Fiza Singh

Association of impaired EEG mu wave suppression, negative symptoms and social functioning in biological motion processing in first episode of psychosis

BACKGROUND Event related desynchronization (ERD) of mu waves, or mu suppression, over sensorimotor cortex has been observed in response to self-generated movement, viewing movement, or imaging movement. Mu suppression is especially pronounced when the movement has social relevance and is being generated by a biological entity indicating successful social adaptation. And since social adaptation problems are common in schizophrenia, the authors designed a study to test mu wave suppression in a first episode of psychosis population. METHODS A total of 32 subjects (first episode of psychosis patients N=20; healthy comparison subjects N=12) aged 13-34 watched movement videos with and without socially relevant cues, executed by biological or non-biological agents. Scalp electrode EEG recordings of mu rhythm (8-13 Hz) over sensorimotor cortex during the session were used to calculate mu wave suppression. Average mu suppression was compared within and between groups, as well as correlations between mu suppression and clinical measures. RESULTS First episode patients showed significantly reduced mu wave suppression over sensorimotor cortex when viewing biological motion, compared to healthy subjects. In addition, negative symptom burden and poor social adjustment correlated with impaired mu wave suppression. CONCLUSIONS Our finding provides the first description of impaired event related desynchronization of mu waves in response to biological motion and its correlation with negative symptoms and social adjustment in the first episode of psychosis. Future studies can be conducted to determine if mu wave suppression represents an endophenotype with potential applications in biological treatments of negative symptoms and social functioning deficits in schizophrenia.

Sleep disturbances are associated with psychotic experiences: Findings from the National Comorbidity Survey Replication

Sleep disturbances have been linked to psychotic experiences in the general adult populations of multiple countries, but this association has yet to be confirmed in the United States using robust diagnostic measures. We analyzed a subsample (n=2304) of the National Comorbidity Survey Replication, and found that when compared with those who did not report any sleep problems, individuals with sleep disturbances lasting two weeks or longer over the past 12months were significantly more likely to report at least one psychotic experience during that same time frame. Specifically, difficulty falling asleep, waking up during the night, early morning awakenings, and feeling sleepy during the day were each associated with greater odds of reporting psychotic experiences over the past year after controlling for socio-demographic variables. However, only difficulty falling asleep and early morning awakenings were still significant after adjusting for DSM comorbid disorders. Reporting three or four types of sleep disturbances was especially predictive of psychotic experiences. Our findings underscore the importance of detecting and reducing sleep problems among individuals who report PE.

Ethical implications for clinical practice and future research in "at risk" individuals.

The last 15 years have witnessed a shift in schizophrenia research with increasing interest in earlier stages of illness with the hope of early intervention and ultimately prevention of psychotic illness. Large-scale longitudinal studies have identified clinical and biological risk factors associated with increased risk of psychotic conversion, which together with symptomatic and demographic risk factors may improve the power of prediction algorithms for psychotic transition. Despite these advances, 45-70% of at risk subjects in most samples do not convert to frank psychosis, but continue to function well below their age matched counterparts. The issue is of utmost importance in light of the upcoming DSM-V and the possible inclusion of the attenuated psychotic symptoms syndrome (APSS) diagnosis, with clinical and ethical implications. Clinical considerations include feasibility of reliably diagnosing the at risk state in non-academic medical centers, variable psychotic conversion rates, a non-uniform definition of conversion and extensive debate about treatment for individuals with an ill-defined outcome. On the ethical side, diagnosing APSS could lead to unnecessary prescribing of antipsychotics with long-term deleterious consequences, slow research by providing a false sense of comfort in the diagnosis, and have psychosocial implications for those who receive a diagnosis. Thus it may be prudent to engage at risk populations early and to use broad-spectrum treatments with low risk benefit ratios to relieve functional impairments, while simultaneously studying all subsets of the at risk population.

Effects of intranasal oxytocin on neural processing within a socially relevant neural circuit.

Dysregulation of the Mirror Neuron System (MNS) in schizophrenia (SCZ) may underlie the cognitive and behavioral manifestations of social dysfunction associated with that disorder. In healthy subjects intranasal (IN) oxytocin (OT) improves neural processing in the MNS and is associated with improved social cognition. OTs brain effects can be measured through its modulation of the MNS by suppressing EEG mu-band electrical activity (8-13Hz) in response to motion perception. Although IN OTs effects on social cognition have been tested in SCZ, OTs impact on the MNS has not been evaluated to date. Therefore, we designed a study to investigate the effects of two different OT doses on biological motion-induced mu suppression in SCZ and healthy subjects. EEG recordings were taken after each subject received a single IN administration of placebo, OT-24IU and OT-48IU in randomized order in a double-blind crossover design. The results provide support for OTs regulation of the MNS in both healthy and SCZ subjects, with the optimal dose dependent on diagnostic group and sex of subject. A statistically significant response was seen in SCZ males only, indicating a heightened sensitivity to those effects, although sex hormone related effects cannot be ruled out. In general, OT appears to have positive effects on neural circuitry that supports social cognition and socially adaptive behaviors.

Biomarkers in psychosis: an approach to early identification and individualized treatment

Numerous biomarkers for somatic disorders are used in routine medical practice. Yet, despite remarkable advances in mental health research, we are not able to identify biomarkers with established clinical utility for mental disorders such as schizophrenia. While identification and characterization of biomarkers are crucial first steps in this process, their predictive diagnostic and treatment utility need to be better developed for clinical practice. The heterogeneity of psychotic disorders etiologically, pathologically and symptomatically presents both a challenge and an opportunity for the use of biomarkers in clinical practice. Simply said, a single biomarker might not exist that necessitates the search for a biomarker profile. In this review we discuss research findings in light of such an approach. We summarize some examples of emerging biomarkers in early psychosis research and delineate how these can be applied to a clinical setting to inform treatment on an individual basis fostering a personalized treatment approach.

Bipolar disorder: historic perspective, current pharmacologic treatment options and a review of quetiapine

Bipolar disorder is a complex mental illness that is frequently both under-diagnosed and under-treated. The symptoms of bipolar disorder can be confused with other medical illnesses or drug effects or may even be overlooked entirely as extreme character traits. The consequences of delayed diagnosis or misdiagnosis are potentially devastating, including loss of employment, impaired relationships and a severely impaired quality of life. This article will review the historic perspectives of bipolar disorder, the diagnostic criteria for the phases of the illness, and the pharmacologic options available to treat this condition. Quetiapine, an atypical antipsychotic, will be reviewed indepth. Based on extensive trial data, reviewed in this article, quetiapine is approved by the US Food and Drug Administration for use as monotherapy or as adjunctive therapy with other mood stabilizers for the treatment of acute manic episodes of bipolar I disorder. Clinical trials describing the efficacy of quetiapine in other phases of bipolar disorder and in other patient populations are also reviewed. A discussion of the drug profile of quetiapine includes its chemistry, availability, pharmacodynamics, pharmacokinetics and metabolism. Preclinical studies, postmarketing surveillance, safety, tolerability and regulatory issues are also evaluated. Finally, potential future directions for quetiapine are discussed, together with a review of key issues in bipolar disorder management and details of the information resources used in preparing this article.

Assessing the Effectiveness of Neurofeedback Training in the Context of Clinical and Social Neuroscience

Social neuroscience benefits from the experimental manipulation of neuronal activity. One possible manipulation, neurofeedback, is an operant conditioning-based technique in which individuals sense, interact with, and manage their own physiological and mental states. Neurofeedback has been applied to a wide variety of psychiatric illnesses, as well as to treat sub-clinical symptoms, and even to enhance performance in healthy populations. Despite growing interest, there persists a level of distrust and/or bias in the medical and research communities in the USA toward neurofeedback and other functional interventions. As a result, neurofeedback has been largely ignored, or disregarded within social neuroscience. We propose a systematic, empirically-based approach for assessing the effectiveness, and utility of neurofeedback. To that end, we use the term perturbative physiologic plasticity to suggest that biological systems function as an integrated whole that can be perturbed and guided, either directly or indirectly, into different physiological states. When the intention is to normalize the system, e.g., via neurofeedback, we describe it as self-directed neuroplasticity, whose outcome is persistent functional, structural, and behavioral changes. We argue that changes in physiological, neuropsychological, behavioral, interpersonal, and societal functioning following neurofeedback can serve as objective indices and as the metrics necessary for assessing levels of efficacy. In this chapter, we examine the effects of neurofeedback on functional connectivity in a few clinical disorders as case studies for this approach. We believe this broader perspective will open new avenues of investigation, especially within social neuroscience, to further elucidate the mechanisms and effectiveness of these types of interventions, and their relevance to basic research.

Is smoking tobacco associated with psychotic experiences across racial categories in the United States? Findings from the Collaborative Psychiatric Epidemiological Surveys

Smoking tobacco has been associated with psychosis, though research has yet to fully examine the extent to which this association reaches into the sub-threshold range of the psychosis continuum within the US, and whether this association persists after accounting for co-occurring disorders. We analyzed data from three large racially-diverse surveys of the US population and found that current smokers were more likely to report a lifetime psychotic experience when compared with never smokers after adjusting for socio-demographics. But after controlling for anxiety, mood, and substance use disorders, these effects only remained strong and statistically significant for Asian-Americans.

Therapeutic Considerations in Individuals at Clinical Risk for Developing Psychosis

Opinion statementIn the last two decades, increased focus has been placed on earlier identification and treatment of psychotic illness in an effort to prevent illness onset and/or long-term sequelae of schizophrenia. Typically, a 16- or 17-year-old young man or woman is referred to our clinic by a mental health provider who has noted thought disorder (referential thoughts, suspiciousness) in addition to depression and/or anxiety. The individual is usually someone who has stopped socializing with friends, has poor grades, has experimented with illicit substances (frequently cannabis), endorses unusual beliefs, but maintains insight. We begin by obtaining a thorough history, including collateral sources such as family and school counselors and a medical history to rule out any organic causes. Oftentimes there is a family history of schizophrenia or bipolar disorder, traumatic childhood, and at times a history of social discomfort and bullying. It is not uncommon for our clients to endorse depression and social anxiety in addition to prepsychotic perceptual abnormalities. In our clinic, we use a multimodal risk-reduction approach that matches the risks of illness with risks and benefits of prescribed treatment. For instance, in early-stage patients, we encourage low-risk treatments including cognitive behavior therapy, social skills training, cognitive training, family-focused psychotherapy, relaxation techniques, and neuroprotective agents such as omega-3 fatty acids. Antidepressants are used for prominent neurovegetative symptoms, although they are used with caution, as some individuals meeting criteria for prodromal psychosis, or clinical high-risk criteria, go on to develop bipolar spectrum disorders. Low-dose atypical antipsychotic treatments are reserved for patients closer to psychotic transition. All patients, regardless of stage of illness, are encouraged to optimize physical activity and to abstain from illicit substance use. Looking toward the future, we hope to obtain a biomarker profile (blood tests, neurocognitive, neuroimaging, and neurophysiological assessment) in each patient at the outset which, combined with clinical factors, will guide individualized treatment.

Developing Research Domain Criteria (RDoC) to improve diagnosis and treatment of social deficits in psychiatric disorders: The Mirror Neuron System as a model

Fig. 1. The Mirror Neuron System (MNS) describes a multimodal brain circuit underlying social cognition whose status can be successfully interrogated using several different established brain measuringmodalities (Fabbri-Destro and Rizzolatti, 2008). Perturbation in the MNS gives rise to perturbations in social cognition, and, in turn abnormal behavior and function. In this model, brain based biomarkers of MNS function could be used to 1) identify socially-relevant information processing perturbations inpeople that cut across DSM diagnoses, 2) identify putative treatments that ameliorate these MNS perturbations (e.g. oxytocin, social skills training) and 3) identify patients, independent of their DSM diagnosis, that may benefit from MNS targeting treatments. Developing Research Domain Criteria (RDoC) to improve diagnosis and treatment of social deficits in psychiatric disorders: The Mirror Neuron System as a model