Serum Metabolic Profiles of the Tryptophan-Kynurenine Pathway in the high risk subjects of major depressive disorder.

Previous reports have shown that during chronic inflammation, the tryptophan (TRP)-kynurenine (KYN) pathway plays a pivotal role in the onset of depression. The aim of this study was to investigate the characteristics of the serum TRP-KYN pathway metabolite profile in high-risk subjects of major depressive disorder (HRMDD) defined by depression scores. The concentrations of TRP-KYN pathway metabolites {TRP, KYN, 3-hydroxyanthranilic acid (3HAA), 3-hydroxykynurenine (3HK), kynurenic acid (KYNA) and anthranilic acid (AA)} were assessed in serum from HRMDD, chronic pain disorder patients and healthy controls. In serum from HRMDD, elevated levels of AA and decreased levels of TRP were observed, but the levels of other metabolites were not changed. Furthermore, the change in the AA2nd/AA1st ratio in subjects who progressed from a health. y state to a depressive state was correlated with an increase in the CES-D score. The level of IL-1 receptor antagonist (IL-1RA) was negatively correlated with that of AA. Interestingly, we confirmed AA as a possible biomarker for depression-related symptoms, since the metabolite profiles in the chronic pain disorder group and chronic unpredictable mild stress model mice were similar to those in the HRMDD. These results suggest that AA may be an effective marker for HRMDD.

Exploration of coping styles in male patients with head and neck cancer: a prospective cohort study.

Majority of head and neck cancer (HNC) patients are male, and more than 85% of patients with HNC have the habit of smoking and drinking. Due to the specific demographic characteristics, HNC patients are anticipated to have specific coping styles, affecting psychological distress, survival, and quality of life. We explored the subscales of the Mental Adjustment to Cancer (MAC) Scale in male patients with HNC, and then examined the correlation between revised subscales of the MAC scale and anxiety/depression. Participants were 150 male inpatients with HNC, and their demographic and medical data were obtained. Coping style was assessed by MAC scale. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Out of 40 items in the original MAC scale, 19 items were excluded by factor analysis, and the remaining 21 items were divided into three factors: Negative Adjustment, Positive Adjustment, and Abandonment. Negative and Positive Adjustments were similar to the copings of mixed gender patients with heterogeneous cancers, and Abandonment was a new subscale specific to male patients with HNC. This subscale had a weak positive correlation with anxiety and depression. Male HNC patients revealed a specific coping style of Abandonment, related with psychological distress. We believe that an understanding of the Abandonment coping style revealed in our study will improve the psychological support offered to male patients with HNC.

Effect of antidepressant treatment on plasma levels of neuroinflammation-associated molecules in patients with somatic symptom disorder with predominant pain around the orofacial region.

OBJECTIVE: Burning mouth syndrome (BMS) and atypical odontalgia (AO) are examples of somatic symptom disorders with predominant pain around the orofacial region. Neuroinflammation is thought to play a role in the mechanisms, but few studies have been conducted. We aimed to better understand the role of neuroinflammation in the pathophysiology and treatment of BMS/AO. METHODS: Plasma levels of 28 neuroinflammation-related molecules were determined in 44 controls and 48 BMS/AO patients both pretreatment and 12-week post-treatment with duloxetine. RESULTS: Baseline plasma levels of interleukin (IL)-1ß (p < .0001), IL-1 receptor antagonist (p < .001), IL-6 (p < .0001), macrophage inflammatory protein-1ß (p < .0001), and platelet-derived growth factor-bb (.04) were significantly higher in patients than in controls. Plasma levels of granulocyte macrophage colony stimulating factor were significantly higher in patients than in controls (p < .001) and decreased with treatment (.009). Plasma levels of eotaxin, monocyte chemoattractant protein-1, and vascular endothelial growth factor decreased significantly with treatment (p < .001, .022, and .029, respectively). CONCLUSIONS: Inflammatory mechanisms may be involved in the pathophysiology and/or treatment response of somatic symptom disorders with predominant pain around the orofacial region.

Duloxetine Plasma Concentrations and Its Effectiveness in the Treatment of Nonorganic Chronic Pain in the Orofacial Region.

OBJECTIVE: The purpose of this study was to examine the relationship between the pain-relieving effects of duloxetine and its plasma concentrations in patients with burning mouth syndrome and atypical odontalgia characterized by chronic nonorganic pain in the orofacial region. METHODS: We administered duloxetine to 77 patients diagnosed as having burning mouth syndrome or atypical odontalgia for 12 weeks. The initial dose of duloxetine was established as 20 mg/d and was increased to 40 mg/d after week 2. We evaluated pain using the visual analog scale and depressive symptoms using the Structured Interview Guide for the Hamilton Depression Rating Scale at weeks 0, 2, 4, 6, 8, 10, and 12 and measured plasma concentrations of duloxetine 12 weeks after the start of its administration. RESULTS: Visual analog scale scores were significantly lower 12 weeks after than at the start of the administration of duloxetine (paired t test, t = 6.65, P < 0.0001). We examined the relationship between the rate of decreases in visual analog scale scores and plasma concentrations of duloxetine. There was no significant linear regression or quadratic regression. CONCLUSIONS: Duloxetine significantly relieved pain in patients with chronic nonorganic pain in the orofacial region. However, no relationship was observed between its pain-relieving effects and plasma concentrations.

Five Patients With Burning Mouth Syndrome in Whom an Antidepressant (Serotonin-Noradrenaline Reuptake Inhibitor) Was Not Effective, but Pregabalin Markedly Relieved Pain.

Burning mouth syndrome (BMS) causes idiopathic pain or a burning sensation in clinically normal oral mucosa. Burning mouth syndrome is a chronic disease with an unknown etiology. Burning mouth syndrome is also idiopathic, and a consensus regarding diagnosis/treatment has not been reached yet. Recent studies have supported the suggestion that BMS is a neuropathic pain disorder in which both the peripheral and central nervous systems are involved. Tricyclic antidepressants (nortriptyline and amitriptyline), serotonin-noradrenaline reuptake inhibitors (SNRIs) (duloxetine and milnacipran), and antiepileptic drugs, potential-dependent calcium channel α2δ subunit ligands (gabapentine and pregabalin), are currently recommended as the first-choice drugs for neuropathic pain. In this study, we report 5 patients with BMS in whom there was no response to SNRI (milnacipran or duloxetine), or administration was discontinued because of adverse reactions, but in whom pregabalin therapy markedly reduced or led to the disappearance of pain in a short period. Pregabalin, whose mechanism of action differs from that of SNRIs, may become a treatment option for BMS patients who are not responsive to or are resistant to SNRIs.

Temperament and character profiles of patients with burning mouth syndrome.

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic disease in which patients feel a burning sensation and pain in the oral cavity. Although personality traits have been suggested to influence the development and course of BMS, they have not yet been examined in detail. We therefore investigated the personality traits of BMS patients. METHODS: Sample consisted of 65 BMS patients presenting to the Aichi-Gakuin Dental School Hospital between May 2005 and April 2009. They were also diagnosed as having pain disorder by a psychiatrist. The control group consisted of 116 healthy subjects. The Temperament and Character Inventory (TCI) was used to evaluate personality traits, while the Beck Depression Inventory (BDI) was used to evaluate the depression rate in both groups. RESULTS: In TCI, we found that, in comparison to the control group, the novelty seeking score was significantly lower (p = 0.009), the harm avoidance score was significantly higher (p < 0.001), and the self-directedness score was significantly lower (p = 0.039) in the BMS group. To remove the influence of depression, we performed an analysis of covariance of each TCI item using the BDI score as a covariate. No significant differences were observed in harm avoidance or self-directedness, whereas the differences noted in novelty seeking were significant (p = 0.008). CONCLUSION: The novelty seeking score was low in BMS patients in comparison to the control group. They also had high harm avoidance and low self-directedness tendencies, but these were attributed to the influence of depression.

Preoperative level of depression is a predictor of postoperative levels of depression in patients with head and neck cancer.

OBJECTIVE: Emotional distress is considered to be higher in patients with head and neck cancer than other types of cancer. The present study aimed to identify predictors of the postoperative levels of depression in patients with head and neck cancer who have undergone surgery. METHODS: Postoperative levels of depression were assessed at 3, 6 and 12 months after surgery. The preoperative factors that were significant predictors of the postoperative level of depression at each time point were extracted using multiple regression analyses. RESULTS: The preoperative level of depression was a significant predictor of the postoperative level of depression at the 3rd, 6th and 12th postoperative months. At the sixth postoperative month, negative adjustment to cancer at baseline was also a significant predictor of the postoperative level of depression. CONCLUSION: Evaluating the level of depression and negative adjustment before surgery is considered to be effective for identifying patients who will develop depression after surgery.

Effectiveness of duloxetine for the treatment of chronic nonorganic orofacial pain.

OBJECTIVE: We examined the pain-relieving effect of duloxetine on chronic nonorganic orofacial pain (burning mouth syndrome and atypical odontalgia), considering the influence of baseline depressive symptoms. METHODS: In this study of 12 weeks, duloxetine was administered in a fixed-flexible dose of 20 to 40 mg/d to 41 patients with burning mouth syndrome and/or atypical odontalgia. Pain was evaluated using the visual analog scale (VAS) at baseline and at 2, 4, 6, 8, 10, and 12 weeks of treatment. Depressive symptoms were assessed using the Hamilton Depression Rating Scale at baseline and at 12 weeks of treatment. RESULTS: We analyzed the data from 29 patients who completed the study. The VAS score at 12 weeks of treatment was significantly lower than that at baseline. The time course of the VAS scores revealed its significant decrease from 2 weeks of treatment compared to the baseline score. To investigate the influence of baseline depressive symptoms on the pain-relieving effect of duloxetine, the subjects were divided into 2 groups based on the Hamilton Depression Rating Scale score on initial consultation: groups with (≥8) and without (≤7) depressive symptoms. Two-way repeated-measures analysis of variance revealed no significant interaction between time and initial presence or absence of depression. An additional intent-to-treat last-observation-carried-forward analysis including dropped-out patients revealed a similar result. CONCLUSION: Duloxetine significantly relieved chronic nonorganic orofacial pain. Its pain-relieving effect appeared from 2 weeks of treatment. Furthermore, the pain-relieving effects of duloxetine similarly appeared regardless of the presence or absence of baseline depressive symptoms.

Plasma levels of milnacipran and its effectiveness for the treatment of chronic pain in the orofacial region.

OBJECTIVES: This study was performed to assess the relationship between plasma levels of milnacipran and its analgesic/antidepressive effect in patients with chronic orofacial pain treated with this drug. METHODS: A total of 44 patients took milnacipran for 12 weeks. Patients were assessed for their pain and depressive symptoms using the visual analog scale (VAS) and Hamilton Depression Rating Scale, respectively. The plasma milnacipran level was also assessed at week 12. RESULTS: Forty patients completed study treatment and were included in the analysis. In these patients, the VAS score at week 12 significantly decreased from the baseline score (t = 5.15, p < 0.0001). The dose of milnacipran was positively correlated in a linear manner with the plasma level of the drug (Y = 44.86 + 0.33X, r = 0.54, R(2) = 0.29, p = 0.0004). A quadratic regression curve was plotted between the percentage of decrease in the VAS score and plasma milnacipran level (Y = 27.39 + 0.76X - 0.008X(2) , p = 0.048, r = 0.40, R(2) = 0.16). On the other hand, no significant relationship was noted between the percentage of decrease in the Hamilton Depression Rating Scale score and plasma milnacipran level. CONCLUSION: The analgesic effect of milnacipran was suppressed in the presence of the plasma level of the drug outside the therapeutic range, whereas its antidepressant effect was not affected by its plasma level.

The immunohistochemical analysis of pendrin in the mouse inner ear.

Pendred's syndrome (PS) is an autosomal recessive disorder characterized by deafness and goiter, which are caused by mutations in the Pendred's syndrome gene (PDS). PDS encodes a membrane protein named pendrin that is considered to act as an anion transporter. An expression pattern of the PDS ortholog (Pds) mRNA in the auditory and vestibular systems has been reported in mice, and the localization of pendrin has been reported recently. We generated antipeptide antibodies against human pendrin, and performed immunohistochemical analysis of mouse inner ears. We detected pendrin in the endolymphatic duct and sac, and the utricle, saccule, and external sulcus. In the endolymphatic duct and sac, the expression of pendrin was apparent at the apical membrane. In addition, we detected pendrin in the spiral ligament, Claudius cells, Deiter's cells, and the spiral ganglion of the cochlea. Our results are key to defining the role of pendrin in inner ear development and elucidating the pathogenic mechanisms underlying deafness in PS.