Alcoholism vulnerability; Children of alcoholics (CoAs); Externalizing behaviors; Graph theory; rsfMRI; Adolescent; Age Factors; Alcoholism/physiopathology; Brain/physiopathology; Cerebellum/physiopathology; Child; Frontal Lobe/physiopathology; Humans; Male; Nerve Net/physiopathology; Parietal Lobe/physiopathology; Rest/physiology; Risk Factors; Young Adult; Alcoholism; Brain; Cerebellum; Frontal Lobe; Nerve Net; Parietal Lobe; Rest; Neuroscience (miscellaneous); Radiology, Nuclear Medicine and Imaging; Psychiatry and Mental Health
Abstract :
[en] Familial susceptibility to alcoholism is likely to be linked to the externalizing diathesis seen in high-risk offspring from high-density alcohol use disorder (AUD) families. The present study aimed at comparing resting brain functional connectivity and their association with externalizing symptoms and alcoholism familial density in 40 substance-naive high-risk (HR) male offspring from high-density AUD families and 30 matched healthy low-risk (LR) males without a family history of substance dependence using graph theory-based network analysis. The HR subjects from high-density AUD families compared with LR, showed significantly reduced clustering, small-worldness, and local network efficiency. The frontoparietal, cingulo-opercular, sensorimotor and cerebellar networks exhibited significantly reduced functional segregation. These disruptions exhibited independent incremental value in predicting the externalizing symptoms over and above the demographic variables. The reduction of functional segregation in HR subjects was significant across both the younger and older age groups and was proportional to the family loading of AUDs. Detection and estimation of these developmentally relevant disruptions in small-world architecture at critical brain regions sub-serving cognitive, affective, and sensorimotor processes are vital for understanding the familial risk for early onset alcoholism as well as for understanding the pathophysiological mechanism of externalizing behaviors.
Disciplines :
Psychiatry
Author, co-author :
Holla, Bharath; Centre for Addiction Medicine, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India. Electronic address: hollabharath@gmail.com
Panda, Rajanikant ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group ; Cognitive Neuroscience Centre and Department of Neuroimaging and Interventional Radiology (NIIR), NIMHANS, Hosur Road, Bangalore, India
Venkatasubramanian, Ganesan; Translational Psychiatry Laboratory, Department of Psychiatry, NIMHANS, Hosur Road, Bangalore, India
Biswal, Bharat; Department of Biomedical Engineering, New Jersey Institute of Technology (NJIT), University Heights, Newark, NJ, USA
Bharath, Rose Dawn; Cognitive Neuroscience Centre and Department of Neuroimaging and Interventional Radiology (NIIR), NIMHANS, Hosur Road, Bangalore, India. Electronic address: drrosedawn@yahoo.com
Benegal, Vivek; Centre for Addiction Medicine, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, India. Electronic address: vbenegal@gmail.com
Language :
English
Title :
Disrupted resting brain graph measures in individuals at high risk for alcoholism.
Achard, S., Bullmore, E., Efficiency and cost of economical brain functional networks. PLoS Comput. Biol., 3, 2007, e17.
Acheson, A., Robinson, J.L., Glahn, D.C., Lovallo, W.R., Fox, P.T., Differential activation of the anterior cingulate cortex and caudate nucleus during a gambling simulation in persons with a family history of alcoholism: studies from the Oklahoma Family Health Patterns Project. Drug Alcohol Depend. 100 (2009), 17–23.
Annett, M., The binomial distribution of right, mixed and left handedness. Q. J. Exp. Psychol. 19 (1967), 327–333.
Aron, A.R., Robbins, T.W., Poldrack, R.A., Inhibition and the right inferior frontal cortex. Trends Cogn. Sci. 8 (2004), 170–177.
Bechara, A., Dolan, S., Hindes, A., Decision-making and addiction (part II): myopia for the future or hypersensitivity to reward?. Neuropsychologia 40 (2002), 1690–1705.
Beck, A., Wustenberg, T., Genauck, A., Wrase, J., Schlagenhauf, F., Smolka, M.N., Mann, K., Heinz, A., Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients. Arch. General. Psychiatry 69 (2012), 842–852.
Benegal, V., Jain, S., Subbukrishna, D.K., Channabasavanna, S.M., P300 amplitudes vary inversely with continuum of risk in first degree male relatives of alcoholics. Psychiatr. Genet. 5 (1995), 149–156.
Benegal, V., Antony, G., Venkatasubramanian, G., Jayakumar, P.N., Gray matter volume abnormalities and externalizing symptoms in subjects at high risk for alcohol dependence. Addict. Biol. 12 (2007), 122–132.
Biswal, B., Yetkin, F.Z., Haughton, V.M., Hyde, J.S., Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn. Reson. Med. 34 (1995), 537–541.
Bornovalova, M.A., Hicks, B.M., Iacono, W.G., McGue, M., Familial transmission and heritability of childhood disruptive disorders. Am. J. Psychiatry 167 (2010), 1066–1074.
Brook, D.W., Brook, J.S., Zhang, C., Koppel, J., Association between attention-deficit/hyperactivity disorder in adolescence and substance use disorders in adulthood. Arch. Pediatr. Adolesc. Med. 164 (2010), 930–934.
Bucholz, K.K., Cadoret, R., Cloninger, C.R., Dinwiddie, S.H., Hesselbrock, V.M., Nurnberger, J.I. Jr., Reich, T., Schmidt, I., Schuckit, M.A., A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA. J. Stud. Alcohol 55 (1994), 149–158.
Bullmore, E., Sporns, O., Complex brain networks: graph theoretical analysis of structural and functional systems. Nat. Rev. Neurosci. 10 (2009), 186–198.
Chen, Z., Liu, M., Gross, D.W., Beaulieu, C., Graph theoretical analysis of developmental patterns of the white matter network. Front. Hum. Neurosci., 7, 2013, 716.
Chikazoe, J., Konishi, S., Asari, T., Jimura, K., Miyashita, Y., Activation of right inferior frontal gyrus during response inhibition across response modalities. J. Cogn. Neurosci. 19 (2007), 69–80.
Cloninger, C.R., Sigvardsson, S., Reich, T., Bohman, M., Inheritance of risk to develop alcoholism. NIDA Res. Monogr. 66 (1986), 86–96.
Corral, M., Holguin, S.R., Cadaveira, F., Neuropsychological characteristics of young children from high-density alcoholism families: a three-year follow-up. J. Stud. Alcohol 64 (2003), 195–199.
Cortese, S., Kelly, C., Chabernaud, C., Proal, E., Di Martino, A., Milham, M.P., Castellanos, F.X., Toward systems neuroscience of ADHD: a meta-analysis of 55 fMRI studies. Am. J. Psychiatry 169 (2012), 1038–1055.
Cotton, N.S., The familial incidence of alcoholism: a review. J. Stud. Alcohol 40 (1979), 89–116.
Cservenka, A., Neurobiological phenotypes associated with a family history of alcoholism. Drug Alcohol Depend. 158 (2016), 8–21.
Cservenka, A., Casimo, K., Fair, D.A., Nagel, B.J., Resting state functional connectivity of the nucleus accumbens in youth with a family history of alcoholism. Psychiatry Res. 221 (2014), 210–219.
Cservenka, A., Alarcon, G., Jones, S.A., Nagel, B.J., Advances in human neuroconnectivity research: applications for understanding familial history risk for alcoholism. Alcohol Res.: Curr. Rev. 37 (2015), 89–95.
Cservenka, A., Gillespie, A.J., Michael, P.G., Nagel, B.J., Family history density of alcoholism relates to left nucleus accumbens volume in adolescent girls. J. Stud. Alcohol Drugs 76 (2015), 47–56.
Depue, B.E., Burgess, G.C., Willcutt, E.G., Ruzic, L., Banich, M.T., Inhibitory control of memory retrieval and motor processing associated with the right lateral prefrontal cortex: evidence from deficits in individuals with ADHD. Neuropsychologia 48 (2010), 3909–3917.
Dick, D.M., Aliev, F., Wang, J.C., Grucza, R.A., Schuckit, M., Kuperman, S., Kramer, J., Hinrichs, A., Bertelsen, S., Budde, J.P., Hesselbrock, V., Porjesz, B., Edenberg, H.J., Bierut, L.J., Goate, A., Using dimensional models of externalizing psychopathology to aid in gene identification. Arch. General. Psychiatry 65 (2008), 310–318.
Fair, D.A., Nigg, J.T., Iyer, S., Bathula, D., Mills, K.L., Dosenbach, N.U., Schlaggar, B.L., Mennes, M., Gutman, D., Bangaru, S., Buitelaar, J.K., Dickstein, D.P., Di Martino, A., Kennedy, D.N., Kelly, C., Luna, B., Schweitzer, J.B., Velanova, K., Wang, Y.F., Mostofsky, S., Castellanos, F.X., Milham, M.P., Distinct neural signatures detected for ADHD subtypes after controlling for micro-movements in resting state functional connectivity MRI data. Front. Syst. Neurosci., 6, 2012, 80.
Fornito, A., Zalesky, A., Bullmore, E.T., Network scaling effects in graph analytic studies of human resting-state FMRI data. Front. Syst. Neurosci., 4, 2010, 22.
Fornito, A., Zalesky, A., Bassett, D.S., Meunier, D., Ellison-Wright, I., Yucel, M., Wood, S.J., Shaw, K., O'Connor, J., Nertney, D., Mowry, B.J., Pantelis, C., Bullmore, E.T., Genetic influences on cost-efficient organization of human cortical functional networks. J. Neurosci.: Off. J. Soc. Neurosci. 31 (2011), 3261–3270.
Fox, M.D., Raichle, M.E., Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat. Rev. Neurosci. 8 (2007), 700–711.
Friston, K.J., Williams, S., Howard, R., Frackowiak, R.S., Turner, R., Movement-related effects in fMRI time-series. Magn. Reson. Med. 35 (1996), 346–355.
Garavan, H., Ross, T.J., Stein, E.A., Right hemispheric dominance of inhibitory control: an event-related functional MRI study. Proc. Natl. Acad. Sci. USA 96 (1999), 8301–8306.
Gierski, F., Hubsch, B., Stefaniak, N., Benzerouk, F., Cuervo-Lombard, C., Bera-Potelle, C., Cohen, R., Kahn, J.P., Limosin, F., Executive functions in adult offspring of alcohol-dependent probands: toward a cognitive endophenotype?. Alcohol., Clin. Exp. Res. 37:Suppl 1 (2013), E356–E363.
Glahn, D.C., Winkler, A.M., Kochunov, P., Almasy, L., Duggirala, R., Carless, M.A., Curran, J.C., Olvera, R.L., Laird, A.R., Smith, S.M., Beckmann, C.F., Fox, P.T., Blangero, J., Genetic control over the resting brain. Proc. Natl. Acad. Sci. USA 107 (2010), 1223–1228.
Goodwin, D.W., Alcoholism and heredity. A review and hypothesis. Arch. Gen. Psychiatry 36 (1979), 57–61.
Hauser, T.U., Iannaccone, R., Ball, J., Mathys, C., Brandeis, D., Walitza, S., Brem, S., Role of the medial prefrontal cortex in impaired decision making in juvenile attention-deficit/hyperactivity disorder. JAMA Psychiatry 71 (2014), 1165–1173.
He, Y., Dagher, A., Chen, Z., Charil, A., Zijdenbos, A., Worsley, K., Evans, A., Impaired small-world efficiency in structural cortical networks in multiple sclerosis associated with white matter lesion load. Brain: J. Neurol. 132 (2009), 3366–3379.
Herting, M.M., Fair, D., Nagel, B.J., Altered fronto-cerebellar connectivity in alcohol-naive youth with a family history of alcoholism. NeuroImage 54 (2011), 2582–2589.
Hicks, B.M., Foster, K.T., Iacono, W.G., McGue, M., Genetic and environmental influences on the familial transmission of externalizing disorders in adoptive and twin offspring. JAMA Psychiatry 70 (2013), 1076–1083.
Hilgetag, C.C., Goulas, A., Is the brain really a small-world network?. Brain Struct. Funct. 221 (2016), 2361–2366.
Hill, S.Y., O'Brien, J., Psychological and neurobiological precursors of alcohol use disorders in high risk youth. Curr. Addict. Rep. 2 (2015), 104–113.
Hill, S.Y., Wang, S., Carter, H., McDermott, M.D., Zezza, N., Stiffler, S., Amygdala volume in offspring from multiplex for alcohol dependence families: the moderating influence of childhood environment and 5-HTTLPR variation. J. Alcohol. Drug Depend.(Suppl. 1), 2013.
Hill, S.Y., Shen, S., Locke, J., Steinhauer, S.R., Konicky, C., Lowers, L., Connolly, J., Developmental delay in P300 production in children at high risk for developing alcohol-related disorders. Biol. Psychiatry 46 (1999), 970–981.
Hill, S.Y., Wang, S., Carter, H., Tessner, K., Holmes, B., McDermott, M., Zezza, N., Stiffler, S., Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: association with allelic variation in GABRA2 and BDNF. Psychiatry Res. 194 (2011), 304–313.
Hill, S.Y., Wang, S., Kostelnik, B., Carter, H., Holmes, B., McDermott, M., Zezza, N., Stiffler, S., Keshavan, M.S., Disruption of orbitofrontal cortex laterality in offspring from multiplex alcohol dependence families. Biol. Psychiatry 65 (2009), 129–136.
Hussong, A., Bauer, D., Chassin, L., Telescoped trajectories from alcohol initiation to disorder in children of alcoholic parents. J. Abnorm. Psychol. 117 (2008), 63–78.
Hussong, A.M., Wirth, R.J., Edwards, M.C., Curran, P.J., Chassin, L.A., Zucker, R.A., Externalizing symptoms among children of alcoholic parents: entry points for an antisocial pathway to alcoholism. J. Abnorm. Psychol. 116 (2007), 529–542.
Jacob, T., Waterman, B., Heath, A., True, W., Bucholz, K.K., Haber, R., Scherrer, J., Fu, Q., Genetic and environmental effects on offspring alcoholism: new insights using an offspring-of-twins design. Arch. Gen. Psychiatry 60 (2003), 1265–1272.
Krueger, R.F., Markon, K.E., Patrick, C.J., Iacono, W.G., Externalizing psychopathology in adulthood: a dimensional-spectrum conceptualization and its implications for DSM-V. J. Abnorm. Psychol. 114 (2005), 537–550.
Kumar, N., Gupta, N., Kishore, J., Kuppuswamy's socioeconomic scale: updating income ranges for the year 2012. Indian J. Public Health 56 (2012), 103–104.
Kuperman, S., Chan, G., Kramer, J.R., Bierut, L., Bucholz, K.K., Fox, L., Hesselbrock, V., Numberger, J.I. Jr., Reich, T., Reich, W., Schuckit, M.A., Collaborative Study on the Genetics of, A, Relationship of age of first drink to child behavioral problems and family psychopathology. Alcohol. Clin. Exp. Res. 29 (2005), 1869–1876.
Lee, M.H., Smyser, C.D., Shimony, J.S., Resting-state fMRI: a review of methods and clinical applications. AJNR Am. J. Neuroradiol. 34 (2013), 1866–1872.
Lewis, S.W., Murray, R.M., Obstetric complications, neurodevelopmental deviance, and risk of schizophrenia. J. Psychiatr. Res. 21 (1987), 413–421.
MacDonald, A.W. 3rd, Cohen, J.D., Stenger, V.A., Carter, C.S., Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science 288 (2000), 1835–1838.
Maxwell, M., Family Interview for Genetic Studies (FIGS): A Manual for FIGS, Clinical Neurogenetics Branch, Intramural Research Program. 1992, National Institute of Mental Health, Bethesda, MD.
McGue, M., Iacono, W.G., Legrand, L.N., Malone, S., Elkins, I., Origins and consequences of age at first drink. I. Associations with substance-use disorders, disinhibitory behavior and psychopathology, and P3 amplitude. Alcohol. Clin. Exp. Res. 25 (2001), 1156–1165.
Nigg, J.T., Glass, J.M., Wong, M.M., Poon, E., Jester, J.M., Fitzgerald, H.E., Puttler, L.I., Adams, K.M., Zucker, R.A., Neuropsychological executive functioning in children at elevated risk for alcoholism: findings in early adolescence. J. Abnorm. Psychol. 113 (2004), 302–314.
Power, J.D., Schlaggar, B.L., Petersen, S.E., Recent progress and outstanding issues in motion correction in resting state fMRI. NeuroImage 105 (2015), 536–551.
Power, J.D., Barnes, K.A., Snyder, A.Z., Schlaggar, B.L., Petersen, S.E., Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. NeuroImage 59 (2012), 2142–2154.
Rangaswamy, M., Porjesz, B., Ardekani, B.A., Choi, S.J., Tanabe, J.L., Lim, K.O., Begleiter, H., A functional MRI study of visual oddball: evidence for frontoparietal dysfunction in subjects at risk for alcoholism. Neuroimage 21 (2004), 329–339.
Rubinov, M., Sporns, O., Complex network measures of brain connectivity: uses and interpretations. NeuroImage 52 (2010), 1059–1069.
Salvador, R., Suckling, J., Coleman, M.R., Pickard, J.D., Menon, D., Bullmore, E., Neurophysiological architecture of functional magnetic resonance images of human brain. Cereb. cortex 15 (2005), 1332–1342.
Salvatore, J.E., Gottesman, I.I., Dick, D.M., Endophenotypes for alcohol use disorder: an update on the field. Curr. Addict. Rep. 2 (2015), 76–90.
Sato, J.R., Salum, G.A., Gadelha, A., Picon, F.A., Pan, P.M., Vieira, G., Zugman, A., Hoexter, M.Q., Anes, M., Moura, L.M., Gomes Del'Aquilla, M.A., Amaro, E. Jr., McGuire, P., Crossley, N., Lacerda, A., Rohde, L.A., Miguel, E.C., Bressan, R.A., Jackowski, A.P., Age effects on the default mode and control networks in typically developing children. J. Psychiatr. Res. 58 (2014), 89–95.
Schuckit, M.A., Genetics and the risk for alcoholism. JAMA 254 (1985), 2614–2617.
Schweinsburg, A.D., Paulus, M.P., Barlett, V.C., Killeen, L.A., Caldwell, L.C., Pulido, C., Brown, S.A., Tapert, S.F., An FMRI study of response inhibition in youths with a family history of alcoholism. Ann. N.Y. Acad. Sci. 1021 (2004), 391–394.
Silveri, M.M., Rogowska, J., McCaffrey, A., Yurgelun‐Todd, D.A., Adolescents at risk for alcohol abuse demonstrate altered frontal lobe activation during Stroop performance. Alcohol.: Clin. Exp. Res. 35 (2011), 218–228.
Smit, D.J., Stam, C.J., Posthuma, D., Boomsma, D.I., de Geus, E.J., Heritability of “small-world” networks in the brain: a graph theoretical analysis of resting-state EEG functional connectivity. Hum. Brain Mapp. 29 (2008), 1368–1378.
Smit, D.J., Boersma, M., van Beijsterveldt, C.E., Posthuma, D., Boomsma, D.I., Stam, C.J., de Geus, E.J., Endophenotypes in a dynamically connected brain. Behav. Genet. 40 (2010), 167–177.
Smith, A.B., Taylor, E., Brammer, M., Halari, R., Rubia, K., Reduced activation in right lateral prefrontal cortex and anterior cingulate gyrus in medication-naive adolescents with attention deficit hyperactivity disorder during time discrimination. J. Child Psychol. Psychiatry Allied Discip. 49 (2008), 977–985.
Spadoni, A.D., Simmons, A.N., Yang, T.T., Tapert, S.F., Family history of alcohol use disorders and neuromaturation: a functional connectivity study with adolescents. Am. J. Drug Alcohol Abus. 39 (2013), 356–364.
Sporns, O., Chialvo, D.R., Kaiser, M., Hilgetag, C.C., Organization, development and function of complex brain networks. Trends Cogn. Sci. 8 (2004), 418–425.
Sripada, C., Kessler, D., Fang, Y., Welsh, R.C., Prem Kumar, K., Angstadt, M., Disrupted network architecture of the resting brain in attention-deficit/hyperactivity disorder. Hum. Brain Mapp. 35 (2014), 4693–4705.
Turner, W.M., Cutter, H.S., Worobec, T.G., O'Farrell, T.J., Bayog, R.D., Tsuang, M.T., Family history models of alcoholism: age of onset, consequences and dependence. J. Stud. Alcohol 54 (1993), 164–171.
Venkatasubramanian, G., Anthony, G., Reddy, U.S., Reddy, V.V., Jayakumar, P.N., Benegal, V., Corpus callosum abnormalities associated with greater externalizing behaviors in subjects at high risk for alcohol dependence. Psychiatry Res. 156 (2007), 209–215.
Verhulst, B., Neale, M.C., Kendler, K.S., The heritability of alcohol use disorders: a meta-analysis of twin and adoption studies. Psychol. Med. 45 (2015), 1061–1072.
Vogel, A.C., Church, J.A., Power, J.D., Miezin, F.M., Petersen, S.E., Schlaggar, B.L., Functional network architecture of reading-related regions across development. Brain Lang. 125 (2013), 231–243.
Wetherill, R.R., Bava, S., Thompson, W.K., Boucquey, V., Pulido, C., Yang, T.T., Tapert, S.F., Frontoparietal connectivity in substance-naive youth with and without a family history of alcoholism. Brain Res. 1432 (2012), 66–73.
Witkiewitz, K., King, K., McMahon, R.J., Wu, J., Luk, J., Bierman, K.L., Coie, J.D., Dodge, K.A., Greenberg, M.T., Lochman, J.E., Pinderhughes, E.E., Conduct Problems Prevention Research, G, Evidence for a multi-dimensional latent structural model of externalizing disorders. J. Abnorm. Child Psychol. 41 (2013), 223–237.
