Ventral Prefrontal Network Response to Alcohol in Young Adults with Bipolar Disorder: a Within-subject Randomized Placebo-controlled Alcohol Administration Study

Overview

Journal Neuropsychopharmacology

Date 2023 Jul 20

PMID 37474761

Authors

Dylan E Kirsch

Raquel Kosted

Vanessa Le

Jorge R C Almeida

Kim Fromme

Stephen M Strakowski

Elizabeth T C Lippard

Affiliations

Soon will be listed here.

Abstract

Bipolar disorder co-occurs with alcohol use disorder at a rate 3-5 times higher than the general population. We recently reported that individuals with bipolar disorder differ in the positive stimulating and anxiolytic effects of alcohol compared with healthy peers. This study used a randomized, placebo-controlled, cross-over, within-subject alcohol administration design to investigate neurobiological mechanisms within ventral prefrontal cortical (vPFC) systems that may underlie altered sensitivity to alcohol in bipolar disorder (NCT04063384). Forty-seven young adults (n = 23 with bipolar disorder, 64% women) completed clinical assessment and two beverage administration sessions (alcohol and placebo, counter-balanced). Participants were dosed to 0.08 g% breath alcohol concentration during the alcohol condition and completed measures of subjective response to alcohol and an emotional processing fMRI task during the ascending limb. Timing during the placebo condition mirrored the alcohol session. Acute alcohol was associated with reduced functional connectivity between the insula - subcallosal cingulate cortex, and increased connectivity between the left nucleus accumbens - ventromedial PFC in bipolar disorder, but with no change in functional connectivity between these regions in healthy peers. Alcohol-related increases in nucleus accumbens - ventromedial PFC functional connectivity was associated with greater positive stimulating effects of alcohol in bipolar disorder and heavier recent alcohol use. Results suggest vPFC brain systems respond differently to acute alcohol during emotional processing in young adults with bipolar disorder compared with healthy peers, and that vPFC system responses relate to the subjective experience of intoxication and recent alcohol use.

References

King A, Vena A, Hasin D, deWit H, OConnor S, Cao D . Subjective Responses to Alcohol in the Development and Maintenance of Alcohol Use Disorder. Am J Psychiatry. 2021; 178(6):560-571. PMC: 8222099. DOI: 10.1176/appi.ajp.2020.20030247. View

Margulies D, Kelly A, Uddin L, Biswal B, Castellanos F, Milham M . Mapping the functional connectivity of anterior cingulate cortex. Neuroimage. 2007; 37(2):579-88. DOI: 10.1016/j.neuroimage.2007.05.019. View

Carmiol N, Peralta J, Almasy L, Contreras J, Pacheco A, Escamilla M . Shared genetic factors influence risk for bipolar disorder and alcohol use disorders. Eur Psychiatry. 2013; 29(5):282-7. PMC: 4160878. DOI: 10.1016/j.eurpsy.2013.10.001. View

Gorka S, Fitzgerald D, King A, Phan K . Alcohol attenuates amygdala-frontal connectivity during processing social signals in heavy social drinkers: a preliminary pharmaco-fMRI study. Psychopharmacology (Berl). 2013; 229(1):141-54. PMC: 3740023. DOI: 10.1007/s00213-013-3090-0. View

Goldberg J . Bipolar disorder with comorbid substance abuse: diagnosis, prognosis, and treatment. J Psychiatr Pract. 2005; 7(2):109-22. DOI: 10.1097/00131746-200103000-00004. View

Schreiter S, Spengler S, Willert A, Mohnke S, Herold D, Erk S . Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder. Psychol Med. 2016; 46(15):3187-3198. DOI: 10.1017/S0033291716001963. View

Liu R, Wang Y, Chen X, Zhang Z, Xiao L, Zhou Y . Anhedonia correlates with functional connectivity of the nucleus accumbens subregions in patients with major depressive disorder. Neuroimage Clin. 2021; 30:102599. PMC: 7930634. DOI: 10.1016/j.nicl.2021.102599. View

Alexander G, DeLong M, Strick P . Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci. 1986; 9:357-81. DOI: 10.1146/annurev.ne.09.030186.002041. View

Gorka S, Phan K, Childs E . Acute calming effects of alcohol are associated with disruption of the salience network. Addict Biol. 2017; 23(3):921-930. DOI: 10.1111/adb.12537. View

10.

Corbin W, Hartman J, Bruening A, Fromme K . Contextual influences on subjective alcohol response. Exp Clin Psychopharmacol. 2020; 29(1):48-58. PMC: 8405099. DOI: 10.1037/pha0000415. View

11.

McKenna B, Anthenelli R, Smith T, Schuckit M . Low versus high level of response to alcohol affects amygdala functional connectivity during processing of emotional stimuli. Alcohol Clin Exp Res. 2022; 46(1):66-76. PMC: 8820383. DOI: 10.1111/acer.14744. View

12.

Padula C, Simmons A, Matthews S, Robinson S, Tapert S, Schuckit M . Alcohol attenuates activation in the bilateral anterior insula during an emotional processing task: a pilot study. Alcohol Alcohol. 2011; 46(5):547-52. PMC: 3201697. DOI: 10.1093/alcalc/agr066. View

13.

Paulus M, Schuckit M, Tapert S, Tolentino N, Matthews S, Smith T . High versus low level of response to alcohol: evidence of differential reactivity to emotional stimuli. Biol Psychiatry. 2012; 72(10):848-55. PMC: 3433640. DOI: 10.1016/j.biopsych.2012.04.016. View

14.

Gilman J, Ramchandani V, Crouss T, Hommer D . Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns. Neuropsychopharmacology. 2011; 37(2):467-77. PMC: 3242308. DOI: 10.1038/npp.2011.206. View

15.

Schuckit M, Smith T, Kalmijn J, Danko G . A cross-generational comparison of alcohol challenges at about age 20 in 40 father-offspring pairs. Alcohol Clin Exp Res. 2005; 29(11):1921-7. DOI: 10.1097/01.alc.0000187154.94681.65. View

16.

Pizzagalli D, Goetz E, Ostacher M, Iosifescu D, Perlis R . Euthymic patients with bipolar disorder show decreased reward learning in a probabilistic reward task. Biol Psychiatry. 2008; 64(2):162-8. PMC: 2464620. DOI: 10.1016/j.biopsych.2007.12.001. View

17.

Strakowski S, Adler C, Almeida J, Altshuler L, Blumberg H, Chang K . The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disord. 2012; 14(4):313-25. PMC: 3874804. DOI: 10.1111/j.1399-5618.2012.01022.x. View

18.

Curtin J, Fairchild B . Alcohol and cognitive control: implications for regulation of behavior during response conflict. J Abnorm Psychol. 2003; 112(3):424-36. DOI: 10.1037/0021-843x.112.3.424. View

19.

Lippard E, Mazure C, Johnston J, Spencer L, Weathers J, Pittman B . Brain circuitry associated with the development of substance use in bipolar disorder and preliminary evidence for sexual dimorphism in adolescents. J Neurosci Res. 2016; 95(1-2):777-791. PMC: 5123602. DOI: 10.1002/jnr.23901. View

20.

Behzadi Y, Restom K, Liau J, Liu T . A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage. 2007; 37(1):90-101. PMC: 2214855. DOI: 10.1016/j.neuroimage.2007.04.042. View