The genetic association between bipolar disorder and dementia: a qualitative review.

Bipolar disorder is a chronic disorder characterized by fluctuations in mood state and energy and recurrent episodes of mania/hypomania and depression. Bipolar disorder may be regarded as a neuro-progressive disorder in which repeated mood episodes may lead to cognitive decline and dementia development. In the current review, we employed genome-wide association studies to comprehensively investigate the genetic variants associated with bipolar disorder and dementia. Thirty-nine published manuscripts were identified: 20 on bipolar disorder and 19 on dementia. The results showed that the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A were overlapping between patients with bipolar disorder and dementia. In conclusion, the genes CACNA1C, GABBR2, SCN2A, CTSH, MSRA, and SH3PXD2A may be associated with the neuro-progression of bipolar disorder to dementia. Further genetic studies are needed to comprehensively clarify the role of genes in cognitive decline and the development of dementia in patients with bipolar disorder.

Association between irritable temperament and glucose metabolism in the left insula and the right cerebellum.

INTRODUCTION: Affective temperaments are assumed to have biological and neural bases. In the present study, we analyzed 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images of healthy participants to explore the neural basis of affective temperaments. METHOD: We utilized data of affective temperament measured by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire and 18F-FDG PET images of healthy participants from two of our previous studies. A multiple regression analysis was performed to assess the association between 18F-FDG uptake and temperament scores using Statistical Parametric Mapping 12. RESULTS: The final sample included 62 healthy participants. Whole-brain analysis revealed a cluster of 18F-FDG uptake that was significantly and positively associated with irritable temperament scores in the right cerebellum (Crus II, VIII, and IX). After further adjustment for the other four temperament scores, whole-brain analysis revealed a cluster of 18F-FDG uptake significantly and positively associated with irritable temperament scores in the left insula and right cerebellum (Crus II, VIII, and IX). However, no significant association was found between 18F-FDG uptake and the other four temperaments (depressive, cyclothymic, hyperthymic, and anxious). CONCLUSIONS: The left insula and right cerebellum of the cerebrocerebellar circuit may be one of the neural bases of irritable temperament.

Suicide attempt during ramelteon addition to flunitrazepam: A case report.

Background: Benzodiazepines, such as flunitrazepam, may be at risk of disinhibition, leading to aggressiveness, impulsivity, self-harm, and possibly suicide attempts, whereas ramelteon may be far from disinhibition. Case Presentation: In a 43-year-old female with primary insomnia, flunitrazepam alone did not induce any type of disinhibition, but the addition of ramelteon to flunitrazepam brought about disinhibition, leading to aggressiveness and finally to her suicide attempt. Her disinhibition rapidly subsided as soon as ramelteon alone was discontinued. Conclusion: These findings suggest that a suicide attempt may occur during ramelteon and flunitrazepam combination in a susceptible patient.

Increased volume of the left hippocampal dentate gyrus after 4 weeks of bright light exposure in patients with mood disorders: a randomized controlled study.

Bright light exposure (BL) induces neurogenesis in the rat hippocampal dentate gyrus (DG). We had previously conducted a randomized controlled trial (RCT) in which a 4-week period of BL in healthy participants resulted in increased volume of the left DG-head. This study aimed to investigate the effects of BL on the DG in patients with mood disorders. A 4-week RCT was conducted in which patients with mood disorders were randomly assigned to either a BL group (10,000 lx) or dim light exposure group (DL group; 50 lx). All patients underwent clinical assessment and magnetic resonance imaging at baseline and after the intervention. The study registration number is UMIN000019220. Our final sample included 24 patients (BL group, n = 12; DL group, n = 12). A significant effect of time and group was detected in the volumes of the left DG-head (F (1, 22) = 11.6, partial η2 = 0.35, p = 0.003) and left DG-total (left DG-total = left DG-head + left DG-body; [F (1, 22) = 6.5, partial η2 = 0.23, p = 0.02]). Additionally, the BL group demonstrated a significant increase in the volume of the left DG-head (95% CI: -5.4 to -1.6, d = 1.2, p = 0.002) and left DG-total (95% CI: -6.3 to -1.5, d = 1.06, p = 0.005) as well as a positive correlation between the percentage change in the volume of the left DG-total and the percentage change in the scores of the mood visual analog scale (r = 0.58, p = 0.04). In conclusion, our study results suggest that compared to DL, BL leads to a significantly greater increase in the left DG volume in patients with mood disorders. This increase in the left DG volume may be associated with mood improvement in the patients.

Refractory Depression With Persistent Sore Throat and Hypochondriacal Delusion of SARS-CoV-2 Infection: A Case Study.

ABSTRACT: Herein, we present a case of a female patient with a persistent sore throat, which preceded a hypochondriacal delusion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Both the sore throat and hypochondriacal delusion persisted together, despite the repeatedly negative results of reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 and a moderate improvement in her depression. Four possibilities for the patient's sore throat were discussed: pain symptoms of somatic symptom disorder, pain symptoms of depression, delusion of pain in her throat, and somatic hallucination as a sore throat. Consequently, somatic hallucinations were considered the most likely. In any case, the present findings suggest that sore throat can precede hypochondriacal delusion of SARS-CoV-2 infection in some noninfected patients. When patients continue to complain of a sore throat despite the negative results of SARS-CoV-2 by the RT-PCR test, we should consider that it might be a somatic hallucination and soon hypochondriacal delusions may occur, leading to the manifestation of other symptoms of psychiatric disorders, such as depression, which may be refractory and/or suicidal.

Self-reported low self-esteem due to poor maternal care improves with the existential approach in bipolar disorder: a case report.

Parental nurturing attitudes influence children and are linked to the establishment of self-esteem. Females who have experienced poor maternal care during their childhood may have low self-esteem, and this factor may significantly augment the likelihood of depression. Particularly, childhood maltreatment among individuals with bipolar disorder is associated with unfavorable clinical features, such as a heightened risk of severe manic, depressive, or psychotic symptoms, as well as suicide attempts. Here, we report a case of a woman with bipolar disorder who had self-reported low self-esteem due to poor maternal care, which subsequently improved via an existential approach. This existential approach confers meaning to the lives of every individual, even in the face of adversity. Our findings suggest that the existential approach may enable the discovery of more positive life values during times of hardship and could improve self-reported low self-esteem due to poor maternal and change the way of life in patients with bipolar disorder.

Lithium in drinking water and Alzheimer's dementia: Epidemiological Findings from National Data Base of Japan.

OBJECTIVES: The aim of this study was to investigate the association between lithium levels in drinking water and prevalence of Alzheimer's dementia (AD). METHODS: Lithium levels in the drinking water of 808 cities and wards (i.e., 785 Japanese cities of 46 prefectures and 23 wards of Tokyo) in Japan were examined in relation to the prevalence of AD during the 5 years from 2010 to 2014, which was calculated on the basis of the national data base of Ministry of Health, Labor, and Welfare of Japan. Multiple regression analyses were used to investigate the association of lithium levels with the prevalence of AD with adjustment for relevant factors (proportions of one-person households as a family factor and people in primary industry employment as a job factor, annual total sunshine hours as a meteorological factor, and total number of beds of psychiatric hospitals as a medical factor) in total, male, and female elderly populations. RESULTS: The adjusted model showed a significant inverse association of lithium levels with female, but not with male, or total prevalence of AD. CONCLUSIONS: These findings suggest that higher lithium levels in drinking water may be associated with lower prevalence of AD in female, but not male, populations.

Effects of a rework program in a university hospital and predictors of work restoration and maintenance in the participants.

During sickness absence, it appears necessary for psychiatric patients suffering from depression or bipolar disorder to undergo a psychiatric rehabilitation called the rework program that aids in work restoration and maintenance. However, few studies have investigated the effects of such a program and predictors of work restoration and maintenance in the participants. Here, we aimed to investigate the effects of a rework program as well as to examine whether cognitive function and mental state at the end of the rework program predict the probability of work restoration and maintenance and whether the frequency of rework program participation predicts successful work restoration and maintenance. The rework program included both patients absent from work and unemployed patients. Patients completed assessments including Trail Making Test Type B (TMT-B), the Wisconsin Card Sorting Test, and the Social Adaptation Self-Evaluation Scale just before graduating from the rework program. Simultaneously, their depressive state was assessed using the Hamilton Depression Rating scale. The patients were divided into the job group, comprising 94 patients who were able to restore their work or get a new job, and the non-job group, comprising 34 patients who were not able to do so. We found that the program was more effective in patients absent from work than in unemployed patients, TMT-B could predict work restoration and maintenance, and the frequency of rework program participation could predict work restoration but not work maintenance. Based on the findings, we propose "Yamashita's criterion" where a TMT-B completion time of 70 s is the cut-off point for work restoration. The present findings may provide useful evidence that could aid in the further development of rework program(s).

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.

A case of improvement of clozapine-induced low leukocyte counts by adenine, cepharanthin and ninjin-yoei-to in a patient with treatment-resistant schizophrenia.

BACKGROUND: Although clozapine is the optimal drug for patients with treatment-resistant schizophrenia, the drug has harmful adverse effects such as leukopenia. Adenine and cepharanthine are known to be effective for radiation- or drug-induced leukopenia. Furthermore, ninjin-yoei-to, a Chinese herbal medicine, augments the production of granulocyte-macrophage colony-stimulating factor. Thus, these drugs may be useful for clozapine-induced leukopenia. CASE PRESENTATION: A 21 years-old woman with schizophrenia was hospitalized for initiation of clozapine treatment. Despite concomitant use of adenine, cepharanthine, and lithium carbonate having activities of increasing leukocytes, a decrease in leukocyte counts occurred after the initiation of clozapine. Additional administration of ninjin-yoei-to increased leukocyte counts, which prevented the development of leukopenia. CONCLUSIONS: This is the first case that concomitant use of adenine, cepharanthin, and ninjin-yoei-to exhibited the effectiveness of reversing the decrease in leukocytes caused by clozapine. Monitoring leukocyte counts and preventing leukopenia are essential for successful treatment with clozapine for refractory schizophrenia. These medicines may be a potential option for preventing clozapine-induced leukopenia.