Anti-LGI1 encephalitis preceded by psychiatric symptoms: A case report.

Background: To date, only a few reports of anti-LGI1 encephalitis with isolated psychiatric symptoms in the initial phase have been reported. We present a relatively rare case of antileucine-rich glioma-inactivated 1 (LGI1) encephalitis that developed only psychiatric symptoms at the onset. Case Presentation: The patient was a male in his 40s who developed anxiety and panic symptoms and was started on antidepressants after being diagnosed with panic disorder by a psychiatrist. He visited our hospital 2 months later presenting with hallucinations, delusions, mild cognitive decline, and faciobrachial dystonic seizures in the left upper extremity and face. Fluid-attenuated inversion recovery magnetic resonance imaging revealed swelling and hyperintensities in the right caudate nucleus and putamen. Cerebrospinal fluid analysis did not show increased protein levels or cell counts and revealed positive oligoclonal bands. Subsequently, positive results for anti-LGI1 antibodies were observed in the cerebrospinal fluid. Therefore, the patient was diagnosed with anti-LGI1 encephalitis. Conclusion: This case highlights the need to consider anti-LGI1 encephalitis therapy in patients with acute-onset psychiatric symptoms.

Longitudinal Changes of Regional Cerebral Blood Flow on a Single-Photon Emission Computed Tomography (SPECT) Scan in a Patient With Schizophrenia Having Cotard's Syndrome.

Cotard's syndrome is a rare clinical condition characterized by the presence of nihilistic delusions, delusions of immortality, depressive mood, and anxiety. Longitudinal changes in regional cerebral blood flow (rCBF) obtained under different conditions with and without Cotard's syndrome have rarely been reported in the literature. We report a case of a patient with Cotard's syndrome in whom longitudinal rCBF was assessed using single-photon emission computed tomography (SPECT). The patient was a 52-year-old man suffering from schizophrenia and mild mental retardation. He was transported to our hospital because of lumbar fractures caused by a suicidal attempt. In the second week after admission, he displayed Cotard's syndrome, i.e., nihilistic delusions, suicidal thoughts, and depressive mood. SPECT with 99mTc-ethyl cysteinate dimer was performed, and the rCBF increased in the bilateral prefrontal cortex but decreased in the occipital and parietal lobes. He was treated with pharmacotherapy mainly using lurasidone, and his Cotard's symptoms disappeared. SPECT was performed again. The increased rCBF in the bilateral prefrontal cortex and the decreased rCBF in the right occipital and parietal lobes were improved. The present case suggests that increased rCBF in the prefrontal cortex and decreased rCBF in the right occipital and parietal lobes are associated with the development of Cotard's syndrome.

Comparison of dysfunctional attitudes, cognitive vulnerability to depression, before and during the COVID-19 pandemic in healthy participants.

BACKGROUND: During the COVID-19 pandemic, depression and suicide rates increased worldwide, and in Japan. Presumably, an increase of neuroticism-related personality traits mediates the relation linking the COVID-19 pandemic with depression and suicide. This study examined COVID-19 pandemic effects on dysfunctional attitudes, cognitive vulnerability to depression, in healthy participants. METHODS: The study used Dysfunctional Attitude Scale (DAS) -24 data of three subscales (i.e., achievement, dependency, and self-control) obtained from 270 Japanese medical students during October 2017 - June 2022. Participants were divided into two groups: those for whom DAS-24 was assessed before the pandemic (phase 1 group, October 2017 - March 2020, n = 178) and those for whom DAS-24 was assessed during the pandemic (phase 2 group, April 2020 - June 2022, n = 92). RESULTS: Total DAS-24 scores of the phase 2 group were significantly (p = 0.047) lower than those of the phase 1 group. Scores of the dependency subscale for the phase 2 group were significantly (p = 0.002) lower than those for the phase 1 group, but no significant difference was found in the scores of the achievement and self-control subscales. CONCLUSIONS: These findings suggest that a decrease in DAS-24 scores, particularly of the dependency subscale, occurred during the COVID-19 pandemic. Possible mechanisms underlying these results are 1) individuals became less preoccupied with receiving evaluation, 2) individuals realized that self-cognition depending on the approval of others is unimportant, and 3) high levels of dysfunctional attitude were maladaptive for obtaining affective benefits via social interactions during the COVID-19 pandemic.

Jitteriness/anxiety syndrome caused by coadministration of celecoxib, a selective COX-2 inhibitor, with escitalopram and trazodone in a patient with depression and spondylolisthesis.

Antidepressant-induced jitteriness/anxiety syndrome is characterized as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, and (hypo)mania, which appear immediately after initiation or increased dosage of an antidepressant. This report describes a case of the jitteriness/anxiety syndrome caused by the coadministration of celecoxib with escitalopram and trazodone in a patient with depression and spondylolisthesis. The depression of a patient, a woman in her 60 s, had been in remission at least for 5 years under treatment using escitalopram and trazodone. Immediately after coadministration of celecoxib because of her buttock and limb pain, she showed anxiety, agitation, akathisia, insomnia, irritability, aggressiveness, impulsivity, and hypomania. These symptoms disappeared after the discontinuation of celecoxib. The present case suggests that coadministration of celecoxib with escitalopram and trazodone can cause the jitteriness/anxiety syndrome, presumably via a pharmacokinetic interaction of celecoxib with these antidepressants and/or the effects of celecoxib on serotonergic neurotransmission.

A fatal case of fulminant neuroleptic malignant syndrome: A case report.

Background: Neuroleptic malignant syndrome (NMS), a rare but potentially life-threatening adverse reaction to treatment with antipsychotic drugs, is characterized by hyperthermia, muscle rigidity, impaired consciousness, and autonomic disturbances. Some reports have described rapidly progressing cases of NMS resulting in death within several days. This report describes a clinical course of fatal and fulminant NMS in a patient with schizoaffective disorder. Case Presentation: A 67-year-old man had long been in a stable condition under antipsychotic pharmacotherapy. At 3 days before admission to our hospital, he complained of diarrhea, fatigue, and reduced appetite. On admission to our hospital, he showed fever, mild muscle rigidity at the four extremities, elevated heart rate, hypertension, excessive diaphoresis, and decreased percutaneous oxygen saturation (SpO2). He was diagnosed as having NMS. Within 3 days after the onset of NMS, he displayed severe hyperthermia up to 41.4°C and severe autonomic disturbances, including elevated heart rate and hypertension. Despite treatments with dantrolene and bromocriptine, he went into shock and died on the fourth day after admission. Conclusion: The present case suggests that severe hyperthermia and severe autonomic disturbances at the early stage of the onset might be signs of fatal and fulminant NMS. It may be recommended that clinicians consider electro-convulsive therapy when treating fulminant NMS with these symptoms.

Associations of the A118G OPRM1 polymorphism with sociotropy and interpersonal sensitivity.

BACKGROUND: The µ-opioid receptor (MOR) plays an important role in social bonding behaviors, while it is implicated in the pathophysiology of depression. It is shown that the A118G polymorphism (rs1799971) of the MOR gene (OPRM1) causes amino-acid exchange from Asn to Asp, and that this polymorphism is associated with altered mu-opioid receptor function. Meanwhile, sociotropy/autonomy and interpersonal sensitivity are personality vulnerabilities to depression characterized by distinctive interpersonal styles. The present study tested the hypothesis that the functional A118G OPRM1 polymorphism influences these personality traits. METHODS: The subjects were 402 physically and mentally healthy Japanese volunteers. Sociotropy and autonomy were measured by the Sociotropy-Autonomy Scale, and interpersonal sensitivity was evaluated by the Interpersonal Sensitivity Measure. The A118G polymorphism of the OPRM1 was determined by the PCR method. RESULTS: In one factor analysis of covariance, there were differences in scores of sociotropy (uncorrected p < .001, corrected p < .003) and interpersonal sensitivity (uncorrected p = .015, corrected p = .045), but not autonomy, among the A/A, A/G, and G/G genotypes. Post hoc LSD tests showed that sociotropy scores were higher in the A/A group than in the A/G (p = .029) and G/G (p < .001) groups, and higher in the A/G group than in the G/G group (p = .004). Interpersonal sensitivity scores were higher in the A/A group than in the A/G (p = .023) and G/G (p = .009) groups. CONCLUSION: This study suggests that the A118G OPRM1 polymorphism is associated with sociotropy and interpersonal sensitivity, interpersonal vulnerabilities to depression.

Serotonin syndrome induced by overdose of atomoxetine alone in a patient with attention-deficit hyperactivity disorder: A case report.

Background: Serotonin syndrome is characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. This syndrome results from various medications that engender serotonergic overactivity. Atomoxetine is a norepinephrine reuptake inhibitor used for the treatment of attention-deficit hyperactivity disorder (ADHD). Two case reports have described serotonin syndrome induced by the combination of atomoxetine with venlafaxine or methylphenidate, but no report describes this syndrome induced by atomoxetine alone. This report describes serotonin syndrome induced solely by an overdose of atomoxetine in a patient with ADHD. Case Presentation: The patient in this case was a 21-year-old man who had been treated with atomoxetine for ADHD. He was transported to our hospital 1 h after intentional ingestion of 1200 mg of atomoxetine in a suicide attempt. On admission, he showed profuse diaphoresis, marked agitation, somnolence, slight fever, tachycardia, prolonged QT interval, myoclonus, tremor, and hyperreflexia. He was diagnosed as having serotonin syndrome and was treated with administration of activated charcoal and massive infusion. Three days later, his serotonin syndrome symptoms had disappeared completely. Conclusion: Findings in this case suggest that atomoxetine alone can cause serotonin syndrome presumably via its effects of serotonin reuptake inhibition. Clinicians should consider this syndrome induced by atomoxetine overdose.

Oxytocin receptor polymorphism influences characterization of harm avoidance by moderating susceptibility to affectionless control parenting.

INTRODUCTION: Oxytocin receptor (OXTR) gene polymorphism reportedly moderates effects of negative environments during childhood on mental function and behavior such as depressive symptoms and externalizing problems. This study examined OXTR gene polymorphism effects on personality traits in healthy participants, considering interaction effects of polymorphism with affectionless control (AC) parenting which is one of the dysfunctional and pathogenic parenting styles. METHODS: For 496 Japanese volunteers, personality was evaluated using the Temperament and Character Inventory. The Parental Bonding Instrument, which has subscales of care and protection, was used to assess perceived parental rearing. AC parenting was defined as low care and high protection. A/G polymorphism of the OXTR gene (rs53576) was detected using TaqMan SNP Genotyping Assay. RESULTS: Two-way analysis of covariance revealed significant interaction effects between the genotype and the number of AC parents on scores of harm avoidance, with no significant main effect of genotype on any personality. Post-hoc analysis revealed that the harm avoidance scores were increased in a stepwise manner with respect to the increase of the number of AC parents in the A allele carriers. No similar association was observed in the A allele noncarriers. CONCLUSION: The results of this study suggest that OXTR polymorphism influences characterization of harm avoidance by moderating susceptibility to AC parenting.

Case Report: Changes in Regional Cerebral Blood Flow in Chronic Akathisia of a Depressed Patient Before and After Electroconvulsive Therapy Treatment.

Akathisia, which characterized by subjective restlessness and objective hyperactivity, is induced mostly by antipsychotics and antidepressants. Chronic akathisia is defined as persistence of symptoms for more than 3 months. The pathophysiology of chronic akathisia remains unclear. This report describes a depressed patient, a 66-year-old woman with a diagnosis of major depressive disorder, with chronic akathisia. Her regional cerebral blood flow (rCBF) was measured using single photon emission computed tomography (SPECT) before and after the treatment with electroconvulsive therapy (ECT). She had experienced akathisia-like symptoms three times prior because of risperidone, escitalopram, and clomipramine administration, accompanied by major depression. After levomepromazine was added to quetiapine to treat insomnia, she developed akathisia symptoms such as a sense of restlessness and inability to sit in one place for a few minutes. These antipsychotics were withdrawn. Propranolol was administered, leading to no apparent improvement for 8 months. After she was diagnosed as having major depressive disorder and chronic akathisia, she received 10 sessions of bilateral ECT. Her depressive symptoms improved greatly. Akathisia disappeared completely after ECT. SPECT revealed that rCBF was decreased in the middle frontal gyrus and parietal lobe, that it was increased in the thalamus, fusiform gyrus, and cerebellum before ECT, and that these abnormalities in rCBF were approaching normal levels after ECT. Findings presented in this report suggest ECT as a beneficial treatment for chronic akathisia. Altered rCBF in the middle frontal gyrus, parietal lobe, thalamus, fusiform gyrus, and cerebellum, and especially decreased rCBF in the parietal lobe, may be related to the pathophysiology of chronic akathisia.

Mu-Opioid Receptor Polymorphism Moderates Sensitivity to Parental Behaviors During Characterization of Personality Traits.

PURPOSE: Attachment research shows that attachment experiences with parents in childhood influence the characterization of personality traits. Meanwhile, it is known that mu-opioid receptor function is involved in human attachment. Furthermore, a few studies suggest that the A118G polymorphism of the mu-opioid receptor gene (OPRM1) is associated with altered mu-opioid receptor function. Thus, we examined if the OPRM1 polymorphism moderates the sensitivity to parental behaviors and thereby contributes to the characterization of personality traits. MATERIALS AND METHODS: Participants were 725 healthy Japanese. Parenting practices of their parents were evaluated by the Parental Bonding Instrument (PBI) with the care and protection subscales. Personality was evaluated using the Temperament and Character Inventory (TCI). The OPRM1 A118G polymorphism was detected by a PCR method. RESULTS: Multiple regression analyses revealed significant effects of the interaction between the OPRM1 genotype and maternal protection on scores of the self-directedness and cooperativeness dimensions, while significant main effects of the OPRM1 genotype on scores of the TCI were not found. Further analyses showed that there were significant negative correlations between maternal protection scores and the two dimensional scores in the A/A and A/G genotypes with higher correlation coefficients in the former, but not in the G/G genotype. CONCLUSION: The present study suggests that the OPRM1 polymorphism contributes to the characterization of personality traits by moderating the sensitivity to parental behaviors, especially maternal protection.

Interrelation Between Increased BDNF Gene Methylation and High Sociotropy, a Personality Vulnerability Factor in Cognitive Model of Depression.

PURPOSE: It is suggested that increased methylation of the brain-derived neurotrophic factor (BDNF) gene is involved in the pathogenesis of depression, while sociotropy and autonomy are proposed as personality vulnerability factors in cognitive model of depression. We examined the interrelation between BDNF gene methylation and sociotropy or autonomy, with taking into account the previously reported deleterious effect of parental overprotection on sociotropy. MATERIALS AND METHODS: The participants consisted of 90 healthy Japanese volunteers. Methylation levels of the BDNF gene in peripheral blood were quantified by bisulfite pyrosequencing. Sociotropy and autonomy were assessed by the Sociotropy-Autonomy Scale, and perceived parental protection was evaluated by the Parental Bonding Instrument. RESULTS: In Pearson's correlation analysis, there was a positive correlation between methylation levels of the BDNF gene and sociotropy scores (p<0.05) but not autonomy scores, and a positive correlation between maternal protection scores and sociotropy scores (p<0.05). In structural equation modeling, two models were proposed; the first one is that hypermethylation of the BDNF gene and maternal overprotection independently contribute to high sociotropy, and the second one is that maternal overprotection contributes to high sociotropy which then leads to hypermethylation of the BDNF gene. CONCLUSION: The present study suggests an interrelation between increased BDNF gene methylation and high sociotropy.

Implication of core beliefs about negative-self in neuroticism.

Objective: Core beliefs about negative-self are beliefs about self-deficiencies in basic aspects of human adaptation. Meanwhile, neuroticism is a personality trait characterised by negative emotionality, i.e., a tendency to react to stress with negative emotions. The present study tested the hypothesis that core beliefs about negative-self are implicated in neuroticism.Methods: The subjects were 309 Japanese healthy volunteers. Core beliefs about negative-self were evaluated by the Brief Core Schema Scales, and neuroticism was evaluated by the NEO Personality Inventory-Revised.Results: In both multiple regression analysis and structural equation modelling, higher neuroticism was strongly predicted by higher levels of core beliefs about negative-self.Limitations: The present study cannot determine the causal relationship between core beliefs about negative-self and neuroticism, because of its cross sectional design.Conclusions: The present study suggests that core beliefs about negative-self are deeply implicated in neuroticism.Key PointsImplication of core beliefs about negative-self in neuroticism was examined.Neuroticism was predicted by higher levels of these core beliefs.These core beliefs may be involved in negative emotionality of neuroticism.

Link of negative core beliefs about the self with perceived dysfunctional parenting.

Cognitive theory posits the central role of negative core beliefs about the self in cognitive vulnerabilities to depression, and this position is supported by empirical studies. It is also hypothesized that these core beliefs develop as a result of negative interactions with significant others in early life. To test the hypothesis that negative core beliefs about the self are formed by dysfunctional parenting, we examined their relations with perceived parental rearing. The subjects were 355 Japanese healthy volunteers. Core beliefs of negative-self were assessed by the corresponding subscale of the Brief Core Schema Scales. Perceived parental care and protection were evaluated by the corresponding subscales of the Parental Bonding Instrument. In both multiple regression analysis and structural equation modeling, core beliefs of negative-self were predicted by perceptions of high maternal protection and low paternal care. The present study shows that negative core beliefs about the self are linked with perceived dysfunctional parenting, suggesting that the formation mechanism of these core beliefs is at least partly ascribable to dysfunctional parenting.

Relation of high neuroticism with increased methylation of the BDNF gene.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has an important function in neuroplasticity and neuronal development. It is suggested that increased methylation of the BDNF gene resulting in decreased BDNF activity is associated with depression. Meanwhile, neuroticism is a well-known risk factor for developing depression. In the present study, the relationship between methylation of the BDNF gene and personality traits including neuroticism was examined. SUBJECTS AND METHODS: The subjects were 98 healthy Japanese. Methylation levels of the BDNF gene were determined by the bisulfite-pyrosequencing method. Personality traits including neuroticism were assessed by the NEO Personality Inventory-Revised. RESULTS: There was a positive correlation between neuroticism scores and methylation levels of the BDNF gene. The subjects with higher neuroticism scores had higher levels of BDNF gene methylation compared with those with lower neuroticism scores. Meanwhile, other personality traits were not associated with BDNF gene methylation. CONCLUSION: The present study suggests that high neuroticism is related to increased methylation of the BDNF gene.

Interrelations among negative core beliefs, attachment anxiety and low self-directedness, putative central constructs of depression vulnerabilities in cognitive, attachment and psychobiological personality theories.

The present study examined the interrelations among negative core beliefs, attachment anxiety and low self-directedness, to test if the central constructs of depression vulnerabilities in cognitive, attachment and psychobiological personality theories are integrated into negative self-image. The subjects were 410 healthy Japanese medical students and staff. Negative core beliefs, attachment anxiety and self-directedness were evaluated by the Brief Core Schema Scales, Experiences in Close Relationships and Temperament and Character Inventory, respectively. There were strong interrelations among the three factors. The present study suggests that the central constructs of depression vulnerabilities in the three theories are integrated into negative self-image.

Implication of the DGKH genotype in openness to experience, a premorbid personality trait of bipolar disorder.

AIMS: The diacylglycerol kinase η gene (DGKH) is one of the few replicated risk genes for bipolar disorder. Meanwhile, specific personality traits, especially openness to experience, have been suggested as premorbid personality traits of the disorder. The aim of the present study was to examine the relation of the DGKH genotype with broad dimensions of personality, to obtain further evidence for its implication in the etiology of bipolar disorder. METHODS: The subjects were 319 Japanese healthy volunteers. Personality was assessed by the NEO Personality Inventory-Revised, which has the neuroticism, extraversion, openness to experience, agreeableness and conscientiousness dimensions. The A/G polymorphism of DGKH (rs9525580) was detected by a PCR-RFLP method. The subjects were divided into two groups with respect to the presence or absence of the A allele, which is a putative risk allele for bipolar disorder. RESULTS: The group with the A allele had significantly (p < 0.05) higher scores of openness to experience compared to that without this allele. Scores of other dimensions were not different between the two groups. LIMITATIONS: The subjects had a homogeneous but rather specific background, and we did not employ a longitudinal design. CONCLUSIONS: The present study shows that a bipolar-risk allele of DGKH is associated with higher openness to experience, providing further evidence for the implication of this gene in the etiology of bipolar disorder.

Marked differences in core beliefs about self and others, between sociotropy and autonomy: personality vulnerabilities in the cognitive model of depression.

OBJECTIVE: The cognitive model of depression posits two distinctive personality vulnerabilities termed sociotropy and autonomy, each of which is composed of a cluster of maladaptive self-schemas. It is postulated that negative core beliefs about self underlie maladaptive self-schemas as a whole, whereas those about others may be implicated in the autonomous self-schemas. Therefore, the present study examined the relations of sociotropy and autonomy with core beliefs about self and others. METHODS: The sample of this study consisted of 321 healthy Japanese volunteers. Sociotropy and autonomy were evaluated by the corresponding subscales of the Sociotropy-Autonomy Scale. Core beliefs about self and others were assessed by the negative-self, positive-self, negative-other and positive-other subscales of the Brief Core Schema Scales. RESULTS: In the forced multiple regression analysis, sociotropy scores were correlated with negative-self scores (ß = 0.389, P < 0.001). Meanwhile, autonomy scores were correlated with positive-self scores (ß = 0.199, P < 0.01) and negative-other scores (ß = 0.191, P < 0.01). CONCLUSION: The present study suggests marked differences in core beliefs about self and others between sociotropy and autonomy, further contrasting the two personality vulnerabilities to depression.

Close relation of interpersonal sensitivity with negative core beliefs about the self, the central construct of cognitive vulnerability to depression.

Interpersonal sensitivity is a personality trait linked with anxious attachment conceptualized in attachment theory. This personality trait is comprised of four components, i.e., interpersonal awareness, separation anxiety, timidity and fragile inner-self, which are measured by the corresponding subscales of the Interpersonal Sensitivity Measure (IPSM). Meanwhile, one study showed that six items of the IPSM tentatively used as negative self-schemas predicted the onset of depression. To clarify if interpersonal sensitivity reflects cognitive vulnerability, we examined the relation of this personality trait with negative core beliefs about the self. The study population consisted of 335 Japanese volunteers. Interpersonal sensitivity was measured by the IPSM, and negative core beliefs about the self were assessed by the negative-self subscale of the Brief Core Schema Scales (BCSS). Multiple regression analysis showed that scores of the four subscales of the IPSM were strongly correlated with those of the negative-self subscale of the BCSS (P < 0.001). Similarly, sequential equation modeling demonstrated that the four components of interpersonal sensitivity were strongly predicted by core beliefs of negative-self (P < 0.001). The present study shows that interpersonal sensitivity is closely related to negative core beliefs about the self, suggesting that this personality trait can be regarded as a cognitive vulnerability to depression.

Relationship of negative and positive core beliefs about the self with dysfunctional attitudes in three aspects of life.

OBJECTIVE: Cognitive theory assumes a pivotal role of negative core beliefs about the self in dysfunctional attitudes predisposing to depression. Meanwhile, the role of positive core beliefs about the self in cognitive vulnerability to depression is unknown. Therefore, we examined the relationship of negative and positive core beliefs about the self with dysfunctional attitudes in three aspects of life. METHODS: The subjects were 311 Japanese volunteers. Core beliefs of negative-self and positive-self were evaluated by the corresponding subscales of the Brief Core Schema Scales. Dysfunctional attitudes in the areas of achievement, dependency and self-control were measured by the corresponding subscales of the 24-item Dysfunctional Attitude Scale. RESULTS: The negative-self subscale was correlated with the achievement, dependency and self-control subscales. The positive-self subscale was correlated with the achievement and self-control subscales. CONCLUSION: The present study suggests that negative core beliefs about the self underlie all types of dysfunctional attitudes, while positive core beliefs about the self have some connections with dysfunctional attitudes related to achievement and self-control.