Externally-triggerable optical pump-probe scanning tunneling microscopy with a time resoloution of tens-picosecond.

Photoinduced carrier dynamics of nanostructures play a crucial role in developing novel functionalities in advanced materials. Optical pump-probe scanning tunneling microscopy (OPP-STM) represents distinctive capabilities of real-space imaging of such carrier dynamics with nanoscale spatial resolution. However, combining the advanced technology of ultrafast pulsed lasers with STM for stable time-resolved measurements has remained challenging. The recent OPP-STM system, whose laser-pulse timing is electrically controlled by external triggers, has significantly simplified this combination but limited its application due to nanosecond temporal resolution. Here we report an externally-triggerable OPP-STM system with a temporal resolution in the tens-picosecond range. We also realize the stable laser illumination of the tip-sample junction by placing a position-movable aspheric lens driven by piezo actuators directly on the STM stage and by employing an optical beam stabilization system. We demonstrate the OPP-STM measurements on GaAs(110) surfaces, observing carrier dynamics with a decay time of [Formula: see text] ps and revealing local carrier dynamics at features including a step edge and a nanoscale defect. The stable OPP-STM measurements with the tens-picosecond resolution by the electrical control of laser pulses highlight the potential capabilities of this system for investigating nanoscale carrier dynamics of a wide range of functional materials.

Probing with randomly interleaved pulse train bridges the gap between ultrafast pump-probe and nanosecond flash photolysis.

Despite the long-standing importance of transient absorption (TA) spectroscopy, many researchers remain frustrated by the difficulty of measuring the nanosecond range in a wide spectral range. To address this shortcoming, we propose a TA spectrophotometer in which there is no synchronization between a pump pulse and a train of multiple probe pulses from a picosecond supercontinuum light source, termed the randomly-interleaved-pulse-train (RIPT) method. For each pump pulse, many monochromatized probe pulses impinge upon the sample, and the associated pump-probe time delays are determined passively shot by shot with subnanosecond accuracy. By repeatedly pumping with automatically varying time delays, a TA temporal profile that covers a wide dynamic range from subnanosecond to milliseconds is simultaneously obtained. By scanning wavelength, this single, simple apparatus acquires not only wide time range TA profiles, but also broadband TA spectra from the visible through the near-infrared regions. Furthermore, we present a typical result to demonstrate how the RIPT method may be used to correct for fluorescence, which often pollutes TA curves.

Association of TMEM132D, COMT, and GABRA6 genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic and major depressive disorder.

OBJECTIVE: The aim of the study was to evaluate the association of transmembrane protein 132D (TMEM132D), catechol-O-methyltransferase (COMT), and gamma-aminobutyric acid (GABA) receptor alpha 6 subunit (GABRA6) genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic disorder (PD) and major depressive disorder (MDD). METHOD: The single nucleotide polymorphisms (SNPs) in TMEM132D, COMT, and GABRA6 were examined in patients with MDD, PD, and healthy controls. Functional magnetic resonance imaging (fMRI) was performed in patients with MDD, PD, and healthy controls. RESULTS: rs4680 in COMT and rs3219151 in GABRA6 showed positive associations with PD and MDD. A dynamic fearful face was shown to the participants during fMRI scanning. In PD patients, responses in the bilateral anterior cingulate were stronger in carriers of the AA genotype of SNP rs11060369 in TMEM132D compared with carriers of the AC + CC genotype, and stronger in CT + TT genotype carriers of SNP rs3219151 in GABRA6 compared with carriers of the CC genotype. The response in the medial orbital frontal cortex was stronger in carriers of the CT + TT genotypes of SNP rs3219151 in PD. In MDD patients, the response in the right parahippocampus of carriers of the GG genotype of rs4680 in COMT was stronger than that of carriers of the AA + AG genotype. CONCLUSION: These results suggest that TMEM132D, GABRA6, and COMT variants may increase vulnerability to panic.

The thyrotropin-releasing hormone test may predict recurrence of clinical depression within ten years after discharge.

OBJECTIVES: The underlying pathogenic mechanisms and predictors of recurrence in major depressive disorder are still largely unknown. Hypothalamic-pituitary-thyroid (HPT) axis and hypothalamus-pituitary-adrenocortical (HPA) axis dysregulation are thought to be related to the development and course of depression. DESIGN AND SETTING: Over a ten-year period, we investigated whether the results of thyrotropin-releasing hormone (TRH) testing and combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) testing could be correlated with the recurrence of depression in 25 outpatients with clinically remitted major depression for at least 10 years. MATERIALS AND METHODS: Twenty-five patients (16 women and 9 men, 48.1 years of age, SD=11.4, range 22-84) with major depressive disorder were available for evaluation during hospitalization. TRH and DEX/CRH tests were administered at admission. RESULTS: Patients who recurred within ten years after remission exhibited significantly higher thyroid stimulating hormone (TSH) responses to TRH at the time of admission compared to those who did not recur. There was no significant correlation between recurrence and DEX/CRH levels after controlling for age, sex, and body mass index. CONCLUSION: The findings of this study suggest that the TRH test may predict future recurrence in patients with depression.

Association between corticotropin-releasing hormone receptor 1 and 2 (CRHR1 and CRHR2) gene polymorphisms and personality traits.

Previous studies have reported that the hypothalamic-pituitary-adrenal axis is involved with personality traits. We examined the association between corticotropin-releasing hormone receptor (CRHR) genes and personality traits. We investigated the 12 single-nucleotide polymorphisms of intron CRHR (six in CRHR1 and six in CRHR2, respectively) in 218 healthy volunteers using TaqMan PCR assays. Personality traits were assessed using the Revised NEO-Personality Inventory, the Temperament and Character Inventory, and the State-Trait Anxiety Inventory. No significant associations were observed between CRHR1 and CRHR2 expression and personality traits. These results fail to provide support for an association of CRHR1 and CRHR2 with personality traits in a Japanese adult population.

The value of ethyl cysteinate dimer single photon emission computed tomography in predicting antidepressant treatment response in patients with major depression.

OBJECTIVE: The purpose of this study is to examine whether the reversal of compromised regional cerebral blood flow (rCBF) in older patients with major depressive disorder (MDD) is dependent on specific parameters of selective serotonin reuptake inhibitor (SSRI) treatment and to examine the efficacy of such treatment. METHODS: Forty-five patients with moderate MDD were studied following 8 weeks of treatment with SSRIs. Twelve patients displayed a positive response to SSRIs, whereas 33 patients did not respond to SSRI treatment. A comparison group of 30 healthy volunteers was also studied. The age of all participants was greater than 50 years. Age, gender, and the Hamilton Rating Scale for Depression scores were examined. The rCBF was assessed using 99mTc-ethyl cysteinate dimer single photon emission computed tomography after SSRI treatment. RESULTS: The rCBF levels in the right middle frontal cortex in non-responsive MDD patients were lower compared with responsive MDD patients. Compared with healthy controls, non-responders had significantly lower rCBF levels in the bilateral middle frontal cortex and insula and had significantly higher rCBF levels in the bilateral inferior frontal cortex and left middle temporal cortex. Compared with healthy controls, responders had significantly higher rCBF levels in the left inferior frontal, middle temporal, precentral, and fusiform gyrus. We found no changes in single photon emission computed tomography between pre-treatment and post-treatment stages for the responders to SSRI treatment. CONCLUSION: Hypoperfusion in older, non-responsive MDD patients was primarily localized in the middle frontal cortex. It is possible that the responders to SSRI treatment at baseline already displayed higher rCBF values in the frontal regions.

Hippocampal agenesis in an individual who engaged in violent criminal behaviors after discontinuing carbamazepine and paroxetine treatment.

Antidepressant discontinuation syndrome (ADS) occurs after abrupt discontinuation of an antidepressant medication. A 23-year-old man with right hippocampal agenesis demonstrated sexual crime (hypersexuality) since the age of eight and had been successfully treated with carbamazepine since the age of 13. He had required increased doses of paroxetine and carbamazepine owing to the development of an unstable affect after quitting his job. He abruptly stopped taking his medication for 3 days and his criminal behaviors re-emerged. We examined changes in brain structure and activity before and after medication cessation, using MRI and functional MRI (fMRI). The image of a girl in a swimsuit increased activity in the thalamus only after medication discontinuation. The alteration in thalamic activity might induce hypersexuality. We conclude that a primary hypersexuality had been suppressed with carbamazepine and paroxetine treatment, and the discontinuation of the medication caused the hypersexuality.

Serum ghrelin levels and the effects of antidepressants in major depressive disorder and panic disorder.

BACKGROUND: Two opposing models for the action of ghrelin in the behavioral responses to stress were recently proposed. Some studies suggest that an increase in ghrelin contributes to the mechanisms responsible for the development of stress-induced depression and anxiety, while others suggest that it helps minimize what otherwise would be more severe manifestations of depression and anxiety following stress. METHODS: We measured serum ghrelin levels, Profile of Mood States (POMS) scores and State-Trait Anxiety Inventory scores in nonresponders (treatment-resistant patients; 30) and responders (38) with major depressive disorder (MDD), nonresponders (29) and responders (51) with panic disorder and 97 healthy controls. RESULTS: The ghrelin concentration in nonresponders with MDD was higher than that of responders with MDD and normal controls. The ghrelin concentration in nonresponders with panic disorder was higher than that of normal controls. POMS vigor scores in patients with MDD and panic disorder were significantly decreased compared with those in healthy controls. Other POMS scores in patients with MDD and panic disorder were significantly increased compared with those of healthy controls. Trait and state anxiety of the State-Trait Anxiety Inventory in MDD and panic disorder patients were higher than those in healthy controls. CONCLUSIONS: These results indicate that decreased serum ghrelin levels might be associated with antidepressant treatment to confer the maximum therapeutic effect in patients with MDD and panic disorder.

An uncommon case of random fire-setting behavior associated with Todd paralysis: a case report.

BACKGROUND: The association between fire-setting behavior and psychiatric or medical disorders remains poorly understood. Although a link between fire-setting behavior and various organic brain disorders has been established, associations between fire setting and focal brain lesions have not yet been reported. Here, we describe the case of a 24-year-old first time arsonist who suffered Todd's paralysis prior to the onset of a bizarre and random fire-setting behavior. CASE PRESENTATION: A case of a 24-year-old man with a sudden onset of a bizarre and random fire-setting behavior is reported. The man, who had been arrested on felony arson charges, complained of difficulties concentrating and of recent memory disturbances with leg weakness. A video-EEG recording demonstrated a close relationship between the focal motor impairment and a clear-cut epileptic ictal discharge involving the bilateral motor cortical areas. The SPECT result was statistically analyzed by comparing with standard SPECT images obtained from our institute (easy Z-score imaging system; eZIS). eZIS revealed hypoperfusion in cingulate cortex, basal ganglia and hyperperfusion in frontal cortex,. A neuropsychological test battery revealed lower than normal scores for executive function, attention, and memory, consistent with frontal lobe dysfunction. CONCLUSION: The fire-setting behavior and Todd's paralysis, together with an unremarkable performance on tests measuring executive function fifteen months prior, suggested a causal relationship between this organic brain lesion and the fire-setting behavior. The case describes a rare and as yet unreported association between random, impulse-driven fire-setting behavior and damage to the brain and suggests a disconnection of frontal lobe structures as a possible pathogenic mechanism.

Differences in salivary alpha-amylase and cortisol responsiveness following exposure to electrical stimulation versus the Trier Social Stress Tests.

BACKGROUND: Cortisol is an essential hormone in the regulation of the stress response along the HPA axis, and salivary cortisol has been used as a measure of free circulating cortisol levels. Recently, salivary alpha-amylase (sAA) has also emerged as a novel biomarker for psychosocial stress responsiveness within the sympathetic adrenomedullary (SAM) system. PRINCIPAL FINDINGS: We measured sAA and salivary cortisol in healthy volunteers after exposure to the Trier Social Stress Test (TSST) and electric stimulation stress. One hundred forty-nine healthy volunteers participated in this study. All subjects were exposed to both the TSST and electric stimulation stress on separate days. We measured sAA and salivary cortisol levels three times immediately before, immediately after, and 20 min after the stress challenge. The State (STAI-S) and Trait (STAI-T) versions of the Spielberger Anxiety Inventory test and the Profile of Mood State (POMS) tests were administered to participants before the electrical stimulation and TSST protocols. We also measured HF, LF and LF/HF Heart Rate Variability ratio immediately after electrical stimulation and TSST exposure. Following TSST exposure or electrical stimulation, sAA levels displayed a rapid increase and recovery, returning to baseline levels 20 min after the stress challenge. Salivary cortisol responses showed a delayed increase, which remained significantly elevated from baseline levels 20 min after the stress challenge. Analyses revealed no differences between men and women with regard to their sAA response to the challenges (TSST or electric stimulations), while we found significantly higher salivary cortisol responses to the TSST in females. We also found that younger subjects tended to display higher sAA activity. Salivary cortisol levels were significantly correlated with the strength of the applied electrical stimulation. CONCLUSIONS: These preliminary results suggest that the HPA axis (but not the SAM system) may show differential response patterns to distinct kinds of stressors.

Association of CRHR1 and CRHR2 with major depressive disorder and panic disorder in a Japanese population.

Major depressive disorder (MDD) and panic disorder (PD) are common and disabling medical disorders with stress and genetic components. Dysregulation of the stress response of the hypothalamic-pituitary-adrenal axis, including the corticotrophin-releasing hormone (CRH) signaling via primary receptors (CRHR1 and CRHR2), is considered to play a major role for onset and recurrence in MDD and PD. To confirm the association of CRHR1 and CRHR2 with MDD and PD, we investigated 12 single nucleotide polymorphisms (SNPs) (rs4076452, rs7209436, rs110402, rs242924, rs242940, and rs173365 for CRHR1 and rs4722999, rs3779250, rs2267710, rs1076292, rs2284217, and rs226771 for CRHR2) in MDD patients (n = 173), PD patients (n = 180), and healthy controls (n = 285). The SNP rs110402 and rs242924 in the CRHR1 gene and the rs3779250 in the CRHR2 gene were associated with MDD. The SNP rs242924 in the CRHR1 gene was also associated with PD. The T-A-T-G-G haplotype consisting of rs7209436 and rs173365 in CRHR1 was positively associated with MDD. The T-A haplotype consisting of rs7209436 and rs110402 in CRHR1 was positively associated with MDD. The C-C haplotype consisting of rs4722999 and rs37790 in CRHR1 was associated with PD. These results provide support for an association of CRHR1 and CRHR2 with MDD and PD.

Salivary α-amylase and cortisol responsiveness following electrical stimulation stress in panic disorder patients.

Psychosocial stress-induced activation of salivary α-amylase (sAA) functions is as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in panic disorder patients. The present study measured sAA and salivary cortisol levels in patients with panic disorder following electrical stimulation stress. The authors determined Profile of Mood State (POMS) scores and State-Trait anxiety Inventory (STAI) scores, heart rate variability (HRV), and levels of sAA and salivary cortisol in 34 patients with panic disorder and 41 healthy volunteers following the application of electrical stimulation stress. 34 alprazolam-treated patients with panic disorder were divided into non-responder and responder group. Vigor scores in patients with panic disorder were significantly decreased compared with healthy controls. Another score in POMS in patients with panic disorder were significantly increased compared with healthy controls. Trait and state anxiety of STAI in panic disorder patients were higher than healthy controls. There was no difference in either HRV or threshold of electrical stimulation applied between panic disorder patients and healthy controls. SAA levels in the responder group were significantly elevated compared with the non-responder group and controls both before and after electrical stimulation. In addition, there were no differences in salivary cortisol levels between responder and non-responder groups of patients with panic disorder and control. The sample may not be representative of the general population. These preliminary results suggest that sAA might be useful predictive biological markers of treatment responsiveness in patients with panic disorder.

Aripiprazole augmentation in 13 patients with refractory obsessive-compulsive disorder: a case series.

OBJECTIVES: The primary treatment for obsessive-compulsive disorder (OCD) is selective serotonin reuptake inhibitors (SSRI). However, approximately a third of patients do not respond to SSRIs and remain chronically affected. METHODS: Therefore, we added aripiprazole to SSRI therapy for 13 patients with treatment-refractory OCD (subjects who failed to respond to SSRI therapy for at least 2 months, and for an average of 508 days). Participants underwent at least 7 weeks of treatment with aripiprazole augmentation. RESULTS: Patients were evaluated using the Y-BOCS and GAF scales. Aripiprazole (3-12 mg)/SSRI co-therapy significantly improved Y-BOCS and GAF scores. However, many patients needed to take antiparkinsonian drugs to control extrapyramidal symptoms. CONCLUSIONS: These results suggest that aripiprazole augmentation of SSRI therapy may be effective for treatment-refractory OCD.

Salivary alpha-amylase and cortisol responsiveness following electrical stimulation stress in major depressive disorder patients.

Major depressive disorder (MDD) is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis by chronic stress. In comparison, psychosocial stress-induced activation of salivary α-amylase (sAA) functions as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in MDD patients. The present study measured sAA and salivary cortisol levels in patients with MDD. The authors determined Profile of Mood State (POMS) and State-Trait anxiety Inventory (STAI) scores, Heart Rate Variability (HRV), and sAA and salivary cortisol levels in 88 patients with MDD and 41 healthy volunteers following the application of electrical stimulation stress. Patients with major depressive disorder were 8 points or more on Hamilton Depression Scale (HAM-D) scores. Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion scores in patients with major depressive disorder were significantly increased compared to healthy controls. In contrast, Vigor scores in patients with MDD were significantly decreased compared with healthy controls. There was no difference in heart rate variability measures between MDD patients and healthy controls. The threshold of electrical stimulation applied in MDD patients was lower than that in healthy controls. SAA levels in female MDD patients were significantly elevated relative to controls both before and after electrical stimulation. Finally, there were no differences in salivary cortisol levels between major depressive patients and controls. In the present study only three time points were explored. Furthermore, the increased secretion of sAA before and after stimulation could allude to an increased responsiveness of novel and uncontrollable situations in patients with MDD. These preliminary results suggest that sAA might be a useful biological marker of MDD.

Infrared radiation has potential antidepressant and anxiolytic effects in animal model of depression and anxiety.

BACKGROUND: Bright light therapy has been shown to have antidepressant and anxiolytic effects in humans. OBJECTIVE: The antidepressant and anxiolytic effects of infrared radiation were evaluated using an experimental animal model. METHODS: Rats were randomly assigned to either an acutely or chronically exposed infrared radiation group or to a nonexposed control group. Acutely exposed rats were treated with an infrared radiation machine for one session, whereas chronically exposed animals were treated with an infrared radiation for 10 sessions. Control group rats were exposed to the sound of the infrared radiation machine as a sham treatment. After infrared radiation or control exposure, rats underwent behavioral evaluation, including elevated plus maze test, light/dark box, and forced swim test. RESULTS: Chronic infrared radiation exposure decreased indicators of depression- and anxiety-like behavior. No significant effect on general locomotor activity was observed. The number of BrdU-positive cells in CA1 of the hippocampus was significantly increased in both acutely and chronically exposed infrared radiation groups compared with the control group. CONCLUSIONS: These results indicate that chronic infrared radiation might produce antidepressant- and anxiolytic-like effects.

Serum hepatocyte growth factor levels and the effects of antidepressants in panic disorder.

Previous animal studies have suggested that hepatocyte growth factor (HGF) could be associated with depression- and anxiety-related behaviors. Our aim was to relate serum HGF levels with State-Trait Anxiety Inventory (STAI), Profile of Mood State (POMS), and Revised NEO Personality Inventory (NEO-PI-R) scores in patients with panic disorder (with or without agoraphobia) and healthy controls. We examined 67 patients with panic disorders and 97 controls. Patients were split into two groups according to whether they exhibited a 50% improvement in test scores (good/high response group: n = 26) or not (poor/low response group: n = 41). In both healthy control and panic disorder individuals, there were no significant associations between HGF serum levels and STAI or NEO-PI-R scores. However, there was a significant correlation between serum HGF levels and fatigue in healthy control subjects in as scored by POMS testing. HGF concentration in the good/high response group was significantly elevated compared to both the low/poor response group (p < 0.01) and the control group (p < 0.01). HGF levels in the poor response group did not differ from the control group (p = 0.48). These results indicate that increased serum HGF levels might be a requirement for antidepressant efficacy in patients with panic disorders.

Elevated salivary α-amylase and cortisol levels in unremitted and remitted depressed patients.

Abstract Objective. Major depressive disorder (MDD) is often associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis via chronic stress. Psychosocial stress-induced activation of salivary α-amylase (sAA) represents sympathoadrenal medullary system (SAM) activity, and sAA has become an emerging biomarker for sympathetic nervous system activity. In contrast to salivary cortisol, sAA has been less extensively studied in depressed patients. The present study sought to address this problem by measuring sAA and salivary cortisol levels in patients with major depressive disorder. Methods. The authors recorded Spielberger State-Trait Anxiety Inventory (STAI) scores along with, levels of sAA and salivary cortisol in 28 patients with unremitted major depressive disorder, 43 remitted patients and 103 healthy volunteers. Results. STAI (State or Trait) measurements in unremitted patients with MDD were significantly increased compared with healthy controls and remitted patients. SAA and cortisol levels in unremitted patients were also significantly elevated compared to controls and remitted patients. Finally, sAA levels were significantly correlated with HRSD in unremitted patients with MDD. Conclusion. These preliminary results suggest that sAA may be a state-dependent marker of major depressive disorder in addition to salivary cortisol.

Social support and enhanced suppression of adrenocorticotropic hormone and cortisol responses to hypothalamic-pituitary-adrenal function and thyrotropin-releasing hormone tests in patients with major depressive disorder.

The results of the thyrotropin-releasing hormone (TRH) stimulation test and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test are believed to correlate with social support status in patients with major depressive disorder. We studied 41 consecutive patients hospitalized for major depressive disorder and tested their responses to DEX/CRH and TRH on hospital days 4-7. DeltaMAX TSH and DeltaMAX cortisol were measured. Multiple regression analysis found that social support questionnaire (SSQ-A) and SSQ-B scores were significantly related to DeltaMAX cortisol and DeltaMAX TSH, respectively, at the time of admission. Social support might contribute partially to the TRH and DEX/CRH test results in patients with major depressive disorder.