Disturbances of visual motion perception in bipolar disorder.

OBJECTIVES: While cognitive deficits have been well documented in patients with bipolar disorder, visual perception has been less well characterized. Such deficits appear in schizophrenia, which shares genetic risk factors with bipolar disorder, and may contribute to disturbances in visual cognition and learning. METHODS: The present study investigated visual perception in bipolar disorder using psychophysical tests of contrast sensitivity, dot motion discrimination, and form discrimination. The relationship of these measures to mood state, medication status, and cognitive function was investigated. Sixty-one patients with type I bipolar disorder and 67 comparison subjects were tested. RESULTS: Results indicated a deficit in dot motion trajectory discrimination in both euthymic and ill individuals with bipolar disorder, as well as a global deficit in moving grating contrast sensitivity. Ill individuals with bipolar disorder were impaired in psychomotor processing, but this finding was not related to visual processing performance. CONCLUSIONS: These findings could be due to disturbances in specific visual pathways involved in the processing of motion properties, or to a more general deficit which impairs processing of temporally modulated stimuli.

The Relationship Between Antipsychotics, Cognitive Enhancers, and Major Adverse Cardiovascular/Cerebrovascular Events (MACCE) in Older Adults with Behavioral and Psychological Symptoms of Dementia.

BACKGROUND AND OBJECTIVES: Antipsychotics and cognitive enhancers are often used to treat psychosis and behavioral disturbances in individuals with dementia; however, these drugs have been linked with various adverse events including both metabolic and cerebro/cardiovascular events. Thus, this study sought to estimate the risk of major adverse cardiovascular/cerebrovascular events (MACCE) across four behavioral and psychological symptoms of dementia (BPSD) treatment models by exploring potential associations between antipsychotics (APs), cognitive-enhancing medications, dosage, and earlier MACCE onset. METHODS: Patients were obtained from the Loma Linda University Medical Center database who were age ≥ 50 or older and who were diagnosed with dementia and BPSD symptoms. Treatment group and drug dosing were analyzed using Cox regression analyses to predict time until MACCE onset. Patient age at dementia diagnosis, sex, smoking status, race/ethnicity, and previous MACCE diagnoses were included as covariate variables. RESULTS: The final study population consisted of 1162 individuals. Results indicated a significant effect of medication type on duration until MACCE, (p < 0.001), with the odds of experiencing a MACCE being 96.3% higher for individuals treated with both APs and cognitive enhancers (p < 0.001). There was also a significant effect of AP dosage on duration until MACCE (p < 0.001) and a significant effect of cognitive enhancer dosage on duration until a MACCE, (p < 0.001). The odds of experiencing a MACCE sooner were 238% higher for those on high doses of APs (p < 0.001) and 76% higher for individuals on high doses of cognitive enhancers (p < 0.010). CONCLUSION: The use of APs at high doses was associated with the greatest risk of an adverse medical outcome in older adults with dementia with concurrent behavioral symptoms. Use of AP medications in this population should include close monitoring for cardiovascular/cerebrovascular events.

Auditory steady state response in bipolar disorder: relation to clinical state, cognitive performance, medication status, and substance disorders.

OBJECTIVES: Abnormalities in auditory steady state response (ASSR) at gamma range frequencies have been found in bipolar disorder, but the relationship of these neurophysiological disturbances to clinical factors has not been well characterized. We therefore evaluated the ASSR in bipolar disorder and examined its sensitivity to clinical symptoms, cognitive function, and pharmacological treatment. METHODS: A total of 68 patients with bipolar disorder and 77 control participants were evaluated. Click trains presented at 20, 30, 40, and 50 Hz evoked ASSRs. Mean trial power (MTP) and phase locking factor (PLF) measured response magnitude and phase synchronization of the ASSR at each stimulation frequency. Clinical state, pharmacological treatment, and neuropsychological performance were assessed, and their respective relationships with ASSR measures were evaluated. RESULTS: Patients with bipolar disorder showed reduced MTP and PLF compared to control participants. Bipolar disorder patients taking psychotropic medications had decreased PLF relative to patients withdrawn from medications. Control participants performed better on neuropsychological tests than bipolar disorder patients; however, test scores did not correlate with ASSR measures. CONCLUSIONS: Deficits in the generation and maintenance of ASSR are present in bipolar disorder, implicating disturbances in auditory pathways. ASSR may be sensitive to medication status. Other clinical features, including mood state, psychotic features, cognitive performance, smoking, or history of substance use disorder, were unrelated to MTP or PLF.

Abnormal beta and gamma frequency neural oscillations mediate auditory sensory gating deficit in schizophrenia.

BACKGROUND: Sensory gating is a process in which the brain's response to irrelevant and repetitive stimuli is inhibited. The sensory gating deficit in schizophrenia (SZ) is typically measured by the ratio or difference score of the P50 event-related potential (ERP) amplitudes in response to a paired click paradigm. While the P50 gating effect has usually been measured in relation to the peak amplitude of the S1 and S2 P50 ERPs, there is increasing evidence that inhibitory processes may be reflected by evoked or induced oscillatory activity during the inter-click interval in the beta (20-30 Hz) and gamma (30-50 Hz) frequency bands. We therefore examined the relationship between frequency specific activity in the inter-click interval with gating effects in the time and frequency domains. METHOD: Paired-auditory stimuli were presented to 131 participants with schizophrenia and 196 healthy controls (HC). P50 ERP amplitudes to S1 and S2as well as averaged- and single-trial beta (20-30 Hz) and gamma (30-50 Hz) frequency power during the inter-click interval were measured from the CZ electrode site. RESULTS: In the time domain, P50 gating deficits were apparent in both ratio and difference scores. This effect was mainly due to smaller S1 amplitudes in the patient group. SZ patients exhibited less evoked beta and gamma power, particularly at the 0-100 ms time point, in response to S1. Early (0-100 ms) evoked beta and gamma responses were critical in determining the S1 amplitude and extent of P50 gating across the delay interval for both HC and SZ. CONCLUSION: Our findings support a disruption in initial sensory registration in those with SZ, and do not support an active mechanism throughout the delay interval. The degree of response to S1 and early beta and gamma frequency oscillations in the delay interval provides information about the mechanisms supporting auditory sensory gating, and may provide a framework for studying the mechanisms that support sensory inhibition.

Use of Machine Learning for Predicting Escitalopram Treatment Outcome From Electroencephalography Recordings in Adult Patients With Depression.

Importance: Social and economic costs of depression are exacerbated by prolonged periods spent identifying treatments that would be effective for a particular patient. Thus, a tool that reliably predicts an individual patient's response to treatment could significantly reduce the burden of depression. Objective: To estimate how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic (EEG) data on patients with depression. Design, Setting, and Participants: This prognostic study used a support vector machine classifier to predict treatment outcome using data from the first Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study. The CAN-BIND-1 study comprised 180 patients (aged 18-60 years) diagnosed with major depressive disorder who had completed 8 weeks of treatment. Of this group, 122 patients had EEG data recorded before the treatment; 115 also had EEG data recorded after the first 2 weeks of treatment. Interventions: All participants completed 8 weeks of open-label escitalopram (10-20 mg) treatment. Main Outcomes and Measures: The ability of EEG data to predict treatment outcome, measured as accuracy, specificity, and sensitivity of the classifier at baseline and after the first 2 weeks of treatment. The treatment outcome was defined in terms of change in symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale, before and after 8 weeks of treatment. A patient was designated as a responder if the Montgomery-Åsberg Depression Rating Scale score decreased by at least 50% during the 8 weeks and as a nonresponder if the score decrease was less than 50%. Results: Of the 122 participants who completed a baseline EEG recording (mean [SD] age, 36.3 [12.7] years; 76 [62.3%] female), the classifier was able to identify responders with an estimated accuracy of 79.2% (sensitivity, 67.3%; specificity, 91.0%) when using only the baseline EEG data. For a subset of 115 participants who had additional EEG data recorded after the first 2 weeks of treatment, use of these data increased the accuracy to 82.4% (sensitivity, 79.2%; specificity, 85.5%). Conclusions and Relevance: These findings demonstrate the potential utility of EEG as a treatment planning tool for escitalopram therapy. Further development of the classification tools presented in this study holds the promise of expediting the search for optimal treatment for each patient.

Relationships between auditory event-related potentials and mood state, medication, and comorbid psychiatric illness in patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) exhibit aberrations in auditory event-related potentials (ERPs), although the relationships between these measures and mood state at testing, comorbid psychiatric illness, presence of psychotic features, and medication usage are unclear. The purpose of this study was to investigate the relationships between these factors and auditory ERP measures in BD patients. METHODS: An auditory 'oddball' discrimination task was used to elicit ERPs from 69 patients with type I BD and 52 healthy controls. Patients were placed into subgroups based upon their mood state at testing (euthymic or symptomatic), and ANOVA was used to compare amplitude and peak latency measures from the N100, P200, N200, and P300 ERP components across subgroups. Multiple regression was used to investigate relationships between ERP measures and comorbid psychiatric diagnosis, history of psychotic features, and medication status. RESULTS: Relative to healthy control participants, euthymic and symptomatic BD patients exhibited reduced P300 and P200 amplitude, but ERP measures did not differ among BD patients on the basis of mood status. A history of a comorbid anxiety disorder was associated with reduced N200 peak latency, but prolonged P300 peak latency among BD patients. No other relationships between clinical variables and ERP measures were significant. CONCLUSIONS: The results suggest that disrupted auditory attention may be observed in BD patients regardless of their mood state at testing, medication status, or history of psychosis. These results extend previous findings, and provide further evidence for aberrations in the P300 ERP as an endophenotype for BD.

Is there a common vulnerability in cannabis phenomenology and schizotypy? The role of the N170 ERP.

Cannabis use is a known risk factor for the development of psychosis, although the precise nature of this relationship is unclear. The phenomenological experiences associated with cannabis use vary dramatically, and for some resemble certain features of psychosis. We hypothesized that individuals who report particularly unusual experiences associated with cannabis use would demonstrate similar electrophysiological patterns to those who score high on schizotypal personality traits. The Cannabis Experiences Questionnaire (CEQ) and the Schizotypal Personality Questionnaire (SPQ) were used to measure these experiences and traits. A sample of 97 individuals were placed into one of three experimental or two control groups based on their questionnaire scores. These were the "High CEQ", "High SPQ", "High on Both", "Average Users" and "Control" (non-using) groups. Participants completed a visual face perception task. Electroencephalography was used to measure the neural response to the stimuli. The N170 event-related potential (ERP) was used to measure perceptual encoding of the stimulus. The experimental groups elicited significantly reduced N170 ERPs compared to the Control group. The Average User group did not significantly differ from the Control group, and approached significance with the High SPQ group. None of the high scoring groups significantly differed in N170 ERP response from each other. Replicating past research, the CEQ and SPQ scales moderately correlated with each other. The attenuated N170 ERP demonstrated by the high scoring experimental groups may reflect a manifestation of an underlying shared vulnerability.

The comparative effectiveness of electroencephalographic indices in predicting response to escitalopram therapy in depression: A pilot study.

BACKGROUND: This study aims to compare the effectiveness of EEG frequency band activity including interhemispheric asymmetry and prefrontal theta cordance in predicting response to escitalopram therapy at 8-weeks post-treatment, in a multi-site initiative. METHODS: Resting state 64-channel EEG data were recorded from 44 patients with a diagnosis of major depressive disorder (MDD) as part of a larger, multisite discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). Clinical response was measured at 8-weeks post-treatment as change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 50% or more. EEG measures were analyzed at (1) pre-treatment baseline (2) 2 weeks post-treatment and (3) as an ''early change" variable defined as change in EEG from baseline to 2 weeks post-treatment. RESULTS: At baseline, treatment responders showed elevated absolute alpha power in the left hemisphere while non-responders showed the opposite. Responders further exhibited a cortical asymmetry in the parietal region. Groups also differed in pre-treatment relative delta power with responders showing greater power in the right hemisphere over the left while non-responders showed the opposite. At 2 weeks post-treatment, responders exhibited greater absolute beta power in the left hemisphere relative to the right and the opposite was noted for non-responders. A reverse pattern was noted for absolute and relative delta power at 2 weeks post-treatment. Responders exhibited early reductions in relative alpha power and early increments in relative theta power. Non-responders showed a significant early increase in prefrontal theta cordance. CONCLUSIONS: Hemispheric asymmetries in the alpha and delta bands at baseline and at 2 weeks post-treatment have moderately strong predictive utility in predicting response to antidepressant treatment.

The Factor Structure of the Schizotypal Personality Questionnaire in Undergraduate and Community Samples.

The prevailing theoretical model of the Schizotypal Personality Questionnaire (SPQ) is a three-factor model based on subscale-level analyses. However, recent item-level factor analyses of the SPQ suggest a four- or five-factor model. To examine the factor structure of the SPQ and how this structure may differ between undergraduate and community samples, the authors conducted exploratory and confirmatory item-level factor analyses of this measure on undergraduate (N = 1,850) and community participants (N = 1,464). A clear three-factor solution was found in the community sample, whereas a somewhat equivocal four-factor solution was found in the undergraduate sample. Both structures displayed gender invariance. This is the first study to address the issues of undergraduate sample generalizability and gender invariance in an item-level exploratory factor analysis of the SPQ. Given the disparate findings in the samples, this study indicates the importance of using both community and undergraduate samples when examining the factor structure of the SPQ.

Standardization of electroencephalography for multi-site, multi-platform and multi-investigator studies: insights from the canadian biomarker integration network in depression.

Subsequent to global initiatives in mapping the human brain and investigations of neurobiological markers for brain disorders, the number of multi-site studies involving the collection and sharing of large volumes of brain data, including electroencephalography (EEG), has been increasing. Among the complexities of conducting multi-site studies and increasing the shelf life of biological data beyond the original study are timely standardization and documentation of relevant study parameters. We present the insights gained and guidelines established within the EEG working group of the Canadian Biomarker Integration Network in Depression (CAN-BIND). CAN-BIND is a multi-site, multi-investigator, and multi-project network supported by the Ontario Brain Institute with access to Brain-CODE, an informatics platform that hosts a multitude of biological data across a growing list of brain pathologies. We describe our approaches and insights on documenting and standardizing parameters across the study design, data collection, monitoring, analysis, integration, knowledge-translation, and data archiving phases of CAN-BIND projects. We introduce a custom-built EEG toolbox to track data preprocessing with open-access for the scientific community. We also evaluate the impact of variation in equipment setup on the accuracy of acquired data. Collectively, this work is intended to inspire establishing comprehensive and standardized guidelines for multi-site studies.

Facial emotion memory in schizophrenia: From encoding to maintenance-related EEG.

OBJECTIVE: Persons with schizophrenia exhibit deficits recognizing facial emotions, which may impact social functioning. Whether these deficits reflect aberrant sensory processing, an inability to maintain information in memory, or dysfunctional integration of these two functions remains unclear. METHODS: A facial emotion memory paradigm was administered to 38 schizophrenia patients (SZ) and 42 healthy controls (HC). P100, N170 and N250 ERP amplitudes were measured to assess sensory processing. Evoked theta power during the delay interval was quantified to assess memory maintenance. RESULTS: The N170 ERP was larger to negative compared to neutral facial expressions in both groups, while SZ exhibited increased evoked theta power during the delay interval. Increased theta power was associated with worse behavioral performance in response to sad and fearful expressions for HC, but this relationship was only found in response to fearful expressions for SZ. Finally, only HC showed consistent correlations between N170 amplitude and theta power during the delay interval. CONCLUSIONS: Integration between measures of sensory processing and memory functioning may be affected in SZ. SIGNIFICANCE: These findings may indicate that the oscillatory networks subserving emotion processing and sustained attention are intertwined, and comprise part of the social brain network that is affected in schizophrenia.

Personality traits in schizophrenia and related personality disorders.

We investigated whether schizophrenia spectrum disorders share common personality characteristics or traits. Participants with a diagnosis of schizophrenia or schizoaffective disorder (SZ) or with a schizophrenia spectrum personality disorder (schizophrenia spectrum PD: schizoid, paranoid, and schizotypal personality disorder) were compared with non-psychiatric control subjects on the five-factor model of personality and the psychosis-proneness scales. On the five-factor personality scales, SZ subjects showed higher levels of neuroticism, and lower levels of openness, agreeableness, extraversion, and conscientiousness than control subjects. Higher scores on openness and lower scores on neuroticism distinguished schizophrenia spectrum PD from SZ. On the psychosis-proneness scales, both PD and SZ participants scored high relative to non-psychiatric control participants on magical ideation and perceptual aberration, while PD participants scored intermediate between non-psychiatric control participants and SZ on social anhedonia. Discriminant analysis indicated that schizophrenia spectrum patients could be distinguished from PDs by more severe social withdrawal and maladjustment, while subjects with PDs could be best distinguished from control subjects on the basis of odd or novel ideation and decreased conscientiousness.

EEG synchronization to modulated auditory tones in schizophrenia, schizoaffective disorder, and schizotypal personality disorder.

OBJECTIVE: The authors tested whether neural synchronization deficits were present in subjects with schizophrenia and schizotypal personality disorder. METHOD: Amplitude-modulated tones were used to evaluate auditory steady-state evoked potential entrainment in a combined group of 21 subjects with schizophrenia or schizoaffective disorder, 11 subjects with schizotypal personality disorder, and 22 nonpsychiatric comparison subjects. RESULTS: The schizophrenia or schizoaffective disorder group exhibited decreased power compared to the schizotypal personality disorder and nonpsychiatric comparison groups. There were no differences between groups in N100 amplitude. CONCLUSIONS: Subjects with schizophrenia but not subjects with schizotypal personality disorder have deficits in steady-state responses to periodic stimuli, despite an intact response to sensory-evoked potentials (N100). These deficits reflect aberrant neural synchronization or resolution and may contribute to disturbed perceptual and cognitive integration in schizophrenia.

Psychometrically matched visual-processing tasks in schizophrenia spectrum disorders.

Patients with schizophrenia show deficits in visual perception and working memory, but the relationship between these deficits has not been characterized with psychometrically matched tasks. The authors administered 2 visual discrimination and 6 recognition tasks to 43 schizophrenia spectrum patients and 22 nonpsychiatric subjects. When performing difficulty-matched tasks, spectrum subjects showed more severe impairments for motion compared with form processing. When tasks were matched on true score variance, spectrum subjects exhibited worse performance on both form and motion discrimination, and a differential deficit in motion recognition with a short display duration and long interstimulus interval. These results provide evidence of differential deficits in visual processing in schizophrenia that appear to be dependent on the temporal characteristics of the tasks.

Visual processing and neuropsychological function in schizophrenia and schizoaffective disorder.

Persons with schizophrenia and schizoaffective disorder exhibit deficits in both visual processing and neuropsychological tasks. Little is known, however, about whether these deficits are related to one another. We administered psychophysical tests of visual discrimination and recognition, and neuropsychological tests of abstract flexibility, verbal learning, visual memory, working memory and attention to 42 outpatients with stable but chronic schizophrenia or schizoaffective disorder. Multiple regression analyses were performed to determine the relationship between these measures of neuropsychological function and visual psychophysical performance. Results indicated that motion perception was associated with working memory, and that the addition of a memory component to motion perception (motion recognition) was associated with both working memory and visual memory. Visual performance was not associated with symptom severity as measured by the PANSS. These results suggest that psychophysical tests of visual processing may contribute to deficits on neuropsychological tests of visual cognition, and may also reflect cross-modal disturbances of working memory function.

Cognitive-behavioral therapy for medication-resistant psychosis: a meta-analytic review.

Patients with schizophrenia often continue to experience disabling positive symptoms, despite adequate trials of medication. In these situations, patients may be prescribed an adjunctive medication, but a more effective choice may be cognitive-behavioral therapy (CBT). This review of 16 published articles from 12 randomized controlled trials found that CBT was associated with robust improvements in the positive symptoms of psychotic disorders. In addition, the improvements were sustained at follow-up, the authors reported.

The role of encoding and attention in facial emotion memory: an EEG investigation.

Facial expressions are encoded via sensory mechanisms, but meaning extraction and salience of these expressions involve cognitive functions. We investigated the time course of sensory encoding and subsequent maintenance in memory via EEG. Twenty-nine healthy participants completed a facial emotion delayed match-to-sample task. P100, N170 and N250 ERPs were measured in response to the first stimulus, and evoked theta power (4-7Hz) was measured during the delay interval. Negative facial expressions produced larger N170 amplitudes and greater theta power early in the delay. N170 amplitude correlated with theta power, however larger N170 amplitude coupled with greater theta power only predicted behavioural performance for one emotion condition (very happy) out of six tested (see Supplemental Data). These findings indicate that the N170 ERP may be sensitive to emotional facial expressions when task demands require encoding and retention of this information. Furthermore, sustained theta activity may represent continued attentional processing that supports short-term memory, especially of negative facial stimuli. Further study is needed to investigate the potential influence of these measures, and their interaction, on behavioural performance.

Affect modulated startle in schizophrenia: subjective experience matters.

Data suggests that emotion reactivity as measured by the affect-modulated startle paradigm in those with schizophrenia (SZ) may be similar to healthy controls (HC). However, normative classification of the stimuli may not accurately reflect emotional experience, especially for those with SZ. To examine this possibility, the present study measured the affect-modulated startle response with images classified according to both normative and subjective ratings. Seventeen HC and 17 SZ completed an image viewing task during which startle probes were presented, followed by subjective valence and arousal ratings. Both groups exhibited inhibited startle responses to positive images, intermediate startle amplitudes to neutral images, and potentiated startle amplitudes to negative images. SZ rated the positive images as less positive than HC. When images were reclassified based on subjective valence ratings, both groups' startle magnitudes increased in response to subjectively rated positive images and decreased to subjectively rated neutral images. The number of trials classified into each valence condition suggested a tendency for SZ to classify neutral images as negative more often than HC. Overall, these findings suggest that affective stimuli modulate the startle response in HC and SZ in similar ways, but subjective emotional experience may differ in those with schizophrenia.

Resting state EEG power and coherence abnormalities in bipolar disorder and schizophrenia.

Resting state electroencephalogram (EEG) abnormalities in schizophrenia and bipolar disorder patients suggest alterations in neural oscillatory activity. However, few studies directly compare these anomalies between patient groups, and none have examined EEG coherence. Therefore, this study investigated whether these electrophysiological characteristics differentiate clinical populations from one another, and from non-psychiatric controls. To address this question, resting EEG power and coherence were assessed in 76 bipolar patients (BP), 132 schizophrenia patients (SZ), and 136 non-psychiatric controls (NC). We conducted separate repeated-measures ANOVAs to examine group differences within seven frequency bands across several brain regions. BP showed significantly greater power relative to SZ at higher frequencies including Beta and Gamma across all regions. In terms of intra-hemispheric coherence, while SZ generally exhibited higher coherence at Delta compared to NC and BP, both SZ and BP showed higher coherence at Alpha1 and Alpha2. In contrast, BP and HC showed higher coherence within hemispheres compared to SZ at Beta 1. In terms of inter-hemispheric coherence, SZ displayed higher coherence compared to NC at temporal sites at both Alpha1 and Alpha2. Taken together, BP exhibited increased high frequency power with few disruptions in neural synchronization. In contrast, SZ generally exhibited enhanced synchronization within and across hemispheres. These findings suggest that resting EEG can be a sensitive measure for differentiating between clinical disorders.

Auditory steady state response in the schizophrenia, first-degree relatives, and schizotypal personality disorder.

The power and phase synchronization of the auditory steady state response (ASSR) at 40 Hz stimulation is usually reduced in schizophrenia (SZ). The sensitivity of the 40 Hz ASSR to schizophrenia spectrum phenotypes, such as schizotypal personality disorder (SPD), or to familial risk has been less well characterized. We compared the ASSR of patients with SZ, persons with schizotypal personality disorder, first degree relatives of patients with SZ, and healthy control participants. ASSRs were obtained to 20, 30, 40 and 50 Hz click trains, and assessed using measures of power (mean trial power or MTP) and phase consistency (phase locking factor or PLF). The MTP to 40 Hz stimulation was reduced in relatives, and there was a trend for MTP reduction in SZ. The 40 Hz ASSR was not reduced in SPD participants. PLF did not differ among groups. These data suggest the 40 Hz ASSR is sensitive to familial risk factors associated with schizophrenia.