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.

Case report: A case of anti-recoverin antibody-positive encephalitis exhibiting Cotard and Capgras delusions that was successfully treated with electroconvulsive therapy.

Recoverin is a neuron-specific calcium-binding protein that is mainly located in the retina and pineal gland. Few reports have described patients with anti-recoverin antibody-positive encephalitis, and no cases of psychosis associated with this encephalitis have been reported. We report a patient with anti-recoverin antibody-positive encephalitis with Cotard and Capgras delusions who was successfully treated with electroconvulsive therapy (ECT). The patient was a 25-year-old woman. She exhibited disorientation, executive function deficits, tremors in the upper limbs, generalized athetoid-like involuntary movements, hallucinations, incontinence, and fever, which led to her admission to our hospital. Upon admission, she complained of Cotard delusions. Various diagnostic tests, including cerebrospinal fluid analysis, antibody screening, and brain imaging, were unremarkable, except for positivity for serum anti-recoverin antibodies, non-specific general slowing on electroencephalography and decreased regional cerebral blood flow (rCBF) in the frontal and occipital lobes, and increased rCBF in the basal ganglia and pons on single-photon emission computed tomography. She was eventually diagnosed with encephalitis positive for anti-recoverin antibodies and treated with immunoglobulins and steroids. Her neurological symptoms improved temporarily, but three months later, psychiatric symptoms, i.e., suicidal thoughts and Cotard and Capgras delusions, were exaggerated. After ECT, her condition significantly improved. In conclusion, the present report suggests that pineal gland dysfunction due to anti-recoverin antibody or its cross-reactivity with neuron-specific calcium-binding proteins may contribute to the neuropsychiatric symptoms observed in anti-recoverin antibody-positive encephalitis and that ECT can be a viable treatment option if immunotherapy proves ineffective. Additionally, decreased rCBF in the prefrontal cortex may be associated with the clinical features of Capgras and Cotard delusions.

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.

Regional cerebral blood flow in a patient with asystole episodes associated with anti-NMDA receptor encephalitis.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a rare and severe autoimmune encephalitis that displays neuropsychiatric symptoms and autonomic instability, e.g., hypoventilation and cardiac arrhythmia. Severe arrhythmia including asystole associated with this encephalitis is rare. Several causes have been suggested. Nevertheless, no report of the literature has described examination by functional brain imaging of a patient with asystole during anti-NMDA receptor encephalitis. This case is that of a 34-year-old woman diagnosed as having anti-NMDA receptor encephalitis. She repeatedly showed 10-20 s asystole episodes necessitating a temporary transvenous pacemaker. After resection of the bilateral ovarian cystic tumor, her symptoms improved. Regional cerebral blood flow (rCBF) was evaluated using single-photon emission computed tomography. The rCBF was increased in the amygdala, hypothalamus, anterior cingulate, hippocampus, and anterior temporal lobes, but decreased in the dorsolateral frontal lobes, parietal lobes, and occipital lobes. Findings in this case suggest that altered rCBF in the patient with asystole episodes associated with anti-NMDA receptor encephalitis was observed in several brain lesions. The rCBF increases in the central autonomic networks, i.e., the amygdala, hypothalamus, and anterior cingulate, might be associated with dysregulation of sympathetic and parasympathetic nervous systems leading to asystole.

[Analysis of Factors Affecting Proteinuria Onset Timing in Patients Treated with Bevacizumab].

Bevacizumab (BV) is a recombinant and humanized monoclonal antibody that inhibits vascular endothelial growth factor. BV is used to treat various types of cancer. Proteinuria is a characteristic adverse event that occurs as a result of treatment with BV. However, the onset timing of proteinuria after BV administration remains unclear. In the present study, we examined the risk factors affecting the timing of proteinuria onset upon BV administration. Medical records of 135 patients (62 males and 73 females; mean age: 67.8±10.7 years) treated with BV were reviewed at the Kindai University Nara Hospital from April 2011 to December 2019. Proteinuria was identified in 44.4% (60/135) of the studied patients. The time to the first onset of proteinuria was significantly shorter in the administration of doses of BV (≥10) and history of diabetes mellitus. The median cumulative dose associated with the onset of proteinuria was 30.0 (16.1-58.8) mg/kg. When this cumulative dose was compared with 10 mg/kg, no significant difference was observed (p=0.319). The present study demonstrated that the administration of doses of BV (≥10) and history of diabetes mellitus are one of the main risk factors for early-onset proteinuria. These findings may be useful for the future treatment of early-onset proteinuria in patients treated with BV.

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.

Catatonia as the Initial Manifestation of Dementia with Lewy Bodies.

BACKGROUND Catatonia can occur in various neuropsychiatric disorders and is usually treated with benzodiazepines. So far, although 1 case of dementia with Lewy bodies (DLB) with catatonia has been reported, there have been no reports on patients with DLB whose initial symptom was a catatonia. Here, we present a patient who developed benzodiazepine-resistant catatonia and was subsequently diagnosed with DLB based on DLB biomarkers. CASE REPORT The patient was a 92-year-old woman who had not been diagnosed with dementia before. At the age of 91, she experienced catatonia and was initially treated with lorazepam, which did not improve her condition. Later, she transferred to our hospital and was treated with amantadine. Amantadine improved her catatonic symptoms; however, a decline in her cognitive function was observed. We therefore explored the cause of cognitive impairment through imaging studies. We found that the patient did not have the core clinical features of DLB (ie, visual hallucinations, parkinsonism, cognitive fluctuations, and rapid eye movement sleep behavior disorder) but had 2 indicative biomarkers on 123I-metaiodobenzylguanidine myocardial scintigraphy and dopamine transporter imaging. Possible DLB was diagnosed according to the diagnostic criteria. CONCLUSIONS Our case study suggests that catatonia can be an initial symptom of DLB. Moreover, considering the plausible pathophysiology of catatonia in DLB, amantadine treatment may be the most rational choice for the condition when benzodiazepine treatment is ineffective.

Musical Hallucinations Induced by Conventional Doses of Paroxetine.

BACKGROUND A musical hallucination (MH) is a type of auditory hallucination, and is defined as hearing music, sounds, or songs in the absence of external auditory stimuli. There are several case reports of conventional doses of tri- or tetracyclic antidepressants inducing MHs, but no such report for selective serotonin reuptake inhibitors. Here we report a case of a patient with MHs induced by conventional doses of paroxetine. CASE REPORT The patient was a 22-year-old woman with panic disorder (PD) and major depressive disorder (MDD). On the 10th day of treatment with paroxetine 20 mg/d, olanzapine 5 mg/d, and lorazepam 1.5 mg/d, she developed MHs such as "an opera song sung by a female singer." The MHs occurred several times a day, and once continued for 5 to 10 min. Because of a suspicion of paroxetine-induced MHs and poor clinical improvement, paroxetine was reduced and discontinued on the 31st day, whereas venlafaxine was started and increased to 75 mg/d. Two days after the discontinuation of paroxetine, the MHs disappeared and symptoms of PD and MDD were much improved. Several weeks later, in response to a negative life event, her symptoms of PD and MDD returned to the original levels, but MHs were not observed. CONCLUSIONS The present report suggests that conventional doses of paroxetine can induce MHs, which are most likely ascribable to the anticholinergic effects of the drug. This adverse effect should be differentially diagnosed from psychotic symptoms arising from psychiatric disorders, especially MDD.

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.

Relationship between serum calcium and creatinine in hematopoietic stem cell transplantation patients treated with foscarnet
.

OBJECTIVE: The relationship between serum creatinine and calcium (Ca) was investigated in hematopoietic stem cell transplantation (HSCT) patients treated with foscarnet. MATERIALS AND METHODS: A retrospective study was performed to investigate the development of foscarnet-induced renal dysfunction in patients who received HSCT from April 2010 to November 2018 at the Kindai University Nara Hospital. A total of 80 patients were identified from the medical records, and 42 patients who met the inclusion criteria were enrolled in this study. Renal dysfunction was classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. RESULTS: A significant inverse relationship was observed between serum creatinine and Ca levels (r = -0.372; p < 0.0001; y = -0.537x + 9.268). A separate analysis divided into renal dysfunction and non-renal dysfunction groups showed that there was a significant relationship between serum creatinine and Ca levels in the renal dysfunction group (r = -0.531; p < 0.0001; y = -0.617x + 9.239) but not in the non-renal dysfunction group (r = -0.011; p = 0.561; y = -0.023x + 8.934). The optimal cutoff for the minimum Ca level was calculated to be 8.1 mg/mL. CONCLUSION: A significant inverse relationship was observed between serum creatinine and Ca levels in HSCT patients with foscarnet-induced renal dysfunction. Foscarnet-induced renal dysfunction should be noted if Ca levels fall below 8.1 mg/dL. Monitoring Ca levels may be useful for detecting renal dysfunction at early stages in patients treated with foscarnet.

Relationship between the blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplant recipients
.

OBJECTIVE: We aimed to clarify the drug interaction between tacrolimus and voriconazole and investigate the relationship between blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplantation (HSCT) patients. MATERIALS AND METHODS: A retrospective study was conducted to investigate the relationship between blood concentration of tacrolimus and that of voriconazole at the Kindai University Nara Hospital. Patients who received HSCT and tacrolimus and were prescribed voriconazole for the prevention or treatment of aspergillosis from April 2010 to July 2018 were identified from the medical records. A total of 13 patients (administration route of tacrolimus: intravenously in 6 patients, orally in 7 patients) were enrolled in the present study. RESULTS: No significant correlation was observed between the blood concentration/dose (C/D) ratio of tacrolimus and the blood concentration of voriconazole (r = 0.38; p = 0.402; y = 102.8x + 928.1). However, a significant correlation was observed between the C/D ratio of tacrolimus and the blood concentration of voriconazole in the intravenous-administration group (r = 0.94; p = 0.0048; y = 421.9x + 810.5). Meanwhile, no significant correlation was observed in the oral-administration group (r = 0.43; p = 0.34; y = 7.9x + 719). CONCLUSION: The C/D ratio of tacrolimus was significantly correlated with the blood concentration of voriconazole when tacrolimus was intravenously administered. There was a difference in the mechanism of drug interaction between tacrolimus and voriconazole depending on the administration routes.

Voriconazole trough concentration and hepatotoxicity in patients with low serum albumin
.

OBJECTIVE: We aimed to investigate the relationship between voriconazole (VRCZ) trough concentrations and hepatotoxicity and to evaluate whether the recommended trough concentration is adequate in our clinical setting. MATERIALS AND METHODS: A retrospective study was performed to investigate the relationship between serum VRCZ concentrations and the development of hepatotoxicity at the Kindai University Nara Hospital. Patients treated with VRCZ from March 2010 to January 2018 were identified from the medical records. A total of 42 patients (mean age of 61.9 ± 16.9 years; 33 males and 9 females) were enrolled in this study. RESULTS: Hepatotoxicity developed in 28.6% (12/42) of patients treated with VRCZ, and 91.7% (11/12) of these patients developed hepatotoxicity within 3 weeks after initiating the treatment. Significantly increased aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.001), and alanine aminotransferase (p = 0.001) levels were observed after the initiation of VRCZ therapy. In addition, significant positive correlations between AST and VRCZ trough concentrations (p = 0.017) and between ALP and VRCZ trough concentrations (p = 0.012) were observed. VRCZ trough concentration was identified as a significant independent risk factor for hepatotoxicity (adjusted odds ratio: 1.611, 95% confidence interval: 1.131 - 2.579, p = 0.006), and the cutoff serum trough concentration was calculated to be 4.2 µg/mL. CONCLUSION: VRCZ-induced hepatotoxicity should be noted in the early stages of therapy. A sustained VRCZ trough concentration of ~ < 4.2 µg/mL is recommended to prevent hepatotoxicity in patients with low serum albumin levels.

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.

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.