derek eder | University of Gothenburg (original) (raw)
Papers by derek eder
Sleep medicine, Jan 1, 2010
Objective: Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA)... more Objective: Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA), is sympathetically mediated. We compared the effect of Doxazosin (DO, a peripheral a-receptor inhibitor) and Enalapril (EN, an ACE inhibitor) on digital vasoconstriction and nocturnal blood pressure (BP) in hypertensive OSA patients. Methods: A double-blind, crossover study comparing equipotent dosages of DO (4 mg/day for 2 weeks with 8 mg/day for an additional 2 weeks) and EN (10 mg/day and 20 mg/day, respectively) was undertaken in 16 male OSA patients (age 55 ± 7 years, body mass index 30.1 ± 3.8 kg/m 2 ) with hypertension. Assessments including ambulatory 24-h BP, full-night polysomnography with simultaneous peripheral arterial tone (PAT) and beat-to-beat finger BP monitoring (Finapres) were made at the end of each treatment period. Nighttime BP and digital vasoconstrictions associated with apneic events (measured as the ratio of PAT amplitudes during and after apneas) were analyzed. Results: There were no differences between the two treatments in the 24-h BP profile and OSA severity. But the nighttime average beat-to-beat finger BP was significantly higher under DO treatment (systolic BP 129 ± 13 vs. 119 ± 23 mm Hg, P = 0.02; diastolic BP 81 ± 12 vs. 74 ± 14 mm Hg, P = 0.04, DO and EN respectively). In a linear mixed effects regression model, the PAT ratio during apnea increased 5.3% under DO compared with EN (P < 0.0001). Each percentage decrease of apneic related oxygen desaturation was associated with 0.9% decrease in the PAT ratio (P < 0.0001). REM sleep was associated with 2.2% decrease of PAT ratio compared to NREM sleep (P = 0.002).
Sleep medicine, Jan 1, 2009
Objective and Background: Pulse wave amplitude (PWA) derived from the digital vascular bed has be... more Objective and Background: Pulse wave amplitude (PWA) derived from the digital vascular bed has been used in sleep studies. The nocturnal attenuation of PWA has been shown to reflect sympathetic activation during sleep. We assessed the relationship between nocturnal PWA attenuation and office blood pressure (BP). Methods: Eighty-one subjects (46 men; age 60 ± 7 years; body mass index [BMI] 28.2 ± 4.3 kg/m 2 ; apnea hypopnea index [AHI], 25.4 ± 22.6 events/h; systolic BP 137 ± 15 mmHg; diastolic BP 79 ± 7 mmHg) recruited from a population based cohort underwent simultaneous ambulatory polysomnography (PSG) and peripheral arterial tonometry (PAT) recording. Episodic attenuations of PWA derived from the pulse waveform of the PAT signal were identified and characterized. Generalized least squares regression models were used to identify the associations between median PWA attenuation (PWA.att), office BP and sleep-related disordered breathing. Results: We found that the association between PWA.att and office BP was independent of gender, age, BMI, antihypertensive medication, number of attenuation episodes, AHI, oxygen desaturation P4% index (ODI4) and arousal index. Each 10% increase in PWA.att was associated with increases of 5.0 mmHg systolic BP (P = 0.02) and 3.0 mmHg diastolic BP (P = 0.005). We also found independent relationships between systolic/diastolic BP and BMI (P = 0.0006/0.001), AHI (P = 0.03/0.1) and ODI4 (P = 0.03/0.03). Conclusions: The degree of PWA attenuation during the night is associated with office BP independent of sleep-disordered breathing. Continuous assessment of PWA during sleep may provide novel insights into cardiovascular physiology and morbidity.
Current opinion in investigational drugs (London, …, Jan 1, 2002
CEE-03-310 is a selective dopamine D1-like receptor antagonist with no appreciable binding affini... more CEE-03-310 is a selective dopamine D1-like receptor antagonist with no appreciable binding affinity for other receptors. Although originally developed by Novo Nordisk A/S as NNC-687 for the treatment of schizophrenia, the company changed its therapeutic focus in the mid-1990s and the full rights to CEE-03-310 and several related compounds were subsequently granted to CeNeS Pharmaceuticals in 1999. CeNeS is currently investigating the drug&amp;#39;s potential in the treatment of insomnia and alcohol dependency [340965], [382293], [401496],[416026]. A phase II, double-blind, placebo-controlled trial of CEE-03-310 demonstrated a dose-dependent enhancement of NREM sleep at the beginning of the night without any effects on the quantity of REM sleep [410739].
Journal of affective …, Jan 1, 2002
Patients with winter depression, (seasonal affective disorder, SAD) frequently complain of diffic... more Patients with winter depression, (seasonal affective disorder, SAD) frequently complain of difficulty awakening in the morning. Dawn simulation has been found effective in treating SAD, but its effect on difficulty awakening has not been assessed. Fifty medication-free patients with SAD associated with hypersomnia were randomized to receive either 1 week of dawn simulation (250 lux) or a dim (0.2-2 lux) placebo signal. The patients assessed their level of drowsiness upon awakening during the baseline week and during the treatment week using the Stanford sleepiness scale (SSS). A psychiatrist rated difficulty awakening after the baseline week and after the treatment week. Dawn simulation lowered both the difficulty awakening score (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and the SSS score (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) compared to the placebo dawn signal. Replication is necessary. No biological markers of circadian phase were measured. Compared to a placebo condition, dawn simulation appears effective in decreasing both prospectively assessed morning drowsiness and retrospectively assessed difficulty awakening. The symptom of difficulty awakening is consistent with the phase delay hypothesis of SAD. Assessment of difficulty awakening could prove useful in the evaluation of SAD.
Psychiatry research, Jan 1, 2001
Significant somatosensory evoked potential (SEP) P50 gating has previously been found in young he... more Significant somatosensory evoked potential (SEP) P50 gating has previously been found in young healthy men by the use of identical paired stimuli. In this study, the exploration of the gating paradigm was extended with the addition of a mixed modality paradigm where three different pairs of identical stimuli (clicks, right median nerve electric stimulations and proprioceptive stimuli of changing load on a handheld weight) were presented over a 12-s cycle. In both modalities repeated measures analyses of variance demonstrated no effect of paradigm. This mixed-modality recording paradigm could be used in further experiments to examine gating deficits across modalities.
Neuroscience …, Jan 1, 2000
We studied cerebral evoked potentials on the scalp to the stimulation of the right hand from a ch... more We studied cerebral evoked potentials on the scalp to the stimulation of the right hand from a change in weight of 400± 480 g in ten subjects. Rise-time was 20g/10 ms, Inter Stimulus Interval 2s and stimulus duration was 100 ms. The cerebral activations were a double positive contralateral C3'/P70, P190, and a single negative frontal Fz/N70 component. We conclude that a brisk change of a hand held load elicits a signi®cant evoked potential (EP) unlike the electrical somatosensory EP (SEP). The stimulus is perceived as applied force. For this reason we call it a proprioceptive EP (PEP). Further studies of the PEP are needed to assess the in¯uence of load manipulations and of muscle contraction and to explore the effect of attentional manipulation. q
SLEEP-NEW YORK …, Jan 1, 2004
Study Objective: To characterize the role of alpha-receptors in autonomic control of digital skin... more Study Objective: To characterize the role of alpha-receptors in autonomic control of digital skin blood flow change in response to obstructive apnea-hypopnea events. Design: Experimental intervention study. Setting: Sleep laboratory in a university hospital. Patients: Eight male patients with severe obstructive sleep apnea (OSA). Interventions: Patients received four cumulative dosage steps of phentolamine (0.066, 0.2, 2 and 5[n=3] µg/min/100ml forearm tissue) via brachial artery infusion during nonrapid eye movement sleep (stage 1 and 2).
Psychiatry research, Jan 1, 2001
A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-process... more A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-processing deficits in schizophrenia. The relationship between gating of the mid-latency evoked potentials (EP) in the somatosensory and the auditory modalities has not been studied together before. In schizophrenia, we might expect the processing deficits to act on multiple modalities. We have examined the gating of median nerve somatosensory EP (SEP) following paired stimulation identical to the AEP P50 gating paradigm using interstimulus intervals (ISI) of 500, 750 and 1000 ms and the correlation of gating to the skin conductance orienting response (SCOR) in 20 healthy men. We measured mid-latency vertex components (SEP: P50, N65, P85 and N100; AEP: P30, N45, P50 and N80). The gating was most pronounced at ISI 500 ms where the SEP P50 and N100 gating were 0.59 and 0.37, respectively, as compared to a gating of 0.61 in P30, 0.33 in P50 and 0.45 in N80 in the AEP. Repetition effects in the two modalities were not correlated. AEP P50 gating was correlated to skin conductance level (SCL). The combination of recording repetition effects on the mid-latency EP in two modalities could provide a method for investigating if deficits of information processing in schizophrenia are cross-modal.
Biological …, Jan 1, 2001
Background: Some small controlled studies have found that dawn simulation is effective in treatin... more Background: Some small controlled studies have found that dawn simulation is effective in treating seasonal affective disorder (SAD). With a larger sample size and a longer duration of treatment, we compared dawn simulation with bright light therapy and a placebo condition in patients with SAD. Method: Medication-free patients with SAD were randomly assigned to one of three conditions: bright light therapy (10,000 lux for 30 min, from 6:00 AM to 6:30 AM), dawn simulation (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 250 lux), and a placebo condition, a dim red light (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 0.5 lux.) Over the subsequent 6 weeks, the subjects were blindly rated by a psychiatrist using the Structured Interview Guide for the Hamilton Depression Rating-Seasonal Affective Disorder Version (SIGH-SAD). We modeled the profiles of the remissions (SIGH-SAD Յ 8) and response (Ն50% decrease in SIGH-SAD) to treatment over time using Cox proportional hazards models. Results: The sample consisted of 95 subjects who were randomized to the three conditions: bright light (n ϭ 33), dawn simulation (n ϭ 31) and placebo (n ϭ 31). Dawn simulation was associated with greater remission (p Ͻ .05) and response (p Ͻ .001) rates compared to the placebo. Bright light did not differ significantly from the placebo. Dawn simulation was associated with greater remission (p Ͻ .01) and response (p Ͻ .001) rates compared to the bright light therapy. The mean daily hours of sunshine during the week before each visit were associated with a significant increase in likelihood of both remission (p Ͻ .001) and response (p Ͻ .001). Conclusions: Dawn simulation was associated with greater remission and response rates compared to the placebo and compared to bright light therapy. The hours of sunshine during the week before each assessment were associated with a positive clinical response. Biol Psychi-atry 2001;50:205-216
Biological …, Jan 1, 1997
Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms during a constant ... more Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms during a constant routine were assessed in 6 female controls and 6 female patients with hypersomnic winter depression (seasonal affective disorder, SAD) before and after morning bright light treatment. After sleep was standardized for 6 days, the subjects were sleep-deprived and at bed rest for 27 hours while rectal temperature, cortisol, and TSH levels were assessed. The minimum of the fitted rectal temperature rhythm was phase-delayed in the SAD group compared to the controls 5:42 AM vs. 3:16 AM (p < .005); with bright light treatment, the minimum advanced from 5:42 AM to 3:36 AM (p = .06). The minimum of the cortisol rhythm was phase-delayed in the SAD group compared to the control group, 12.'11 AM vs. 11:03 eM (p < .05); with bright light treatment, the minimum advanced from 12:11 AM to 11:38 PM (p = .06). The acrophase of the TSH rhythm was not signifcantly phase-delayed in SAD subjects compared to control, though the trend appeared to be toward a phase-delay (p = .07). After bright light therapy, the TSH acrophase was not significantly different in the SAD subjects; the trend was a phase-advance (p = .09). Overall, the data suggest that circadian rhythms are phase-delayed relative to sleep in SAD patients and that morning bright light phase-advances those rhythms.
Sleep medicine, Jan 1, 2010
Objective: Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA)... more Objective: Pulse wave attenuation, which occurs in association with obstructive sleep apnea (OSA), is sympathetically mediated. We compared the effect of Doxazosin (DO, a peripheral a-receptor inhibitor) and Enalapril (EN, an ACE inhibitor) on digital vasoconstriction and nocturnal blood pressure (BP) in hypertensive OSA patients. Methods: A double-blind, crossover study comparing equipotent dosages of DO (4 mg/day for 2 weeks with 8 mg/day for an additional 2 weeks) and EN (10 mg/day and 20 mg/day, respectively) was undertaken in 16 male OSA patients (age 55 ± 7 years, body mass index 30.1 ± 3.8 kg/m 2 ) with hypertension. Assessments including ambulatory 24-h BP, full-night polysomnography with simultaneous peripheral arterial tone (PAT) and beat-to-beat finger BP monitoring (Finapres) were made at the end of each treatment period. Nighttime BP and digital vasoconstrictions associated with apneic events (measured as the ratio of PAT amplitudes during and after apneas) were analyzed. Results: There were no differences between the two treatments in the 24-h BP profile and OSA severity. But the nighttime average beat-to-beat finger BP was significantly higher under DO treatment (systolic BP 129 ± 13 vs. 119 ± 23 mm Hg, P = 0.02; diastolic BP 81 ± 12 vs. 74 ± 14 mm Hg, P = 0.04, DO and EN respectively). In a linear mixed effects regression model, the PAT ratio during apnea increased 5.3% under DO compared with EN (P < 0.0001). Each percentage decrease of apneic related oxygen desaturation was associated with 0.9% decrease in the PAT ratio (P < 0.0001). REM sleep was associated with 2.2% decrease of PAT ratio compared to NREM sleep (P = 0.002).
Sleep medicine, Jan 1, 2009
Objective and Background: Pulse wave amplitude (PWA) derived from the digital vascular bed has be... more Objective and Background: Pulse wave amplitude (PWA) derived from the digital vascular bed has been used in sleep studies. The nocturnal attenuation of PWA has been shown to reflect sympathetic activation during sleep. We assessed the relationship between nocturnal PWA attenuation and office blood pressure (BP). Methods: Eighty-one subjects (46 men; age 60 ± 7 years; body mass index [BMI] 28.2 ± 4.3 kg/m 2 ; apnea hypopnea index [AHI], 25.4 ± 22.6 events/h; systolic BP 137 ± 15 mmHg; diastolic BP 79 ± 7 mmHg) recruited from a population based cohort underwent simultaneous ambulatory polysomnography (PSG) and peripheral arterial tonometry (PAT) recording. Episodic attenuations of PWA derived from the pulse waveform of the PAT signal were identified and characterized. Generalized least squares regression models were used to identify the associations between median PWA attenuation (PWA.att), office BP and sleep-related disordered breathing. Results: We found that the association between PWA.att and office BP was independent of gender, age, BMI, antihypertensive medication, number of attenuation episodes, AHI, oxygen desaturation P4% index (ODI4) and arousal index. Each 10% increase in PWA.att was associated with increases of 5.0 mmHg systolic BP (P = 0.02) and 3.0 mmHg diastolic BP (P = 0.005). We also found independent relationships between systolic/diastolic BP and BMI (P = 0.0006/0.001), AHI (P = 0.03/0.1) and ODI4 (P = 0.03/0.03). Conclusions: The degree of PWA attenuation during the night is associated with office BP independent of sleep-disordered breathing. Continuous assessment of PWA during sleep may provide novel insights into cardiovascular physiology and morbidity.
Current opinion in investigational drugs (London, …, Jan 1, 2002
CEE-03-310 is a selective dopamine D1-like receptor antagonist with no appreciable binding affini... more CEE-03-310 is a selective dopamine D1-like receptor antagonist with no appreciable binding affinity for other receptors. Although originally developed by Novo Nordisk A/S as NNC-687 for the treatment of schizophrenia, the company changed its therapeutic focus in the mid-1990s and the full rights to CEE-03-310 and several related compounds were subsequently granted to CeNeS Pharmaceuticals in 1999. CeNeS is currently investigating the drug&amp;#39;s potential in the treatment of insomnia and alcohol dependency [340965], [382293], [401496],[416026]. A phase II, double-blind, placebo-controlled trial of CEE-03-310 demonstrated a dose-dependent enhancement of NREM sleep at the beginning of the night without any effects on the quantity of REM sleep [410739].
Journal of affective …, Jan 1, 2002
Patients with winter depression, (seasonal affective disorder, SAD) frequently complain of diffic... more Patients with winter depression, (seasonal affective disorder, SAD) frequently complain of difficulty awakening in the morning. Dawn simulation has been found effective in treating SAD, but its effect on difficulty awakening has not been assessed. Fifty medication-free patients with SAD associated with hypersomnia were randomized to receive either 1 week of dawn simulation (250 lux) or a dim (0.2-2 lux) placebo signal. The patients assessed their level of drowsiness upon awakening during the baseline week and during the treatment week using the Stanford sleepiness scale (SSS). A psychiatrist rated difficulty awakening after the baseline week and after the treatment week. Dawn simulation lowered both the difficulty awakening score (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and the SSS score (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) compared to the placebo dawn signal. Replication is necessary. No biological markers of circadian phase were measured. Compared to a placebo condition, dawn simulation appears effective in decreasing both prospectively assessed morning drowsiness and retrospectively assessed difficulty awakening. The symptom of difficulty awakening is consistent with the phase delay hypothesis of SAD. Assessment of difficulty awakening could prove useful in the evaluation of SAD.
Psychiatry research, Jan 1, 2001
Significant somatosensory evoked potential (SEP) P50 gating has previously been found in young he... more Significant somatosensory evoked potential (SEP) P50 gating has previously been found in young healthy men by the use of identical paired stimuli. In this study, the exploration of the gating paradigm was extended with the addition of a mixed modality paradigm where three different pairs of identical stimuli (clicks, right median nerve electric stimulations and proprioceptive stimuli of changing load on a handheld weight) were presented over a 12-s cycle. In both modalities repeated measures analyses of variance demonstrated no effect of paradigm. This mixed-modality recording paradigm could be used in further experiments to examine gating deficits across modalities.
Neuroscience …, Jan 1, 2000
We studied cerebral evoked potentials on the scalp to the stimulation of the right hand from a ch... more We studied cerebral evoked potentials on the scalp to the stimulation of the right hand from a change in weight of 400± 480 g in ten subjects. Rise-time was 20g/10 ms, Inter Stimulus Interval 2s and stimulus duration was 100 ms. The cerebral activations were a double positive contralateral C3'/P70, P190, and a single negative frontal Fz/N70 component. We conclude that a brisk change of a hand held load elicits a signi®cant evoked potential (EP) unlike the electrical somatosensory EP (SEP). The stimulus is perceived as applied force. For this reason we call it a proprioceptive EP (PEP). Further studies of the PEP are needed to assess the in¯uence of load manipulations and of muscle contraction and to explore the effect of attentional manipulation. q
SLEEP-NEW YORK …, Jan 1, 2004
Study Objective: To characterize the role of alpha-receptors in autonomic control of digital skin... more Study Objective: To characterize the role of alpha-receptors in autonomic control of digital skin blood flow change in response to obstructive apnea-hypopnea events. Design: Experimental intervention study. Setting: Sleep laboratory in a university hospital. Patients: Eight male patients with severe obstructive sleep apnea (OSA). Interventions: Patients received four cumulative dosage steps of phentolamine (0.066, 0.2, 2 and 5[n=3] µg/min/100ml forearm tissue) via brachial artery infusion during nonrapid eye movement sleep (stage 1 and 2).
Psychiatry research, Jan 1, 2001
A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-process... more A defect in auditory evoked potential (AEP) P50 gating supports the theory of information-processing deficits in schizophrenia. The relationship between gating of the mid-latency evoked potentials (EP) in the somatosensory and the auditory modalities has not been studied together before. In schizophrenia, we might expect the processing deficits to act on multiple modalities. We have examined the gating of median nerve somatosensory EP (SEP) following paired stimulation identical to the AEP P50 gating paradigm using interstimulus intervals (ISI) of 500, 750 and 1000 ms and the correlation of gating to the skin conductance orienting response (SCOR) in 20 healthy men. We measured mid-latency vertex components (SEP: P50, N65, P85 and N100; AEP: P30, N45, P50 and N80). The gating was most pronounced at ISI 500 ms where the SEP P50 and N100 gating were 0.59 and 0.37, respectively, as compared to a gating of 0.61 in P30, 0.33 in P50 and 0.45 in N80 in the AEP. Repetition effects in the two modalities were not correlated. AEP P50 gating was correlated to skin conductance level (SCL). The combination of recording repetition effects on the mid-latency EP in two modalities could provide a method for investigating if deficits of information processing in schizophrenia are cross-modal.
Biological …, Jan 1, 2001
Background: Some small controlled studies have found that dawn simulation is effective in treatin... more Background: Some small controlled studies have found that dawn simulation is effective in treating seasonal affective disorder (SAD). With a larger sample size and a longer duration of treatment, we compared dawn simulation with bright light therapy and a placebo condition in patients with SAD. Method: Medication-free patients with SAD were randomly assigned to one of three conditions: bright light therapy (10,000 lux for 30 min, from 6:00 AM to 6:30 AM), dawn simulation (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 250 lux), and a placebo condition, a dim red light (1.5 hour dawn signal from 4:30 AM to 6:00 AM peaking at 0.5 lux.) Over the subsequent 6 weeks, the subjects were blindly rated by a psychiatrist using the Structured Interview Guide for the Hamilton Depression Rating-Seasonal Affective Disorder Version (SIGH-SAD). We modeled the profiles of the remissions (SIGH-SAD Յ 8) and response (Ն50% decrease in SIGH-SAD) to treatment over time using Cox proportional hazards models. Results: The sample consisted of 95 subjects who were randomized to the three conditions: bright light (n ϭ 33), dawn simulation (n ϭ 31) and placebo (n ϭ 31). Dawn simulation was associated with greater remission (p Ͻ .05) and response (p Ͻ .001) rates compared to the placebo. Bright light did not differ significantly from the placebo. Dawn simulation was associated with greater remission (p Ͻ .01) and response (p Ͻ .001) rates compared to the bright light therapy. The mean daily hours of sunshine during the week before each visit were associated with a significant increase in likelihood of both remission (p Ͻ .001) and response (p Ͻ .001). Conclusions: Dawn simulation was associated with greater remission and response rates compared to the placebo and compared to bright light therapy. The hours of sunshine during the week before each assessment were associated with a positive clinical response. Biol Psychi-atry 2001;50:205-216
Biological …, Jan 1, 1997
Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms during a constant ... more Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms during a constant routine were assessed in 6 female controls and 6 female patients with hypersomnic winter depression (seasonal affective disorder, SAD) before and after morning bright light treatment. After sleep was standardized for 6 days, the subjects were sleep-deprived and at bed rest for 27 hours while rectal temperature, cortisol, and TSH levels were assessed. The minimum of the fitted rectal temperature rhythm was phase-delayed in the SAD group compared to the controls 5:42 AM vs. 3:16 AM (p < .005); with bright light treatment, the minimum advanced from 5:42 AM to 3:36 AM (p = .06). The minimum of the cortisol rhythm was phase-delayed in the SAD group compared to the control group, 12.'11 AM vs. 11:03 eM (p < .05); with bright light treatment, the minimum advanced from 12:11 AM to 11:38 PM (p = .06). The acrophase of the TSH rhythm was not signifcantly phase-delayed in SAD subjects compared to control, though the trend appeared to be toward a phase-delay (p = .07). After bright light therapy, the TSH acrophase was not significantly different in the SAD subjects; the trend was a phase-advance (p = .09). Overall, the data suggest that circadian rhythms are phase-delayed relative to sleep in SAD patients and that morning bright light phase-advances those rhythms.