Early recognition of obsessive-compulsive disorder.

The early course in clinical and neurobiological terms of obsessive-compulsive disorder (OCD) is almost completely unknown. The disease often begins in early childhood and adolescence, but the first behavioral changes and symptoms preceding OCD have not been assessed to date. In this retrospective approach, 40 patients with OCD (23 females/17 males; 39.4 [10.1] years old in average; with scores on the Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] of 19 [9.3]) were given an author-developed questionnaire. Twenty-three patients reported first changes before having reached the age of 20 years. Rather unspecific symptoms such as "anxiety" and "lacking self-trust" seem to have been more frequent as first signs of developing OCD. Further specific symptoms indicating OCD were "enhanced feeling of responsibility," "exact attention concerning details," "being eager for order and cleanness," "difficulties with decisions," and "repetitive controlling," but were less remembered. There was no significant relationship between these first changes and later OCD-related psychopathology as measured with the Y-BOCS, but there was a relationship with later depressive comorbidity (Hamilton Depression Rating Scale). This substantiates the view that OCD-similar to other psychiatric disorders such as schizophrenia and bipolar disorder-seems to be characterized by a psychopathologically less specific prodrome with rather depressive symptoms. However, this was a retrospective study with preliminary data, which has to be replicated prospectively with a larger sample.

Ventral striatal prediction error signaling is associated with dopamine synthesis capacity and fluid intelligence.

Fluid intelligence represents the capacity for flexible problem solving and rapid behavioral adaptation. Rewards drive flexible behavioral adaptation, in part via a teaching signal expressed as reward prediction errors in the ventral striatum, which has been associated with phasic dopamine release in animal studies. We examined a sample of 28 healthy male adults using multimodal imaging and biological parametric mapping with (1) functional magnetic resonance imaging during a reversal learning task and (2) in a subsample of 17 subjects also with positron emission tomography using 6-[(18) F]fluoro-L-DOPA to assess dopamine synthesis capacity. Fluid intelligence was measured using a battery of nine standard neuropsychological tests. Ventral striatal BOLD correlates of reward prediction errors were positively correlated with fluid intelligence and, in the right ventral striatum, also inversely correlated with dopamine synthesis capacity (FDOPA K inapp). When exploring aspects of fluid intelligence, we observed that prediction error signaling correlates with complex attention and reasoning. These findings indicate that individual differences in the capacity for flexible problem solving relate to ventral striatal activation during reward-related learning, which in turn proved to be inversely associated with ventral striatal dopamine synthesis capacity.

Patient satisfaction with specialized mental health service for obsessive-compulsive disorder.

BACKGROUND: Patient satisfaction is an important outcome variable that is increasingly used in mental health service evaluation. There are no results available for patients with obsessive-compulsive disorder (OCD) yet. METHODS: Using the Verona Service Satisfaction Scale, patient satisfaction with a specialized mental health service was examined in patients with OCD. RESULTS: OCD patients were overall satisfied with the professional help provided, whereas satisfaction with the professional involvement of relatives within the treatment and health care process was found to be quite low. Patients with more severe OCD, as measured by the Yale-Brown Obsessive-Compulsive Scale, as well as chronically ill and more disabled patients were more likely to be dissatisfied with the overall care they received. Patient satisfaction plays an important role in the long-term course of an illness such OCD. This seems to be decreased so longer illness is not or badly treated. There is a stronger need for involvement of family members in the treatment and health care of patients with OCD. CONCLUSIONS: More OCD-specific treatment offers have to be established for patients with this long-term illness such as psychotherapy in groups.

Detecting alcohol abuse: traditional blood alcohol markers compared to ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) measurement in hair.

Alcohol abuse is a common problem in society; however, the technical capabilities of evaluating individual alcohol consumption using objective biomarkers are rather limited at present. In recent years research has focused on alcohol markers using hair analysis but data on performance and reliable cut-off values are still lacking. In this study 169 candidates were tested to compare traditional biomarkers, such as carbohydrate-deficient-transferrin (CDT), gamma glutamyl transferase (GGT), aspartate amino transferase, alanine amino transferase and the mean corpuscular volume of the erythrocytes, with alcohol markers detectable in hair such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs). This study revealed that EtG, GGT and CDT showed the best results, demonstrating areas under the curve calculated from receiver operating characteristics of 0.941, 0.943 and 0.899 respectively. The lowest false-negative and false-positive rates were obtained by using a combined interpretation system for hair EtG and FAEEs. All markers demonstrated only low to moderate correlations. Optimum cut-off values for differentiation between social and chronic excessive drinking calculated for hair EtG and FAEEs were 28 pg/mg and 0.675 ng/mg, respectively. The critical values published in the "Consensus on Alcohol Markers 2012" by the Society of Hair Testing were confirmed.

Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

BACKGROUND: Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. METHODS: One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. RESULTS: Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. CONCLUSION: Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

Development and psychometric characteristics of the Dissociation Tension Scale.

The newly developed Dissoziations-Spannungs-Skala (Dissociation Tension Scale; DSS) is a self-rating instrument for the assessment of psychological and somatoform dissociative features (ranging from normal up to pathological) as well as aversive inner tension occurring within the past 7 days. The DSS contains 21 items assessing dissociative symptoms and 1 additional item assessing aversive inner tension. Ratings are made on a time-oriented scale ranging from 0% (never) to 100% (constantly). We measured the psychometric qualities of the DSS in a total of 294 patients and healthy controls. Internal consistency of the DSS was high (Cronbach's alpha = .92; Gutmann's split-half r = .92). We found good support for convergent, discriminant, and differential validity. There was clear evidence for the DSS being a sensitive instrument for the assessment of changing symptomatology. Assessment of dissociation and other psychopathological features over the same period of time are now possible.

Degree of pineal calcification (DOC) is associated with polysomnographic sleep measures in primary insomnia patients.

OBJECTIVE: Melatonin plays a key role in the proper functioning of the circadian timing system (CTS), and exogenous melatonin has been shown to be beneficial in cases of CTS and sleep disturbances. Nevertheless, the concept of "melatonin deficit" has yet to be defined. The aim of our study was, therefore, to determine the relationship between the degree of pineal calcification (DOC) and a range of sleep parameters measured objectively using polysomnography (PSG). METHODS: A total of 31 outpatients (17 women, 14 men, mean age 45.9 years; SD 14.4) with primary insomnia were included in our study. Following an adaptation night, a PSG recording night was performed in the sleep laboratory. Urine samples were collected at predefined intervals over a 32-h period that included both PSG nights. The measurement of 6-sulphatoxymelatonin (aMT6s) levels was determined using ELISA. DOC and volume of calcified pineal tissue (CPT) and uncalcified pineal tissue (UPT) were estimated by means of cranial computed tomography. RESULTS: UPT was positively associated with 24-h aMT6s excretion (r=0.569; P=0.002), but CPT was not. After controlling for age, aMT6s parameters, CPT, and UPT did not correlate with any of the PSG parameters evaluated. In contrast, DOC was negatively associated with REM sleep percentage (r=-0.567, P=0.001), total sleep time (r=-0.463, P=0.010), and sleep efficiency (r=-0.422, P=0.020). CONCLUSION: DOC appears to be a superior indicator of melatonin deficit compared to the absolute amount of melatonin in the circulation. High DOC values indicate changes predominantly in the PSG parameters governed by the circadian timing system. DOC may thus serve as a marker of CTS instability.

Elevated [18F]fluorodopamine turnover in brain of patients with schizophrenia: an [18F]fluorodopa/positron emission tomography study.

Previous positron emission tomography (PET) studies with levodopa analogs have revealed a modestly increased capacity for dopamine synthesis in the striatum of patients with schizophrenia compared with healthy age-matched control subjects. We hypothesized that not just the synthesis but also the turnover of radiolabeled dopamine is elevated in patients. To test the hypothesis, we reanalyzed 2-h-long [18F]fluorodopa (FDOPA)/PET recordings from eight unmedicated patients with schizophrenia and 15 healthy age-matched control subjects, using new methods for the quantification of [18F]fluorodopamine steady-state kinetics. The fractional rate constant for the catabolism and elimination of [18F]fluorodopamine was elevated nearly twofold in striatum, the largest biochemical difference in brain of schizophrenics yet reported. The magnitude of the intrinsic blood-brain FDOPA clearance with correction for this loss of [18F]fluorodopamine metabolites was increased by 20% in caudate and putamen and by 50% in amygdala and midbrain of the patients. However, the magnitude of the steady-state storage of FDOPA and its decarboxylated metabolites (V(d)) was reduced by one-third in the caudate nucleus and amygdala of the schizophrenic group. Thus, reduced steady-state storage of [18F]fluorodopamine occurs in the midst of accelerated synthesis in brain of untreated patients. Positive scores of the positive and negative syndrome scale correlated inversely with the magnitude of V(d) in amygdala, suggesting an association between positive symptoms and impaired steady-state storage of FDOPA metabolites in that structure.

Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine.

RATIONALE: High blockade of dopamine D2 receptors in the ventral striatum including the nucleus accumbens may interfere with reward anticipation and cause secondary negative symptoms such as apathy or anhedonia. This may not be the case with newer neuroleptics such as olanzapine, which show less dopamine D2 receptor blockade and a faster off-rate from the receptor. OBJECTIVES: We used functional magnetic resonance imaging to assess the blood oxygenation level dependent response in the ventral striatum of schizophrenics medicated with typical neuroleptics (T1) and after switching them to olanzapine (T2) and of healthy control subjects at corresponding time points during reward anticipation. MATERIALS AND METHODS: Ten schizophrenics, while medicated with typical neuroleptics (T1) and after having been switched to olanzapine (T2), and ten matched healthy volunteers participated in a monetary incentive delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain or have no consequence. RESULTS: During reward anticipation, healthy volunteers showed significantly higher ventral striatal activation compared to schizophrenic patients treated with typical neuroleptics but not olanzapine, which was reflected in a significant interaction between group and session. In patients treated with typical neuroleptics, but not with olanzapine, decreased left ventral striatal activation was correlated with negative symptoms. CONCLUSIONS: Failure to activate the ventral striatum during reward anticipation was pharmacologically state-dependent and observed only in patients treated with typical neuroleptics but not with olanzapine, which may indicate that this drug did not induce secondary negative symptoms via interference with reward anticipation.

Switching schizophrenia patients from typical neuroleptics to olanzapine: effects on BOLD response during attention and working memory.

Dysfunctional activation of the dorsolateral prefrontal cortex (DLPFC) during working memory (WM) in schizophrenia patients has repeatedly been observed, however little is known about specific medication effects on the modulation of DLPFC activation. We measured activation of DLPFC during a WM task in a longitudinal fMRI study in ten schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to olanzapine (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points. We analyzed the fMRI data with SPM5 in a 2 x 2 x 2 design (group x session x task). Schizophrenia patients showed fewer correct responses compared to healthy controls at both time points. The fMRI data revealed a significant group by task interaction in the bilateral DLPFC and the right parietal cortex, indicating a reduced BOLD response in the patient group. After switching to olanzapine, schizophrenia patients displayed a significant increase in the BOLD response during the 0-back condition in the DLPFC. This study showed that switching patients from conventional neuroleptics to olanzapine did not significantly alter the frontal or parietal BOLD response during working memory task. However, medication status had influences on the activation during attentional task (0-back), emphasizing the importance of baseline selection in pharmacological fMRI studies.

Evaluation of time memory in acutely depressed patients, manic patients, and healthy controls using a time reproduction task.

Patients with affective disorders have often been reported to experience subjective changes in how they perceive the flow of time. Time reproduction tasks provide information about the memory component of time perception and are thought to remain unaffected by pulse rate disturbances in the pacemaker of the internal clock. In our study, 30 patients with acute depression, 30 patients with acute mania, and 30 healthy subjects of all age groups were presented with a time reproduction task. Participants were asked to observe a stimulus presented on a computer screen for a certain length of time and, subsequently, to reproduce the stimulus for a similar length of time by pressing the space bar on the computer keyboard. Stimuli were presented to each subject for 1, 6, and 37s. On average, the time intervals reproduced by manic patients were shorter than those reproduced by depressed patients. Manic patients reproduced the short time interval (6s) correctly, but under-reproduced the long time interval (37s, P<0.001). Depressed patients correctly reproduced the long time interval, but over-reproduced the short time interval (P<0.001). Remembering time intervals as having been longer than they actually were may lead to a slowed experience of time, as has been described in depressed patients; precisely the converse seems to apply to manic patients.

Age effects on trail making test during acute depressive and manic episode.

Impairment of executive functions and attention has been found in patients with acute depressive episodes but has rarely been investigated in manic patients to date. At the same time, executive functions decline with age. Thus, it is currently a matter of debate how to best measure decreased executive performance in elderly patients with affective disorders. In our study, we examined 30 depressed patients, 28 manic patients, and 30 healthy subjects of all age groups, using the Trail Making Test (TMT). Both depressed and manic patients needed twice as long as healthy subjects to perform the TMT Part A. In addition to this reduced performance due to affective disorders, we were also able to detect a decline in performance due to age. One could thus postulate that age and affective disorders each influence a different neuropsychological function, age affecting executive performance and affective disorders affecting attention, as measured in both cases by the TMT.

Persistent dysfunctional frontal lobe activation in former smokers.

OBJECTIVE: Chronic smoking and nicotine exposure are accompanied by impaired cognitive task performance, modulated cerebral activity in brain imaging studies, and neuritic damage in experimental animals. The profile of the described dysfunctions matches frontal lobe circuits which also play a role in reward processing and reinforcement behavior. However, it is largely unknown if cerebral dysfunctions are reversible or persist during long term abstinence. MATERIALS AND METHODS: Cortical activation during auditory target processing (oddball task, P300 component) was recorded with 32-channel EEG in 247 healthy subjects consisting of 84 smokers, 53 former smokers (mean time of abstinence 11.9 years), and 110 never smokers. RESULTS: Both current smokers and former smokers exhibited significantly diminished P300 amplitudes (Cz, Pz) relative to never smokers. Neuroelectric source analysis (low resolution brain electromagnetic tomography) revealed a hypoactivation of the anterior cingulate, orbitofrontal, and prefrontal cortex in smokers compared to never smokers. A similar profile of hypoactivation was observed in former smokers. CONCLUSION: For the first time, evidence is provided that dysfunctional activation of frontal lobe networks in smokers is also present in long term abstainers.

Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics.

RATIONALE: Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia. OBJECTIVE: We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation. METHODS: Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence. RESULTS: Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms. CONCLUSIONS: Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.

Borderline personality disorder and comorbid addiction: epidemiology and treatment.

BACKGROUND: Borderline personality disorder (BPD) affects 2.7% of adults. About 78% of adults with BPD also develop a substance-related disorder or addiction at some time in their lives. These persons are more impulsive and clinically less stable than BPD patients without substance dependency. They display suicidal behavior to a greater extent, drop out of treatment more often, and have shorter abstinence phases. The combination of borderline personality disorder with addiction requires a special therapeutic approach. METHOD: This review is based on a selective literature search about the treatment of patients with BPD and addiction, with particular attention to Cochrane Reviews and randomized controlled trials (RCT). RESULTS: The available evidence is scant. In two RCTs, Dialectical Behavior Therapy for Substance Use Disorders (DBT-SUD) was found to improve patients' overall functional level (standardized mean difference, 1.07-1.78) and to increase the number of abstinence days (effect strength [ES], 1.03) and negative urine samples (ES, 0.75). Dual focus schema therapy (DFST) was evaluated in three RCTs. Because of methodological problems, however, no useful quantitative comparison across trials is possible. In one RCT, dynamic deconstructive psychotherapy (DDP) was found to have only a moderate, statistically insignificant effect. Only a single study provides data about potentially helpful drug therapy over the intermediate term. CONCLUSION: Patients with borderline personality disorder and comorbid addiction should be treated as early as possible for both conditions in a thematically hierarchical manner. There is no evidence for any restriction on drug therapy to prevent recurrent addiction in these patients. The psychotherapeutic techniques that can be used (despite the currently inadequate evidence base) include DBT-SUD, DFST, and DDP. These patients need qualified expert counseling in choosing a suitable type of psychotherapy. Specific treatment is available in only a few places, and the relevant treatment networks in Germany are just beginning to be constructed.

"Glass fairies" and "bone children": adolescents and young adults with anorexia nervosa show positive reactions towards extremely emaciated body pictures measured by the startle reflex paradigm.

In this study, we investigated the emotional processing of extremely emaciated body cues in adolescents and young adults with (n = 36) and without (n = 36) anorexia nervosa (AN), introducing a new picture type, which was taken from websites that promote extreme thinness and is targeted specifically at adolescents interested in extreme thinness. A startle reflex paradigm was used for implicit reactions, while a self-assessment instrument was used for subjective responses. We found a significant group difference with a startle inhibition (appetitive response) among the patients and a startle potentiation (aversive response) among the controls, whereas no such difference for subjective measures was found. The results are in contrast to previous studies, which proposed a general failure to activate the appetitive motivational system in AN, but in keeping with findings from other addictions, where the same response pattern has been found. Implications for prevention and therapy are discussed.

Increased turnover of dopamine in caudate nucleus of detoxified alcoholic patients.

A previous study of the DOPA decarboxylase substrate 6-[(18)F]fluoro-L-DOPA (FDOPA) with positron emission tomography (PET) detected no difference of the net blood-brain transfer rate (Kin(app)) between detoxified alcoholic patients and healthy controls. Instead, the study revealed an inverse correlation between Kin (app) in left ventral striatum and alcohol craving scores. To resolve the influx and efflux phases of radiolabeled molecules, we independently estimated the unidirectional blood-brain FDOPA clearance rate (K) and the washout rate of [(18)F]fluorodopamine and its deaminated metabolites (k(loss)), and we also calculated the total distribution volume of decarboxylated metabolites and unmetabolized FDOPA as a steady-state index of the dopamine storage capacity (V(d)) in brain. The craving scores in the 12 alcoholics correlated positively with the rate of loss (k(loss)) in the left ventral striatum. We conclude that craving is most pronounced in the individuals with relatively rapid dopamine turnover in the left ventral striatum. The blood-brain clearance rate (K), corrected for subsequent loss of radiolabeled molecules from brain, was completely normal throughout the brain of the alcoholics, in whom the volume of distribution (V(d)) was found to be significantly lower in the left caudate nucleus. The magnitude of Vd in the left caudate head was reduced by 43% relative to the 16 controls, consistent with a 58% increase of k(loss). We interpret the findings as indicating that a trait for rapid dopamine turnover in the ventral striatum subserves craving and reward-dependence, leading to an acquired state of increased dopamine turnover in the dorsal striatum of detoxified alcoholic patients.

Context insensitivity during positive and negative emotional expectancy in depression assessed with functional magnetic resonance imaging.

Patients with depression show an enhanced preoccupation with negative expectations and are often unable to look forward to positive events. Here we studied anticipatory emotional processes in unmedicated depressed patients using functional magnetic resonance imaging. Consistent with a negative processing bias, we hypothesized enhanced responses to negative and attenuated responses to positive expectancy cues in brain areas associated with emotional expectancy. Participants comprised 19 drug-free depressed patients and 19 matched healthy control subjects who viewed affective photographs. Pictures were preceded by an expectancy cue which signaled the emotional valence of the upcoming picture in half of the trials. Depressed patients showed attenuated blood-oxygen-level-dependent responses in the left lateral prefrontal cortex (inferior frontal gyrus, Brodmann area 44) during positive expectancy and-contrary to our hypothesis-in the right lateral orbitofrontal cortex (middle frontal gyrus, Brodmann area 47) during negative expectancy. This attenuation was specific for the anticipation (as opposed to the perception) of emotional pictures and correlated with a clinical measure of depressive symptoms. The observed attenuation suggests emotion-context insensitivity rather than a negative processing bias during anticipatory emotional processes in depression. This hyporeactivity may contribute to clinical features like anergia, apathy, and loss of motivation in the context of both positive and negative incentives.

Hemispheric asymmetry for affective stimulus processing in healthy subjects--a fMRI study.

BACKGROUND: While hemispheric specialization of language processing is well established, lateralization of emotion processing is still under debate. Several conflicting hypotheses have been proposed, including right hemisphere hypothesis, valence asymmetry hypothesis and region-specific lateralization hypothesis. However, experimental evidence for these hypotheses remains inconclusive, partly because direct comparisons between hemispheres are scarce. METHODS: The present fMRI study systematically investigated functional lateralization during affective stimulus processing in 36 healthy participants. We normalized our functional data on a symmetrical template to avoid confounding effects of anatomical asymmetries. Direct comparison of BOLD responses between hemispheres was accomplished taking two approaches: a hypothesis-driven region of interest analysis focusing on brain areas most frequently reported in earlier neuroimaging studies of emotion; and an exploratory whole volume analysis contrasting non-flipped with flipped functional data using paired t-test. RESULTS: The region of interest analysis revealed lateralization towards the left in the medial prefrontal cortex (BA 10) during positive stimulus processing; while negative stimulus processing was lateralized towards the right in the dorsolateral prefrontal cortex (BA 9 & 46) and towards the left in the amygdala and uncus. The whole brain analysis yielded similar results and, in addition, revealed lateralization towards the right in the premotor cortex (BA 6) and the temporo-occipital junction (BA 19 & 37) during positive stimulus processing; while negative stimulus processing showed lateralization towards the right in the temporo-parietal junction (BA 37,39,42) and towards the left in the middle temporal gyrus (BA 21). CONCLUSION: Our data suggests region-specific functional lateralization of emotion processing. Findings show valence asymmetry for prefrontal cortical areas and left-lateralized negative stimulus processing in subcortical areas, in particular, amygdala and uncus.

Decreased Verbal Learning but not Recognition Performance in Alcohol-dependent Individuals During Early Abstinence.

OBJECTIVE: Alcoholism ultimately leads to impairment of memory and other cognitive functions. This can interfere with treatment, if cognitively impaired alcohol-dependent individuals have difficulties recalling and implementing skills acquired during therapy. We investigate if alcohol-dependent individuals without clinically apparent withdrawal symptoms may still be impaired in higher-order cognitive functions. METHODS: Thirty-four alcohol-dependent patients and 20 matched healthy controls were tested with the Verbal Learning and Memory Test which includes seven measurement points. The test comprises free recall, free recall after distraction and after 30 minute delay, and a word recognition task. Testing was performed between day seven and day 10 after the beginning of abstinence, when clinical withdrawal symptoms had ceased. RESULTS: Compared to healthy controls, alcohol-dependent patients performed worse in free recall after delay, but not in word recognition. Healthy controls showed a more linear progression of improvement in verbal memory performance. Overall, alcohol-dependent individuals showed reduced verbal learning efficiency. The extent of impaired recall after distraction was positively associated (one-tailed test) with history of delirium (r=0.34, p=0.04), seizures (r=0.46, p=0.01), and years since diagnosis for alcohol dependency (r=0.39, p=0.01). CONCLUSIONS: Our results provide evidence that unmedicated alcohol-dependent patients without obvious withdrawal symptoms had impaired verbal recall, but normal recognition performance, at seven to 10 days after onset of abstinence. This deficit may deteriorate treatment outcomes due to poorer implementation of skills newly-learned during this time period.