Five-year radiological findings from a randomized controlled trial of four periodontitis treatment strategies.

Radiographic findings from long-term studies of periodontitis treatment have rarely been reported. Although bone destruction is a prominent feature of periodontitis, the long-term effect on alveolar bone levels of different treatment strategies, with or without adjunctive metronidazole (MTZ), has not been reported. We investigated the 5-year radiographic outcome of therapy in patient groups treated with conventional scaling and root planing (SRP) or same-day full-mouth disinfection (FDIS), with or without adjunctive MTZ. Following a 3-month oral hygiene phase, 184 periodontitis patients were randomly allocated to one of four treatment regimens: (i) FDIS+MTZ; (ii) FDIS+placebo; (iii) SRP+MTZ; or (iv) SRP+placebo. Following active treatment, patients received biannual maintenance. In total, 161 patients (87.5%) completed the 5-year follow-up examination, at which the radiographic bone level (RBL), clinical attachment level, probing pocket depth, presence of plaque, and bleeding were recorded again. At the 5-year follow up examination, minor radiological bone loss was observed in the intervention groups FDIS+placebo, SRP+MTZ, and SRP+placebo; by contrast, the FDIS+MTZ group did not show any change in RBL. Full-mouth disinfection did not generally perform better than conventional SRP performed over a period of 2 to 4 weeks.

A double-masked Randomized Clinical Trial (RCT) comparing four periodontitis treatment strategies: 5-year clinical results.

AIM: To test the hypothesis of no difference in the 5-year clinical outcome of therapy between groups of patients treated with conventional over-weeks scaling and root planing or same-day full-mouth-disinfection, with or without adjunctive metronidazole (MTZ). MATERIALS AND METHODS: Following a three-month oral hygiene phase, 184 periodontitis patients were randomly allocated to one of four treatment regimens (1) full-mouth disinfection (FDIS)+ MTZ, (2) FDIS +placebo, (3) scaling and root planing+ MTZ and (4) scaling and root planing+placebo. Following active treatment, patients received biannual maintenance; 161 patients completed the five-year follow-up maintenance and examination, where clinical attachment level (CAL), probing pocket depth (PPD), presence of plaque and bleeding were registered. RESULTS: Metronidazole increased the highest CAL recording statistically insignificantly by an average of 0.17 mm while FDIS decreased it by an average of 0.12 mm. The corresponding values for the highest PPD were 0.00 and 0.05 mm, respectively. CONCLUSION: While single-level analyses showed statistically significant differences, they could not be confirmed with more appropriate analyses and were too small to recommend MTZ, with its risk of patient side effects and environmental consequences, for the treatment of patients with severe periodontitis.

The effect of metronidazole on the presence of P. gingivalis and T. forsythia at 3 and 12 months after different periodontal treatment strategies evaluated in a randomized, clinical trial.

OBJECTIVE: The benefit of full-mouth disinfection (FDIS) over traditional scaling and root planing (SRP) in the treatment of chronic, destructive periodontitis remains equivocal and it is not known whether the use of adjunctive antibiotics may enhance the effect of FDIS. Therefore, the aim of this study was to evaluate the effect of conventional SRP completed over 21 days or 1-day FDIS, with or without systemically delivered adjunctive metronidazole (MET) on the presence of P. gingivalis and T. forsythia after 3 and 12 months. MATERIALS AND METHODS: One hundred and eighty-four patients with moderate-to-severe periodontitis were randomly allocated to one of four treatment groups; (1) FDIS+MET; (2) FDIS+placebo; (3) SRP+MET; (4) SRP+placebo. Prior to treatment, pooled subgingival samples were obtained from the five deepest pockets. The same sites were sampled again 3 and 12 months after treatment. All samples were analyzed for P. gingivalis and T. forsythia by PCR, whereas A. actinomycetemcomitans and other bacteria were identified by culture techniques. RESULTS: At baseline, 47% of the samples were positive for P. gingivalis, while almost all samples were positive for T. forsythia. The occurrence of P. gingivalis and T. forsythia was significantly reduced at 3 and 12 months after treatment in the FDIS+MET group, but not in the other treatment groups. CONCLUSION: FDIS+MET had a significant effect in patients with P. gingivalis and T. forsythia, resulting in a significant reduction in number of patients where these micro-organisms could be detected at 3 and 12 months post-therapy.

Patients' perception of own efforts versus clinically observed outcomes of non-surgical periodontal therapy in a Norwegian population: an observational study.

BACKGROUND: Most periodontal intervention studies have focused on biomedical qualities like change in pocket depth and clinical attachment levels. Very few studies have described patient response in terms of how patients' general lives are affected by disease, treatment, and communication with therapy providers. Thus the aim of the present study was to investigate patient response to systematic periodontal information, motivation and treatment strategy (primary aim) by comparing the patients' perception of own efforts and results with those clinically registered in a trans-sectional, observational study (secondary aim). METHODS: One year after treatment of 184 patients, 152 completed a questionnaire covering aspects of received oral health information and instruction, expectations, communication with the therapeutic team, behavioral change, self-perceived outcomes and satisfaction. RESULTS: More than 90% of the patients were satisfied with the interaction with the specialist team. 98% were satisfied with the information and instruction they had been given. 84% said that the information had been necessary to make them change their behavior towards better oral hygiene. Pain and discomfort, as well as bleeding were reduced substantially from before to after treatment, and 28 patients reported to have stopped smoking. In all questions regarding well-being there were statistically significant changes towards positive impact following therapy. CONCLUSIONS: Periodontal treatment, including customized information and education on the etiology and pathogenesis, prevention and treatment as well as maintenance of periodontal diseases resulted in a high degree of short- and long term compliance, and very good patient centered outcomes, which again had a positive impact on the patients' satisfaction. The patient centered outcomes correlated mostly with the compared clinical endpoints. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01318928.

Baseline adjustment and change revisited: effect of smoking on change in periodontal status following periodontal therapy.

Smokers have frequently been reported to have more severe periodontitis, to respond less favorably to periodontal therapy, and to show elevated rate of recurrence compared with non-smokers. The aims of this study was to compare the results of baseline-adjusted and -unadjusted analyses when assessing the effect of smoking on change in periodontal status following therapy and to discuss the methodological issues involved. This is a secondary analysis of data from 180 periodontitis patients enrolled in a randomized controlled clinical intervention trial. Information on smoking habits was elicited from the participants before, and 12 months after, therapy. The clinical parameters analyzed were probing pocket depth and clinical attachment level, using both simple analysis of change (SAC) and analysis of covariance (ancova), adjusting for age, gender, and treatment group. The current smokers presented with more severe periodontitis at baseline than did former and never smokers. Results of the SAC indicated that the current smokers benefitted more from treatment than did former or never smokers, whereas the results of the baseline-adjusted ancova indicated no such differences. Both sets of results are likely to be biased with respect to valid conclusions regarding the 'causal' effect of smoking. Possible sources of bias are discussed.

Effect of nonsurgical periodontal therapy and strict plaque control on preterm/low birth weight: a randomized controlled clinical trial.

OBJECTIVE: This randomized controlled clinical trial was carried out to assess the effect of comprehensive nonsurgical periodontal treatment and strict plaque control performed during pregnancy on the reduction of preterm and/or low birth weight rates (PTLBW). MATERIAL AND METHODS: Three hundred and three women were randomly allocated to receive periodontal treatment either during pregnancy (n = 147, test group) or after delivery (n = 156, control group). During pregnancy, the control group received only one session of supragingival scaling and oral hygiene instruction. In contrast, the test group received comprehensive periodontal treatment including multiple sessions of scaling and root planing, oral hygiene instructions, and frequent maintenance visits. RESULTS: At baseline, periodontal inflammation was observed in approximately 50% of sites and attachment loss affected <15% of sites. Compared to controls, women in the test group had significant reductions in the percentage of sites with plaque (48.5% vs. 10.3%, p < 0.001), gingival bleeding (23.3% vs. 2.5%, p < 0.001), calculus (21.3% vs. 4.1%, p < 0.001), bleeding on probing (38.1% vs. 2.6%, p < 0.001) and probing depth ≥3 mm (19.97% vs. −2.45%, p < 0.001). No significant differences were observed between the groups in the occurrence of PT (11.7% vs. 9.1%, p = 0.57), LBW (5.6 % vs. 4.1%, p = 0.59), and PTLBW (4.15% vs. 2.60%, p = 0.53). CONCLUSIONS: Comprehensive periodontal treatment and strict plaque control significantly improved periodontal health; however, no reduction of PTLBW rates was observed. Thus, remaining periodontal inflammation posttreatment cannot explain the lack of effect of periodontal treatment on PTLBW. Clinical relevance This study demonstrated that periodontal diseases may be successfully treated during pregnancy. Our results do not support a potential beneficial effect of periodontal treatment on PTLBW.

Periodontitis in psoriasis patients: a blinded, case-controlled study.

OBJECTIVE: Destructive periodontitis is one of the most frequent and widespread bacterial infections in humans. Psoriasis is a common condition in the general population. Since both psoriasis and periodontal diseases are characterized by an exaggerated response of the immune system to the epithelial surface microbiota, there may possibly be an association between these two conditions. The aim of the present pilot study was to investigate the prevalence of periodontal disease in psoriasis patients compared to healthy controls. MATERIAL AND METHODS: Dental bite-wing X-rays were obtained from 155 psoriasis patients aged 45-60 years, as well as from 155 age- and gender-matched controls. All X-rays were examined by the same investigator for accumulated destructive periodontitis using bone level and loss of teeth as endpoints. RESULTS: A significantly lower radiographic bone level (p < 0.001) and a significantly higher number of missing teeth (p < 0.001) were observed in the psoriasis cases compared to the controls. CONCLUSION: Our study indicates that psoriasis patients experience more bone loss than age- and gender-matched controls.

A randomized, single-blind, parallel-group clinical study to evaluate the effect of soluble beta-1,3/1,6-glucan on experimental gingivitis in man.

BACKGROUND: Gingivitis is an inflammatory disorder of the periodontium induced by dental plaque bacteria. Soluble beta-1,3/1,6-glucan (SBG) is known to enhance infection defense by preventing excessive inflammatory responses caused by bacterial endotoxins. AIM: The aim of the present study was to investigate the effect of SBG on experimental gingivitis in man. MATERIAL AND METHODS: Experimental gingivitis was induced over a period of 24 days in 30 healthy volunteers who were simultaneously treated with SBG. Two groups (n=10/group) rinsed twice daily with an SBG mouthwash that was either swallowed or expectorated. A third group (n=10) received a water rinse as a control. Plaque index (Pl.I), gingival index (GI), and amount of gingival crevicular fluid (GCF) were assessed at baseline and at six times during the study. RESULTS: The results showed that in the SBG groups, GCF decreased significantly during the study. The swallow group experienced a significant increase in GCF during the first week. The control group followed the expected pattern of experimental gingivitis, with a significant increase in the gingival fluid secretion during the test period. There was a significant increase in GI and Pl.I during the study for all groups, with no significant differences between them. No adverse effects of SBG were recorded. CONCLUSIONS: In this 24-day experimental gingivitis study of subjects who used either a SBG or a control mouthrinse: (1) all subjects had increased plaque and gingivitis, (2) GCF increased in control-rinse subjects and GCF decreased in SBG-rinse subjects. The only statistically significant difference between the SBG-rinse and control-rinse subjects was an increase in GCF at day 7 for subjects who rinsed and swallowed SBG.

A Randomized Double-Masked Clinical Trial Comparing Four Periodontitis Treatment Strategies: 5-Year Tooth Loss Results.

BACKGROUND: Tooth loss is the ultimate negative consequence of periodontitis, and reports of the extent to which different treatment strategies may influence long-term tooth loss are hard to find. This study aims to test the hypothesis that there is no difference in 5-year clinical outcome of therapy in terms of tooth mortality between groups of patients treated with conventional scaling and root planing (SRP) over weeks or same-day full-mouth disinfection (FDIS), with or without adjunctive metronidazole (MET). METHODS: One hundred eighty-four patients with moderate-to-severe periodontitis were randomly allocated to one of four treatment groups: 1) FDIS+MET; 2) FDIS+placebo; 3) SRP+MET; and 4) SRP+placebo. Total 161 patients (88%) completed the 5-year follow-up examination, and data on number and timing of tooth extractions as well as pre-extraction diagnoses and reasons for extractions were analyzed. RESULTS: No differences were observed between groups with regard to number of, reasons for, or time of extractions in the four groups at baseline and 1, 3, and 5 years after treatment. CONCLUSION: If extraction or retention of teeth is regarded as a measure of failure or success 5 years after completion of periodontal therapy, none of the four strategies produced an end result better than the other.

Clinical and radiographic effects of enamel matrix derivative in the treatment of intrabony periodontal defects: a 12-month longitudinal placebo-controlled clinical trial in adult periodontitis patients.

BACKGROUND: This randomized, double-masked, placebo-controlled clinical trial evaluated the effect of enamel matrix derivative (EMD) on clinical and radiographic parameters of periodontal intrabony defects. METHODS: A split-mouth design was used in 16 chronic periodontitis patients who had similar defects (> or =6 mm of probing depth). Both groups underwent scaling and root planing and were acid-etched with EDTA. The test sites received the EMD solution and the controls a placebo. Clinical examinations of all 16 patients and radiographs of 14 patients were available at baseline and 6 and 12 months after surgery. Clinical outcomes included probing depth (PD) and clinical attachment level (CAL); radiographic analysis was performed using computerized linear measurements. Intergroup comparisons were performed by paired samples t test, and over time comparisons were made by general linear model (alpha = 0.05). RESULTS: A statistically significant improvement over time for PD and CAL and a decrease of the vertical component of the defect was detected in both groups. Comparisons between groups revealed at baseline a mean+/-SD value of CAL of 12.93+/-2.00 and 13.47+/-2.93 for test and control groups, respectively. These values decreased to 10.92+/-1.92 and 11.31+/-1.86 after 12 months for test and control. No statistically significant differences could be observed between groups. PD displayed similar results from 7.57+/-1.02 and 7.38+/-1.16 for test and control groups at baseline to 3.40+/-1.82 and 2.99+/-1.07 after 12 months. If the data are divided into smokers and non-smokers, no differences are observed. CONCLUSION: Use of EMD did not result in more improvement in clinical and radiographic parameters compared to the placebo.

Microbiologic Observations After Four Treatment Strategies Among Patients With Periodontitis Maintaining a High Standard of Oral Hygiene: Secondary Analysis of a Randomized Controlled Clinical Trial.

BACKGROUND: The benefit of full-mouth disinfection (FDIS) over traditional scaling and root planing (SRP), with or without adjunctive metronidazole, when treating chronic destructive periodontitis remains equivocal, as does the long-term association between clinical and microbiologic outcomes after such strategies. The aim of this study is to examine the relationship between clinical and microbiologic outcomes of four different treatment strategies for chronic destructive periodontitis among patients who maintain excellent oral hygiene and low gingival bleeding scores. METHODS: One hundred eighty-four patients with periodontitis and capable of maintaining a high standard of oral hygiene were randomly allocated to one of four treatment groups: 1) FDIS + metronidazole; 2) FDIS + placebo; 3) SRP + metronidazole; and 4) SRP + placebo. Recordings of plaque, bleeding on probing, probing depth (PD), and clinical attachment level were carried out in four sites per tooth at baseline, 3 and 12 months after treatment. Before treatment, pooled subgingival samples were obtained from the five deepest pockets, which were sampled again 3 and 12 months after treatment. Microbiologic assessments of eight putative periodontal pathogens were performed using the checkerboard DNA-DNA hybridization method. RESULTS: Levels of bacterial species were already relatively low at baseline. The only microbial factor statistically significantly associated with the clinical outcomes of treatment after 12 months was the association between reductions of Tannerella forsythia and being free from PD ≥5 mm. CONCLUSION: In this clinical trial, the only microbial factor associated with the clinical outcomes after 12 months was a statistically significant association between the reductions of T. forsythia and being free from PD ≥5 mm.

Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood.

BACKGROUND AND OBJECTIVE: Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. MATERIAL AND METHODS: Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. RESULTS: Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1ß in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. CONCLUSION: Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis.

A randomized, double-masked clinical trial comparing four periodontitis treatment strategies: 1-year clinical results.

BACKGROUND: The benefit of full-mouth disinfection (FDIS) over traditional scaling and root planing (SRP) remains equivocal, and it is not known whether the use of adjunctive antibiotics may enhance the effect of FDIS. The aim of the present study is to test the hypothesis that there is no difference in the 1-year clinical outcome of therapy among groups of patients treated with conventional SRP performed over 2 to 3 weeks, or same-day FDIS, with or without adjunctive metronidazole. METHODS: A total of 184 patients with moderate-to-severe periodontitis were randomly allocated to one of four treatment groups: 1) FDIS+metronidazole; 2) FDIS+placebo; 3) SRP+metronidazole; or 4) SRP+placebo. Recordings of plaque, bleeding on probing, probing depth (PD), and clinical attachment level (CAL) were carried out in four sites per tooth at baseline and at 3 and 12 months after treatment. RESULTS: No differences were observed in the mean CAL or PD values between the four experimental groups at baseline and 3 or 12 months post-treatment. All four groups displayed significant improvements in all parameters. However, using absence of pockets ≥5 mm as the criterion for treatment success, the two groups receiving adjunctive metronidazole performed significantly better than the two placebo groups. CONCLUSION: Metronidazole had a significant, adjunctive effect in patients with a metronidazole-sensitive subgingival microbiota on the clinical parameters of CAL, PD, and absence of pockets ≥5 mm.

The lifetime direct cost of periodontal treatment: a case study from a Norwegian specialist practice.

BACKGROUND: Successful periodontal treatment requires a commitment to regular lifelong maintenance and may be perceived by patients to be costly. This study calculates the total lifetime cost of periodontal treatment in the setting of a specialist periodontal practice and investigates the cost implications of choosing not to proceed with such treatment. METHODS: Data from patients treated in a specialist practice in Norway were used to calculate the total lifetime cost of periodontal treatment that included baseline periodontal treatment, regular maintenance, retreatment, and replacing teeth lost during maintenance. Incremental costs for alternative strategies based on opting to forego periodontal treatment or maintenance and to replace any teeth lost with either bridgework or implants were calculated. RESULTS: Patients who completed baseline periodontal treatment but did not have any additional maintenance or retreatment could replace only three teeth with bridgework or two teeth with implants before the cost of replacing additional teeth would exceed the cost of lifetime periodontal treatment. Patients who did not have any periodontal treatment could replace ≤ 4 teeth with bridgework or implants before a replacement strategy became more expensive. CONCLUSIONS: Within the limits of the assumptions made, periodontal treatment in a Norwegian specialist periodontal practice is cost-effective when compared to an approach that relies on opting to replace teeth lost as a result of progressive periodontitis with fixed restorations. In particular, patients who have initial comprehensive periodontal treatment but do not subsequently comply with maintenance could, on average, replace ≤ 3 teeth with bridgework or two teeth with implants before this approach would exceed the direct cost of lifetime periodontal treatment in the setting of the specialist practice studied.

Systemic chemical desensitization of peptidergic sensory neurons with resiniferatoxin inhibits experimental periodontitis.

BACKGROUND AND OBJECTIVE: The immune system is an important player in the pathophysiology of periodontitis. The brain controls immune responses via neural and hormonal pathways, and brain-neuro-endocrine dysregulation may be a central determinant for pathogenesis. Our current knowledge also emphasizes the central role of sensory nerves. In line with this, we wanted to investigate how desensitization of peptidergic sensory neurons influences the progression of ligature-induced periodontitis, and, furthermore, how selected cytokine and stress hormone responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation are affected. MATERIAL AND METHODS: Resiniferatoxin (RTX; 50 µg/kg) or vehicle was injected subcutaneously on days 1, 2, and 3 in stress high responding and periodontitis-susceptible Fischer 344 rats. Periodontitis was induced 2 days thereafter. Progression of the disease was assessed after the ligatures had been in place for 20 days. Two h before decapitation all rats received LPS (150 µg/kg i.p.) to induce a robust immune and stress response. RESULTS: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays. LPS provoked a significantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone. CONCLUSIONS: In this model RTX-induced chemical desensitization of sensory peptidergic neurons attenuated ligature-induced periodontitis and promoted a shift towards stronger pro-inflammatory cytokine and weaker stress hormone responses to LPS. The results may partly be explained by the attenuated transmission of immuno-inflammatory signals to the brain. In turn, this may weaken the anti-inflammatory brain-derived pathways.

Antibiotic prescribing practices among Norwegian dentists.

OBJECTIVE: There is little information on antibiotic prescribing habits among dentists in general. In 1992 we reported a study among Norwegian dentists, and the present investigation was undertaken to find out if the patterns of antibiotic prescription had changed since then. MATERIAL AND METHODS: A total of 470 randomly selected dentists (10% of total) received a questionnaire and a letter describing the survey and 313 responded. RESULTS: Results indicated that 35% did not issue any prescriptions in a typical week, while 3% issued > or =5. Fifty percent reported that they might prescribe antibiotics when treating periodontal diseases, but only 3.4% reported the use of microbial diagnosis before selecting an antibiotic; 71% of the respondents reported use of antibiotics occasionally to prevent general complications of dental treatment; 80% prescribed antibiotics for prophylactic use if the patient revealed a history of endocarditis, while 5% reported never doing so. CONCLUSION: These findings are in concert with the results obtained 11 years ago, but indicating that dentists who had attended postgraduate courses on antibiotics prescribed such drugs more frequently. This was not statistically significant. However, it is of great concern that 5% never prescribed antibiotics when treating patients with a history of endocarditis, and that 20% did not know that amoxicillin was a penicillin. Such lack of knowledge may cause fatal results of therapy.

Enhanced susceptibility to periodontitis in an animal model of depression: reversed by chronic treatment with the anti-depressant tianeptine.

OBJECTIVE: To test the hypothesis that the olfactory bulbectomy model of depression in rats could influence susceptibility to ligature-induced periodontitis, and that chronic treatment with the anti-depressant drug tianeptine could attenuate this effect. MATERIAL AND METHODS: Tianeptine was given twice daily (10 mg/kg, i.p.) during the entire experiment, starting 29 days before induction of olfactory bulbectomy and periodontitis. Olfactory bulbectomized (OB) rats and sham-operated rats were given saline in a similar manner. Periodontal disease was assessed when the ligatures had been in place for 21 days. Two hours before decapitation, rats were injected with lipopolysaccharide (LPS;100 microg/kg, i.p.) to induce a robust immune and stress response. RESULTS: Compared with sham-operated controls, OB rats developed significantly more periodontal bone loss, exhibited characteristic behavioural responses in a novel open field test, and showed a decreased expression of glucocorticoid receptors (GRs) in the hippocampus. LPS provoked a significantly larger increase in circulating levels of the stress hormone corticosterone and the cytokine transformation growth factor (TGF)-1beta but smaller tumour necrosis factor (TNF)-alpha levels. Tianeptine treatment of OB rats significantly inhibited peridodontal bone loss, normalized behavioural responses, enhanced TGF-1beta levels, and abolished TNF-alpha decrease, but did not attenuate the increased corticosterone response and the decreased hippocampal GR expression. CONCLUSIONS: These experimental results are consistent with an emerging literature showing that life stress, anxiety, depression, pathological grief, and poor coping behaviour may dysregulate regulatory mechanisms within the brain involved in immune regulation, and thereby alter immune responses and influence the susceptibility/resistance to inflammatory disorders.