Progesterone Attenuates the Stress Response in Individuals with Alcohol Dependence and Post-Traumatic Stress Disorder - A Pilot Study.

OBJECTIVE: Evidence from laboratory studies suggests that progesterone may be effective in reducing stress and craving, and may improve cognitive performance in smokers and individuals with cocaine dependence. The objective of this study was to examine if progesterone would attenuate stress-induced craving, anxiety, affect and physiological measures, as well as improve stress-induced cognitive performance (processing speed and selective attention) in individuals diagnosed with alcohol use disorder (AUD) and post traumatic stress disorder (PTSD). METHODS: This laboratory study included (n = 13) participants who were diagnosed with current AUD and PTSD who were randomly assigned to recive either progesterone (200mg bid) or placebo in identical looking capsules for 3 days. On the fourth day they completed a laboratory session. In the morning of the test session, they received the last dose of medication and completed the rest of the laboratory procedures. The procedures included presentation in random order of personalized trauma and neutral scripts with relaxation in between. Main outcomes included measure of craving, anxiety, affect and cognitive performance. RESULTS: Consistent with other research, trauma scripts produced significantly greater increases in craving, anxiety and negative affect when compared with neutral scripts. Progesterone significantly reduced stress-induced symptoms of craving, anxiety, fear, anger and sadness but had no effect on positive emotions (joy, relaxation). Progesterone was effective in ameliorating stress-induced decreases in cognitive performance. CONCLUSIONS: The findings from this study demonstrate that progesterone can be effective in reducing stress-induced craving, anxiety and negative affect in a laboratory setting in individuals with comorbid AUD and PTSD. Interestingly, progesterone also improved cognitive performance. These findings require replication in a larger clinical trial and may have implications for treatment among individuals with AUD and PTSD.This study was registered as NCT02187224, at www.clinicaltrials.gov.

Alcohol Craving and Psychiatric Disorders Among Current Drinkers.

BACKGROUND AND OBJECTIVES: Previous research has shown that alcohol craving is associated with psychiatric comorbidities. However, no population studies have examined the odds of psychiatric disorders in cravers and noncravers. The purpose of this study was to investigate current prevalence rates and odds ratios of psychiatric disorders among alcohol drinkers with and without alcohol craving in a population-based sample. We also compared four craving groups (cravers with and without alcohol use disorder [AUD], noncravers with and without AUD) for psychiatric comorbidities. METHODS: The study data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). A subset of the NESARC sample (N = 22 000) who reported alcohol use during the past 12 months was included. Prevalence rates of psychiatric disorders were compared among current drinkers with alcohol craving (N = 900) and without alcohol craving (N = 21 500). RESULTS: Cravers had higher prevalence rates of current psychiatric disorders than noncravers. Even after adjustment for other psychiatric disorders including AUD, cravers had significantly higher odds of any substance use disorder (adjusted odds ratio [AOR], 9.01), any mood disorder (AOR, 1.78), any anxiety disorder (AOR, 1.86), and any personality disorder (AOR, 1.92) than noncravers. Interestingly, cravers without AUD had even higher rates of any anxiety disorder and any personality disorder than noncravers with AUD. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Alcohol craving is associated with a higher prevalence of various psychiatric disorders. These findings suggest that alcohol craving may be related to transdiagnostic features that are present across various psychiatric disorders. (Am J Addict 2021;30:34-42).

Donepezil and cognitive remediation therapy to augment treatment of alcohol use disorder related mild cognitive impairment (AUD-MCI): An open label pilot study with historical controls.

Background: Pharmacological and psychosocial interventions have only modest efficacy for Alcohol Use Disorder (AUD), and continued alcohol use has brain effects on neurocognition, which place heavy drinkers at increased risk of early onset dementia. The most common neurocognitive deficits are in the domains of executive function and memory, and these deficits may impact AUD treatment outcomes. AUD related Mild Cognitive Impairment (AUD-MCI) is a diagnosis in DSM-V and ICD-10. Donepezil, a cholinesterase inhibitor, is currently FDA approved for treatment of dementia, and recent preclinical research suggests anticholinesterase agents may treat alcoholism. Another approach to cognitive recovery is Cognitive Remediation Therapy (CRT). Recent research supports CRT efficacy in schizophrenia and related disorders, and some research suggests that CRT could improve neurocognition in substance abuse disorders (SUDs). This is the first report of an open-label clinical trial that combined donepezil with CRT to improve neurocognitive and clinical outcomes in the early phase of AUD recovery. Methods: Eleven older male US Veterans with AUD-MCI as determined by Level II neurocognitive criteria and who had recently relapsed participated in an open-label trial of 13 weeks of donepezil combined with CRT. They were compared with matched historical control samples on neurocognitive and clinical outcomes. Results: Participants had excellent adherence to donepezil and CRT. Neurocognitive improvements were highly significant on a composite score of learning and memory and executive function measures (p < .0001) and was significantly better than historical matched controls (p < .001). On a Clinical Global Impression scale, 90.9% of participants had a good clinical recovery compared with 59.5% of historical matched controls (p <.052). Conclusions: AUD-MCI has not received much research attention but is of considerable public health importance. Findings in this open-label trial of donepezil + CRT should encourage further investigation into the clinical benefit of this combined treatment for AUD-MCI.

Zonisamide as an Adjunctive Treatment to Cognitive Processing Therapy for Veterans With Posttraumatic Stress Disorder and Comorbid Alcohol Use Disorder: A Pilot Study.

BACKGROUND AND OBJECTIVES: There are high rates of comorbid alcohol use disorder (AUD) among those who have posttraumatic stress disorder (PTSD). Ideally, treatment for comorbidity should address both disorders simultaneously. Zonisamide, an anticonvulsant, may be effective in decreasing alcohol use and may attenuate symptoms of PTSD. Treatment strategies can include medication in combination with a proven evidence-based psychotherapy designed to treat PTSD, such as cognitive processing therapy (CPT). METHODS: This 12-week pilot study was designed to test feasibility, acceptability, and preliminary efficacy of zonisamide (400 mg) as an adjunct to CPT for veterans with PTSD and comorbid AUD. Veterans (n = 24) with PTSD and current alcohol dependence were randomized in a 3:1 ratio to receive zonisamide or placebo in a double-blind fashion. All subjects received CPT enhanced to include sessions addressing drinking behavior. RESULTS: Subjects overall reported a significant decrease in drinking outcomes, craving, and symptoms of PTSD. Zonisamide was well-tolerated and easily administered with CPT, which was also well-tolerated. Exploratory analysis of comparison of groups suggests there was no advantage of zonisamide vs placebo in drinking or PTSD outcomes. There was a numeric but nonsignificant higher rate of abstinence with zonisamide (50%) vs placebo (33%). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: The interpretation of the results is limited by the pilot nature of this study. The combination of psychosocial treatment with medication management mimics real-world treatment. In order to isolate the individual contributions of medication vs psychotherapy a much larger study would need to be conducted. (Am J Addict 2020;29:515-524).

Methadone-Related Delirium: Prevalence, Causes, and Outcomes.

Goals consist of determining 5-year prevalence and recurrence of methadone-related delirium (MRD), along with causes, treatments, and outcomes. Sample comprised 81 patients in methadone maintenance treatment. Criteria for MRD encompassed delirium with high methadone serum levels plus alleviation of delirium upon lowering methadone serum levels. MRD occurred in 14 cases who had 25 episodes. MRD precipitants included physician prescribing (i.e., excessive methadone or medications slowing methadone metabolism), drug misuse, and renal-fluid alterations. Social affiliation (housing with family, intimate partner) reduced MRD; employment increased MRD. Recovery occurred in 23/25 episodes of MRD; two episodes progressed to dementia. Obtaining serum methadone levels fostered prompt recognition.

A Pilot Randomized, Placebo-Controlled Trial of Glycine for Treatment of Schizophrenia and Alcohol Dependence.

Objectives: The hypofunctioning of N-methyl-D-aspartate (NMDA) receptors are thought to play an important role in the pathophysiology of schizophrenia. The augmentation of the glutamatergic system through the NMDA receptor may attenuate alcohol craving and use. This study was designed to evaluate the efficacy of glycine, an agonist of the glycine B co-agonist site of the NMDA receptor on alcohol consumption and cravings as well as on negative symptoms in schizophrenia. Methods: Participants (N = 20) were given 0.8 g/kg glycine or matching placebo (provided in bottles with mixed in solution) each week for the duration of the 12-week trial. Primary outcome measures included drinking, craving for alcohol, and symptoms of schizophrenia. Cognitive functioning (attention, concentration, and memory) was also evaluated. Results: Glycine showed no benefit over placebo in the reduction of heavy drinking days or craving for alcohol over a 12-week treatment period. Nor was there an effect on negative symptoms of schizophrenia or on cognitive functioning. Conclusions: Although our study showed no beneficial effect of glycine over placebo, our results are consistent with the largest trial of glycine treatment in schizophrenia. Diagnosed schizophrenia and alcohol dependence might be more difficult to treat because of more severe psychopathology. This is the first study to date to examine an innovative treatment approach with an amino acid, glycine, as potentially acting on both alcohol intake and negative symptoms of schizophrenia.

Long QTc During Methadone Maintenance: Contributors and Interventions Over 4 Years.

Our goal consisted of describing the 4-year prevalence, contributors, and interventions for long QTc's in methadone maintenance treatment. Cardiologists' diagnosis of long QTc defined case-ness in 62 patients. Long QTc categories, drawn from epidemiological reports, encompassed 440 to 469 (borderline), 470 to 499 (moderate), and 500+ milliseconds (severe). Data collection included electrocardiograms, demographic characteristics, contributors to long QTc, and interventions-plus-outcomes (defined by resolution of long QTc). Of 62 patients, 21 had 39 long QTc episodes-a 4-year case prevalence of 34%, and an annual episode incidence of 15.7 per 100. Contributing factors identified in 36 of 39 episodes consisted of medication management (n = 19), illicit drug use (n = 11), and other factors (n = 6). Long QTc reverted to normal in 38 of 39 episodes. Of 21 patients, 12 (57%) experienced one or two recurrences. Methadone maintenance treatment physicians normalized most episodes as outpatients, often in collaboration with patients' primary care physicians. One fifth of episodes required hospitalization and other specialty care. Lack of timely QTc normalization may have accounted for one sudden death.

Effect of Antidepressant Switching vs Augmentation on Remission Among Patients With Major Depressive Disorder Unresponsive to Antidepressant Treatment: The VAST-D Randomized Clinical Trial.

IMPORTANCE: Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. OBJECTIVE: To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. DESIGN, SETTING, AND PARTICIPANTS: From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. INTERVENTIONS: Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). MAIN OUTCOMES AND MEASURES: The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C16] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. RESULTS: Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. CONCLUSIONS AND RELEVANCE: Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01421342.

Methadone maintenance dose/weight ratio, long QTc, and EKG screening.

BACKGROUND AND OBJECTIVES: Electrocardiogram (EKG) monitoring during methadone maintenance treatment (MMT) has been recommended to prevent potentially fatal prolonged computed QT intervals (QTc). However, risk indicators for obtaining EKGs do not exist. This study assessed 23 variables that might help identify prolonged QTc during MMT. METHODS: EKGs concurrent with methadone serum levels were obtained from 69 veterans during a 5-year study, encompassing 302.8 person-years. Two cardiologists hand-measured QT intervals, selecting each patient's longest QTc. QTc categories included: normal duration <440 ms; borderline duration of 440-469 ms; and abnormal duration ≥470 ms. QTc's were compared with seven methadone parameters and 16 bio-psycho-social variables using two QTc cut-offs (440 and 470 ms). RESULTS: Among the 69 patients, 19 had normal QTc's, 28 had borderline QTc's, and 22 had abnormal QTc's. Methadone dose/weight was moderately correlated with QTc, and independently associated with longer QTc at both 440 and 470 cut-offs. DISCUSSION AND CONCLUSION: Dose/weight ≥.49 is useful for screening EKGs for QTc's ≥440 cut-off. Dose/weight ≥.65 produces high-yield abnormal QTc's ≥470 cut-off. SCIENTIFIC SIGNIFICANCE: Methadone dose/weight provides moderately reliable thresholds for making routine screening decisions and urgent clinical decisions to obtain an EKG for prolonged QTc. (Am J Addict 2016;25:499-507).

Correlates of major depressive disorder with and without comorbid alcohol use disorder nationally in the veterans health administration.

BACKGROUND AND OBJECTIVES: This study assesses medical and psychiatric comorbidities, service utilization, and psychotropic medication prescriptions in veterans with comorbid major depressive disorder (MDD) and alcohol use disorder (AUD) relative to veterans with MDD alone. METHODS: Using cross-sectional administrative data (fiscal year [FY]2012: October 1, 2011-September 30, 2012) from the Veterans Health Administration (VHA), we identified veterans with a diagnosis of current (12-month) MDD nationally (N = 309,374), 18.8% of whom were also diagnosed with current (12-month) AUD. Veterans with both MDD and AUD were compared to those with MDD alone on sociodemographic characteristics, current (12-month) medical and psychiatric disorders, service utilization, and psychotropic prescriptions. We then used logistic regression analyses to calculate odds ratio and 95% confidence interval of characteristics that were independently different between the groups. RESULTS: Dually diagnosed veterans with MDD and AUD, relative to veterans with MDD alone, had a greater number of comorbid health conditions, such as liver disease, drug use disorders, and bipolar disorder as well as greater likelihood of homelessness and higher service utilization. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Dually diagnosed veterans with MDD and AUD had more frequent medical and psychiatric comorbidities and more frequently had been homeless. These data suggest the importance of assessing the presence of comorbid medical/psychiatric disorders and potential homelessness in order to provide appropriately comprehensive treatment to dually diagnosed veterans with MDD and AUD and indicate a need to develop more effective treatments for combined disorders.

Suicidal ideation and suicide attempts in five groups with different severities of gambling: Findings from the National Epidemiologic Survey on Alcohol and Related Conditions.

BACKGROUND AND OBJECTIVES: Problem and pathological gamblers show high rates of suicidal behavior. However, previous research of suicide among this population has been inconsistent. Discrepancies may stem from methodological issues, including variable use of suicide nomenclature and selection bias in study samples. Furthermore, earlier research has rarely examined gambling severity aside from problem or pathological categories. This study utilized subgroups derived from a nationally representative data set, examining different characteristics of suicidal behavior and several gambling levels, including subclinical groups. METHODS: Participants included 13,578 individuals who participated in the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and provided information on gambling behavior, lifetime suicidal ideation, and/or lifetime suicide attempts. Five gambling groups were derived using DSM-IV criteria for pathological gambling; non-gambling, low-risk gambling, at-risk gambling, problem gambling, and pathological gambling. RESULTS: Problem gambling was associated with suicidal ideation [adjusted odds ratio (AOR) = 1.64, 95% confidence interval (CI) = 1.19-2.26] and suicide attempts [(AOR) = 2.42, 95% (CI) = 1.60-3.67] after adjustment for sociodemographic variables. Pathological gambling was associated with suicidal ideation [(AOR) = 2.86, 95% (CI) = 1.98-4.11] and suicide attempts [(AOR) = 2.77, 95% (CI) = 1.72-4.47) after adjustment for sociodemographic variables. DISCUSSION, CONCLUSIONS, AND SCIENTIFIC SIGNIFICANCE: Our results from this population sample reinforce increased rates of suicidal behavior amongst smaller, clinical samples of problem and pathological gamblers. Education for providers about gambling is recommended, including screening for gambling-related symptoms such as suicidal behavior.

Internalizing disorder in adopted versus non-adopted adults: a NESARC based study.

The objective of the study consisted of comparing lifetime prevalence rates and odds ratios of anxiety, mood, and psychotic disorders in adopted-versus-non-adopted people in a nationally representative sample. The data were drawn from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). The main outcome measure was the prevalence of lifetime internalizing psychiatric disorders in adopted (n=378) versus non-adopted (n=42,503) individuals. Adoptees and non-adoptees were compared to estimate the odds of lifetime internalizing disorders using logistic regression analyses. Adoptees had higher prevalence rates of several lifetime mood and anxiety disorders compared with non-adoptees, with a 1.61-fold increase (95% CI 1.29-2.02) in the odds of any mood disorder and a 1.49-fold increase (95% CI 1.18-1.89) in the odds of any anxiety disorder compared with non-adoptees. Regarding specific mood and anxiety disorders, adoptees had increased odds of major depressive disorder, bipolar I disorder, panic disorder without agoraphobia, specific phobia, and generalized anxiety disorder. Disorders not differing between adoptees and non-adoptees included dysthymia, bipolar II disorder, panic disorder with agoraphobia, social phobia, and psychotic disorder. One adoption-specific risk factor was associated with lifetime mood disorder (i.e., Asian/Pacific Island). In conclusion, adoptees in a large sample from the general population had higher rates of mood and anxiety disorders compared to non-adoptees.

Altered corollary discharge in the auditory cortex could reflect louder inner voice experience in patients with verbal hallucinations, a pilot fMRI study.

INTRODUCTION: Wide range of evidence associates auditory verbal hallucinations (AVH) with frontotemporal corollary discharge deficit. AVH likely reflect altered experiences of the inner voice and are phenomenologically diverse. The aspects of hallucinations (and related inner voice experiences) that could be explained by this deficit remain unclear. To address this important subject, we examined the temporal cortex activity during two tasks with and without corollary discharge. METHODS: We carried out an event-related BOLD fMRI study to examine temporal cortex activity in seven patients and eight healthy controls during two tasks with and without corollary discharge: reading aloud and hearing, respectively. Data were denoised by removing independent components related to head movement and subsequently processed using finite impulse response basis function to address hemodynamic response variations. To mitigate the small sample size, final analyses were carried out using permutation-based analysis of variance. RESULTS: There was a significant group interaction in the Read relative to Hear condition during the early post-stimulus stage in the left Heschl's Gyrus (p<0.01, corrected for multiple comparisons, at peak voxel [-72,53,41]). This effect was driven by a higher activity in the Read relative to the Hear condition in the same area in the patients (p<0.02, corrected). CONCLUSIONS: Our results are consistent with prior literature indicating abnormal frontotemporal disconnection in participants with hallucinations. The functional repercussions of this deficit were limited to the primary auditory cortex in early post-stimulus stage, which suggests louder experience of the inner voice in patients and could account for the loudness of their hallucinations.

Altered corollary discharge in the auditory cortex could reflect louder inner voice experience in patients with verbal hallucinations, a pilot fMRI study.

INTRODUCTION: Wide range of evidence associates auditory verbal hallucinations (AVH) with frontotemporal corollary discharge deficit. AVH likely reflect altered experiences of the inner voice and are phenomenologically diverse. The aspects of hallucinations (and related inner voice experiences) that could be explained by this deficit remain unclear. To address this important subject, we examined the temporal cortex activity during two tasks with and without corollary discharge. METHODS: We carried out an event-related BOLD fMRI study to examine temporal cortex activity in seven patients and eight healthy controls during two tasks with and without corollary discharge: reading aloud and hearing, respectively. Data were denoised by removing independent components related to head movement and subsequently processed using finite impulse response basis function to address hemodynamic response variations. To mitigate the small sample size, final analyses were carried out using permutation-based analysis of variance. RESULTS: There was a significant group interaction in the Read relative to Hear condition during the early post-stimulus stage in the left Heschl's Gyrus (p < 0.01, corrected for multiple comparisons, at peak voxel [-72,53,41]). This effect was driven by a higher activity in the Read relative to the Hear condition in the same area in the patients (p < 0.02, corrected). CONCLUSIONS: Our results are consistent with prior literature indicating abnormal frontotemporal disconnection in participants with hallucinations. The functional repercussions of this deficit were limited to the primary auditory cortex in early post-stimulus stage, which suggests louder experience of the inner voice in patients and could account for the loudness of their hallucinations.

Safety, tolerability, and feasibility of high-dose naltrexone in alcohol dependence: an open-label study.

OBJECTIVE: Prior trials testing standard-dose naltrexone (50 mg/day) have generated mixed results in the treatment of alcohol dependence. The purpose of this study was to evaluate the short-term safety, tolerability, and feasibility of high-dose naltrexone (150 mg/day) for treating alcohol-dependent patients with prominent alcohol craving. METHODS: Twenty-four alcohol-dependent outpatients received high-dose naltrexone at a dose of 150 mg/day in an 8-week open-label pilot study. All patients had current alcohol dependence and alcohol craving symptoms. Safety and tolerability were assessed weekly. Liver function tests were obtained at weeks 0, 3, 5, 7, and 9. The main outcome measures were percentage of drinking days and number of drinks per drinking day. RESULTS: High-dose naltrexone was safe and well tolerated using the procedure described. No serious adverse effects were reported. The mean of γ-glutamyl transferase showed an improvement trend (p = 0.06), and other hepatic transaminase profiles were stable during the trial. High-dose naltrexone significantly reduced alcohol consumption (percentage of drinking days (p < 0.0001); and number of drinks per drinking day (p < 0.0001)). CONCLUSIONS: High-dose naltrexone may serve as a viable treatment option for alcohol-dependent patients with prominent alcohol craving. Further controlled studies are needed to confirm our findings.

Keeping the inner voice inside the head, a pilot fMRI study.

INTRODUCTION: The inner voice is experienced during thinking in words (inner speech) and silent reading and evokes brain activity that is highly similar to that associated with external voices. Yet while the inner voice is experienced in internal space (inside the head), external voices (one's own and those of others) are experienced in external space. In this paper, we investigate the neural basis of this differential spatial localization. METHODS: We used fMRI to examine the difference in brain activity between reading silently and reading aloud. As the task involved reading aloud, data were first denoised by removing independent components related to head movement. They were subsequently processed using finite impulse response basis function to address the variations of the hemodynamic response. Final analyses were carried out using permutation-based statistics, which is appropriate for small samples. These analyses produce spatiotemporal maps of brain activity. RESULTS: Reading silently relative to reading aloud was associated with activity of the "where" auditory pathway (Inferior parietal lobule and middle temporal gyrus), and delayed activity of the primary auditory cortex. CONCLUSIONS: These pilot data suggest that internal space localization of the inner voice depends on the same neural resources as that for external space localization of external voices-the "where" auditory pathway. We discuss the implications of these findings on the possible mechanisms of abnormal experiences of the inner voice as is the case in verbal hallucinations.

Measuring cultural identity: validation of a modified Cortes, Rogler and Malgady Bicultural Scale in three ethnic groups in New York.

Cultural identity is central to health. Acculturation may be formulated with a bicultural model, assessing in parallel the degree of identification with both the original and the host culture. The Cortes, Rogler and Malgady Bicultural Scale (CRM-BS) is composed of two subscales: "original" culture and "mainstream-United States" (US) culture. It was modified into three ethnic versions: Latino, Korean and Chinese. Validation of the CRM-BS was conducted using health professionals and psychiatric patients from the above three ethnic groups and a control sample of mainstream-US (main-US) health professionals in New York City (n = 394). Mean time of completion was 3.7 min and 73% judged it to be easy to use. Strong test-retest reliability correlation coefficients were found (original culture, 0.78; mainstream-US, 0.82). The internal consistency was documented by high Cronbach's alpha values (original culture, 0.88; mainstream-US, 0.80). Factorial analysis revealed two factors, the first one involving all the items of the original culture and the second all of the mainstream-US items. Concerning its discriminant validity, non-main-US subjects scored significantly higher than main-US subjects on the original culture subscale, and vice versa. Construct validity was assessed comparing intergenerational mean scores on both subscales; as generations become older, mean scores for the original culture decreased, while those for the "host" culture increased. Results for each specific ethnic version are also presented. Cutoff scores were calculated to categorize the involvement with the original culture or the host culture, both of them, or neither.