Mathematical Modeling of Risk-Taking in Bipolar Disorder: Evidence of Reduced Behavioral Consistency, With Altered Loss Aversion Specific to Those With History of Substance Use Disorder

Bipolar disorder (BD) is associated with excessive pleasure-seeking risk-taking behaviors that often characterize its clinical presentation. However, the mechanisms of risk-taking behavior are not well-understood in BD. Recent data suggest prior substance use disorder (SUD) in BD may represent certain trait-level vulnerabilities for risky behavior. This study examined the mechanisms of risk-taking and the role of SUD in BD via mathematical modeling of behavior on the Balloon Analogue Risk Task (BART). Three groups—18 euthymic BD with prior SUD (BD+), 15 euthymic BD without prior SUD (BD–), and 33 healthy comparisons (HC)—completed the BART. We modeled behavior using four competing hierarchical Bayesian models, and model comparison results favored the Exponential-Weight Mean-Variance (EWMV) model, which encompasses and delineates five cognitive components of risk-taking: prior belief, learning rate, risk preference, loss aversion, and behavioral consistency. Both BD groups, regardless of SUD history, showed lower behavioral consistency than HC. BD+ exhibited more pessimistic prior beliefs (relative to BD– and HC) and reduced loss aversion (relative to HC) during risk-taking on the BART. Traditional measures of risk-taking on the BART (adjusted pumps, total points, total pops) detected no group differences. These findings suggest that reduced behavioral consistency is a crucial feature of risky decision-making in BD and that SUD history in BD may signal additional trait vulnerabilities for risky behavior even when mood symptoms and substance use are in remission. This study also underscores the value of using mathematical modeling to understand behavior in research on complex disorders like BD

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

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145368/1/bdi12587.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145368/2/bdi12587_am.pd

Eye gaze perception in bipolar disorder: Self‐referential bias but intact perceptual sensitivity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142550/1/bdi12564.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142550/2/bdi12564_am.pd

Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs

IL10 Haplotype Associated with Tuberculin Skin Test Response but Not with Pulmonary TB

Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions −2849 , −1082 , −819 , and −592 and reconstructed the haplotypes. The IL10 low-producer haplotype −2849A/−1082A/−819C/−592C, compared to the high-producer haplotype −2849G/−1082G/−819C/−592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3–3.6) and PPD-positive controls (OR 2.09, CI 1.2–3.5). Lower IL-10 plasma levels in homozygous −2849A/−1082A/−819C/−592C carriers, compared to homozygous −2849G/−1082G/−819C/−592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy

Eye Gaze Processing in Schizophrenia.

Accurately perceiving self-referential social signals, particularly eye contact, is critical to social adaptation. Schizophrenia (SCZ) is a severe mental disorder often accompanied by deficits in social cognition, but it is unclear whether this includes gaze discrimination deficits. This dissertation used a multi-method approach to examine whether and how eye gaze information is processed differently in schizophrenia, its functional consequences, and the role of basic visual perception in abnormal gaze perception. In Study 1, 26 participants with SCZ and 23 healthy controls (HC) made eye-contact judgments for faces in varying gaze direction (from averted to direct in ten 10%-increments), head orientation (forward, 30-degree averted), and emotion (neutral, fearful). Psychophysical analyses demonstrated that SCZ participants exhibited abnormal eye-contact perception characterized by over-attribution of self-directed intention to ambiguous gaze and decreased dichotomy of eye-contact perception. These abnormalities were related to more severe negative symptoms and explained deficits in broader socio-emotional functioning beyond a general deficit problem. In Study 2, 25 SCZ and 26 HC participants completed a gaze discrimination task while their event-related brain potentials (ERPs) were recorded. SCZ participants displayed ERP deviations that could not be accounted for by differential performance, including a heightened encoding sensitivity (N170) to faces signaling external threat, a tendency to integrate less the contextual cue of head orientation, and reduced mental resources for stimulus categorization (P300). In Study 3, 29 SCZ and 23 HC participants completed two tasks that measured visual integration, the ability to effectively integrate individual local visual elements into a holistic picture. SCZ participants showed poorer visual integration than HC, and compromised visual integration significantly predicted deficits in eye-contact perception and emotional intelligence in SCZ and explained group differences in these two social cognitive processes. Taken together, this dissertation showed that abnormal gaze perception is present in SCZ and bears important clinical and functional implications, and it may be driven by deficits in basic visual perception. The nature and functional relevance of gaze perception in SCZ informed by this dissertation may help developing treatment options targeting at specific brain areas/functions for persons with or at risk for SCZ in the future.PHDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/93943/1/ivytso_1.pd

Segregation of salience network predicts treatment response of depression to repetitive transcranial magnetic stimulation

Background: The present study tested the hypothesis that network segregation, a graph theoretic measure of functional organization of the brain, is correlated with treatment response in patients with major depressive disorder (MDD) undergoing repetitive transcranial magnetic stimulation (rTMS). Methods: Network segregation, calculated from resting state functional magnetic resonance imaging scans, was measured in 32 patients with MDD who entered a sham-controlled, double-blinded, randomized trial of rTMS to the left dorsolateral prefrontal cortex, and a cohort of 20 healthy controls (HCs). Half of the MDD patients received sham treatment in the blinded phase, followed by active rTMS in the open-label phase. The analyses focused on segregation of the following networks: default mode (DMN), salience (SN), fronto-parietal (FPN), cingulo-opercular (CON), and memory retrieval (MRN). Results: There was no differential change in network segregation comparing sham to active treatment. However, in the combined group of patients who completed active rTMS treatment (in the blinded plus open-label phases), higher baseline segregation of SN significantly predicted more symptom improvement after rTMS. Compared to HCs at baseline, MDD patients showed decreased segregation in DMN, and trend-level decreases in SN and MRN. Conclusion: The results highlight the importance of network segregation in MDD, particularly in the SN, where more normal baseline segregation of SN may predict better treatment response to rTMS in depression. Keywords: Repetitive transcranial magnetic stimulation, Depression, Segregation, Salience network, Default mode networ

Evidence for embracing normative modeling

In this work, we expand the normative model repository introduced in Rutherford et al., 2022a to include normative models charting lifespan trajectories of structural surface area and brain functional connectivity, measured using two unique resting-state network atlases (Yeo-17 and Smith-10), and an updated online platform for transferring these models to new data sources. We showcase the value of these models with a head-to-head comparison between the features output by normative modeling and raw data features in several benchmarking tasks: mass univariate group difference testing (schizophrenia versus control), classification (schizophrenia versus control), and regression (predicting general cognitive ability). Across all benchmarks, we show the advantage of using normative modeling features, with the strongest statistically significant results demonstrated in the group difference testing and classification tasks. We intend for these accessible resources to facilitate the wider adoption of normative modeling across the neuroimaging community

The “social brain” is highly sensitive to the mere presence of social information: An automated meta-analysis and an independent study

<div><p>How the human brain processes social information is an increasingly researched topic in psychology and neuroscience, advancing our understanding of basic human cognition and psychopathologies. Neuroimaging studies typically seek to isolate one specific aspect of social cognition when trying to map its neural substrates. It is unclear if brain activation elicited by different social cognitive processes and task instructions are also spontaneously elicited by general social information. In this study, we investigated whether these brain regions are evoked by the mere presence of social information using an automated meta-analysis and confirmatory data from an independent study of simple appraisal of social vs. non-social images. Results of 1,000 published fMRI studies containing the keyword of “social” were subject to an automated meta-analysis (<a href="http://neurosynth.org/" target="_blank">http://neurosynth.org</a>). To confirm that significant brain regions in the meta-analysis were driven by a social effect, these brain regions were used as regions of interest (ROIs) to extract and compare BOLD fMRI signals of social vs. non-social conditions in the independent study. The NeuroSynth results indicated that the dorsal and ventral medial prefrontal cortex, posterior cingulate cortex, bilateral amygdala, bilateral occipito-temporal junction, right fusiform gyrus, bilateral temporal pole, and right inferior frontal gyrus are commonly engaged in studies with a prominent social element. The social–non-social contrast in the independent study showed a strong resemblance to the NeuroSynth map. ROI analyses revealed that a social effect was credible in 9 out of the 11 NeuroSynth regions in the independent dataset. The findings support the conclusion that the “social brain” is highly sensitive to the mere presence of social information.</p></div