Longitudinal Interplay Between Alcohol Use, Mood, and Functioning in Bipolar Spectrum Disorders.

Importance: Alcohol use disorder (AUD) is present in nearly half of individuals with bipolar disorder (BD) and is associated with markedly worsening outcomes. Yet, the concurrent treatment of BD and AUD remains neglected in both research and clinical care; characterizing their dynamic interplay is crucial in improving outcomes. Objective: To characterize the longitudinal alcohol use patterns in BD and examine the temporal associations among alcohol use, mood, anxiety, and functioning over time. Design, Setting, and Participants: This cohort study selected participants and analyzed data from the Prechter Longitudinal Study of Bipolar Disorder (PLS-BD), an ongoing cohort study that recruits through psychiatric clinics, mental health centers, and community outreach events across Michigan and collects repeated phenotypic data. Participants selected for the present study were those with a diagnosis of BD type I (BDI) or type II (BDII) who had been in the study for at least 5 years. Data used were extracted from February 2006 to April 2022, and follow-up ranged from 5 to 16 years. Main Outcomes and Measures: Alcohol use was measured using the Alcohol Use Disorders Identification Test. Depression, mania or hypomania, anxiety, and functioning were measured using the 9-Item Patient Health Questionnaire, the Altman Self-Rating Mania Scale, the 7-item Generalized Anxiety Disorder assessment scale, and the Life Functioning Questionnaire, respectively. Results: A total of 584 individuals (386 females (66.1%); mean [SD] age, 40 [13.6] years) were included. These participants had a BDI (445 [76.2%]) or BDII (139 [23.8%]) diagnosis, with or without a lifetime diagnosis of AUD, and a median (IQR) follow-up of 9 (0-16) years. More problematic alcohol use was associated with worse depressive (ß = 0.04; 95% credibility interval [CrI], 0.01-0.07) and manic or hypomanic symptoms (ß = 0.04; 95% CrI, 0.01-0.07) as well as lower workplace functioning (ß = 0.03; 95% CrI, 0.00-0.06) over the next 6 months, but increased depressive and manic or hypomanic symptoms were not associated with greater subsequent alcohol use. These latter 2 associations were more pronounced in BDII than BDI (mania or hypomania: ß = 0.16 [95% CrI, 0.02-0.30]; workplace functioning: ß = 0.26 [95% CrI, 0.06-0.45]). Alcohol use was not associated with anxiety over time. Conclusions and Relevance: This study found that alcohol use, regardless of diagnostic status, was associated with mood instability and poorer work functioning in BD, but increased mood symptoms were not associated with subsequent alcohol use. Given its prevalence and repercussions, dimensional and longitudinal assessment and management of alcohol use are necessary and should be integrated into research and standard treatment of BD.

Reductions in regional theta power and fronto-parietal theta-gamma phase-amplitude coupling during gaze processing in bipolar disorder.

Impaired social cognition is common in bipolar disorder (BD) and predicts poor functional outcomes. A critical determinant of social cognition is the ability to discriminate others' gaze direction, and its alteration may contribute to functional impairment in BD. However, the neural mechanisms underlying gaze processing in BD are unclear. Because neural oscillations are crucial neurobiological mechanisms supporting cognition, we aimed to understand their role in gaze processing in BD. Using electroencephalography (EEG) data recorded during a gaze discrimination task for 38 BD and 34 controls (HC), we examined: theta and gamma power over bilateral posterior and midline anterior locations associated with early face processing and higher-level cognitive processing, and theta-gamma phase-amplitude coupling (PAC) between locations. Compared to HC, BD showed reduced midline-anterior and left-posterior theta power, and diminished bottom-up/top-down theta-gamma PAC between anterior/posterior sites. Reduced theta power and theta-gamma PAC related to slower response times. These findings suggest that altered theta oscillations and anterior-posterior cross-frequency coupling between areas associated with higher-level cognition and early face processing may underlie impaired gaze processing in BD. This is a crucial step towards translational research that may inform novel social cognitive interventions (e.g., neuromodulation to target specific oscillatory dynamics) to improve functioning in BD.

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.

Sleep quality and neuropsychological functioning in bipolar I disorder.

BACKGROUND: Individuals with bipolar I disorder (BD-I) experience both poor sleep and neuropsychological dysfunction relative to non-psychiatric populations, which limits functional recovery. Poor sleep adversely affects learning, memory, and executive functioning in healthy individuals; however, little is known about the role of poor sleep in neuropsychological functioning in BD-I. We tested whether sleep disturbance was greater in BD-I than healthy control participants (HC), and compared the effect of sleep quality on learning, memory, and executive functioning between BD-I and HC. METHODS: Participants with BD-I (N=250) and HC (N=206) completed the Pittsburgh Sleep Quality Index, neuropsychological testing, and clinician-administered mood measures as part of a naturalistic study of bipolar disorder. We examined effects of both diagnosis and sleep quality on neuropsychological functioning. RESULTS: Relative to HC, BD-I showed poorer sleep quality and neuropsychological functioning in verbal learning, verbal and visual memory, processing speed, psychomotor speed, inhibitory control, and selective attention (7/9 domains). Poor sleep quality was associated with poorer verbal learning, verbal fluency, processing speed, and interference control (4/9). Effects of poor sleep on neuropsychological functioning did not differ between BD-I and HC. LIMITATIONS: The assessment of sleep quality using a self-report measure and the effects of medications/sleeping aids (given the naturalistic study design) should be considered when interpreting results. CONCLUSIONS: Those with BD-I experiencing poor sleep may also be more vulnerable to verbal learning and executive functioning impairments. The findings of poor sleep in relation to poorer neuropsychological functioning have implications for assessment and treatment of sleep disturbance in BD-I.

Preliminary Evidence for Sociotropy and Autonomy in Relation to Antidepressant Treatment Outcome.

Sociotropy and autonomy are cognitive-personality styles that have been hypothesized to confer vulnerability to different presentations of major depressive disorder (MDD), which may respond differentially to treatment. Specifically, the profile of low sociotropy and high autonomy is hypothesized to indicate a positive response to antidepressant medication. The current study examines sociotropy and autonomy in relation to sertraline treatment response in individuals with MDD. As part of an ancillary study to the larger Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) project, individuals with MDD participated in an 8-week trial of sertraline and completed a self-report questionnaire of sociotropy and autonomy. Discriminant function analyses were used to examine whether sociotropy and autonomy scores could distinguish antidepressant treatment responders (determined by a 50% or greater reduction in depressive symptoms) from non-responders. The sociotropy scale successfully discriminated sertraline treatment responders from non-responders. Further, lower sociotropy was associated with greater improvements in depressive symptomology following sertraline treatment. The current findings suggest individuals with MDD characterized by low sociotropy are more likely to benefit from sertraline. Given the promising results of the Sociotropy-Autonomy Scale in discriminating treatment responders from non-responders, the low resources necessary for administration, and the ease of translation into routine clinical care, the scale warrants further research attention.

Neuropsychological functioning in early and chronic stages of schizophrenia and psychotic bipolar disorder.

BACKGROUND: Neuropsychological impairment is common in schizophrenia and psychotic bipolar disorder. It has been hypothesized that the pathways leading to impairment differ between disorders. Cognitive impairment in schizophrenia is believed to result largely from atypical neurodevelopment, whereas bipolar disorder is increasingly conceptualized as a neuroprogressive disorder. The current investigation tested several key predictions of this hypothesis. METHODS: Current neuropsychological functioning and estimated premorbid intellectual ability were assessed in healthy individuals (n = 260) and a large, cross-sectional sample of individuals in the early and chronic stages of psychosis (n = 410). We tested the following hypotheses: 1) cognitive impairment is more severe in schizophrenia in the early stage of psychosis; and 2) cognitive decline between early and chronic stages is relatively greater in psychotic bipolar disorder. Additionally, individuals with psychosis were classified as neuropsychologically normal, deteriorated, and compromised (i.e. below average intellectual functioning) to determine if the frequencies of neuropsychologically compromised and deteriorated patients were higher in schizophrenia and psychotic bipolar disorder, respectively. RESULTS: Neuropsychological impairment in the early stage of psychosis was more severe in schizophrenia. Psychotic bipolar disorder was not associated with relatively greater cognitive decline between illness stages. The frequency of neuropsychologically compromised patients was higher in schizophrenia; however, substantial portions of both schizophrenia and psychotic bipolar disorder patients were classified as neuropsychologically compromised and deteriorated. CONCLUSIONS: While schizophrenia is associated with relatively greater neurodevelopmental involvement, psychotic bipolar disorder and schizophrenia cannot be strictly dichotomized into purely neuroprogressive and neurodevelopmental illness trajectories; there is evidence of both processes in each disorder.