Schizophrenia Bulletin - current issue

Leaping Tall Buildings--The Science-to-Service Gap in Schizophrenia Treatment

Lehman, A. F. — 2009-06-15

Psychiatry and Oppression: A Personal Account of Compulsory Admission and Medical Treatment

Gray, B. — 2009-06-15

Toward a Model of Impaired Reality Testing in Rats

McDannald, M., Schoenbaum, G. — 2009-06-15

Schizophrenia is a chronic brain disorder that affects about 1.1% of the adult US population annually. Hallucinations, delusions, and impaired reality testing are prominent symptoms of the disorder. Modeling these symptoms is difficult because it is unclear how to assess impaired reality testing in animals. Animals cannot discuss their beliefs; however, a century of learning experiments has shown us that they, like us, construct complex internal representations of their world. Presumably, these representations can become confused with reality for animals in much the same way that they do for schizophrenic patients. Indeed, there is evidence from studies of Pavlovian conditioning that this happens even in normal animals. For example, early in training a cue that has been paired with reward elicits a highly realistic, sensory representation of that reward, which is to some extent indistinguishable from reality. With further training, this sensory hallucination of reward is replaced by a more abstract representation, termed a reward expectancy. Reward expectancies reflect the sensory and other qualities of the impending reward but are distinguishable from the actual reward. Notably, the hallucinatory representations depend on subcortical regions, such as amygdala, whereas reward expectancies require the progressive involvement of prefrontal areas, such as orbitofrontal cortex. Abnormal prefrontal function is associated with schizophrenia; impaired reality testing may result from a failure of the normal shift from highly realistic, sensory representations to more abstract, prefrontal expectancies. The Pavlovian procedures discussed here could be applied to animal models and schizophrenic patients to test this hypothesis.

From Real-World Events to Psychosis: The Emerging Neuropharmacology of Delusions

Morrison, P. D., Murray, R. M. — 2009-06-15

The earliest stages of delusion are characterized by an overabundance of meaningful coincidences impinging on the sufferer's existing worldview. Successive events are seen by him as pointing to, and then confirming, a fundamentally new reality that takes him over and engulfs his everyday life. Research over the last 4 decades has revealed the importance of dopamine (DA), D2 receptors, and the basal ganglia in psychotic thinking. Recent work has implicated the aberrant reward learning initiated by the excess release of striatal DA in the attribution of excessive importance or "salience" to insignificant stimuli and events. But our knowledge of what is happening beyond D2 receptors has remained scant. The gap is especially apparent at the cellular and microcircuit levels, encompassing the plastic changes, which are believed to be essential for new learning, and whose processes may go awry in major mental illness. Now new pharmacological findings are advancing our understanding of information processing and learning within the striatum. DA has an important role in setting the strength of individual striatal connections, but it does not act in isolation. Two other modulator systems are critical, the endocannabinoids and adenosine. Thus, at medium spiny neurons belonging to the indirect pathway, D2 stimulation evokes endocannabinoid-mediated depression of cortical inputs. Adenosine acting at A2A receptors elicits the opposite effect. Remarkably, drugs that target the endocannabinoid and purinergic systems also have pro- or antipsychotic properties. Here, we discuss how the 3 modulators regulate learning within the striatum and how their dysfunction may lead to delusional thinking.

Dance Therapy for People with Schizophrenia

Xia, J., Grant, T. J. — 2009-06-15

The Science-to-Service Gap in Real-World Schizophrenia Treatment: The 95% Problem

Drake, R. E., Essock, S. M. — 2009-06-15

Unmet Need for Mental Health Care in Schizophrenia: An Overview of Literature and New Data From a First-Admission Study

Mojtabai, R., Fochtmann, L., Chang, S.-W., Kotov, R., Craig, T. J., Bromet, E. — 2009-06-15

We present an overview of the literature on the patterns of mental health service use and the unmet need for care in individuals with schizophrenia with a focus on studies in the United States. We also present new data on the longitudinal course of treatments from a study of first-admission patients with schizophrenia. In epidemiological surveys, approximately 40% of the respondents with schizophrenia report that they have not received any mental health treatments in the preceding 6–12 months. Clinical epidemiological studies also find that many patients virtually drop out of treatment after their index contact with services and receive little mental health care in subsequent years. Clinical studies of patients in routine treatment settings indicate that the treatment patterns of these patients often fall short of the benchmarks set by evidence-based practice guidelines, while at least half of these patients continue to experience significant symptoms. The divergence from the guidelines is more pronounced with regard to psychosocial than medication treatments and in outpatient than in inpatient settings. The expansion of managed care has led to further reduction in the use of psychosocial treatments and, in some settings, continuity of care. In conclusion, we found a substantial level of unmet need for care among individuals with schizophrenia both at community level and in treatment settings. More than half of the individuals with this often chronic and disabling condition receive either no treatment or suboptimal treatment. Recovery in this patient population cannot be fully achieved without enhancing access to services and improving the quality of available services. The recent expansion of managed care has made this goal more difficult to achieve.

Disengagement From Mental Health Treatment Among Individuals With Schizophrenia and Strategies for Facilitating Connections to Care: A Review of the Literature

Kreyenbuhl, J., Nossel, I. R., Dixon, L. B. — 2009-06-15

Disengagement from mental health services can lead to devastating consequences for individuals with schizophrenia and other serious mental illnesses who require ongoing treatment. We review the extent and correlates of dropping out of mental health treatment for individuals with schizophrenia and suggest strategies for facilitating treatment engagement. Although rates vary across studies, reviews of the literature suggest that up to one-third of individuals with serious mental illnesses who have had some contact with the mental health service system disengage from care. Younger age, male gender, ethnic minority background, and low social functioning have been consistently associated with disengagement from mental health treatment. Individuals with co-occurring psychiatric and substance use disorders, as well as those with early-onset psychosis, are at particularly high risk of treatment dropout. Engagement strategies should specifically target these high-risk groups, as well as high-risk periods, including following an emergency room or hospital admission and the initial period of treatment. Interventions to enhance engagement in mental health treatment range from low-intensity interventions, such as appointment reminders, to high-intensity interventions, such as assertive community treatment. Disengagement from treatment may reflect the consumer's perspective that treatment is not necessary, is not meeting their needs, or is not being provided in a collaborative manner. An emerging literature on patient-centered care and shared decision making in psychiatry provides suggestive evidence that efforts to enhance client-centered communication and promote individuals’ active involvement in mental health treatment decisions can also improve engagement in treatment.

Implementing Evidence-Based Practices for People With Schizophrenia

Drake, R. E., Bond, G. R., Essock, S. M. — 2009-06-15

Over the last decade, a consensus has emerged regarding a set of evidence-based practices for schizophrenia that address symptom management and psychosocial functioning. Yet, surveys suggest that the great majority of the population of individuals with schizophrenia do not receive evidence-based care. In this article, we review the empirical literature on implementation of evidence-based practices for schizophrenia patients. We first examine lessons learned from implementation studies in general medicine. We then summarize the implementation literature specific to schizophrenia, including medication practices, psychosocial interventions, information technology, and state- and federal-level interventions. We conclude with recommendations for future directions.

Science to Practice: Making What We Know What We Actually Do

Sederer, L. I. — 2009-06-15

The perspective of the medical director of a large public mental health agency is provided regarding how to close the gap between what we know and what we do in mental health care. Tools for change, actions required, and key actors are identified. The author believes the moment is propitious for improving care systemically.

Multimedia Consent for Research in People With Schizophrenia and Normal Subjects: a Randomized Controlled Trial

2009-06-15

Limitations of printed, text-based, consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity, such as those with schizophrenia. We conducted a randomized controlled comparison of the effectiveness of a multimedia vs routine consent procedure (augmented with a 10-minute control video presentation) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects. The primary outcome measure was manifest decisional capacity (understanding, appreciation, reasoning, and expression of choice) for participation in a (hypothetical) clinical drug trial, as measured with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the University of California San Diego (UCSD) Brief Assessment for Capacity to Consent (UBACC). The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition. Additional assessments included standardized measures of psychopathology and cognitive functioning. Relative to patients in the routine consent condition, schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR understanding and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition (as categorized with several previously established criteria). Among the healthy subjects, there were few significant effects of consent condition. These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity, particularly for complex and/or high-risk research protocols.

Worth the Risk? Relationship of Incentives to Risk and Benefit Perceptions and Willingness to Participate in Schizophrenia Research

Dunn, L. B., Kim, D. S., Fellows, I. E., Palmer, B. W. — 2009-06-15

Objective: Providing incentives for research participation is widely practiced but minimally studied. In schizophrenia research, questions about capacity to consent and potential vulnerability may raise concerns when offering incentives for participation. Despite empirical attention focused on consent and decision-making capacity in schizophrenia, the issue of incentives has been essentially ignored. We examined willingness to participate in research, in relation to perceived risks and benefits, among people with schizophrenia and schizoaffective disorder. Method: Forty-six people with schizophrenia or schizoaffective disorder rated perceived risks and benefits of 5 hypothetical research vignettes. They also indicated whether they would be willing to participate at each of 5 incentive levels (including no compensation). Cognition was assessed with Mattis Dementia Rating Scale. Results: Ratings of risk and potential personal benefit were inversely correlated. For all scenarios, significant correlations were found between perceived risk and willingness to participate for greater compensation. Conversely, lower perceived likelihood of benefit was associated with a higher compensation threshold for participation in each scenario. Even at the highest proffered payment level for each scenario, however, a substantial proportion of respondents were not willing to participate. Risk assessment and willingness to participate (at all levels of compensation) were not associated with demographic variables or cognitive status. Conclusions: Determining whether incentives impede voluntarism remains an important task for empirical ethics research. Assessing potential research participants’ understanding and perceptions of risks, benefits, and alternatives to participation will help ensure that informed consent fulfills its mission—embodying the ethical principle of respect for persons.

Neurocognition, Social Cognition, Perceived Social Discomfort, and Vocational Outcomes in Schizophrenia

Bell, M., Tsang, H. W. H., Greig, T. C., Bryson, G. J. — 2009-06-15

Social cognition has been suggested to be an important mediating variable in the relationship between neurocognition and functional outcome. The present study tested this model in relation to work rehabilitation outcome and added self-reported social discomfort as a possible mediator. One hundred fifty-one participants with schizophrenia or schizoaffective disorder participated in a 26-week work therapy program. Neurocognition was constructed as a latent construct comprised of selected variables from our intake test battery representing executive functioning, verbal memory, attention and working memory, processing speed, and thought disorder. Social cognition at intake was the other latent construct comprised of variables representing affect recognition, theory of mind, self-reported egocentricity, and ratings of rapport. The 2 latent constructs received support from confirmatory factor analysis. Social discomfort on the job was based on their self-report on a weekly questionnaire. In addition, we constructed a composite rehabilitation outcome that was based on how many hours they worked, how well they worked, and how complex was the job that they were doing. Path analysis showed direct effects of neurocognition on rehabilitation outcome and indirect effects mediated by social cognition and social discomfort. This model proved to be a good fit to the data and far superior to another model where only social cognition was the mediating variable between neurocognition and rehabilitation outcome. Findings suggest that neurocognition affects social cognition and that poorer social cognition leads to social discomfort on the job, which in turn leads to poorer rehabilitation outcomes. Implications for rehabilitation interventions are discussed.

Neuroleptic Drugs Revert the Contextual Fear Conditioning Deficit Presented by Spontaneously Hypertensive Rats: A Potential Animal Model of Emotional Context Processing in Schizophrenia?

2009-06-15

Schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD) present abnormalities in emotion processing. A previous study showed that the spontaneously hypertensive rats (SHR), a putative animal model of ADHD, present reduced contextual fear conditioning (CFC). The aim of the present study was to characterize the deficit in CFC presented by SHR. Adult male normotensive Wistar rats and SHR were submitted to the CFC task. Sensitivity of the animals to the shock and the CFC performance after repeated exposure to the task were investigated. Pharmacological characterization consisted in the evaluation of the effects of the following drugs administered previously to the acquisition of the CFC: pentylenetetrazole (anxiogenic) and chlordiazepoxide (anxiolytic); methylphenidate and amphetamine (used for ADHD); lamotrigine, carbamazepine, and valproic acid (mood stabilizers); haloperidol, ziprasidone, risperidone, amisulpride, and clozapine (neuroleptic drugs); metoclopramide and SCH 23390 (dopamine antagonists without antipsychotic properties); and ketamine (a psychotomimmetic). The effects of paradoxical sleep deprivation (that worsens psychotic symptoms) and the performance in a latent inhibition protocol (an animal model of schizophrenia) were also verified. No differences in the sensitivity to the shock were observed. The repeated exposure to the CFC task did not modify the deficit in CFC presented by SHR. Considering pharmacological treatments, only the neuroleptic drugs reversed this deficit. This deficit was potentiated by proschizophrenia manipulations. Finally, a deficit in latent inhibition was also presented by SHR. These findings suggest that the deficit in CFC presented by SHR could be a useful animal model to study abnormalities in emotional context processing related to schizophrenia.

Are Psychiatrist Characteristics Associated With Postdischarge Suicide of Schizophrenia Patients?

Lee, H.-C., Lin, H.-C. — 2009-06-15

Information on the relationship between characteristics of mental healthcare providers, including hospitals and psychiatrists, and postdischarge suicide is scanty. This study aims to identify the risk factors for suicide among schizophrenia patients in the 3-month postdischarge period. The study cohort comprised all patients with a principal diagnosis of schizophrenia discharged from psychiatric inpatient care from 2002 to 2004 who committed suicide within 90 days of discharge. The control cohort consisted of all surviving schizophrenia patients discharged from psychiatric inpatient care in the same period and were matched to cases for age, gender, and date of discharge. There were 87 and 348 cases in the study and control cohorts, respectively. For suicide cases, death most frequently occurred on the first day after leaving the hospital (16.1%). The adjusted hazard ratios for committing suicide during the 90-day postdischarge period were 2.639 times greater for patients without previous psychiatric admission than for those hospitalized more than 3 times in the year preceding the index hospitalization. The adjusted suicide hazard for schizophrenia patients treated by male psychiatrists was significantly higher than for patients treated by female psychiatrists, by a multiple of 5.117 (P = .032). The adjusted suicide hazard among patients treated by psychiatrists over age 44 years was 2.378 times (P = .043) that for patients treated by psychiatrists aged younger than 35 years. Risk factors related to psychiatric hospitalization, including number of psychiatric admissions in the previous year and length of stay, together with gender and age of the psychiatrist providing inpatient care, are identified.

Subjective Experience of Cognitive Failures as Possible Risk Factor for Negative Symptoms of Psychosis in the General Population

Pfeifer, S., van Os, J., Hanssen, M., Delespaul, P., Krabbendam, L. — 2009-06-15

Objective: The aim of this study was to examine whether proneness to subjective cognitive failure (cognitive based mistakes) increases the risk for the development of symptoms of psychosis and to what degree any association was familial. Methods: At baseline, the Cognitive Failure Questionnaire (CFQ) and the Community Assessment of Psychic Experiences (CAPE) questionnaire were administered in a general population sample of genetically related individuals (n = 755). Individuals scoring high (>75th percentile) or average on the CAPE (between 40th and 60th percentile) (n = 488) were reinterviewed with the CAPE and Structured Interview for Schizotypy—Revised (SIS-R) at follow-up (mean interval = 7.7 months, SD = 4.8 months). Results: Cross-trait, within-relative analysis showed a significant association between the CFQ and the negative dimension, assessed with both the CAPE and SIS-R, whereas no association was found between the CFQ and the positive dimension. Cross-trait, between-relative analyses showed no association between the CFQ in one relative and any of the dimensions of the subclinical psychosis phenotype in the other relative. Conclusion: Proneness to subjective cognitive failure possibly contributes to the development or persistence of negative symptoms and can be seen as potential risk factor for negative symptoms of psychosis. This overlap is due to individual effects rather than familial liability.

Dropout Rates in Randomized Clinical Trials of Antipsychotics: A Meta-analysis Comparing First- and Second-Generation Drugs and an Examination of the Role of Trial Design Features

Rabinowitz, J., Levine, S. Z., Barkai, O., Davidov, O. — 2009-06-15

Dropout is often used as an outcome measure in clinical trials of antipsychotic medication. Previous research is inconclusive regarding (a) differences in dropout rates between first- and second-generation antipsychotic medications and (b) how trial design features reduce dropout. Meta-analysis of randomized controlled trials (RCTs) of antipsychotic medication was conducted to compare dropout rates for first- and second-generation antipsychotic drugs and to examine how a broad range of design features effect dropout. Ninety-three RCTs that met inclusion criteria were located (n = 26 686). Meta-analytic random effects models showed that dropout was higher for first- than second-generation drugs (odds ratio = 1.49, 95% confidence interval: 1.31–1.66). This advantage persisted after removing study arms with excessively high dosages, in flexible dose studies, studies of patients with symptom exacerbation, nonresponder patients, inpatients, and outpatients. Mixed effects models for meta-analysis were used to identify design features that effected dropout and develop formulae to derive expected dropout rates based on trial design features, and these assigned a pivotal role to duration. Collectively, dropout rates are lower for second- than first-generation antipsychotic drugs and appear to be partly explained by trial design features thus providing direction for future trial design.

Cortical Dopamine D2/D3 Receptors Are a Common Site of Action for Antipsychotic Drugs--An Original Patient Data Meta-analysis of the SPECT and PET In Vivo Receptor Imaging Literature

Stone, J. M., Davis, J. M., Leucht, S., Pilowsky, L. S. — 2009-06-15

Subject numbers in neuroreceptor imaging studies of antipsychotic treatment in schizophrenia are generally insufficient to directly test the relationship of regional D₂/D₃ and 5HT_2A receptor binding to clinical efficacy. We selected positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies of antipsychotic dose vs occupancy at both temporal cortex and striatal D₂/D₃ receptors. We selected corresponding SPECT and PET studies of 5HT_2A receptor occupancy. We also selected randomized double-blind clinical trials of antipsychotics, where patients were treated with randomly assigned fixed doses. For each antipsychotic drug, we compared the optimum effective antipsychotic dose with the dose inducing maximal occupancy of D₂/D₃ receptors in striatum and in temporal cortex as well as at 5HT_2A receptors. Both first- and second-generation antipsychotic (FGA, SGA) drugs produced high temporal cortex D₂/D₃ occupancy. Only FGA produced high striatal D₂/D₃ receptor occupancy. The clinically effective dose showed correlation with doses inducing maximal dopamine D₂/D₃ receptor occupancy both in striatum and in temporal cortex, the strongest correlation being with temporal cortex binding. Extrapyramidal side effects (EPSE) were primarily related to striatal D₂/D₃ receptor occupancy. There was no correlation between 5HT_2A occupancy and clinically effective dose. We conclude that cortical dopamine D₂/D₃ receptor occupancy is involved in antipsychotic efficacy, with striatal D₂/D₃ occupancy having a likely therapeutic role while also inducing EPSE. We found no evidence for 5HT_2A blockade involvement in antipsychotic action, although we cannot exclude this possibility.

Defeatist Beliefs as a Mediator of Cognitive Impairment, Negative Symptoms, and Functioning in Schizophrenia

Grant, P. M., Beck, A. T. — 2009-06-15

Poor social and vocational outcomes have long been observed in schizophrenia. Two of the most consistent predictors are negative symptoms and cognitive impairment. We investigate the hypothesis that cognitive content—defeatist beliefs regarding performance—provides a link between cognitive impairment, negative symptoms, and poor functioning in schizophrenia. A total of 77 individuals (55 patients diagnosed with schizophrenia or schizoaffective disorder and 22 healthy controls) participated in a cross-sectional study of psychopathology. Tests of memory, abstraction, attention, and processing speed, as well as current psychopathology, functioning, and endorsement of defeatist beliefs, were employed. Greater neurocognitive impairment was associated with elevated defeatist belief endorsement, higher negative symptom levels, and worse social and vocational functioning. Notably, statistical modeling indicated that defeatist belief endorsements were mediators in the relationship between cognitive impairment and both negative symptoms and functioning. These effects were independent of depression and positive symptom levels. The results add to the emerging biopsychosocial understanding of negative symptoms and introduce defeatist beliefs as a new psychotherapeutic target.

Errorless Learning for Training Individuals With Schizophrenia at a Community Mental Health Setting Providing Work Experience

2009-06-15

The effects of errorless learning (EL) on work performance, tenure, and personal well-being were compared with conventional job training in a community mental health fellowship club offering 12-week time-limited work experience. Participants were 40 clinically stable schizophrenia and schizoaffective disorder outpatients randomly assigned to EL vs conventional instruction (CI) at a thrift-type clothing store. EL participants received training on how to perform their assigned job tasks based on principles of EL, such as error reduction and automation of task performance. CI participants received training common to other community-based entry-level jobs that included verbal instruction, a visual demonstration, independent practice, and corrective feedback. Participants were scheduled to work 2 hours per week for 12 weeks. For both groups, job training occurred during the first 2 weeks at the worksite. Work performance (assessed using the Work Behavior Inventory, WBI) and personal well-being (self-esteem, job satisfaction, and work stress) were assessed at weeks 2, 4, and 12. Job tenure was defined as the number of weeks on the job or total number of hours worked prior to quitting or study end. The EL group performed better than the CI group on the Work Quality Scale from the WBI, and the group differences were relatively consistent over time. Results from the survival analyses of job tenure revealed a non-significant trend favoring EL. There were no group differences on self-esteem, job satisfaction, or work stress. The findings provide modest support for the extensions of EL to community settings for enhancing work performance.

Extended Visual Simultaneity Thresholds in Patients With Schizophrenia

2009-06-15

Clinical observations suggest that the experience of time phenomenology is disturbed in schizophrenia, possibly originating disorders in dynamic cognitive functions such as language or motor planning. We examined the subjective evaluation of temporal structure using an experimental approach involving judgments of simultaneity of simple, visually presented stimuli. We included a priming procedure, ie, a subthreshold presentation of simultaneous or asynchronous stimuli. This allowed us to evaluate the effects of subthreshold synchrony and to check for bias effects, ie, changes in the criteria used by the subjects to rate the stimuli. Primes were adapted to the responses of the subjects. Bias effects were thus expected to yield a change in the efficiency of the prime and to induce a change in the amplitude of the priming effect. Nineteen outpatients with schizophrenia and their individually matched controls participated in the study. In all tests, patients required longer delays between stimuli to detect that they were asynchronous. In other words, they judged stimuli to be synchronous even when their onset was separated by delays of 100 milliseconds and even more in some cases. These results contrasted with preserved effects of subthreshold synchrony. Our findings argue against the hypothesis that the patients’ responses were influenced by biases. We conclude that the subjective evaluation of simultaneity/asynchrony is impaired in schizophrenia, thus leading to impairment in the phenomenology of event-structure coding. The method used in the present study provides a novel approach to the assessment of those disturbances related to time in patients with schizophrenia.

Genetic and Disorder-Specific Aspects of Resting State EEG Abnormalities in Schizophrenia

Venables, N. C., Bernat, E. M., Sponheim, S. R. — 2009-06-15

We evaluated whether abnormal frequency composition of the resting state electroencephalogram (EEG) in schizophrenia was associated with genetic liability for the disorder by studying first-degree biological relatives of schizophrenia patients. The study included a data-driven method for defining EEG frequency components and determined the specificity of resting state EEG frequency abnormalities by assessing schizophrenia patients, bipolar disorder patients, and relatives of both patient groups. Schizophrenia patients and their relatives, but not bipolar patients or their relatives, exhibited increased high-frequency activity (beta) providing evidence for disturbances in resting state brain activity being specific to genetic liability for schizophrenia. Schizophrenia patients exhibited augmented low-frequency EEG activity (delta, theta), while bipolar disorder patients and the 2 groups of relatives generally failed to manifest similar low-frequency EEG abnormalities. The Val¹⁵⁸Met polymorphism for the catechol-O-methyl transferase (COMT) gene was most strongly associated with delta and theta activity in schizophrenia patients. Met homozygote schizophrenia patients exhibited augmented activity for the 2 low-frequency bands compared with control subjects. Excessive high-frequency EEG activity over frontal brain regions may serve as an endophenotype that reflects cortical expression of genetic vulnerability for schizophrenia. Low-frequency resting state EEG anomalies in schizophrenia may relate to disorder-specific pathophysiology in schizophrenia and the influence of the COMT gene on tonic dopamanergic function.