Abstract
The neurochemical basis of aggressive behavior in humans is not fully understood. In this study we explored the relationship between aggressiveness (as measured by the Overt Aggression Scale), cognitive performance (as measured by the Mini Mental State Examination), and biochemical markers of dopamine neurotransmission (homovanillic acid, HVA) and nitric oxide synthesis (nitrite plus nitrate, NO x ) in cerebrospinal fluid from 70 patients with acute brain disorders, mainly brain infections. Aggressive behavior and cognitive performance showed an inverse correlation. NO x /HVA ratio was inversely correlated to aggressive behavior, and positively correlated to cognitive performance. A subanalysis with antipsychotic-naïve patients confirmed those results. The balance between nitric oxide and dopamine could be related to the cognitive control of aggressive impulse.
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Grafman J, Schwab K, Warden D, Pridgen A, Brown HR, Salazar AM (1996) Frontal lobe injuries, violence, and aggression: a report of the Vietnam head injury study. Neurology 46:1231–1238
Ramirez-Bermudez J, Ruiz-Chow A, Pérez-Neri I, Soto-Hernández JL, Flores-Hernández R, Nente F, Montes S, Rios C (2008) Cerebrospinal fluid homovanillic acid is correlated to psychotic symptoms in neurological patients with delirium. Gen Hosp Psychiatry 30:337–343
Kunik ME, Snow AL, Davila JA, Steele AB, Balasubramanyam V, Doody RS, Schulz PE, Kalavar JS, Morgan RO (2010) Causes of aggressive behavior in patients with dementia. J Clin Psychiatry. Epub ahead of print
Reif A, Jacob CP, Rujescu D, Herterich S, Lang S, Gutknecht L, Baehne CG, Strobel A, Freitag CM, Giegling I, Romanos M, Hartmann A, Rösler M, Renner TJ, Fallgatter AJ, Retz W, Ehlis AC, Lesch KP (2009) Influence of functional variant of neuronal nitric oxide synthase on impulsive behaviors in humans. Arch Gen Psychiatry 66:41–50
Chiavegatto S, Nelson RJ (2003) Interaction of nitric oxide and serotonin in aggressive behaviour. Horm Behav 44:233–241
Neumann ID, Veenema AH, Beiderbeck DI (2010) Aggression and anxiety: social context and neurobiological links. Front Behav Neurosci 4:1–16
Trainor BC, Workman JL, Jessen R, Nelson RJ (2007) Impaired nitric oxide synthase signaling dissociates social investigation and aggression. Behav Neurosci 121:362–369
Nelson RJ, Trainor BC, Chiavegatto S, Demas GE (2006) Pleiotropic contributions of nitric oxide to aggressive behavior. Neurosci Biobehav Rev 30:346–355
Craig IW, Halton KE (2009) Genetics of human aggressive behaviour. Hum Genet 126:101–113
Arancio O, Kiebler M, Lee CJ, Lev-Ram V, Tsien RY, Kandel ER, Hawkins RD (1996) Nitric oxide acts directly in the presynaptic neuron to produce long-term potentiation in cultured hippocampal neurons. Cell 87:1025–1035
Seo D, Patrick CJ (2008) Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders. Aggress Violent Behav 13:83–395
Tsiouris JA (2010) Pharmacotherapy for aggressive behaviours in persons with intellectual disabilities: treatment or mistreatment? J Intellect Disabil Res 54:1–16
Rudissaar R, Harro J, Pruus K, Rinken A, Allikmets L (2008) Repeated administration of the dopaminergic agonist apomorphine: development of apomorphine aggressiveness and changes in the interaction between dopamine D2 receptors and G-proteins. Pharmacol Rep 60:827–833
Smith JCE, Whitton PS (2001) The regulation of NMDA-evoked dopamine release by nitric oxide in the frontal cortex and raphe nuclei of the freely moving rat. Brain Res 889:57–62
Karolewicz B, Paul IA, Antkiewicz-Michaluk L (2001) Effect of nos inhibitor on forced swim test and neurotransmitters turnover in the mouse brain. Pol J Pharmacol 53:587–596
Hoque KE, Indorkar RP, Sammut S, West AR (2010) Impact of dopamine–glutamate interactions on striatal neuronal nitric oxide synthase activity. Psychopharmacology 207:571–581
Ramirez J, Garnica R, Boll MC, Montes S, Rios C (2004) Low concentration of nitrite and nitrate in the cerebrospinal fluid from schizophrenic patients: a pilot study. Schizophr Res 68:357–361
Perez-Neri I, Castro E, Montes S, Boll MC, Barges-Coll J, Soto-Hernández JL, Ríos C (2007) Arginine, citrulline and nitrate concentrations in the cerebrospinal fluid from patients with acute hydrocephalus. J Chromatogr B 851:250–256
American Psychiatric Assciation (1994) DSM-IV. American Psychiatric Press, Washington
Yudofsky SC, Silver JM, Jackson W, Endicott J, Williams D (1986) Aggression scale for the objective rating of verbal and physical aggression. Am J Psychiatry 143:35–39
Paez F, Licon E, Fresan A, Apiquian R, Herrera-Estrella M, Garcia-Anaya M, Robles-Garcia R, Pinto T (2002) Estudio de validez y confiabilidad de la escala de agresividad explícita en pacientes psiquiátricos. Salud Mental 25:21–26
Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Nelson RJ, Trainor BC (2007) Neural mechanisms of aggression. Nat Rev Neurosci 8:536–546
Jollant F, Lawrence NS, Olie E, O’Daly O, Malafosse A, Courtet P, Phillips ML (2010) Decreased activation of lateral orbitofrontal cortex during risky choices under uncertainty is associated with disadvantageous decision-making and suicidal behavior. Neuroimage 51:1275–1281
Bondar NP, Boyarskikh UA, Kovalenko IL, Filipenko ML, Kudryavtseva NN (2009) Molecular implications of repeated aggression: TH, DAT1, SNCA and BDNF gene expression in the VTA of victorious male mice. PLoS One 4:e4190
Soderstrom H, Blennow K, Sjodin AK, Forsman A (2003) New evidence for an association between the CSF HVA: 5-HIAA ratio and psychopathic traits. J Neurol Neurosurg Psychiatry 74:918–921
Wultsch T, Chourbaji S, Fritzen S, Kittel S, Grünblatt E, Gerlach M, Gutknecht L, Chizat F, Golfier G, Schmitt A, Gass P, Lesch KP, Reif A (2007) Behavioural and expressional phenotyping of nitric oxide synthase-I knockdown animals. J Neural Trans Suppl 72:69–85
Weitzdoerfer R, Hoeger H, Engidawork E, Engelmann M, Singewald N, Lubec G, Lubec B (2004) Neuronal nitric oxide synthase knock-out mice show impaired cognitive performance. Nitric Oxide 103:130–140
Rujescu D, Giegling I, Mandelli L, Schneider B, Hartmann AM, Schnabel A, Maurer K, Möller HJ, Serretti A (2008) NOS-I and -III gene variants are differentially associated with facets of suicidal behavior and aggression-related traits. Am J Med Genet B Neuropsychiatr Genet 147B:42–48
Wegener G, Volke V, Rosenberg R (2000) Endogenous nitric oxide decreases hippocampal levels of serotonin and dopamine in vivo. Br J Pharmacol 130:575–580
Wang JQ, Lau YS (2001) Dose-related alteration in nitric oxide synthase mRNA expression induced by amphetamine and the full D1 dopamine receptor agonist SKF-82958 in mouse striatum. Neurosci Lett 311:5–8
Hoptman MJ, D’Angelo D, Catalano D, Mauro CJ, Shehzad ZE, Kelly AM, Castellanos FX, Javitt DC, Milham MP (2009) Amygdalofrontal functional disconnectivity and aggression in schizophrenia. Schizophr Bull. doi:10.1093/schbul/sbp012
Cruz-Rizzolo RJ, Horta-Júnior Jde A, Bittencourt JC, Ervolino E, de Oliveira JA, Casatti CA (2006) Distribution of NADPH-diaphorase-positive neurons in the prefrontal cortex of the Cebus monkey. Brain Res 1083(1):118–133
Reif A, Herterich S, Strobel A, Ehlis AC, Saur D, Jacob CP, Wienker T, Töpner T, Fritzen S, Walter U, Schmitt A, Fallgatter AJ, Lesch KP (2006) A neuronal nitric oxide synthase (NOS-I) haplotype associated with schizophrenia modifies prefrontal cortex function. Mol Psychiatry 11:286–300
Sammut S, Park DJ, West AR (2007) Frontal cortical afferents facilitate striatal nitric oxide transmission in vivo via a NMDA receptor and neuronal NOS-dependent mechanism. J Neurochem 103:1145–1156
Overeem KA, Ota KT, Monsey MS, Ploski JE, Schafe GE (2010) A role for nitric oxide-driven retrograde signaling in the consolidation of a fear memory. Front Behav Neurosci 4:2
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Ramírez-Bermudez, J., Perez-Neri, I., Montes, S. et al. Imbalance Between Nitric Oxide and Dopamine May Underly Aggression in Acute Neurological Patients. Neurochem Res 35, 1659–1665 (2010). https://doi.org/10.1007/s11064-010-0227-y
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DOI: https://doi.org/10.1007/s11064-010-0227-y