Cognitive training and remediation interventions for substance use disorders: a Delphi consensus study.

AIMS: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. DESIGN, SETTING AND PARTICIPANTS: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. MEASUREMENTS: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. FINDINGS: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. CONCLUSIONS: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

Disordered eating symptoms in Austrian men of different ages in the context of fitness centers.

PURPOSE: To assess eating behavior and associated factors in male fitness-center attendees. METHODS: An anonymous questionnaire was administered to male fitness center members of Innsbruck (Austria), aged 18-80 years to assess socio-demographic features, weight history, sports activity, eating behavior including disordered eating based on the Eating Disorder Examination Questionnaire (EDE-Q) and DSM-5 key symptoms for eating disorders (anorexia nervosa, binge eating, bulimia nervosa, purging disorder) and body image. Three age groups (younger-middle-aged-older men) were compared regarding the variables described above. RESULTS: A total of 307 men included displayed high rates of disordered eating as described by EDE-Q cutoff scores (5-11%) as well as by DSM-5 eating disorder symptoms (10%). While EDE-Q cutoff scores did not differentiate between the groups, the prevalences of DSM-5 eating disorder symptoms yielded significant differences indicating a clear decrease with increasing age. Binge eating and bulimic symptoms with excessive exercising as the purging method were the most often reported symptoms. CONCLUSION: Although described as typically female, disordered eating does occur in male fitness-gym attendees across all ages. The older the men, the less prevalent are the symptoms. Awareness of disordered eating and possible negative effects need to be addressed for attendees and trainers of the gym. LEVEL OF EVIDENCE: V-descriptive survey study.

Do Social Cognition Deficits Recover with Abstinence in Alcohol-Dependent Patients?

BACKGROUND: Despite growing evidence of the presence and clinical relevance of deficits in social cognition in individuals with alcohol use disorder (AUD), less is known about the potential of "natural" recovery with abstinence in this neurocognitive domain. This study investigated the abstinence-based recovery of neurocognitive social abilities in alcohol-dependent patients (ADP) using a prospective longitudinal design with follow-up assessment under controlled conditions of abstinence during alcohol dependence inpatient treatment. METHODS: Seventy-seven participants (42 ADP and 35 healthy controls [HC]) performed social cognition testing, including facial emotion recognition, perspective taking, and affective responsiveness twice (baseline/T1 and follow-up/T2) during comparable follow-up periods. Assessment of social cognition in abstinent ADP was conducted at the beginning (T1; within the first 2 weeks) and at the end (T2; within the last 2 weeks) of long-term (2 months) abstinence-oriented alcohol dependence inpatient treatment. Only patients abstinent for >14 days (last heavy drinking day >21 days) at baseline (T1) and who remained abstinent at follow-up (T2) were included. RESULTS: ADP, who on average were nearly 2 months abstinent at T1, showed poorer social cognition in all 3 areas (emotion recognition, perspective taking, and affective responsiveness) than HC. There was no difference between groups on the change in performance over time, and group differences (ADP vs. HC) remained significant at T2, indicating persistent social cognition deficits in ADP following controlled abstinence during inpatient treatment. CONCLUSIONS: Our findings indicate no natural recovery of social cognition impairments in ADP during an intermediate to long-term period of abstinence (2+ months), the usual active treatment phase. Research aimed at developing interventions that focus on the improvement of social cognition deficits (e.g., social cognition training) and determining whether they benefit short- and long-term clinical outcomes in AUD seems warranted.

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

Impact of Social Cognition on Alcohol Dependence Treatment Outcome: Poorer Facial Emotion Recognition Predicts Relapse/Dropout.

BACKGROUND: Despite growing evidence for neurobehavioral deficits in social cognition in alcohol use disorder (AUD), the clinical relevance remains unclear, and little is known about its impact on treatment outcome. This study prospectively investigated the impact of neurocognitive social abilities at treatment onset on treatment completion. METHODS: Fifty-nine alcohol-dependent patients were assessed with measures of social cognition including 3 core components of empathy via paradigms measuring: (i) emotion recognition (the ability to recognize emotions via facial expression), (ii) emotional perspective taking, and (iii) affective responsiveness at the beginning of inpatient treatment for alcohol dependence. Subjective measures were also obtained, including estimates of task performance and a self-report measure of empathic abilities (Interpersonal Reactivity Index). According to treatment outcomes, patients were divided into a patient group with a regular treatment course (e.g., with planned discharge and without relapse during treatment) or an irregular treatment course (e.g., relapse and/or premature and unplanned termination of treatment, "dropout"). RESULTS: Compared with patients completing treatment in a regular fashion, patients with relapse and/or dropout of treatment had significantly poorer facial emotion recognition ability at treatment onset. Additional logistic regression analyses confirmed these results and identified poor emotion recognition performance as a significant predictor for relapse/dropout. Self-report (subjective) measures did not correspond with neurobehavioral social cognition measures, respectively objective task performance. Analyses of individual subtypes of facial emotions revealed poorer recognition particularly of disgust, anger, and no (neutral faces) emotion in patients with relapse/dropout. CONCLUSIONS: Social cognition in AUD is clinically relevant. Less successful treatment outcome was associated with poorer facial emotion recognition ability at the beginning of treatment. Impaired facial emotion recognition represents a neurocognitive risk factor that should be taken into account in alcohol dependence treatment. Treatments targeting the improvement of these social cognition deficits in AUD may offer a promising future approach.

Impulsivity and Alcohol Dependence Treatment Completion: Is There a Neurocognitive Risk Factor at Treatment Entry?

BACKGROUND: Although there is considerable support for the relationship between impulsivity and alcohol dependence, little is known about the impact of neurocognitive aspects of impulsivity on treatment outcome. The aim of this study was to prospectively investigate the impact of neurocognitive impulsivity at treatment onset on treatment completion. METHODS: Forty-three alcohol-dependent patients entering inpatient treatment for alcohol dependence completed neurocognitive measures of impulsivity at the beginning of treatment. Assessments included prototypical measures of impulsive action (Go/No-go task [GNG] and Stop Signal Task [SST]) and impulsive choice (Delay Discounting Test [DDT], and Iowa Gambling Task). According to treatment outcomes, patients were divided into a patient group with regular treatment completion (e.g., with planned discharges, and without relapse during treatment) or irregular treatment course (e.g., premature and unplanned termination of treatment, "dropout," and/or relapse). RESULTS: Results show that, relative to patients completing treatment in a regular fashion (regular treatment completers [RTC]; 67%), those with an irregular course of treatment (relapse and/or dropout) (irregular treatment completers [ITC]; 33%) had significantly poorer GNG response inhibition performance (p = 0.011), and showed a trend toward greater delay discounting (DDT; p = 0.052) at treatment onset. Additional logistic regression analyses identified poor GNG response inhibition performance as a significant predictor for an irregular treatment course (GNG: p = 0.021; DDT: p = 0.067), particularly for relapse (GNG: p = 0.023). CONCLUSIONS: Neurocognitive impulsivity impacts upon treatment completion and appears sensitive for the prediction of relapse and dropout in alcohol-dependent patients. Poorer GNG response inhibition and a tendency toward steeper discounting of delayed rewards should be regarded as neurocognitive risk factors, which can be identified early in the course of alcohol dependence treatment.

Prevalence of eating disorders in middle-aged women.

OBJECTIVE: Little is known about the prevalence and correlates of eating disorders (ED) in middle-aged women. METHOD: We mailed anonymous questionnaires to 1,500 Austrian women aged 40-60 years, assessing ED (defined by DSM-IV), subthreshold ED, body image, and quality of life. We broadly defined "subthreshold ED" by the presence of either (1) binge eating with loss of control or (2) purging behavior, without requiring any of the other usual DSM-IV criteria for frequency or severity of these symptoms. RESULTS: Of the 715 (48%) responders, 33 [4.6%; 95% confidence interval (CI): 3.3-6.4%] reported symptoms meeting full DSM-IV criteria for an ED [bulimia nervosa = 10; binge eating disorder = 11; eating disorder not otherwise specified (EDNOS) = 12]. None displayed anorexia nervosa. Another 34 women (4.8%; CI: 3.4-6.6%) displayed subthreshold ED. These women showed levels of associated psychopathology virtually equal to the women with full-syndrome diagnoses. DISCUSSION: ED appear common in middle-aged women, with a preponderance of binge eating disorder and EDNOS diagnoses as compared to the "classical" diagnoses of anorexia and bulimia nervosa. Interestingly, middle-aged women with even very broadly defined subthreshold ED showed distress and impairment comparable to women with full-scale ED.

The menopausal transition--a possible window of vulnerability for eating pathology.

OBJECTIVE: No published studies, to our knowledge, have examined the association of menopausal status with eating disorders and body image in women. We assessed these associations in a large sample of middle-aged women. METHOD: We administered an anonymous questionnaire to a randomly selected nonclinical sample of women aged 40-60 in Innsbruck, Austria. The questionnaire covered demographic items, menopausal status, weight history, measures of body image, and current eating disorders as diagnosed by DSM-IV criteria. Using modified WHO criteria, we classified the respondents' current stage of menopausal transition as premenopausal (N = 192), perimenopausal (N = 110), or naturally postmenopausal (N = 134). In a separate analysis, we also examined the small group of women with surgically induced menopause (N = 12). RESULTS: The three groups were similar in all demographic features except age, and did not differ significantly on current body mass index (BMI), weight-control behaviors, or dieting history after age adjustment. However, perimenopausal women reported a significantly greater prevalence of eating disorders as compared to premenopausal women. Perimenopausal women also reported significantly higher self-ratings of "feeling fat" and higher Body Shape Questionnaire scores than premenopausal women. Women with surgically induced menopause also showed an elevated prevalence of eating and body image pathology. DISCUSSION: Our data suggest that the menopausal transition is associated with an increased prevalence of eating disorders and negative body image. Menopause, like puberty, may perhaps represent a window of vulnerability to these conditions, likely because of changes in hormonal function, body composition, and conceptions of womanhood.

Cognitive remediation therapy during treatment for alcohol dependence.

OBJECTIVE: Cognitive impairments in individuals with alcohol dependence may interfere with the progress of treatment and contribute to the progression of the disease. This study aimed to determine whether cognitive remediation (CR) therapy applied during treatment for alcohol dependence improves cognitive functioning in alcohol-dependent inpatients. A secondary aim was to evaluate whether the benefits of CR generalize to noncognitive clinically meaningful outcomes at the end of inpatient treatment. METHOD: Forty-one alcohol-dependent patients entering inpatient treatment for alcohol dependence were randomly assigned to receive conventional treatment (n = 21) or an additional 12 sessions of computer-assisted CR focusing on cognitive enhancement in attention/executive function and memory domains (n = 20). Assessments of cognitive abilities in these domains as well as of psychological well-being and alcohol craving were conducted at baseline (at the beginning of inpatient treatment) and after CR (at the end of treatment). RESULTS: Results indicated that, relative to patients completing conventional treatment, those who received supplemental CR showed significant improvement in attention/executive function and memory domains, particularly in attention (alertness, divided attention), working memory, and delayed memory (recall). In addition, patients receiving CR during alcohol-dependence treatment showed significantly greater improvements in psychological well-being (Symptom Checklist-90-Revised) and in the compulsion aspect of craving (Obsessive Compulsive Drinking Scale-German version). CONCLUSIONS: CR during inpatient treatment for alcohol dependence is effective in improving cognitive impairments in alcohol-dependent patients. The benefits generalize to noncognitive outcomes, demonstrating that CR may be an efficacious adjunctive intervention for the treatment of alcohol dependence.

Olfactory function and schizophrenia: an update.

PURPOSE OF REVIEW: Olfaction is a field of growing interest in schizophrenia research. This article reviews recent studies on olfactory functions in schizophrenia. RECENT FINDINGS: The current literature provides additional insights into olfactory deficits, abnormalities, and olfactory hedonic dysfunction in schizophrenia. Recent findings reinforce particular associations with negative symptoms and deficit syndrome schizophrenia. Studies indicate that abnormalities in patients with schizophrenia extend to more peripheral olfactory structures and functions, including olfactory receptor neuron dysfunction. Olfactory identification ability was found to relate to prodromal disorganization symptoms in young high-risk patients. Further support for the notion of a genetic contribution to olfactory dysfunction in schizophrenia derives from studies reporting physiological olfactory dysfunction (olfactory event-related potentials) in unaffected relatives, and an odor-specific hyposmia, present in both patients with schizophrenia and family members. SUMMARY: Further research is needed to improve our understanding of olfactory dysfunction in schizophrenia. Recent encouraging findings underscore that the olfactory system is a field of research that holds promise for advancing our understanding of the pathophysiology of schizophrenia and possibly as a useful endophenotypic marker of neurodevelopmental vulnerability.

Anterior cingulate grey-matter deficits and cannabis use in first-episode schizophrenia.

BACKGROUND: Despite the high prevalence of cannabis use in schizophrenia, few studies have examined the potential relationship between cannabis exposure and brain structural abnormalities in schizophrenia. AIMS: To investigate prefrontal grey and white matter regions in patients experiencing a first episode of schizophrenia with an additional diagnosis of cannabis use or dependence (n=20) compared with similar patients with no cannabis use (n=31) and healthy volunteers (n=56). METHOD: Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous magnetic resonance images and automatically segmented into grey and white matter. RESULTS: Patients who used cannabis had less anterior cingulate grey matter compared with both patients who did not use cannabis and healthy volunteers. CONCLUSIONS: A defect in the anterior cingulate is associated with a history of cannabis use among patients experiencing a first episode of schizophrenia and could have a role in poor decision-making and in choosing more risky outcomes.

Executive function and memory in relation to olfactory deficits in alcohol-dependent patients.

BACKGROUND: Prior research indicates that chronic alcoholism is accompanied by olfactory deficits. These have been suggested to reflect dysfunctions in olfactory brain regions. The present study investigated the role of neurocognitive functioning in tests (executive function and memory) sensitive to the functional integrity of brain areas that are crucial to olfactory processing in patients with alcohol dependence. METHODS: Performance on olfactory functions (detection threshold, quality discrimination, identification), executive function (Wisconsin Card Sorting Test), and memory (German version of the California Verbal Learning Test) was assessed in 32 alcohol-dependent patients and 30 healthy comparison subjects, comparable in age, gender, and smoking status. RESULTS: Compared with controls, alcohol-dependent patients were impaired in all 3 domains, olfactory functions, executive function, and memory. In patients, olfactory discrimination ability was positively correlated with executive function performance. Regression analyses conducted to clarify the relation between group (patients vs controls), executive function, memory, and olfactory functions indicated that group was the only significant predictor of olfactory detection threshold and identification, and both group and executive function were found to be the significant predictors of olfactory discrimination. CONCLUSIONS: Olfactory deficits in alcohol dependence appear to be associated with prefrontal cognitive dysfunction. Results indicate that olfactory quality discrimination deficits are related to executive function impairment. These findings add to the available research on frontal lobe dysfunction in alcoholism, suggesting that alcohol-related olfactory discrimination deficits may be associated with impairment in the functional integrity of the prefrontal lobe.

Childhood body-focused behaviors and social behaviors as risk factors of eating disorders.

BACKGROUND: The risk factors for adolescent eating disorders are poorly understood. It is generally agreed, however, that interactions with one's body and interactions with others are two important features in the development of anorexia and bulimia nervosa. Therefore, we assessed a variety of childhood body-focused behaviors and childhood social behaviors in eating-disordered patients as compared to non-eating-disordered subjects. METHOD: We compared 50 female inpatients with eating disorders (anorexia or bulimia nervosa), 50 female inpatients with polysubstance dependence, and 50 nonpatient female control subjects with no history of eating or substance abuse disorders (all defined by DSM-IV criteria), using a semi-structured interview of our own design. We asked questions about (1) childhood body-focused behaviors (e.g. thumb-sucking) and body-focused family experiences (e.g. bodily caresses), and (2) childhood social behaviors (e.g. numbers of close friends) and family social styles (e.g. authoritarian upbringing). RESULTS: Many body-focused measures, such as feeding problems, auto-aggressive behavior, lack of maternal caresses, and family taboos regarding nudity and sexuality, characterized eating-disordered patients as opposed to both comparison groups, as did several social behaviors, such as adjustment problems at school and lack of close friends. However, nail-biting, insecure parental bonding, and childhood physical and sexual abuse were equally elevated in both psychiatric groups. CONCLUSION: It appears that eating-disordered patients, as compared to substance-dependent patients and healthy controls, show a distinct pattern of body-focused and social behaviors during childhood, characterized by self-harm, a rigid and 'body-denying' family climate, and lack of intimacy.

Various bilateral olfactory deficits in male patients with schizophrenia.

Olfactory identification deficits in schizophrenia patients are well documented. Less is known about the functioning of other olfactory domains and the possibility of lateralized dysfunctions. Thirty male schizophrenia patients and 30 male healthy controls underwent unirhinal assessment of various olfactory domains: detection threshold (dimethyl disulfide, phenyl ethanol), quality discrimination, and odor ratings (familiarity, pleasantness, edibility, intensity) of pure chemicals (Munich Olfaction Test), as well as familiarity and edibility judgments and identification of everyday odors. Aside from impaired identification, patients showed impaired familiarity and edibility judgments of everyday odors. With regard to odor ratings of pure chemicals, group differences were observed only in pleasantness ratings, with higher ratings in patients. Furthermore, patients had reduced sensitivity with dimethyl disulfide and reduced quality discrimination compared with controls. Further analyses showed that identification deficits were not attributable to reduced sensitivity but may be associated with impairments in quality discrimination. Olfactory dysfunctions were found across both nostrils. Results suggest specific dysfunctions in olfactory processing in schizophrenia patients, including early stages of the odor identification process.

Olfactory functions and volumetric measures of orbitofrontal and limbic regions in schizophrenia.

OBJECTIVE: Olfactory deficits in schizophrenia patients have been suggested to reflect medial temporal and/or prefrontal brain abnormalities. In this study, we examined the relationship between different olfactory functions and volumes of the hippocampus-amygdala complex (HAC) and the orbitofrontal brain region using magnetic resonance imaging (MRI). METHODS: Thirty-three young men with schizophrenia (DSM-IV) and 40 healthy controls performed unirhinal olfactory assessment including the main olfactory functions (threshold, discrimination, and identification), and odor judgements (intensity, edibility, familiarity, and pleasantness). Volumes of regions in the medial temporal lobe (hippocampus and amygdala) and the prefrontal region (orbitofrontal gray and white matter) were measured on MRI scans. RESULTS: Compared with controls, patients showed bilaterally impaired thresholds, quality discrimination and identification, as well as edibility judgements. Olfactory deficits were not attributable to smoking, premorbid intelligence, or impaired thresholds. Relative to controls, patients had bilateral reduced hippocampus and amygdala volumes. In patients, smaller hippocampus volumes were associated with poorer olfactory discrimination ability. CONCLUSIONS: Olfactory deficits in schizophrenia appear to be associated with morphometric abnormalities in the medial temporal rather than the orbitofrontal region (OFR). These results indicate that olfactory quality discrimination deficits are related to structural hippocampus abnormalities. Future studies of genetic and behavioral high-risk samples seem warranted.

Body-image dissatisfaction in gay versus heterosexual men: is there really a difference?

BACKGROUND: Gay men are thought to experience body-image concerns or disorders more frequently than heterosexual men. It is unclear, however, whether these putative concerns are due to unrealistic body ideals (aspiring to a body shape that is difficult or impossible to attain), body-image distortion (misperceiving the actual shape of one's body), or both. METHOD: We administered a well-established computerized body-image test, the "somatomorphic matrix," to 37 gay men recruited from the community in April 1999 and compared the results with previous data from 49 community-recruited heterosexual comparison men and 24 clinic-recruited heterosexual men with eating disorders. RESULTS: Gay men were indistinguishable from the community-recruited heterosexual comparison men on measures of both body ideals and body-image distortion. By contrast, eating-disordered men were significantly distinguishable from both other groups on body-image distortion. The lack of differences between community gay and heterosexual men on body-image indices seems unlikely to represent a type II error, since the somatomorphic matrix showed ample power to detect abnormalities in the eating-disordered men, despite the smaller sample size of the latter group. CONCLUSION: Contrary to our hypotheses, gay men did not differ significantly from heterosexual men on measures of body image. These unexpected findings cast doubt on the widespread belief that gay men experience greater body-image dissatisfaction than heterosexual men. If our findings are valid, it follows that some previous studies of body image in gay men may possibly have been influenced by selection bias.

Olfactory functioning in patients with alcohol dependence: impairments in odor judgements.

AIMS: Prior studies indicate that alcohol-dependent patients have impaired olfactory sensitivity, odor quality discrimination and identification ability. However, olfactory functioning with regard to the immediate, perception driven odor associations is unknown. Therefore, this study assessed olfactory judgements in nonamnesic and nondemented patients with alcohol dependence. METHODS: Thirty alcohol-dependent patients and 30 healthy control subjects, well matched for gender, age and smoking status, and screened for olfactory sensitivity, were asked to rate intensity, familiarity, edibility and pleasantness of 16 odors using visual rating scales. RESULTS: Compared with controls, patients showed lower scores in odor familiarity and impaired edibility judgements. These impairments were observed bilaterally, were present independently of age, gender, general mental abilities and length of abstinence, and not attributable to smoking or impaired olfactory sensitivity. No differences between groups were found in odor intensity and pleasantness judgements. CONCLUSION: These results extend prior findings of alcohol-related olfactory deficits, indicating impairments in olfactory processes of odor familiarity and edibility in alcohol-dependent patients. Although the basis of these deficits is still unknown, our finding of a distinct pattern of olfactory functional impairment and sparing (intensity, pleasantness) [corrected] suggests that there is no generalized [corrected] olfactory dysfunction, but [corrected] neural olfactory networks may be affected differently. However, alcoholism appears to be associated with a variety of disturbances in olfactory processing [corrected]

No deterioration of cognitive performance in an aggressive unilateral and bilateral antidepressant rTMS add-on trial.

BACKGROUND: Cognitive functions were assessed before and following a course of repetitive transcranial magnetic stimulation (rTMS) in patients with depression participating in a sham-controlled, randomized trial of rTMS as adjunct to antidepressant treatment. METHOD: Forty-one medicated inpatients with a DSM-IV diagnosis of a depressive episode were consecutively randomly assigned to 1 of 3 groups comparing 2 active rTMS conditions with sham stimulation. The rTMS was applied either at high frequency over the left dorsolateral-prefrontal cortex (DLPFC) (10 sessions x 10 trains x 10 seconds 20 Hz at 100% motor threshold [MT], 90-second intertrain interval) or in a combined high- and low-frequency manner to the left and right DLPFC, respectively (10 sessions x 1 train x 10 minutes at 120% MT). Thirty-eight patients completed a neuropsychological test battery at baseline and following day 14. The cognitive assessment focused on motor skills, attention, executive functions, learning, and memory. Data were collected from November 1999 to August 2002. RESULTS: Active treatment groups did not differ with respect to assessed cognitive measures and thus were pooled. A comparison of short-term changes (baseline-day 14) in neuropsychological performance revealed a more favorable time course of the actively treated patients for encoding in the verbal memory test compared with the sham-stimulated patients. CONCLUSIONS: Unilateral rTMS as well as bilateral combined rTMS revealed no detrimental effects on cognition, as compared with the sham group. Moreover, neither the add-on design nor the used aggressive parameters had a negative impact on cognitive measures in comparison with sham. Repetitive transcranial magnetic stimulation might have mild beneficial cognitive effects partly independent of its antidepressant efficacy.