Correction to: Molecular Psychiatry advance online publication, 14 August 2012; doi:10.1038/mp.2012.85 The name of coauthor LK Davis was omitted from the author line. Dr Davis should have been listed as the tenth author (between ER Gamazon and L Osiecki). Her affiliation is as follows: Department ofMedicine, University of Chicago, Chicago, IL, USA.

National security professionals have few scientifically valid methods for detecting deception in people who deny being involved in illicit activities relevant to national security. Numerous detecting deception studies have demonstrated that the Modified Cognitive Interviewing (MCI) method is one such method - yielding detecting deception rates (i.e. 80-85%) that are significantly above those achieved by chance (i.e. 50%) or by human judgments (i.e. 54-56%). To date, however, no MCI studies have involved dilemmas of ethological interest to national security professionals. This project begins to address this gap in the scientific literature. In it, we compared the efficacy of MCI to that of human judgments for detecting deception in scientists with expertise in biological materials. Sixty-four scientists were recruited for study; 12 met with a “terrorist” and were paid to make biological materials for illicit purposes. All 64 scientists were interviewed by investigators with law enforcement experience about the bio-threat issue. MCI elicited speech content differences in deceptive, compared to truthful scientists. This resulted in a classification accuracy of 84.4%; Accuracies for Human Judgments (interviewers/raters) were 54% and 46%, respectively. MCI required little time and its efficacy suggests it is reasonable to recommend its use to national security experts.

Correction to: Molecular Psychiatry (2006) 11, 622–632. doi: 10.1038/sj.mp.4001823 Following publication of the above article, the authors noted the following: while the captions for Figures 4 and 5 were correct, the actual figures themselves were incorrectly transposed. They appear correctly below:

BACKGROUND:Gamma-aminobutyric acid (GABA)ergic adaptations contribute to the neurobiology of ethanol dependence and withdrawal. Clinical data suggest that tobacco smoking attenuates alcohol withdrawal symptoms. This study's objective was to measure time-dependent cortical GABA levels with sobriety in ethanol-dependent patients with mild to moderate withdrawal severity, controlling for alcoholism-related neurotoxicity and smoking.METHODS:Proton magnetic resonance spectroscopy (MRS) was used to measure occipital cortical N-acetylaspartate (NAA), glutamate plus glutamine, and GABA in 12 ethanol-dependent men at approximately 1 week and 1 month of medication-free sobriety on an inpatient unit. Eight healthy men were studied once. The tissue composition of the MRS volume was determined.RESULTS:Adjusting for less white matter in patients, GABA differed insignificantly between ethanol-dependent patients (smokers plus nonsmokers) and healthy subjects. In early sobriety, nonsmoking patients had more GABA than did smoking patients, but by 1 month, GABA decreased in nonsmokers without changing in smokers. Smoking was associated with increased glutamate plus glutamine in patients and healthy subjects, adjusting for NAA levels.CONCLUSIONS:These data do not show that deficits in cortical GABA contribute directly to acute ethanol withdrawal. If smoking prevents withdrawal-related changes in cortical GABA systems, it may contribute to comorbidity of alcoholism and tobacco smoking.

RATIONALE:We recently conducted a pilot study supporting the feasibility, safety, and validity of a human laboratory model of ad libitum cocaine administration in which subjects self-selected the timing of infusions. The current study extends this work to include a randomized design with a test-retest component in a larger sample.OBJECTIVES:To investigate the regulation of cocaine intake by humans and its effects on subjective and cardiovascular responses.MATERIALS AND METHODS:Subjects were 14 non-treatment seeking volunteers (10 M, 4 F) with cocaine abuse/dependence. Subjects self-administered cocaine infusions (0, 8, 16, and 32 mg/70 kg) over a 2-h period under a fixed ratio 1, 5-min time-out schedule on 4 consecutive days. A fifth session was conducted at 16-mg dose to assess the paradigm's test-retest reliability.RESULTS:Subjects regulated their cocaine intake in a dose-dependent fashion. Self-reports of cocaine-related subjective effects (e.g., "high" and "stimulated") also varied in a dose-dependent way. Test-retest data and the randomized design support the conclusion that such effects are not due to tolerance or other experimental artifacts.CONCLUSION:The current study replicates prior work demonstrating the feasibility, safety, and validity of our human laboratory paradigm of cocaine administration in a larger sample using a randomized design. The current study also shows the test-retest reliability of these methods, establishing its utility for comparisons of experimental interventions (e.g., pharmacological treatments). Finally, the current study suggests that factors other than drug-induced euphoria (i.e., "high") contribute to the regulation of cocaine-taking behaviors in humans.

Sasso, David A. MD, MPH; Kalanithi, Paul S.A. MPhil; Trueblood, Kevin V. MD; Pittenger, Christopher MD, PhD; Kelmendi, Ben BA; Wayslink, Suzanne RN; Malison, Robert T. MD; Krystal, John H. MD; Coric, Vladimir MD Author Information

Background: Most patients with obsessive-compulsive disorder (OCD) show only partial reduction of symptoms with standard therapy. Recent imaging data suggests glutamatergic dysfunction in the corticostriatal pathway in OCD. We investigated the efficacy of augmentation therapy with riluzole, a glutamate-modulating agent, in treatment-resistant OCD.Methods: Thirteen patients aged between 18 and 65 years with a primary diagnosis of OCD that bad proven resistant to standard treatment were treated with the addition of riluzole to their existing pharmacotherapy. Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Inventory (HAM-D), and Hamilton Anxiety Inventory (HAM-A) scores were obtained weekly.Results., Thirteen treatment-resistant OCD patients received riluzole 50 mg twice a day. Y-BOCS scores improved significantly over time. Of 13 patients, 7 (54016) demonstrated a > 35% reduction in Y-BOCS scores, and 5 (3990 were categorized as treatment responders. HAM-D and HAM-A scores for the group also significantly improved over time. Riluzole was well tolerated with no serious adverse effects noted.Conclusions: Riluzole appears to have significant antiobsessional, antidepressant, and antianxiety properties. The addition of this agent may be of practical clinical benefit inpatients with OCD.

Sleep disturbance has been implicated in cocaine use; however, the nature of the disturbance and its potential effects on cognition and learning are largely unknown. Twelve chronic cocaine users completed a 23-day inpatient study that included randomized, placebo-controlled, cocaine self-administration sessions. Six subjects received cocaine on each of days 4–6 and placebo on days 18–20, the other six received cocaine on each of days 18–20 and placebo on days 4–6. Sleep was measured by polysomnography, the Nightcap® sleep monitor, and self-reported measures. Simple and vigilance reaction times were measured daily; a motor-sequence test of procedural learning was administered four times. Electrophysiological measures of sleep showed a different pattern than self-reported sleep across cocaine administration and abstinence: total sleep time and sleep latency were at their worst by 14–17 days of abstinence while self-reported sleep was at its best. Vigilance correlated positively with electrophysiologically measured sleep and negatively with self-reported measures. Similarly, sleep-dependent procedural learning correlated with total sleep time and was impaired at 17 days abstinence relative to 2- and 3-days abstinence. Slow-wave activity was lowest at days 4–9 of abstinence and highest during use and days 10–17 of abstinence. With sustained abstinence, chronic cocaine users exhibit decreased sleep, impaired vigilance and sleep-dependent procedural learning, and spectral activity suggestive of chronic insomnia. However, they report subjectively improving sleep, indicating they are unaware of this “occult” insomnia. These results suggest the possibility of homeostatic sleep drive dysregulation in chronic cocaine users.

Article AbstractBecause this piece has no abstract, we have provided for your benefit the first 3 sentences of the full text.Sir: Self-injurious behavior (SIB) in patients with borderlinepersonality disorder (BPD), especially cutting, represents aserious and often intractable clinical problem.1 There are fewvalidated pharmacologic strategies for managing SIB.1-3 Wedescribe our initial experience using glutamate-modulatingagents in 2 patients with BPD and prominent SIBs.†‹

Back to table of contents Previous article Next article Letter to the EditorFull AccessRiluzole Augmentation for Treatment-Resistant DepressionGERARD SANACORA, M.D., Ph.D., STEVEN F. KENDELL, M.D., LISA FENTON, Psy.D., VLADIMIR CORIC, M.D., and JOHN H. KRYSTAL, M.D., GERARD SANACORA, M.D., Ph.D., STEVEN F. KENDELL, M.D., LISA FENTON, Psy.D., VLADIMIR CORIC, M.D., and JOHN H. KRYSTAL, M.D., New Haven, Conn.Published Online:1 Nov 2004https://doi.org/10.1176/appi.ajp.161.11.2132AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Glutamate is implicated in the pathophysiology and treatment of mood disorders (1). The following case reports pertain to the use of riluzole, a putative antiglutamatergic agent indicated for the treatment of amyotrophic lateral sclerosis, as add-on therapy for treatment-resistant major depressive disorder.Ms. A was a 42-year-old woman with a history of major depressive disorder. Despite pharmacotherapy strategies, including fluoxetine, fluoxetine augmented with lithium, and her current regimen of bupropion (100 mg b.i.d.) and venlafaxine (up to 300 mg/day), she remained depressed, with scores of 21 on the 25-item Hamilton Depression Rating Scale and 17 on the Beck Depression Inventory. After we obtained written informed consent, riluzole, 50 mg b.i.d., was added to her current medication regimen. Within 1 week, her Hamilton depression scale and Beck Depression Inventory scores decreased by 16 and 10 points, respectively. Repeated measures of her depression severity reflected scores in the remitted range, with a score of 1 on the Hamilton depression scale and 0 on the Beck Depression Inventory at the end of 6 weeks and a Hamilton depression scale score of 4 and a Beck Depression Inventory score of 4 at the end of 12 weeks of continued treatment.Ms. B was a 55-year-old woman with a 33-year history of major depressive disorder. Her pharmacotherapy history included adequate courses of various tricyclic and selective serotonin reuptake inhibitor monotherapies, nefazodone, and the combination of sertraline and bupropion. Immediately after an index course of seven bifrontal ECT treatments, her Beck Depression Inventory score was 15; however, within 2 weeks, her score rose to 32 despite continued weekly ECT treatments. For the previous 6 months, while her mood was maintained with fluoxetine (80 mg/day), methylphenidate (58 mg/day), and ongoing cognitive behavior therapy, her Beck Depression Inventory scores fluctuated between 17 and 31. After we obtained written informed consent, treatment with riluzole, 50 mg b.i.d., was started. Ms. B's Hamilton depression scale and Beck Depression Inventory scores before riluzole were 34 and 27, respectively. Within 1 week, her Hamilton depression scale score dropped to 22, and her Beck Depression Inventory score decreased to 11. At week 6, her Hamilton depression scale and Beck Depression Inventory scores were both 7; at week 12, her scores were 9 and 5, respectively.Baseline laboratory evaluations, including liver function tests and a CBC with differential, were collected before study initiation. Additional tests were performed at 2–3-week intervals for 12 weeks and then monthly to monitor riluzole's known risk of serum aminotransferase elevations and neutropenia. Neither patient experienced significant aminotransferase elevations (more than five times the normal upper limits) or neutropenia or endorsed any other side effect.Although case studies necessitate cautious interpretation, these results are consistent with a recent finding suggesting riluzole's effectiveness in treating depression (2) and further substantiate accruing evidence indicating that several classes of glutamatergic agents possess antidepressant properties (3).References1. Sanacora G, Rothman DL, Mason GF, Krystal JH: Clinical studies implementing glutamate neurotransmission in mood disorders. Ann NY Acad Sci 2003; 1003:292–308Crossref, Medline, Google Scholar2. Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK: An open-label trial of riluzole in patients with treatment-resistant major depression. Am J Psychiatry 2004; 161:171–174Link, Google Scholar3. Paul IA, Skolnick P: Glutamate and depression: clinical and preclinical studies. Ann NY Acad Sci 2003; 1003:252–270Crossref, Google Scholar FiguresReferencesCited byDetailsCited byCombination therapy with neuropeptides for the treatment of anxiety disorderNeuropeptides, Vol. 86Pharmacology & Therapeutics, Vol. 204A Randomized Placebo-Controlled Cross-Over Pilot Study of Riluzole for Drug-Refractory Irritability in Autism Spectrum Disorder11 April 2018 | Journal of Autism and Developmental Disorders, Vol. 48, No. 9Inflammatory Mediators in Mood Disorders: Therapeutic OpportunitiesAnnual Review of Pharmacology and Toxicology, Vol. 58, No. 1Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression14 February 2017 | Drugs, Vol. 77, No. 4European Neuropsychopharmacology, Vol. 27, No. 5Journal of Psychiatric Research, Vol. 75Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 64International Journal of Neuropsychopharmacology, Vol. 18, No. 1Glutamate and its receptors in the pathophysiology and treatment of major depressive disorder8 December 2013 | Journal of Neural Transmission, Vol. 121, No. 8Glutamate Receptor Antagonists as Fast-Acting Therapeutic Alternatives for the Treatment of Depression: Ketamine and Other CompoundsAnnual Review of Pharmacology and Toxicology, Vol. 54, No. 1CNS Spectrums, Vol. 19, No. 2Glial Glutamate and Metabolic Transporters as a Target for Neurodegenerative Therapy and Biomarkers27 September 2014Ketamine, magnesium and major depression – From pharmacology to pathophysiology and backJournal of Psychiatric Research, Vol. 47, No. 7Biological Psychiatry, Vol. 73, No. 12An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression1 September 2012 | International Journal of Neuropsychopharmacology, Vol. 15, No. 8Glutamatergic antidepressants27 June 2012Psychopharmacology, Vol. 219, No. 3Neuropharmacology, Vol. 62, No. 1The International Journal of Neuropsychopharmacology, Vol. 15, No. 02Bipolar Disorders, Vol. 14, No. 1Neurotoxicity Research, Vol. 19, No. 2European Neuropsychopharmacology, Vol. 21Journal of Affective Disorders, Vol. 132Pharmacology & Therapeutics, Vol. 132, No. 3Psychopharm Review, Vol. 46, No. 12Magnetic Resonance Spectroscopy Studies of Glutamate-Related Abnormalities in Mood DisordersBiological Psychiatry, Vol. 68, No. 9Rapid Antidepressant Effect of Ketamine Anesthesia During Electroconvulsive Therapy of Treatment-Resistant DepressionThe Journal of ECT, Vol. 26, No. 3Neurochemical Research, Vol. 35, No. 8CNS Drugs, Vol. 24, No. 2Combining Medications to Achieve Remission17 August 2010Brain Research Reviews, Vol. 61, No. 2Journal of Affective Disorders, Vol. 118, No. 1-3Psychiatry Research: Neuroimaging, Vol. 173, No. 3Expert Opinion on Emerging Drugs, Vol. 14, No. 3Hippocampal N-Acetylaspartate Concentration and Response to Riluzole in Generalized Anxiety DisorderBiological Psychiatry, Vol. 63, No. 9European Archives of Psychiatry and Clinical Neuroscience, Vol. 258, No. S2Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 32, No. 1Journal of the American Academy of Child & Adolescent Psychiatry, Vol. 47, No. 11CNS Drugs, Vol. 22, No. 9Increased Levels of Glutamate in Brains from Patients with Mood DisordersBiological Psychiatry, Vol. 62, No. 11The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression24 April 2007 | Molecular Psychiatry, Vol. 12, No. 11Biological Psychiatry, Vol. 61, No. 6Biological Psychiatry, Vol. 61, No. 6Stress, Vol. 10, No. 3Expert Opinion on Drug Discovery, Vol. 2, No. 10Visual Hallucinations from the Addition of Riluzole to Memantine and BupropionJournal of Clinical Psychopharmacology, Vol. 26, No. 2Psychopharmacology, Vol. 184, No. 2NeuroRX, Vol. 3, No. 1European Journal of Neuroscience, Vol. 24, No. 12Expert Opinion on Investigational Drugs, Vol. 15, No. 12Expert Review of Neurotherapeutics, Vol. 6, No. 7Open-Label Trial of Riluzole in Generalized Anxiety DisorderSanjay J. 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In the course of training and in their work, military personnel are often required to spend considerable time under intense conditions with other people. Due to the performance demands and the intensity of the situations, the interactions between individuals may become charged with negative feelings of frustration, anger, as well as a sense of being without support. When these feelings are experienced for extended periods of time, they can be draining to an individual and can lead to burnout. Maslach and her group [1, 2] argue that our current concept of stress is too broad and subject to misinterpretation, since some stress might be "difficult" but positive in nature, or negative in nature etc. (the idea of eustress and distress). She has developed the concept of burnout to address how well a person is able to relate to his or her environment and has assessed this along an axis of emotional exhaustion, cynicism (or depersonalization a sense of disconnection from conspecifics) and personal accomplishment. Within this framework one might conceive of a situation where a person feels stress, but will react differently to that challenge depending on the balance between their sense of emotional exhaustion, disconnection from others, and personal accomplishment. In this vein of thought, we may have a higher capacity to tolerate very difficult situations as long as we feel we are accomplishing something worthwhile and as long as we are supported by those to whom we feel connected. Burnout is a non-psychiatric syndrome that has been mainly observed in individuals whose professional demands include a both

Although many people are exposed to trauma, only some develop stress related illnesses such as PTSD. Most do not. It is possible that individuals differ in the degree to which stress induces neurobiological perturbations of fear/alarm systems—resulting in a differential capacity to cope with highly threatening experiences. Pre clinical evidence supports the hypothesis that dysregulation of opposing neuro-transmitters involved in alarm responses may contribute to anxiety and stress vulnerability. We studied neurohormonal indices, psychological indices, and performance measures in two groups of soldiers participating in survival training. Subjects were tested at baseline, during threat, 24 hours after cessation of stress and at a 4 month follow up. Although subjective evaluations regarding stress did not differ between groups, there were significant differences in hormonal and psychological indices. In the stress hardy, special forces soldiers significantly greater levels of NPY, NE, and significantly lower levels of cortisol were observed in response to stress. In addition, significant depletions of E and NPY were observed in general troop soldiers. Correlations were observed between endocrine indices and psychological dissociation as well as performance. Regression analyses indicated that bioavailable cortisol accounted for 20% of the variance in performance, and 40% of the variance in physical health complaints. At the time of abstract preparation, data from the 4 month follow is being analyzed. The data from this study are consistent with the hypothesis that individuals differ significantly in the degree to which they are affected by stress. Such differences are related to constructs such as stress hardiness and stress vulnerability. Special Forces soldiers exhibit neuro endocrine response profiles similar to animals which have been stress toughened. The relationship between hormone responses, psychological dissociation and performance may provide clues regarding the neural factors involved in psychological and physical resilience to uncontrollable stress.

Previous investigation of the neuroendocrine responses of humans exposed to highly intense, uncontrollable stress indicate that special forces soldiers (Green Berets) differ significantly from general troop soldiers (Rangers/Marines). Although the two groups did not differ when assessed prior to stress exposure, significant differences became evident during and after stress exposure. HPA axis activation was significantly less, and NE release significantly greater in Special Forces soldiers. In addition, plasma NPY release during stress was also significantly greater in these individuals. 24 hours after stress exposure, NPY and E were depleted in general troop soldiers, but not in Special Forces troops.