Thomas B. Cooper

Baylor College of Medicine, Houston, Texas, United States

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Publications (400)2459.86 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Many, but not all studies of suicide attempters' cortisol response to stress-either social stress or pharmacological challenge-report an exaggerated response. Recent studies of resting baseline cortisol in past suicide attempters, however, have found lower baseline levels. Methods: In this study, baseline salivary cortisols were obtained prior to a stress procedure from adults with lifetime diagnoses of a mood disorder (N=69), 31.9% of whom had made a prior suicide attempt. Data were collected during the piloting of this stress procedure, at various times of day and with/without an additional confederate in the room. Results: Adjusting for procedural, demographic and clinical variables that affect salivary cortisol levels-including time of day of sampling, order of procedure with respect to other assessments, past alcohol abuse, current medication use, and bipolar diagnosis-past suicide attempters had lower baseline cortisol levels compared to non-attempters. Limitations: This is a pilot study with modest sample sizes using statistical, rather than experimental control of numerous variables affecting salivary cortisol levels. Conclusions: Results confirm previous studies. Low baseline cortisol levels have been associated with childhood adversity and externalizing disorders, suggesting a potential role in reducing inhibitions for risky and dangerous behaviors. Further research is needed to more fully characterize these associations and their role in suicidal behavior risk.
    Journal of Affective Disorders 10/2015; 190:187-192. DOI:10.1016/j.jad.2015.10.012 · 3.38 Impact Factor
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    ABSTRACT: Studies looking at the relationship of the hypothalamic-pituitary-adrenal axis (HPA) to suicidal behavior and its risk factors, such as depression, childhood abuse, and impulsive aggression, report inconsistent results. These studies also do not always differentiate between subjects who go on to attempt suicide, suicidal subjects who never attempted suicide, and non-suicidal subjects with psychiatric disorders. In this study, we examined cortisol responses to an experimental stressor, the Trier Social Stress Test (TSST), in 208 offspring of parents with mood disorder. Offspring suicide attempters showed lower total cortisol output [β=-0.47, 95% CI (-0.83, -0.11), p=0.01] compared to offspring with suicide-related behavior but never attempted, non-suicidal offspring, and a healthy control group. The result remained significant even after controlling for sex, age, race, ethnicity, site, socioeconomic status, and hour of the day when the TSST was conducted. Suicide attempters also showed lower baseline cortisol prior to the TSST [β=-0.45, 95% CI (-0.74, -0.17), p=0.002]. However, there were no significant differences between the groups on cortisol reactivity to stress [β=4.5, 95% CI (-12.9, 22), p=0.61]. Although subjects with suicide attempt and suicide-related behavior have similar clinical and psychosocial characteristics, this is the first study to differentiate them biologically on HPA axis indices. Blunted HPA axis activity may increase risk for suicide attempt among individuals with psychopathology by reducing their ability to respond adaptively to ongoing stressors. These results may help better identify subjects at high-risk for suicidal behavior for targeted prevention and intervention efforts.Neuropsychopharmacology accepted article preview online, 09 October 2015. doi:10.1038/npp.2015.309.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 10/2015; DOI:10.1038/npp.2015.309 · 7.05 Impact Factor
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    ABSTRACT: The N-methyl-D-aspartate receptor antagonist ketamine can improve major depressive disorder (MDD) within hours. To evaluate the putative role of glutamatergic and GABAergic systems in ketamine's antidepressant action, medial prefrontal cortical (mPFC) levels of glutamate+glutamine (Glx) and γ-aminobutyric acid (GABA) were measured before, during, and after ketamine administration using proton magnetic resonance spectroscopy. Ketamine (0.5 mg kg(-1) intravenously) was administered to 11 depressed patients with MDD. Glx and GABA mPFC responses were measured as ratios relative to unsuppressed voxel tissue water (W) successfully in 8/11 patients. Ten of 11 patients remitted (50% reduction in 24-item Hamilton Depression Rating Scale and total score ⩽10) within 230 min of commencing ketamine. mPFC Glx/W and GABA/W peaked at 37.8%±7.5% and 38.0%±9.1% above baseline in ~26 min. Mean areas under the curve for Glx/W (P=0.025) and GABA/W (P=0.005) increased and correlated (r=0.796; P=0.018). Clinical improvement correlated with 90-min norketamine concentration (df=6, r=-0.78, P=0.023), but no other measures.Molecular Psychiatry advance online publication, 18 August 2015; doi:10.1038/mp.2015.83.
    Molecular Psychiatry 08/2015; DOI:10.1038/mp.2015.83 · 14.50 Impact Factor

  • SOBP 2015; 05/2015

  • SOBP 2015; 05/2015
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    ABSTRACT: Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n=22) and without (n=39) history of suicide attempt, and age- and sex-matched healthy volunteers (n=59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator (LASSO) logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.
    Frontiers in Neurology 04/2015; 6. DOI:10.3389/fneur.2015.00092
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    ABSTRACT: Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (i.e. quicker and higher peak concentrations). Here, we evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic the clinical drug delivery profile. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20,30,or 60 mg/kg/day; as well as dual-dosages of 4 and 10 mg/kg/day, 20 and 30 mg/kg/day, or 30 and 60 mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 hours of drinking the high dose). Blood was sampled and plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60 mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~ 30 ng/mL), while the 4/10 mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~ 8 ng/mL). Treatment with the higher dual-dosage (HD; 30/60 mg/kg) resulted in hyperactivity, while the lower (LD; 4/10 mg/kg) had no effect. Next, chronic effects of these dual-dosages were assessed on behavior throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle; decreased exploratory behavior; and increased anxiolytic behavior. These findings suggest that this dual-dosage-drinking-paradigm can be used to examine the effects of clinically relevant pharmacokinetic doses of MP, and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes.
    Pharmacology Biochemistry and Behavior 01/2015; 131. DOI:10.1016/j.pbb.2015.01.005 · 2.78 Impact Factor
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    ABSTRACT: Background Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems. Methods and MaterialsPatients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale. ResultsPsychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA. Conclusions Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients.
    Depression and Anxiety 10/2014; 31(10). DOI:10.1002/da.22278 · 4.41 Impact Factor
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    ABSTRACT: Major depressive disorder (MDD) is associated with low levels of omega-3 polyunsaturated fatty acids (PUFAs), holding promise for new perspectives on disease etiology and treatment targets. As aggressive and impulsive behaviors are associated with low omega-3 PUFA levels in some clinical contexts, we investigated plasma PUFA relationships with trait aggression and impulsivity in patients with MDD. Medication-free MDD patients (n=48) and healthy volunteers (HV, n=35) were assessed with the Brown-Goodwin Aggression Inventory. A subset (MDD, n=39; HV, n=33) completed the Barratt Impulsiveness Scale. Plasma PUFAs eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6) were quantified and ln-transformed to mitigate distributional skew. Ln-transformed PUFA (lnPUFA) levels were predictors in regression models, with aggression or impulsivity scores as outcomes, and cofactors of sex and diagnostic status (MDD with or without a history of substance use disorder [SUD], or HV). Interactions were tested between relevant PUFAs and diagnostic status. Additional analyses explored possible confounds of depression severity, self-reported childhood abuse history, and, in MDD patients, suicide attempt history. Among PUFA, lnEPA but not lnDHA predicted aggression (F1,76=12.493, p=0.001), and impulsivity (F1,65=5.598, p=0.021), with interactions between lnEPA and history of SUD for both aggression (F1,76=7.941, p=0.001) and impulsivity (F1,65=3.485, p=0.037). Results remained significant when adjusted for childhood abuse, depression severity, or history of suicide attempt. In conclusion, low EPA levels were associated with aggression and impulsivity only in patients with MDD and comorbid SUD, even though in most cases SUD was in full sustained remission.
    Journal of Psychiatric Research 10/2014; 57(1). DOI:10.1016/j.jpsychires.2014.06.012 · 3.96 Impact Factor
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    ABSTRACT: Background Considerable evidence suggests that testosterone may play a role in the pathophysiology of mood disorders in females. This is the first prospective study to examine whether blood testosterone levels predict suicide attempts in females with bipolar disorder. Methods Females with a DSM-IV diagnosis of a bipolar disorder in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. Patients were followed up prospectively for up to 2.5 years. Results At baseline, testosterone levels positively correlated with the number of previous major depressive episodes and suicide attempts. Cox proportional hazards regression analysis found that higher baseline testosterone levels predicted suicide attempts during the follow-up period. Limitations A limitation of the study is that the sample size is modest. Another limitation is that we did not have a bipolar nonattempter or healthy volunteer control group for comparison. Conclusion Testosterone levels may predict suicidal behavior in women with bipolar disorder.
    Journal of Affective Disorders 09/2014; 166:98–102. DOI:10.1016/j.jad.2014.04.068 · 3.38 Impact Factor
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    J P Kahn · A S Perumal · R J Gully · T M Smith · T B Cooper · D F Klein ·
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    ABSTRACT: In 17 healthy young men who had a parent with documented early coronary disease, ratings of type A behaviour correlated with upregulated lymphocyte Beta2 receptor density and inversely with the ratio of platelet Alpha1 to lymphocyte Beta2 receptor density ratio. This indicates a correlation of type A behaviour with receptor based determinations of increased peripheral Alpha-adrenergic balance, consistent with increased coronary arterial vasoconstriction, perhaps leading to coronary artery disease.
  • Leo Sher · Maria A Oquendo · Ainsley K Burke · Thomas B Cooper · J John Mann ·
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    ABSTRACT: The hypothalamic-pituitary-adrenal (HPA) axis is dysfunctional in a subgroup of mood disorders. We compared cortisol and adrenocorticotropic hormone (ACTH) responses in major depression and healthy volunteers to the combined dexamethasone suppression-corticotrophin-releasing hormone stimulation (DEX-CRH) test. Unlike other published studies, the study patients were medication-free and the healthy volunteers did not have first-degree relatives with a mood or psychotic disorder. Demographics, DSM-IV diagnoses and other clinical parameters were evaluated in major depressive disorder (MDD) and healthy control groups. Participants received an oral dose of 1.5mg dexamethasone at 11pm the day before CRH administration. On the following day, at 3pm, 100µg of ovine CRH was infused. Blood samples for determination of cortisol and ACTH were collected every 15min from 3pm to 4:15pm. Cortisol and ACTH responses were calculated as areas under the curve. Controlling for age, baseline (i.e., post-dexamethasone) ACTH levels were higher in depressed patients compared to controls (p=0.01). There was a trend for higher ACTH responses in depressed patients compared to the control group (p=0.08). In depressed patients, cortisol and ACTH responses correlated positively with age, duration of illness and number of hospitalizations. Because of the cross-sectional study design we can only evaluate the nature of potential HPA axis disturbances that were present in patients when they are acutely depressed. Feedback inhibition of ACTH secretion by cortisol is compromised in MDD, and this is independent of an age effect on the HPA axis function.
    Journal of Affective Disorders 07/2013; 151(3). DOI:10.1016/j.jad.2013.06.049 · 3.38 Impact Factor
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    ABSTRACT: Although lower levels of omega-3 polyunsaturated fatty acids (PUFAs) are found in major depressive disorder, less is known about PUFA status and anxiety disorders. Medication-free participants with DSM-IV-defined major depressive disorder (MDD), with (n = 18) and without (n = 41) comorbid DSM-IV anxiety disorders, and healthy volunteers (n = 62) were recruited from October 2006 to May 2010 for mood disorder studies at the New York State Psychiatric Institute. Participants were 18-73 years of age (mean age, 35.8 ± 12.6 years). Depression and anxiety severity was assessed using depression and anxiety subscales from the 17-item Hamilton Depression Rating Scale. Plasma PUFAs eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) and the ratio of arachidonic acid (AA; 22:4n-6) to EPA (AA:EPA) were quantified. This secondary analysis employed analysis of variance with a priori planned contrasts to test for diagnostic group differences in log-transformed PUFA levels (logDHA, logEPA, and logAA:EPA). Plasma levels of logDHA (F2,118 = 4.923, P = .009), logEPA (F2,118 = 6.442, P = .002), and logAA:EPA (F2,118 = 3.806, P = .025) differed across groups. Participants with MDD had lower logDHA (t118 = 2.324, P = .022) and logEPA (t118 = 3.175, P = .002) levels and higher logAA:EPA levels (t118 = -2.099, P = .038) compared with healthy volunteers. Lower logDHA (t118 = 2.692, P = .008) and logEPA (t118 = 2.524, P = .013) levels and higher logAA:EPA levels (t118 = -2.322, P = .022) distinguished anxious from nonanxious MDD. Depression severity was not associated with PUFA plasma levels; however, anxiety severity across the entire sample correlated negatively with logDHA (rp = -0.22, P = .015) and logEPA (rp = -0.25, P = .005) levels and positively with logAA:EPA levels (rp = 0.18, P = .043). The presence and severity of comorbid anxiety were associated with the lowest EPA and DHA levels. Further studies are needed to elucidate whether omega-3 PUFA supplementation may preferentially alleviate MDD with more severe anxiety.
    The Journal of Clinical Psychiatry 07/2013; 74(7):732-8. DOI:10.4088/JCP.12m07970 · 5.50 Impact Factor
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    ABSTRACT: Objective: To determine whether starting antidepressant medication at the start of electroconvulsive therapy (ECT) reduces post-ECT relapse and to determine whether continuation pharmacotherapy with nortriptyline (NT) and lithium (Li) differs in efficacy or adverse effects from continuation pharmacotherapy with venlafaxine (VEN) and Li. Methods: During an acute ECT phase, 319 patients were randomized to treatment with moderate dosage bilateral ECT or high-dosage right unilateral ECT. They were also randomized to concurrent treatment with placebo, NT, or VEN. Of 181 patients to meet post-ECT remission criteria, 122 (67.4%) participated in a second continuation pharmacotherapy phase. Patients earlier randomized to NT or VEN continued on the antidepressant, whereas patients earlier randomized to placebo were now randomized to NT or VEN. Lithium was added for all patients who were followed until relapse or 6 months. Results: Starting an antidepressant medication at the beginning of the ECT course did not affect the rate or timing of relapse relative to starting pharmacotherapy after ECT completion. The combination of NT and Li did not differ from VEN and Li in any relapse or adverse effect measure. Older age was strongly associated with lower relapse risk, whereas the type of ECT administered in the acute phase and medication resistance were not predictive. Across sites, 50% of the patients relapsed, 33.6% continued in remission 6 months after ECT, and 16.4% dropped out. Conclusions: Starting an antidepressant medication during ECT does not affect relapse, and there are concerns about administering Li during an acute ECT course. Nortriptyline and VEN were equally effective in prolonging remission, although relapse rates after ECT are substantial despite intensive pharmacology. As opposed to the usual abrupt cessation of ECT, the impact of an ECT taper should be evaluated.
    The journal of ECT 01/2013; 29(1). DOI:10.1097/YCT.0b013e31826ea8c4 · 1.39 Impact Factor
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    ABSTRACT: The best known neurobehavioral effects of testosterone are on sexual function and aggression. However, testosterone and other androgens may be involved in the pathophysiology of mood disorders and suicidal behavior. This is the first study to examine whether there is a relation between testosterone levels and clinical parameters in bipolar suicide attempters. Patients with a DSM-IV diagnosis of a bipolar disorder (16 males and 51 females), in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters, including lifetime suicidal behavior, were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. The number of major depressive episodes, the maximum lethality of suicide attempts, and the testosterone levels were higher in men compared to women. Current suicidal ideation scores were higher in women compared to men. Controlling for sex, we found that testosterone levels positively correlated with the number of manic episodes and the number of suicide attempts. Our findings are consistent with previous observations of the association between testosterone levels and parameters of mood and behavior. This study suggests that testosterone levels may be related to the course of bipolar disorder and suicidal behavior. Further studies of the role of testosterone in the neurobiology of mood disorders and suicidal behavior are merited.
    Journal of Psychiatric Research 07/2012; 46(10):1267-71. DOI:10.1016/j.jpsychires.2012.06.016 · 3.96 Impact Factor
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    ABSTRACT: While the etiology of depression is not clearly understood at the present time, this mental disorder is thought be a complex and multifactorial trait with important genetic and environmental contributing factors. The role of the endocannabinoid (eCB) system in depressive behavior was examined in Wistar Kyoto (WKY) rat strain, a genetic model of depression. Our findings revealed selective abnormalities in the eCB system in the brains of WKY rats compared to Wistar (WIS) rats. Immunoblot analysis indicated significantly higher levels of fatty acid amide hydrolase (FAAH) in frontal cortex and hippocampus of WKY rats with no alteration in the level of N-arachidonyl phosphatidyl ethanolamine specific phospholipase-D (NAPE-PLD). Significantly higher levels of CB1 receptor-mediated G-protein coupling and lower levels of anandamide (AEA) were found in frontal cortex and hippocampus of WKY rats. While the levels of brain derived neurotropic factor (BDNF) were significantly lower in frontal cortex and hippocampus of WKY rats compared to WIS rats, pharmacological inhibition of FAAH elevated BDNF levels in WKY rats. Inhibition of FAAH enzyme also significantly increased sucrose consumption and decreased immobility in the forced swim test in WKY rats. These findings suggest a critical role for the eCB system and BDNF in the genetic predisposition to depressive-like behavior in WKY rats and point to the potential therapeutic utility of eCB enhancing agents in depressive disorder.
    PLoS ONE 05/2012; 7(5):e36743. DOI:10.1371/journal.pone.0036743 · 3.23 Impact Factor
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    ABSTRACT: In utero exposure to tetrahydrocannabinol, the psychoactive component of marijuana, is associated with an increased risk for neurodevelopmental defects in the offspring by interfering with the functioning of the endocannabinoid (eCB) system. At the present time, it is not clearly known whether the eCB system is present before neurogenesis. Using an array of biochemical techniques, we analyzed the levels of CB1 receptors, eCBs (AEA and 2-AG), and the enzymes (NAPE-PLD, DAGLα, DAGLβ, MAGL, and FAAH) involved in the metabolism of the eCBs in chick and mouse models during development. The findings demonstrate the presence of eCB system in early embryo before neurogenesis. The eCB system might play a critical role in early embryogenesis and there might be adverse developmental consequences of in utero exposure to marijuana and other drugs of abuse during this period.
    Birth Defects Research Part B Developmental and Reproductive Toxicology 04/2012; 95(2):137-50. DOI:10.1002/bdrb.20348 · 0.77 Impact Factor
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    ABSTRACT: There are mixed reports on nicotine's effects on alcohol-induced impairment in cognitive performance and behavior in humans. The main objective of this study was to characterize the interactive effects of acute intravenous (IV) alcohol and nicotine administration on behavior and cognition in healthy nonsmokers. Healthy subjects aged 21-44 years participated in 3 test days. On each test day, they received in a double-blind randomized manner one of three IV alcohol infusion conditions using a "clamp": placebo, targeted breathalyzer of 40 mg%, or targeted breathalyzer of 80 mg%. Alcohol infusion was delivered over 20 min and lasted for 120 min. They also received both placebo and active nicotine in a fixed order delivered intravenously. Placebo nicotine was delivered first over 10 min at the timepoint when the breath alcohol was "clamped"; active nicotine (1.0 mcg/kg/min) was delivered for 10 min, 70 min after the alcohol infusion was clamped. Subjective effects of alcohol were measured using the Biphasic Alcohol Effects Scale and the Number of Drinks Scale. Cognitive inhibition and attention were measured by the Continuous Performance Task-Identical Pairs and working memory by the Rey Auditory Verbal Learning Task (RAVLT). Nicotine significantly reversed subjective intoxication and sedation of alcohol at the low dose. Alcohol impaired performance on the RAVLT, and nicotine further impaired verbal learning and recall at both doses of alcohol. The data showed that nicotine had an effect on subjective alcohol effects but did not reverse and actually worsened alcohol-induced deficits in memory.
    Nicotine & Tobacco Research 12/2011; 14(5):596-606. DOI:10.1093/ntr/ntr258 · 3.30 Impact Factor
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    ABSTRACT: The present study was undertaken to examine whether genetically predetermined differences in components of the endocannabinoid system were present in the brain of Sardinian alcohol-preferring (sP) and Sardinian alcohol-non-preferring (sNP) rats, a pair of rat lines selectively bred for opposite alcohol preference. The effects of acquisition and maintenance of alcohol drinking, alcohol withdrawal, and alcohol re-exposure on the endocannabinoid system was also assessed in the striatum of sP rats. The findings revealed significantly higher density of the CB1 receptors and levels of CB1 receptor mRNA, CB1 receptor-mediated G-protein coupling, and endocannabinoids in the cerebral cortex, hippocampus and striatum of alcohol-naive sP rats than sNP rats. A significantly lower expression of mFAAH enzyme was evident in the hippocampus of alcohol-naive sP rats. Alcohol drinking (during both acquisition and maintenance phases) in sP rats resulted in a significant reduction in striatal CB1 receptor-mediated G-protein coupling whereas alcohol withdrawal attenuated this effect. Alcohol consumption was also associated with markedly increased levels of endocannabinoids in the striatum. Co-administration of the CB1 receptor antagonist, rimonabant (SR141716A) reduced alcohol intake, and reversed alcohol-induced changes in CB1 receptor-mediated G-protein activation. These findings provided a new insight into a potential genetic basis of excessive alcohol consumption, suggesting innate differences in the endocannabinoid system might be associated with higher alcohol preference in sP rats. The data also indicate a modulation of CB1 receptor-mediated signaling following alcohol consumption, and further strengthen the potential of the endocannabinoid system as a target for the treatment of alcohol related behaviors.
    Addiction Biology 02/2011; 17(1):62-75. DOI:10.1111/j.1369-1600.2010.00299.x · 5.36 Impact Factor
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    ABSTRACT: The role of n-3 polyunsaturated fatty acids (PUFAs) in psychiatric illness is a topic of public health importance. This report describes development and biomarker validation of a 21-item, self-report food frequency questionnaire (FFQ) intended for use in psychiatric research to assess intake of α-linolenic acid (18:3n-3 [ALA]), docosahexaenoic acid (22:6n-3 [DHA]), and eicosapentaenoic acid (20:5n-3 [EPA]). In a cross-sectional study conducted from September 2006 to September 2008, sixty-one ethnically diverse adult participants with (n=34) and without (n=27) major depressive disorder completed this n-3 PUFA FFQ and provided a plasma sample. Plasma levels of n-3 PUFAs EPA and DHA, and n-6 PUFA arachidonic acid (20:4n-6 [AA]) were quantified by gas chromatography. Using Spearman's ρ, FFQ-estimated intake correlated with plasma levels of DHA (r=0.50; P<0.0001) and EPA (r=0.38; P=0.002), but not with ALA levels (r=0.22; P=0.086). Participants were classified into quartiles by FFQ-estimated intake and plasma PUFA concentrations. Efficacy of the FFQ to rank individuals into same or adjacent plasma quartiles was 83% for DHA, 78.1% for EPA, and 70.6% for ALA; misclassification into extreme quartiles was 4.9% for DHA, 6.5% for EPA, and 8.2% for ALA. FFQ-estimated EPA intake and plasma EPA were superior to plasma AA levels as predictors of the plasma AA to EPA ratio. This brief FFQ can provide researchers and clinicians with valuable information concerning dietary intake of DHA and EPA.
    Journal of the American Dietetic Association 01/2011; 111(1):117-123.e1-2. DOI:10.1016/j.jada.2010.10.007 · 3.92 Impact Factor

Publication Stats

16k Citations
2,459.86 Total Impact Points


  • 2015
    • Baylor College of Medicine
      • Department of Pathology & Immunology
      Houston, Texas, United States
  • 1985-2015
    • Nathan Kline Institute
      Orangeburg, New York, United States
    • University of South Carolina
      • Department of Neuropsychiatry and Behavioral Science
      Columbia, South Carolina, United States
  • 1984-2015
    • New York State Psychiatric Institute
      • Anxiety Disorders Clinic
      New York, New York, United States
  • 1983-2014
    • Columbia University
      • • Department of Psychiatry
      • • Department of Anesthesiology
      • • College of Physicians and Surgeons
      New York, New York, United States
    • Buffalo Psychiatric Center
      Buffalo, New York, United States
  • 1981-2008
    • CUNY Graduate Center
      New York, New York, United States
  • 2004
    • William Penn University
      Filadelfia, Pennsylvania, United States
    • University of North Carolina at Chapel Hill
      North Carolina, United States
  • 2003
    • University of Kentucky
      Lexington, Kentucky, United States
  • 1997-2003
    • University of Pittsburgh
      • Department of Radiology
      Pittsburgh, Pennsylvania, United States
  • 2002
    • New York Presbyterian Hospital
      New York, New York, United States
  • 1998
    • University of Oslo
      Kristiania (historical), Oslo, Norway
  • 1993
    • Western Psychiatric Institute and Clinic
      Pittsburgh, Pennsylvania, United States
  • 1991
    • Keck School of Medicine USC
      Los Angeles, California, United States
    • Pennsylvania Psychiatric Institute
      Arkansas, United States
  • 1989
    • Gracie Square Hospital, New York, NY
      New York, New York, United States
  • 1987
    • Mount Sinai Medical Center
      New York, New York, United States
    • The Ohio State University
      • Department of Psychiatry
      Columbus, Ohio, United States
  • 1986
    • NYU Langone Medical Center
      New York, New York, United States
  • 1982
    • Analytical Research Laboratories
      Oklahoma City, Oklahoma, United States