Alcohol-dependent Patients (alcohol-dependent + patient)

Distribution by Scientific Domains


Selected Abstracts


Effects of Alcohol Cue Exposure on Response Inhibition in Detoxified Alcohol-Dependent Patients

ALCOHOLISM, Issue 9 2010
Siegfried Gauggel
Background:, There is evidence that exerting self-control during alcohol craving can diminish performance on subsequent tasks that require self-control. Based on the resource depletion model (Muraven and Baumeister, 2000), we examined the influence of alcohol cue exposure on detoxified alcohol-dependent patients' ability to inhibit ongoing responses. Methods:, Twenty alcohol-dependent patients were randomly assigned to an alcohol-cue exposure and a control-cue exposure condition and thereafter had to perform an inhibition task (i.e., stop-signal task). Results:, Participants who sniffed alcohol before performing the inhibition task reported a stronger urge to drink alcohol than the control group that sniffed water. Participants who sniffed alcohol were also impaired in their inhibitory performance but not in their noninhibitory performance on the stop-signal task. Conclusions:, The urge to drink presumably reduced participants' self-control, and this interfered with their ability to inhibit responding. [source]


Recruitment of Additional Brain Regions to Accomplish Simple Motor Tasks in Chronic Alcohol-Dependent Patients

ALCOHOLISM, Issue 6 2010
Mitchell H. Parks
Background:, Chronic alcohol-dependent patients (ALC) exhibit neurocognitive impairments attributed to alcohol-induced fronto-cerebellar damage. Deficits are typically found in complex task performance, whereas simple tasks may not be significantly compromised, perhaps because of little understood compensatory changes. Methods:, We compared finger tapping with either hand at externally paced (EP) or maximal self-paced (SP) rates and concomitant brain activation in ten pairs of right-hand dominant, age-, and gender-matched, severe, uncomplicated ALC and normal controls (NC) using functional magnetic resonance imaging (fMRI). Results:, Mean tapping rates were not significantly different in ALC and NC for either task, but SP tapping variances were greater in ALC for both hands. SP tapping was more rapid with dominant hand (DH) than non-dominant hand (NDH) for both groups. EP and SP tapping with the non-dominant hand demonstrated significantly more activation in ALC than NC in the pre and postcentral gyri, inferior frontal gyrus, inferior parietal lobule, and the middle temporal gyrus. Areas activated only by ALC (not at all by NC) during NDH tapping included the inferior frontal gyrus, middle temporal gyrus, and postcentral gyrus. There were no significant group activation differences with DH tapping. No brain regions activated more in NC than ALC. SP tapping in contrast to EP activated fronto-cerebellar networks in NC, including postcentral gyrus, anterior cingulate, and the anterior lobe and vermis of the cerebellum, but only parietal precuneus in ALC. Conclusions:, These findings with NDH finger tapping support previous reports of neurocognitive inefficiencies in ALC. Inferior frontal activation with EP in ALC, but not in NC, suggests engagement of regions needed for planning, organization, and impulse regulation; greater contralateral parietal lobe activation with SP in ALC may reflect right hemispheric impairments in visuospatial performance. Contrasting brain activation during SP and EP suggests that ALC may not have enlisted a fronto-cerebellar network as did NC but rather employed a higher order planning mode by recruiting parietal lobe functions to attain normal mean finger tapping rates. Elucidation of the compensatory neural mechanisms that allow near normal performance by ALC on simple tasks can inform functional rehabilitation of patients in recovery. [source]


Effect of Extended-Release Naltrexone (XR-NTX) on Quality of Life in Alcohol-Dependent Patients

ALCOHOLISM, Issue 2 2009
Helen M. Pettinati
Background:, Extended-release naltrexone (XR-NTX) is a once-a-month injectable formulation for the treatment of alcohol dependence previously shown to reduce drinking and heavy drinking relative to placebo (Garbutt et al., 2005). A 24-week, randomized, double-blind, placebo-controlled study established the efficacy and safety of XR-NTX in this patient population. In this report, the effect of XR-NTX on quality of life (QOL) was examined. Methods:, Alcohol-dependent patients were randomly assigned to receive XR-NTX 380 mg (N = 205), XR-NTX 190 mg (N = 210), or placebo (N = 209), combined with a standardized psychosocial intervention. QOL was assessed using the Medical Outcomes Study 36-item short-form health survey, administered at baseline and at 4-week intervals during 24 weeks of treatment. Results:, Compared with U.S. population norms, patients showed initial impairment in the health-related QOL domains of mental health, social functioning, and problems with work or other daily activities due to emotional problems. Adherence to all 6 injections was 65% for XR-NTX 190 mg, 63% for XR-NTX 380 mg, and 64% for placebo. Generalized estimating equations analyses using an intention-to-treat sample revealed that XR-NTX 380 mg was associated with significantly greater improvements from baseline in mental health (p = 0.0496), social functioning (p = 0.010), general health (p = 0.048), and physical functioning (p = 0.028), compared with placebo. Linear regression analyses revealed that reductions from baseline in drinking (percentage of drinking days and percentage of heavy drinking days in the last 30 days) were significantly (p < 0.05) correlated with improvements in quality of life. Conclusion:, Extended-release naltrexone 380 mg in combination with psychosocial intervention was associated with improvements in QOL, specifically in the domains of mental health, social functioning, general health, and physical functioning. [source]


Effects of Alcohol Withdrawal on 24 Hour Ambulatory Blood Pressure Among Alcohol-Dependent Patients

ALCOHOLISM, Issue 12 2003
Ramón Estruch
Background: Although epidemiologic studies have reported an association between alcohol intake and high blood pressure (BP), the results of intervention studies have shown inconsistent results. We embarked on a study to determine whether different subgroups of alcohol-dependent patients may be identified in relation to the effect of alcohol on BP. Methods: Fifty alcohol-dependent men (mean age, 41.4 years) received 0.4 g of ethanol per kilogram of body weight every 4 hr in 200 ml of orange juice during 24 hr and the same amount of orange juice without ethanol during another 24 hr. Twenty-four hour ambulatory BP monitoring was performed during ethanol and orange juice intakes, as was hormonal and biochemical analysis. Results: Thirty-five (75%) alcohol-dependent men were normotensive and 15 (30%) hypertensive. Eighteen (51%) normotensive and 12 (80%) hypertensive subjects showed a significant decrease in 24 hr mean BP after ethanol withdrawal (mean decrease of 8.4 mm Hg [95% confidence interval, ,11.2 to ,5.7] and 12.5 mm Hg [confidence interval, ,16.2 to ,8.8], respectively) and were considered as sensitive to alcohol. The remaining alcohol-dependent subjects were considered as resistant to alcohol. Normotensive subjects sensitive to ethanol showed a significantly greater left ventricular mass and a significantly lower ejection fraction than those normotensive patients whose BP did not change after ethanol withdrawal (both p < 0.01). Conclusions: More than three fourths of the hypertensive and more than half of the normotensive alcohol-dependent patients showed sensitivity to the pressor effects of ethanol. Impairment also was observed in heart function in normotensive patients sensitive to the pressor effects of ethanol. [source]


The European NEAT Program: An Integrated Approach Using Acamprosate and Psychosocial Support for the Prevention of Relapse in Alcohol-Dependent Patients With a Statistical Modeling of Therapy Success Prediction

ALCOHOLISM, Issue 10 2002
Isidore Pelc
Background A multicenter, prospective study was conducted in five European countries to observe outcome in alcohol misusers treated for 24 weeks with acamprosate and various psychosocial support techniques, within the setting of standard patient care. Methods Patients diagnosed as alcohol dependent using DSM-III-R criteria were treated, for 24 weeks, with acamprosate and appropriate psychosocial support. Potential predictor variables were recorded at inclusion. Drinking behavior was monitored throughout; the proportion of cumulative abstinence days was the principal outcome measure. The influence of baseline clinical and demographic variables on outcome was assessed using multiple regression analysis. Adverse events were recorded systematically. Results A total of 1289 patients were recruited; 1230 took at least one dose of the drug and provided at least one set of follow-up data; 543 (42.1%)patients were observed for the full 24-week period. The overall proportion of cumulative abstinence days was 0.48. Multiple physical and psychiatric comorbidities and a history of drug addiction were negatively correlated with outcome, as were, to a lesser extent, multiple previous episodes of detoxification, unemployment, and living alone. Older age and stable employment were positively associated with outcome. The difference in the unadjusted proportion of cumulative abstinence days between countries was significant (p < 0.001) but less so when adjusted for the predictive factors identified in the multivariate model (p < 0.019). Overall, outcome was not influenced by the nature of the psychosocial support provided. Adverse events were generally mild, with gastrointestinal disorders, which occurred in 21.5% of patients, being the most frequent. Conclusions This open-label study confirms the efficacy and safety of acamprosate in the treatment of alcohol dependence in the setting of standard patient care. Treatment benefit was observed irrespective of the nature of the psychosocial support provided. Predictors of the response to treatment were identified; their heterogeneous distribution within the study population explained, at least in part, the differences in outcome between countries. [source]


Recollective experience in alcohol dependence: a laboratory study

ADDICTION, Issue 12 2008
Patrizia Thoma
ABSTRACT Aims Alcohol dependence has been linked to dysfunction of fronto-temporo-striatal circuits which mediate memory and executive function. The present study aimed to explore the specificity of recognition memory changes in alcohol dependence. Design, setting and participants Twenty hospitalized alcohol-dependent detoxified patients and 20 healthy control subjects completed a verbal list discrimination task. Measurements Hits and false alarm rates were analysed. Additionally, both the dual process signal detection model (DPSD) and the process dissociation procedure (PDP) were used to derive estimates of the contribution of recollection and familiarity processes to the recognition memory performance in patients and controls. Findings Alcohol-dependent patients showed intact hit rates, but increased false alarm rates and an impaired ability to remember the learning context. Both the DPSD model and PDP estimates yielded significantly reduced recollection estimates in the alcohol-dependent compared to control subjects. Whether or not familiarity was impaired, depended upon the sensitivity of the estimation procedure. Conclusion Taken together, the result pattern suggests a significant impairment in recollection and mild familiarity changes in recently detoxified, predominantly male, alcohol-dependent subjects. [source]


Polymorphisms of the IL-1 Gene Complex Are Associated With Alcohol Dependence in Spanish Caucasians: Data From an Association Study

ALCOHOLISM, Issue 12 2009
Pilar A. Saiz
Background:, There is growing evidence for involvement of pro-inflammatory cytokines in alcohol dependence. The aim of this study was to investigate whether 4 functionally relevant polymorphisms of the interleukin-1 (IL-1) and tumor necrosis factor-alpha genes were associated with alcohol dependence and with measures of clinical severity and treatment outcome. Methods:, Two hundred alcohol-dependent (AD) patients and 420 healthy controls from the same Spanish Caucasian population were genotyped using standard methods. Baseline and 6-month assessments included alcohol intake, addiction severity, and biomarkers of alcohol intake. Results:, Alcohol-dependent patients showed an excess of IL-1,,889 C/T [50.8% vs. 39.3%, ,2 (df) = 7.30 (2), uncorrected p = 0.026, corrected p = 0.104] and IL-1RA (86 bp)n A1/A1 genotypes [64.8% vs. 50.8%, ,2 (df) = 12.65 (3), corrected p = 0.020]. The A1/A1 excess was associated with alcohol dependence only in men [69.9% vs. 49.5%, ,2 (df) = 15.72 (2), corrected p < 0.001]. Six-month clinical and hematological outcome measures did not vary by genotype of the 4 polymorphisms. Haplotype analysis revealed an excess of the IL-1,,889 C/IL-1, +3953 C/IL-1RA A2 haplotype in the control group compared with AD patients [20.0% vs. 14.1%, ,2 (df) = 7.25 (1), p = 0.007; odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.46,0.89] and in the abstainers after 6 months of treatment compared with nonabstinent patients [14.7% vs. 6.2%, ,2 (df) = 5.65 (1), p = 0.017; OR = 2.56, 95% CI = 1.15,5.62]. Conclusions:, Our findings provide further tentative evidence of the role of IL-1 in alcohol dependence as well as evidence that the nature of the associations may be direct, gender-specific, or involve haplotype effects. However, findings from single association studies constitute tentative knowledge and must be interpreted carefully and precise replication is required. [source]


Effect of Extended-Release Naltrexone (XR-NTX) on Quality of Life in Alcohol-Dependent Patients

ALCOHOLISM, Issue 2 2009
Helen M. Pettinati
Background:, Extended-release naltrexone (XR-NTX) is a once-a-month injectable formulation for the treatment of alcohol dependence previously shown to reduce drinking and heavy drinking relative to placebo (Garbutt et al., 2005). A 24-week, randomized, double-blind, placebo-controlled study established the efficacy and safety of XR-NTX in this patient population. In this report, the effect of XR-NTX on quality of life (QOL) was examined. Methods:, Alcohol-dependent patients were randomly assigned to receive XR-NTX 380 mg (N = 205), XR-NTX 190 mg (N = 210), or placebo (N = 209), combined with a standardized psychosocial intervention. QOL was assessed using the Medical Outcomes Study 36-item short-form health survey, administered at baseline and at 4-week intervals during 24 weeks of treatment. Results:, Compared with U.S. population norms, patients showed initial impairment in the health-related QOL domains of mental health, social functioning, and problems with work or other daily activities due to emotional problems. Adherence to all 6 injections was 65% for XR-NTX 190 mg, 63% for XR-NTX 380 mg, and 64% for placebo. Generalized estimating equations analyses using an intention-to-treat sample revealed that XR-NTX 380 mg was associated with significantly greater improvements from baseline in mental health (p = 0.0496), social functioning (p = 0.010), general health (p = 0.048), and physical functioning (p = 0.028), compared with placebo. Linear regression analyses revealed that reductions from baseline in drinking (percentage of drinking days and percentage of heavy drinking days in the last 30 days) were significantly (p < 0.05) correlated with improvements in quality of life. Conclusion:, Extended-release naltrexone 380 mg in combination with psychosocial intervention was associated with improvements in QOL, specifically in the domains of mental health, social functioning, general health, and physical functioning. [source]


Effect of Tryptophan Depletion on Alcohol Cue-Induced Craving in Abstinent Alcoholic Patients

ALCOHOLISM, Issue 8 2001
Ismene L. Petrakis
Background: The capacity of alcohol cues to precipitate the desire to drink may be an important determinant of relapse to alcohol use in recovering alcohol-dependent patients. This study evaluated whether attenuation of serotonin synthesis via depletion of its precursor tryptophan reduces the magnitude of cue-induced craving for alcohol in recently abstinent alcoholic individuals. Methods: Alcohol-dependent patients (n= 16), 1 to 3 months after detoxification, who exhibited a 20% or greater increase in reported craving when presented with an alcoholic beverage, completed two additional alcohol cue-exposure test days, 1 week apart. Each cue exposure was preceded by administration of a concentrated amino acid drink that resulted in a rapid and significant decline in plasma free tryptophan (active depletion, no tryptophan supplementation) or a similar drink containing tryptophan (placebo depletion). Tests were conducted in a randomized, double-blind fashion. Results: There were no significant changes in the magnitude of cue-induced craving with active tryptophan depletion compared with placebo. Conclusions: These data question the dependence of alcohol cue-induced craving in sober alcoholics on the ongoing synthesis of serotonin. [source]


Alcohol-dependent patients attempting and not attempting suicide: a comparison

ACTA NEUROPSYCHIATRICA, Issue 4 2004
Özkan Pekta
Background:, Alcohol dependence is a psychiatric disorder associated with an increased risk of suicidal behaviour. This is also associated with an increased number of suicide risk factors. Objective:, The current study examined the sociodemographic and clinical characteristics of a number of alcohol-dependent patients who attempted suicide. Methods:, We studied a consecutive series of 377 alcohol-dependent patients in our in-patient clinics. Their alcohol-use histories were assessed through semistructured interviews. The Suicidal Behaviors Questionnaire, the Childhood Trauma Questionnaire, the Michigan Alcoholism Screening Test and the Hamilton Depression Rating Scale were administered to all patients. Serum total cholesterol levels, mean corpuscular volume, the liver enzymes gamma glutamyl transferase, aspartate aminotransferase and alanine aminotransferase were routinely measured. In the statistical analyses, Student's t -test and chi-squared tests were applied. Results:, Of the 377 alcohol-dependent patients, 89 (23.6%) had histories of attempted suicide. Thirty-four (42.5%) of the 80 female alcohol-dependent patients and 55 (18.5%) of the 297 male alcohol-dependent patients had attempted suicide; this gender difference was statistically significant (,2 = 27.7, P < 0.001). A greater proportion of the suicide attempters than of the non-attempters met the Diagnostic Statistical Manual IV criteria for another psychiatric disorder (60.6%, n = 54, vs. 40.6%, n = 117; ,2 = 14.8; df = 6; P < 0.05). The difference of total cholesterol levels between female (mean = 144.0, SD = 58.3; mean = 158.0, SD = 83.9; t = 4.5; P < 0.05) and male (mean = 133.7, SD = 50.5; mean = 163.6, SD = 69.7; t = 11.7; P < 0.01) attempters and non-attempters was statistically significant. Conclusion:, These results suggest that suicide attempts in alcohol-dependent patients are associated with more profound biopsychosocial pathology and decreased serum cholesterol levels. [source]


Individualized assessment and treatment program for alcohol dependence: results of an initial study to train coping skills

ADDICTION, Issue 11 2009
Mark D. Litt
ABSTRACT Aims Cognitive,behavioral treatments (CBT) are among the most popular interventions offered for alcohol and other substance use disorders, but it is not clear how they achieve their effects. CBT is purported to exert its beneficial effects by altering coping skills, but data supporting coping changes as the mechanism of action are mixed. The purpose of this pilot study was to test a treatment in which coping skills were trained in a highly individualized way, allowing us to determine if such training would result in an effective treatment. Design Participants were assigned randomly to a comprehensive packaged CBT program (PCBT), or to an individualized assessment and treatment program (IATP). The IATP program employed experience sampling via cellphone to assess coping skills prior to treatment, and provided therapists with a detailed understanding of patients' coping strengths and deficits. Setting Out-patient treatment. Participants A total of 110 alcohol-dependent men and women. Measurements Participants in both conditions completed experience sampling of situations, drinking and coping efforts prior to, and following, 12 weeks of treatment. Time-line follow-back procedures were also used to record drinking at baseline and post-treatment. Findings IATP yielded higher proportion of days abstinent (PDA) at post-treatment (P < 0.05) than did PCBT, and equivalent heavy drinking days. IATP also elicited more momentary coping responses and less drinking in high-risk situations, as recorded by experience sampling at post-treatment. Post-treatment coping response rates were associated with decreases in drinking. Conclusions The IATP approach was more successful than PCBT at training adaptive coping responses for use in situations presenting a high risk for drinking. The highly individualized IATP approach may prove to be an effective treatment strategy for alcohol-dependent patients. [source]


Urinary ethyl glucuronide (EtG) and ethyl sulphate (EtS) assessment: valuable tools to improve verification of abstention in alcohol-dependent patients during in-patient treatment and at follow-ups

ADDICTION, Issue 6 2009
Klaus Junghanns
ABSTRACT Aims The aims of this study were (i) to assess the effect of additional urinary ethyl glucuronide (EtG) and ethyl sulphate (EtS) assessment on diagnosed relapse rates in detoxified alcohol-dependent patients; and (ii) to compare dropout rates between EtG- and EtS-negative and -positive patients. Design Two studies on detoxified alcohol-dependent patients. If patients had no indication of relapse they were asked for a urinary sample at discharge from in-patient treatment 3, 6 and 12 weeks after discharge (study 1) and 1, 3 and 6 weeks after discharge (study 2), respectively. Setting Department of Psychiatry, University of Luebeck, Germany. Participants A total of 107 and 32 detoxified alcohol-dependent patients having participated in a 3-week in-patient motivation enhancement programme. Measurement Personal interviews, breathalyzer tests, assessment of urinary EtG and EtS with liquid chromatography-tandem mass spectrometry (LC-MS/MS analysis). Finding Urinary EtG and EtS were always positive at the same time. In the first study 13.5% of the patients were already positive before being discharged from hospital. At the follow-ups 3, 6 and 12 weeks after discharge 12.2, 19.4 and 28.0%, respectively, of the patients coming to the follow-up and denying relapse were positive on urinary EtG and EtS. In the second study, of those patients showing up for follow-up after 1 week and denying relapse, EtG and EtS were positive in four cases (17.4%). Only one EtG- and EtS-positive relapser (3.1%) came to the next follow-ups. In both studies the rates of detected relapses were significantly higher for early follow-ups if urinary EtG and EtS results were considered additionally. Dropout rates until the next follow-up were significantly higher among positive than EtG- and EtS-negative patients. Conclusion Urinary EtG and EtS improve verification of abstinence in studies of alcohol-dependent patients. [source]


A breath test to assess compliance with disulfiram

ADDICTION, Issue 12 2006
Keron Fletcher
ABSTRACT Aims To evaluate the ability of a hand-held breath analyser, the Zenalyser® (Zenics Medical), to identify alcohol-dependent patients receiving disulfiram therapy and to assess the sensitivity and specificity of the instrument at different time intervals post-disulfiram dosing. Design Breath samples were taken from two groups of alcohol-dependent patients, one group on a daily disulfiram regimen and one group receiving no disulfiram. The breath samples were analysed for the combined concentration of carbon disulphide and acetone produced from the metabolism of disulfiram. From these data, two reference ranges were prepared and used for sensitivity and specificity assessments. Setting Breath samples for the reference ranges were obtained from patients at Shelton Hospital, Shrewsbury. Breath samples used to assess the sensitivity and specificity of the instrument were obtained from patients at the Edinburgh Alcohol Problems Clinic. Participants Twenty in-patients from Shelton Hospital receiving a daily 200 mg disulfiram regimen and 20 in-patients receiving no disulfiram. At the Edinburgh Clinic, 54 patients taking a thrice-weekly disulfiram regimen and 22 patients not on disulfiram. Measurements A total of 489 breath samples from Shelton Hospital and 391 breath samples from the Edinburgh Clinic were analysed for the combined concentrations of carbon disulphide and acetone. Findings The breath analyser produced results that distinguished between the disulfiram-treated and untreated groups (P < 0.001). At 1 day post-dose, the sensitivity was 100% and the specificity was 100%. At 2 and 3 days post-dose, the sensitivities and specificities were 84.6% and 100% and 88.2% and 100%, respectively. Conclusion The breath analyser can improve the assessment of the compliance status of patients receiving a daily dose regimen of disulfiram, but is less useful for this purpose if disulfiram is taken on a thrice-weekly regimen. [source]


An Assessment of the Potential Value of Elevated Homocysteine in Predicting Alcohol-withdrawal Seizures

EPILEPSIA, Issue 5 2006
Stefan Bleich
Summary:,Purpose: Higher homocysteine levels were found in actively drinking patients with alcohol dependence. Recent studies have shown that high homocysteine levels are associated with alcohol-withdrawal seizures. The aim of the present study was to calculate the best predictive cutoff value of plasma homocysteine levels in actively drinking alcoholics (n = 88) with first-onset alcohol-withdrawal seizures. Methods: The present study included 88 alcohol-dependent patients of whom 18 patients had a first-onset withdrawal seizure. All patients were active drinkers and had an established diagnosis of alcohol dependence, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Sensitivity and specificity were calculated by using every homocysteine plasma level found in the study population as cut-off value. A Bayes theorem was used to calculate positive (PPV) and negative (NPV) predictive values for all cutoff values used. Results: The highest combined sensitivity and specificity was reached at a homocysteine plasma cutoff value of 23.9 ,M. Positive predictive values ranged from 0.23 to 0.745; the maximum was reached at a homocysteine plasma level of 41.7 ,M. Negative predictive values ranged from 0.50 to 0.935, with a maximum at a homocysteine plasma level of 15.8,M. Conclusions: Homocysteine levels above this cutoff value on admission are a useful screening tool to identify actively drinking patients at higher risk of alcohol-withdrawal seizures. This pilot study gives further hints that biologic markers may be helpful to predict patients at risk for first-onset alcohol-withdrawal seizures. [source]


REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?

ADDICTION BIOLOGY, Issue 2 2010
Markus Heilig
ABSTRACT The role of withdrawal-related phenomena in the development and maintenance of alcohol addiction remains under debate. A ,self-medication' framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol-dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that in most patients, these symptoms abate over 3,6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: (1) are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence?; (2) is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal?; and (3) to what extent is susceptibility to negative affect that persists into protracted abstinence heritable? [source]


CLINICAL STUDY/BIOMARKER: Phosphatidylethanol: normalization during detoxification, gender aspects and correlation with other biomarkers and self-reports

ADDICTION BIOLOGY, Issue 1 2010
Friedrich Martin Wurst
ABSTRACT Phosphatidylethanol (PEth) is a direct ethanol metabolite, and has recently attracted attention as biomarker of ethanol intake. The aims of the current study are: (1) to characterize the normalization time of PEth in larger samples than previously conducted; (2) to elucidate potential gender differences; and (3) to report the correlation of PEth with other biomarkers and self-reported alcohol consumption. Fifty-seven alcohol-dependent patients (ICD 10 F 10.25; 9 females, 48 males) entering medical detoxification at three study sites were enrolled. The study sample was comprised of 48 males and 9 females, with mean age 43.5. Mean gamma glutamyl transpeptidase (GGT) was 209.61 U/l, average mean corpuscular volume (MCV) was 97.35 fl, mean carbohydrate deficient transferrin (%CDT) was 8.68, and mean total ethanol intake in the last 7 days was 1653 g. PEth was measured in heparinized whole blood with a high-pressure liquid chromatography method, while GGT, MCV and %CDT were measured using routine methods. PEth levels at day 1 of detoxification ranged between 0.63 and 26.95 µmol/l (6.22 mean, 4.70 median, SD 4.97). There were no false negatives at day 1. Sensitivities for the other biomarkers were 40.4% for MCV, 73.1% for GGT and 69.2% for %CDT, respectively. No gender differences were found for PEth levels at any time point. Our data suggest that PEth is (1) a suitable intermediate term marker of ethanol intake in both sexes; and (2) sensitivity is extraordinary high in alcohol dependent patients. The results add further evidence to the data that suggest that PEth has potential as a candidate for a sensitive and specific biomarker, which reflects longer-lasting intake of higher amounts of alcohol and seemingly has the above mentioned certain advantages over traditional biomarkers. [source]


CLINICAL STUDY: Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators

ADDICTION BIOLOGY, Issue 3 2009
Wendy Ooteman
ABSTRACT Acamprosate and naltrexone are effective medications in the treatment of alcoholism. However, effect sizes are modest. Pharmacogenomics may improve patient-treatment-matching and effect sizes. It is hypothesized that naltrexone exerts its effect through genetic characteristics associated with the dopaminergic/opioidergic positive reinforcement system, whereas acamprosate works through the glutamatergic/GABAergic negative reinforcement system. Alcohol-dependent subjects were randomly assigned to either acamprosate or naltrexone. Subjects participated in a cue-exposure experiment at the day before and at the last day of medication. Reductions in cue-induced craving and physiological cue reactivity were measured. Differential effects of naltrexone and acamprosate on these outcomes were tested for different polymorphisms of the opioid, dopamine, glutamate and GABA-receptors. Significant matching effects were found for polymorphisms at the DRD2, GABRA6 and GABRB2 gene. In addition, a trend was found for the OPRM1 polymorphism. This provides evidence for the matching potential of genotypes. It is expected that more effective treatments can be offered when genetic information is used in patient-treatment-matching. [source]


CLINICAL STUDY: Attentional bias in alcohol-dependent patients: the role of chronicity and executive functioning

ADDICTION BIOLOGY, Issue 2 2009
Sabine Loeber
ABSTRACT It has been suggested that the attention towards alcohol-related stimuli increases with the duration of drinking and alcohol dependence. The present study aimed to assess whether an attentional bias was present in detoxified alcohol-dependent patients, and if the magnitude of the attentional bias depended on the subject's drinking history and variables of executive functioning. Attentional bias was assessed in 30 alcohol-dependent patients using a visual dot-probe task with a picture presentation time of 50 ms. In addition, patients completed a variety of different cognitive tasks such as attention, continuous performance, working memory, set shifting and inhibitory control tests. Based on correlation analysis we split the patient sample on the median with regard to the duration of alcohol dependence and our results indicated a significant attentional bias towards alcohol-associated pictures in patients dependent for less than 9 years, but not in patients with a longer duration of dependence. The two patient samples differed significantly with regard to attention and working memory functioning with patients who were dependent for more than 9 years showing a greater impairment. When impairment of attention and working memory were controlled for, the group differences in attentional bias were no longer significant. Our results indicate that differences with regard to drinking-related variables as well as cognitive functioning seem to modulate attentional bias and need to be taken into account in models of drinking maintenance. [source]


CLINICAL STUDY: Prolactin response to fenfluramine in abstinent, alcohol-dependent patients

ADDICTION BIOLOGY, Issue 3-4 2008
Richard J. Porter
ABSTRACT It has been suggested that serotonin (5HT) function is abnormal in alcoholics even during abstinence. The prolactin response to fenfluramine (PRF) is generally believed to reflect the activity of the 5HT system and has been previously used to investigate 5HT activity in a variety of conditions, including alcoholism. The origin of the cortisol (CORT) response to fenfluramine is less clear. The objectives of this paper are to examine the prolactin (PRL) and CORT response to dl -fenfluramine in a large cohort of males with alcohol dependence who had been abstinent for 3 weeks, and to compare this with an age-matched control group. Ninety-four subjects with a DSM-III-R diagnosis of moderate to severe alcohol dependence who had been abstinent for 3 weeks, and 23 control subjects underwent neuroendocrine challenge with dl -fenfluramine (10 mg per 10 kg body weight). PRL and CORT responses were measured. No significant difference was found in PRF between abstinent, alcoholic patients and controls (F = 2.7, d.f. = 1.115, P = 0.10). CORT response was significantly lower in abstinent alcoholics than in controls (F = 10.0, d.f. = 1.116, P = 0.002). The results suggest no clear difference in 5HT function between abstinent alcoholics and healthy controls. The reduced CORT response in abstinent alcoholics further supports evidence of hypofunction of the adrenocortical system in this group. [source]


BIOMARKER: Phosphatidylethanol as a sensitive and specific biomarker,comparison with gamma-glutamyl transpeptidase, mean corpuscular volume and carbohydrate-deficient transferrin

ADDICTION BIOLOGY, Issue 1 2007
Susanne Hartmann
ABSTRACT Phosphatidylethanol (PEth), a direct ethanol metabolite, is detectable in blood for more than 2 weeks after sustained ethanol intake. Our aim was to assess the usefulness of PEth [comparing sensitivity, specificity and the area under the curve (AUC)] as compared with carbohydrate-deficient transferrin (CDT), gamma-glutamyl transpeptidase (GGT) and mean corpuscular volume (MCV), calculating the results from sober patients against those from alcohol-dependent patients during withdrawal. Fifty-six alcohol-dependent patients (ICD-10 F 10.25) in detoxification, age 43 years, GGT 81 U/l, MCV 96.4 fl, %CDT 4.2, 1400 g ethanol intake in the last 7 days (median), were included in the study. Over the time of 1 year, 52 samples from 35 sober forensic psychiatric addicted in-patients [age 34 years, GGT 16 U/l, MCV 91 fl, CDT 0.5 (median)] in a closed ward were drawn and used for comparison . PEth was measured in heparinized whole blood with a high-performance liquid chromatography method. GGT, MCV and %CDT were measured using routine methods. A receiver operating characteristic curve analysis was carried out, with ,current drinking status' (sober/drinking) as the state variable and PEth, MCV, GGT and CDT as test variables. The resulting AUC was 0.974 (P < 0.0001, confidence interval 0.932,1.016) for PEth. At a cut-off of 0.36 µmol/l, the sensitivity was 94.5% and specificity 100%. The AUC for CDT, GGT and MCV were 0.931, 0.894 and 0.883, respectively. A significant Spearman's rank correlation was found between PEth and GGT (r = 0.739), CDT (r = 0.643), MVC (r = 0.639) and grams of ethanol consumed in the last 7 days (r = 0.802). Our data suggest that PEth has potential to be a sensitive and specific biomarker, having been found in previous studies to indicate longer lasting intake of higher amounts of alcohol. [source]


A psychometric evaluation of the Chinese version of the stage of change-readiness and treatment-eagerness scale

JOURNAL OF CLINICAL NURSING, Issue 17 2009
Mei-Yu Yeh
Aims., The present study analysed the psychometric properties of a Chinese version of the stage of change-readiness and treatment-eagerness scale among alcohol-dependent patients and investigated whether a three-factor structure fit the data. Background., The stage of change-readiness and treatment-eagerness scale is a 19-item instrument designed to measure alcohol-dependent patients' motivation for change. However, this instrument had not been translated and validated for use in Taiwan. Design., Survey. Methods., A sample of 161 alcohol-dependent patients receiving alcohol-related treatment in psychiatric hospital outpatient and inpatient units was included. Confirmatory factor analyses were conducted on three-factor measurement models of the stage of change-readiness and treatment-eagerness scale. Results., Confirmatory factor analyses supported the presence of a three-factor modified model (ambivalence, recognition and taking steps) among alcohol-dependent patients. Higher internal item consistency was found for the recognition and taking step factors, while the ambivalence factor was shown to have lower internal consistency. Convergent, discriminant and concurrent validity were obtained for the assessment of severity of alcohol dependence. Conclusions., The results indicated that the 11-item, three-factor modified Chinese version of the stage of change readiness and treatment eagerness scale provided best goodness of fit for the data in this study. This study demonstrated that the Chinese version of the stage of change readiness and treatment eagerness scale is a reliable and valid self-report measure for the assessment of changing motivation in alcohol-dependent patients. Relevance to clinical practice., The Chinese version of stage of change readiness and treatment eagerness scale is applicable for use in clinical treatment and research, predicting motivation for change and evaluating intervention outcomes in Taiwan. [source]


Temperament, character, and dissociation among detoxified male inpatients with alcohol dependency

JOURNAL OF CLINICAL PSYCHOLOGY, Issue 6 2008
Cuneyt Evren
Abstract The aim of this study was to determine possible relationships of pathological dissociation with temperament, character, and concurrent psychopathological features in a consecutive series of male alcohol-dependent patients. Fifty-eight patients with pathological dissociation were compared with 118 nondissociative patients classified by dissociative taxon membership. Beside higher scores on anxiety, depression, and alcoholism scales, a larger proportion of dissociative group reported childhood abuse, suicide attempts, and self-mutilation than did the nondissociative group. They also had higher scores of novelty seeking and harm avoidance, but lower scores of persistence, self-directedness, and cooperativeness. Trait anxiety, depression, and severity of alcoholism predicted dissociative experiences; however, none of the temperament or character measures did. Rather than being a derivative of temperament or character features, dissociative experiences of male alcohol-dependent patients are associated with overall concurrent psychopathology. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:717,727, 2008. [source]


Effects of Alcohol Cue Exposure on Response Inhibition in Detoxified Alcohol-Dependent Patients

ALCOHOLISM, Issue 9 2010
Siegfried Gauggel
Background:, There is evidence that exerting self-control during alcohol craving can diminish performance on subsequent tasks that require self-control. Based on the resource depletion model (Muraven and Baumeister, 2000), we examined the influence of alcohol cue exposure on detoxified alcohol-dependent patients' ability to inhibit ongoing responses. Methods:, Twenty alcohol-dependent patients were randomly assigned to an alcohol-cue exposure and a control-cue exposure condition and thereafter had to perform an inhibition task (i.e., stop-signal task). Results:, Participants who sniffed alcohol before performing the inhibition task reported a stronger urge to drink alcohol than the control group that sniffed water. Participants who sniffed alcohol were also impaired in their inhibitory performance but not in their noninhibitory performance on the stop-signal task. Conclusions:, The urge to drink presumably reduced participants' self-control, and this interfered with their ability to inhibit responding. [source]


Recruitment of Additional Brain Regions to Accomplish Simple Motor Tasks in Chronic Alcohol-Dependent Patients

ALCOHOLISM, Issue 6 2010
Mitchell H. Parks
Background:, Chronic alcohol-dependent patients (ALC) exhibit neurocognitive impairments attributed to alcohol-induced fronto-cerebellar damage. Deficits are typically found in complex task performance, whereas simple tasks may not be significantly compromised, perhaps because of little understood compensatory changes. Methods:, We compared finger tapping with either hand at externally paced (EP) or maximal self-paced (SP) rates and concomitant brain activation in ten pairs of right-hand dominant, age-, and gender-matched, severe, uncomplicated ALC and normal controls (NC) using functional magnetic resonance imaging (fMRI). Results:, Mean tapping rates were not significantly different in ALC and NC for either task, but SP tapping variances were greater in ALC for both hands. SP tapping was more rapid with dominant hand (DH) than non-dominant hand (NDH) for both groups. EP and SP tapping with the non-dominant hand demonstrated significantly more activation in ALC than NC in the pre and postcentral gyri, inferior frontal gyrus, inferior parietal lobule, and the middle temporal gyrus. Areas activated only by ALC (not at all by NC) during NDH tapping included the inferior frontal gyrus, middle temporal gyrus, and postcentral gyrus. There were no significant group activation differences with DH tapping. No brain regions activated more in NC than ALC. SP tapping in contrast to EP activated fronto-cerebellar networks in NC, including postcentral gyrus, anterior cingulate, and the anterior lobe and vermis of the cerebellum, but only parietal precuneus in ALC. Conclusions:, These findings with NDH finger tapping support previous reports of neurocognitive inefficiencies in ALC. Inferior frontal activation with EP in ALC, but not in NC, suggests engagement of regions needed for planning, organization, and impulse regulation; greater contralateral parietal lobe activation with SP in ALC may reflect right hemispheric impairments in visuospatial performance. Contrasting brain activation during SP and EP suggests that ALC may not have enlisted a fronto-cerebellar network as did NC but rather employed a higher order planning mode by recruiting parietal lobe functions to attain normal mean finger tapping rates. Elucidation of the compensatory neural mechanisms that allow near normal performance by ALC on simple tasks can inform functional rehabilitation of patients in recovery. [source]


Greater Activation in Left Hemisphere Language-Related Regions During Simple Judgment Tasks Among Substance-Dependent Patients in Treatment for Alcoholism

ALCOHOLISM, Issue 2 2010
Jodi M. Gilman
Background:, Alcoholism is often associated with impaired emotional control. Alcoholics have also been found to have deficits in frontal lobe executive functions. Recent functional imaging studies have suggested that alcoholics show greater activation than nonalcoholics in circuits involving frontal lobes, as well as more posterior brain regions, when engaged in executive-type tasks. In this study, we compared brain activations of alcohol-dependent patients and healthy nonalcoholics while they performed 2 simple judgment tasks designed to activate frontal circuits involved in a basic form of decision making. Participants completed 1 judgment task that required an emotional judgment and 1 task that did not, which enabled us to study whether alcoholics had greater brain activation while performing executive tasks, and to determine if emotional tasks elicited even greater activation than nonemotional tasks. Methods:, We performed functional magnetic resonance imaging scans while alcoholic patients and nonalcoholic controls viewed pictures from the International Affective Picture System. In 3 separate runs, participants viewed the images without making a judgment, determined whether the images were indoor or outdoor scenes, or decided if they liked or disliked the images. Results:, There was little difference in brain activation between alcoholics and controls when no judgment was required. When participants made judgments about either the location or whether they liked or disliked an image, however, we observed significantly increased activation in frontal, limbic, and temporal regions in the patients relative to the controls. Increases were particularly robust in the frontal lobe and in areas of the brain associated with language. When we compared the emotional to the nonemotional judgment, the alcoholics, but not the controls, showed greater activation in the ventral mesial frontal cortex. Conclusions:, Alcoholic patients appear to use brain language areas more than nonalcoholics while making judgments about the setting or liking of emotionally arousing visual images. This increased activation may reflect a compensatory recruitment of brain regions to perform simple decision-making tasks. [source]


Understanding and Treating Patients With Alcoholic Cirrhosis: An Update

ALCOHOLISM, Issue 7 2009
Giovanni Addolorato
Alcoholic cirrhosis represents the terminal stage of alcoholic liver disease (ALD) and one of the main causes of death among alcohol abusers. The aim of this review was to provide an update on alcoholic cirrhosis, with an emphasis on recent findings. Increased alcohol consumption in developing countries is expected to increase cirrhosis mortality. There is a need, therefore, to develop new approaches to the prevention of ALD, including more attention to co-factors that may increase risk of ALD (i.e., obesity and diabetes, chronic HCV infection, and smoking). Furthermore, a better understanding of the pathological mechanisms on the basis of alcohol cirrhosis represents a cornerstone in order to develop new pharmacological treatments. Inflammatory and immune responses along with oxidative stress and alterations in adipokine secretion might contribute in different ways to the evolution of alcohol-induced fibrosis/cirrhosis. As of this date, patients with severe alcoholic hepatitis with a Maddrey Discriminant Factor (MDF) 32 should be offered pentoxifylline and/or corticosteroids unless contraindications exist. For ambulatory patients, S-adenosylmethionine (SAMe) may be considered in a motivated patient with nutritional support. Current studies do not support use of anti-tumor necrosis factor (TNF)-alpha antibody. Finally, achieving total alcohol abstinence should represent the main aim in the management of patients affected by any stage of cirrhosis. In the last decades, several drugs able to increase abstinence and prevent alcohol relapse have been evaluated and some of them have obtained approval for alcohol dependence. Patients with alcoholic cirrhosis; however, are usually excluded from such treatments. A recent study demonstrated the efficacy and safety of baclofen in inducing and maintaining alcohol abstinence in cirrhotic alcohol-dependent patients with cirrhosis. All together the information available suggests the need of a multimodal approach in the clinical management of these patients. [source]


Factor Structure and Concurrent Validity of the Obsessive Compulsive Drinking Scale in a Group of Alcohol-Dependent Subjects of Mexico City

ALCOHOLISM, Issue 7 2009
Marta Cordero
Background:, Obsessive thoughts and compulsive drinking behaviors have been proposed as key factors associated with the loss of control over alcohol consumption experienced by alcohol-dependent patients. The self-report 14-item Obsessive Compulsive Drinking Scale (OCDS; Anton et al., 1995) was designed in order to rate these features. Methods:, A Spanish-translated version of the OCDS was applied to a group of 159 alcohol-dependent subjects while in abstinence, and data were analyzed in order to evaluate the factor structure and concurrent validity of the scale. Results:, Several solutions were explored after applying the principal factor analysis to the data. The most plausible result was obtained after excluding the items on quantity and frequency of drinking. This model explaining 56.9% of the variance included 2 factors: obsessive thoughts related to drinking and interference/behaviors related to drinking. Additionally, OCDS scores were significantly correlated with measures for the Alcohol Dependence Scale, number of DSM-IV criteria met for alcohol dependence as well as the number of days in a week engaged in heavy drinking, indicating concurrent validity. Conclusions:, Our results support the use of OCDS as a valid self-rated instrument that can be broadly applied in research and treatment settings. However, its current version includes questions that may not represent the core concept of craving. The abridged 12-item version of the scale (excluding the items on drinking habits) maintains good psychometrics features and seems to be adequate when different cognitive and behavioral dimensions are explored. [source]


Chronic and High Alcohol Consumption Has a Negative Impact on Sleep and Sleep-Associated Consolidation of Declarative Memory

ALCOHOLISM, Issue 5 2009
Klaus Junghanns
Background., The importance of sleep for memory consolidation has become a major focus of research. While it is known that abstaining alcohol-dependent patients often have sleep disorders and that there is some cognitive impairment during early abstention a possible interaction of disturbed sleep with overnight memory consolidation has not been addressed in a study as yet. Methods., Twenty-four alcohol-dependent patients with a short abstention period (mean 21.9 ± 7.6 days) were compared with 12 patients with an abstention period of several months (115.7 ± 43.8 days). Groups did not differ with respect to daily alcohol consumption before treatment, duration of alcohol dependence, and age. Before sleep all patients learned a list of semantically associated word pairs and a face name association task to a fixed criterion (at least 60% of correct recall) and they performed a mirror tracing task. After a polysomnographically registered night the patients were tested for retention of the learned declarative material by cued recall and had to perform the mirror tracing task again. Results., The groups did not differ with respect to sleep parameters or sleep-associated memory consolidation. Across both groups the duration of alcohol dependence correlated negatively with the amount of non-REM sleep and recall in the face name association task correlated negatively with daily alcohol consumption before abstention. Among the longer-term abstainers the duration of abstention correlated with the amount of slow wave sleep. Conclusions., Our data support the hypothesis that chronic and high alcohol consumption negatively affects sleep and declarative memory consolidation during the first months of abstention. Between an abstention period of a few weeks and of several months no change in sleep parameters and nightly memory consolidation could be demonstrated, however. [source]


Association Between Val66Met Brain-Derived Neurotrophic Factor (BDNF) Gene Polymorphism and Post-Treatment Relapse in Alcohol Dependence

ALCOHOLISM, Issue 4 2009
Marcin Wojnar
Background:, The purpose of this study was to examine relationships between genetic markers of central serotonin (5-HT) and dopamine function, and risk for post-treatment relapse, in a sample of alcohol-dependent patients. Methods:, The study included 154 patients from addiction treatment programs in Poland, who met DSM-IV criteria for alcohol dependence. After assessing demographics, severity of alcohol use, suicidality, impulsivity, depression, hopelessness, and severity of alcohol use at baseline, patients were followed for approximately 1 year to evaluate treatment outcomes. Genetic polymorphisms in several genes (TPH2, SLC6A4, HTR1A, HTR2A, COMT, and BDNF) were tested as predictors of relapse (defined as any drinking during follow-up) while controlling for baseline measures. Results:, Of 154 eligible patients, 123 (80%) completed follow-up and 48% (n = 59) of these individuals relapsed. Patients with the Val allele in the Val66Met BDNF polymorphism and the Met allele in the Val158Met COMT polymorphism were more likely to relapse. Only the BDNF Val/Val genotype predicted post-treatment relapse [odds ratio (OR) = 2.62; p = 0.019], and time to relapse (OR = 2.57; p = 0.002), after adjusting for baseline measures and other significant genetic markers. When the analysis was restricted to patients with a family history of alcohol dependence (n = 73), the associations between the BDNF Val/Val genotype and relapse (OR = 5.76, p = 0.0045) and time to relapse (hazard ratio = 4.93, p = 0.001) were even stronger. Conclusions:, The Val66Met BDNF gene polymorphism was associated with a higher risk and earlier occurrence of relapse among patients treated for alcohol dependence. The study suggests a relationship between genetic markers and treatment outcomes in alcohol dependence. Because a large number of statistical tests were conducted for this study and the literature on genetics and relapse is so novel, the results should be considered as hypothesis generating and need to be replicated in independent studies. [source]


Effects of Alcoholism Typology on Response to Naltrexone in the COMBINE Study

ALCOHOLISM, Issue 1 2009
Michael P. Bogenschutz
Background:, This study investigated whether subgroups of alcohol-dependent patients responded differently to naltrexone versus placebo in the NIAAA COMBINE study. In particular, the A versus B and the Early Onset versus Late Onset typologies were examined. Relative to Type A alcoholics, Type B alcoholics are characterized by greater severity, earlier onset, stronger family history, more childhood risk factors (e.g., conduct disorder), and greater frequency of comorbid psychiatric and substance use disorders. Methods:, COMBINE study participants were categorized as Type A or Type B using k-means cluster analysis and variables from 5 domains that have been shown to replicate the original Babor typology efficiently. Early Onset was defined as alcohol dependence beginning before age 25. For the planned analyses, the sample was reduced to the 618 participants receiving naltrexone alone or placebo, either with medical management (MM) alone or with MM plus the Combined Behavioral Intervention (CBI). The a priori primary outcome was percent heavy drinking days during treatment in the groups receiving MM without CBI. Results:, Among those receiving MM without CBI, Type A alcoholics had better drinking outcomes with naltrexone than placebo, whereas medication condition did not influence outcomes significantly in the Type Bs. Age of onset was not significantly related to outcome. For those receiving CBI, no significant effects were found for either typology. Conclusions:, In this sample, the beneficial effects of opioid antagonism were limited to Type A alcoholics receiving treatment in a MM model. Future studies should investigate the relationship between clinically relevant genotypes, phenotypes such as typologies, and treatment response. More work is also needed to develop practical algorithms for phenotypic assignment. [source]