to overcome the above limitations.

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.

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.

Bipolar temperaments and light.

BACKGROUND: Converging lines of evidence have established a relationship between exposure to ambient light and both mood state and mood disorders. In view of the association between mood disorder and affective disposition, in this study, the relationship between temperament (depressive, cyclothymic, hyperthymic, irritable and anxious) and daily light exposure was closely examined. METHODS: Fifty-six subjects completed the Japanese standardized version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-auto questionnaire version (TEMPS-A) and illuminance of daytime using actigraphy. RESULTS: Cyclothymic temperament scores were significantly and negatively associated with illuminance of daytime whereas hyperthymic temperament scores were significantly and positively associated with illuminance of daytime. LIMITATIONS: Sample size was relatively small and they were only healthy subjects and no patients. CONCLUSIONS: The findings suggest that illuminance of daytime may be related to both cyclothymic and hyperthymic temperaments but that the associations lie in opposite directions. If this is the case, it seems important to consider individual patients' temperaments when light therapy is used to treat their depressive episode. Further studies are required to determine why and how these temperaments are associated with illuminance.

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.

Is serotonergic function associated with the antidepressant effects of modified-electroconvulsive therapy?

BACKGROUND: The effect of modified-electroconvulsive therapy (m-ECT) on central serotonergic function has not been sufficiently investigated. The aim of the present study is to investigate this effect via the neuroendocrine challenge test. METHODS: Sixteen inpatients (9 men and 7 women) with major depressive disorder who were receiving m-ECT at our university hospital were recruited. A neuroendocrine challenge test to estimate central serotonergic function was performed both before and after m-ECT treatment. RESULTS: On the whole, depressive symptoms significantly improved, but the improvement was not associated with changes in serotonergic function. LIMITATIONS: The study was open-labeled and performed with a small number of subjects and no control group. CONCLUSION: Serotonergic function may not be associated with the antidepressant effects of ECT.

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 Gakuin's 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.

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.

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.