Major depressive disorder after heart transplantation with partial response to antidepressant therapy and remission with aripiprazole augmentation: A case report.

The incidence of major depressive disorder (MDD) after heart transplantation is high; however, there are no reports on treatment options when antidepressant therapy fails to improve the condition. We herein report on the case of a woman with MDD after heart transplantation who partially improved with antidepressant treatment but continued to have a loss of appetite. Augmentation treatment with aripiprazole improved her appetite, and her MDD went into remission. When antidepressant treatment is not sufficiently effective for MDD after heart transplantation, augmentation treatment with antipsychotics, such as aripiprazole, should be considered.

Exacerbation of restless legs syndrome following amygdalohippocampectomy: A case report.

Background: Restless legs syndrome (RLS) is a neurological sensorimotor disorder characterized by an uncontrollable urge to move the legs. In the perioperative period, patients with RLS may experience an acute exacerbation of symptoms. Although studies on the exacerbation of RLS after brain surgery are limited, we present a case wherein symptoms worsened following left amygdalohippocampectomy. Case Presentation: A 58-year-old woman diagnosed with mesiotemporal lobe epilepsy accompanied by left hippocampal sclerosis underwent a left amygdalohippocampectomy. The patient reported uncomfortable sensations in the lower limbs preoperatively. However, the urge to move her legs was manageable and not distinctly diagnosed with RLS. The symptoms began to deteriorate on the fifth postoperative day primarily affecting the legs and back, with a notable emphasis on the right side. Pramipexole treatment effectively ameliorated these symptoms. Conclusion: No reports are available highlighting the exacerbation of RLS after amygdalohippocampectomy. Perioperative factors, such as anesthesia and iron deficiency due to hemorrhage, have been proposed as aggravating factors for RLS; however, the asymmetry of RLS, particularly the atypical right-sided exacerbation in this case, makes it unlikely that this was the primary cause. A negative correlation between opioid receptor availability in the amygdala and RLS severity has been reported, suggesting that amygdalohippocampectomy contributes to the exacerbation of RLS symptoms. This case provides valuable insights into the possible involvement of the amygdala in the pathophysiology of RLS and practical considerations for the clinical management of the condition.

Parasomnia induced by lemborexant: a case report.

Lemborexant, an orexin receptor antagonist, is effective not only for sleep disorders but also for preventing and treating delirium. To date, no complex sleep-related behaviors due to lemborexant have been reported. Herein, we present the case of a 69-year-old male patient who was hospitalized for oral floor and tongue cancer and developed delirium after surgery; however, upon lemborexant dosage increase, used to treat insomnia, he developed abnormal nocturnal behavior. This symptom rapidly improved when lemborexant was discontinued. Distinguishing parasomnia from delirium is important because the treatment of these two conditions differs. Although rapid eye movement sleep behavior or sleepwalking was the cause of this parasomnia, a definitive diagnosis could not be established. If qualitatively distinct abnormal behavior is observed compared to delirium after increasing lemborexant dosage, the possibility of parasomnia should be considered.

Association between Children's Difficulties, Parent-Child Sleep, Parental Control, and Children's Screen Time: A Cross-Sectional Study in Japan.

Children's screen time may affect their growth and development. However, differences in the impact of various psychiatric and psychological factors on children's screen time is a research gap. This study aimed to explore the differences in the influence of related factors affecting children's screen time based on their sleep, difficulties, and parental control among Japanese elementary and junior high school students. A cross-sectional survey was conducted among parents in Japan. Data on screen time duration, parent-child background, strengths and difficulties, sleep variables, and parental control types were collected from 225 households. A regression analysis revealed that high Strengths and Difficulties Questionnaire (SDQ) scores (ß = 0.166, p = 0.008), sleep duration (ß = -0.281, p < 0.001), and parental control (ß = -0.204, p = 0.001) were significantly related to children's screen time. Additionally, it was found that parents' late bedtimes affect children's screen time by mediating children's sleep duration. This study, together with previous research, provides comprehensive insights into design interventions to decrease the screen time of children in the Japanese context.

Sodium Valproate Use in Japanese Patients with Schizophrenia and Coronavirus Disease Is Associated with an Increased Risk of Pneumonia.

Schizophrenia is a known risk factor for coronavirus disease (COVID-19) infection and severity, and certain psychotropic drugs have been linked to increased mortality in infected patients with schizophrenia. However, little evidence exists regarding this risk. We retrospectively examined the association between mood stabilizers and the risk of pneumonia in patients with schizophrenia. This study included 99 patients with schizophrenia or schizoaffective disorder who were infected with COVID-19 in 2022 and met the inclusion criteria. After conducting propensity score matching to align patient backgrounds and concomitant medications, we assessed the impact of mood stabilizers, specifically sodium valproate, on the risk of pneumonia development. Univariate analysis revealed that patients with schizophrenia and COVID-19 who developed pneumonia were more likely to be older (64.5 [14.2] vs. 57.4 [11.5] years, p = 0.008) and using sodium valproate (44.4% vs. 16.7%, p = 0.004). Even after propensity score matching, patients who developed pneumonia were still more likely to be receiving sodium valproate than not (58.8% vs. 20.0%, p = 0.003). Sodium valproate use may be a risk factor for the development of pneumonia in patients with chronic schizophrenia who are infected with COVID-19 during long-term hospitalization.

Connective differences between patients with depression with and without ASD: A case-control study.

BACKGROUND: Researchers find it difficult to distinguish between depression with ASD (Depress-wASD) and without ASD (Depression) in adult patients. We aimed to clarify the differences in brain connectivity between patients with depression with ASD and without ASD. METHODS: From April 2017 to February 2019, 22 patients with suspected depression were admitted to the hospital for diagnosis or follow-up and met the inclusion criteria. The diagnosis was determined according to the Diagnostic and Statistical Manual of Mental Disorders-5 by skilled psychiatrists. The Hamilton Depression Rating Scale (HAM-D), Young Mania Raging Scale (YMRS), Mini-International Neuropsychiatric Interview, Parent-interview ASD Rating Scale-Text Revision (PARS-TR), and Autism-Spectrum Quotient-Japanese version (AQ-J) were used to assess the patients' background and help with diagnosis. Resting-state functional magnetic resonance imaging (rs-fMRI) was performed using the 3-T-MRI system. rs-fMRI was processed using the CONN functional connectivity toolbox. Voxel-based morphometry was performed using structural images. RESULTS: No significant difference was observed between the Depress-wASD and Depression groups using the HAM-D, YMRS, AQ-J, Intelligence Quotient (IQ), and verbal IQ results. rs-fMRI for the Depress-wASD group indicated a positive connection between the salience network (SN) and right supramarginal gyrus (SMG) and a negative connection between the SN and hippocampus and para-hippocampus than that for the Depression group. No significant structural differences were observed between the groups. CONCLUSIONS: We identified differences in the SN involving the SMG and hippocampal regions between the Depress-wASD and Depression groups.

Orexin receptor antagonists versus antipsychotics for the management of delirium in intensive care unit patients with cardiovascular disease: A retrospective observational study.

OBJECTIVE: Although antipsychotics are often used in the pharmacological treatment of delirium, recent reports suggest the efficacy of orexin receptor antagonists. This study investigated whether orexin receptor antagonists could be a possible treatment option for delirium. METHOD: A nonblinded nonrandomized routine clinical treatment was performed. Patients treated in intensive care units (ICU) for cardiovascular disease and receiving psychiatric intervention were studied retrospectively. The scores from the Intensive Care Delirium Screening Checklist (ICDSC) were compared between patients treated with orexin receptor antagonists and those treated with antipsychotics. RESULTS: The mean (standard deviation) ICDSC scores were 4.5 (1.8) at day -1 and 2.6 (2.6) at day 7 for orexin receptor antagonist group (n = 25) and 4.6 (2.4) at day -1 and 4.1 (2.2) at day 7 for antipsychotic group (n = 28). The orexin receptor antagonist group showed significantly lower ICDSC scores than the antipsychotic group (p = 0.021). CONCLUSION: While precise efficacy cannot be determined from our retrospective, observational, and uncontrolled pilot study, this analysis encourages a future double-blind randomized placebo-controlled trial of orexin-antagonists for delirium treatment.

Analysis of the effect of brexpiprazole on sleep architecture in patients with schizophrenia: A preliminary study.

BACKGROUND: Brexpiprazole is an atypical antipsychotic drug widely used in Japan for the treatment of schizophrenia. Previous studies have investigated the therapeutic effects of some antipsychotics on sleep variables; however, to our knowledge, the effects of brexpiprazole on sleep architecture have not been examined in patients with schizophrenia. Therefore, we aimed to exploratorily investigate the effect of brexpiprazole on sleep variables measured by polysomnography in patients with schizophrenia. METHODS: This study included 10 patients with schizophrenia who were originally treated with haloperidol alone. Sleep variables of the participants were measured using polysomnography. After excluding those who did not meet the study criteria, seven patients (five men and two women; mean age [SD], 59.0 [10.0] years) were eligible for further analysis. Polysomnography was repeated at 4 weeks after the participants were prescribed brexpiprazole in addition to haloperidol. We compared the sleep architecture of the participants, measured using polysomnography, before and after taking brexpiprazole. RESULTS: Add-on brexpiprazole significantly prolonged rapid eye movement latency, increased the duration and percentage of stage N2 and stage N3 sleep (min, %), and decreased the duration and percentage of stage rapid eye movement sleep (min, %) at a significance level of nominal p < 0.05. CONCLUSION: Although not significant after correcting for multiple comparisons, the present results showed that add-on brexpiprazole could alter the sleep architecture of patients with schizophrenia. Future studies are warranted to replicate these findings and to further investigate the beneficial influence of brexpiprazole on sleep.

Cerebellar network changes in depressed patients with and without autism spectrum disorder: A case-control study.

Pathophysiological difference of depression in patients with and without autistic spectrum disorder (ASD) has not been investigated previously. Therefore, we sought to determine whether there were differences between non-ASD and ASD groups on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with depression. We performed 3T MRI under resting state in 8 patients with depression and ASD and 12 patients with depression but without ASD. The ASD group showed increased functional connectivity in the cerebellar network of the left posterior inferior temporal gyrus and anterior cerebellar lobes compared to the non-ASD group in an analysis of covariance. Adding antipsychotics, antidepressants, benzodiazepines, nonbenzodiazepines, anxiolytics, hypnotics, or age as covariates showed a similar increase in functional connectivity. Thus, this study found that depressive patients with ASD had increased functional connectivity in the cerebellar network. Our findings suggest that fMRI may be able to evaluate differences in depressed patients with and without ASD.

Outcomes of an interdisciplinary return to work intervention including occupational therapy for mood and adjustment disorders: A single-arm clinical trial.

BACKGROUND: Mood and adjustment disorders are two major causes of long-term sick leave among employees, leading to large social losses. Therefore, a return to work (RTW) intervention was attempted, targeting patients with mood and adjustment disorders. OBJECTIVE: This study aimed to investigate the outcome of an interdisciplinary RTW intervention including occupational therapy implemented within the Japanese healthcare framework. METHODS: An interdisciplinary RTW intervention including occupational therapy was conducted five times a week for approximately three months, targeting individuals with mood and adjustment disorders who took a leave of absence. Their mental symptoms, cognitive functioning, job performance, temperament, social adaptation, psychosocial state, and readiness to RTW before and after the intervention were evaluated. Full-time RTW ratios at 3, 6, 12, 18, and 24 months from baseline were followed up and compared with those of prior studies. RESULTS: A total of 30 individuals completed the intervention. After the intervention, participants' psychological symptoms, cognitive function, vocational aptitude, temperament, social adaptation, psychosocial state, and readiness to RTW improved (p≤0.001-0.0279). The ratios of RTW at 3, 6, 12, 18, and 24 months from the baseline were 6.7%, 46.7%, 73.3%, 77.8%, and 82.6%, respectively, reflecting a higher pattern than prior reports. CONCLUSIONS: The interdisciplinary RTW intervention including occupational therapy has the potential to improve not only depressive symptoms but also cognitive functioning, job performance, social adaptation, and readiness to RTW. They can also raise RTW ratios.

Improvement of catatonia-induced rapid respiratory failure with electroconvulsive therapy: A case report.

We encountered a case of sudden respiratory failure during treatment of catatonia that required intensive care. Electroconvulsive therapy (ECT) was administered in the intensive care unit while the patient was under systemic control. The catatonia symptom was relieved, and respiratory failure improved. Although a proximal venous thrombus was observed, anticoagulation therapy was continued during ECT, and the patient was successfully treated without causing a pulmonary embolism. It is crucial to monitor the patient's physical and psychological symptoms because respiratory status may deteriorate rapidly in a catatonic state.

Altered levels of salivary cytokines in patients with major depressive disorder.

OBJECTIVE: Accumulating evidence indicate the involvement of inflammation in the pathogenesis of mental disorders. Numerous studies have shown that proinflammatory cytokines were elevated in peripheral blood of patients with major depressive disorder (MDD). A few recent research have explored the possibility of using saliva as a biomarker for depressive symptoms. The objective of this study is to examine the salivary cytokine levels in patients with MDD and healthy controls. METHODS: Participants were 19 patients with MDD and 50 healthy controls. The levels of 27 cytokines in saliva were measured by multiplex bead array assay. RESULTS: The Mann-Whitney U-test showed that the levels of IL-1ß, IL-6, IL-9, IL-12p70, IL-13, Chemokine CCL11 (Eotaxin), MIP-1α, RANTES, and VEGF were significantly higher in patients than controls. The quantile regression analysis showed that IL-1ß, IL-12p70, CCL11, and VEGF remained significant after controlling for possible confounding factors. CONCLUSION: The findings were in line with previous studies that showed elevated peripheral levels of cytokines in patients with MDD. Our present data provide preliminary support for altered salivary cytokine levels in patients with MDD and suggest that salivary cytokines may serve as a novel target for elucidating the pathophysiology underlying MDD.

Role of advanced glycation end products in the longitudinal association between muscular strength and psychotic symptoms among adolescents.

Muscular strength, assessed by handgrip, is a risk indicator for psychiatric disorders, including psychosis. However, the biological mechanisms underlying this association remain unclear. Since advanced glycation end products (AGEs) play a key role in skeletal muscle underdevelopment and psychosis, we examined the role of AGEs in the longitudinal association between muscular strength and psychotic symptoms among adolescents. We first evaluated the direction of the relationship between handgrip strength and urine levels of pentosidine, a representative AGEs in a population-based birth cohort of 1,542 adolescents at ages 12 and 14. Then, we examined the role of AGEs in the longitudinal association between handgrip strength and thought problems (TP), as a psychotic symptom indicator, in a subsample of 256 adolescents at ages 13 and 14. An autoregressive cross-lagged model revealed that handgrip strength at age 12 negatively predicted pentosidine levels at age 14 (ß = -0.20, p < 0.001), whereas pentosidine levels at age 12 did not predict handgrip strength at age 14 (ß = 0.04, p = 0.062). Moreover, pentosidine levels had a significant indirect effect on the relationship between handgrip strength and TP (standard indirect effect = -0.051, p = 0.012), which remained significant after adjusting for gender and preceded TP and pentosidine levels. Thus, adolescents with low muscular strength are at a high risk of developing psychotic symptoms, which could be mediated by AGEs. Future studies need to investigate whether interventions focused on muscular strength prevent the accumulation of AGEs and thereby prevent the development of psychosis.

Prevention of end-stage renal disease with percutaneous endoscopic gastrojejunostomy tubes in a patient with recurrent episodes of binge eating and purging.

Background: Bulimia nervosa (BN) and the binge-eating/purging subtype of anorexia nervosa (b/p AN) are characterized by binge eating and unsafe compensatory behaviors, such as laxatives or diuretic abuse, self-induced vomiting, and excessive exercise. BN often causes miscellaneous physical complications that can lead to death. However, there have been very few prior reports on the physical complications of chronic BN. Case Presentation: We report a case of chronic BN of over 10 years. Her compensatory behaviors caused dehydration more easily than before. Repeated dehydration may result in end-stage renal disease (ESRD). Therefore, we had to prevent dehydration by placing a percutaneous endoscopic gastrojejunostomy (PEG-J) tube. After PEG-J placement, dehydration did not reoccur, thereby protecting her renal involvement from progressing to ESRD. Conclusion: Chronic BN exposure may cause repeated dehydration with time. Therefore, the PEG-J tube would be effective in preventing dehydration, which leads to ESRD.

Hyperactive/impulsive symptoms and autistic trait in institutionalized children with maltreatment experience.

The present study examined how maltreatment experience was associated with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) symptoms in children under institutional care. The key caregivers of children and adolescents aged 6 to 18 years who were under institutional care in Nagano prefecture, Japan were asked to answer the background questionnaire, ADHD-Rating Scale, and the Japanese children's version of the Autism-Spectrum Quotient. A total of 378 valid responses were obtained, of which 222 reported maltreatment experience prior to institutionalization. Both hyperactive/impulsive and inattentive scores were significantly higher in the maltreated group. Maltreatment experience was significantly associated with the presence of hyperactive/impulsive symptoms (p = 0.003) and inattentive symptoms (p = 0.027). Particularly, those who had experienced physical abuse were significantly more likely to have hyperactive/impulsive symptoms (p = 0.012) and autistic trait (p = 0.002). Thorough assessment of neurodevelopmental symptoms should be performed when placing children with maltreatment experience into institutional care.

AKR1A1 Variant Associated With Schizophrenia Causes Exon Skipping, Leading to Loss of Enzymatic Activity.

Schizophrenia is a heterogeneous psychiatric disorder characterized by positive symptoms such as hallucinations and delusions, negative symptoms such as anhedonia and flat affect, and cognitive impairment. Recently, glucuronate (GlucA) levels were reported to be significantly higher in serum of patients with schizophrenia than those in healthy controls. The accumulation of GlucA is known to be related to treatment-resistant schizophrenia, since GlucA is known to promote drug excretion by forming conjugates with drugs. However, the cause of GlucA accumulation remains unclear. Aldo-keto reductase family one member A1 (AKR1A1) is an oxidoreductase that catalyzes the reduction of GlucA. Genetic loss of AKR1A1 function is known to result in the accumulation of GlucA in rodents. Here, we aimed to explore genetic defects in AKR1A1 in patients with schizophrenia, which may result in the accumulation of GlucA. We identified 28 variants of AKR1A1 in patients with schizophrenia and control subjects. In particular, we identified a silent c.753G > A (rs745484618, p. Arg251Arg) variant located at the first position of exon 8 to be associated with schizophrenia. Using a minigene assay, we found that the c.753G > A variant induced exon 8 skipping in AKR1A1, resulting in a frameshift mutation, which in turn led to truncation of the AKR1A1 protein. Using the recombinant protein, we demonstrated that the truncated AKR1A1 completely lost its activity. Furthermore, we showed that AKR1A1 mRNA expression in the whole blood cells of individuals with the c.753G > A variant tended to be lower than that in those without the variants, leading to lower AKR activity. Our findings suggest that AKR1A1 carrying the c.753G > A variant induces exon skipping, leading to a loss of gene expression and enzymatic activity. Thus, GlucA patients with schizophrenia with the c.753G > A variant may show higher GlucA levels, leading to drug-resistant schizophrenia, since drug excretion by GlucA is enhanced.

Sex differences in serum levels of 5α-androstane-3ß, 17ß-diol, and androstenediol in the young adults: A liquid chromatography-tandem mass spectrometry study.

Animal experiments have consistently shown that estrogen receptor ß (ERß)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ERß include 5α-androstane-3ß, 17ß-diol (3ßAdiol) and androstenediol (Δ5-diol). We determined, for the first time, the exact serum levels of 3ßAdiol and Δ5-diol in young healthy volunteers using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4±7.8 years) and 25 men (mean age = 31.4±7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC-MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17ß-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3ßAdiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3ßAdiol and Δ5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3ßAdiol and Δ5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3ßAdiol and E2 levels, not by Δ5-diol level.