Browsing by Author "Strakowski, Stephen M."
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Item Alcohol Use and Prefrontal Cortex Volume Trajectories in Young Adults with Mood Disorders and Associated Clinical Outcomes(MDPI, 2022-02-22) Kirsch, Dylan E.; Tretyak, Valeria; Le, Vanessa; Huffman, Ansley; Fromme, Kim; Strakowski, Stephen M.; Lippard, Elizabeth T. C.; Psychiatry, School of MedicineBackground: Alcohol use in the course of mood disorders is associated with worse clinical outcomes. The mechanisms by which alcohol use alters the course of illness are unclear but may relate to prefrontal cortical (PFC) sensitivity to alcohol. We investigated associations between alcohol use and PFC structural trajectories in young adults with a mood disorder compared to typically developing peers. Methods: 41 young adults (24 with a mood disorder, agemean = 21 ± 2 years) completed clinical evaluations, assessment of alcohol use, and two structural MRI scans approximately one year apart. Freesurfer was used to segment PFC regions of interest (ROIs) (anterior cingulate, orbitofrontal cortex, and frontal pole). Effects of group, alcohol use, time, and interactions among these variables on PFC ROIs at baseline and follow-up were modeled. Associations were examined between alcohol use and longitudinal changes in PFC ROIs with prospective mood. Results: Greater alcohol use was prospectively associated with decreased frontal pole volume in participants with a mood disorder, but not typically developing comparison participants (time-by-group-by-alcohol interaction; p = 0.007); however, this interaction became a statistical trend in a sensitivity analysis excluding one outlier in terms of alcohol use. Greater alcohol use and a decrease in frontal pole volume related to longer duration of major depression during follow-up (p’s < 0.05). Conclusion: Preliminary findings support more research on alcohol use, PFC trajectories, and depression recurrence in young adults with a mood disorder including individuals with heavier drinking patterns.Item Association between poor tolerability of antidepressant treatment and brain functional activation in youth at risk for bipolar disorder(Brazilian Psychiatric Association, 2021-02-01) Nery, Fabiano G.; Masifi, Sheela L.; Strawn, Jeffrey R.; Duran, Luis R.; Weber, Wade A.; Welge, Jeffrey A.; Adler, Caleb M.; Strakowski, Stephen M.; DelBello, Melissa P.; Psychiatry, School of MedicineObjective: To investigate whether poor antidepressant tolerability is associated with functional brain changes in children and adolescents of parents with bipolar I disorder (at-risk youth). Methods: Seventy-three at-risk youth (ages 9-20 years old) who participated in a prospective study and had an available baseline functional magnetic resonance imaging (fMRI) scan were included. Research records were reviewed for the incidence of adverse reactions related to antidepressant exposure during follow-up. The sample was divided among at-risk youth without antidepressant exposure (n=21), at-risk youth with antidepressant exposure and no adverse reaction (n=12), at-risk youth with antidepressant-related adverse reaction (n=21), and healthy controls (n=20). The fMRI task was a continuous performance test with emotional distracters. Region-of-interest mean activation in brain areas of the fronto-limbic emotional circuit was compared among groups. Results: Right amygdala activation in response to emotional distracters significantly differed among groups (F3,66 = 3.1, p = 0.03). At-risk youth with an antidepressant-related adverse reaction had the lowest amygdala activation, while at-risk youth without antidepressant exposure had the highest activation (p = 0.004). Conclusions: Decreased right amygdala activation in response to emotional distracters is associated with experiencing an antidepressant-related adverse reaction in at-risk youth. Further studies to determine whether amygdala activation is a useful biomarker for antidepressant-related adverse events are needed.Item Childhood maltreatment, prefrontal-paralimbic gray matter volume, and substance use in young adults and interactions with risk for bipolar disorder(Springer Nature, 2021-01-08) Kirsch, Dylan E.; Tretyak, Valeria; Radpour, Sepeadeh; Weber, Wade A.; Nemeroff, Charles B.; Fromme, Kim; Strakowski, Stephen M.; Lippard, Elizabeth T. C.; Psychiatry, School of MedicineChildhood maltreatment is associated with adverse effects on the brain, and an increased risk for psychopathology, including mood and substance use disorders. Individuals vary on the degree to which they exhibit neurobiological and clinical differences following maltreatment. Individuals with bipolar disorder exhibit greater magnitude of maltreatment-related prefrontal-paralimbic gray matter volume (GMV) deficits compared to typically developing individuals. It is unclear if greater structural differences stem from greater neural vulnerability to maltreatment in bipolar disorder, or if they relate to presence of other clinical features associated with childhood maltreatment, e.g., elevated prevalence of comorbid substance use disorders. To investigate this, we compared young adults with a family history of bipolar disorder (n = 21), but who did not fulfill diagnostic criteria for bipolar disorder, with typically developing young adults without a family history of bipolar disorder (n = 26). Participants completed structural neuroimaging, clinical and family history interviews, and assessment of childhood maltreatment and recent alcohol and cannabis use patterns. We examined relations between childhood maltreatment and prefrontal-paralimbic GMV by modeling main effects of maltreatment and family history group by maltreatment interactions on prefrontal-paralimbic GMV. We also examined relations between maltreatment and associated GMV changes with recent alcohol and cannabis use. Childhood maltreatment correlated with lower ventral, rostral and dorsolateral prefrontal and insular cortical GMV across all participants regardless of the presence or absence of familial history of bipolar disorder. However, exploratory analyses did reveal greater maltreatment-related GMV differences in individuals with prodromal symptoms of depression. Lower insula GMV was associated with greater frequency of cannabis use across all participants and greater quantity of alcohol use only in those with familial risk for bipolar disorder. Results suggest familial risk for bipolar disorder, and presumably genetic risk, may relate to outcomes following childhood maltreatment and should be considered in prevention/early intervention strategies.Item Neural Functional Connectivity Changes to Psychosocial Stress in Young Adults with Bipolar Disorder and Preliminary Associations with Clinical Trajectories(Wiley, 2022) Kirsch, Dylan E.; Preston, Alex; Tretyak, Valeria; Le, Vanessa; Weber, Wade; Strakowski, Stephen M.; Lippard, Elizabeth T. C.; Psychiatry, School of MedicineBackground: Stress-related mechanisms are implicated in the pathophysiology of bipolar disorder and may contribute to heterogeneity in illness course. Yet, there is a lack of study investigating the neural mechanisms underlying the stress response in this condition. This study investigated changes in amygdala activation and functional connectivity in response to acute psychosocial stress in young adults with bipolar disorder and explored relations with clinical phenotype and prospective mood symptoms. Methods: 42 young adults [19 with bipolar disorder, agemean ± SD =21.4 ± 2.2 years] completed a modified version of the Montreal Imaging Stress Task. Amygdala activation and functional connectivity with prefrontal cortex (PFC) regions of interest was calculated for control and stress conditions. Main effects of group, condition, and group by condition interaction on amygdala activation and connectivity were modeled. A subset of bipolar participants completed 1-year follow-up assessments. Relations between neural responses to stress with concurrent substance use and prospective mood symptoms were explored. Results: There were no between-group differences in amygdala activation or functional connectivity during the control condition. Increased right amygdala-right rostral PFC (rPFC) functional connectivity to stress was observed in bipolar disorder, compared to typically developing controls. In bipolar disorder, greater increase in right amygdala-right rPFC functional connectivity to stress was associated with less frequent cannabis use, and prospectively with shorter duration and lower severity of depression symptoms over follow-up. Conclusion: Results from this preliminary study suggest differences in frontolimbic functional connectivity responses to stress in young adults with bipolar disorder and associations with cannabis use and prospective mood symptoms.Item Nucleus accumbens functional connectivity changes underlying alcohol expectancies in bipolar disorder and prospective alcohol outcomes: a within-subject randomized placebo-controlled alcohol administration fMRI study(Frontiers Media, 2025-04-09) Lippard, Elizabeth T. C.; Kirsch, Dylan E.; Le, Vanessa; Lee, Skyler; Bibb, Nadia; Meek, Kaitlyn; Kosted, Raquel; Huffman, Ansley; Almeida, J. R. C.; Fromme, Kim; Strakowski, Stephen M.; Psychiatry, School of MedicineIntroduction: Alcohol use disorder (AUD) occurs at higher rates in individuals with bipolar disorder compared to the general population. A paucity of data are available on specific mechanisms that may contribute to bipolar and AUD co-occurrence. We recently reported differences in alcohol expectancies and placebo response during alcohol administration in early-stage bipolar disorder, compared to healthy young adults. This current report investigated subjective and neural response following placebo beverage consumption in young adults with bipolar disorder. Methods: As part of a within-subject placebo-controlled alcohol administration study, 54 young adults (53% with bipolar disorder type I, age mean + SD = 23 + 2 years, 64% female) completed resting state functional MRI (rsfMRI) scans at baseline (pre-beverage) and following placebo and alcohol consumption (counter-balanced). Participants completed subjective response measures during placebo and alcohol beverage conditions. Between-group differences in subjective response and placebo-related changes in functional connectivity of the Nucleus Accumbens (NAc) with other brain regions, compared to a pre-beverage rsfMRI baseline condition, were investigated. Fisher-transformed correlation coefficients between ROIs and seed-to-clusters showing a significant group-by-condition (placebo, pre-beverage rsfMRI) interaction were calculated. Associations with prospective alcohol use and problems were explored in a subgroup with longitudinal data. Results: Young adults with bipolar disorder reported greater intoxication during the placebo condition, compared to healthy young adults (main effects of group: p < 0.05). Compared to pre-beverage rsfMRI, the placebo condition related to increased connectivity between bilateral NAc and regions within the sensorimotor network in bipolar disorder. Comparison participants showed the opposite pattern of placebo-related changes in connectivity (group-by-condition, p-FDR < 0.05). Greater anxiolytic effects endorsed during placebo and associated increases in NAc functional connectivity related to greater alcohol use and alcohol problems at follow-up in bipolar disorder (p < 0.05). Discussion: Results suggest differences in placebo response in bipolar disorder, including distinct neural correlates, that may relate to prospective alcohol use/problems. Given the theoretical association between placebo response and self-reported alcohol expectancies, findings could open the door to interventions aimed at changing expectancies.Item Pretreatment Alterations and Acute Medication Treatment Effects on Brain Task-related Functional Connectivity in Youth With Bipolar Disorder: A Neuroimaging Randomized Clinical Trial(Elsevier, 2022) Li, Wenbin; Lei, Du; Tallman, Maxwell J.; Ai, Yuan; Welge, Jeffrey A.; Blom, Thomas J.; Fleck, David E.; Klein, Christina C.; Patino, Luis R.; Strawn, Jeffrey R.; Gong, Qiyong; Strakowski, Stephen M.; Sweeney, John A.; Adler, Caleb M.; DelBello, Melissa P.; Psychiatry, School of MedicineObjective: Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established. Method: A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies. Patients, who were untreated for at least 7 days at baseline, and controls were scanned at pretreatment baseline and at weeks 1 and 6. After baseline testing, patients (n = 71) were randomly assigned to 6-week double-blind treatment with lithium (n = 26; 1.0-1.2 mEq/L) or quetiapine (n = 45; 400-600 mg). Weighted seed-based connectivity (wSBC) was used to assess regional brain interactions during the attention task compared with the control condition. Results: At baseline, youths with BD showed reduced connectivity between bilateral anterior cingulate cortex and both left ventral lateral prefrontal cortex and left insula and increased connectivity between left ventral lateral prefrontal cortex and left temporal pole, left orbital frontal cortex and right postcentral gyrus, and right amygdala and right occipital pole compared with controls. At 1-week follow-up, quetiapine, but not lithium, treatment led to a significant shift of connectivity patterns toward those of the controls. At week 6, compared with baseline, there was no difference between treatment conditions, at which time both patient groups showed significant normalization of brain connectivity toward that of controls. Conclusion: Functional alterations in several brain regions associated with cognitive processing and the integration of cognitive and affective processing were demonstrated in untreated youths with BD before treatment. Treatment reduced several of these alterations, with significant effects at week 1 only in the quetiapine treatment group. Normalization of functional connectivity might represent a promising biomarker for early target engagement in youth with BD.Item Recent Perceived Stress, Amygdala Reactivity to Acute Psychosocial Stress, and Alcohol and Cannabis Use in Adolescents and Young Adults With Bipolar Disorder(Frontiers Media, 2021-11-15) Le, Vanessa; Kirsch, Dylan E.; Tretyak, Valeria; Weber, Wade; Strakowski, Stephen M.; Lippard, Elizabeth T. C.; Psychiatry, School of MedicineBackground: Psychosocial stress negatively affects the clinical course of bipolar disorder. Studies primarily focused on adults with bipolar disorder suggest the impact of stress is progressive, i.e., stress response sensitizes with age. Neural mechanisms underlying stress sensitization are unknown. As stress-related mechanisms contribute to alcohol/substance use disorders, variation in stress response in youth with bipolar disorder may contribute to development of co-occurring alcohol/substance use disorders. This study investigated relations between psychosocial stress, amygdala reactivity, and alcohol and cannabis use in youth with bipolar disorder, compared to typically developing youth. Methods: Forty-two adolescents/young adults [19 with bipolar disorder, 23 typically developing, 71% female, agemean ± SD = 21 ± 2 years] completed the Perceived Stress Scale (PSS), Daily Drinking Questionnaire modified for heaviest drinking week, and a modified Montreal Imaging Stress functional MRI Task. Amygdala activation was measured for both the control and stress conditions. Main effects of group, condition, total PSS, and their interactions on amygdala activation were modeled. Relationships between amygdala response to acute stress with recent alcohol/cannabis use were investigated. Results: Greater perceived stress related to increased right amygdala activation in response to the stress, compared to control, condition in bipolar disorder, but not in typically developing youth (group × condition × PSS interaction, p = 0.02). Greater amygdala reactivity to acute stress correlated with greater quantity and frequency of alcohol use and frequency of cannabis use in bipolar disorder. Conclusion: Recent perceived stress is associated with changes in amygdala activation during acute stress with amygdala reactivity related to alcohol/cannabis use in youth with bipolar disorder.Item SARS-CoV-2 Humoral Immune Responses in Convalescent Individuals Over 12 Months Reveal Severity-Dependent Antibody Dynamics(medRxiv, 2023-12-07) Siles, Nadia; Schuler, Maisey; Maguire, Cole; Amengor, Dzifa; Nguyen, Annalee; Wilen, Rebecca; Rogers, Jacob; Bazzi, Sam; Caslin, Blaine; DiPasquale, Christopher; Abigania, Melissa; Olson, Eric; Creaturo, Janelle; Hurley, Kerin; Triplett, Todd A.; Rousseau, Justin F.; Strakowski, Stephen M.; Wylie, Dennis; Maynard, Jennifer; Ehrlich, Lauren I. R.; Melamed, Esther; Psychiatry, School of MedicineBackground: Understanding the kinetics and longevity of antibody responses to SARS-CoV-2 is critical to informing strategies toward reducing Coronavirus disease 2019 (COVID-19) reinfections, and improving vaccination and therapy approaches. Methods: We evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) of spike in 98 convalescent participants who experienced asymptomatic, mild, moderate or severe COVID-19 disease and in 17 non-vaccinated, non-infected controls, using four different antibody assays. Participants were sampled longitudinally at 1, 3, 6, and 12 months post-SARS-CoV-2 positive PCR test. Findings: Increasing acute COVID-19 disease severity correlated with higher anti-N and anti-RBD antibody titers throughout 12 months post-infection. Anti-N and anti-RBD titers declined over time in all participants, with the exception of increased anti-RBD titers post-vaccination, and the decay rates were faster in hospitalized compared to non-hospitalized participants. <50% of participants retained anti-N titers above control levels at 12 months, with non-hospitalized participants falling below control levels sooner. Nearly all hospitalized and non-hospitalized participants maintained anti-RBD titers above controls for up to 12 months, suggesting longevity of protection against severe reinfections. Nonetheless, by 6 months, few participants retained >50% of their 1-month anti-N or anti-RBD titers. Vaccine-induced increases in anti-RBD titers were greater in non-hospitalized relative to hospitalized participants. Early convalescent antibody titers correlated with age, but no association was observed between Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or acute steroid treatment and convalescent antibody titers. Interpretation: Hospitalized participants developed higher anti-SARS-CoV-2 antibody titers relative to non-hospitalized participants, a difference that persisted throughout 12 months, despite the faster decline in titers in hospitalized participants. In both groups, while anti-N titers fell below control levels for at least half of the participants, anti-RBD titers remained above control levels for almost all participants over 12 months, demonstrating generation of long-lived antibody responses known to correlate with protection from severe disease across COVID-19 severities. Overall, our findings contribute to the evolving understanding of COVID-19 antibody dynamics.Item Subjective cognitive impairment and its relationship to sleep impairment, anxiety severity, and depressive symptoms in individuals with bipolar disorder(Elsevier, 2022) Siegel-Ramsay, Jennifer E.; Wu, Bryan; Bond, Mark; Spelber, David; Chiang, Karl S.; Lanza di Scalea, Teresa; Collier, Sam J.; Smith, Tawny; Nunez, Leyna; Fuller, Ersten; Strakowski, Stephen M.; Lippard, Elizabeth; Almeida, Jorge R. C.; Psychiatry, School of MedicineObjectives: Individuals with bipolar disorder commonly report cognitive impairment which is associated with several psychosocial factors (e.g., mood symptoms). Within this study, we investigated the relationship between these psychosocial factors and the perception of cognitive impairment in individuals with bipolar disorder. Methods: We measured the relationship between subjective cognitive impairment and mood symptoms, quality of life, age, gender, bipolar disorder subtype, anxiety and sleep disturbance in 140 individuals with bipolar disorder with a mixed linear regression model. Our primary outcome measures were obtained via National Institute of Health (NIH)-sponsored PROMIS cognition scores. Results: Results from the model suggest that both the PROMIS Cognitive Function and Cognitive Function-Abilities scores were significantly negatively correlated with sleep disturbance and depression symptoms (p≤0.05). PROMIS Cognitive Function was also significantly negatively correlated with anxiety (p≤0.05). Limitations: Limitations of this study include the absence of a healthy control group, limited demographic diversity, and cross-sectional study design. Conclusions: Perceived cognitive impairment in individuals with bipolar disorder is associated with increased sleep disturbance, depression, and anxiety. Future studies with objective cognitive measures combined with PROMIS self-report scores might further clarify the expression of cognitive impairment in bipolar disorder.Item Subjective response to alcohol: Associated alcohol use and orbitofrontal gray matter volume in bipolar disorder(Elsevier, 2021) Tretyak, Valeria; Kirsch, Dylan E.; Radpour, Sepeadeh; Weber, Wade A.; Fromme, Kim; Strakowski, Stephen M.; Lippard, Elizabeth T. C.; Psychiatry, School of MedicineBackground: Alcohol use disorders (AUDs) are highly prevalent in bipolar disorder, however the developmental etiology of this comorbidity remains unknown. Structural differences in the orbitofrontal cortex (OFC) have been linked to problematic drinking in bipolar disorder and typically developing youth, with evidence implicating variations in OFC in differential subjective response to alcohol in typical development. Methods: Subjective response to alcohol, recent alcohol use, impulsivity, and variation in OFC gray matter volume were investigated in 48 emerging adults (24 with bipolar disorder, 24 typically developing). On average 1.5 years later, drinking patterns were reassessed and relations between subjective response and changes in alcohol use were explored. Results: Groups did not differ in baseline alcohol use or subjective response. At baseline, decreased subjective response to alcohol was associated with increased alcohol use in both groups. Lower gray matter volume in medial OFC in bipolar disorder was associated with increased subjective response to alcohol, whereas lower gray matter volume in OFC in typically developing participants was associated with decreased subjective response to alcohol. Increase in alcohol use (baseline to follow-up) was associated with increased baseline subjective response to alcohol in bipolar disorder, and decreased baseline subjective response in the typically developing group. Limitations: Preliminary study with a small sample size. Conclusion: Underlying OFC biology may contribute to differences in alcohol sensitivity in bipolar disorder which may also relate to prospective changes in alcohol use patterns. Future studies are needed to examine how these factors prospectively relate to development of AUDs in bipolar disorder.