Users Online: 220

Home Print this page Email this page Small font sizeDefault font sizeIncrease font size

Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Login 
     

   Table of Contents      
REVIEW ARTICLE
Year : 2014  |  Volume : 4  |  Issue : 5  |  Page : 1-5

Impact of alcohol on the developing brain


Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India

Date of Web Publication19-Dec-2014

Correspondence Address:
Sujita Kumar Kar
Department of Psychiatry, King George's Medical University, Lucknow - 226 003, Uttar Pradesh
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0738.147454

Rights and Permissions

How to cite this article:
Dalal PK, Kar SK. Impact of alcohol on the developing brain. Int J Nutr Pharmacol Neurol Dis 2014;4, Suppl S1:1-5

How to cite this URL:
Dalal PK, Kar SK. Impact of alcohol on the developing brain. Int J Nutr Pharmacol Neurol Dis [serial online] 2014 [cited 2020 Sep 18];4, Suppl S1:1-5. Available from: http://www.ijnpnd.com/text.asp?2014/4/5/1/147454


   Introduction Top


Ethanol is the consumable form of alcohol. It is reported that nearly 2.5 million deaths worldwide occur because of alcohol, every year. [1],[2] The use of alcohol is increasing globally. A national household survey attempted to estimate the burden of different substances of abuse including alcohol in India and found that the prevalence (current) of alcohol abuse in India is ∼21%. [1],[3] As per the World Health Organization (WHO) report, 2011, the prevalence of alcohol use disorder among the above-15-year-old population is 3.47% in males and 0.42% in females. [4] Alcohol has a significant adverse impact on different organ systems by alteration of the normal physiological functions and homeostasis of the body. [5] It also has substantial impact on the nervous system (cerebral cortex, subcortical group of nuclei, cranial and spinal nerves, cerebellum, and spinal cord). [5] The effect of alcohol on the nervous system is dependent on many factors like: Age of onset, quantity, frequency, duration of alcohol use, gender, general health condition, and genetic configuration of the individual. [5],[6]

Development of the brain

The development of the brain in a fetus is a complex process. In the early fetal life, brain development follows a sequence of events like - formation of the neural plate, neural crest, and neural tube. This is followed by complex modulation of the neural tube to form the brain vesicles, which expand and undergo intricate modifications to form the brain, spinal cord, and other related neural elements. At the cellular level of the brain, development advances through neurogenesis, neuronal migration, neuronal maturation, synapse formation, pruning, and myelination. [7]

The development of the brain continues after birth in early childhood. However, following this neuronal regeneration, multiplication gets restricted to specific areas of the brain, although myelination continues till adolescence. Besides this, any insult to the brain is followed by a natural healing process and repair by the glial cells. The growth and development of the brain is mediated by certain neurotrophic growth factors. Many factors influence brain development in the prenatal period, which can be genetic, environmental or nutritional. [8]

The complex interplay of these factors leads to growth and development of the brain. Deterioration of brain development results, if there is any deficiency or negative effect of any of the factors, in the critical stages of development. [8],[9] The most critical periods of brain development are during the last trimester of pregnancy and in the first three years following birth. [10]

The brain development of the child during the prenatal period (as in the fetus) and infancy, is more strongly influenced by the environmental factor than by any other factors. [8],[9] Maximum cognitive development occurs during adolescence. [11] An individual's ability to take decisions, abstract reasoning, and social cognition takes shape during this critical phase of development. [11]

Chronic stress has a negative impact on brain development (especially the hippocampus), as the neuronal survival is reduced due to inadequate expression of the neurotrophic factors. [12] The factors that negatively effect the growth and development of the brain are - Environmental factors (Lipid peroxidation - mediated by toxins, alcohol, [13] and environmental neurotoxins), [14],[15] Nutritional factors (decreased nerve growth factors - nutritional, toxin-mediated (alcohol), [16],[17] Metabolic disturbances - (diabetes, [17] homocystinemia, [18],[19] and stress), [20],[21],[22] and Genetic factors (Decreased nerve growth factors). [16],[17] Many nutritional factors that affect brain development are - protein, certain fats, folic acid, vitamin A, choline, and many other micronutrients (iron, selenium, zinc, copper). [23]

Impact of alcohol on the developing brain

Alcohol has neurotoxic effects, which can be explained though several mechanisms. [24] Chronic use of alcohol induces neuronal damage by: Oxidation, microglial activation, and neuronal inflammation. [25],[26],[27]

Alcohol-induced neurodegeneration is mediated through oxidative stress and proinflammatory mediators. [28] Ethanol induces the hepatic CYP 450 enzyme system and facilitates the production of reactive oxygen species and nitrous oxide, which in turn produces neuronal injury. [26],[29]

Experience from animal studies

Alcohol has a significant negative impact on the brain. Experiment on animal models revealed that alcohol binge drinking leads to significant structural and functional changes, particularly in the areas of the prefrontal cortex and hippocampus. [30] Shabanov et al., in their experiment on alcoholized rats, in gestation and feeding period, found that alcohol affects the serotonergic and dopaminergic systems of the fetal rat brain resulting in the under-activity of these systems. [31] In another animal study, it was found that alcohol reduces the mass of the cerebral cortex in a periadolescent mouse in comparison to adult mouse, whereas, the length of the corpus callosum is affected more in an adult mouse in comparison to a periadolescent mouse. [32] Alcohol (ethanol) has a toxic effect on the cerebellum as the Purkinje cells and granule cells of the cerebellum are sensitive to ethanol. [32] The growth of the Bergmann glia, which coordinates the development of these cerebellar cells, is mediated by the liver X receptors. [32] Therefore, activation of the liver X receptors helps in the protection of cerebellar Purkinje and granular cells. [32] Research is going on to find pharmaceutical agents that will facilitate the expression of the liver X receptor in order to protect the cerebellum from the toxic effects of alcohol. [32] On the other hand, as alcohol causes a significant adverse impact on the liver, the expression of the liver X receptors may be hampered, leading to loss of protection of the cerebellar Bergmann glia. In animal studies, it was found that the hippocampal mass gets reduced on exposure to alcohol prenatally, as a result of which, there occurs impairment of memory. [33] Maternal alcohol use affects the fetal brain growth and it causes neuronal loss from specific areas of the brain like the cerebellum, hippocampus, corpus callosum, thalamus, olfactory bulb, and optic nerve as proved by the animal studies. [34] In experimental animals, prenatal alcohol exposure leads to hypermethylation in certain brain regions like the prefrontal cortex and hippocampus. [35] Tiwari et al., in their study on the effect of alcohol (ethanol) on the different neurotransmitter pathways in the mouse brain found that: [36]

  • The levels of glutamate and aspartate were reduced in the cerebral cortex following acute exposure to alcohol
  • Astroglial metabolism remained unaffected to the acute exposure of alcohol in naïve mice
  • Acute exposure also differentially decreased the excitatory and inhibitory activity in the different cortical regions
  • The Tri Carboxylic Acid (TCA) cycle and neurotransmitter cycles associated with GABAergic and Glutaminergic neurons were diminished across the cortical and sub-cortical regions.


In a recent study on experimental animals (rats), it was found that prenatal exposure to alcohol resulted in a disproportionate increase in the cholesterol content in the brain during adulthood and the brain phospholipid-cholesterol ratio had also increased (by 1.3 fold). [37] Chronic binge drinking in adolescent rats led to impairment in neuronal differentiation and decreased neuronal survival in the hippocampus. [38] In chronic adolescent rat binge drinkers, there was a decrease in the brain-derived neurotrophic factor (BDNF) activity during the withdrawal period, which impaired the process of neuronal growth and differentiation. [38]

Experience from human studies

Prenatal exposure to alcohol has adverse consequences on the brain, which usually gets manifested in the form of a learning disability, hyperactivity or disruptive behavior, and seems to be due to acetyl choline deficiency. [39] The executive function is an important cortical function responsible for task performance, reasoning, analysis, and abstraction. Substantial exposure to alcohol during the prenatal period results in impairment of the executive function. [40],[41] Prenatal exposure to alcohol leads to a decreased volume of basal ganglia in adolescents. [42] Among the different nuclei of basal ganglia, the caudate nucleus is affected the most. [42] The white matter of the cerebellum is more vulnerable to be affected in prenatal exposure to alcohol. [42] Among the cerebral cortical structures, the parietal lobes are disproportionately more affected than the temporal and occipital lobes. [42]

Prenatal exposure to alcohol has a toxic effect on the corpus callosum, which leads to thinning and even agenesis of the corpus callosum. [43] As the corpus callosum is responsible for attention processing, verbal memory, executive functioning, and several other cognitive functions, degeneration of it results in impairment of these cognitive functions. [43] Alcohol exposure also leads to a disproportionate loss of the mass of the cerebellum. [42]

During adolescence, females are more susceptible to the neurotoxic side effects of alcohol in comparison to males and show comparatively more impairment in the spatial working memory. [29],[44] Use of alcohol in adults' leads to impairment in the spatial working memory, learning, spatial skills, and executive functioning, and again females are more vulnerable to the neurotoxic effects of alcohol. [45],[46],[47],[48] The frontoparietal cortex responsible for the working memory develops earlier in females than in males. [49],[50] In studies on adolescents with alcohol use disorder, it is found that the domains of attention and verbal and visual retention are significantly impaired in comparison to adolescents without alcohol use disorder. [51],[52],[53] During adolescence, an expansion of the white fibers occurs due to the process of myelination, which is helpful in cognitive processing, and any toxic insult that affects this process leads to improper cognitive development. [54],[55],[56],[57] Studies also suggest that the degree of cortical involvement depends on the age of onset of alcohol use. [54] Those having onset of alcohol use during their adolescence have more cortical white matter involvement, than those who have a later age of onset of alcohol use. [54] Alcohol also affects the expression of microRNA (miRNA) in the prefrontal cortex of humans as well as animal models, thereby attributing to the neuroinflammation and dysregulation of neurotransmission. [58] The impact of alcohol on the adolescent brain is more than that in adults, giving rise to resilient cognitive deficits. [59]

In adults, chronic use of alcohol leads to development of degenerative changes in the brain resulting in cortical atrophy and development of features of dementia, which usually manifest in the form of difficulty in task performance, inattentiveness, and impairment of memory. [1],[5] Alcohol-induced dementia is usually a reversible condition. [1] The degenerative changes following chronic alcohol abuse are a result of direct alcohol-induced neurotoxicity, oxidative stress, due to alcohol use-related nutritional deficiency or a combination of the above factors. [1] Alcohol is a known cause of vasculopathy and is a potential vascular risk factor of dementia. [60] The ethanol-induced process of neurodegeneration results in loss of cortical and subcortical brain matter and compensatory dilatation of the ventricular system. [28] The cholinergic system of the brain, which is responsible for the cognitive function, is highly sensitive to the effects of alcohol (ethanol). [61],[62] Long-term ethanol use causes leakage of the blood-brain barrier and activation of microglial cells in the brain. [60]

Recent evidences

A preliminary study to assess the acute impact of alcohol on a healthy adult brain was conducted by Weber et al. [63] In this study 11 healthy male volunteers were subjected to alcohol consumption in a measured amount followed by a series of post-consumption assessments (Resting state blood oxygen level dependent (rsBOLD) magnetic resonance imaging (MRI) scans). Before each rsBOLD scan, pointed-resolved spectroscopy (PRESS) and H-MRS (magnetic resonance spectroscopy) scans were done. [63] It was found that the functional connectivity of the default mode network (DMN) and temporal fractal properties, which were responsible for personal identity and social behavior, were significantly affected. [63] Di Guio et al., in their study on cortical morphology in children with fetal alcohol spectrum disorders, found that there was a decrease in complexity of the cortical folding resulting in a reduced buried cortical surface. [64] The cortical fold opening was believed to be the strongest anatomical correlate of prenatal alcohol intake. [64] Adolescent intermittent binge ethanol (AIE) exposure led to structural changes in the brain during adulthood, as found in the study of Coleman et al. [65] This study has revealed that there was an increase in the volume of certain brain areas (Orbitofrontal cortex, Cerebellum, Thalamus, Internal capsule, and genu of the corpus callosum) without any change in the total brain volume. [65] AIE exposure also leads to increased expression of certain extracellular matrix proteins like, Brevican, Neurocan, Tenascin-C, and HABP, and also results in loss of flexibility in behavior. [65] In a study on the effect of alcohol on the electrophysiological activities of adult brain, Lee et al., found that alcohol caused deficient coupling of the theta-phase gamma amplitude and predicted that this cross-frequency coupling could be a useful tool to study the effects of alcohol on the brain. [66] It was found that exposure to alcohol during the second trimester of pregnancy could adversely affect the spatial learning in juvenile rats. [67] López-Caneda and Yun, et al., in their study attempted to see the correlation between impulsive behavior and alcohol use in adolescents and young adults. [68] In this study it was found that loss of inhibitory control was an important risk factor of alcohol use and alcohol use further impaired an individual's ability to control the impulses, ultimately resulting in a vicious cycle of alcohol-use disorder. [68]


   Conclusion Top


Alcohol affects the brain during all stages of development. No organ in the body is resistant to the toxic effects of alcohol. Alcohol-induced effects may be reversible or irreversible. Extensive research in this area (both in experimental animals and human subjects) are suggestive of the significant adverse effect of alcohol on the developing brain.

 
   References Top

1.
Mohan I, Lal R, Rao R. Substance Use Disorder Manual for Physicians, All India Institute of Medical Sciences; 2005. Available from: http://www.aiims.edu/aiims/departments/spcenter/nddtc/Substance%20Use%20Disorder%20-%20Manual%20for%20Physicians.pdf. [Last assessed on 2013 Oct 22].  Back to cited text no. 1
    
2.
World Health Organization (WHO). Management of Substance Use. Global Strategy to Reduce Harmful Use of Alcohol 2010. Available from: http://www.who.int/substance_abuse/activities/gsrhua/en/index.html. [Last assessed on 2013 Oct 22].  Back to cited text no. 2
    
3.
Ray R. The Extent, Pattern and Trends of Drug Abuse in India, National Survey; 2004.  Back to cited text no. 3
    
4.
World Health Organization (WHO). Management of Substance Use: Country Profile 2011 India. Available from: http://www.who.int/substance_abuse/publications/global_alcohol_report/profiles/ind.pdf. [Last assessed on 2013 Oct 22].  Back to cited text no. 4
    
5.
Dalal PK, Kar SK. Complications of alcoholism. Indian J Behav Sci 2011;21:32-41.  Back to cited text no. 5
    
6.
Parsons OA. Alcohol abuse and alcoholism. In: Nixon SJ, editor. Neuropsychology for Clinical Practice. Washington, DC: American Psychological Press; 1996. p. 175-201.  Back to cited text no. 6
    
7.
Kolb B, Gibb R. Brain plasticity and behaviour in the developing brain. J Can Acad Child Adolesc Psychiatry 2011;20:265-76.  Back to cited text no. 7
    
8.
Zamenhof S, Van Marthens E. Study of factors influencing prenatal brain development. Mol Cell Biochem 1974;4:157-68.  Back to cited text no. 8
    
9.
WHO. Media Centre: Early Child Development August 2009. Available from: http://www.who.int/mediacentre/factsheets/fs332/en/index.html. [Last assessed on 2013 Oct 22].  Back to cited text no. 9
    
10.
Singh M. Nutrition, brain and environment: How to have smarter babies? Indian Pediatr 2003;40:213-20.  Back to cited text no. 10
    
11.
Yurgelun-Todd D. Emotional and cognitive changes during adolescence. Curr Opin Neurobiol 2007;17:251-7.  Back to cited text no. 11
    
12.
Smith MA, Makino S, Kvetnansky R, Post RM. Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 1995;15:1768-77.  Back to cited text no. 12
    
13.
Rango M, Canesi M, Ghione I, Farabola M, Righini A, Bresolin N, et al. Parkinson′s disease, chronic hydrocarbon exposure and striatal neuronal damage: A 1-H MRS study. Neurotoxicology 2006;27:164-8.  Back to cited text no. 13
    
14.
Segura Aguilar J, Kostrzewa RM. Neurotoxins and neurotoxic species implicated in neurodegeneration. Neurotox Res 2004;6:615-30.  Back to cited text no. 14
    
15.
Khalil M, Abudiab M, Ahmed AE. Clinical evaluation of 1, 3-butadiene neurotoxicity in humans. Toxicol Ind health 2007;23:141-6.  Back to cited text no. 15
    
16.
Sarter M, Bruno JP. Developmental origins of the age-related decline in cortical cholinergic function and associated cognitive abilities. Neurobiol Aging 2004;25:1127-39.  Back to cited text no. 16
    
17.
Sturchler E, Galichet A, Weibel M, Leclerc E, Heizmann CW. Site-specific blockade of RAGE-Vd prevents amyloid-beta oligomer neurotoxicity. J Neurosci 2008;28:5149-58.  Back to cited text no. 17
    
18.
Parameshwaran K, Dhanasekaran M, Suppiramaniam V. Amyloid beta peptides and glutamatergic synaptic dysregulation. Exp Neurol 2008;210:7-13.  Back to cited text no. 18
    
19.
Dubey M, Shea TB. Potentiation of arsenic neurotoxicity by folate deprivation: Protective role of S-adenosyl methionine. Nutr Neurosci 2007;10:199-204.  Back to cited text no. 19
    
20.
Michaud K, Matheson K, Kelly O, Anisman H. Impact of stressors in a natural context on release of cortisol in healthy adult humans: A meta-analysis. Stress 2008;11:177-97.  Back to cited text no. 20
    
21.
Turna B, Apaydin E, Semerci B, Altay B, Cikili N, Nazli O. Women with low libido: Correlation of decreased androgen levels with female sexual function index. Int J Impot Res 2005;17:148-53.  Back to cited text no. 21
    
22.
McDonald RJ, Craig LA, Hong NS. Enhanced cell death in hippocampus and emergence of cognitive impairments following a localized mini-stroke in hippocampus if preceded by a previous episode of acute stress. Eur J Neurosci 2008;27:2197-209.  Back to cited text no. 22
    
23.
Georgieff MK. Nutrition and the developing brain: Nutrient priorities and measurement. Am J Clin Nutr 2007;85:614S-20S.  Back to cited text no. 23
    
24.
Crews FT, Collins MA, Dlugos C, Littleton J, Wilkins L, Neafsey EJ, et al. Alcohol-induced neurodegeneration: When, where and why? Alcohol Clin Exp Res 2004;28:350-64.  Back to cited text no. 24
    
25.
Baydas G, Tuzcu M. Protective effects of melatonin against ethanol-induced reactive gliosis in hippocampus and cortex of young and aged rats. Exp Neurol 2005;194:175-81.  Back to cited text no. 25
    
26.
Rump TJ, Abdul Muneer PM, Szlachetka AM, Lamb A, Haorei C, Alikunju S, et al. Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain. Free Radic Biol Med 2010;49:1494-504.  Back to cited text no. 26
    
27.
Potula R, Haorah J, Knipe B, Leibhart J, Chrastil J, Heilman D, et al. Alcohol abuse enhances neuroinflammation and impairs immune responses in an animal model of human immunodeficiency virus-1 encephalitis. Am J Pathol 2006;168:1335-44.  Back to cited text no. 27
    
28.
Crews FT, Nixon K. Mechanisms of neurodegeneration and regeneration in alcoholism. Alcohol Alcohol 2009;44:115-27.  Back to cited text no. 28
    
29.
Haorah J, Ramirez SH, Floreani N, Gorantla S, Morsey B, Persidsky Y. Mechanism of alcohol-induced oxidative stress and neuronal injury. Free Radic Biol Med 2008;45:1542-50.  Back to cited text no. 29
    
30.
Cadaveira Mahía F. Alcohol and adolescent brain. Adicciones 2009;21:9-14.  Back to cited text no. 30
    
31.
Shabanov PD, Lebedev AA, Bychkov ER. The effect of ethanol exposure in pregnancy on maturation of monoaminergic systems in the developing rat bran. Ross Fiziol Zh Im I M Sechenova 2012;98:202-11.  Back to cited text no. 31
    
32.
Yang Y, Tang Y, Xing Y, Zhao M, Bao X, Sun D, et al. Activation of liverxreceptor is protective against ethanol-induced developmental impairment of Bergmann glia and Purkinje neurons in the mouse cerebellum. 2014;49:176-86.  Back to cited text no. 32
    
33.
Berman RF, Hannigan JH. Effects of prenatal alcohol exposure on the hippocampus: Spatial behavior, electrophysiology, and neuroanatomy. Hippocampus 2000;10:94-110.  Back to cited text no. 33
    
34.
Livy DJ, Miller EK, Maier SE, West JR. Fetal alcohol exposure and temporal vulnerability: Effects of binge-like alcohol exposure on the developing rat hippocampus. Neurotoxicol Teratol 2003;25:447-58.  Back to cited text no. 34
    
35.
Otero NK, Thomas JD, Saski CA, Xia X, Kelly SJ. Choline supplementation and DNA methylation in the hippocampus and prefrontal cortex of rats exposed to alcohol during development. Alcohol Clin Exp Res 2012;36:1701-9.  Back to cited text no. 35
    
36.
Tiwari V, Veeraiah P, Subramaniam V, Patel AB. Differential effects of ethanol on regional glutamatergic and GABAergic neurotransmitter pathways in mouse brain. J Neurochem 2014;128:628-40.  Back to cited text no. 36
    
37.
Barceló-Coblijn G, Wold LE, Ren J, Murphy EJ. Prenatal ethanol exposure increases brain cholesterol content in adult rats. Lipids 2013;48:1059-68.  Back to cited text no. 37
    
38.
Briones TL, Woods J. Chronic binge-like alcohol consumption in adolescence causes depression-like symptoms possibly mediated by the effects of BDNF on neurogenesis. Neuroscience 2013;254:324-34.  Back to cited text no. 38
    
39.
Monk BR, Leslie FM, Thomas JD. The effects of perinatal choline supplementation on hippocampal cholinergic development in rats exposed to alcohol during the brain growth spurt. Hippocampus 2012;22:1750-7.  Back to cited text no. 39
    
40.
Kodituwakku PW, Handmaker NS, Cutler SK, Weathersby EK, Handmaker SD. Specific impairments in self-regulation in children exposed to alcohol prenatally. Alcohol Clin Exp Res 1995;19:1558-64.  Back to cited text no. 40
    
41.
Mattson SN, Goodman AM, Caine C, Delis DC, Riley EP. Executive functioning in children with heavy prenatal alcohol exposure. Alcohol Clin Exp Res 1999;23:1808-15.  Back to cited text no. 41
    
42.
Archibald SL, Fennema-Notestine C, Gamst A, Riley EP, Mattson SN, Jernigan TL. Brain dysmorphology in individuals with severe prenatal alcohol exposure. Dev Med Child Neurol 2001;43:148-54.  Back to cited text no. 42
    
43.
Roebuck TM, Mattson SN, Riley EP. A review of the neuroanatomical findings in children with fetal alcohol syndrome or prenatal exposure to alcohol. Alcohol Clin Exp Res 1998;22:339-44.  Back to cited text no. 43
    
44.
Squeglia LM, Schweinsburg AD, Pulido C, Tapert SF. Adolescent binge drinking linked to abnormal spatial working memory brain activation: Differential gender effects. Alcohol Clin Exp Res 2011;35:1831-41.  Back to cited text no. 44
    
45.
Chanraud S, Pitel AL, Rohlfing T, Pfefferbaum A, Sullivan EV. Dual tasking and working memory in alcoholism: Relation to frontocerebellar circuitry. Neuropsychopharmacology 2010;35:1868-78.  Back to cited text no. 45
    
46.
Pfefferbaum A, Desmond JE, Galloway C, Menon V, Glover GH, Sullivan EV. Reorganization of frontal systems used by alcoholics for spatial working memory: An fMRI study. Neuroimage 2001;14:7-20.  Back to cited text no. 46
    
47.
Hommer D, Momenan R, Rawlings R, Ragan P, Williams W, Rio D, et al. Decreased corpus callosum size among alcoholic women. Arch Neurol 1996;53:359-63.  Back to cited text no. 47
    
48.
Hommer D, Momenan R, Kaiser E, Rawlings RR. Evidence for a gender-related effect of alcoholism on brain volumes. Am J Psychiatry 2001;158:198-204.  Back to cited text no. 48
    
49.
Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, et al. Brain development during childhood and adolescence: A longitudinal MRI study. Nat Neurosci 1999;2:861-3.  Back to cited text no. 49
    
50.
Wager TD, Smith EE. Neuroimaging studies of working memory: A meta-analysis. Cogn Affect Behav Neurosci 2003;3:255-74.  Back to cited text no. 50
    
51.
Tapert SF, Granholm E, Leedy NG, Brown SA. Substance use and withdrawal: Neuropsychological functioning over 8 years in youth. J Int Neuropsychol Soc 2002;8:873-83.  Back to cited text no. 51
    
52.
Brown SA, Tapert SF, Granholm E, Delis DC. Neurocognitive functioning of adolescents: Effects of protracted alcohol use. Alcohol Clin Exp Res 2000;24:164-71.  Back to cited text no. 52
    
53.
Thoma RJ, Monnig MA, Lysne PA, Ruhl DA, Pommy JA, Bogenschutz M, et al. Adolescent substance abuse: The effects of alcohol and marijuana on neuropsychological performance. Alcohol Clin Exp Res 2011;35:39-46.  Back to cited text no. 53
    
54.
Jacobus J, Squeglia LM, Infante MA, Bava S, Tapert SF. White matter integrity pre- and post marijuana and alcohol initiation in adolescence. Brain Sci 2013;3:396-414.  Back to cited text no. 54
    
55.
Giedd JN. The teen brain: Insights from neuroimaging. J Adolesc Health 2008;42:335-43.  Back to cited text no. 55
    
56.
Fryer SL, Frank LR, Spadoni AD, Theilmann RJ, Nagel BJ, Schweinsburg AD, et al. Microstructural integrity of the corpus callosum linked with neuropsychological performance in adolescents. Brain Cogn 2008;67:225-33.  Back to cited text no. 56
    
57.
Squeglia LM, Jacobus J, Tapert SF. The influence of substance use on adolescent brain development. Clin EEG Neurosci 2009;40:31-8.  Back to cited text no. 57
    
58.
Nunez YO, Mayfield RD. Understanding alcoholism through microRNA signatures in brains of human alcoholics. Front Genet 2012;3:43.  Back to cited text no. 58
    
59.
Broadwater M, Spear LP. Consequences of ethanol exposure on cued and contextual fear conditioning and extinction differ depending on timing of exposure during adolescence or adulthood. Behav Brain Res 2013;256:10-9.  Back to cited text no. 59
    
60.
Ehrlich D, Pirchl M, Humpel C. Effects of long-term moderate ethanol and cholesterol on cognition, cholinergic neurons, inflammation, and vascular impairment in rats. Neuroscience 2012;205:154-66.  Back to cited text no. 60
    
61.
Floyd EA, Young-Seigler AC, Ford BD, Reasor JD, Moore EL, Townsel JG, et al. Chronic ethanol ingestion produces cholinergic hypofunction in rat brain. Alcohol 1997;14:93-8.  Back to cited text no. 61
    
62.
Arendt T. Impairment in memory function and neurodegenerative changes in the cholinergic basal forebrain system induced by chronic intake of ethanol. J Neural Transm Suppl 1994;44:173-87.  Back to cited text no. 62
    
63.
Weber AM, Soreni N, Noseworthy MD. A preliminary study on the effects of acute ethanol ingestion on default mode network and temporal fractal properties of the brain. MAGMA 2013. [Epub ahead of print].  Back to cited text no. 63
    
64.
De Guio F, Mangin JF, Rivière D, Perrot M, Molteno CD, Jacobson SW, et al. A study of cortical morphology in children with fetal alcohol spectrum disorders. Hum Brain Mapp 2014;35:2285-96.  Back to cited text no. 64
    
65.
Coleman LG Jr, Liu W, Oguz I, Styner M, Crews FT. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility. Pharmacol Biochem Behav 2014;116:142-51.  Back to cited text no. 65
    
66.
Lee J, Yun K. Alcohol reduces cross-frequency theta-phase gamma-amplitude coupling in resting electroencephalography. Alcohol Clin Exp Res 2014;38:770-6.  Back to cited text no. 66
    
67.
Elibol-Can B, Dursun I, Telkes I, Kilic E, Canan S, Jakubowska-Dogru E. Examination of age-dependent effects of fetal ethanol exposure on behavior, hippocampal cell counts, and doublecortin immunoreactivity in rats. Dev Neurobiol 2014;74:498-513.  Back to cited text no. 67
    
68.
López-Caneda E, Rodríguez Holguín S, Cadaveira F, Corral M, Doallo S. Impact of alcohol use on inhibitory control (and vice versa) during adolescence and young adulthood: A review. Alcohol Alcohol 2014;49:173-81.  Back to cited text no. 68
    




 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
   Introduction
   Conclusion
    References

 Article Access Statistics
    Viewed2983    
    Printed63    
    Emailed0    
    PDF Downloaded131    
    Comments [Add]    

Recommend this journal