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.

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.

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.

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.

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.

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.

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.

Low effective organizational strategies in visual memory performance of unmedicated alcoholics during early abstinence.

OBJECTIVE: Alcohol-dependent patients in early abstinence show an impairment of cognitive functions which can be seen in poor implementation of newly learned skills for avoiding relapse. Executive dysfunction may persist during abstinence in alcohol-dependent persons, thus mitigating long-term abstinence. This study assessed visual memory function and choice of organizational strategies in alcoholics, as these are major factors necessary to implement ongoing behavior changes which are required for maintaining abstinence. METHODS: We investigated 25 severely alcohol-dependent male patients between days 7 to 10 of abstinence, immediately after clinical withdrawal symptoms have ceased, compared to 15 healthy age, sex, and education matched controls. Pharmacological therapy had been terminated at least four half-lifes before inclusion into the study. Visual perceptual learning and organizational strategies were assessed with the Rey-Osterrieth Complex Figure Test (R-OCF). RESULTS: There were no group differences in copying or recalling the figure, but time differences occurred. Alcoholics and healthy controls performed worse in recalling than in copying. But, alcoholics used less effective organizational strategies. CONCLUSIONS: There was a deficit in choice of organizational strategy in newly abstinent and unmedicated alcohol-dependent patients. Due to the imperfect organizational strategies, alcoholics might need auxiliary therapeutic care to strengthen their cognitive ability.

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.

Ventral striatal activation during reward anticipation correlates with impulsivity in alcoholics.

BACKGROUND: Alcohol dependence is often associated with impulsivity, which may be correlated with dysfunction of the brain reward system. We explored whether functional brain activation during anticipation of incentive stimuli is associated with impulsiveness in detoxified alcoholics and healthy control subjects. METHODS: Nineteen detoxified male alcoholics and 19 age-matched healthy men participated in a functional magnetic resonance imaging (fMRI) study using a monetary incentive delay (MID) task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain, avoidance of monetary loss, or no consequence. Impulsivity was assessed with the Barratt Impulsiveness Scale-Version 10 (BIS-10). RESULTS: Detoxified alcoholics showed reduced activation of the ventral striatum during anticipation of monetary gain relative to healthy control subjects. Low activation of the ventral striatum and anterior cingulate during gain anticipation was correlated with high impulsivity only in alcoholics, not in control subjects. CONCLUSIONS: This study suggests that reduced ventral striatal recruitment during anticipation of conventional rewards in alcoholics may be related to their increased impulsivity and indicate possibilities for enhanced treatment approaches in alcohol dependence.

[Gamma-hydroxybutyrat (GHB)-dependence and -withdrawal in the case of previous alcohol dependence]. / Gamma-Hydroxybutyrat (GHB)-Abhängigkeit und -Entzug bei vorbestehender Alkoholabhängigkeit.

OBJECTIVE: gamma-Hydroxybutyrat (GHB) is used medically for narcolepsy and as a narcotic. It is also a rare illegal drug. In this case report the development of a GHB-dependency against the background of a primary alcohol dependency is described. METHODS: Based on established alcohol withdrawal scales (AWSS by Wetterling, CIWA) and neuropsychological testing procedures (CGI, GAF, SKID-II, PISQ, analog-scale for Craving), the initial situation, the development of psychopathological findings, and the course of detoxification were shown. RESULTS/CONCLUSION: The combined detoxication of GHB and alcohol was successfully finished by a reduction schedule of diazepam. Withdrawal-assessment scales for alcohol were helpful, but show limitations for GHB-withdrawal symptoms. The patient suffers, according to ICD-10, from a multiple drug dependence (alcohol, GHB, abstinence from amphetamines). Symptoms of insomnia, major depression, and generalized anxiety disorder can be associated with the use of GHB.

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.

Dopamine in amygdala gates limbic processing of aversive stimuli in humans.

Dopamine is released under stress and modulates processing of aversive stimuli. We found that dopamine storage capacity in human amygdala, measured with 6-[(18)F]fluoro-L-DOPA positron emission tomography, was positively correlated with functional magnetic resonance imaging blood oxygen level-dependent signal changes in amygdala and dorsal anterior cingulate cortex that were evoked by aversive stimuli. Furthermore, functional connectivity between these two regions was inversely related to trait anxiety. Our results suggest that individual dopamine storage capacity in amygdala subserves modulation of emotional processing in amygdala and dorsal cingulate, thereby contributing to individual differences in anxious temperament.

Psychotherapy of personality disorders and concomitant substance dependence.

PURPOSE OF REVIEW: Psychotherapy of patients with personality disorder and concomitant substance dependence requires an integrative approach. Although a number of studies have evaluated psychotherapy for one of these disorders, only few studies have described the effectiveness of treatment programs in comorbid patients. These limited findings provide a basis for the further development of treatments for personality disorder and concomitant substance dependence. This review gives an overview of the current state of research in this field. RECENT FINDINGS: Although a large number of evaluation studies tested the effectiveness of several therapies for alcohol dependence, far fewer evaluated nonalcohol substance dependence. There are very few evaluations of the efficacy of psychotherapy for other forms of drug dependence. Only dialectical behavior therapy and dual-focus schema therapy have been tested for the treatment of personality disorder and substance dependence. SUMMARY: To date, two randomized controlled trials in 59 female-only patients with borderline personality disorder and substance abuse provided the best evidence-based data for the effectiveness of dialectical behavior therapy. For dual-focus schema therapy, a single randomized controlled trial indicated a curative effect in a small group of patients with personality disorder and substance dependence. Although the results of these studies are encouraging, further clinical trials need to be conducted in larger populations including male participants.

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.