Abstract
Psychogenic nonepileptic seizures (PNES) are relatively common occurrences in epilepsy centers, but their pathophysiology is still poorly understood. Research that elucidates the pathophysiology of PNES, including their neurobiological basis and biomarkers, may have important clinical implications. The literature provides some evidence that genetic factors, intrinsic factors, and environmental factors probably play a significant role as the biological underpinnings of PNES. Researchers may be able to learn more about the pathophysiology of PNES by investigating the effects of each of these factors on functional and structural brain connectivity.
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References
Asadi-Pooya AA, Emami Y, Emami M (2014) Psychogenic non-epileptic seizures in Iran. Seizure 23(3):175–177
Asadi-Pooya AA, Sperling MR (2015) Epidemiology of psychogenic non-epileptic seizures. Epilepsy Behav 46:60–65
O’Sullivan SS, Spillane JE, McMahon EM et al (2007) Clinical characteristics and outcome of patients diagnosed with psychogenic non-epileptic seizures: a 5-year review. Epilepsy Behav 11:77–84
Hubsch C, Baumann C, Hingray C et al (2011) Clinical classification of psychogenic non-epileptic seizures based on video-EEG analysis and automatic clustering. J Neurol Neurosurg Psychiatry 82:955–960
Bodde NM, Brooks JL, Baker GA et al (2009) Psychogenic non-epileptic seizures-definition, etiology, treatment and prognostic issues: a critical review. Seizure 18:543–553
Barzegaran E, Carmeli C, Rossetti AO, Frackowiak RS, Knyazeva MG (2015) Weakened functional connectivity in patients with psychogenic non-epileptic seizures (PNES) converges on basal ganglia. J Neurol Neurosurg Psychiatry. doi: 10.1136/jnnp-2014-309483. (pii: jnnp-2014-309483, Epub ahead of print)
Labate A, Cerasa A, Mula M et al (2012) Neuroanatomic correlates of psychogenic nonepileptic seizures: a cortical thickness and VBM study. Epilepsia 53(2):377–385
Ristić AJ, Daković M, Kerr M, Kovačević M, Parojčić A, Sokić D (2015) Cortical thickness, surface area and folding in patients with psychogenic nonepileptic seizures. Epilepsy Res 112:84–91
Hernando KA, Szaflarski JP, Ver Hoef LW, Lee S, Allendorfer JB (2015) Uncinate fasciculus connectivity in patients with psychogenic nonepileptic seizures: A preliminary diffusion tensor tractography study. Epilepsy Behav 45:68–73
Lee S, Allendorfer JB, Gaston TE et al (2015) White matter diffusion abnormalities in patients with psychogenic non-epileptic seizures. Brain Res 1620:169–176
Ding JR, An D, Liao W et al (2013) Altered functional and structural connectivity networks in psychogenic non-epileptic seizures. PLoS One 8(5):e63850
Ding J, An D, Liao W et al (2014) Abnormal functional connectivity density in psychogenic non-epileptic seizures. Epilepsy Res 108(7):1184–1194
Li R, Liu K, Ma X et al (2015) Altered functional connectivity patterns of the insular subregions in psychogenic non-epileptic seizures. Brain Topogr 28(4):636–645
van der Kruijs SJ, Jagannathan SR, Bodde NM et al (2014) Resting-state networks and dissociation in psychogenic non-epileptic seizures. J Psychiatr Res 54:126–133
van der Kruijs SJ, Bodde NM, Vaessen MJ et al (2012) Functional connectivity of dissociation in patients with psychogenic non-epileptic seizures. J Neurol Neurosurg Psychiatry 83(3):239–247
Li R, Li Y, An D, Gong Q, Zhou D, Chen H (2015) Altered regional activity and inter-regional functional connectivity in psychogenic non-epileptic seizures. Sci Rep 5:11635
Allendorfer JB, Szaflarski JP (2014) Contributions of fMRI towards our understanding of the response to psychosocial stress in epilepsy and psychogenic nonepileptic seizures. Epilepsy Behav 35:19–25
Arthuis M, Micoulaud-Franchi JA, Bartolomei F, McGonigal A, Guedj E (2015) Resting cortical PET metabolic changes in psychogenic non-epileptic seizures (PNES). J Neurol Neurosurg Psychiatry 86(10):1106–1112
Barzegaran E, Joudaki A, Jalili M, Rossetti AO, Frackowiak RS, Knyazeva MG (2012) Properties of functional brain networks correlate with frequency of psychogenic non-epileptic seizures. Front Hum Neurosci 6:335
Asadi-Pooya AA (2015) Neurobiological origin of psychogenic nonepileptic seizures: a review of imaging studies. Epilepsy Behav 52(Pt A):256–259
Reuber M (2009) The etiology of psychogenic non-epileptic seizures: toward a biopsychosocial model. Neurol Clin 27:909–924
Amstadter AB, Nugent NR, Koenen KC (2009) Genetics of PTSD: fear conditioning as a model for future research. Psychiatr Ann 39(6):358–367
Sokolowska E, Hovatta I (2013) Anxiety genetics—findings from cross-species genome-wide approaches. Biol Mood Anxiety Disord 3(1):9
Flint J, Kendler KS (2014) The genetics of major depression. Neuron 81(3):484–503
Guerrini R, Noebels J (2014) How can advances in epilepsy genetics lead to better treatments and cures? Adv Exp Med Biol 813:309–317
Smoller JW, Ripke S, Lee PH, Cross-Disorder Group of the Psychiatric Genomics Consortium et al (2013) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381(9875):1371–1379
Thomas AA, Preston J, Scott RC, Bujarski KA (2013) Diagnosis of probable psychogenic nonepileptic seizures in the outpatient clinic: does gender matter? Epilepsy Behav 29(2):295–297
Noe KH, Grade M, Stonnington CM, Driver-Dunckley E, Locke DE (2012) Confirming psychogenic non-epileptic seizures with video-EEG: sex matters. Epilepsy Behav 23(3):220–223
An D, Wu X, Yan B et al (2010) Clinical features of psychogenic non-epileptic seizures: a study of 64 cases in southwest China. Epilepsy Behav 17:408–411
Lesser RP (1996) Psychogenic seizures. Neurology 46(6):1499–1507
Asadi-Pooya AA, Emami M, Emami Y (2013) Gender differences in manifestations of psychogenic non-epileptic seizures in Iran. J Neurol Sci 332(1–2):66–68
Yang X, Wang S, Kendrick KM et al (2015) Sex differences in intrinsic brain functional connectivity underlying human shyness. Soc Cogn Affect Neurosci 10(12):1634–1643
Meyer-Lindenberg A (2009) Neural connectivity as an intermediate phenotype: brain networks under genetic control. Hum Brain Mapp 30(7):1938–1946
Posthuma D, de Geus EJ, Mulder EJ, Smit DJ, Boomsma DI, Stam CJ (2005) Genetic components of functional connectivity in the brain: the heritability of synchronization likelihood. Hum Brain Mapp 26(3):191–198
Reuber M, Pukrop R, Bauer J, Helmstaedter C, Tessendorf N, Elger CE (2003) Outcome in psychogenic nonepileptic seizures: 1 to 10-year follow-up in 164 patients. Ann Neurol 53:305–311
Durrant J, Rickards H, Cavanna AE (2011) Prognosis and outcome predictors in psychogenic nonepileptic seizures. Epilepsy Res Treat 2011:274736
Hyman S (2014) Mental health: depression needs large human-genetics studies. Nature 515(7526):189–191
Doré J, Simrén M, Buttle L, Guarner F (2013) Hot topics in gut microbiota. United Eur Gastroenterol J 1(5):311–318
Cryan JF, Dinan TG (2012) Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13(10):701–712
Roberfroid M, Gibson GR, Hoyles L et al (2010) Prebiotic effects: metabolic and health benefits. Br J Nutr 104(Suppl 2):S1–63
Magrone T, Jirillo E (2013) The interaction between gut microbiota and age-related changes in immune function and inflammation. Immun Ageing 10(1):31
Vaarala O (2013) Human intestinal microbiota and type 1 diabetes. Curr Diab Rep 13(5):601–607
Borre YE, Moloney RD, Clarke G, Dinan TG, Cryan JF (2014) The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. Adv Exp Med Biol 817:373–403
Diaz Heijtz R, Wang S, Anuar F et al (2011) Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci USA 108:3047–3052
Tillisch K, Labus J, Kilpatrick L et al (2013) Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144(7):1394–1401
Bravo JA, Forsythe P, Chew MV et al (2011) Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci USA 108(38):16050–16055
Williams BB, Van Benschoten AH, Cimermancic P et al (2014) Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe 16(4):495–503
Asadi-Pooya AA, Emami M (2013) Demographic and clinical manifestations of psychogenic non-epileptic seizures: the impact of co-existing epilepsy in patients or their family members. Epilepsy Behav 27(1):1–3
LaFrance WC Jr, Baird GL, Barry JJ, NES Treatment Trial (NEST-T) Consortium et al (2014) Multicenter pilot treatment trial for psychogenic non-epileptic seizures: a randomized clinical trial. JAMA Psychiatry 71(9):997–1005
Messaoudi M, Lalonde R, Violle N et al (2011) Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 105:755–764
LaFrance WC Jr, Leaver K, Stopa EG, Papandonatos GD, Blum AS (2010) Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures. Neurology 75(14):1285–1291
Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM (2002) Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 109:143–148
Hashimoto K, Iwata Y, Nakamura K et al (2006) Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism. Prog Neuropsychopharmacol Biol Psychiatry 30:1529–1531
Reis HJ, Nicolato R, Barbosa IG, Teixeira do Prado PH, Romano-Silva MA, Teixeira AL (2008) Increased serum levels of brain-derived neurotrophic factor in chronic institutionalized patients with schizophrenia. Neurosci Lett 439:157–159
Laske C, Stransky E, Eschweiler GW et al (2007) Increased BDNF serum concentration in fibromyalgia with or without depression or antidepressants. J Psychiatr Res 41:600–605
Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127
Bakvis P, Spinhoven P, Giltay EJ et al (2010) Basal hypercortisolism and trauma in patients with psychogenic nonepileptic seizures. Epilepsia 51(5):752–759
Pelletier A, Barul C, Féart C et al (2015) Mediterranean diet and preserved brain structural connectivity in older subjects. Alzheimers Dement 11(9):1023–1031
Astle DE, Barnes JJ, Baker K, Colclough GL, Woolrich MW (2015) Cognitive training enhances intrinsic brain connectivity in childhood. J Neurosci 35(16):6277–6283
Weissman DG, Schriber RA, Fassbender C et al (2015) Earlier adolescent substance use onset predicts stronger connectivity between reward and cognitive control brain networks. Dev Cogn Neurosci 16:121–129
Kim YJ, Cha EJ, Kim SM, Kang KD, Han DH (2015) The effects of Taekwondo training on brain connectivity and body intelligence. Psychiatry Investig 12(3):335–340
Herringa RJ, Birn RM, Ruttle PL et al (2013) Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence. Proc Natl Acad Sci USA 110(47):19119–19124
Elton A, Tripathi SP, Mletzko T et al (2014) Childhood maltreatment is associated with a sex-dependent functional reorganization of a brain inhibitory control network. Hum Brain Mapp 35(4):1654–1667
Acknowledgment
This is an unfunded study. I thank Jennifer Fisher Wilson for editorial assistance.
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Asadi-Pooya, A.A. Biological underpinnings of psychogenic nonepileptic seizures: directions for future research. Neurol Sci 37, 1033–1038 (2016). https://doi.org/10.1007/s10072-016-2540-y
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DOI: https://doi.org/10.1007/s10072-016-2540-y