Joseph Wu | University of California, Irvine (original) (raw)

Papers by Joseph Wu

Research paper thumbnail of Prediction of Antidepressant Effects of Sleep Deprivation by Metabolic Rates in the Ventral Anterior Cingulate and Medial Prefrontal Cortex

American Journal of Psychiatry

Objective: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of de... more Objective: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. Method: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. Results: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. Conclusions: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.

Research paper thumbnail of The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology

Bipolar Disorders, 2019

AimsTo systematically review the literature on the efficacy and tolerability of the major chronot... more AimsTo systematically review the literature on the efficacy and tolerability of the major chronotherapeutic treatments of bipolar disorders (BD)—bright light therapy (LT), dark therapy (DT), treatments utilizing sleep deprivation (SD), melatonergic agonists (MA), interpersonal social rhythm therapy (IPSRT), and cognitive behavioral therapy adapted for BD (CBTI‐BP)—and propose treatment recommendations based on a synthesis of the evidence.MethodsPRISMA‐based systematic review of the literature.ResultsThe acute antidepressant (AD) efficacy of LT was supported by several open‐label studies, three randomized controlled trials (RCTs), and one pseudorandomized controlled trial. SD showed rapid, acute AD response rates of 43.9%, 59.3%, and 59.4% in eight case series, 11 uncontrolled, studies, and one RCT, respectively. Adjunctive DT obtained significant, rapid anti‐manic results in one RCT and one controlled study. The seven studies on MA yielded very limited data on acute antidepressant a...

Research paper thumbnail of Evidence for the Efficacy of Bright Light Therapy for Bipolar Depression

The American journal of psychiatry, 2018

Research paper thumbnail of Patterns of Regional Cerebral Blood Flow as a Function of Age Throughout the Lifespan

Journal of Alzheimer's disease : JAD, Jan 3, 2018

Understanding the influence of aging on the brain remains a challenge in determining its role as ... more Understanding the influence of aging on the brain remains a challenge in determining its role as a risk factor for Alzheimer's disease. To identify patterns of aging in a large neuroimaging cohort. A large psychiatric cohort of 31,227 individuals received brain SPECT at rest and during a concentration task for a total of 62,454 scans. ANOVA was done to identify the mean age trends over the course of the age range in this group, 0- 105 years. A regression model in which brain SPECT regions of interest was used to predict chronological age (CA) was then utilized to derive brain estimated age (BEA). The difference between CA and BEA was calculated to determine increased brain aging in common disorders in our sample such as depression, dementia, substance use, and anxiety. Throughout the lifespan, variations in perfusion were observed in childhood, adolescence, and late life. Increased brain aging was seen in alcohol use, cannabis use, anxiety, bipolar, schizophrenia, attention-defi...

Research paper thumbnail of Clinical Neurochemical Implications of Sleep Deprivation's Effects on the Anterior Cingulate of Depressed Responders

Neuropsychopharmacology, 2001

The antidepressant and cerebral metabolic effects of total sleep deprivation (TSD) or partial sle... more The antidepressant and cerebral metabolic effects of total sleep deprivation (TSD) or partial sleep deprivation (PSD) for one night has been studied with functional neuroimaging in seven publications from five different groups. Despite the variations in methods and techniques, the overall findings were relatively consistent. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders and normal controls, in the orbital medial prefrontal cortex, and especially the ventral portions of the anterior cingulate cortex. Second, after sleep deprivation, these hyperactive areas normalize in the responders. One functional imaging study suggested that synaptic dopamine release was associated with the antidepressant effects of TSD. The neurochemical implications of these findings are explored. Possible dopaminergic and serotonergic mechanisms are discussed.

Research paper thumbnail of CRY2 Is Associated with Depression

PLoS ONE, 2010

Background: Abnormalities in the circadian clockwork often characterize patients with major depre... more Background: Abnormalities in the circadian clockwork often characterize patients with major depressive and bipolar disorders. Circadian clock genes are targets of interest in these patients. CRY2 is a circadian gene that participates in regulation of the evening oscillator. This is of interest in mood disorders where a lack of switch from evening to morning oscillators has been postulated.

Research paper thumbnail of Decreasing Striatal 6-FDOPA Uptake with Increasing Duration of Cocaine Withdrawal

Neuropsychopharmacology, 1997

It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence o... more It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold 1985; Markou and Koob 1991). This study measured striatal 6-fluorodopa (6-FDOPA) uptake, an index of dopaminergic presynaptic activity, using positron emission tomography (PET) in 11 drug-free cocaine addicts compared to eight normal subjects.

Research paper thumbnail of Frontal Lobe Metabolic Decreases with Sleep Deprivation not Totally Reversed by Recovery Sleep

Neuropsychopharmacology, 2006

We studied the effects of total sleep deprivation and recovery sleep in normal subjects using pos... more We studied the effects of total sleep deprivation and recovery sleep in normal subjects using position emission tomography with 18Fdeoxyglycose. Sleep deprivation resulted in a significant decrease in relative metabolism of the frontal cortex, thalamus, and striatum. Recovery sleep was found to have only a partial restorative effect on frontal lobe function with minimal reversal of subcortical deficits. Sleep may be especially important for maintenance of frontal lobe activity.

Research paper thumbnail of D1 receptor alleles predict PET metabolic correlates of clinical response to clozapine

Molecular Psychiatry, 2003

Research paper thumbnail of Reversing Brain Damage in Former NFL Players: Implications for Traumatic Brain Injury and Substance Abuse Rehabilitation

Journal of Psychoactive Drugs, 2011

View related articles Citing articles: 44 View citing articles Amen et al.

Research paper thumbnail of Impact of Playing American Professional Football on Long-Term Brain Function

Journal of Neuropsychiatry, 2011

The authors recruited 100 active and former National Football League players, representing 27 tea... more The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brainimaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Research paper thumbnail of Cardiovascular phase relationships to the cortical event-related potential of schizophrenic, depressed, and normal subjects

Biological Psychiatry, 1992

Cardiovascular phase, especially diastole, influences attention and the event-related potential (... more Cardiovascular phase, especially diastole, influences attention and the event-related potential (ERP) of the right hemisphere of the brain. Depression and schizophrenia are characterized by attentional deficits, unique lateralization of brain function, and deviant phase relationships of biological oscillators. In the present study, the ERP was recorded during stimulation triggered by diastole and systole in control (n = 16), depressed (n = 16), and schizophrenic (n = 9) subjects. Fifty tones were presented and subjects were instructed to count them silently. Previous findings were supported of delayed latencies and increased amplitude in depressed patients and decreased amplitudes and delayed latencies in schizophrenics. An exaggerated effect of diastole on the ERP in the right hemisphere was observed in depressed patients, however, no cardiovascular effect on the ERP was apparent in schizophrenic patients. Results suggested that heartlbrain networks are tightly coupled in normal controls, perhaps "overdriven" in depressed patients, and uncoupled in schizophrenics.

Research paper thumbnail of Rapid and Sustained Antidepressant Response with Sleep Deprivation and Chronotherapy in Bipolar Disorder

Biological Psychiatry, 2009

BACKGROUND: The development of a rapid-acting and sustainable treatment for bipolar disorder (BPD... more BACKGROUND: The development of a rapid-acting and sustainable treatment for bipolar disorder (BPD) depression has been a goal for decades. The most widely documented rapid-onset antidepressant therapy is sleep deprivation (SD), which acts within 24-48 hours in 40%-60% of depressed patients. Conventional antidepressants usually require 2-8 weeks to meet response criteria. The delay, which may prolong suffering and increase suicidal risk, underlines the urgency of alternative treatment strategies. This study evaluates the combined efficacy of three established circadian-related treatments (SD, bright light [BL]), sleep phase advance [SPA]) as adjunctive treatment to lithium and antidepressants. METHODS: Forty-nine BPD patients were randomly assigned to a chronotherapeutic augmentation (CAT; SD+ BL+ SPA) or to a medication-only (MED) group. Clinical outcome was assessed using the Hamilton Rating Scale for Depression. RESULTS: Significant decreases in depression in the CAT versus MED patients were seen within 48 hours of SD and were sustained over a 7-week period. CONCLUSIONS: This is the first study to demonstrate the benefit of adding three noninvasive circadian-related interventions to SD in medicated patients to accelerate and sustain antidepressant responses and provides a strategy for the safe, fast-acting, and sustainable treatment of BPD.

Research paper thumbnail of Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ε4 carriers

Alzheimer's & Dementia, 2012

BackgroundThe possibility that ε4 may modulate the effects of fitness in the brain remains contro... more BackgroundThe possibility that ε4 may modulate the effects of fitness in the brain remains controversial. The present exploratory FDG‐PET study aimed to better understand the relationship among ε4, fitness, and cerebral metabolism in 18 healthy aged women (nine carriers, nine noncarriers) during working memory.MethodsParticipants were evaluated using maximal level of oxygen consumption, California Verbal Learning Test, and FDG‐PET, which were collected at rest and during completion of the Sternberg working memory task.ResultsResting FDG‐PET did not differ between carriers and noncarriers. Significant effects of fitness on FDG‐PET during working memory were noted in the ε4 carriers only. High fit ε4 carriers had greater glucose uptake in the temporal lobe than the low fit ε4 carriers, but low fit ε4 carriers had greater glucose uptake in the frontal and parietal lobes.ConclusionsWe demonstrate that fitness differentially affects cerebral metabolism in ε4 carriers only, consistent wit...

Research paper thumbnail of Cortical glucose metabolic rate correlates of abstract reasoning and attention studied with positron emission tomography

Research paper thumbnail of Case report: Significant quantitative MRI brain volumetric finding associated with electrical brain injury

Research paper thumbnail of Wu JC, Buchsbaum MS, Johnson JC, Hershey TG, Wagner EA, Teng C et al. Magnetic resonance imaging and positron emission tomography imaging of the corpus callosum: size, shape and metabolic rate in unipolar depression. J Affect Disord 28: 15-25

Journal of Affective Disorders

Research paper thumbnail of Brain glucose metabolism during non-rapid eye movement sleep in major depression: A positron emission tomography study

Archives of General Psychiatry

Depression is characterized by several sleep-related abnormalities shortly before and after sleep... more Depression is characterized by several sleep-related abnormalities shortly before and after sleep onset, such as prolonged sleep latency, loss of stage 3-4 sleep, reduced rapid eye movement (REM) latency, increased nocturnal core body temperature, and abnormal hormone secretion patterns. Sleep deprivation is associated with a temporary improvement in depression. We hypothesized that depressed patients may be "overaroused" and that absolute cerebral glucose metabolism would be elevated during the first nocturnal non-REM sleep period in depressed patients compared with normal controls. In addition, since hypofrontality (greater metabolic activity in occipital compared with frontal cortical activity) has been reported in waking positron emission tomographic studies of depressed patients compared with controls, we predicted significant hypofrontality in depressed patients during the first non-REM period. Positron emission tomography with fludeoxy-glucose F 18 was used to compa...

Research paper thumbnail of Wu, J. et al. Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and the medial prefrontal cortex. Am. J. Psychiatry 156, 1149-1158

American Journal of Psychiatry

Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed pat... more Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingul...

Research paper thumbnail of Localized and lateralized cerebral glucose metabolism associated with eye movements during REM sleep and wakefulness: a positron emission tomography (PET) study

Sleep, 1995

In order to study the neural substrate for eye movements during rapid eye movement (REM) sleep, w... more In order to study the neural substrate for eye movements during rapid eye movement (REM) sleep, we analyzed the positron emission tomography (18Fluorodeoxyglucose positron emission tomography) scan data obtained from normal subjects. Eye movement data were available on nine subjects studied during nighttime REM sleep and six control subjects studied during waking as they periodically moved their eyes. The number of eye movements during REM sleep was positively correlated with glucose metabolic rate in the areas corresponding to (a) the saccadic eye movement system (frontal eye field and dorsolateral prefrontal cortex, statistically significant only on the right side), (b) the midline attentional system (cingulate and medial frontal cortex, precuneus) and (c) the parietal visual spatial attentional system (bilateral superior parietal lobules, right inferior parietal lobule); and negatively correlated with relative metabolic rate in the left inferior parietal lobule. Positive correlat...

Research paper thumbnail of Prediction of Antidepressant Effects of Sleep Deprivation by Metabolic Rates in the Ventral Anterior Cingulate and Medial Prefrontal Cortex

American Journal of Psychiatry

Objective: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of de... more Objective: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. Method: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. Results: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. Conclusions: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.

Research paper thumbnail of The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology

Bipolar Disorders, 2019

AimsTo systematically review the literature on the efficacy and tolerability of the major chronot... more AimsTo systematically review the literature on the efficacy and tolerability of the major chronotherapeutic treatments of bipolar disorders (BD)—bright light therapy (LT), dark therapy (DT), treatments utilizing sleep deprivation (SD), melatonergic agonists (MA), interpersonal social rhythm therapy (IPSRT), and cognitive behavioral therapy adapted for BD (CBTI‐BP)—and propose treatment recommendations based on a synthesis of the evidence.MethodsPRISMA‐based systematic review of the literature.ResultsThe acute antidepressant (AD) efficacy of LT was supported by several open‐label studies, three randomized controlled trials (RCTs), and one pseudorandomized controlled trial. SD showed rapid, acute AD response rates of 43.9%, 59.3%, and 59.4% in eight case series, 11 uncontrolled, studies, and one RCT, respectively. Adjunctive DT obtained significant, rapid anti‐manic results in one RCT and one controlled study. The seven studies on MA yielded very limited data on acute antidepressant a...

Research paper thumbnail of Evidence for the Efficacy of Bright Light Therapy for Bipolar Depression

The American journal of psychiatry, 2018

Research paper thumbnail of Patterns of Regional Cerebral Blood Flow as a Function of Age Throughout the Lifespan

Journal of Alzheimer's disease : JAD, Jan 3, 2018

Understanding the influence of aging on the brain remains a challenge in determining its role as ... more Understanding the influence of aging on the brain remains a challenge in determining its role as a risk factor for Alzheimer's disease. To identify patterns of aging in a large neuroimaging cohort. A large psychiatric cohort of 31,227 individuals received brain SPECT at rest and during a concentration task for a total of 62,454 scans. ANOVA was done to identify the mean age trends over the course of the age range in this group, 0- 105 years. A regression model in which brain SPECT regions of interest was used to predict chronological age (CA) was then utilized to derive brain estimated age (BEA). The difference between CA and BEA was calculated to determine increased brain aging in common disorders in our sample such as depression, dementia, substance use, and anxiety. Throughout the lifespan, variations in perfusion were observed in childhood, adolescence, and late life. Increased brain aging was seen in alcohol use, cannabis use, anxiety, bipolar, schizophrenia, attention-defi...

Research paper thumbnail of Clinical Neurochemical Implications of Sleep Deprivation's Effects on the Anterior Cingulate of Depressed Responders

Neuropsychopharmacology, 2001

The antidepressant and cerebral metabolic effects of total sleep deprivation (TSD) or partial sle... more The antidepressant and cerebral metabolic effects of total sleep deprivation (TSD) or partial sleep deprivation (PSD) for one night has been studied with functional neuroimaging in seven publications from five different groups. Despite the variations in methods and techniques, the overall findings were relatively consistent. First, before sleep deprivation, responders have significantly elevated metabolism compared with non-responders and normal controls, in the orbital medial prefrontal cortex, and especially the ventral portions of the anterior cingulate cortex. Second, after sleep deprivation, these hyperactive areas normalize in the responders. One functional imaging study suggested that synaptic dopamine release was associated with the antidepressant effects of TSD. The neurochemical implications of these findings are explored. Possible dopaminergic and serotonergic mechanisms are discussed.

Research paper thumbnail of CRY2 Is Associated with Depression

PLoS ONE, 2010

Background: Abnormalities in the circadian clockwork often characterize patients with major depre... more Background: Abnormalities in the circadian clockwork often characterize patients with major depressive and bipolar disorders. Circadian clock genes are targets of interest in these patients. CRY2 is a circadian gene that participates in regulation of the evening oscillator. This is of interest in mood disorders where a lack of switch from evening to morning oscillators has been postulated.

Research paper thumbnail of Decreasing Striatal 6-FDOPA Uptake with Increasing Duration of Cocaine Withdrawal

Neuropsychopharmacology, 1997

It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence o... more It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold 1985; Markou and Koob 1991). This study measured striatal 6-fluorodopa (6-FDOPA) uptake, an index of dopaminergic presynaptic activity, using positron emission tomography (PET) in 11 drug-free cocaine addicts compared to eight normal subjects.

Research paper thumbnail of Frontal Lobe Metabolic Decreases with Sleep Deprivation not Totally Reversed by Recovery Sleep

Neuropsychopharmacology, 2006

We studied the effects of total sleep deprivation and recovery sleep in normal subjects using pos... more We studied the effects of total sleep deprivation and recovery sleep in normal subjects using position emission tomography with 18Fdeoxyglycose. Sleep deprivation resulted in a significant decrease in relative metabolism of the frontal cortex, thalamus, and striatum. Recovery sleep was found to have only a partial restorative effect on frontal lobe function with minimal reversal of subcortical deficits. Sleep may be especially important for maintenance of frontal lobe activity.

Research paper thumbnail of D1 receptor alleles predict PET metabolic correlates of clinical response to clozapine

Molecular Psychiatry, 2003

Research paper thumbnail of Reversing Brain Damage in Former NFL Players: Implications for Traumatic Brain Injury and Substance Abuse Rehabilitation

Journal of Psychoactive Drugs, 2011

View related articles Citing articles: 44 View citing articles Amen et al.

Research paper thumbnail of Impact of Playing American Professional Football on Long-Term Brain Function

Journal of Neuropsychiatry, 2011

The authors recruited 100 active and former National Football League players, representing 27 tea... more The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brainimaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Research paper thumbnail of Cardiovascular phase relationships to the cortical event-related potential of schizophrenic, depressed, and normal subjects

Biological Psychiatry, 1992

Cardiovascular phase, especially diastole, influences attention and the event-related potential (... more Cardiovascular phase, especially diastole, influences attention and the event-related potential (ERP) of the right hemisphere of the brain. Depression and schizophrenia are characterized by attentional deficits, unique lateralization of brain function, and deviant phase relationships of biological oscillators. In the present study, the ERP was recorded during stimulation triggered by diastole and systole in control (n = 16), depressed (n = 16), and schizophrenic (n = 9) subjects. Fifty tones were presented and subjects were instructed to count them silently. Previous findings were supported of delayed latencies and increased amplitude in depressed patients and decreased amplitudes and delayed latencies in schizophrenics. An exaggerated effect of diastole on the ERP in the right hemisphere was observed in depressed patients, however, no cardiovascular effect on the ERP was apparent in schizophrenic patients. Results suggested that heartlbrain networks are tightly coupled in normal controls, perhaps "overdriven" in depressed patients, and uncoupled in schizophrenics.

Research paper thumbnail of Rapid and Sustained Antidepressant Response with Sleep Deprivation and Chronotherapy in Bipolar Disorder

Biological Psychiatry, 2009

BACKGROUND: The development of a rapid-acting and sustainable treatment for bipolar disorder (BPD... more BACKGROUND: The development of a rapid-acting and sustainable treatment for bipolar disorder (BPD) depression has been a goal for decades. The most widely documented rapid-onset antidepressant therapy is sleep deprivation (SD), which acts within 24-48 hours in 40%-60% of depressed patients. Conventional antidepressants usually require 2-8 weeks to meet response criteria. The delay, which may prolong suffering and increase suicidal risk, underlines the urgency of alternative treatment strategies. This study evaluates the combined efficacy of three established circadian-related treatments (SD, bright light [BL]), sleep phase advance [SPA]) as adjunctive treatment to lithium and antidepressants. METHODS: Forty-nine BPD patients were randomly assigned to a chronotherapeutic augmentation (CAT; SD+ BL+ SPA) or to a medication-only (MED) group. Clinical outcome was assessed using the Hamilton Rating Scale for Depression. RESULTS: Significant decreases in depression in the CAT versus MED patients were seen within 48 hours of SD and were sustained over a 7-week period. CONCLUSIONS: This is the first study to demonstrate the benefit of adding three noninvasive circadian-related interventions to SD in medicated patients to accelerate and sustain antidepressant responses and provides a strategy for the safe, fast-acting, and sustainable treatment of BPD.

Research paper thumbnail of Cardiovascular fitness is associated with altered cortical glucose metabolism during working memory in ε4 carriers

Alzheimer's & Dementia, 2012

BackgroundThe possibility that ε4 may modulate the effects of fitness in the brain remains contro... more BackgroundThe possibility that ε4 may modulate the effects of fitness in the brain remains controversial. The present exploratory FDG‐PET study aimed to better understand the relationship among ε4, fitness, and cerebral metabolism in 18 healthy aged women (nine carriers, nine noncarriers) during working memory.MethodsParticipants were evaluated using maximal level of oxygen consumption, California Verbal Learning Test, and FDG‐PET, which were collected at rest and during completion of the Sternberg working memory task.ResultsResting FDG‐PET did not differ between carriers and noncarriers. Significant effects of fitness on FDG‐PET during working memory were noted in the ε4 carriers only. High fit ε4 carriers had greater glucose uptake in the temporal lobe than the low fit ε4 carriers, but low fit ε4 carriers had greater glucose uptake in the frontal and parietal lobes.ConclusionsWe demonstrate that fitness differentially affects cerebral metabolism in ε4 carriers only, consistent wit...

Research paper thumbnail of Cortical glucose metabolic rate correlates of abstract reasoning and attention studied with positron emission tomography

Research paper thumbnail of Case report: Significant quantitative MRI brain volumetric finding associated with electrical brain injury

Research paper thumbnail of Wu JC, Buchsbaum MS, Johnson JC, Hershey TG, Wagner EA, Teng C et al. Magnetic resonance imaging and positron emission tomography imaging of the corpus callosum: size, shape and metabolic rate in unipolar depression. J Affect Disord 28: 15-25

Journal of Affective Disorders

Research paper thumbnail of Brain glucose metabolism during non-rapid eye movement sleep in major depression: A positron emission tomography study

Archives of General Psychiatry

Depression is characterized by several sleep-related abnormalities shortly before and after sleep... more Depression is characterized by several sleep-related abnormalities shortly before and after sleep onset, such as prolonged sleep latency, loss of stage 3-4 sleep, reduced rapid eye movement (REM) latency, increased nocturnal core body temperature, and abnormal hormone secretion patterns. Sleep deprivation is associated with a temporary improvement in depression. We hypothesized that depressed patients may be "overaroused" and that absolute cerebral glucose metabolism would be elevated during the first nocturnal non-REM sleep period in depressed patients compared with normal controls. In addition, since hypofrontality (greater metabolic activity in occipital compared with frontal cortical activity) has been reported in waking positron emission tomographic studies of depressed patients compared with controls, we predicted significant hypofrontality in depressed patients during the first non-REM period. Positron emission tomography with fludeoxy-glucose F 18 was used to compa...

Research paper thumbnail of Wu, J. et al. Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and the medial prefrontal cortex. Am. J. Psychiatry 156, 1149-1158

American Journal of Psychiatry

Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed pat... more Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingul...

Research paper thumbnail of Localized and lateralized cerebral glucose metabolism associated with eye movements during REM sleep and wakefulness: a positron emission tomography (PET) study

Sleep, 1995

In order to study the neural substrate for eye movements during rapid eye movement (REM) sleep, w... more In order to study the neural substrate for eye movements during rapid eye movement (REM) sleep, we analyzed the positron emission tomography (18Fluorodeoxyglucose positron emission tomography) scan data obtained from normal subjects. Eye movement data were available on nine subjects studied during nighttime REM sleep and six control subjects studied during waking as they periodically moved their eyes. The number of eye movements during REM sleep was positively correlated with glucose metabolic rate in the areas corresponding to (a) the saccadic eye movement system (frontal eye field and dorsolateral prefrontal cortex, statistically significant only on the right side), (b) the midline attentional system (cingulate and medial frontal cortex, precuneus) and (c) the parietal visual spatial attentional system (bilateral superior parietal lobules, right inferior parietal lobule); and negatively correlated with relative metabolic rate in the left inferior parietal lobule. Positive correlat...