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.

Non-linear Entropy Analysis in EEG to Predict Treatment Response to Repetitive Transcranial Magnetic Stimulation in Depression.

Background: Biomarkers that predict clinical outcomes in depression are essential for increasing the precision of treatments and clinical outcomes. The electroencephalogram (EEG) is a non-invasive neurophysiological test that has promise as a biomarker sensitive to treatment effects. The aim of our study was to investigate a novel non-linear index of resting state EEG activity as a predictor of clinical outcome, and compare its predictive capacity to traditional frequency-based indices. Methods: EEG was recorded from 62 patients with treatment resistant depression (TRD) and 25 healthy comparison (HC) subjects. TRD patients were treated with excitatory repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) for 4 to 6 weeks. EEG signals were first decomposed using the empirical mode decomposition (EMD) method into band-limited intrinsic mode functions (IMFs). Subsequently, Permutation Entropy (PE) was computed from the obtained second IMF to yield an index named PEIMF2. Receiver Operator Characteristic (ROC) curve analysis and ANOVA test were used to evaluate the efficiency of this index (PEIMF2) and were compared to frequency-band based methods. Results: Responders (RP) to rTMS exhibited an increase in the PEIMF2 index compared to non-responders (NR) at F3, FCz and FC3 sites (p < 0.01). The area under the curve (AUC) for ROC analysis was 0.8 for PEIMF2 index for the FC3 electrode. The PEIMF2 index was superior to ordinary frequency band measures. Conclusion: Our data show that the PEIMF2 index, yields superior outcome prediction performance compared to traditional frequency band indices. Our findings warrant further investigation of EEG-based biomarkers in depression; specifically entropy indices applied in band-limited EEG components. Registration in ClinicalTrials.Gov; identifiers NCT02800226 and NCT01887782.

The Network Structure of Schizotypal Personality Traits.

Elucidating schizotypal traits is important if we are to understand the various manifestations of psychosis spectrum liability and to reliably identify individuals at high risk for psychosis. The present study examined the network structures of (1) 9 schizotypal personality domains and (2) 74 individual schizotypal items, and (3) explored whether networks differed across gender and culture (North America vs China). The study was conducted in a sample of 27001 participants from 12 countries and 21 sites (M age = 22.12; SD = 6.28; 37.5% males). The Schizotypal Personality Questionnaire (SPQ) was used to assess 74 self-report items aggregated in 9 domains. We used network models to estimate conditional dependence relations among variables. In the domain-level network, schizotypal traits were strongly interconnected. Predictability (explained variance of each node) ranged from 31% (odd/magical beliefs) to 55% (constricted affect), with a mean of 43.7%. In the item-level network, variables showed relations both within and across domains, although within-domain associations were generally stronger. The average predictability of SPQ items was 27.8%. The network structures of men and women were similar (r = .74), node centrality was similar across networks (r = .90), as was connectivity (195.59 and 199.70, respectively). North American and Chinese participants networks showed lower similarity in terms of structure (r = 0.44), node centrality (r = 0.56), and connectivity (180.35 and 153.97, respectively). In sum, the present article points to the value of conceptualizing schizotypal personality as a complex system of interacting cognitive, emotional, and affective characteristics.

Comparisons of schizotypal traits across 12 countries: Results from the International Consortium for Schizotypy Research.

BACKGROUND: Schizotypal traits are expressions of underlying vulnerability to psychotic disorders which have a potential impact on mental health status, neurocognition, quality of life, and daily functioning. To date, little research has examined epidemiologic landscape of schizotypal traits at the cross-national level. Our aim was to study the expression of schizotypal traits by sex, age, and country in a combined sample gathered from 12 countries. METHODS: A total of 27,001 participants completed the Schizotypal Personality Questionnaire (SPQ). The mean age of participants was 22.12 (SD=6.28); 37.5% (n=10,126) were males. RESULTS: Schizotypal traits varied according to sex, age, and country. Females scored higher than males in the positive dimension, whereas males scored higher in the disorganization dimension. By age, a significant decrease in the positive schizotypal traits was observed. Epidemiological expression of schizotypal traits varied by country. Moreover, several interactions by sex, age, and country were found. CONCLUSIONS: This pattern is similar to those found in patients with psychosis and psychotic-like experiences. These findings provide new insights and the opportunity to explore the phenotypic expression of schizotypal traits at cross-national level.

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.

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.

Brief assessment of schizotypal traits: A multinational study.

The Schizotypal Personality Questionnaire-Brief (SPQ-B) was developed with the aim of examining variations in healthy trait schizotypy, as well as latent vulnerability to psychotic-spectrum disorders. No previous study has studied the cross-cultural validity of the SPQ-B in a large cross-national sample. The main goal of the present study was to analyze the reliability and the internal structure of SPQ-B scores in a multinational sample of 28,426 participants recruited from 14 countries. The mean age was 22.63years (SD=7.08; range 16-68years), 37.7% (n=10,711) were men. The omega coefficients were high, ranging from 0.86 to 0.92 for the total sample. Confirmatory factor analysis revealed that SPQ-B items were grouped either in a theoretical structure of three first-order factors (Cognitive-Perceptual, Interpersonal, and Disorganized) or in a bifactor model (three first-order factors plus a general factor of schizotypal personality). In addition, the results supported configural but not strong measurement invariance of SPQ-B scores across samples. These findings provide new information about the factor structure of schizotypal personality, and support the validity and utility of the SPQ-B, a brief and easy tool for assessing self-reported schizotypal traits, in cross-national research. Theoretical and clinical implications for diagnostic systems, psychosis models, and cross-national mental health strategies are derived from these results.

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.

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.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort.

BACKGROUND: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. METHODS: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. DISCUSSION: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01655706 . Registered July 27, 2012.

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.

Occurrence of Postictal α/ß Activity During Maintenance Course of Electroconvulsive Therapy.

We are aware of a report of postictal α activity after seizures in Epilepsy and Behavior. We would like to report another case of a similar phenomenon in a woman receiving maintenance electroconvulsive therapy.

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.

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.

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.

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.

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.

Prospective predictors of mood episodes in bipolar disorder.

BACKGROUND: : Bipolar disorder (BD) is associated with alterations in mood, personality, cognition and event-related potential (ERP) measures. The relationship between these multidimensional measures of state and subsequent course of the illness is not well understood. Therefore, this study aimed to prospectively identify factors that predicted the course of mood episodes. METHODS: : Sixty-five participants with BD were administered the auditory P300 oddball task, clinical assessment instruments and cognitive tests at baseline, and were subsequently administered the SCID interview once a month by telephone for 12 months. RESULTS: : Hierarchical regression analyses indicated that the Montgomery-Asberg Depression Rating Scale (MADRS) predicted the number of months spent in a depressed state (p<.001) and in a mixed state (p=.001), while both the MADRS (p<.001) and time to complete Trails A (p=.033) predicted total number of months in a mood episode (across all mood states). Among euthymic patients at entry, Cox regression analyses indicated that higher ratings on both the MADRS (p=.017) and Hypomanic Personality Scale (HPS; p<.001) were associated with both increased likelihood of a mood episode and less time until the onset of a mood episode. LIMITATIONS: : The sample size is relatively small, not all participants completed 12 months, and follow-up assessments were conducted via telephone. CONCLUSIONS: : Our results suggest that affective and cognitive measures, and personality factors, especially the MADRS and HPS, serve as important predictors of the course of mood episodes or relapse in BD patients. These prospective markers of acute mood states may be used to guide treatment decisions.