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.

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 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.

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.

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.

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.

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.

[The pathophysiology and diagnosis of anxiety disorder].

In addition to genetic factors, the role of epigenetic and other environmental factors in the promotion of anxiety disorder has attracted much attention in psychiatric research. When stress is encountered in the environment, the hypothalamus-pituitary adrenal system (HPA system) is activated and cortisol is secreted. CRHR gene function is closely related to this response. As a result of haplotype analysis of CRHR genes in depression and panic disorder patients, it was found that genetic polymorphism of CRHR1 and CRHR2 was related to both disorders. It is reported that abused children are more susceptible to developing depression and anxiety disorder upon reaching adulthood, but there also exist genetic polymorphisms that may moderate this relationship. Direct methylation of DNA (typically repressing gene expression) and modification of chromatin structure (complexes of histone proteins and DNA) via acetylation (typically facilitating gene expression) represent epigenetic modifications that are thought to influence behavioral phenotypes. For example, it is rare that schizophrenia develops in identical twins brought up together in the same environment, and thus phenotypic differences cannot be explained simply by genetic polymorphism. We also evaluated salivary cortisol and amylase reactivity (indices of the HPA system and sympathoadrenal medullary system, respectfully) after electrical stimulation stress and Trier Social Stress Test (TSST) administration. Here we found differences in the cortisol stress response between electrical stimulation and TSST stressors, in contrast to the theory of Selye. In addition, we found alterations in activity patterns and difficulties integrating sensorimotor information in panic disorder patients, suggesting links between sensorimotor integration and stress in panic disorder. Moreover, state and trait anxiety may be associated with stabilograph factors.

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.

Functional brain mapping during recitation of Buddhist scriptures and repetition of the Namu Amida Butsu: a study in experienced Japanese monks.

BACKGROUND: The invocation Namu Amida Butsu (Nembutsu), voices the hope of rebirth into Amida's Pure Land. In the Nembutsu, Buddhists imagine that they are absorbed into Amida's Pure Land. Shiritori, a Japanese word chain game, is a common task used to activate language related regions in Japanese. The purpose of this study was to identify the regions activated during praying of the Namo Amida Butsu (Nembutsu), and the reciting of Buddhist scriptures (Sutra). MATERIAL AND METHOD: Functional MRI (fMRI) was used to identify the regions activated by the Nenbutsu, the Sutra and the Shiritori in eight highlytrained Japanese monks. RESULTS: The task of repeating the Nenbutsu activates the medial frontal gyrus, which is mainly related to mental concentration and visuospatial attention, similar to the areas activated by meditation. The task of reciting the Sutra activates the left lateral middle frontal gyrus, the right angular gyrus, and the right supramarginal gyrus, which are related to visuospatial attention also involved in the area activated by meditation. CONCLUSION: These results suggest that different types of meditation in Japanese Buddhism showed different brain regional activation. The Nenbutsu activated the prefrontal cortex, and the Sutra activated the left dorsolateral prefrontal cortex and right parietal cortex.

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.

Administration of antisense DNA for hepatocyte growth factor causes an depressive and anxiogenic response in rats.

Hepatocyte growth factor (HGF) is induced in neurons during ischemia and is neuroprotective against post-ischemic delayed neuronal death in the hippocampus. HGF might play an important role in the maturation and functioning of these neurons in the hippocampus. Our aim was to determine what effect HGF antisense has on depression and anxiety in rats. HGF antisense was infused at a constant rate into cerebral lateral ventricles and its effect on anxiety in rats was monitored. In forced swimming test, rats that received antisense DNA increased the length of time that they were immobile in the water. In the elevated plus maze test, the black and white box test and conditioned fear test, HGF antisense administration caused all indicators of anxiety to increase. Number of HGF-positive cells in C1 of hippocampus was significantly decreased in the HGF antisense-infused group compared to the vehicle- and scrambled oligonucleotide-treated group. No significant effect on general locomotor activity was seen. These results indicate that inhibition of HGF induces an increase in depression and anxiety-related behaviors suggesting a depressive and anxiogenic-like effect.

Anticipatory anxiety-induced changes in human lateral prefrontal cortex activity.

It has been suggested that frontal brain asymmetry is associated with differences in basic emotional dimensions, particularly in activation of systems underlying avoidance-withdrawal behavior. We examined regional cerebral oxygenated hemoglobin (O2Hb) levels in human medial prefrontal cortex (MPFC) using near-infrared reflection spectroscopy (NIRS) prior to and during anticipatory anxiety to determine if NIRS could detect any anxiety-related changes. Transient anxiety was induced in 56 normal volunteers by anticipation and a painful shock to the right-hand's median nerve. Pre- and post-anxiety affective statuses were measured using the State-Trait Anxiety Inventory (STAI) and Temperature Character Inventory (TCI). NIRS recorded from the left and right frontal brain regions. Right MPFC O2Hb was significantly increased relative to left MPFC O2Hb during anticipation of the shock. Right-sided O2Hb increases were significantly correlated with the TCI Harm Avoidance subscale. These results support the hypothesis that O2Hb levels in the right frontal region correlate with anxiety or heightened negative affect.

[Biologic base of anxiety disorders: recent progress].

We reviewed recent knowledge and a biologic base of anxiety disorders. As for brain image study, mainly study on PET, fMRI and NIRS has advanced. The neural circuit hypothesis of Gorman still attracts attention. We will think that characteristics of each anxiety disorder disease will become clear from these studies in future. We think that a genetic role will be associated with personality, character and gene study. We mention the connection between neuropeptides and anxiety in animal experiments. In addition, the past sensory stimulation in the amygdala, regarded as the center of anxiety, and the reinforcement of emotional ties is pointed out as an important thing for anxiety formation.

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.

Administration of antisense DNA for ghrelin causes an antidepressant and anxiolytic response in rats.

RATIONALE: Ghrelin is a peptide of 28 amino acids found in mammals that increases the release of growth hormone, food intake, and body weight. OBJECTIVES: We investigated the relationship between ghrelin and the states of anxiety and depression by giving rats either antisense DNA for ghrelin, scrambled DNA or vehicle into the lateral ventricle of rats. RESULTS: In forced swimming tests, rats that received antisense DNA decreased the length of time that they were immobile in the water. Ghrelin antisense oligonucleotides produced an anxiolytic-like effects in the elevated plus maze test, black and white test, or conditioned fear tests. Treatment with antisense DNA for ghrelin significantly decreased rat body weight. No significant effect on general locomotor activity was seen. CONCLUSIONS: These results suggest that administration of antisense DNA for ghrelin causes an antidepressant and anxiolytic response in rats.

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.