Nano-structural bioactive gradient coating fabricated by computer controlled plasma-spraying technology.

The poor mechanical property of hydroxyapatite was the major problem for load bearing and implant coating in clinical applications. To overcome this weakness, a bioactive gradient coating with a special design composition of hydroxyapatite (HA), ZrO2, Ti, bioglass was developed. This 120 microm coating with an upper layer of 30-50 microm porous HA produced by computer controlled plasma spraying which maintained energy level of the plasma which ensure proper melting of powder. The crystal size of the coating was 18.6-26.2 nm. Transformation of t-ZrO2 to m-ZrO2 reduced the thermal stress that weakened the coating and lowered down interfacial strength of the coating and metal substrate. Thermal stress of sprayed coating was 16.4 MPa which was much smaller than the sample without thermal treatment of 67.1 MPa. Interfacial strength between the coating and metal substrate was 53 MPa which is much higher than conventional Hydroxyapatite coating. Based on XRD analysis crystallinity of HA approached 98%. Therefore, high temperature treatment improved long term stability of the coating through improved crystallinity of hydroxyapatite and reduced other impure calcium phosphate phase.

Clinical guidelines for the treatment of depressive disorders. IV. Medications and other biological treatments.

BACKGROUND: The Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments partnered to produce clinical guidelines for psychiatrists for the treatment of depressive disorders. METHODS: A standard guidelines development process was followed. Relevant literature was identified using a computerized Medline search supplemented by review of bibliographies. Operational criteria were used to rate the quality of scientific evidence, and the line of treatment recommendations included consensus clinical opinion. This section, "Medications and Other Biological Treatments," is 1 of 7 articles that were drafted and reviewed by clinicians. Revised drafts underwent national and international expert peer review. RESULTS: Evidence-based recommendations are presented for 1) choosing an antidepressant, based on efficacy, tolerability, and safety; 2) the optimal use of antidepressants, including augmentation, combination, and switching strategies; 3) maintenance treatment; and 4) electroconvulsive therapy (ECT), light therapy, and additional somatic treatments. Evidence from metaanalyses is presented first, followed by conclusions from randomized controlled trials (RCTs) and, if appropriate, open-label data. CONCLUSIONS: There is significant evidence to support the role of selective serotonin reuptake inhibitors (SSRIs), novel agents, and classic agents in the treatment of major depressive disorder (MDD). There is also evidence to support the use of somatic treatments, including ECT and light therapy, for some patients with MDD. There is limited evidence for the use of specific medications to treat subtypes of MDD. There is emerging evidence to support augmentation and combination strategies for patients previously nonresponsive to medication.

An open trial of light therapy for women with seasonal affective disorder and comorbid bulimia nervosa.

OBJECTIVE: Many patients with seasonal affective disorder (SAD) have dysfunctional eating behaviors. Conversely, many women with bulimia nervosa have marked winter worsening of mood and bulimic symptoms. Controlled studies of light therapy in SAD and in bulimia nervosa have shown beneficial effects on mood and binge/purge symptoms. We explored the clinical use of light therapy in women with SAD who also had comorbid bulimia nervosa. METHOD: Twenty-two female patients diagnosed using DSM-IV criteria with both bulimia nervosa and major depressive disorder with a seasonal (winter) pattern were treated with an open design, 4-week trial of light therapy (10,000 lux fluorescent light box with an ultraviolet filter, 30 to 60 minutes per day in the early morning). Patients were assessed before and after treatment with depression scales and with binge/purge diaries. RESULTS: Light therapy resulted in significant improvement in mood, with a mean 56% reduction in 29-item Hamilton Rating Scale for Depression scores following treatment (p < .001). The frequency of binges and purges per week also significantly decreased (p < .001) from baseline by a mean of 46% and 36%, respectively. Two (9%) of 22 patients became abstinent of binge/ purge episodes, compared with 10 (45%) of 22 patients who met criteria for remission of depressive symptoms. The light therapy was well tolerated by patients. CONCLUSION: These results suggest that therapeutic effects of light therapy on mood and bulimic symptoms in patients with SAD and comorbid bulimia nervosa are sustained over at least 4 weeks. However, the low abstinence rate in bulimic symptoms indicates that light therapy may be most effectively used as an adjunctive treatment to medications and/or psychotherapy for bulimia nervosa.

Immune-inflammatory markers in patients with seasonal affective disorder: effects of light therapy.

BACKGROUND: There is increasing evidence that an activation of the immune-inflammatory system is involved in the pathophysiology of depressive disorders. The purposes of this study were to (1) compare immune-inflammatory markers in patients with seasonal affective disorder (SAD) with those in matched normal controls; and (2) examine the effects of light therapy on the immune-inflammatory markers in patients with SAD. METHODS: Plasma concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble IL-2 receptor (sIL-2R) were measured in 15 patients with SAD and 15 age- and sex-matched normal controls. Of the 15 patients, 14 had repeated blood sampling for these variables following 2 weeks of light therapy. RESULTS: We found that patients with SAD had significantly increased IL-6 levels compared to normal controls (P<0.0005). There was a trend toward increased sIL-2R in patients with SAD (P=0.09). There was no significant difference in sIL-6R level between the two diagnostic groups (P=0.18), but the product term (IL-6xsIL-6R) was significantly higher in patients with SAD than that in normal control controls (P<0.0003). Furthermore, all 14 patients who completed the study improved with 2 weeks of light therapy and nine of them (64%) had 50% reduction in score of the Hamilton Depression Rating Scale-SAD version post-treatment compared to baseline. However, the initially increased immune markers in SAD patients were not significantly altered by the therapeutic light therapy. LIMITATIONS: This study was limited to a small sample size and other immune inflammatory markers should be measured for further evidence of immune activation in seasonal depression. CONCLUSIONS: Our results of increased IL-6, IL-6xsIL-6R, and sIL-2R in patients with SAD suggest an activation of the immune-inflammatory system in winter depression, which is not altered by 2 weeks of successful light therapy.

Seasonal depression: the dual vulnerability hypothesis revisited.

OBJECTIVE: In DSM-IV, winter seasonal affective disorder (SAD) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer. However, other groups with "winter depression" have been identified, including patients with incomplete summer remission (ISR) and subsyndromal SAD (sub-SAD, winter depressive symptoms that do not meet criteria for major depression). In this study, we compare the clinical characteristics of these three seasonal groups and their response to light therapy. METHOD: 558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria. Clinical information was recorded using a checklist at index assessment. A subset of patients (N=192) were treated with an open, 2 week trial of light therapy using a 10000 lux fluorescent light box for 30 min per day in the early morning. Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50% improvement in scores. RESULTS: The rates of some melancholic symptoms, anxiety, panic, suicidal ideation, and family history of mood disorder were lowest in the sub-SAD group. The clinical response rates to light therapy were highest in the sub-SAD group (N=32, 78%), intermediate in the SAD group (N=113, 66%), and lowest in the ISR group (N=47, 51%). LIMITATIONS: This was a retrospective study of patients seen in a specialty clinic, although information was obtained in a standardized format. The light therapy trial had an open design so that placebo response could not be determined. CONCLUSIONS: There are differences in both the patterns of clinical symptoms and the response to light therapy in these three groups with winter depression. These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression.

Pathophysiology of seasonal affective disorder: a review.

The study of the pathophysiology of seasonal affective disorder (SAD, also known as winter depression) has historically been intimately linked to investigations into the mechanisms of action of light therapy. This paper reviews the studies on the pathophysiology of SAD with emphasis on circadian, neurotransmitter, and genetic hypotheses. There is substantial evidence for circadian phase shift and serotonergic hypotheses, but conflicting results may indicate that SAD is a biologically heterogeneous condition. Recent progress in defining the molecular mechanisms of the human circadian clock and retinal phototransduction of light will provide important new directions for future studies of the etiology and pathophysiology of SAD.

Effects of light therapy on suicidal ideation in patients with winter depression.

BACKGROUND: Recent case reports suggest that some patients with seasonal affective disorder (SAD) may become suicidal after initial treatment with light therapy. This retrospective study sought to determine the effects of light therapy on suicidal ideation in patients with SAD. METHOD: The cases of 191 depressed patients with SAD by DSM-III-R or DSM-IV criteria treated with an open trial of morning light therapy using cool white fluorescent light boxes (2500 lux for 2 hours per day or 10,000 lux for 30 minutes per day) for 2 weeks were retrospectively analyzed. Patients had been rated before and after treatment with the expanded Hamilton Depression Rating Scale (SIGH-SAD). RESULTS: Sixty-seven percent of patients were rated as clinical responders to light therapy. There was significant improvement in the SIGH-SAD suicide item score, with 45% of patients showing a reduction in score. Only 6 patients (3%) had slight worsening of suicide scores. No patients attempted suicide or discontinued light therapy because of emergent suicidality. CONCLUSION: Light therapy relieves suicidal ideation in patients with SAD consistent with overall clinical improvement. Emergence of suicidal ideas or behaviors is very uncommon with light therapy.

Effects of rapid tryptophan depletion in patients with seasonal affective disorder in natural summer remission.

BACKGROUND: Serotonergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder (SAD) and the therapeutic effect of bright-light treatment. Previously, we showed that SAD patients, in clinical remission with light therapy during the winter, experienced transient depressive relapses after a rapid tryptophan depletion (RTD) technique, which results in decreased brain serotonin levels. The objective of this study was to investigate the effect of RTD in SAD patients who were in natural summer remission. METHODS: Twelve drug-free patients with SAD by DSM-IV criteria and 10 normal subjects participated in this double-blind, placebo-controlled, crossover study. SAD patients were in natural summer remission for at least 8 weeks. Behavioural ratings and plasma tryptophan levels were obtained before, and 5 h after, ingesting an amino acid (AA) mixture +/- tryptophan. Experimental RTD and control sessions were scheduled 1 week apart. RESULTS: The RTD session resulted in significant reduction in total and free plasma tryptophan levels compared to the control session. The behavioural data were analysed using repeated measures analysis of variance. This analysis found significant main effects of time (higher scores after AA ingestion) and diagnosis (higher scores in SAD patients), but no main effect of session or significant interaction effects between the three factors. Thus, there were no significant behavioural effects of RTD compared to the sham depletion control session. CONCLUSIONS: The summer remission experienced by SAD patients is not dependent on plasma tryptophan levels (and presumably brain serotonin function) in the same manner as that of remission after light therapy. These results conflict with those of other laboratories, perhaps because of differences in study samples.

A controlled study of light therapy in women with late luteal phase dysphoric disorder.

Previous studies suggest that light therapy, as used to treat seasonal affective disorder, may be beneficial for pre-menstrual depressive disorders. We conducted a six-menstrual cycle randomized, double-blind, counter-balanced, crossover study of dim vs. bright light therapy in women with late luteal phase dysphoric disorder (LLPDD). Fourteen women who met DSM-III-R criteria for LLPDD completed two menstrual cycles of prospective baseline monitoring of pre-menstrual symptoms, followed by two cycles of each treatment. During the 2-week luteal phase of each treatment cycle, patients were randomized to receive 30 min of evening light therapy using: (1) 10000 lx cool-white fluorescent light (active condition); or (2) 500 lx red fluorescent light (placebo condition), administered by a light box at their homes. After two menstrual cycles of treatment, patients were immediately crossed over to the other condition for another two cycles. Outcome measures were assessed at the mid-follicular and luteal phases of each cycle. Results showed that the active bright white light condition significantly reduced depression and pre-menstrual tension scores during the symptomatic luteal phase, compared to baseline, while the placebo dim red light condition did not. These results suggest that bright light therapy is an effective treatment for LLPDD.

Growth hormone response to baclofen in patients with seasonal affective disorder: effects of light therapy.

There is evidence for gamma-aminobutyric acid (GABA) dysfunction in the pathophysiology and treatment response of patients with major depression, but this has not been studied in seasonal affective disorder (SAD). Growth hormone (GH) response to a challenge with a GABAB receptor agonist, baclofen, is considered an in vivo index of hypothalamic GABAB receptor function in humans. To explore the role of GABAB receptor function in SAD, we compared the GH response to baclofen challenge in 15 patients with SAD and 20 matched healthy controls. Of the 15 patients with SAD, 14 had repeat baclofen challenge following 2-week treatment with light therapy. The results showed that baclofen administration led to a significant increase in GH release both in patients with SAD and normal controls. There was no significant difference in the GH response to baclofen between the two groups. Furthermore, 2-week treatment with light therapy did not significantly alter the baclofen-induced GH response in patients with SAD, in spite of a clear therapeutic effect. The results of this study suggest that hypothalamic GABAB receptor function, as measured by baclofen induced GH release, is not altered in patients with SAD or by light therapy.

Seasonality of symptoms in women with late luteal phase dysphoric disorder.

OBJECTIVE: Both late luteal phase dysphoric disorder (LLPDD) and seasonal affective disorder are cyclical disorders often manifested by "atypical" depressive features. The goal of this study was to determine whether patients with LLPDD demonstrate substantial seasonal variation in symptoms. METHOD: Consecutive female patients attending a subspecialty clinic in a university teaching hospital were assessed by means of DSM-III-R criteria. All subjects completed the Seasonal Pattern Assessment Questionnaire, modified to include items on the seasonality of premenstrual symptoms. The results were compared with those of a group of female nonclinical subjects (N = 50). RESULTS: One hundred patients met the DSM-III-R criteria for LLPDD. Compared to the nonclinical group, the LLPDD patients had a significantly higher mean global seasonality score (an index of seasonality of mood and vegetative symptoms) and a significantly higher rate of seasonal affective disorder (38% versus 8%) as determined by Seasonal Pattern Assessment Questionnaire criteria. Twenty-five percent of the LLPDD group rated their seasonal variation in premenstrual symptoms as marked or severe, while 30% considered seasonal changes in overall symptoms to be a marked or severe problem. CONCLUSIONS: These results suggest that patients with LLPDD have substantial seasonal patterns in mood and premenstrual symptoms. These seasonal patterns have implications for the clinical assessment and treatment of LLPDD. For example, light therapy may be beneficial for women with seasonal worsening of LLPDD.

Growth hormone response to sumatriptan (5-HT1D agonist) challenge in seasonal affective disorder: effects of light therapy.

To explore the role of serotonergic system in seasonal affective disorder (SAD), we compared growth hormone (GH) responses to a challenge with a novel 5-HT1D receptor agonist sumatriptan between 11 patients with SAD and nine healthy controls. Of the 11 patients with SAD, nine had repeat sumatriptan challenge following treatment with light therapy. The results showed that GH responses were significantly blunted during winter depression in patients with SAD compared to healthy controls. The GH responses normalized following treatment with light therapy to similar levels in controls. The results of this study provide a support for the role of serotonergic system in pathophysiology of SAD and in the mechanism of action of light therapy.

L-tryptophan augmentation of light therapy in patients with seasonal affective disorder.

OBJECTIVE: Up to one-third of patients with seasonal affective disorder (SAD) do not have a full response to light therapy. Given the evidence for serotonergic dysregulation in SAD, we examined the possible role of l-tryptophan as an augmentation strategy for nonresponders and partial responders to light therapy. METHOD: Eligible drug-free patients meeting DSM-IV criteria for SAD were treated for 2 weeks using a standard morning light therapy regimen (10,000 lux cool-white fluorescent light for 30 minutes). Partial and nonresponders were treated for 2 weeks with open-label l-tryptophan (1 g 3 times daily) while light therapy was continued. Ratings at baseline and follow-up included the 29-item Structured Interview Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) and the Clinical Global Impression (CGI) scale. RESULTS: Sixteen patients began the l-tryptophan augmentation phase. Two patients discontinued medications within 3 days because of side effects. In the 14 patients completing treatment, the addition of l-tryptophan resulted in significant reduction of mean depression scores. Nine of 14 patients (64%) showed very good clinical responses to combined treatment and minimal side effects. CONCLUSION: This open-label study suggests that l-tryptophan may be an effective augmentation strategy for those patients with SAD who show limited or poor response to bright ligh therapy. Further placebo-controlled studies are warranted to demonstrate efficacy.

Effects of rapid tryptophan depletion in patients with seasonal affective disorder in remission after light therapy.

BACKGROUND: Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic, but not noradrenergic, antidepressant drugs in patients with remitted nonseasonal depression. The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder (SAD) that was in clinical remission after light therapy. METHODS: Patients who met DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern (equivalent to SAD), were treated with a standard course of light therapy. Ten patients with SAD in clinical remission after light therapy underwent rapid tryptophan depletion in a placebo-controlled, double-blind crossover study. Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion. RESULTS: Plasma total and free tryptophan levels were significantly reduced to 20% of normal levels by the rapid tryptophan depletion. The depletion session resulted in significant increases in depression scores compared with the sham control session. Six of 10 patients had a clinically significant relapse of their depression following the tryptophan depletion session. CONCLUSIONS: Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD. This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism.

Treatment of seasonal affective disorder: a review.

OBJECTIVE: To review the status of current treatment of seasonal affective disorder (SAD). METHOD: Treatment studies of SAD published between January 1989 and March 1995 were identified using a computerized MEDLINE literature search. Additional citations were obtained from the reference sections of these articles. Studies included in this review were selected using operational methodologic criteria. RESULTS: Many studies support the efficacy of bright light therapy using a fluorescent light box. The best studied protocol is > 2500 lux white light for 2 hours per day, but newer protocols using 10,000 lux for 30 minutes have comparable response rates. Studies of light visors and other head-mounted devices also report similar response rates, but have not yet shown superiority over putative control conditions. There are fewer medication studies in SAD, but controlled studies suggest that fluoxetine, d-fenfluramine and propranolol are effective. Other treatments such as dawn simulation require further study. No studies of psychological treatments for SAD were found. Many studies had methodologic limitations, including brief treatment periods, small sample sizes, and lack of replication, that limit the generalizability of findings. CONCLUSION: There are several well-studied, effective treatments for SAD, including light therapy and medications. However, further research must be done to demonstrate sustained treatment response over time, to clarify the intensity-response relationship of light therapy, to clarify the role of light therapy and medications, and to assess combination treatments.

A controlled study of light therapy for bulimia nervosa.

OBJECTIVE: Winter worsening of mood and eating symptoms, similar to that of seasonal affective disorder, has recently been reported in patients with bulimia nervosa. To assess the effectiveness of light therapy for treatment of bulimia nervosa, the authors conducted a study of light therapy during winter comparing an active (bright white light) condition to a control (dim red light) condition in bulimic patients who were not selected for a seasonal pattern of bulimia. METHOD: After a 2-week baseline assessment, 17 female patients with a DSM-III-R diagnosis of bulimia nervosa underwent early morning light treatment with 2 weeks of bright white light exposure (10,000 lux for 30 min/day) and 2 weeks of dim red light exposure (500 lux for 30 min/day) in a counterbalanced, crossover design. Outcome measures included daily binge/purge diaries, objective and subjective measures of mood, and the Eating Attitudes Test. Expectation of response for each condition was also assessed before treatment. RESULTS: Although pretreatment expectation ratings were similar for each condition, the bright white light condition was superior to the dim red light condition for all mood and eating outcome measures. Patients with "seasonal" bulimia (N = 7) had significantly greater improvement after the bright white light treatment than patients with nonseasonal bulimia (N = 10). No significant order effects were noted, nor differential effects for patients taking concurrent antidepressant medications (N = 4). CONCLUSIONS: These data suggest that bright white light therapy is an effective short-term treatment for both mood and eating disturbances associated with bulimia nervosa, although the therapeutic effect may be greater in those patients with a seasonal pattern.

Morning light therapy for winter depression: predictors of response.

Bright-light therapy is widely regarded as an effective treatment for winter seasonal affective disorder (SAD). We attempted to identify predictors of light therapy response in 54 depressed, drug-free outpatients diagnosed with SAD by DSM-III-R criteria. After a baseline week, patients were treated for 2 weeks with 2500-lx cool-white fluorescent light exposure from 0600 to 0800 daily. The results showed that light therapy significantly reduced depression scores. Several indices of atypical and typical symptoms correlated with response, but none was clearly superior to the pre-treatment depression score. A multiple regression analysis identified 3 factors (hypersomnia, increased eating and younger age) that predicted light-therapy response. These results suggest that specific symptoms of hypersomnia and hyperphagia are predictors of response to morning bright-light therapy in SAD.

Side effects of light therapy in seasonal affective disorder.

The authors report the frequency of side effects of light therapy in 105 patients with seasonal affective disorder treated with three intensities of light. Common symptoms to emerge during treatment were headache (19%), eyestrain (17%), and feeling "wired" (14%). There was no relationship between side effects and intensity of light used.