Role of coping with negative emotions in cognitive behavioral therapy for persistent somatoform pain disorder: Is it more important than pain catastrophizing?

AIM: Cognitive behavioral therapy (CBT) is known to be effective for patients with persistent somatoform pain disorder (PSPD). Improvement of negative emotions in interpersonal stressful situations has been reported to reduce PSPD-related clinical pain. However, these associations in CBT remain unclear. Therefore, we examined the relation between changes in negative emotions and clinical pain symptoms after CBT by using a multiple regression analysis that included pain catastrophizing. METHODS: We analyzed negative emotional intensity scores in stressful situations of 38 patients with PSPD who had completed CBT treatment and all the daily worksheets. Negative emotional intensity scores were recorded in daily worksheets during 12 weekly CBT sessions. Scores for the Pain Catastrophizing Scale (PCS), Visual Analogue Scale (VAS) as clinical pain intensity, Beck Depression Inventory - Second Edition (BDI-II), and State-Trait Anxiety Inventory (STAI) were also obtained at pre- and post-treatment. A multiple regression analysis was conducted using changes in VAS scores after CBT as the dependent variable, and changes in negative emotional intensity, PCS, BDI-II, and STAI scores after CBT, age, and sex as independent variables. RESULTS: Negative emotional intensity scores decreased after CBT. In a multiple regression analysis, the emotional changes resulting from CBT depicted a modest positive relation with changes in VAS scores (ß = 0.37; P < 0.05); however, there was no relation between changes in PCS scores after CBT and changes in VAS scores after CBT (ß = 0.03). CONCLUSION: The results show that negative emotions play an important role in the treatment effects of CBT for PSPD.

The role of root size versus root efficiency in phosphorus acquisition in rice.

In rice, genotypic differences in phosphorus (P) uptake from P-deficient soils are generally proportional to differences in root biomass or surface area (RSA). It is not known to what extent genotypic variation for root efficiency (RE) exists or contributes to P uptake. We evaluated 196 rice accessions under P deficiency and detected wide variation for root biomass which was significantly associated with plant performance. However, at a given root size, up to 3-fold variation in total biomass existed, indicating that genotypes differed in how efficiently their root system acquired P to support overall plant growth. This was subsequently confirmed, identifying a traditional genotype, DJ123, with 2.5-fold higher RE (32.5 µg P cm(-2) RSA) compared with the popular modern cultivar IR64. A P depletion experiment indicated that RE could not be explained by P uptake kinetics since even IR64 depleted P to <20nM. A genome-wide association study identified loci associated with RE, and in most cases the more common marker type improved RE. This may indicate that modern rice cultivars lost the ability for efficient P uptake, possibly because they were selected under highly fertile conditions. One association detected on chromosome 11 that was present in a small group of seven accessions (including DJ123) improved RE above the level already present in many traditional rice accessions. This subspecies is known to harbor genes enhancing stress tolerance, and DJ123 may thus serve as a donor of RE traits and genes that modern cultivars seem to have lost.

Behavioral activation for late adolescents with subthreshold depression: a randomized controlled trial.

The main behavioral characteristic of subthreshold depression that is observed in adolescents is the low frequency of exposure to environmental rewards. Therefore, it was considered that a simple intervention conducted in short sessions, focusing on increasing access to positively reinforcing activities, would be efficacious in increasing the availability of rewards. We conduct a randomized controlled trial to examine the efficacy of such a behavioral activation program that was conducted weekly for 5 weeks in 60-min sessions. Late adolescent university students aged 18-19 years with subthreshold depression were randomly allocated to a treatment (n = 62) or a control group (n = 56). The primary outcome of the study was the Beck Depression Inventory-II score. Results indicated that late adolescent students in the treatment group showed significant improvements in their depressive symptoms (effect size -0.90, 95 % CI -1.28 to -0.51) compared to the control group. Students in the treatment group also showed significant improvements in self-reported rating of quality of life and in behavioral characteristics. It is concluded that this intervention had a large and significant effect despite being short and simple and that this low-intensity cognitive behavioral therapy program could be conducted in many different types of institutions. It is suggested that the long-term effects of the treatment program should be targeted for investigation in future studies.

[Neuroimaging studies of depression: Current status and future direction.]

Recent advances in neuroimaging studies enable us to measure brain function non-invasively. Over the past several decades, neuroimaging measurement has been substantially applied to elucidate the neurobiological mechanisms underlying major depressive disorder (MDD). Since MDD is a wide spectrum which consists of various symptoms such as low mood or loss of interest and is considered to affect a biologically het- erogeneous population, we have not yet elucidated the biological underpinnings of MDD. It seems to be more promising to consider MDD as an integral network abnormality instead of deficits in specific brain regions or neurotransmitters. We firstly provide a comprehensive review of the extant neuroimaging literature including structural and functional magnetic resonance imaging, magnetic resonance spectroscopy, single pho- ton emission computed tomography, and positron emission tomography studies. Then we show our neuroimaging studies for MDD toward po- tential application as a biomarker for diagnosis and treatment. We believe it will facilitate the development, of a more integrative model of neural dysfunction in MDD.

Predicting Ventral Striatal Activation During Reward Anticipation From Functional Connectivity at Rest.

Reward anticipation is essential for directing behavior toward positively valenced stimuli, creating motivational salience. Task-related activation of the ventral striatum (VS) has long been used as a target for understanding reward function. However, some subjects may not be able to perform the respective tasks because of their complexity or subjects' physical or mental disabilities. Moreover, task implementations may differ, which results in limited comparability. Hence, developing a task-free method for evaluating neural gain circuits is essential. Research has shown that fluctuations in neuronal activity at rest denoted individual differences in the brain functional networks. Here, we proposed novel models to predict the activation of the VS during gain anticipation, using the functional magnetic resonance imaging data of 45 healthy subjects acquired during a monetary incentive delay task and under rest. In-sample validation and held-out data were used to estimate the generalizability of the models. It was possible to predict three measures of reward activation (sensitivity, average, maximum) from resting-state functional connectivity (Pearson's r = 0.38-0.54 in validation data). Especially high contributions to the models were observed from the default mode network. These findings highlight the potential of using functional connectivity at rest as a task-free alternative for predicting activation in the VS, offering a possibility to estimate reward response in the broader sampling of subject populations.

Effects of behavioral activation on default mode network connectivity in subthreshold depression: A preliminary resting-state fMRI study.

BACKGROUND: Subthreshold depression is a risk factor for major depressive disorder, and it is known to have a negative impact on quality of life (QOL). Although behavioral activation, which is one type of cognitive behavioral therapy, is an effective psychological intervention for subthreshold depression, neural mechanisms of behavioral activation are unclear. Enhanced functional connectivity between default mode network (DMN) and the other regions has been demonstrated in participants with subthreshold depression. The purpose of this study was to examine the effects of behavioral activation on DMN abnormalities by using resting-state functional MRI (rs-fMRI). METHODS: Participants with subthreshold depression (N =40) were randomly assigned to either an intervention group or a non-intervention group. They were scanned using rs-fMRI before and after the intervention. Independent component analysis indicated three subnetworks of the DMN. RESULTS: Analyzing intervention effects on functional connectivity of each subnetwork indicated that connectivity of the anterior DMN subnetwork with the dorsal anterior cingulate was reduced after the intervention. Moreover, this reduction was correlated with an increase in health-related QOL. LIMITATIONS: We did not compare the findings with healthy participants. Further research should be conducted by including healthy controls to verify the results of this study. CONCLUSIONS: Mechanisms of behavioral activation might be related to enhanced ability to independently use the dACC and the DMN, which increases an attention control to positive external stimuli. This is the first study to investigate neural mechanisms of behavioral activation using rs-fMRI.

Enduring effects of a 5-week behavioral activation program for subthreshold depression among late adolescents: an exploratory randomized controlled trial.

BACKGROUND: No significant effect of psychological treatment has been reported from meta-analysis of subthreshold depression patients and control subjects at 1-year follow-up. However, behavioral activation is a simpler and more cost-effective treatment than cognitive behavioral therapy. The primary purpose of this study was to assess by comparison to an assessment-only control group whether the effects of behavioral activation program for depressive symptoms can persist up to 1-year follow-up without the use of antidepressants or other psychotherapy. PATIENTS AND METHODS: Late adolescent students were the population targeted in this study. Participants were allocated randomly to an intervention group (n=62) or a control group (n=56). Treatment consisted of five-weekly 60-minute sessions. Participants underwent a structured interview and completed self-report scales at 1 year post-assessment. RESULTS: Late adolescent students receiving treatment had significantly lower mean Beck Depression Inventory, second edition scores at 1-year follow-up than control group students. The effect size (Hedges' g) for between-group differences at 1-year follow-up was -0.41. CONCLUSION: Our behavioral activation program is simple and short. Nevertheless, the results obtained at 1-year follow-up of the control group and late adolescent students receiving treatment indicated a significant difference in their Beck Depression Inventory, second edition scores. Our 5-week behavioral activation program based on behavioral characteristics for subthreshold depression might be promising for subthreshold depression. The sample examined for this study imposed some study limitations.

Effects of behavioural activation on the neural circuit related to intrinsic motivation.

BACKGROUND: Behavioural activation is an efficient treatment for depression and can improve intrinsic motivation. Previous studies have revealed that the frontostriatal circuit is involved in intrinsic motivation; however, there are no data on how behavioural activation affects the frontostriatal circuit.AimsWe aimed to investigate behavioural activation-related changes in the frontostriatal circuit. METHOD: Fifty-nine individuals with subthreshold depression were randomly assigned to either the intervention or non-intervention group. The intervention group received five weekly behavioural activation sessions. The participants underwent functional magnetic resonance imaging scanning on two separate occasions while performing a stopwatch task based on intrinsic motivation. We investigated changes in neural activity and functional connectivity after behavioural activation. RESULTS: After behavioural activation, the intervention group had increased activation and connectivity in the frontostriatal region compared with the non-intervention group. The increased activation in the right middle frontal gyrus was correlated with an improvement of subjective sensitivity to environmental rewards. CONCLUSIONS: Behavioural activation-related changes to the frontostriatal circuit advance our understanding of psychotherapy-induced improvements in the neural basis of intrinsic motivation.Declaration of interestNone.

Patients with major depressive disorder exhibit reduced reward size coding in the striatum.

BACKGROUND: Anhedonia is a core symptom of major depressive disorder (MDD). While recent evidence suggests that reduced motivation for reward may be a core feature of anhedonia, the abnormalities in modulatory neural responses to variable reward amounts in MDD patients remain unclear. We investigated whether MDD patients' ability to represent variable-sized monetary rewards in the striatum is disrupted. METHODS: Twelve MDD patients and 12 healthy volunteers completed an assessment of psychometric status and participated in a functional magnetic resonance imaging (fMRI) task that involved the anticipation of financial reward (monetary incentive delay task). The size of the monetary reward was varied among trial conditions and was cued with geometric stimuli. Patients participated in additional fMRI sessions after a 6-week pharmacological treatment with escitalopram, an SSRI. RESULTS: In healthy volunteers, striatal activity increased in proportion to the size of the monetary reward during reward anticipation. This pattern was altered in MDD patients, and significant group-by-reward size interaction effects were observed in the bilateral putamen and the left ventral striatum. Reward sensitivity in motor response and striatum activity at three regions were correlated in healthy controls. In MDD patients, this neurobehavioral coupling was not observed. In addition, changes in the neural reward sensitivity parameter at the left ventral striatum in response to treatment were positively correlated with a reduction of depressive symptoms. CONCLUSIONS: Patients with MDD exhibit reduced ability to modulate neural response when adjusting for variable amount of reward. This result suggests that reward size coding in the striatum may represent a neural correlate of motivational anhedonia in MDD patients.

The neural correlates of the metacognitive function of other perspective: a multiple regression analysis study.

Perspective taking is defined as the social cognitive function of imagining the world or imagining oneself from another's viewpoint. Previously, we reported that behavioral activation increased the dorsal medial prefrontal cortex (dmPFC) activation during other perspective self-referential processing for positive words in subthreshold depression, but did not report whether metacognitive function was related to the dmPFC activation. Therefore, we sought to test the relationship between the dmPFC activation during other perspective self-referential processing for positive words and an individual's metacognitive evaluation of other perspective. Thirty-four healthy individuals underwent functional MRI scans during a referential task with two viewpoints (self/other) and two emotional valences (positive/negative). Neural activation during other perspective self-referential processing for positive words was correlated with the metacognitive function of participants measured by the Interpersonal Reactivity Index (IRI). We found a positive correlation between the score in perspective taking of the IRI and activation in the dmPFC during other perspective self-referential processing for positive words. The present findings showed that self-report questionnaires assessing participants' metacognitive evaluation of other perspective were correlated with dmPFC activation during positive metacognition of other perspective task. However, we did not conduct a behavioral activation intervention in the present study. The present students were healthy. The IRI is a subjective measure of multidimensional trait empathy. It is necessary to develop an objective measurement for the metacognitive function of other perspective in the near future.

Behavioral activation can normalize neural hypoactivation in subthreshold depression during a monetary incentive delay task.

BACKGROUND: Late adolescents are under increased risk of developing depressive symptoms. Behavioral activation is an effective treatment for subthreshold depression, which can prevent the development of subthreshold depression into a major depressive disorder. However, the neural mechanisms underlying the efficacy of behavioral activation have not been clearly understood. We investigated neural responses during reward processing by individuals with subthreshold depression to clarify the neural mechanisms of behavioral activation. METHODS: Late adolescent university students with subthreshold depression (n=15, age 18-19 years) as indicated by a high score on the Beck's Depression Inventory-ll (BDI-ll) and 15 age-matched controls with a low BDI-ll score participated in functional magnetic resonance imaging scanning conducted during a monetary incentive delay task on two occasions. The Individuals in the subthreshold depression group received five, weekly behavioral activation sessions between the two scanning sessions. Moreover, they did not receive any medication until the study was completed. RESULTS: Behavioral activation significantly reduced depressive symptoms. Moreover, compared to the changes in brain functions in the control group, the behavioral activation group showed functional changes during loss anticipation in brain structures that mediates cognitive and emotional regulation, including the left ventrolateral prefrontal cortex and angular gyrus. LIMITATIONS: Replication of the study with a larger sample size is required to increase the generalizability of these results. CONCLUSIONS: Behavioral activation results in improved functioning of the fronto-parietal region during loss anticipation. These results increase our understanding of the mechanisms underlying specific psychotherapies.

HLA-G expression is regulated by miR-365 in trophoblasts under hypoxic conditions.

INTRODUCTION: Hypoxia occurs in the first trimester of placental development and is implicated in the regulation of trophoblast differentiation. Prolonged hypoxic conditions in the placenta are related to the development of preeclampsia. MicroRNAs (miRNAs) are noncoding, single-stranded RNAs that modulate gene expression by targeting messenger RNA. We hypothesized that, under hypoxic conditions, trophoblasts may have a unique miRNA profile that may play a critical role in placental development. METHODS: Total RNA was extracted from human trophoblast, HChEpC1b, exposed to normoxia (20% O2) or hypoxia (2% O2) for 24 h, and the miRNA expression profiles were investigated using a microRNA array. Several differential miRNAs were selected and validated using real-time reverse transcription PCR. We identified potential targets of these miRNAs using in silico analysis. We confirmed a potential target protein by western blot analysis and luciferase assays. RESULTS: The expression of miR-365 was significantly upregulated under hypoxic conditions. In silico analysis showed that miR-365 targeted human leukocyte antigen (HLA)-G. Both hypoxic conditions and overexpression of miR-365 inhibited the expression of HLA-G proteins. The overexpression of miR-365 also decreased the activity of the luciferase reporter containing the 3'-untranslated region (UTR) of HLA-G with the predicted miR-365-binding site. DISCUSSION: HLA-G is a non-classical HLA class-Ib molecule that is expressed mainly in extravillous trophoblasts and which plays a key role in maintaining immune tolerance at the maternal-fetal interface. Our results indicate that miR-365 targets the HLA-G 3' UTR to repress its expression. The expression of miR-365 may play an important role in human placental development and in immunoprotection of the semiallogenic embryo.

Mechanisms of behavioral activation for late adolescents: Positive reinforcement mediate the relationship between activation and depressive symptoms from pre-treatment to post-treatment.

BACKGROUND: It is suggested that there is some support for notion that frequency of activity can lead to improved mood in behavioral activation, but this research is relatively imprecise. We investigated whether positive reinforcement mediates the relationship between activation and alleviation of depressive symptoms METHODS: Late adolescents with sub-threshold depressive symptoms participated in the study. We conducted an intervention using behavioral activation with the participants. Then, pre-and post-treatment results of behavioral activation were compared. We used mediation analysis using the bootstrapping method to examine whether changes in reinforcement mediated the relationship between changes in activation and improvements in depressive symptoms. RESULTS: Participants improved significantly at the post-intervention assessment, compared to the baseline assessment. Results of mediation analysis indicated that reinforcement significantly mediated the relationship between activation and depressive symptoms, whereas activation alone had no a direct effect on depressive symptoms. LIMITATIONS: Further studies with more diverse samples of participants are required in order to generalize the results of this study to more diverse populations. CONCLUSIONS: The study provides the first full mediational test of behavioral activation model including both measures of activation and positive reinforcement, and we found support for behavioral activation's presumed mechanism of action that contact with positive reinforcement mediates the relation between activity and depression.

Unmasking Novel Loci for Internal Phosphorus Utilization Efficiency in Rice Germplasm through Genome-Wide Association Analysis.

Depletion of non-renewable rock phosphate reserves and phosphorus (P) fertilizer price increases has renewed interest in breeding P-efficient varieties. Internal P utilization efficiency (PUE) is of prime interest because there has been no progress to date in breeding for high PUE. We characterized the genotypic variation for PUE present within the rice gene pool by using a hydroponic system that assured equal plant P uptake, followed by mapping of loci controlling PUE via Genome-Wide Association Studies (GWAS). Loci associated with PUE were mapped on chromosomes 1, 4, 11 and 12. The highest PUE was associated with a minor indica-specific haplotype on chromosome 1 and a rare aus-specific haplotype on chromosome 11. Comparative variant and expression analysis for genes contained within the chromosome 1 haplotype identified high priority candidate genes. Differences in coding regions and expression patterns between genotypes of contrasting haplotypes, suggested functional alterations for two predicted nucleic acid-interacting proteins that are likely causative for the observed differences in PUE. The loci reported here are the first identified for PUE in any crop that is not confounded by differential P uptake among genotypes. Importantly, modern rice varieties lacked haplotypes associated with superior PUE, and would thus benefit from targeted introgressions of these loci from traditional donors to improve plant growth in phosphorus-limited cropping systems.

Rice Genotype Differences in Tolerance of Zinc-Deficient Soils: Evidence for the Importance of Root-Induced Changes in the Rhizosphere.

Zinc (Zn) deficiency is a major constraint to rice production and Zn is also often deficient in humans with rice-based diets. Efforts to breed more Zn-efficient rice are constrained by poor understanding of the mechanisms of tolerance to deficiency. Here we assess the contributions of root growth and root Zn uptake efficiency, and we seek to explain the results in terms of specific mechanisms. We made a field experiment in a highly Zn-deficient rice soil in the Philippines with deficiency-tolerant and -sensitive genotypes, and measured growth, Zn uptake and root development. We also measured the effect of planting density. Tolerant genotypes produced more crown roots per plant and had greater uptake rates per unit root surface area; the latter was at least as important as root number to overall tolerance. Tolerant and sensitive genotypes took up more Zn per plant at greater planting densities. The greater uptake per unit root surface area, and the planting density effect can only be explained by root-induced changes in the rhizosphere, either solubilizing Zn, or neutralizing a toxin that impedes Zn uptake (possibly [Formula: see text] or Fe(2+)), or both. Traits for these and crown root number are potential breeding targets.

Arachidonic acid release and prostaglandin F2alpha formation induced by phenylarsine oxide in PC12 cells: possible involvement of secretory phospholipase A2 activity.

Activation of phospholipase A2 (PLA2) causing arachidonic acid (AA) release is involved in neuronal cell functions. Previously, we reported AA release and prostaglandin F(2alpha) (PGF(2alpha)) formation via activation of cytosolic PLA2 by orthovanadate (Na3VO4), an inhibitor of tyrosine phosphatases, in rat pheochromocytoma PC12 cells. We investigated the effects of phenylarsine oxide (PAO), which reacts with sulfhydryl groups of proteins and thus acts as an inhibitor of tyrosine phosphatases, on AA release and PGF(2alpha) formation in PC12 cells. PAO stimulated [3H]AA release from the prelabeled cells and PGF(2alpha) formation. The PAO responses were dependent upon the concentrations used (10 microM to 0.5mM) and on extracellular CaCl2. [3H]AA release induced by PAO was decreased significantly by inhibition of secretory, but not cytosolic, PLA2. [3H]AA release by PAO was not reversed by washing the cells, but the addition of dithiol compounds such as 2,3-dimercapto-1-propanol decreased the release from the PAO-treated cells. The existence of mRNA of types IB and IIC secretory PLA2 in PC12 cells was detected by reverse transcriptase-polymerase chain reaction using specific primers. Addition of secretory PLA2 from bee venom to the assay mixture stimulated [3H]AA release, and PAO enhanced the response synergistically. The addition of 0.1mM PAO directly enhanced the activity of secretory PLA2 from bee venom. These findings suggest that PAO stimulates AA release and PGF(2alpha) formation probably via activation of secretory PLA2 in PC12 cells.

Disposable eyelid-warming device for the treatment of meibomian gland dysfunction.

PURPOSE: To assess the clinical efficacy of a newly developed disposable eyelid-warming device (Eye Warmer) for the treatment of meibomian gland dysfunction (MGD). METHODS: The Eye Warmer was applied for 5 minutes to 44 eyes of 22 patients who exhibited decreased tear break-up time (BUT) and dry-eye symptoms. Its efficacy was assessed on the basis of BUT and dry-eye symptoms in the short-term study. In the therapeutic study, the Eye Warmer was applied to 34 eyes of 17 MGD patients with decreased BUT and dry-eye symptoms for 5 minutes once a day for 2 weeks. The 16 eyes of 8 patients served as untreated controls. We examined tear film lipid layer interference patterns, BUT, meibomian gland secretion, and dry-eye symptoms in both groups before and after the treatment. RESULTS: BUT and dry-eye symptoms significantly improved after the treatment in both the short-term and the therapeutic study (P<.01). The incidence of normal tear lipid layer in the treated group was significantly higher after treatment (28 eyes [82.4%]) than before (19 eyes [55.9%]) (P=.036). The incidence of meibomian gland obstruction was significantly decreased after treatment (14 eyes [41.2%]) compared to before treatment (26 eyes [76.5%]) (P=.006). CONCLUSIONS: Warming the eyelids with the Eye Warmer improved the stability and uniformity of the tear lipid layer in MGD patients by melting the meibomian gland lipid. Our study demonstrates the usefulness of the Eye Warmer for the treatment of MGD.

Behavioral characteristics of subthreshold depression.

BACKGROUND: This study examines differences in behavioral characteristics among individuals who are not depressed and individuals with subthreshold depression, and depression. METHODS: We conducted structured interviews with 111 undergraduate students, who also completed self-report scales. The participants were divided into a non-depression group, a subthreshold depression group, and a depression group based on results of the structured interview and the BDI-II. RESULTS: There were significant differences in avoidance between depression group and other two groups. Also, for the environmental rewards, there were significant difference between the non-depressed group and the other two groups. LIMITATIONS: The sample of depressed participants was small. The overall sample consisted only undergraduate students. CONCLUSIONS: This study reported that there are different behavioral characteristics among non-depression, subthreshold depression, and depression groups. Whereas depression group is characterized by high frequency of avoidance and low environmental rewards, subthreshold depression group is characterized by only low environmental rewards.

Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis.

During mammalian development, neuroepithelial cells function as mitotic progenitors, which self-renew and generate neurons. Although spindle orientation is important for such polarized cells to undergo symmetric or asymmetric divisions, its role in mammalian neurogenesis remains unclear. Here we show that control of spindle orientation is essential in maintaining the population of neuroepithelial cells, but dispensable for the decision to either proliferate or differentiate. Knocking out LGN, (the G protein regulator), randomized the orientation of normally planar neuroepithelial divisions. The resultant loss of the apical membrane from daughter cells frequently converted them into abnormally localized progenitors without affecting neuronal production rate. Furthermore, overexpression of Inscuteable to induce vertical neuroepithelial divisions shifted the fate of daughter cells. Our results suggest that planar mitosis ensures the self-renewal of neuroepithelial progenitors by one daughter inheriting both apical and basal compartments during neurogenesis.