Biomedical subjects

I S Shiah

Publications and source records attributed to I S Shiah.

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↗

PubMed2000

Nomifensine attenuates d-amphetamine-induced dopamine terminal neurotoxicity in the striatum of rats.

Long-term or high dose administration of d-amphetamine (AMPH) in the rat has been shown to result in dopamine terminal neurotoxicity in the striatum of rats. This phenomenon includes depletion of dopamine content, decreased activity of tyrosine hydroxylase and diminish in the number of dopamine reuptake transporter. Recent studies implicate a role of oxidative stress induced by dopamine in the AMPH-induced neurotoxicity. However, the primary source of dopamine responsible for radical formation during AMPH challenge has remained elusive. To elucidate this issue, the study was designed to examine the effects of nomifensine, a dopamine transporter blocker, and deprenyl, a monoamine oxidase B (MAO-B) inhibitor, on the prevention of striatal dopamine neurotoxicity in AMPH-treated rats. The results showed that nomifensine but not deprenyl protected against AMPH-induced long-term dopamine depletion. Correspondingly, the hydroxyl radical formation caused by AMPH in the striatum was attenuated by nomifensine, whereas its formation was not abolished by deprenyl. In conclusion, this study suggests that intracellular oxidative stress is more likely involved in the AMPH-induced dopamine terminal toxicity in the rat striatum, while this phenomenon is not mediated by MAO-B pathway.

Animals↗

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

Serotonin in mania and in the mechanism of action of mood stabilizers: a review of clinical studies.

OBJECTIVES: Serotonin (5-hydroxytryptamine, 5-HT) was implicated in the pathophysiology of manic-depressive illness as early as 1958. Although extensive evidence has accumulated since then to support 5-HT's role in depression, relatively fewer studies examined its role in mania. The purpose of this paper was to review and summarize the current state of knowledge on the role of 5-HT in mania and its treatment. METHODS: We systemically reviewed clinical studies of 1) 5-HT function in mania and 2) 5-HT in the mechanism of action of mood stabilizers, including lithium and anticonvulsants. RESULTS: Review showed that cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and tryptophan depletion studies provided some evidence to support the hypothesis that a 5-HT deficit is involved in mania and that enhancement of 5-HT neurotransmission exerts a mood-stabilizing effect. CONCLUSIONS: There is some evidence from clinical studies for the contribution of 5-HT in mania and in the mechanism of action of mood stabilizers. However, it is very likely that other neurotransmitters also play important roles. Future directions for research include 1) in vivo study of 5-HT receptor subtypes using positron emission tomography, 2) investigation of the interaction between 5-HT and other neurotransmitter systems, and 3) determination of the relationships between diagnostic subtypes of mania and 5-HT function and other neurotransmitter systems.

Anticonvulsants↗

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

Divalproex sodium increases plasma GABA levels in healthy volunteers.

The purpose of this study was to ascertain the effects of divalproex sodium (DVP), an anticonvulsant and mood stabilizer, on plasma gamma-aminobutyric acid (GABA) levels in healthy humans. Twenty healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. Each subject received DVP 1000 mg per day for 1 week. Blood samples for assay of plasma levels of GABA were taken from each subject before and after the administration of DVP. GABA concentrations were analysed using high pressure liquid chromatography with fluorescence detection after derivatization with o-phthaldialdehyde. It was found that DVP administration for 1 week resulted in a small, but significant, increase in plasma levels of GABA. Our results suggest that DVP enhances GABA activity in humans. Further treatment studies of DVP on GABA function in patients with psychiatric disorders are needed to explore the significance of the enhancing effect of DVP on GABA activity.

Adult↗

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↗

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↗

PubMed1998

The lower limits of dexamethasone window in Chinese depressives.

BACKGROUND: Previous studies have shown wide variation in plasma dexamethasone (DEX) concentrations following a standard 1-mg dexamethasone suppression test (DST), and significantly lower DEX concentrations in DST nonsuppressors compared with suppressors, suggesting that DEX pharmacokinetics/bioavailability is an important variable associated with DST nonsuppression. METHODS: To determine the effect of plasma DEX levels on the DST in Chinese depressives, we measured plasma DEX and post-DEX cortisol levels at 4:00 PM in a group of 50 depressed outpatients, 28 anxiety outpatients, and 33 normal subjects during the course of 1-mg oral overnight DST. RESULTS: We found a significant difference in the plasma DEX levels between DST nonsuppressors and suppressors in the depression group and overall subject population, and a significant negative correlation between the plasma DEX and cortisol levels in the depression, anxiety, and total groups. Within a DEX "window", the DST performance was enhanced, whereas the relationships between plasma DEX and post-DEX cortisol levels remained equally strong. CONCLUSIONS: Our findings support a relationship between plasma DEX and post-DEX cortisol levels, a relationship that might be superimposed on the hypothalamic-pituitary-adrenal axis. Comparing our "window" range with those of previous studies, we suggest that Chinese depressives may have lower limits of plasma DEX window, and that ethnicity may be an intervening variable in both DST response and pharmacokinetics of DEX.

Adult↗

PubMed1998

GABA function in mood disorders: an update and critical review.

Over the past twenty years, several lines of evidence from preclinical and clinical studies has accumulated suggesting that a GABA deficit may be involved in mood disorders, particularly in depression, and that increasing GABAergic neurotransmission may exert an antidepressant effect and perhaps a mood stabilizing effect. Given that GABA has an inhibitory effect on biogenic amine neurotransmitters such as norepinephrine and serotonin and this inhibition may be involved in local circuits and interneurons, it has been suggested that the hypothesis of a GABA deficit in mood disorders does not compete with but complements the well-established hypotheses of alterations in noradrenergic and serotonergic function in mood disorders. In this paper, we systematically reviewed the results from preclinical and clinical studies of GABA function in the pathophysiology of mood disorders and in the mechanism of action of mood stabilizers, antidepressants and electroconvulsive therapy. We also discussed the unifying theory of the neurochemistry of mood disorders, which integrates the GABA hypothesis into the biogenic amine hypotheses, and indicated future directions for research.

Animals↗

PubMed1998

Effects of lamotrigine on the 5-HT1A receptor function in healthy human males.

BACKGROUND: Lamotrigine, a new anticonvulsant, has recently been reported to be effective in treating patients with bipolar mania, depression, and schizoaffective disorder, suggesting that it is perhaps a mood stabilizer with antimanic and antidepressant properties. However, the mechanism of action underlying its efficacy in mood disorders is still unknown. METHODS: To explore the role of 5-HT1A receptors in the mechanism of action of lamotrigine, we measured the body temperature and plasma cortisol responses to a challenge with a selective 5-HT1A receptor agonist ipsapirone in ten healthy human males. Each subject received 0.3 mg/kg of ipsapirone hydrochloride tablets at time "0". Body temperature readings and blood samples for cortisol levels were obtained at 0, 30, 60, 90, 120, 150, 180 min. The ipsapirone challenge tests were repeated after 1 week treatment with lamotrigine (100 mg/day). RESULTS: Treatment with lamotrigine for 1 week did not significantly alter the hypothermic or cortisol responses to ipsapirone. LIMITATIONS: The limitations of this study included small sample size, low treatment dose, short treatment interval, and lack of placebo control. CONCLUSIONS: Our findings might suggest that 5-HT1A receptor function is not involved in the mechanism of action of lamotrigine in humans. Further placebo-controlled studies with a higher lamotrigine dose and a longer treatment interval in a larger number of subjects are needed to verify this.

Adult↗