Low back pain (LBP) is the most common cause of chronic pain. Numerous clinical scales are available for evaluating pain, but their objective criteria in the management of LBP patients remain ...unclear. This study aimed to determine an objective cutoff value for a change in the Pain Intensity Numerical Rating Scale (ΔPI-NRS) three months after LBP treatment. Its utility was compared with changes in six commonly used clinical scales in LBP patients: Pain Disability Assessment Scale (PDAS), Pain Self-Efficacy Questionnaire (PSEC), Pain Catastrophizing Scale (PCS), Athens Insomnia Scale (AIS), EuroQoL 5 Dimension (EQ5D), and Locomo 25. We included 161 LBP patients treated in two representative pain management centers. Patients were partitioned into two groups based on patient's global impression of change (PGIC) three months after treatment: satisfied (PGIC = 1, 2) and unsatisfied (3-7). Multivariate logistic regression analysis was performed to explore relevant scales in distinguishing the two groups. We found ΔPI-NRS to be most closely associated with PGIC status regardless of pre-treatment pain intensity, followed by ΔEQ5D, ΔPDAS, ΔPSEC, and ΔPCS. The ΔPI-NRS cutoff value for distinguishing the PGIC status was determined by ROC analysis to be 1.3-1.8 depending on pre-treatment PI-NRS, which was rounded up to ΔPI-NRS = 2 for general use. Spearman's correlation coefficient revealed close relationships between ΔPI-NRS and the six other clinical scales. Therefore, we determined cutoff values of these scales in distinguishing the status of ΔPI-NRS≥2 vs. ΔPI-NRS<2 to be as follows: ΔPDAS, 6.71; ΔPSEC, 6.48; ΔPCS, 6.48; ΔAIS, 1.91; ΔEQ5D, 0.08; and ΔLocomo 25, 9.31. These can be used as definitive indicator of therapeutic outcome in the management of chronic LBP patients.
Recent studies have indicated potential links between short bouts of physical activity like stair-climbing and enhanced creative thinking. However, previous research featured limitations, such as ...using an uncommon 3 flights round-trip design and lacking baseline creative thinking evaluations. To rectify these limitations and build a more comprehensive understanding, the present study adopts a between-subjects pretest posttest comparison design to scrutinize the effects of ascending stair-climbing on both divergent and convergent thinking. 52 subjects underwent a pretest, followed by random assignment to one of four interventions: ascending stair-climbing for 2, 5, or 8 flights, or taking an elevator for 8 flights, before progressing to a posttest. The results revealed a notable improvement in convergent thinking, measured by the increased number of solved matchstick arithmetic problems (d = 1.165), for participants who climbed 2 flights of stairs compared to those who took the elevator. However, climbing 5 or 8 flights showed no such impact on convergent thinking, and stair-climbing, regardless of the number of flights, did not influence divergent thinking. These findings underscore the utility of brief stair-climbing as an accessible means to enhance convergent thinking in everyday settings, providing a nuanced insight into the relationship between physical activity and creative thinking processes.
The heterogeneity of depression (due to factors such as varying age of onset) may explain why biological markers of major depressive disorder (MDD) remain uncertain. We aimed to identify gene ...expression markers of MDD in leukocytes using microarray analysis. We analyzed gene expression profiles of patients with MDD (age ≥50, age of depression onset <50) (N = 10, depressed state; N = 13, remitted state). Seven-hundred and ninety-seven genes (558 upregulated, 239 downregulated when compared to those of 30 healthy subjects) were identified as potential markers for MDD. These genes were then cross-matched to microarray data obtained from a mouse model of depression (676 genes, 148 upregulated, 528 downregulated). Of the six common genes identified between patients and mice, five genes (SLC35A3, HIST1H2AL, YEATS4, ERLIN2, and PLPP5) were confirmed to be downregulated in patients with MDD by quantitative real-time polymerase chain reaction. Of these genes, HIST1H2AL was significantly decreased in a second set of independent subjects (age ≥20, age of onset <50) (N = 18, subjects with MDD in a depressed state; N = 19, healthy control participants). Taken together, our findings suggest that HIST1H2AL may be a biological marker of MDD.
Patients with anorexia nervosa (AN) often have complications of hematologic abnormalities and pancytopenia, which can be fatal. In patients with AN, the rates of anemia, leukopenia, and ...thrombocytopenia have been reported as 16.7-39%, 7.9-39%, and 5-11%, respectively; in patients with severe AN, the rates of anemia, leukopenia, thrombocytopenia, and pancytopenia have been reported as 47-83%, 49.5-79%, 16.8-25%, and 16.4-23%, respectively. Hematologic abnormalities are often associated with morphological myeloid transformations such as hypoplasia, aplasia, and gelatinous marrow transformation (GMT). Hypocellularity, such as hypoplastic or aplastic, often results in a dry tap, whereas GMT does not usually result in this because of the aspiration of gelatinous material. Therefore, bone marrow aspiration in patients with pancytopenia with AN usually does not show a dry tap. The bone marrow adipocyte (BMA) volume increases in patients with AN, except in those with severe malnutrition. Patients with AN experiencing pancytopenia often exhibit GMT associated with atrophy of the originally increased volume of BMAs. Herein, we report the case of a patient with pancytopenia with AN who exhibited a dry tap on bone marrow aspiration. A bone marrow biopsy revealed sparse GMT with decreased BMA volume and areas of hematopoietic cells, adipocytes, and no GMT. A 13-year-old Japanese girl weighing 25.8 kg (BMI: 10.0 kg/m
) was admitted to our hospital and received nutritional therapy. The patient presented with pancytopenia and fever, prompting the conduct of bone marrow examinations. Bone marrow aspiration resulted in a dry tap, and the bone marrow biopsy revealed sparse GMT with a decreased volume of BMAs. Additionally, an area devoid of hematopoietic cells, adipocytes, or GMT was observed. Nutritional therapy resulted in weight gain and improved pancytopenia. Upon discharge, the patient weighed 40.0 kg (BMI: 15.5 kg/m
) with a normal WBC count, hemoglobin levels, and platelet count. It is significant to study hematological and bone marrow changes because patients with AN often present with hematologic abnormalities. The identification of sparse GMT, which is associated with a decrease in BMA volume and the presence of an area devoid of hematopoietic cells, adipocytes, or GMTs, is a novel finding. The improvement in pancytopenia following nutritional therapy suggests a link between myeloid transformation and malnutrition. Consequently, in patients with pancytopenia associated with AN exhibiting these bone marrow findings, nutritional therapy is necessary.
Recent studies suggest that the dysfunction of neural plasticity is associated with mood disorders. Hypoxia-inducible factor-1 (HIF-1), which is a transcriptional activator of vascular endothelial ...growth factor (VEGF), activates the cellular response to hypoxia. HIF-1 is ubiquitously expressed in all cells, including peripheral leukocytes. However, little is known about the role of HIF-1 in mood disorder.
In the present study, we investigated the mRNA expression levels of HIF-1 (α and β) and its target genes (VEGF, GLUT1, PGK1, PFKFB3, and LDHA) in the peripheral white blood cells of patients with major depressive disorder (MDD) and bipolar disorder (BPD). We found increased expression of HIF- 1α and HIF-1β mRNA, as well as the target genes, VEGF, and PFKFB3 in both MDD and BPD patients in a depressive state compared to healthy control subjects. Furthermore, the mRNA expression levels of GLUT1, PGK1, and LDHA were increased in MDD patients in a depressive state compared to healthy control subjects. We also found increased expression of HIF-1α and LDHA mRNA in MDD patients in a remissive state, whereas the mRNA expression levels of other genes in a remissive state were comparable to those in healthy control subjects.
There was no significant difference in mRNA expression levels of the genes examined among patients receiving any type of antidepressant or mood stabilizer.
Our data suggest that altered expression of HIF-1 and its target genes mRNA in peripheral blood cells are associated—mainly in a state-dependent manner—with mood disorders (especially with MDD). In addition, altered expression of HIF-1 and its target genes may be associated with the pathophysiology of depression.
► We investigated HIF-1 mRNA in the leukocytes of patients with mood disorder. ► HIF-1 and its target genes mRNA were increased mainly in a state-dependent manner. ► HIF-1 may be associated with the pathophysiology of depression.
Recent studies show that even a brief bout of aerobic exercise may enhance creative thinking. However, few studies have investigated the effect of exercise conducted in natural settings. Here, in a ...crossover randomized controlled trial, we investigated the effect of a common daily activity, stair-climbing, on creative thinking. As experimental intervention, subjects were asked to walk downstairs from the fourth to the first floor and back at their usual pace. As control intervention, they walked the same path but using the elevator instead. Compared to using the elevator, stair-climbing enhanced subsequent divergent but not convergent thinking in that it increased originality on the Alternate Use Test (
= 0.486). Subjects on average generated 61% more original uses after stair-climbing. This is the first study to investigate the effect of stair-climbing on creative thinking. Our findings suggest that stair-climbing may be a useful strategy for enhancing divergent thinking in everyday life.
Aberrant transcriptional regulation in the brain is thought to be one of the key components of the pathogenesis and pathophysiology of neuropsychiatric disorders. Heat shock factors (HSFs) modulate ...cellular homeostasis through the control of gene expression. However, the roles of HSFs in brain function have yet to be elucidated fully. In the present study, we attempted to clarify the role of HSF1-mediated gene regulation in neuronal and behavioral development using HSF1-deficient (HSF1⁻/⁻) mice. We found granule neurons of aberrant morphology and impaired neurogenesis in the dentate gyrus of HSF1⁻/⁻ mice. In addition, HSF1⁻/⁻ mice showed aberrant affective behavior, including reduced anxiety and sociability but increased depression-like behavior and aggression. Furthermore, HSF1 deficiency enhanced behavioral vulnerability to repeated exposure to restraint stress. Importantly, rescuing the HSF1 deficiency in the neonatal but not the adult hippocampus reversed the aberrant anxiety and depression-like behaviors. These results indicate a crucial role for hippocampal HSF1 in neuronal and behavioral development. Analysis of the molecular mechanisms revealed that HSF1 directly modulates the expression of polysialyltransferase genes, which then modulate polysialic acid-neural cell adhesion molecule (PSA-NCAM) levels in the hippocampus. Enzymatic removal of PSA from the neonatal hippocampus resulted in aberrant behavior during adulthood, similar to that observed in HSF1⁻/⁻ mice. Thus, these results suggest that one role of HSF1 is to control hippocampal PSA-NCAM levels through the transcriptional regulation of polysialyltransferases, a process that might be involved in neuronal and behavioral development in mice.
The dorsal raphe nucleus (DRN) has been repeatedly implicated as having a significant relationship with depression, along with its serotoninergic innervation. However, functional connectivity of the ...DRN in depression is not well understood. The current study aimed to isolate functional connectivity of the DRN distinct in later life depression (LLD) compared to a healthy age-matched population. Resting state functional magnetic resonance imaging (rsfMRI) data from 95 participants (33 LLD and 62 healthy) were collected to examine functional connectivity from the DRN to the whole brain in voxel-wise fashion. The posterior cingulate cortex (PCC) bilaterally showed significantly smaller connectivity in the LLD group than the control group. The DRN to PCC connectivity did not show any association with the depressive status. The findings implicate that the LLD involves disruption of serotoninergic input to the PCC, which has been suggested to be a part of the reduced default mode network in depression.
Schizophrenia is a complex mental disorder characterized by significant cognitive and neurobiological alterations. Impairments in cognitive function and eye movement have been known to be promising ...biomarkers for schizophrenia. However, cognitive assessment methods require specialized expertise. To date, data on simplified measurement tools for assessing both cognitive function and eye movement in patients with schizophrenia are lacking.
This study aims to assess the efficacy of a novel tablet-based platform combining cognitive and eye movement measures for classifying schizophrenia.
Forty-four patients with schizophrenia, 67 healthy controls, and 41 patients with other psychiatric diagnoses participated in this study from 10 sites across Japan. A free-viewing eye movement task and 2 cognitive assessment tools (Codebreaker task from the THINC-integrated tool and the CognitiveFunctionTest app) were used for conducting assessments in a 12.9-inch iPad Pro. We performed comparative group and logistic regression analyses for evaluating the diagnostic efficacy of the 3 measures of interest.
Cognitive and eye movement measures differed significantly between patients with schizophrenia and healthy controls (all 3 measures; P<.001). The Codebreaker task showed the highest classification effectiveness in distinguishing schizophrenia with an area under the receiver operating characteristic curve of 0.90. Combining cognitive and eye movement measures further improved accuracy with a maximum area under the receiver operating characteristic curve of 0.94. Cognitive measures were more effective in differentiating patients with schizophrenia from healthy controls, whereas eye movement measures better differentiated schizophrenia from other psychiatric conditions.
This multisite study demonstrates the feasibility and effectiveness of a tablet-based app for assessing cognitive functioning and eye movements in patients with schizophrenia. Our results suggest the potential of tablet-based assessments of cognitive function and eye movement as simple and accessible evaluation tools, which may be useful for future clinical implementation.
Although depression is the leading cause of disability worldwide, its pathophysiology is poorly understood. Recent evidence has suggested that sirtuins (SIRTs) play a key role in cognition and ...synaptic plasticity, yet their role in mood regulation remains controversial. Here, we aimed to investigate whether SIRT function is associated with chronic stress-elicited depression-like behaviors and neuronal atrophy.
We measured SIRT expression and activity in a mouse model of depression. We injected mice with a SIRT1 activator or inhibitor and measured their depression-like behaviors and dendritic spine morphology. To assess the role of SIRT1 directly, we used a viral-mediated gene transfer to overexpress the wild-type SIRT1 or dominant negative SIRT1 and evaluated their depression-like behaviors. Finally, we examined the role of extracellular signal-regulated protein kinases 1 and 2, a potential downstream target of SIRT1, in depression-like behavior.
We found that chronic stress reduced SIRT1 activity in the dentate gyrus of the hippocampus. Pharmacologic and genetic inhibition of hippocampal SIRT1 function led to an increase in depression-like behaviors. Conversely, SIRT1 activation blocked both the development of depression-related phenotypes and aberrant dendritic structures elicited by chronic stress exposure. Furthermore, hippocampal SIRT1 activation increased the phosphorylation level of extracellular signal-regulated protein kinases 1 and 2 in the stressed condition, and viral-mediated activation and inhibition of hippocampal extracellular signal-regulated protein kinase 2 led to antidepressive and prodepressive behaviors, respectively.
Our results suggest that the hippocampal SIRT1 pathway contributes to the chronic stress-elicited depression-related phenotype and aberrant dendritic atrophy.
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