A Preliminary Study of Central Nervous System Arousal and Sleep Quality in Bipolar Disorder.

Sleep disturbances are commonly reported in patients with bipolar I disorder (BPI) and are risk factors for mood episodes. In other populations, central nervous system (CNS) hyperarousal is associated with sleep initiation and maintenance problems, and CNS hypoarousal is associated with increased sleep drive. However, it is unclear whether CNS arousal levels are a useful index of sleep disruption in BPI. This study aimed to investigate daytime CNS arousal levels in relation to perceived sleep quality in BPI. Resting EEG, mood state, and self-reported sleep quality data were collected from 34 individuals with BPI. CNS hyperarousal was associated with pervasive poor subjective sleep quality including increased sleep disturbances, increased sleep latency, and reduced global sleep quality. CNS hypoarousal was associated with greater daytime sleepiness, indicating reduced arousal. These preliminary findings suggest that CNS arousal may be a useful index for identifying individuals at high risk for relapse into a mood episode. A limitation of this study is the use of self-report instruments for sleep quality assessment. Future research should investigate the temporal relationship of CNS arousal to sleep disturbances using objective measurements of sleep quality such as polysomnography. If these findings are replicated, measures of CNS arousals may allow for identification of high-risk patients with BPI.

Altered N170 and mood symptoms in bipolar disorder: An electrophysiological study of configural face processing.

OBJECTIVES: Altered social behavior during mood episodes in bipolar disorder often has detrimental and long-lasting interpersonal consequences. Abnormal face processing may play a role in linking brain functions to clinical symptoms and behavior. This study aimed to understand configural face processing in bipolar disorder as a function of basic communicative attributes of the face and mood symptoms using event-related brain potentials (ERPs). METHODS: Forty-two participants with bipolar I disorder (BP) and 43 healthy controls (HC) viewed face stimuli varying in emotion (neutral or fearful), head orientation (forward or deviated), and gaze direction (direct or averted) while ERPs were recorded. Configural face processing was indexed by the N170 wave. RESULTS: BP participants had comparable overall N170 amplitude and peak latency to HC, although timing was more variable in the BP group. Abnormal N170 modulations by communicative face attributes were observed in BP: exaggerated sensitivity to emotion (fearful > neutral) in the left hemisphere, and reduced sensitivity to gaze-head incongruency (where N170 is normally larger in response to faces with incongruent than congruent gaze and head direction) in the right hemisphere. The former was not associated with mood symptoms, suggesting a heightened trait-like sensitivity to negative emotions. The latter was correlated with greater manic symptoms, indicating that an impaired perceptual sensitivity to faces with features signaling incongruent social attention may underlie social deficits observed during mania. CONCLUSIONS: These findings suggest a pathophysiological role of altered configural face processing in the phenomenology of bipolar disorder, and call for further investigations to evaluate its potential as a biomarker and treatment target.

Reduced theta-band neural oscillatory activity during affective cognitive control in bipolar I disorder.

Individuals with bipolar I disorder (BD) have difficulty inhibiting context-inappropriate responses. However, neural mechanisms of impaired cognitive control over impulsive behaviors, especially in response to emotion, are unclear. Theta-band neural oscillatory activity over midfrontal areas is thought to reflect cognitive control. The current study examined behavioral performance and theta-band activity during inhibition to affective stimuli in BD, relative to healthy control participants (HC). Sixty-seven participants with BD and 48 HC completed a Go/No-Go task with emotional face stimuli during electroencephalography (EEG) recording. Behavior was measured with reaction time, discriminability (d') and response bias (ß). Time-frequency decomposition of EEG data was used to extract event-related theta-band (4-7 Hz) neural oscillatory power and inter-trial phase consistency (ITPC) over midline fronto-central areas. Behavior and theta-band activity were compared between groups, while covarying for age. Participants with BD exhibited slower response execution times on correct Go trials and reduced behavioral discrimination of emotional versus neutral faces, compared to HC. Theta-band power and ITPC were reduced in BD relative to HC. Theta-band power was higher on No-Go trials than Go trials. The magnitude of differences in theta-band activity between Go/No-Go trial types did not differ between groups. Increased theta-band power was associated with faster response execution times, greater discrimination of differing facial expressions, and stronger tendency to respond both across the full sample and within the BD group. Attenuated midline fronto-central theta-band activity may contribute to reduced cognitive control and maladaptive behavioral responding to emotional cues in individuals with BD.

Event-related potential correlates of affective response inhibition in bipolar I disorder: Comparison with schizophrenia.

BACKGROUND: Individuals with bipolar I disorder (BD) have difficulty inhibiting context-inappropriate responses. The neural mechanisms contributing to these difficulties, especially in emotional contexts, are little understood. This study aimed to inform mechanisms of impaired impulsivity control in response to emotion in BD, and whether response inhibition indices are altered to a similar degree in schizophrenia spectrum disorders (SZ). We examined alterations to behavioral performance and event-related potentials (ERPs) during inhibition to affective stimuli in BD, relative to healthy control participants (HC) and SZ. METHODS: Sixty-six participants with BD, 32 participants with SZ, and 48 HC completed a Go/No-Go task with emotional face stimuli while electroencephalography was recorded. Behavioral signal detection metrics (perceptual sensitivity, response bias) and ERPs (N200, P300) were compared across groups. RESULTS: Relative to HC, participants with BD showed reduced (1) discrimination of Go vs. No-Go stimuli (i.e., emotional vs. neutral faces), and (2) P300 amplitudes elicited by emotional faces. Results similarly extended to SZ: BD and SZ groups did not differ on behavioral performance nor ERP amplitudes. LIMITATIONS: Aspects of the Go/No-Go task design may have limited findings, and medication effects on ERP amplitudes in patient samples cannot be fully ruled out. CONCLUSIONS: Findings suggest the difficulty participants with BD and SZ experienced on the current affective response inhibition task lied largely in discriminating between facial expressions. Difficulties with discriminating emotional from neutral expressions may contribute to difficulties with appropriate behavioral responding in social-affective contexts for individuals with BD and SZ.

Prolongation of ERP latency and reaction time (RT) in simultaneous EEG/fMRI data acquisition.

BACKGROUND: Recording EEG and fMRI data simultaneously inside a fully-operating scanner has been recognized as a novel approach in human brain research. Studies have demonstrated high concordance between the EEG signals and hemodynamic response. However, a few studies reported altered cognitive process inside the fMRI scanner such as delayed reaction time (RT) and reduced and/or delayed N100 and P300 event-related brain potential (ERP) components. NEW METHOD: The present study investigated the influence of electromagnetic field (static magnetic field, radio frequency (RF) pulse, and gradient switching) and experimental environment on posterior N100 and P300 ERP components in four different settings with six healthy subjects using a visual oddball task: (1) classic fMRI acquisition inside the scanner (e.g., supine position, mirror glasses for stimulus presentation), (2) standard behavioral experiment outside the scanner (e.g., seated position, keyboard response), (3) controlled fMRI acquisition inside the scanner (e.g., organic light-emitting diode (OLED) goggles for stimulus presentation) inside; and (4) modified behavioral experiment outside the scanner (e.g., supine position, OLED goggles). RESULTS: The study findings indicated that the experimental environment in simultaneous EEG/fMRI acquisition could substantially delay N1P, P300 latency, and RT inside the scanner, and was associated with a reduced N1P amplitude. COMPARISON WITH EXISTING METHODS: There was no effect of electromagnetic field in the prolongation of RT, N1P and P300 latency inside the scanner. N1P, but not P300, latency was sensitive to stimulus presentation method inside the scanner. CONCLUSION: Future simultaneous EEG/fMRI data collection should consider experimental environment in both design and analysis.

Negative affect predicts social functioning across schizophrenia and bipolar disorder: Findings from an integrated data analysis.

Most people with a serious mental illness experience significant functional impairment despite ongoing pharmacological treatment. Thus, in order to improve outcomes, a better understanding of functional predictors is needed. This study examined negative affect, a construct comprised of negative emotional experience, as a predictor of social functioning across serious mental illnesses. One hundred twenty-seven participants with schizophrenia, 113 with schizoaffective disorder, 22 with psychosis not otherwise specified, 58 with bipolar disorder, and 84 healthy controls (N=404) completed self-report negative affect measures. Elevated levels of negative affect were observed in clinical participants compared with healthy controls. For both clinical and healthy control participants, negative affect measures were significantly correlated with social functioning, and consistently explained significant amounts of variance in functioning. For clinical participants, this relationship persisted even after accounting for cognition and positive/negative symptoms. The findings suggest that negative affect is a strong predictor of outcome across these populations and treatment of serious mental illnesses should target elevated negative affect in addition to cognition and positive/negative symptoms.

Altered attentional and perceptual processes as indexed by N170 during gaze perception in schizophrenia: Relationship with perceived threat and paranoid delusions.

Using gaze information to orient attention and guide behavior is critical to social adaptation. Previous studies have suggested that abnormal gaze perception in schizophrenia (SCZ) may originate in abnormal early attentional and perceptual processes and may be related to paranoid symptoms. Using event-related brain potentials (ERPs), this study investigated altered early attentional and perceptual processes during gaze perception and their relationship to paranoid delusions in SCZ. Twenty-eight individuals with SCZ or schizoaffective disorder and 32 demographically matched healthy controls (HCs) completed a gaze-discrimination task with face stimuli varying in gaze direction (direct, averted), head orientation (forward, deviated), and emotion (neutral, fearful). ERPs were recorded during the task. Participants rated experienced threat from each face after the task. Participants with SCZ were as accurate as, though slower than, HCs on the task. Participants with SCZ displayed enlarged N170 responses over the left hemisphere to averted gaze presented in fearful relative to neutral faces, indicating a heightened encoding sensitivity to faces signaling external threat. This abnormality was correlated with increased perceived threat and paranoid delusions. Participants with SCZ also showed a reduction of N170 modulation by head orientation (normally increased amplitude to deviated faces relative to forward faces), suggesting less integration of contextual cues of head orientation in gaze perception. The psychophysiological deviations observed during gaze discrimination in SCZ underscore the role of early attentional and perceptual abnormalities in social information processing and paranoid symptoms of SCZ.

Regulating the High: Cognitive and Neural Processes Underlying Positive Emotion Regulation in Bipolar I Disorder.

Although it is well established that Bipolar Disorder (BD) is characterized by excessive positive emotionality, the cognitive and neural processes that underlie such responses are unclear. We addressed this issue by examining the role that an emotion regulatory process called self-distancing plays in two potentially different BD phenotypes-BD with vs. without a history of psychosis-and healthy individuals. Participants reflected on a positive autobiographical memory and then rated their level of spontaneous self-distancing. Neurophysiological activity was continuously monitored using electroencephalogram. As predicted, participants with BD who have a history of psychosis spontaneously self-distanced less and displayed greater neurophysiological signs of positive emotional reactivity compared to the other two groups. These findings shed light on the cognitive and neural mechanisms underlying excessive positive emotionality in BD. They also suggest that individuals with BD who have a history of psychosis may represent a distinct clinical phenotype characterized by dysfunctional emotion regulation.

Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis.

INTRODUCTION: Several studies have associated cannabis use with the development of schizophrenia. However, it has been difficult to disentangle the effects of cannabis from that of other illicit drugs, as previous studies have not evaluated pure cannabis users. To test whether the onset of cannabis use had an effect on the initiation of psychosis, we examined the time relationship between onset of use and onset of psychosis, restricting our analysis to a cohort of individuals who only used cannabis and no other street drugs. METHODS: Fifty-seven subjects with non-affective psychoses who used cannabis prior to developing a psychosis were interviewed using the Diagnostic Interview for Genetic Studies (DIGS). The Family Interview for Genetic Studies (FIGS) was also used to interview a family informant about psychiatric illness in the patient and the entire family. Multiple linear regression techniques were used to estimate the association between variables. RESULTS: After adjusting for potential confounding factors such as sex, age, lifetime diagnosis of alcohol abuse or dependence, and family history of schizophrenia, the age at onset of cannabis was significantly associated with age at onset of psychosis (ß=0.4, 95% CI=0.1-0.7, p=0.004) and age at first hospitalization (ß=0.4, 95% CI=0.1-0.8, p=0.008). The mean time between beginning to use cannabis and onset of psychosis was 7.0±4.3. Age at onset of alcohol use was not associated with age at onset of psychosis or age at first hospitalization. CONCLUSION: Age at onset of cannabis is directly associated with age at onset of psychosis and age at first hospitalization. These associations remain significant after adjusting for potential confounding factors and are consistent with the hypothesis that cannabis could cause or precipitate the onset of psychosis after a prolonged period of time.