Naturally absorbed lithium may prevent suicide attempts and deliberate self-harm while eicosapentaenoic acid may prevent deliberate self-harm and arachidonic acid may be a risk factor for deliberate self-harm: The updated different findings in new analyses.

Background: Since our previous investigation on the effects of trace lithium, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) on deliberate self-harm and suicide attempts in 2018, to our knowledge, no replication study has been conducted on this topic. Subjects and methods: We increased 37 new patients and totally 234 patients were re-analyzed to further investigate the association of suicide-related behaviors with levels of trace lithium, EPA, DHA, and AA in a different way to avoid multicollinearity. Results: Higher lithium levels were significantly associated with fewer suicide attempts and deliberate self-harm, higher EPA levels were significantly associated with fewer deliberate self-harm, and higher AA levels were significantly associated with more deliberate self-harm. Discussion: Although the sample size was only slightly larger than the previous study, the present results were clearly different from the previous ones due to the use of different statistical analyses to avoid multicollinearity. Conclusion: The present findings suggest that naturally absorbed lithium may protect against suicide and deliberate self-harm, while naturally absorbed EPA may protect against deliberate self-harm. However, naturally absorbed AA may be a risk factor for deliberate self-harm.

Lithium in drinking water and suicide prevention: The largest nationwide epidemiological study from Japan.

OBJECTIVES: The aims of the present study thus were (a) to further investigate the association between lithium levels in drinking water and suicide rates by adjusting relevant factors using the so far largest available dataset in Japan, (b) to confirm sex differences, (c) to estimate the effects of long-term exposure to trace lithium, (d) to investigate the effects of drinking bottled instead of tap water, and (e) to exploratorily investigate which lithium levels may be associated with lower suicide rates. METHODS: Mean lithium levels in drinking water of all 808 cities and wards (ie, 785 cities of 46 prefectures and 23 wards of Tokyo) in Japan were examined in relation to mean suicide standardized mortality ratios (SMRs) during the 7 years from 2010 to 2016. Multiple regression analyses adjusted for the size of each population were used to investigate the association of lithium levels with suicide SMRs with adjustments for relevant factors. RESULTS: The adjusted model showed significant inverse associations of lithium levels with total and male SMRs, but not with female SMRs. Neither the proportion of residents who continued to live in the same city nor the consumption of bottled water changed the association between lithium levels and suicide SMRs. Finally, it was 30 µg/L or more that was associated with lower suicide SMRs. CONCLUSIONS: The present findings reconfirm the inverse association between lithium levels in drinking water and suicide rates particularly in the male population.

Naturally absorbed polyunsaturated fatty acids, lithium, and suicide-related behaviors: A case-controlled study.

OBJECTIVE: Previous studies have investigated the effects of omega-3, omega-6 and lithium on suicide-related behaviors separately. This study was performed to comprehensively investigate the effects of naturally absorbed EPA, DHA, arachidonic acid and lithium in relation to suicide attempt and deliberate self-harm, with adjustment for each other. METHODS: We analyzed plasma EPA, DHA, arachidonic acid levels and serum lithium levels of 197 patients including 33 patients with suicide attempts, 18 patients with deliberate self-harm, and 146 control patients. RESULTS: Multivariate logistic regression analysis with adjustment for age, gender, EPA, DHA, arachidonic acid and log-transformed lithium levels revealed that the negative associations with EPA levels (adjusted OR 0.972, 95% CI 0.947-0.997, p = 0.031) and log-transformed lithium levels (adjusted OR 0.156, 95% CI 0.038-0.644, p = 0.01) and the positive association with DHA levels (adjusted OR 1.026, 95% CI 1.010-1.043, p = 0.002) were significant in patients with suicide attempts than in control patients. The analysis also demonstrated that the positive association with arachidonic acid levels (adjusted OR 1.015, 95% CI 1.005-1.025, p = 0.004) was significant in patients with deliberate self-harm than in control patients. LIMITATIONS: The limitations are relatively small number of patients and the effects of demographics of individual patients could not be adjusted for the analyses. CONCLUSIONS: The present findings suggest that, as naturally absorbed nutrients, higher EPA and lithium levels may be associated with less suicide attempt, and that higher arachidonic acid levels may be associated with more deliberate self-harm.

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.

Serum lithium levels and suicide attempts: a case-controlled comparison in lithium therapy-naive individuals.

BACKGROUND: Several epidemiological studies have shown the inverse association of lithium levels in drinking water and suicide rates; however, it is necessary to perform a clinical study dealing with individual patients. METHODS: We analyzed 199 patients including 31 patients with suicide attempts, 21 patients with self-harm, and 147 control patients. All were transferred to a university emergency department suffering from intoxication or injury, were aged 20 or more years, and were alive at the start of the study. The exclusion criteria consisted of suffering from schizophrenia and a past or present history of lithium therapy. These exclusions were applied because it is difficult to determine whether their suicide attempt was induced by the intent to end their life or by psychotic symptoms such as auditory hallucinations, and if the patient had received lithium therapy, the association between the small amount of lithium taken from drinking water and food and serum lithium levels cannot be detected. RESULTS: There was a significant difference (p = 0.043) between the three groups whereby patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.012) in males but not females. Multivariate logistic regression analysis with adjustment for age and gender revealed that patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.032, odds ratio 0.228, 95% CI 0.059-0.883). LIMITATIONS: The limitations of the present study are the nature of observational research which cannot reveal a causal relationship and the relatively small number of subjects. CONCLUSIONS: The present findings suggest that higher serum lithium levels may be protective against suicide attempts in lithium therapy-naive individuals.

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.

Anxious temperament as a risk factor of suicide attempt.

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

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.

Trace lithium is inversely associated with male suicide after adjustment of climatic factors.

BACKGROUND: Previously, we showed the inverse association between lithium in drinking water and male suicide in Kyushu Island. The narrow variation in meteorological factors of Kyushu Island and a considerable amount of evidence regarding the role of the factors on suicide provoked the necessities of adjusting the association by the wide variation in sunshine, temperature, rain fall, and snow fall. METHODS: To keep the wide variation in meteorological factors, we combined the data of Kyushu (the southernmost city is Itoman, 26°) and Hokkaido (the northernmost city is Wakkanai, 45°). Multiple regression analyses were used to predict suicide SMRs (total, male and female) by lithium levels in drinking water and meteorological factors. RESULTS: After adjustment of meteorological factors, lithium levels were significantly and inversely associated with male suicide SMRs, but not with total or female suicide SMRs, across the 153 cities of Hokkaido and Kyushu Islands. Moreover, annual total sunshine and annual mean temperature were significantly and inversely associated with male suicide SMRs whereas annual total rainfall was significantly and directly associated with male suicide SMRs. LIMITATIONS: The limitations of the present study include the lack of data relevant to lithium levels in food and the proportion of the population who drank tap water and their consumption habits. CONCLUSIONS: The present findings suggest that trace lithium is inversely associated with male but not female suicide after adjustment of meteorological factors.

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 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.

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.