Hypothalamic-pituitary-adrenal axis hyperactivity is normalized after successful intermittent theta-burst stimulation in resistant depressed patients.

The present pilot study assessed the effects of multi-session intermittent theta-burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex in 17 treatment resistant depressed inpatients (TRDs) showing cortisol non-suppression to the overnight dexamethasone suppression test (DST) at baseline (i.e., maximum post-DST cortisol [CORmax] level > 130 nmol/L). After 20 iTBS sessions, the DST was repeated in all TRDs. At baseline, post-DST CORmax levels were higher in TRDs compared to healthy control subjects (HCs; n = 17) (p < 0.0001). After 20 iTBS sessions, post-DST CORmax levels decreased from baseline (p < 0.03) and were comparable to HCs. Decreases in post-DST CORmax levels were related to decreases in 17-item Hamilton Depression Rating Scale (HAMD-17) scores (ρ = 0.53; p < 0.03). At endpoint, 10 TRDs showed DST normalization (among them 7 were responders [i.e., HAMD-17 total score > 50% decrease from baseline]), and 7 did not normalize their DST (among them 6 were non-responders) (p < 0.05). Our results suggest that successful iTBS treatment may restore normal glucocorticoid receptor feedback inhibition at the pituitary level.

Potential efficacy of dopaminergic antidepressants in treatment resistant anergic-anhedonic depression results of the chronic anergic-anhedonic depression open trial - CADOT.

Introduction: Among treatment-resistant depression (TRD), we identified anergic-anhedonic clinical presentations (TRAD) as putatively responsive to pro-dopaminergic strategies. Based on the literature, non-selective monoamine oxidase inhibitors (MAOI) and dopamine D2 receptor agonists (D2RAG) were sequentially introduced, frequently under the coverage of a mood stabilizer. This two-step therapeutic strategy will be referred to as the Dopaminergic Antidepressant Therapy Algorithm (DATA). We describe the short and long-term outcomes of TRAD managed according to DATA guidelines. Method: Out of 52 outpatients with TRAD treated with DATA in a single expert center, 48 were included in the analysis [severity - QIDS (Quick Inventory of Depressive Symptomatology) = 16 ± 3; episode duration = 4.1 ± 2.7 years; Thase and Rush resistance stage = 2.9 ± 0.6; functioning - GAF (Global Assessment of Functioning) = 41 ± 8]. These were followed-up for a median (1st - 3rd quartile) of 4 (1-9) months before being prescribed the first dopaminergic treatment and remitters were followed up 21 (11-33) months after remission. Results: At the end of DATA step 1, 25 patients were in remission (QIDS <6; 52% [38-66%]). After DATA step 2, 37 patients were in remission (77% [65-89%]) to whom 5 patients with a QIDS score = 6 could be added (88% [78-97%]). Many of these patients felt subjectively remitted (GAF = 74 ± 10). There was a significant benefit to combining MAOI with D2RAG which was maintained for at least 18 months in 30 patients (79% [62-95%]). Conclusion: These results support TRAD sensitivity to pro-dopaminergic interventions. However, some clinical heterogeneities remain in our sample and suggest some improvement in the description of dopamine-sensitive form(s).

The Role of Natural Compounds in Optimizing Contemporary Dental Treatment-Current Status and Future Trends.

For a long period of time, natural remedies were the only ailment available for a multitude of diseases, and they have proven effective even after the emergence of modern medicine. Due to their extremely high prevalence, oral and dental disorders and anomalies are recognized as major public health concerns. Herbal medicine is the practice of using plants with therapeutic characteristics for the purpose of disease prevention and treatment. Herbal agents have made a significant entry into oral care products in recent years, complementing traditional treatment procedures due to their intriguing physicochemical and therapeutic properties. There has been a resurgence of interest in natural products because of recent updates, technological advancements, and unmet expectations from current strategies. Approximately eighty percent of the world's population uses natural remedies, especially in poorer nations. When conventional treatments have failed, it may make sense to use natural drugs for the treatment of pathologic oral dental disorders, as they are readily available, inexpensive, and have few negative effects. The purpose of this article is to provide a comprehensive analysis of the benefits and applications of natural biomaterials in dentistry, to gather relevant information from the medical literature with an eye toward its practical applicability, and make suggestions for the directions for future study.

Hypothalamic-prolactin axis regulation in major depressed patients with suicidal behavior.

BACKGROUND: So far, little is known about the control of hypothalamic-prolactin axis activity by dopamine (DA) and thyrotropin-releasing hormone (TRH) in depressed patients with suicidal behavior disorder (SBD). METHODS: We evaluated prolactin (PRL) responses to apomorphine (APO; a DA direct receptor agonist) and 0800 h and 2300 h protirelin (TRH) tests in 50 medication-free euthyroid DSM-5 major depressed inpatients with SBD (either current [n = 22], or in early remission [n = 28]); and 18 healthy hospitalized controls (HCs). RESULTS: Baseline (BL) PRL levels were comparable across the three diagnostic groups. SBDs in early remission did not differ from HCs regarding PRL suppression to APO (PRLs), PRL stimulation to 0800 h and 2300 h TRH tests (∆PRL), and ∆∆PRL values (difference between 2300 h-∆PRL and 0800 h-∆PRL values). Current SBDs showed lower PRLs and ∆∆PRL values than HCs and SBDs in early remission. Further analyses revealed that current SBDs with a history of violent and high-lethality suicide attempts were more likely to exhibit co-occurrence of low ∆∆PRL and PRLS values. CONCLUSIONS: Our results suggest that regulation of the hypothalamic-PRL axis is impaired in some depressed patients with current SBD, particularly those who have made serious suicide attempts. Considering the limitations of our study, our findings support the hypothesis that decreased pituitary D2 receptor functionality (possibly adaptive to increased tuberoinfundibular DAergic neuronal activity) together with decreased hypothalamic TRH drive might be a biosignature for high-lethality violent suicide attempts.

The Effectiveness of Laser Applications and Photodynamic Therapy on Relevant Periodontal Pathogens (Aggregatibacter actinomycetemcomitans) Associated with Immunomodulating Anti-rheumatic Drugs.

Considering the current context of the increasing resistance of bacterial species to antibiotics and other antimicrobial agents, a major objective is to develop other antimicrobial approaches, which would be able to inactivate pathogens with considerable effectiveness. Two such methods are photodynamic disinfection therapy and laser irradiation. In view of the immunocompromised status of some patients under immunosuppressive therapy and potential drug interactions that can be established between systemic antimicrobial agents, the research of local, minimally invasive methods of inactivating periodontal pathogens in the context of these systemic therapies with modifying drugs of the immune response is justified. This in vitro study evaluated the antimicrobial action of a diode laser, wavelength 940 nm, and photodisinfection therapy at 670 nm (photosensitizer, 3,7 dimethyl phenothiazine chloride) on a type strain of Aggregatibacter actinomycetemcomitans, a known periodontal pathogen, in the presence and absence of active substances used in autoimmune disease therapy (Etanercept, Infliximab, Metothrexate). The association of a conventional antirheumatic drug with anti-TNF-α therapy determined a significantly greater inhibition of the strain of A. actinomycetemcomitans compared to monotherapy, in vitro. Photodisinfection caused a significant reduction in bacterial burden after a 30 s exposure in vitro, regardless of the pharmaceutical associations of biological and conventional disease-modifying antirheumatic drugs (DMARDs). Irradiation with a diode laser for 30 s at a power of 5 W caused a greater reduction compared to irradiation with 1 W. The application of laser and photodisinfection induced a significant reduction in Aggregatibacter actinomycetemcomitans in vitro and could be considered important adjunctive measures for the eradication of this oral pathogen in the context of immunomodulating therapy.

Predictors of Oral Health Behaviors among Dental Students.

Background and Objectives: College life is a time when students take more responsibility for health-related behaviors. Aim: To determine the oral health behaviors of dental students, to motivate their transformation into cyanogenic behaviors by applying the planned behavior model, and to determine the degree to which students can modify behavior for oral health. Material and Methods: The results of the initial and final assessment (4 months apart) of the bacterial plaque present by means of the Quigley Hein and API indexes were collected from the student files. The Health-Promoting Lifestyle Profile II -HPLP II and Generalized Self-Efficacy Scale (GSE) questionnaires were used to determine the variables with predictor values that influence the cognitive-perceptual factors. Results: For the "health responsibility" domain, the average total value was 2.53 ± 0.9 (SD). For the "interpersonal relationships" domain, the average value was 2.82 ± 0.79. In the case of the "nutrition" domain, the desire to change the behavior of the participants was moderate (2.53 ± 1.19). "Physical activity" represents an important field in the everyday life of young adults. The results of the study indicated a moderate desire for change (2.52 ± 0.97). In the case of "spiritual growth", in which self-esteem, the way the individual perceives the environment and the adaptation to it were evaluated, a great desire for change was observed (2.74 ± 0.82). Scale GSE questionnaire showed an α coefficient of 28.52 ± 0.82, a value that indicated a moderate to a high level of efficacy and self-confidence. Conclusions: The results of the study showed that students have a moderate tendency to change in all areas, except for interpersonal relationships, where the desire to change something is increased. The participants have a moderate to a high level of self-efficacy and self-confidence.

Dopamine Function and Hypothalamic-Pituitary-Thyroid Axis Activity in Major Depressed Patients with Suicidal Behavior.

Involvement of the dopaminergic (DA) and hypothalamic-pituitary-thyroid (HPT) systems in suicidal behavior is still poorly understood. We assessed multihormonal responses to apomorphine (APO; a short acting DA receptor agonist) and 8 AM and 11 PM protirelin (TRH) tests in 30 medication-free DSM-5 euthyroid major depressed inpatients with suicidal behavior disorder (SBD) (current, n = 14; in early remission, n = 16) and 18 healthy hospitalized control subjects (HCs). Compared to HCs, responses to APO and TRH tests were unaltered in SBDs in early remission. However, current SBDs exhibited increased APO-induced growth hormone (GH) and adrenocorticotropin (ACTH) stimulation, and reduced 11 PM thyrotropin (TSH) and ∆∆TSH values (difference between 11 PM and 8 AM TRH-TSH responses). In current SBDs, the association between high APO-GH concentrations and low ∆∆TSH values was more common in recent suicide attempters than in past suicide attempters. These preliminary results suggest that co-occurring alterations in the DA and HPT systems (i.e., DA receptor hyperresponsiveness associated with decreased hypothalamic TRH drive) may contribute to the pathophysiology of suicidal behavior. Conversely, normalization of DA and TRH functions might reflect a process of recovery from suicidality. Thus, our findings suggest that drugs targeting the DAergic and TRH systems could be relevant in suicide prevention.

Neuroendocrine Assessment of Dopaminergic Function during Antidepressant Treatment in Major Depressed Patients.

The effects of antidepressants on dopamine (DA) receptor sensitivity in the mesolimbic-hypothalamic system have yielded contradictory results. The postsynaptic DA receptor function was evaluated by the cortisol response to apomorphine (APO; 0.75 mg SC) in 16 drug-free DSM-5 major depressed inpatients and 18 healthy hospitalized control (HC) subjects. Cortisol response to the dexamethasone suppression test (DST) was also measured. After two and four weeks of antidepressant treatment (ADT), the DST and APO test were repeated in all patients. Cortisol response to APO (∆COR) was not influenced by the hypothalamic-pituitary-adrenal (HPA) axis activity, as assessed by the DST. Pre-treatment ∆COR values did not differ significantly between patients and HCs. During ADT, ∆COR values were lower than in HCs at week 2 and 4. After four weeks of treatment, among the eight patients who had blunted ∆COR values, seven were subsequent remitters, while among the eight patients who had normal ∆COR values, seven were non-remitters. Considering the limitations of our study, the results suggest that following chronic ADT, the desensitization of postsynaptic DA receptors connected with the regulation of the HPA axis at the hypothalamic level is associated with clinical remission. These results could reflect increased DA levels in the mesolimbic pathway.

Thyroid axis activity and dopamine function in depression.

BACKGROUND: Several lines of evidence suggest alterations in both hypothalamic-pituitary-thyroid (HPT) axis and dopamine (DA) function in depressed patients. However, the functional relationships between HPT and DA systems have not been well defined. METHODS: We examined thyrotropin (TSH) response to 0800 h and 2300 h protirelin (TRH) challenges, and adrenocorticotropic hormone (ACTH), cortisol and growth hormone (GH) responses to apomorphine (APO, a DA receptor agonist), in 58 drug-free DSM-IV major depressed inpatients without a suicidal behavior, and 22 healthy hospitalized controls. RESULTS: Compared with controls, patients showed 1) lower basal serum 2300 h-TSH, 2300 h-∆TSH, and ∆∆TSH (difference between 2300 h-∆TSH and 0800 h-∆TSH) levels, and 2) lower cortisol response to APO (∆COR). A negative relationship between ∆∆TSH values and hormonal responses to APO was observed in the depressed group, but not in the control group. When patients were classified on the basis of their ∆∆TSH status, patients with reduced ∆∆TSH values (< 2.5 mU/L) showed hormonal APO responses comparable to those of controls. Patients with normal ∆∆TSH values exhibited lower ∆ACTH, ∆COR, and ∆GH values than patients with reduced ∆∆TSH values and controls. CONCLUSION: Taken together, these results suggest that hypothalamic DA function is unaltered in depressed patients with HPT dysregulation (i.e., increased hypothalamic TRH drive leading to altered TRH receptor chronesthesy on pituitary thyrotrophs). Conversely, hypothalamic DA-receptor function is decreased in patients with normal HPT axis activity. These findings are discussed in the context of the role of TRH as a homeostatic neuromodulator in depression.

Are the thyroid and adrenal system alterations linked in depression?

BACKGROUND: Disturbances in the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes have been frequently found in major depression. Given that glucocorticoids may inhibit thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) secretion, it has been hypothesized that hypercortisolemia could lead to HPT axis abnormalities. So far, data on interactions between the HPA and HPT axes in depression remain inconclusive. METHODS: In order to investigate this issue, we examined circadian rhythms of serum TSH and cortisol (sampled at 4 -hly intervals throughout a 24 -h span), TSH responses to 0800 h and 2300 h protirelin (TRH) tests and cortisol response to dexamethasone suppression test (DST) in 145 unmedicated inpatients meeting DSM-IV criteria for major depressive disorder (MDDs) and 25 healthy hospitalized control subjects (HCs). RESULTS: The secretion of TSH and cortisol exhibited a significant circadian rhythm both in HCs and MDDs. However, compared to HCs, MDDs showed: 1) reduced TSH mesor and amplitude values; 2) blunted 2300 h-ΔTSH and ΔΔTSH values (i.e. differences between 2300 h and 0800 h TRH-TSH responses); and 3) increased cortisol mesor and post-DST cortisol values. DST nonsuppresssors (n = 40, 27 %) showed higher cortisol mesor than DST suppressors (n = 105, 73 %). There was no difference between DST suppressors and nonsuppressors in their TSH circadian parameters and TRH-TSH responses. In addition, cortisol values (circadian and post-DST) were not related to TRH test responses. CONCLUSION: Our results do not confirm a key role for hypercortisolemia in the HPT axis dysregulation in depression.

Dopaminergic, Noradrenergic, Adrenal, and Thyroid Abnormalities in Psychotic and Affective Disorders.

BACKGROUND: This study aimed to assess hypothalamic-pituitary dopaminergic (DA), noradrenergic (NA), thyroid (HPT), and adrenal (HPA) activity in schizophrenia, in schizoaffective disorder, and in bipolar disorder. METHOD: We investigated a combined approach of hormone responses to (1) apomorphine (APO), a short-acting DA receptor agonist which decreases prolactin secretion (PRL), and stimulates secretion of growth hormone (GH), adrenocorticotropin (ACTH), and cortisol; (2) clonidine (CLO), an alpha 2-adrenoceptor agonist which stimulates GH secretion; (3) 8 AM and 11 PM protirelin (TRH) which stimulates thyrotropin (TSH) secretion; and (4) dexamethasone which suppresses cortisol secretion, in 13 hospitalized healthy male controls and 39 untreated male inpatients: 13 with DSM-IV paranoid schizophrenia, 13 with DSM-IV schizoaffective disorder (bipolar subtype, depressed at the time of the study), and 13 with DSM-IV bipolar disorder (depressed). RESULTS: Compared to controls, paranoid schizophrenic patients showed (1) lower APO-induced ACTH and cortisol stimulation, and (2) higher post-dexamethasone cortisol values. Compared to controls, schizoaffective and bipolar patients showed (1) lower ΔΔTSH values (i.e., difference between 11 PM and 8 AM TRH-TSH responses), (2) lower APO-induced PRL suppression, (3) lower CLO-induced GH stimulation, and (4) higher post-dexamethasone cortisol values. CONCLUSIONS: Although results must be interpreted with caution because of the small sample, this preliminary study suggests that depressed bipolar and schizoaffective patients share common biological dysregulations, distinct from that of paranoid schizophrenic patients. From a pathophysiological viewpoint, paranoid schizophrenic patients can be characterized by hyposensitivity of the hypothalamic DA receptors (possibly resulting from an increase in presynaptic DA release) associated with increased HPA axis activity, while depressed bipolar and schizoaffective patients can be characterized by hyposensitivity of the pituitary TRH and DA-D2 receptors (possibly linked to the activation of the hypothalamic TRH and tuberoinfundibular DA neurons, respectively), together with subsensitive postsynaptic α2-adrenoreceptors at the hypothalamic level (possibly secondary to an erratic release of NA) and increased HPA axis activity.