Neuropsychopharmacology Reviews | Published:

Let’s call the whole thing off: evaluating gender and sex differences in executive function

Neuropsychopharmacology (2018) | Download Citation


The executive functions allow for purposeful, deliberate, and intentional interactions with the world—attention and focus, impulse control, decision making, and working memory. These measures have been correlated with academic outcomes and quality of life, and are impacted by deleterious environmental events throughout the life span, including gestational and early life insults. This review will address the topic of sex differences in executive function including a discussion of differences arising in response to developmental programming. Work on gender differences in human studies and sex differences in animal research will be reviewed. Overall, we find little support for significant gender or sex differences in executive function. An important variable that factors into the interpretation of potential sex differences include differing developmental trajectories. We conclude by discussing future directions for the field and a brief discussion of biological mechanisms.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. 1.

    Morgan PL, Staff J, Hillemeier MM, Farkas G, Maczuga S. Racial and ethnic disparities in ADHD diagnosis from kindergarten to eighth grade. Pediatrics. 2013;132:85–93.

  2. 2.

    Hasson R, Fine JG. Gender differences among children with ADHD on continuous performance tests: a meta-analytic review. J Atten Disord. 2012;16:190–8.

  3. 3.

    Newcorn JH, Halperin JM, Jensen PS, Abikoff HB, Arnold LE, Cantwell DP, et al. Symptom profiles in children with ADHD: effects of comorbidity and gender. J Am Acad Child Adolesc Psychiatry. 2001;40:137–46.

  4. 4.

    Gunther T, Knospe EL, Herpertz-Dahlmann B, Konrad K. Sex differences in attentional performance in a clinical sample with ADHD of the combined subtype. J Atten Disord. 2015;19:764–70.

  5. 5.

    Novik TS, Hervas A, Ralston SJ, Dalsgaard S, Rodrigues Pereira R, Lorenzo MJ, et al. Influence of gender on attention-deficit/hyperactivity disorder in Europe—ADORE. Eur Child Adolesc Psychiatry. 2006;15:I15–24.

  6. 6.

    Omura K, Kusumoto K. Sex differences in neurophysiological responses are modulated by attentional aspects of impulse control. Brain Cogn. 2015;100:49–59.

  7. 7.

    Millenet S, Laucht M, Hohm E, Jennen-Steinmetz C, Hohmann S, Schmidt MH et al. Sex-specific trajectories of ADHD symptoms from adolescence to young adulthood. Eur Child Adolesc Psychiatry. 2018; 8:1067-1075.

  8. 8.

    McGrath J, Saha S, Welham J, El Saadi O, MacCauley C, Chant D. A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology. BMC Med. 2004;2:13.

  9. 9.

    Kessler RC, Birnbaum H, Demler O, Falloon IR, Gagnon E, Guyer M, et al. The prevalence and correlates of nonaffective psychosis in the National Comorbidity Survey Replication (NCS-R). Biol Psychiatry. 2005;58:668–76.

  10. 10.

    Goldstein JM, Cherkerzian S, Tsuang MT, Petryshen TL. Sex differences in the genetic risk for schizophrenia: history of the evidence for sex-specific and sex-dependent effects. Am J Med Genet B Neuropsychiatr Genet. 2013;162B:698–710.

  11. 11.

    Hafner H, an der Heiden W. Epidemiology of schizophrenia. Can J Psychiatry. 1997;42:139–51.

  12. 12.

    Arnold LM. Gender differences in bipolar disorder. Psychiatr Clin North Am. 2003;26:595–620.

  13. 13.

    Hill RA. Sex differences in animal models of schizophrenia shed light on the underlying pathophysiology. Neurosci Biobehav Rev. 2016;67:41–56.

  14. 14.

    Kokras N, Dalla C. Sex differences in animal models of psychiatric disorders. Br J Pharmacol. 2014;171:4595–619.

  15. 15.

    Sanchez MM, Hearn EF, Do D, Rilling JK, Herndon JG. Differential rearing affects corpus callosum size and cognitive function of rhesus monkeys. Brain Res. 1998;812:38–49.

  16. 16.

    Bolandzadeh N, Davis JC, Tam R, Handy TC, Liu-Ambrose T. The association between cognitive function and white matter lesion location in older adults: a systematic review. BMC Neurol. 2012;12:126.

  17. 17.

    Girotti M, Adler SM, Bulin SE, Fucich EA, Paredes D, Morilak DA. Prefrontal cortex executive processes affected by stress in health and disease. Prog Neuropsychopharmacol Biol Psychiatry. 2017; 85:161-179.

  18. 18.

    Hostinar CE, Stellern SA, Schaefer C, Carlson SM, Gunnar MR. Associations between early life adversity and executive function in children adopted internationally from orphanages. Proc Natl Acad Sci USA. 2012;109:17208–12.

  19. 19.

    Kim-Spoon J, Kahn RE, Lauharatanahirun N, Deater-Deckard K, Bickel WK, Chiu PH, et al. Executive functioning and substance use in adolescence: Neurobiological and behavioral perspectives. Neuropsychologia. 2017;100:79–92.

  20. 20.

    Lovic V, Fleming AS. Artificially-reared female rats show reduced prepulse inhibition and deficits in the attentional set shifting task--reversal of effects with maternal-like licking stimulation. Behav Brain Res. 2004;148:209–19.

  21. 21.

    Barnett JH, Heron J, Ring SM, Golding J, Goldman D, Xu K, et al. Gender-specific effects of the catechol-O-methyltransferase Val108/158Met polymorphism on cognitive function in children. Am J Psychiatry. 2007;164:142–9.

  22. 22.

    Lange K, Thamotharan S, Sferra M, Ramos A, Fields S. Effects of weight and gender on a task of inattention. Eat Behav. 2014;15:574–7.

  23. 23.

    Giambra LM, Quilter RE. Sex differences in sustained attention across the adult life span. J Appl Psychol. 1989;74:91–5.

  24. 24.

    Pletzer B, Harris TA, Ortner T. Sex and menstrual cycle influences on three aspects of attention. Physiol Behav. 2017;179:384–90.

  25. 25.

    Riley E, Okabe H, Germine L, Wilmer J, Esterman M, DeGutis J. Gender differences in sustained attentional control relate to gender inequality across countries. PLoS ONE. 2016;11:e0165100.

  26. 26.

    Bezdjian S, Baker LA, Lozano DI, Raine A. Assessing inattention and impulsivity in children during the Go/NoGo task. Br J Dev Psychol. 2009;27:365–83.

  27. 27.

    Conners CK, Epstein JN, Angold A, Klaric J. Continuous performance test performance in a normative epidemiological sample. J Abnorm Child Psychol. 2003;31:555–62.

  28. 28.

    Young JW, Light GA, Marston HM, Sharp R, Geyer MA. The 5-choice continuous performance test: evidence for a translational test of vigilance for mice. PLoS ONE. 2009;4:e4227.

  29. 29.

    Mirsky AF, Rosvold HE. The use of psychoactive drugs as a neuropsychological tool in studies of attention in man. In: Uhr I, Miller JG, editors. Drugs and behavior. New York, NY: Wiley; 1960. p. 375–92. .

  30. 30.

    Wang LJ, Huang YS, Chiang YL, Hsiao CC, Shang ZY, Chen CK. Clinical symptoms and performance on the continuous performance test in children with attention deficit hyperactivity disorder between subtypes: a natural follow-up study for 6 months. BMC Psychiatry. 2011;11:65.

  31. 31.

    Papaleo F, Erickson L, Liu G, Chen J, Weinberger DR. Effects of sex and COMT genotype on environmentally modulated cognitive control in mice. Proc Natl Acad Sci USA. 2012;109:20160–5.

  32. 32.

    Jentsch JD, Taylor JR. Sex-related differences in spatial divided attention and motor impulsivity in rats. Behav Neurosci. 2003;117:76–83.

  33. 33.

    Bayless DW, Darling JS, Stout WJ, Daniel JM. Sex differences in attentional processes in adult rats as measured by performance on the 5-choice serial reaction time task. Behav Brain Res. 2012;235:48–54.

  34. 34.

    Groves NJ, Burne TH. Sex-specific attentional deficits in adult vitamin D deficient BALB/c mice. Physiol Behav. 2016;157:94–101.

  35. 35.

    Grissom NM, Herdt CT, Desilets J, Lidsky-Everson J, Reyes TM. Dissociable deficits of executive function caused by gestational adversity are linked to specific transcriptional changes in the prefrontal cortex. Neuropsychopharmacology. 2015;40:1353–63.

  36. 36.

    Ciampoli M, Contarini G, Mereu M, Papaleo F. Attentional control in adolescent mice assessed with a modified five choice serial reaction time task. Sci Rep. 2017;7:9936.

  37. 37.

    Burton CL, Fletcher PJ. Age and sex differences in impulsive action in rats: the role of dopamine and glutamate. Behav Brain Res. 2012;230:21–33.

  38. 38.

    Anshu K, Nair AK, Kumaresan UD, Kutty BM, Srinath S, Laxmi TR. Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder. Autism Res. 2017;10:1929–44.

  39. 39.

    Lukkes JL, Thompson BS, Freund N, Andersen SL. The developmental inter-relationships between activity, novelty preferences, and delay discounting in male and female rats. Dev Psychobiol. 2016;58:231–42.

  40. 40.

    Eckel CC, Grossman PJ. Men, women and risk aversion: experimental evidence. Handb Exp Econ Results. 2008;1:1061–73.

  41. 41.

    Orsini CA, Setlow B. Sex differences in animal models of decision making. J Neurosci Res. 2017;95:260–9.

  42. 42.

    van den Bos R, Homberg J, de Visser L. A critical review of sex differences in decision-making tasks: focus on the Iowa Gambling Task. Behav Brain Res. 2013b;238:95–108.

  43. 43.

    Dunn BD, Dalgleish T, Lawrence AD. The somatic marker hypothesis: a critical evaluation. Neurosci Biobehav Rev. 2006;30:239–71.

  44. 44.

    Overman WH, Pierce A. Iowa Gambling Task with non-clinical participants: effects of using real+virtual cards and additional trials. Front Psychol. 2013;4:935.

  45. 45.

    Singh V. Sex-differences, handedness, and lateralization in the Iowa Gambling Task. Front Psychol. 2016;7:708.

  46. 46.

    Zhang F, Xiao L, Gu R. Does gender matter in the relationship between anxiety and decision-making? Front Psychol. 2017;8:2231.

  47. 47.

    Gruber KA, Callahan MF. ACTH-(4-10) through gamma-MSH: evidence for a new class of central autonomic nervous system-regulating peptides. Am J Physiol. 1989;257:R681–94.

  48. 48.

    van der Plas EA, Crone EA, van den Wildenberg WP, Tranel D, Bechara A. Executive control deficits in substance-dependent individuals: a comparison of alcohol, cocaine, and methamphetamine and of men and women. J Clin Exp Neuropsychol. 2009;31:706–19.

  49. 49.

    Kim HW, Kang JI, Namkoong K, Jhung K, Ha RY, Kim SJ. Further evidence of a dissociation between decision-making under ambiguity and decision-making under risk in obsessive-compulsive disorder. J Affect Disord. 2015;176:118–24.

  50. 50.

    Overman W, Graham L, Redmond A, Eubank R, Boettcher L, Samplawski O, et al. Contemplation of moral dilemmas eliminates sex differences on the Iowa gambling task. Behav Neurosci. 2006;120:817–25.

  51. 51.

    Starcke K, Agorku JD, Brand M. Exposure to unsolvable anagrams impairs performance on the Iowa Gambling Task. Front Behav Neurosci. 2017;11:114.

  52. 52.

    van den Bos R, Davies W, Dellu-Hagedorn F, Goudriaan AE, Granon S, Homberg J, et al. Cross-species approaches to pathological gambling: a review targeting sex differences, adolescent vulnerability and ecological validity of research tools. Neurosci Biobehav Rev. 2013a;37:2454–71.

  53. 53.

    Dretsch MN, Tipples J. Sex differences moderate decision making behaviour in high impulsive sensation seekers. Cogn Emot. 2011;25:149–55.

  54. 54.

    Chiu YC, Lin CH. Is deck C an advantageous deck in the Iowa Gambling Task? Behav Brain Funct. 2007;3:37.

  55. 55.

    Lin CH, Chiu YC, Lee PL, Hsieh JC. Is deck B a disadvantageous deck in the Iowa Gambling Task? Behav Brain Funct. 2007;3:16.

  56. 56.

    Addicott MA, Pearson JM, Wilson J, Platt ML, McClernon FJ. Smoking and the bandit: a preliminary study of smoker and nonsmoker differences in exploratory behavior measured with a multiarmed bandit task. Exp Clin Psychopharmacol. 2013;21:66–73.

  57. 57.

    Evans KL, Hampson E. Sex-dependent effects on tasks assessing reinforcement learning and interference inhibition. Front Psychol. 2015;6:1044.

  58. 58.

    Kovach CK, Daw ND, Rudrauf D, Tranel D, O’Doherty JP, Adolphs R. Anterior prefrontal cortex contributes to action selection through tracking of recent reward trends. J Neurosci. 2012;32:8434–42.

  59. 59.

    Derntl B, Pintzinger N, Kryspin-Exner I, Schopf V. The impact of sex hormone concentrations on decision-making in females and males. Front Neurosci. 2014;8:352.

  60. 60.

    Weafer J, De Arcangelis J, de Wit H. Sex differences in behavioral impulsivity in at-risk and non-risk drinkers. Front Psychiatry. 2015;6:72.

  61. 61.

    Cross CP, Copping LT, Campbell A. Sex differences in impulsivity: a meta-analysis. Psychol Bull. 2011;137:97–130.

  62. 62.

    Doi H, Nishitani S, Shinohara K. Sex difference in the relationship between salivary testosterone and inter-temporal choice. Horm Behav. 2015;69:50–8.

  63. 63.

    Sidlauskaite J, Gonzalez-Madruga K, Smaragdi A, Riccelli R, Puzzo I, Batchelor M, et al. Sex differences in risk-based decision making in adolescents with conduct disorder. Eur Child Adolesc Psychiatry. 2017; doi: 10.1007/s00787-017-1024-9. [Epub ahead of print].

  64. 64.

    Heilbronner SR. Modeling risky decision-making in nonhuman animals: shared core features. Curr Opin Behav Sci. 2017;16:23–9.

  65. 65.

    van den Bos R, Jolles J, van der Knaap L, Baars A, de Visser L. Male and female Wistar rats differ in decision-making performance in a rodent version of the Iowa Gambling Task. Behav Brain Res. 2012;234:375–9.

  66. 66.

    Orsini CA, Willis ML, Gilbert RJ, Bizon JL, Setlow B. Sex differences in a rat model of risky decision making. Behav Neurosci. 2016;130:50–61.

  67. 67.

    Peak JN, Turner KM, Burne TH. The effect of developmental vitamin D deficiency in male and female Sprague-Dawley rats on decision-making using a rodent gambling task. Physiol Behav. 2015;138:319–24.

  68. 68.

    Weston HI, Weston DD, Allen JL, Cory-Slechta DA. Sex-dependent impacts of low-level lead exposure and prenatal stress on impulsive choice behavior and associated biochemical and neurochemical manifestations. Neurotoxicology. 2014;44:169–83.

  69. 69.

    Brydges NM, Holmes MC, Harris AP, Cardinal RN, Hall J. Early life stress produces compulsive-like, but not impulsive, behavior in females. Behav Neurosci. 2015;129:300–8.

  70. 70.

    Eubig PA, Noe TE, Floresco SB, Sable JJ, Schantz SL. Sex differences in response to amphetamine in adult Long-Evans rats performing a delay-discounting task. Pharmacol Biochem Behav. 2014;118:1–9.

  71. 71.

    Chelonis JJ, Daniels-Shaw JL, Blake DJ, Paule MG. Developmental aspects of delayed matching-to-sample task performance in children. Neurotoxicol Teratol. 2000;22:683–94.

  72. 72.

    Leon I, Cimadevilla JM, Tascon L. Developmental gender differences in children in a virtual spatial memory task. Neuropsychology. 2014;28:485–95.

  73. 73.

    Loe IM, Luna B, Bledsoe IO, Yeom KW, Fritz BL, Feldman HM. Oculomotor assessments of executive function in preterm children. J Pediatr. 2012;161:427–33 e421.

  74. 74.

    Alarcon G, Cservenka A, Fair DA, Nagel BJ. Sex differences in the neural substrates of spatial working memory during adolescence are not mediated by endogenous testosterone. Brain Res. 2014;1593:40–54.

  75. 75.

    Castonguay N, Lussier M, Bugaiska A, Lord C, Bherer L. Executive functions in men and postmenopausal women. J Clin Exp Neuropsychol. 2015;37:193–208.

  76. 76.

    Hsu HL, Chen DY, Tseng YC, Kuo YS, Huang YL, Chiu WT, et al. Sex differences in working memory after mild traumatic brain injury: a functional MR imaging study. Radiology. 2015;276:828–35.

  77. 77.

    Martoni RM, Salgari G, Galimberti E, Cavallini MC, O’Neill J. Effects of gender and executive function on visuospatial working memory in adult obsessive-compulsive disorder. Eur Arch Psychiatry Clin Neurosci. 2015;265:707–18.

  78. 78.

    McCarrey AC, An Y, Kitner-Triolo MH, Ferrucci L, Resnick SM. Sex differences in cognitive trajectories in clinically normal older adults. Psychol Aging. 2016;31:166–75.

  79. 79.

    Rahman Q, Abrahams S, Jussab F. Sex differences in a human analogue of the Radial Arm Maze: the “17-Box Maze Test”. Brain Cogn. 2005;58:312–7.

  80. 80.

    Duff SJ, Hampson E. A sex difference on a novel spatial working memory task in humans. Brain Cogn. 2001;47:470–93.

  81. 81.

    Lejbak L, Vrbancic M, Crossley M. The female advantage in object location memory is robust to verbalizability and mode of presentation of test stimuli. Brain Cogn. 2009;69:148–53.

  82. 82.

    Reed JL, Gallagher NM, Sullivan M, Callicott JH, Green AE. Sex differences in verbal working memory performance emerge at very high loads of common neuroimaging tasks. Brain Cogn. 2017;113:56–64.

  83. 83.

    Voyer D, Voyer SD, Saint-Aubin J. Sex differences in visual-spatial working memory: a meta-analysis. Psychon Bull Rev. 2017;24:307–34.

  84. 84.

    Chai XJ, Jacobs LF. Effects of cue types on sex differences in human spatial memory. Behav Brain Res. 2010;208:336–42.

  85. 85.

    Seymoure P, Juraska JM. Sex differences in radial maze performance: influence of rearing environment and room cues. Psychobiology. 1996;24:33–7.

  86. 86.

    Gibbs RB, Johnson DA. Sex-specific effects of gonadectomy and hormone treatment on acquisition of a 12-arm radial maze task by Sprague Dawley rats. Endocrinology. 2008;149:3176–83.

  87. 87.

    Hall BJ, Abreu-Villaca Y, Cauley M, Junaid S, White H, Kiany A, et al. The ventral hippocampal muscarinic cholinergic system plays a key role in sexual dimorphisms of spatial working memory in rats. Neuropharmacology. 2017;117:106–13.

  88. 88.

    Harris JC, Martinez JM, Grozdanov PN, Bergeson SE, Grammas P, MacDonald CC. The Cstf2t polyadenylation gene plays a sex-specific role in learning behaviors in mice. PLoS ONE. 2016;11:e0165976.

  89. 89.

    Luine V, Gomez J, Beck K, Bowman R. Sex differences in chronic stress effects on cognition in rodents. Pharmacol Biochem Behav. 2017;152:13–9.

  90. 90.

    Bimonte HA, Denenberg VH. Sex differences in vicarious trial-and-error behavior during radial arm maze learning. Physiol Behav. 2000;68:495–9.

  91. 91.

    West RK, Maynard ME, Leasure JL. Binge ethanol effects on prefrontal cortex neurons, spatial working memory and task-induced neuronal activation in male and female rats. Physiol Behav. 2018;188:79–85.

  92. 92.

    Sutcliffe JS, Marshall KM, Neill JC. Influence of gender on working and spatial memory in the novel object recognition task in the rat. Behav Brain Res. 2007;177:117–25.

  93. 93.

    Roddick KM, Schellinck HM, Brown RE. Olfactory delayed matching to sample performance in mice: sex differences in the 5XFAD mouse model of Alzheimer’s disease. Behav Brain Res. 2014;270:165–70.

  94. 94.

    Rodriguez JS, Zurcher NR, Bartlett TQ, Nathanielsz PW, Nijland MJ. CANTAB delayed matching to sample task performance in juvenile baboons. J Neurosci Methods. 2011a;196:258–63.

  95. 95.

    Grilly DM. Sex differences in delayed matching-to-sample performance of chimpanzees. Psychol Rep. 1975;37:203–7.

  96. 96.

    Fridberg DJ, Gerst KR, Finn PR. Effects of working memory load, a history of conduct disorder, and sex on decision making in substance dependent individuals. Drug Alcohol Depend. 2013;133:654–60.

  97. 97.

    Nooner KB, Hooper SR, De Bellis MD. An examination of sex differences on neurocognitive functioning and behavior problems in maltreated youth. Psychol Trauma. 2017; 10:435-443.

  98. 98.

    Lee J, Smith JP. Regional disparities in adult height, educational attainment and gender difference in late-life cognition: findings from the Longitudinal Aging Study in India (LASI). J Econ Ageing. 2014;4:26–34.

  99. 99.

    Lei X, Hu Y, McArdle JJ, Smith JP, Zhao Y. Gender differences in cognition among older adults in China. J Hum Resour. 2012;47:951–71.

  100. 100.

    Lei X, Smith JP, Sun X, Zhao Y. Gender differences in cognition in China and reasons for change over time: evidence from CHARLS. J Econ Ageing. 2014;4:46–55.

  101. 101.

    Pereira VH, Costa PS, Santos NC, Cunha PG, Correia-Neves M, Palha JA, et al. Adult body height is a good predictor of different dimensions of cognitive function in aged individuals: a cross-sectional study. Front Aging Neurosci. 2016;8:217.

  102. 102.

    Shim SY, Cho SJ, Kong KA, Park EA. Gestational age-specific sex difference in mortality and morbidities of preterm infants: a nationwide study. Sci Rep. 2017;7:6161.

  103. 103.

    Skuse DH. Imprinting, the X-chromosome, and the male brain: explaining sex differences in the liability to autism. Pediatr Res. 2000;47:9–16.

  104. 104.

    Vu HD, Dickinson C, Kandasamy Y. Sex difference in mortality for premature and low birth weight neonates: a systematic review. Am J Perinatol. 2017; 35:707-715.

  105. 105.

    Davis EP, Pfaff D. Sexually dimorphic responses to early adversity: implications for affective problems and autism spectrum disorder. Psychoneuroendocrinology. 2014;49:11–25.

  106. 106.

    McCarthy MM. Sex differences in the developing brain as a source of inherent risk. Dialog- Clin Neurosci. 2016;18:361–72.

  107. 107.

    Karemaker R, Heijnen CJ, Veen S, Baerts W, Samsom J, Visser GH, et al. Differences in behavioral outcome and motor development at school age after neonatal treatment for chronic lung disease with dexamethasone versus hydrocortisone. Pediatr Res. 2006;60:745–50.

  108. 108.

    Rodriguez JS, Zurcher NR, Keenan KE, Bartlett TQ, Nathanielsz PW, Nijland MJ. Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons. Am J Obstet Gynecol. 2011b;204:545 e541–10.

  109. 109.

    Rodriguez JS, Bartlett TQ, Keenan KE, Nathanielsz PW, Nijland MJ. Sex-dependent cognitive performance in baboon offspring following maternal caloric restriction in pregnancy and lactation. Reprod Sci. 2012;19:493–504.

  110. 110.

    Lloyd SA, Oltean C, Pass H, Phillips B, Staton K, Robertson CL, et al. Prenatal exposure to psychostimulants increases impulsivity, compulsivity, and motivation for rewards in adult mice. Physiol Behav. 2013;119:43–51.

  111. 111.

    Talge NM, Allswede DM, Holzman C. Gestational age at term, delivery circumstance, and their association with childhood attention deficit hyperactivity disorder symptoms. Paediatr Perinat Epidemiol. 2016;30:171–80.

  112. 112.

    Melchior M, Hersi R, van der Waerden J, Larroque B, Saurel-Cubizolles MJ, Chollet A, et al. Maternal tobacco smoking in pregnancy and children’s socio-emotional development at age 5: the EDEN mother-child birth cohort study. Eur Psychiatry. 2015;30:562–8.

  113. 113.

    Kobrosly RW, Evans S, Miodovnik A, Barrett ES, Thurston SW, Calafat AM, et al. Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6−10 years of age. Environ Health Perspect. 2014;122:521–8.

  114. 114.

    Hehar H, Yeates K, Kolb B, Esser MJ, Mychasiuk R. Impulsivity and concussion in juvenile rats: examining molecular and structural aspects of the frontostriatal pathway. PLoS ONE. 2015;10:e0139842.

  115. 115.

    Wallensteen L, Zimmermann M, Thomsen Sandberg M, Gezelius A, Nordenstrom A, Hirvikoski T, et al. Sex-dimorphic effects of prenatal treatment with dexamethasone. J Clin Endocrinol Metab. 2016;101:3838–46.

  116. 116.

    Andersen HR, Debes F, Wohlfahrt-Veje C, Murata K, Grandjean P. Occupational pesticide exposure in early pregnancy associated with sex-specific neurobehavioral deficits in the children at school age. Neurotoxicol Teratol. 2015;47:1–9.

  117. 117.

    Loi M, Mossink JC, Meerhoff GF, Den Blaauwen JL, Lucassen PJ, Joels M. Effects of early-life stress on cognitive function and hippocampal structure in female rodents. Neuroscience. 2017;342:101–19.

  118. 118.

    Selleck RA, Lake C, Estrada V, Riederer J, Andrzejewski M, Sadeghian K, et al. Endogenous opioid signaling in the medial prefrontal cortex is required for the expression of hunger-induced impulsive action. Neuropsychopharmacology. 2015;40:2464–74.

  119. 119.

    Feja M, Koch M. Ventral medial prefrontal cortex inactivation impairs impulse control but does not affect delay-discounting in rats. Behav Brain Res. 2014;264:230–9.

  120. 120.

    Jupp B, Caprioli D, Saigal N, Reverte I, Shrestha S, Cumming P, et al. Dopaminergic and GABA-ergic markers of impulsivity in rats: evidence for anatomical localisation in ventral striatum and prefrontal cortex. Eur J Neurosci. 2013;37:1519–28.

  121. 121.

    Tessitore A, Santangelo G, De Micco R, Vitale C, Giordano A, Raimo S, et al. Cortical thickness changes in patients with Parkinson’s disease and impulse control disorders. Parkinsonism Relat Disord. 2016; 24:119-25.

  122. 122.

    Yates JR, Darna M, Beckmann JS, Dwoskin LP, Bardo MT. Individual differences in impulsive action and dopamine transporter function in rat orbitofrontal cortex. Neuroscience. 2016;313:122–9.

  123. 123.

    Boy F, Evans CJ, Edden RA, Lawrence AD, Singh KD, Husain M, et al. Dorsolateral prefrontal gamma-aminobutyric acid in men predicts individual differences in rash impulsivity. Biol Psychiatry. 2011;70:866–72.

  124. 124.

    Murphy ER, Fernando AB, Urcelay GP, Robinson ES, Mar AC, Theobald DE, et al. Impulsive behaviour induced by both NMDA receptor antagonism and GABAA receptor activation in rat ventromedial prefrontal cortex. Psychopharmacol (Berl). 2012;219:401–10.

  125. 125.

    Benn A, Robinson ES. Investigating glutamatergic mechanism in attention and impulse control using rats in a modified 5-choice serial reaction time task. PLoS ONE. 2014;9:e115374.

  126. 126.

    Logue SF, Gould TJ. The neural and genetic basis of executive function: attention, cognitive flexibility, and response inhibition. Pharmacol Biochem Behav. 2014;123:45–54.

  127. 127.

    Sanchez-Roige S, Ripley TL, Stephens DN. Alleviating waiting impulsivity and perseverative responding by mu-opioid receptor antagonism in two inbred mouse strains. Psychopharmacol (Berl). 2015;232:1483–92.

  128. 128.

    D’Amour-Horvat V, Leyton M. Impulsive actions and choices in laboratory animals and humans: effects of high vs. low dopamine states produced by systemic treatments given to neurologically intact subjects. Front Behav Neurosci. 2014;8:432.

  129. 129.

    Kolisnyk B, Al-Onaizi MA, Hirata PH, Guzman MS, Nikolova S, Barbash S, et al. Forebrain deletion of the vesicular acetylcholine transporter results in deficits in executive function, metabolic, and RNA splicing abnormalities in the prefrontal cortex. J Neurosci. 2013;33:14908–20.

  130. 130.

    Staiti AM, Morgane PJ, Galler JR, Grivetti JY, Bass DC, Mokler DJ. A microdialysis study of the medial prefrontal cortex of adolescent and adult rats. Neuropharmacology. 2011;61:544–9.

  131. 131.

    Alves NC, Bailey CD, Nashmi R, Lambe EK. Developmental sex differences in nicotinic currents of prefrontal layer VI neurons in mice and rats. PLoS ONE. 2010;5:e9261.

  132. 132.

    Andersen SL, Teicher MH. Sex differences in dopamine receptors and their relevance to ADHD. Neurosci Biobehav Rev. 2000;24:137–41.

  133. 133.

    Gurvich C, Rossell SL. Dopamine and cognitive control: sex-by-genotype interactions influence the capacity to switch attention. Behav Brain Res. 2015;281:96–101.

  134. 134.

    LaRoche RB, Morgan RE. Adolescent fluoxetine exposure produces enduring, sex-specific alterations of visual discrimination and attention in rats. Neurotoxicol Teratol. 2007;29:96–107.

  135. 135.

    Kolb B, Mychasiuk R, Muhammad A, Li Y, Frost DO, Gibb R. Experience and the developing prefrontal cortex. Proc Natl Acad Sci USA. 2012;109:17186–93.

  136. 136.

    Rakic P, Bourgeois JP, Eckenhoff MF, Zecevic N, Goldman-Rakic PS. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science. 1986;232:232–5.

  137. 137.

    Samaco RC, McGraw CM, Ward CS, Sun Y, Neul JL, Zoghbi HY. Female Mecp2+/- mice display robust behavioral deficits on two different genetic backgrounds providing a framework for pre-clinical studies. Hum Mol Genet. 2013;22:96–109.

  138. 138.

    Volk L, Chiu SL, Sharma K, Huganir RL. Glutamate synapses in human cognitive disorders. Annu Rev Neurosci. 2015;38:127–49.

  139. 139.

    Wu EQ, Shi L, Birnbaum H, Hudson T, Kessler R. Annual prevalence of diagnosed schizophrenia in the USA: a claims data analysis approach. Psychol Med. 2006;36:1535–40.

  140. 140.

    Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, et al. The classical complement cascade mediates CNS synapse elimination. Cell. 2007;131:1164–78.

  141. 141.

    Schwarz JM, Sholar PW, Bilbo SD. Sex differences in microglial colonization of the developing rat brain. J Neurochem. 2012;120:948–63.

  142. 142.

    Hanamsagar R, Alter MD, Block CS, Sullivan H, Bolton JL, Bilbo SD. Generation of a microglial developmental index in mice and in humans reveals a sex difference in maturation and immune reactivity. Glia. 2017;65:1504–20.

  143. 143.

    Rahimian R, Cordeau P, Jr., Kriz J. Brain response to injuries: When microglia go sexist. Neuroscience. 2018; doi: 10.1016/j.neuroscience.2018.02.048. [Epub ahead of print].

  144. 144.

    Bollinger JL, Bergeon Burns CM, Wellman CL. Differential effects of stress on microglial cell activation in male and female medial prefrontal cortex. Brain Behav Immun. 2016;52:88–97.

  145. 145.

    Bollinger JL, Collins KE, Patel R, Wellman CL. Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner. PLoS ONE. 2017;12:e0187631.

  146. 146.

    Barton EA, Baker C, Leasure JL. Investigation of sex differences in the microglial response to binge ethanol and exercise. Brain Sci. 2017; 7: 139.

  147. 147.

    Grissom NM, McKee SE, Schoch H, Bowman N, Havekes R, O’Brien WT, et al. Male-specific deficits in natural reward learning in a mouse model of neurodevelopmental disorders. Mol Psychiatry. 2018;23:544–55.

  148. 148.

    Reber J, Tranel D. Sex differences in the functional lateralization of emotion and decision making in the human brain. J Neurosci Res. 2017;95:270–8.

  149. 149.

    Sutterer MJ, Koscik TR, Tranel D. Sex-related functional asymmetry of the ventromedial prefrontal cortex in regard to decision-making under risk and ambiguity. Neuropsychologia. 2015;75:265–73.

  150. 150.

    Tranel D, Bechara A. Sex-related functional asymmetry of the amygdala: preliminary evidence using a case-matched lesion approach. Neurocase. 2009;15:217–34.

  151. 151.

    Tranel D, Damasio H, Denburg NL, Bechara A. Does gender play a role in functional asymmetry of ventromedial prefrontal cortex? Brain. 2005;128:2872–81.

Download references


Support was provided by NIH MH106330 (TMR) and the Simons Foundation Autism Research Initiative (NMG) and the Klarman Family Foundation (NMG).

Author information


  1. Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA

    • Nicola M. Grissom
  2. Department of Psychiatry and Behavioral Neurosciences, University of Cincinnati, Cincinnati, OH, 45237, USA

    • Teresa M. Reyes


  1. Search for Nicola M. Grissom in:

  2. Search for Teresa M. Reyes in:

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Teresa M. Reyes.

About this article

Publication history