Reduced white matter integrity in borderline personality disorder: A diffusion tensor imaging study.

BACKGROUND: Borderline personality disorder (BPD) has a pervasive pattern of instability in interpersonal relationships, self-image, and emotions. BPD may be linked to an abnormal brain anatomy, but little is known about possible impairments of the white matter microstructure in BPD or their relationship with impulsivity or risky behaviors. The aims of the present study were to explore the relationship between BPD and diffusion tensor imaging (DTI) parameters and psychological tests. METHODS: We evaluated 35 un-medicated BPD patients in a medication-free state and 50 healthy controls (HCs). We performed DTI tractography in BPD patients and HCs. The Childhood Trauma Questionnaire (CTQ), Profile of Mood State (POMS), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Social Adaptation Self-Evaluation Scale (SASS), and Depression and Anxiety Cognition Scale (DACS) were administered to BPD patients and HCs. RESULTS: A tract-based spatial statistics (TBSS) revealed that the BPD group had three clusters with a significantly lower axial diffusivity (AD) than the HC group: one located mainly in the cingulum and the other mainly in the inferior front-occipital fasciculus and inferior longitudinal fasciculus. Regarding the AD values, one cluster correlated negatively and significantly with POMS (Depression) and it was located in the cingulum, while another cluster correlated positively and significantly with DACS (Future Denial) and it was located in the inferior front-occipital fasciculus (IFOF). LIMITATIONS: The small sample size of this study prevents us from forming any definitive conclusions, meaning that more studies are needed to confirm our findings. We are unable to generalize our findings to include other ethnic groups. CONCLUSIONS: Our results suggested that hypo-metabolism in a front-limbic network dysfunction is characterized by the cingulum and a front-occipital network dysfunction characterized by the occipital lobe, while an occipital-temporal network dysfunction characterized by the inferior longitudinal fasciculus.

Natural reduced water suppressed anxiety and protected the heightened oxidative stress in rats.

BACKGROUND: In Japan, the effects of reduced water, such as hydrogen-rich electrolyzed reduced water and natural reduced water, like Hita Tenryosui water®, have been examined. The purpose of the present study was to identify the role of natural reduced water in anxiety and blood biochemical analysis. MATERIALS AND METHODS: Natural reduced water and distilled water were administered to rats for 180 consecutive days, and their effect on anxiety-like behavior and depression was examined by using elevated plus maze, light/dark, forced swimming, and conditioned fear tests. Before and after administration of natural reduced or distilled water, we performed blood and urine analyses. RESULTS: Natural reduced water exhibited anxiolytic-like effects in the conditioned fear and elevated plus maze tests. The mean levels of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the natural reduced water were significantly lower than the distilled water group. Natural reduced water group also showed decrease in blood-urea nitrogen levels compared with the distilled water group. CONCLUSION: These results indicate that natural reduced water may decrease anxiety-related behaviors and prevent heightened oxidative stress.

Gender differences in automatic thoughts and cortisol and alpha-amylase responses to acute psychosocial stress in patients with obsessive-compulsive personality disorder.

INTRODUCTION: Obsessive-compulsive personality disorder (OCPD) has a pervasive pattern of preoccupation with orderliness, perfection, and mental and interpersonal control at the expense of flexibility, openness, and efficiency. The aims of the present study were to explore the relationship between OCPD and psychological stress and psychological tests. METHODS: We evaluated 63 OCPD patients and 107 healthy controls (HCs). We collected saliva samples from patients and controls before and after a social stress procedure, the Trier Social Stress Test (TSST), to measure the concentrations of salivary alpha-amylase (sAA) and salivary cortisol. The Childhood Trauma Questionnaire (CTQ), Profile of Mood State (POMS), State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Social Adaptation Self-Evaluation Scale (SASS), and Depression and Anxiety Cognition Scale (DACS) were administered to patients and HCs. RESULTS: Following TSST exposure, the salivary amylase and cortisol levels were significantly decreased in male patients compared with controls. Additionally, OCPD patients had higher CTQ, POMS, STAI, and BDI scores than HCs and exhibited significantly higher anxiety and depressive states. OCPD patients scored higher on future denial and threat prediction as per the DACS tool. According to a stepwise regression analysis, STAI, POMS, and salivary cortisol responses were independent predictors of OCPD. CONCLUSIONS: Our results suggested that attenuated sympathetic and parasympathetic reactivity in male OCPD patients occurs along with attenuated salivary amylase and cortisol responses to the TSST. In addition, there was a significant difference between OCPD patients and HCs in child trauma, mood, anxiety, and cognition. The finding support the modeling role of cortisol (20min) on the relationships between STAI trait and depression among OCPD.

Different functioning of prefrontal cortex predicts treatment response after a selective serotonin reuptake inhibitor treatment in patients with major depression.

BACKGROUND: Major depressive disorder (MDD) is often resistant to treatment with usual approaches. Patients with MDD have shown hypofunction of the frontotemporal cortex in verbal fluency test (VFT)-related near-infrared spectroscopy (NIRS). METHODS: We examined whether the reactions to drug treatment in treatment-naive patients with MDD could be predicted by NIRS outcomes at the initial investigation. All subjects underwent psychological testing to determine levels of anxiety and depression. VFT was used to examine the functioning of the frontotemporal lobes. We administered selective serotonin reuptake inhibitors (SSRIs) for 12 weeks. Subjects included 28 patients with MDD with response to SSRIs (Response group), 19 with no response (Non-Response group), and 63 age-, sex-, and education years-matched healthy controls (HC). RESULTS: We found in the frontotemporal region that hemodynamic responses were significantly smaller in patients with Response and Non-Response groups than in HC before treatment. We also found in the medial frontal region that hemodynamic responses were significantly larger in patients with Response groups than in patients with Non-Response group before treatment. Patients with MDD scored significantly higher anxiety and depressive states than those in HC on several measures. The Response and Non-Response groups also had higher scores in future denial, threat prediction, self-denial, past denial, and interpersonal threat sections of Anxiety Cognition Scale (DACS). According to the stepwise regression analysis, one variable was determined as independent predictors of response: confusion (Post-POMS). LIMITATIONS: The number of patients and healthy controls was relatively small, and we will increase the number of participants in future studies. NIRS has reduced spatial resolution, which confuses the identification of the measurement position when using NIRS alone. CONCLUSION: Cognitive vulnerabilities are associated with predictors of SSRI treatment response. Different hemodynamic activities in the frontotemporal cortex predict response to SSRI treatment in MDD.

Sex determines cortisol and alpha-amylase responses to acute physical and psychosocial stress in patients with avoidant personality disorder.

INTRODUCTIONS: Avoidant personality disorder (AVPD) has excessive and pervasive anxiety and discomfort in social situations. The aims of this study were to explore the relationship between AVPD and physical and psychological stress and psychological tests. METHODS: We evaluated 93 AVPD patients and 355 nonpatient controls by salivary amylase and cortisol responses during exposure to the Trier Social Stress Test (TSST) and electrical stimulation stress. Spielberger state-trait anxiety inventory (STAI), Profile of Mood State (POMS), Beck Depression Inventory (BDI), Depression and Anxiety Cognition Scale (DACS), and Childhood Trauma Questionnaire (CTQ) were administered. RESULTS: Following electrical stimulation, salivary cortisol levels in female AVPD decreased significantly less than that in female's controls, but salivary cortisol levels did not show a difference between male AVPD patients and controls. Salivary alpha-amylase (sAA) levels did not show a difference between females or male AVPD patients and controls. Following TSST exposure, sAA levels did not show a difference between females or male AVPD patients and controls. Salivary cortisol levels did not show a difference between females or male AVPD patients and controls. In the AVPD patients, POMS scores were significantly higher compared with the controls. STAI, BDI, DACS scores, and CTQ significantly increased in the AVPD patients compared with the controls. LF in heart rate variability in AVPD significantly increased more compared with controls. CONCLUSIONS: These results suggest that heightened sympathetic reactivity in female AVPD co-occurs with attenuated salivary cortisol responses to electric stimulation stress and there is a significant difference between AVPD and controls in mood, anxiety, social cognition, and automatic nerve systems.

Hyperfunction of left lateral prefrontal cortex and automatic thoughts in social anxiety disorder: A near-infrared spectroscopy study.

BACKGROUND: Patients with social anxiety disorder (SAD) experience unusual fear in normal social situations. The verbal fluency task (VFT) was administered while subjects were undergoing near-infrared spectroscopy (NIRS) scanning. The purpose of VFT was to examine the functions of the frontal and temporal lobes. METHODS: Subjects included 145 drug-naïve patients with SAD and 152 healthy controls (HCs). All subjects underwent psychological testing to determine levels of anxiety and depression and to evaluate cognition. RESULTS: The scores of patients with SAD indicated significantly higher anxiety and depressive states than those in HCs on several measures: Leibowitz Social Anxiety Scale (LSAS), Profile of Mood States (POMS), Spielberger Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Social Adaptation Self-evaluation Scale (SASS). The patients with SAD also had higher scores on the future denial, threat prediction, self-denial, past denial, and interpersonal threat sections of the Depression and Anxiety Cognition Scale (DACS). NIRS scanning revealed hyperactivity in the left frontal cortex of patients with SAD. Threat prediction scores on DACS were negatively correlated with oxy-Hb responses in the right frontal cortex. LIMITATIONS: Further studies with a larger sample size are required to verify our findings. CONCLUSIONS: The results of this study demonstrate the different mechanisms of the right and left frontal cortex in situations of social anxiety disorder.

FKBP5 is associated with amygdala volume in the human brain and mood state: A voxel-based morphometry (VBM) study.

The present study was to investigate the effects of 6 FK506 binding protein 51 (FKBP5) single nucleotide polymorphisms (SNPs) on brain structure using voxel-based morphometry (VBM) and the psychological tests to psychological stress. We genotyped 112 healthy controls with respect to 6 SNPs (rs) of FKBP5. We examined the Beck Depression Inventory and the State (STAI-S) and Trait (STAI-T) versions of the Spielberger Anxiety Inventory and the Profile of Mood States (POMS) to evaluate mood. The right amygdala was larger in subjects with the minor allele (C) of rs3800373 and rs992105 and the minor allele (T) of rs1360780. The right middle orbitofrontal region in those with the minor allele (C) of rs3800373 and the right inferior orbitofrontal region in those with the minor allele (T) of rs9470080 was larger. Both the amygdala volumes were associated significantly with FKBP5 SNPs. We found significant relationships between factors in POMS and the right and left amygdala and left insula. Our results suggest that FKBP5 SNPs are associated with the alternations of volumes in right amygdala and the right middle and inferior orbitofrontal region. Genetic variants of FKBP5 may be associated with depressive and anxiety state via differential effects on amygdala and orbitofrontal region.

Genetic association of the transcription of neuroplasticity-related genes and variation in stress-coping style.

INTRODUCTION: Stress coping has been defined as the cognitive and behavioral efforts made to conquer, endure, or decrease external and internal demands and the conflicts between them. It has two main elements: the control or modification of the person-environment relationship causing the stress (i.e., problem-focused coping) and/or regulation of stressful feelings (i.e., emotion-focused coping). Research suggests that the expressions of brain-derived neurotrophic factor (BDNF) and neurotrophic tyrosine kinase receptor type 2 (NTRK2) play important roles in brain adaptation to investigate stress. To clarify the genetic basis of stress coping, we investigated the association of stress-coping strategies and social adaptation with single-nucleotide polymorphisms (SNPs) involved in neural plasticity, anxiety, and depression. METHODS: In 252 healthy controls (94 women; 158 men), we measured and estimated the stress-coping style using the Lazarus-type stress-coping inventory, ego aptitude scale (EAS), and social adaptation self-evaluation scale (SASS). We investigated one SNP of BDNF (rs6265, Val/Met) and five SNPs of NTRK2 (rs11140800, rs1187286, rs1867283, rs1147198, and rs10868235). RESULTS: We observed significant associations between BDNF and emotion-focused strategies, seeking social support, self-control, and distancing. We also found significant associations between NTRK2 and cognitive strategies, problem-solving, confrontive- coping, seeking social support, distancing and positive reappraisal. Significant associations were also found between BDNF and critical attitudes and between NTRK2 and all seven ego-related factors on the EAS. In the SASS, the minor allele rs1867283 of NTRK2 had a significantly higher score than the heterozygote. CONCLUSIONS: These findings may provide insights into the partial effects of genetic mutations in BDNF and NTRK2 on stress tolerance and personality.

Gender determines cortisol and alpha-amylase responses to acute physical and psychosocial stress in patients with borderline personality disorder.

Borderline personality disorder (BPD) is characterized by affective instability, unstable relationships, and identity disturbance. We measured salivary alpha-amylase (sAA) and salivary cortisol levels in all participants during exposure to the Trier Social Stress Test (TSST) and an electric stimulation stress. Seventy-two BPD patients were compared with 377 age- and gender- matched controls. The State and Trait versions of the Spielberger Anxiety Inventory test (STAI-S and STAI-T, respectively), the Profile of Mood State (POMS) tests, and the Beck Depression Inventory (BDI), the Depression and Anxiety Cognition Scale (DACS) were administered to participants before electrical stimulation. Following TSST exposure, salivary cortisol levels significantly decreased in female patients and significantly increased in male patients compared with controls. POMS tension-anxiety, depression-dejection, anger-hostility, fatigue, and confusion scores were significantly increased in BPD patients compared with controls. In contrast, vigor scores were significantly decreased in BPD patients relative to controls. Furthermore, STAI-T and STAI-S anxiety scores and BDI scores were significantly increased in BPD patient compared with controls. DACS scores were significantly increased in BPD patient compared with controls. Different stressors (e.g., psychological or physical) induced different responses in the HPA and SAM systems in female or male BPD patients.

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.

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress.

BACKGROUND: Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder. METHODS: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A). RESULTS: A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P<0.05) was demonstrated that revealed different salivary cortisol responses in the TSST but not in electrical stimulation. Met/Met women had stronger cortisol responses than Val/Met and Val/Val individuals in the TSST. Met/Met men exhibited stronger salivary cortisol responses than Val/Met and Val/Val individuals in the TSST. CONCLUSION: These results indicate that a common, functionally significant polymorphism in BDNF had different effects on hypothalamic-pituitary-adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests.

Near-Infrared Spectroscopy during the Verbal Fluency Task before and after Treatment with Image Exposure and SSRI Therapy in Patients with Obsessive-Compulsive Disorder.

Drug therapy with selective serotonin reuptake inhibitors (SSRIs) has been used as a treatment for obsessive-compulsive disorder (OCD). In the present case report, exposure therapy was used in addition to escitalopram (20 mg) to treat a 28-year-old female patient with OCD for 6 months. Her obsessive-compulsive symptoms comprised thoughts of words such as rape, crematorium, neck hanging, unhappy, death, die, and kill and images such as a shelf of gods, a shrine, a Buddhist altar, the sun, the sky, and the faces of her parents, siblings, and relatives. As exposure therapy, she was asked to view the images associated with these symptoms three times a day along with drug therapy. With the combination of drug and exposure therapies, her obsessive-compulsive symptoms improved within 6 months, with no interference in her daily life. Multichannel near-infrared spectroscopy (NIRS) showed improvement of brain function in the temporal and frontal lobes after treatment. These results suggest that NIRS can be used as an indicator of brain function improvement in patients with OCD.

Association of microcephalin 1, syntrophin-beta 1, and other genes with automatic thoughts in the Japanese population.

Automatic thoughts may be risk factors for depression and anxiety, and should be detected early. However, the genetic basis of automatic thoughts remains unclear. This study aims to investigate the genetic association of automatic thoughts with SNPs (single nucleotide polymorphisms) involved in cognition, neurogenesis, neuronal cell structure, neurotransmitters, hypothalamus-pituitary adrenal axis and psychiatric illness. The study included 610 healthy participants. We used the Depression and Anxiety Cognition Scale (DACS), a Japanese psychological questionnaire, to assess automatic thoughts. Twenty-five SNPs including COMT, BDNF, FKBP5, SNTB1 (syntrophin-beta 1, rs4512418), and MCPH1 (microcephalin 1, rs2911968) were selected according to their minor allele frequency. Linear regression models were used to test association of mean DACS scores with each allele (major-allele homozygote, heterozygote, and minor-allele homozygote). The significant α-value was set at α < 0.002. Statistical analysis was conducted using SNPStats. Call rates for all genotypes were >98%. Eighteen SNPs did not deviate from Hardy-Weinberg equilibrium, and 7 were excluded from statistical analysis. Significant associations of SNTB1 with interpersonal threat and MCPH1 with future denial were observed only in females. SNTB1 and MCPH1 are located on chromosome 8, which may be involved in neuroticism, avoidant personality and depression. Our results demonstrated that DACS scores showing significant interaction with the 2 SNPs may be regarded as appropriate traits to detect the diathesis of automatic thoughts. The 2 SNPs may be important loci in research on cognitive vulnerability to depression and anxiety.

Assertive case management versus enhanced usual care for people with mental health problems who had attempted suicide and were admitted to hospital emergency departments in Japan (ACTION-J): a multicentre, randomised controlled trial.

BACKGROUND: Non-fatal suicide attempt is the most important risk factor for later suicide. Emergency department visits for attempted suicide are increasingly recognised as opportunities for intervention. However, no strong evidence exists that any intervention is effective at preventing repeated suicide attempts. We aimed to investigate whether assertive case management can reduce repetition of suicide attempts in people with mental health problems who had attempted suicide and were admitted to emergency departments. METHODS: In this multicentre, randomised controlled trial in 17 hospital emergency departments in Japan, we randomly assigned people aged 20 years and older with mental health problems who had attempted suicide to receive either assertive case management (based on psychiatric diagnoses, social risks, and needs of the patients) or enhanced usual care (control), using an internet-based randomisation system. Interventions were provided until the end of the follow-up period (ie, at least 18 months and up to 5 years). Outcome assessors were masked to group allocation, but patients and case managers who provided the interventions were not. The primary outcome was the incidence of first recurrent suicidal behaviour (attempted suicide or completed suicide); secondary outcomes included completed suicide and all-cause mortality. This study is registered at ClinicalTrials.gov (NCT00736918) and UMIN-CTR (C000000444). FINDINGS: Between July 1, 2006, and Dec 31, 2009, 914 eligible participants were randomly assigned, 460 to the assertive case management group and 456 to the enhanced usual care group. We noted no significant difference in incidence of first recurrent suicidal behaviour between the assertive case management group and the enhanced usual care group over the full study period (log-rank p=0·258). Because the proportional hazards assumption did not hold, we did ad-hoc analyses for cumulative incidence of the primary outcome at months 1, 3, 6, 12, and 18 after randomisation, adjusting for multiplicity with the Bonferroni method. Assertive case management significantly reduced the incidence of first recurrent suicidal behaviour up to the 6-month timepoint (6-month risk ratio 0·50, 95% CI 0·32-0·80; p=0·003), but not at the later timepoints. Prespecified subgroup analyses showed that the intervention had a greater effect in women (up to 18 months), and in participants younger than 40 years and those with a history of previous suicide attempts (up to 6 months). We did not identify any differences between the intervention and control groups for completed suicide (27 [6%] of 460 vs 30 [7%] of 454, log-rank p=0·660) or all-cause mortality (46 [10%] of 460 vs 42 [9%] of 454, log-rank p=0·698). INTERPRETATION: Our results suggest that assertive case management is feasible in real-world clinical settings. Although it was not effective at reducing the incidence of repetition of suicide attempts in the long term, the results of our ad-hoc analyses suggested that it was effective for up to 6 months. This finding should be investigated in future research. FUNDING: The Ministry of Health, Labour, and Welfare of Japan.

Salivary alpha-amylase and cortisol responsiveness following electrically stimulated physical stress in bipolar disorder patients.

BACKGROUND: Bipolar disorder (BP) is often associated with a change in hypothalamus- pituitary-adrenal axis function change due to chronic stress. Salivary α-amylase (sAA) levels increase in response to psychosocial stress and thus function as a marker of sympathoadrenal medullary system activity. However, sAA has been studied less often than salivary cortisol in BP patients. METHOD: We measured Profile of Mood States and State-Trait Anxiety Inventory scores, heart rate variability, and salivary cortisol levels during electrical stimulation stress in 25 BP patients and 22 healthy volunteers. RESULTS: Tension-anxiety, depression-dejection, anger-hostility, fatigue, and confusion scores in BP patients significantly increased compared with those of the healthy controls. In contrast, the vigor scores of BP patients significantly decreased compared with those of the healthy controls. Significant difference in the sAA levels was observed between BP patients and healthy controls. sAA of female patients was significantly higher than that of female healthy controls, and sAA in male patients tended to be higher than that of male healthy controls. No difference in salivary cortisol was observed between BP patients and the healthy controls. Only three time points were measured before and after the electrical stimulation stress. Furthermore, sAA secretion by BP patients increased before and after electrical stimulation. CONCLUSION: These preliminary results suggest that sAA may be a useful biological marker for BP patients.

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.

Salivary alpha-amylase and cortisol responsiveness following electrical stimulation stress in obsessive-compulsive disorder patients.

Salivary α-amylase (sAA) serves as a marker of sympathoadrenal medullary system (SAM) activity. Salivary AA has not been extensively studied in obsessive-compulsive disorder (OCD) patients. In the current study, 45 OCD patients and 75 healthy volunteers were assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Profile of Mood State (POMS), and the State-Trait Anxiety Inventory (STAI). Measures of heart rate variability (HRV), sAA, and salivary cortisol were also obtained following the application of electrical stimulation stress. The Y-BOCS and POMS Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue, and Confusion scores were significantly increased in patients with OCD compared with healthy controls. In contrast, Vigor scores were significantly decreased in patients with OCD relative to scores in healthy controls. There was no difference in HRV between the patients and the controls. Salivary AA levels in female and male OCD patients were significantly elevated relative to controls both before and after electrical stimulation. In contrast, there were no differences in salivary cortisol levels between OCD patients and controls. The elevated secretion of sAA before and after stimulation may suggest an increased responsiveness to novel and uncontrollable situations in patients with OCD. An increase in sAA might be a characteristic change of OCD.