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Biomedical subjects

R W Lam

Publications and source records attributed to R W Lam.

At least 19 recordsLinked to original sources
PubMed2001

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.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

Effects of rapid tryptophan depletion on brain 5-HT(2) receptors: a PET study.

BACKGROUND: The mechanism by which rapid tryptophan depletion (RTD) paradigm induces depressive relapse in recently remitted patients with depression is unknown. AIMS: To determine the effects of RTD on brain 5-HT(2) receptors using positron emission tomography (PET) and (18)F-labelled setoperone. METHOD: Ten healthy women under went two PET scans. Each scan was done 5 h after the ingestion of either a balanced or a tryptophan-deficient amino acid mixture, and the two test sessions were separated by at least 5 days. RESULTS: The RTD decreased plasma free tryptophan levels significantly but it had no significant effects on mood. Subjects showed a significant decrease in brain 5-HT(2) receptor binding in various cortical regions following the RTD session. CONCLUSIONS: When taken with the evidence that antidepressant treatment is associated with a decrease in brain 5-HT(2) receptors, these findings suggest that a decrease in 5-HT(2) binding following RTD might be an adaptive response that provides protection against depressive symptoms.

Adult↗
PubMed2001

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.

Adolescent↗
PubMed2000

Brain serotonin2 receptors in major depression: a positron emission tomography study.

BACKGROUND: Postmortem and brain imaging studies that measured brain serotinin(2) (5-HT(2)) receptors in major depression reported an increase, decrease, and no change compared with controls. In this study, we assessed brain 5-HT(2) receptors in 20 depressed patients (mean +/- SD age, 40.1 +/- 9.5 years; range, 22-60 years) and 20 healthy controls similar in age (37.2 +/- 12.6 years; range, 19-59 years) using positron emission tomography and setoperone labeled with fluorine 18 ([(18)F]setoperone). METHODS: Patients with DSM-IV major depression and healthy controls underwent scanning with [(18)F]setoperone. All study subjects were drug free for at least 2 weeks. The 5-HT(2) binding images were created using region-to-cerebellum ratios. The differences in 5-HT(2) receptor binding potential between the two groups were determined with statistical parametric mapping software and region of interest analysis. RESULTS: There was a significant negative correlation between 5-HT(2) receptor binding potential and age in both patients and controls, and the magnitude of this correlation was similar in both groups. Both statistical parametric mapping and region of interest analyses showed that, compared with healthy controls, depressed patients had significantly lower 5-HT(2) receptor binding potential in frontal, temporal, parietal, and occipital cortical regions. Statistical parametric mapping analysis showed that the mean decrease in 5-HT(2) receptor binding potential for the entire cluster in these regions was 22%, and it ranged from 22% to 27% for local maxima within the clusters of significant voxels. CONCLUSION: This study suggests that brain 5-HT(2) receptors are decreased in patients with major depression.

Adult↗
PubMed2000

A PET study of brain 5-HT2 receptors and their correlation with platelet 5-HT2 receptors in healthy humans.

RATIONALE: Platelets share many properties with brain serotonergic neurons such as active 5-hydroxytryptamine (5-HT) transport, 5-HT2 receptors, and mitochondrial monoamine oxidase. OBJECTIVES: We measured brain 5-HT2 receptors and platelet 5-HT2 receptors in healthy volunteers to determine if there was any correlation between the two measures. METHODS: Ten healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. 5-HT2 receptor binding was determined for each subject with positron emission tomography and [18F]setoperone scan in the brain and with 3H-LSD binding in platelets. RESULTS: We found no significant correlation between 5-HT2 binding potential (BP) in platelets (Bmax/Kd) and a semiquantitative estimate of 5-HT2 BP in frontal, parietal, and temporal cortical regions. SPM voxel based analysis also showed no significant correlation between the 5-HT2 BP in platelets and in the brains of the study subjects. CONCLUSIONS: Brain 5-HT2 receptor binding was not significantly correlated to platelet 3H-LSD binding in healthy subjects. This raises questions about the validity of generalizing findings from platelet studies to 5-HT neurons in the brain.

Adult↗
PubMed2000

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.

Adult↗
PubMed2000

Does the addition of pindolol accelerate the response to electroconvulsive therapy in patients with major depression? A double-blind, placebo-controlled pilot study.

There is evidence that addition of pindolol, a beta-adrenergic/5-hydroxytryptamine-1A antagonist, can accelerate the onset of action of antidepressant medications. The purpose of this study was to determine whether pindolol administration can induce a rapid improvement in depressive symptoms in patients receiving electroconvulsive therapy (ECT) within six ECT treatments. A total of 20 patients with DSM-IV-diagnosed major depression who were undergoing a course of ECT as the clinically indicated treatment were recruited. They were neuroleptic, lithium, and antidepressant free for at least 1 week before the study. Of the 20 patients, 9 patients had been randomly assigned to receive pindolol 2.5 mg three times daily, and 11 patients received identical placebo three times daily for the duration of the first 6 ECT treatments. One of 9 patients in the pindolol group and 4 of 11 patients in the placebo group dropped out of the study. Using an outcome measure of a score < or =12 on the 29-item Hamilton Rating Scale for Depression (HAM-D), the authors found that four (50%) of eight patients responded to the combination treatment of ECT and pindolol within six ECT treatments. In contrast, none (0%) of seven patients who received placebo responded to ECT treatment. Furthermore, both mean 29-item HAM-D and Clinical Global Impression Scale scores after the sixth ECT treatment were significantly lower in patients treated with pindolol compared with those treated with placebo. However, the number of total ECT treatments within a course or the overall efficacy of ECT treatment was not altered by the addition of pindolol. The results of this study suggest that within six ECT treatments, pindolol administration hastens antidepressant effects of ECT in some depressed patients.

Adrenergic beta-Antagonists↗
PubMed2000

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.

Adult↗
PubMed2000

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.

Circadian Rhythm↗
PubMed1999

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.

Adult↗
PubMed1999

Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment: a positron emission tomography study with fluorine-18-labeled setoperone.

BACKGROUND: The neuroreceptor changes involved in therapeutic efficacy of various antidepressants remain unclear. Preclinical studies have shown that long-term administration of various antidepressants causes down-regulation of brain serotonin 2 (5-HT2) receptors in rodents, but it is unknown if similar changes occur following antidepressant treatment in depressed patients. Our purpose, therefore, was to assess the effects of treatment with desipramine hydrochloride on brain 5-HT2 receptors in depressed patients using positron emission tomography (PET) and fluorine-18 (18F)-labeled setoperone. METHODS: Eleven patients who met DSM-IV criteria for major depression as determined by a structured clinical interview for DSM-III-R diagnosis and suitable for treatment with desipramine were recruited. Ten patients underwent a PET scan before and another after 3 to 4 weeks of treatment with desipramine. RESULTS: Eight of the 10 patients responded to desipramine treatment as indicated by more than 50% decrease in Hamilton Depression Rating Scale scores. Depressed patients showed a significant decrease in 5-HT2 receptor binding as measured by setoperone binding in frontal, temporal, parietal, and occipital cortical regions following desipramine treatment. The decrease in 5-HT2 receptor binding was observed bilaterally and was particularly prominent in frontal cortex. CONCLUSIONS: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is unknown if this change in 5-HT2 receptors is due to clinical improvement or an effect of desipramine that is unrelated to clinical status.

Antidepressive Agents, Tricyclic↗
PubMed1999

Growth hormone response to baclofen in patients with mania: a pilot study.

RATIONALE: Growth hormone (GH) response to a challenge with a GABAB receptor agonist, baclofen, is considered to provide an in vivo index of hypothalamic GABAB receptor function in humans. OBJECTIVES: The purpose of this study was to explore the role of GABAB receptors in the pathophysiology of mania by measuring plasma GH response to baclofen in ten manic patients and ten matched healthy controls. METHODS: After obtaining blood samples for baseline GH levels, a single dose of 20 mg baclofen was administered orally to all the subjects, and further blood samples were obtained at 30-min intervals for the following 3 h. RESULTS: We found that baclofen administration led to a significant increase in GH release both in manic patients and healthy controls, but the GH response to baclofen in manic patients was significantly enhanced when compared to healthy controls. CONCLUSIONS: Our results suggest that manic patients may have an up-regulated hypothalamic GABAB receptor function. However, in light of the limitations including small sample size and absence of placebo control, our results should be viewed as preliminary. Further studies with a larger number of manic patients and a placebo control design are needed to replicate our finding before any firm conclusion can be drawn.

Acute Disease↗
PubMed1999

Hypothermic, ACTH, and cortisol responses to ipsapirone in patients with mania and healthy controls.

BACKGROUND: The selective 5-HT1A receptor agonist ipsapirone causes dose-dependent decrease in body temperature and increase in adrenocorticotropic hormone (ACTH) and cortisol release in humans. These responses are attenuated by 5-HT1A receptor antagonists, suggesting that hypothermia, ACTH and cortisol release induced by ipsapirone are indeed mediated by 5-HT1A receptors and that these responses provide a valid index of 5-HT1A receptor function in humans. METHODS: To examine the 5-HT1A receptor sensitivity in patients with mania, we studied six manic patients and six age and sex matched healthy controls. After obtaining a blood sample for baseline hormone levels and measuring body temperature, a single dose of 0.3 mg/kg of ipsapirone was given orally to all the subjects and further bloods and temperature reading were obtained every 30 minutes for 3 hours. RESULTS: We found that ACTH and cortisol responses to ipsapirone were significantly increased in mania when compared to healthy controls, but there was no significant difference in hypothermic response to ipsapirone between the two groups. LIMITATIONS: A lack of placebo control, heterogeneity of patients, and a small sample size are the limitations. CONCLUSIONS: Our findings suggest that manic patients may have enhanced postsynaptic 5-HT1A receptor sensitivity, but presynaptic 5-HT1A receptors are unaltered in this condition. Further placebo-controlled studies with a larger number of manic patients are needed to verify this.

Administration, Oral↗
PubMed1999

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.

Adult↗
PubMed1999

Clinical predictors of short-term outcome in electroconvulsive therapy.

OBJECTIVES: Electroconvulsive therapy (ECT) remains one of the most effective biological treatments for major depression. However, there is little information on the clinical use of ECT, and most studies were conducted before the introduction of newer antidepressants and before improvements in ECT delivery. This study examined ECT use in a university teaching hospital to determine predictors of short-term ECT outcome. METHODS: This was a retrospective chart review of ECT over the period 1994-1996. Data extracted from the chart included demographic information, clinical features of depression, and documented antidepressant trials. Outcome measures, based on the chart notes, included Clinical Global Impression (CGI) and cognitive side effects of ECT at 1 week post-ECT or at discharge if sooner. RESULTS: Of 174 patients who received ECT, 130 had a diagnosis of unipolar major depressive disorder. Of these 130 patients, 92% were refractory to at least 1 antidepressant medication. After a clinical course of ECT, 87% were rated as "much" or "very much" improved on the CGI. Moderate side effects were noted in 16% of patients, while only 7% had marked side effects. Medication resistance was not related to ECT response. No significant clinical predictors (symptoms, chronicity, number of antidepressant trials) of ECT outcome were found on a stepwise multiple-regression analysis. CONCLUSIONS: These results support previous studies showing that ECT results in very good short-term response in major depressive disorder and that the cognitive side effects of ECT are reasonable. Despite the limitations of this study (retrospective, chart review, global measures), the results will inform clinicians who are recommending ECT for their patients.

Adult↗
PubMed1998

Seasonal mood change and personality: an investigation of genetic co-morbidity.

Clinical observations and empirical studies suggest that Seasonal Affective Disorder (SAD) is related to personality. The present study estimates the genetic and environmental correlations between the Global Seasonality Score (GSS) from the Seasonal Pattern Assessment Questionnaire and personality measures, assessed using the NEO Five Factor Inventory (NEO-FFI) and the Dimensional Assessment of Personality Pathology (DAPP) in a volunteer sample of 163 monozygotic (MZ) pairs (102 female and 61 male pairs) and 134 dizygotic (DZ) pairs (70 female, 38 male and 26 opposite-sex pairs). Large genetic correlations were found between the GSS and NEO-FFI Neuroticism (0.52: 95% CI = 0.36-0.71) and DAPP-BQ Cognitive Dysregulation (0.50: 95% CI = 0.30-0.71), Affective Lability (0.49: 95% CI = 0.29-0.77), Anxiousness (0.37: 95% CI = 0.18-0.55) and Stimulus Seeking (0.45: 95% CI = 0.25-0.64) scales. The genetic correlations with the remaining scales, such as Extraversion (0.06: 95% CI = -0.16-0.26), Compulsivity (-0.09: 95% CI = -0.31-0.12) and Submissiveness (0.15: 95% CI = -0.05-0.34) were uniformly small. All environmental correlations between the GSS and personality scales were < or = 0.19. These results provide evidence that the observed correlations between these seasonality and personality dimensions are attributable to common genetic factors and that environmental influences are domain specific.

Adolescent↗