Blood mRNA expression levels of glucocorticoid receptors and FKBP5 are associated with depressive disorder and altered HPA axis.

BACKGROUND: While depression has been associated with alterations in the hypothalamic-pituitary adrenal (HPA) axis function, there is still controversy regarding the nature and extent of the dysfunction, such as in the debate about hypercortisolism vs. hypocortisolism. It may therefore be necessary to understand whether and how HPA axis function in depression is linked to mRNA expression of key genes regulating this system. METHODS: We studied 163 depressed outpatients, most of whom were chronically ill, and 181 healthy controls. Blood mRNA expression levels of NR3C1 (including GRα, GRß, and GR-P isoforms), FKBP4, and FKBP5 were measured at baseline. HPA axis feedback sensitivity was measured by the dexamethasone (Dex)/corticotropin-releasing hormone (CRH) test. The association between mRNA expression levels and HPA axis feedback sensitivity was examined. RESULTS: Compared to controls, patients showed significantly higher expression of GRα and lower expression of FKBP5, and higher post-Dex cortisol levels, even after controlling for age and sex. FKBP5 expression was significantly positively correlated with cortisol levels in patients, while GRα expression was significantly negatively correlated with cortisol levels in controls. LIMITATIONS: Most patients were taking psychotropic medications. The large number of correlation tests may have caused type I errors. CONCLUSIONS: The tripartite relationship between depression, mRNA expression of GR and FKBP5, and HPA axis function suggests that the altered gene expression affects HPA axis dysregulation and, as a result, impacts the development and/or illness course of depressive disorder. The combination of increased GRα expression and decreased FKBP5 expression may serve as a biomarker for chronic depression.

Plasma neuropeptide levels in patients with schizophrenia, bipolar disorder, or major depressive disorder and healthy controls: A multiplex immunoassay study.

AIM: We aimed to compare neuropeptide levels between patients with major psychiatric disorders and healthy controls and examine their association with symptoms and cognitive function. METHODS: The participants were 149 patients with schizophrenia, 115 patients with bipolar disorder (BD), 186 unremitted patients with major depressive disorder (MDD), and 350 healthy controls. Psychiatric (schizophrenic, manic, and depressive) symptoms, sleep state, and cognitive (premorbid intelligence quotient, general cognitive, and memory) functions were evaluated. A multiplex immunoassay kit was used to measure cerebrospinal fluid (CSF) and plasma α-melanocyte-stimulating hormone (MSH), ß-endorphin, neurotensin, oxytocin, and substance P levels. RESULTS: The verification assay revealed that CSF α-MSH, ß-endorphin, neurotensin, oxytocin, and substance P levels were too low to be reliably measured, while plasma α-MSH, ß-endorphin, neurotensin, oxytocin, and substance P levels could be successfully measured. Plasma α-MSH, ß-endorphin, neurotensin, oxytocin, and substance P levels were not significantly different between patients with schizophrenia, BD, or MDD and healthy controls. Plasma α-MSH, ß-endorphin, neurotensin, oxytocin, and substance P levels were not significantly correlated with psychiatric symptom scores in patients with schizophrenia, BD, or MDD and cognitive function scores in patients or healthy controls. CONCLUSION: Our data suggest that plasma neuropeptide levels do not elucidate the involvement of neuropeptides in the pathology of schizophrenia, BD, or MDD.

Association between the Pittsburgh sleep quality index and white matter integrity in healthy adults: a whole-brain magnetic resonance imaging study.

To disclose possible associations between poorer sleep quality and structural brain alterations in a non-psychiatric healthy population, this study investigated the association between the Pittsburgh sleep quality index (PSQI) and brain correlates, using a whole-brain approach. This study included 371 right-handed healthy adults (138 males, mean age: 46.4 ± 14.0 years [range: 18-75]) who were right-handed. Subjective sleep quality was assessed using the Japanese version of the PSQI (PSQI-J), and the cutoff score for poor subjective sleep quality was set at ≥ 6. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to examine whether a higher score of the PSQI-J indicates, poorer sleep quality is associated with gray matter volume and white matter microstructure alternations, respectively. Among the participants, 38.8% had a PSQI-J cutoff score of ≥ 6. VBM did not reveal any correlation between PSQI-J scores and gray matter volume. However, DTI revealed that PSQI-J global scores were significantly and negatively correlated with diffuse white matter fractional anisotropy (FA) values (p < 0.05, corrected). Moreover, the PSQI-J sleep disturbance and use of sleep medication component scores were significantly and negatively correlated with right anterior thalamic radiation and diffuse white matter FA values, respectively (p < 0.05, corrected). There were no significant differences in gray matter volume and white matter metrics (FA, axial, radial, and mean diffusivities) between the groups with PSQI-J scores above or below the cutoff. Our findings suggest that lower sleep quality, especially the use of sleep medication, is associated with impaired white matter integrity in healthy adults. Limitations of this study are relatively small number of participants and cross-sectional design. Fine sleep quality, possibly preventing the use of sleep medication, may contribute to preserve white matter integrity in the brain of healthy adults. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00442-0.

Association of body mass index and its classifications with gray matter volume in individuals with a wide range of body mass index group: A whole-brain magnetic resonance imaging study.

Aim: To examine the association of body mass index (BMI) [kg/m2] and its classifications (underweight [BMI < 18.5], normal [18.5 ≤ BMI < 25], overweight [25 ≤ BMI < 30], and obese [BMI ≥ 30]) with brain structure in individuals with a wide range of BMI group. Materials and methods: The participants included 382 right-handed individuals (mean age: 46.9 ± 14.3 years, 142 men and 240 women). The intelligence quotient was assessed using the Japanese Adult Reading Test. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to analyze the association of BMI and its classifications with gray and white matter structures, respectively. Results: According to VBM, BMI was significantly and negatively correlated with the bilateral cerebellum exterior volumes. In group comparisons, the right cerebellum exterior volume was significantly lower in the overweight or obese group than in the underweight or normal group, while the bilateral cuneus and calcarine cortex, left cuneus, and left precuneus volume was significantly lower in the underweight group than in the non-underweight group. Sex-related stratification analyses for VBM revealed that BMI was significantly and negatively correlated with the bilateral cerebellum exterior volumes only in women. In group comparisons, the left cerebellum exterior volume was significantly lower in obese women than in non-obese women. The left thalamus proper and the right cerebellum exterior volumes were significantly lower in overweight or obese group than in underweight or normal group in men and women, respectively. The bilateral cuneus and calcarine cortex, left cuneus and carcarine cortex, and bilateral cuneus volume was significantly lower in underweight men than in non-underweight men. In contrast, there were no notable findings on DTI. Conclusion: Our results suggest association of continuous BMI, being overweight or obese, and being underweight with decreased gray matter volume in individuals with a wide range of BMI group. Furthermore, sex-related differences are seen in the association of BMI and its classifications with regional gray matter volume reductions. Abnormally high or low BMIs may have a negative influence on regional gray matter volumes.

Gut permeability and its clinical relevance in schizophrenia.

AIM: We aimed to examine the gut permeability in patients with schizophrenia and its relevance to schizophrenia symptoms, medication, cognitive functions, and blood immune markers. METHODS: We selected 22 patients with schizophrenia (mean age: 37.9 ± 10.5 years) comprising 9 men and 13 women. Furthermore, we included 86 healthy controls (mean age: 43.5 ± 11.0 years) comprising 41 men and 45 women. All participants were biologically unrelated and of Japanese descent. We used the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS) to measure the severity of schizophrenia symptoms and cognitive functions, respectively. The lactulose-mannitol loading test was used to measure the permeability of the small intestine. Furthermore, we used the lactulose to mannitol ratio (LMR) as an index of gut permeability. We measured the C-reactive protein and natural killer (NK) cell activity in the blood as highly sensitive immune markers. RESULTS: The patients had a significantly higher rate of "leaky gut" (defined as LMR ≥ 0.1) compared to the control group (22.7% vs. 5.8%, odds ratio: 4.8 [95% confidence interval, 1.2-18.3], Fisher's exact test, P = 0.03). There was no significant correlation between the LMR and PANSS scores or in the daily antipsychotic dose. In addition, the LMR was negatively correlated with the total Z-score of the BACS and NK cell activity in the patients. CONCLUSIONS: Our results suggest a higher rate of abnormally increased gut permeability in patients with schizophrenia than in controls. Moreover, gut permeability may be related to the cognitive and cellular immunity function of patients with schizophrenia.

Relationship between Interpersonal Sensitivity Measure score and clinical symptoms in patients with major psychiatric disorders and healthy individuals.

Aim: We compared the Interpersonal Sensitivity Measure (IPSM) scores between diagnostic groups and examined the relationship between IPSM scores and clinical variables. Methods: This study included 166 patients with schizophrenia, 47 patients with bipolar disorder (BD) Ⅰ, 110 patients with BD Ⅱ, 380 patients with major depressive disorder (MDD), and 558 healthy individuals. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale, 21-item Hamilton Depression Rating Scale (HAMD-21), and Pittsburgh Sleep Quality Index (PSQI). Results: The IPSM interpersonal awareness, separation anxiety, timidity, fragile inner self, and total scores were significantly higher in all the patient groups compared with healthy individuals (corrected p < 0.05). The IPSM need for approval score was significantly higher in patients with BD Ⅰ and those with BD Ⅱ than in those with schizophrenia or MDD (corrected p < 0.05). The PSQI total score and PANSS general psychopathology score, HAMD-21 delusion subscale score, HAMD-21 total score, and HAMD-21 core subscale score and PSQI sleep disturbance subscale score were significantly and positively correlated with the IPSM total score in patients with schizophrenia, those with BD Ⅰ, those with BD Ⅱ, and those with MDD, respectively, while the PSQI total score and daytime dysfunction subscale score were significantly and positively correlated with the IPSM total score in healthy individuals (corrected p < 0.05). Conclusion: Our data suggest that higher interpersonal sensitivity may play a role in the development of major psychiatric disorders and may be involved in some clinical symptom formations.

An fMRI Investigation into the Effects of Ketogenic Medium-Chain Triglycerides on Cognitive Function in Elderly Adults: A Pilot Study.

Evidence suggests that oral intake of medium-chain triglycerides (MCTs), which promote the production of ketone bodies, may improve cognitive functions in elderly people; however, the underlying brain mechanisms remain elusive. We tested the hypothesis that cognitive improvement accompanies physiological changes in the brain and reflects the use of ketone bodies as an extra energy source. To this end, by using functional magnetic resonance imaging, cerebral blood oxygenation level-dependent (BOLD) signals were measured while 20 healthy elderly subjects (14 females and 6 males; mean age: 65.7 ± 3.9 years) were engaged in executive function tasks (N-back and Go-Nogo) after ingesting a single MCT meal (Ketonformula®) or placebo meal in a randomized, double-blind placebo-controlled design (UMIN000031539). Morphological characteristics of the brain were also examined in relation to the effects of an MCT meal. The MCT meal improved N-back task performance, and this was prominent in subjects who had reduced grey matter volume in the dorsolateral prefrontal cortex (DLPFC), a region known to promote executive functions. When the participants were dichotomized into high/low level groups of global cognitive function at baseline, the high group showed improved N-back task performance, while the low group showed improved Go-Nogo task performance. This was accompanied by decreased BOLD signals in the DLPFC, indicative of the consumption of ketone bodies as an extra energy source.

Compressive optic neuropathy (CON) in Graves' disease caused by hypertrophy of levator and superior rectus muscles: A case report.

RATIONALE: Enlargemento of the medial rectus is the most predominant factor of compressive optic neuropathy (CON) in Graves' disease. This case report indicates that CON could develop only from the hypertrophic superior levator and superior rectus (SL/SR) muscle in a patient with poorly controlled Graves' disease, and described the possible risk of FT3-thyrotoxicosis with a prominent goiter to develop the current rare case with a review of the literature. PATIENT CONCERNS: A 66-year-old woman undergoing endocrine management of hyperthyroidism with prominent goiter visited the Department of Ophthalmology due to right-eye upper-eyelid retraction. DIAGNOSES: At initial presentation, the right and left margin reflex distance-1 (MRD-1) was 3.2 mm and 2.1 mm, respectively, and no proptosis or visual dysfunction was observed. Despite insufficient hormonal regulation, she refused to undergo goiter removal. The upper eyelid retraction gradually worsened to 7.7 mm of MRD-1, followed by the onset of 20 prism diopters (PD) of the right hypertropia, resulting in right-eye CON after 6 months. Her free thyroxin level was 3.88 ng/dl and free triiodothyronine was 24.90 pg/ml. Computed tomography and magnetic resonance imaging showed only SL/SR enlargement in the right orbit. INTERVENTIONS: Intravenous steroid and radiation therapy resulted in visual improvement; however, a prominent upper eyelid retraction and 35PD of hypertropia remained in her right eye. Orbital decompression, upper retraction repair, and superior rectus recession were performed to prevent the recurrence of CON and correct any disfigurement. OUTCOMES: The combination of conventional intravenous steroid pulse therapy, radiotherapy, and orbital decompression was effective, and no recurrence was observed for more than 1.5-years postoperatively. LESSONS: Enlargement of the SL/SR muscle complex may independently induce the CON. We believe that strict attention should be paid to patients with triiodothyronine thyrotoxicosis with progressive eyelid retraction and hypertropia.

Performance on the Wechsler Adult Intelligence Scale (WAIS) in Japanese patients with bipolar and major depressive disorders in euthymic and depressed states.

AIM: This study aimed to examine the cognitive performance of patients with bipolar disorder (BD) stratified by illness phase compared to that of patients with major depressive disorder (MDD) and healthy controls. METHODS: Participants were 139 patients with BD (55 euthymic and 84 depressed), 311 patients with MDD (88 euthymic and 223 depressed), and 386 healthy controls who underwent the Wechsler Adult Intelligence Scale-Revised or the Third Edition. They were non-elderly Japanese individuals with normal estimated premorbid intelligence quotient (IQ; >90), group-matched for age, sex, and premorbid IQ. RESULTS: The depressed BD group showed significantly lower scores on verbal IQ, performance IQ, full-scale IQ, and three group indexes of perceptual organization, working memory, and processing speed when compared with healthy controls (all P < 0.001). All IQs and working memory index were also significantly lower than those of the depressed MDD group. The depressed MDD group scored significantly lower than controls in performance IQ (P < 0.001), full-scale IQ, and only in the index of processing speed (P < 0.001). The euthymic BD group scored significantly lower than controls in performance IQ (P = 0.004), whereas the euthymic MDD group scored significantly lower than controls only in processing speed (P = 0.030). CONCLUSION: Patients with BD appear to have global and more intense cognitive impairments in depressed states compared with those with MDD whose impairments seem to be apparent only in processing speed in the Wechsler Adult Intelligence Scale. Attenuated impairments appear to exist in euthymic states of both patients.

Association between obesity and white matter microstructure impairments in patients with schizophrenia: A whole-brain magnetic resonance imaging study.

AIM: We aimed to examine the possible association of obesity (body mass index [BMI] ≥ 30) with symptoms, psychotropic medication, and whole-brain structure in patients with schizophrenia. METHODS: Participants were 65 patients diagnosed with schizophrenia (mean age: 37.2 ± 11.3 years, 32 females). All participants were Japanese and right-handed. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Pittsburgh Sleep Quality Index (PSQI). Voxel based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to analyze the association of obesity with gray and white matter structures, respectively. RESULTS: There was no significant difference in PANSS scores between obese and non-obese patients, while the PSQI score was significantly higher in the former than in the latter (p < 0.05). The daily dose of typical antipsychotics was significantly higher in obese patients than in non-obese patients (p < 0.001). In VBM, there was no significant difference in gray matter volume between obese and non-obese patients. In DTI, fractional anisotropy values in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, and posterior thalamic radiations were significantly lower in obese patients than in non-obese patients (corrected p < 0.05). Axial diffusivity was significantly lower while radial and mean diffusivities values were significantly higher in obese patients than in non-obese patients (corrected p < 0.05) in similar but more restricted brain regions. CONCLUSION: Our results suggest that obesity is related to sleep disturbances, daily dose of typical antipsychotics, and regional white matter microstructure impairments in patients with schizophrenia.

Corrigendum: Correlation Between the Wechsler Adult Intelligence Scale- 3 rd Edition Metrics and Brain Structure in Healthy Individuals: A Whole-Brain Magnetic Resonance Imaging Study.

[This corrects the article DOI: 10.3389/fnhum.2020.00211.].

Correlation Between the Wechsler Adult Intelligence Scale- 3 rd Edition Metrics and Brain Structure in Healthy Individuals: A Whole-Brain Magnetic Resonance Imaging Study.

BACKGROUND: The Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III) is widely used to evaluate the intelligence quotient (IQ). We aimed to investigate the correlation between the WAIS-III metrics and whole-brain structures using magnetic resonance imaging. METHODS: The participants were 266 healthy, right-handed individuals (age: 45.6 ± 12.9 years, 98 males and 168 females). IQs were evaluated using the WAIS-III and Japanese Adult Reading Test (JART). Voxel-based morphometry and diffusion tensor imaging were performed to analyze the correlation of the WAIS-III metrics and JART score with the gray matter volume and white matter integrity, respectively. RESULTS: The verbal IQ significantly and positively correlated with the left gyrus rectus and anterior cingulate gyrus, left posterior insula and planum polare, and left superior and middle frontal gyri volumes (p < 0.05, corrected). The verbal comprehension group index significantly and positively correlated with the left superior and middle frontal gyri, left gyrus rectus and anterior cingulate gyrus, and left middle frontal gyrus volumes, while the processing speed group index significantly and positively correlated with the bilateral various regional white matter fractional anisotropy values (p < 0.05, corrected). In contrast, the JART score showed no correlation with any brain structure. CONCLUSION: These results suggested the neurostructural bases of the WAIS-III IQs and group indices in the brain of healthy individuals.

Eighteen-year follow-up cohort study on hepatitis B and C virus infections related long-term prognosis among hemodialysis patients in Hiroshima.

This study aimed to investigate the prevalence trend of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and their genotype distribution among hemodialysis patients, determining their long-term prognosis and the risk factors to the mortality. This cohort study used both the medical data and the blood samples of hemodialysis patients at nine dialysis centers in Hiroshima from 1999 to 2017. Hepatitis B surface antigen (HBsAg) and anti-HCV were screened and then amplification was done to positive sera by polymerase chain reaction for genotyping. Data were employed for multiple regressions to determine the associated risk factors. A total of 3968 patients were subdivided into three groups: who started hemodialysis before 1990, during 1991 to 2001, and after 2002. The periodic prevalence of HBsAg decreased from 2.8% to 1.3% and that of anti-HCV from 33.3% to 9.5% in the three groups. By multiple regressions, the adjusted hazard ratio of diabetes mellitus (DM) ranges from 1.59 to 2.12 and that of HCV RNA positivity ranges from 1.18 to 1.48 (P < .05). Heart failure is the primary cause of death in all groups. Genotype C2 is predominant for HBV and genotype 1b is predominant for HCV. The decreasing trend of both HBV and HCV was found in the cohort. DM and HCV RNA were the significant risk factors leading to poor prognosis among hemodialysis patients. The similar genotype distribution of both HBV and HCV was found as general population. This alarmed to provide early diagnosis, prompt, and adequate treatment to HCV infection among hemodialysis patients.

Substitution of the CD81 Binding Site and ß-Sandwich Area in E2 of HCV in Cambodia.

The high genetic variability of hepatitis C virus (HCV) is the main obstacle to developing a vaccine. E2 has attracted attention for vaccine development because targeting this protein could potentially overcome issues related to the genetic diversity of HCV. In this study, we analyzed HCV genes in the general population of Cambodia and investigated the E2 locus as a candidate for vaccine development. HCV sero-epidemiological surveys were conducted between the period 2010 and 2014, with an HCV RNA-positive rate of 1.3% (11/868). Follow-up blood samples were collected from four anti-HCV- and HCV RNA- positive patients (genotype 1b: 2 cases, 6e: 1 case, 6r: 1 case) after 4.12 years. Analysis of HCV full-length nucleotide sequences in paired specimens revealed that the mutation rates of HCV genotypes 1b and 6e/6r were 1.61-2.03 × 10-3 and 2.52-2.74 × 10-3 substitutions/site/year, respectively. Non-synonymous substitutions were detected in HVR1, the front layer of the CD81 binding site, and the ß-sandwich, but not in the N-terminal region or adjacent to the CD81 binding site. Therefore, we conclude that the CD81 binding site is a promising locus for HCV vaccine development.

Cerebrospinal fluid neuroplasticity-associated protein levels in patients with psychiatric disorders: a multiplex immunoassay study.

To examine the role of neuroplasticity in the pathology of psychiatric disorders, we measured cerebrospinal fluid (CSF) neuroplasticity-associated protein levels. Participants were 94 patients with schizophrenia, 68 with bipolar disorder (BD), 104 with major depressive disorder (MDD), and 118 healthy controls, matched for age, sex, and ethnicity (Japanese). A multiplex immunoassay (22-plex assay) was performed to measure CSF neuroplasticity-associated protein levels. Among 22 proteins, 11 were successfully measured in the assay. CSF amyloid precursor protein (APP) and glial cell-derived neurotrophic factor (GDNF) levels were significantly lower in patients with schizophrenia, and CSF APP and neural cell adhesion molecule (NCAM)-1 levels were significantly lower in patients with BD, than in healthy controls (all p < 0.05). Positive and Negative Syndrome Scale total, positive, and general scores were significantly and positively correlated with CSF hepatocyte growth factor (HGF) (p < 0.01) and S100 calcium-binding protein B (S100B) (p < 0.05) levels in patients with schizophrenia. Young mania-rating scale score was significantly and positively correlated with CSF S100B level in patients with BD (p < 0.05). Hamilton Depression Rating Scale, core, sleep, activity, somatic anxiety, and delusion subscale scores were significantly and positively correlated with CSF HGF level, while sleep subscale score was positively correlated with CSF S100B and VEGF receptor 2 levels in patients with MDD (p < 0.05). Our results suggest that CSF APP, GDNF, and NCAM-1 levels are associated with psychiatric disorders, and that CSF HGF, S100B, and VEGF receptor 2 levels are related to psychiatric symptoms.

Possible associations between plasma fibroblast growth factor 21 levels and cognition in bipolar disorder.

Bipolar disorder (BD) is a mental disorder characterized by extreme changes in mood polarity. It is also characterized by cognitive and metabolic dysfunctions. Fibroblast growth factor 21 (FGF21) is an endocrine protein that has a multifaceted function such as glucose and lipid regulation in the periphery, and neuroprotection and induction of synaptic plasticity in the central nervous system. Previous studies reported inconsistent results concerning peripheral FGF21 levels in patients with BD. In this study, we compared plasma FGF21 levels between 26 patients with BD and 51 healthy controls using a human FGF21 ELISA Kit. There was no significant difference in plasma FGF21 levels between the patients and controls. We found significant positive correlations between plasma FGF21 levels and some cognitive parameters (word association and motor speed). If our results are replicated that higher peripheral FGF21 may be associated with better cognitive performance in patients with BD.

A Case of Giant Pituitary Adenoma Associated with a Postoperative Mental Disorder That Ultimately Resulted in Bilateral Blindness.

PURPOSE: To report the case of a patient with adrenocorticotropic hormone (ACTH)-producing pituitary adenoma who developed a mental disorder after initial surgery that kept him from undergoing scheduled follow-up visits and who ultimately had a giant recurrent tumor that resulted in blindness. CASE REPORT: A 37-year-old male presented with the primary complaint of decreased visual acuity (VA) in both eyes and visual field defects. Visual field examination revealed bitemporal hemianopia. Magnetic resonance imaging (MRI) showed a pituitary tumor of approximately 4 cm in diameter extending from the intrasellar region to the sphenoid sinus and the suprasellar region. Transnasal transsphenoidal surgery was performed. Immunostaining of tumor tissue collected intraoperatively showed ACTH-positive cells, thus leading to the diagnosis of ACTH-producing pituitary adenoma. Postoperatively, the patient reportedly developed mental disorder that possibly interfered with scheduled appointments or continuous follow-up visits for many years, so we had no postoperative data about the vision/visual filed. Seven years later, he presented with markedly decreased VA (i.e., no light perception) in both eyes. Fundus examination showed bilateral marked optic disc atrophy. MRI showed a larger than 8-cm diameter giant recurrent pituitary adenoma in the suprasellar region, for which craniotomy was performed for partial tumor resection. Preoperatively, his blood cortisol level was low, and the lesion was deemed a nonfunctioning pituitary adenoma. Postoperatively, no significant complications occurred, yet his VA was no light perception OD and light perception OS. CONCLUSIONS: Clinicians should be aware that patients with ACTH-producing pituitary adenomas may develop a mental disorder following surgery and possibly be unable to undergo scheduled follow-up, thus illustrating the importance of establishing an adequate patient follow-up system.

Cerebrospinal Fluid Inflammatory Cytokine Levels in Patients With Major Psychiatric Disorders: A Multiplex Immunoassay Study.

Aim: Accumulating evidence suggests that neural inflammation plays an important role in psychiatric disorders. We aimed to identify inflammatory cytokines involved in the pathophysiology of such disorders by quantifying them in cerebrospinal fluid (CSF) samples from a large sample of patients with major psychiatric disorders and healthy controls. Methods: The subjects included 94 patients with schizophrenia, 68 with bipolar disorder, 104 with major depressive disorder, and 118 healthy controls, matched for age, sex, and ethnicity (Japanese). Lumbar puncture was performed to collect these CSF samples. A multiplex immunoassay was then performed to measure CSF cytokine levels using magnetic on-bead antibody conjugation for 19 inflammatory cytokines. Results: CSF interferon-ß level was significantly higher in total psychiatric patients than in healthy controls (corrected p = 0.000029). In diagnostic group comparisons, CSF interferon-ß level was significantly higher in patients with schizophrenia, or bipolar disorder (corrected p = 0.000047 or 0.0034) than in healthy controls. Conclusion: We present novel evidence that CSF IFN-ß level showed prominent statistical differences between psychiatric groups and healthy controls. This suggests IFN-ß as the most important player among the 19 cytokines tested here in the inflammation-related pathophysiology of major psychiatric disorders.

Altered ethanolamine plasmalogen and phosphatidylethanolamine levels in blood plasma of patients with bipolar disorder.

AIM: Ethanolamine-containing phospholipids are synthesized in endoplasmic reticulum (ER) and mitochondria. ER stress and mitochondrial dysfunction have been implicated in bipolar disorder (BP). In this study, we aimed to examine the relationship of ethanolamine plasmalogen (PLE) and phosphatidylethanolamine (PTE) levels in blood plasma with BP. METHODS: Plasma PLE and PTE levels were compared between 34 patients with BP (DSM-IV) and 38 healthy control participants matched for age, sex, and ethnicity (Japanese). Furthermore, the relationships of plasma PLE and PTE levels with clinical variables were explored. RESULTS: Plasma PLE levels were significantly lower in patients with BP than in healthy controls (P = 0.0033). In subgroup analyses, plasma PLE levels were significantly lower in patients with BP type I (BP I) than in healthy controls (P = 0.0047); furthermore, plasma PTE levels were significantly lower in patients with BP I than in controls (P = 0.016) and patients with BP type II (BP II) (P = 0.010). Receiver-operating characteristic curve analysis revealed that the discriminatory power of plasma PTE levels for distinguishing between BP I and II was fair (area under the curve = 0.78; P = 0.0095). There were no significant correlations of plasma PLE or PTE levels with depression or manic symptoms in patients. CONCLUSIONS: Plasma PLE and PTE levels were associated with BP I, but not with BP II. Moreover, plasma PTE levels differed between patients with BP I and II. Our findings highlight the importance of ethanolamine phospholipids in the pathophysiology of BP, especially BP I.

High possibility of hepatocarcinogenesis in HBV genotype C1 infected Cambodians is indicated by 340 HBV C1 full-genomes analysis from GenBank.

Approximately 75% of hepatocellular carcinomas (HCC) occur in Asia; core promoter mutations are associated with HCC in HBV genotype C, the dominant genotype in Cambodia. We analyzed these mutations in Cambodian residents and compared them with HBV full genomes registered in GenBank. We investigated the characteristics of 26 full-length HBV genomes among 35 residents positive for hepatitis B surface antigen in Siem Reap province, Cambodia. Genotype C1 was dominant (92.3%, 24/26), with one case of B2 and B4 each. Multiple mutations were confirmed in 24 Cambodian C1 isolates, especially double mutation at A1762T/G1764A in 18 isolates (75.0%), and combination mutation at C1653T and/or T1753V and A1762T/G1764A in 14 isolates (58.3%). In phylogenetic analysis, 16 of 24 isolates were located in the cluster with Laos, Thailand, and Malaysia. In 340 GenBank-registered C1 strains, 113 (33.2%) had combination mutation amongst which 16.5%, 34.2%, and 95.2% were found in ASC, chronic hepatitis, and liver cirrhosis (LC)/HCC respectively (P < 0. 001). Mutations were abundantly found in 24 Cambodian C1 isolates, and 340 C1 strains from GenBank showed mutation in genotype C1 brings high possibility of LC/HCC occurrence. Therefore, we suggest that Cambodian people infected with HBV genotype C1 have high possibility of hepatocarcinogenesis.