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S.23.02 Neuropsychological deficits in vascular brain disease
S.23 Cardiovascular diseases and psychiatric disorders the functioning of specific sites from subcortical to cortical regions (i.e., modulating the mesocortical pathway). References [1] Stip E, Fahim C, Mancini-Mar¨ıe A, Mensour B, 2005, Restoration of frontal activation during a treatment with quetiapine: an fMRI study of blunted affect in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 29(1), 21−6. [2] Stip E, Fahim C, Liddle P, Mancini-Marie A, Mensour B, Ait Bentaleb L, Beauregard M, 2005, Neural correlates of sad feelings in schizophrenia. Can J Psychiatry 50(14), 909–917. [3] Fahim C, Stip E, Mancini-Marie A, Gendron A, Mensour B, Beauregard M, 2005, Differential hemodynamic brain activity in schizophrenia patients with blunted affect during quetiapine treatment. J Clin Psychopharmacol 25(4), 367−71.
S.23 Cardiovascular diseases and psychiatric disorders S.23.01 Cardiovascular reflexes: physiological and pathophysiological influences from the brain C. Sevoz-Couche ° , M. Hamon, J.F. Bernard, R. Laguzzi. Facult´e de M´edecine Pierre et Marie Curie, UMR 677 ISERM/UPMC Pierre et Marie Curie-Site, Paris Cedex 13, France Dysautonomias are well known disorders of the autonomic nervous system. In particular, impaired baroreflex sensitivity has been reported in various neuropsychiatric disorders including depression, Parkinson’s disease, schizophrenia, autism and panic attacks, and very probably accounts for cardiovascular alterations associated with these CNS disorders. Impaired baroreflex sensitivity has also been observed during certain stressful situations. Indeed, the baroreflex cardiac response (bradycardia) is suppressed during “active” coping strategies such as the fight/flight defense reaction. Studies in our laboratory have shown that activation of 5-HT3 receptors in the nucleus tractus solitarius (NTS) inhibits the bradycardia of the baroreflex, thereby suggesting that these receptors play a role in stressinduced cardiovascular changes. Further investigations consisted of assessing whether these receptors could also participate in the inhibition of reflex bradycardia occurring during active coping strategies. In urethane-anesthetized rats, electrical stimulation of the dorsolateral part of the periaqueductal gray (dPAG), a bain structure causally related to the defense reaction, was found to deeply reduce similar blockade (by about 80 %) the cardiac response (bradycardia) to systemic administration of phenylephrine (baroreflex) (S´evoz et al., 1996; Callera et al., 1997). As expected from a mediation through NTS 5-HT3 receptors, bilateral intraNTS microinjections of granisetron (200 pmol), a 5-HT3 receptor antagonist, prevented the inhibitory effect of dPAG stimulation. These data show that NTS 5-HT3 receptors play a key role in the inhibition of bradycardia normally associated with the baroreflex. These receptors may therefore represent a relevant target for reducing cardiac complications of psychiatric disorders. References [1] S´evoz C, Nosjean A, Callera J-C, Machado BH, Hamon M, Laguzzi R, 1996, Stimulation of serotonin3 receptors in the NTS inhibits the cardiac Bezold-Jarisch reflex response. Am J Physiol 271, H80−87. [2] Callera J-C, S´evoz C, Laguzzi R, Machado BH, 1997, Microinjections of serotonin3 receptor agonist into the NTS of unanaesthetized rats inhibits the bradycardia evoked by activation of the baro- and chemoreflexes. J Autonom Nerv Syst 63, 127–136.
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S.23.02 Neuropsychological deficits in vascular brain disease M. van Zandvoort1 ° , G.M.S. Nys2 , E.H.F. Haan3 . 1 University Utrecht, Department of experimental Psychology/ Neurology, Utrecht, The Netherlands; 2 Ghent University Hospital, Laboratory for Neuropsychology, Ghent, Belgium; 3 Utrecht University, Department of Experimental Psychology/ Neurology, Utrecht, The Netherlands A cerebrovascular stroke is the number one cause of invalidity in the Western world in which neuropsychological deficits are often the most devastating consequences. In more than 70% of the stroke patients cognitive dysfunctions are present in the long term and hamper daily activities and negatively affect outcome. This even holds for supra and infratentorial single lacunar infarcts in for instance the brainstem that can induce persistent cognitive problems associated with (diffuse) neuronal derangement at distance from the actual lesion [1]. The complex character of the cognitive repercussions of stroke can be best harnessed by employing modern neuropsychological assessment procedures. The cognitive profile in the early stage after a stroke provides a strong prognostic marker for long term outcome which tend to exceed used medical prognostic models [2]. However, not only stroke but already disease of the cerebrovascular vasculature as for instance in diabetes or hypertension can affect cognition and as such form a risk factor for long term dependency and the development of vascular dementia and emotional disturbances (most often depression). In a recent review we conclude that the cognitive and emotional outcome is dependent on a combination of three factors, that is focal damage, diffuse neuronal dysfunction and patients variables such as age, gender and comorbidity [3]. Methods of lesion overlap (structural MRI), fMRI and TMS in combination with neuropsychological examination provide more insight into the underlying cause of the neuropsychological deficits and offer both diagnostic and therapeutic implications for the nearby future. References [1] van Zandvoort MJE, et al, 2005, Cognitive deficits and changes in neurometabolites after a lacunar infarct. J Neurol 252, 183–190. [2] Nys GMS, et al, 2006, The prognostic value of domain-specific cognitive abilities in acute first-ever stroke. Neurology 64, 821–827. [3] de Haan, et al, 2006, Cognitive functioning following stroke and vascular cognitive impairments. Curr Opin Neurol 19, 559–564.
S.23.03 ACE gene polymorphisms and depression: relation to cardiovascular disease T.C. Baghai1 ° , S. Haefner1 , C. Born1 , D. Eser1 , C. Schuele1 , P. Zill1 , G. Bedarida2 , C. von Schacky2 , R. Rupprecht1 , B. Bondy1 . 1 University of Munich, Psychiatry and Psychotherapy, Munich, Germany; 2 University of Munich, Preventive Cardiology, Munich, Germany Major depressive disorder (MDD) has been associated with cardiovascular disorders (CVD) and mortality. An enhanced hypothalamic–pituitary–adrenal (HPA)-axis activity and inflammatory processes have been associated with both disorders. Angiotensin-converting-enzyme (ACE) is assumed to influence the activity of the HPA system. The ACE gene, which is associated with CVD, is therefore a promising candidate gene for affective disorders. We investigated the genetic association between ACE gene polymorphisms and the susceptibility for MDD in two independent case-control samples together with the genetic association
S.23 Cardiovascular diseases and psychiatric disorders S.23.01 Cardiovascular reflexes: physiological and pathophysiological influences from the brain C. Sevoz-Couche ° , M. Hamon, J.F. Bernard, R. Laguzzi. Facult´e de M´edecine Pierre et Marie Curie, UMR 677 ISERM/UPMC Pierre et Marie Curie-Site, Paris Cedex 13, France Dysautonomias are well known disorders of the autonomic nervous system. In particular, impaired baroreflex sensitivity has been reported in various neuropsychiatric disorders including depression, Parkinson’s disease, schizophrenia, autism and panic attacks, and very probably accounts for cardiovascular alterations associated with these CNS disorders. Impaired baroreflex sensitivity has also been observed during certain stressful situations. Indeed, the baroreflex cardiac response (bradycardia) is suppressed during “active” coping strategies such as the fight/flight defense reaction. Studies in our laboratory have shown that activation of 5-HT3 receptors in the nucleus tractus solitarius (NTS) inhibits the bradycardia of the baroreflex, thereby suggesting that these receptors play a role in stressinduced cardiovascular changes. Further investigations consisted of assessing whether these receptors could also participate in the inhibition of reflex bradycardia occurring during active coping strategies. In urethane-anesthetized rats, electrical stimulation of the dorsolateral part of the periaqueductal gray (dPAG), a bain structure causally related to the defense reaction, was found to deeply reduce similar blockade (by about 80 %) the cardiac response (bradycardia) to systemic administration of phenylephrine (baroreflex) (S´evoz et al., 1996; Callera et al., 1997). As expected from a mediation through NTS 5-HT3 receptors, bilateral intraNTS microinjections of granisetron (200 pmol), a 5-HT3 receptor antagonist, prevented the inhibitory effect of dPAG stimulation. These data show that NTS 5-HT3 receptors play a key role in the inhibition of bradycardia normally associated with the baroreflex. These receptors may therefore represent a relevant target for reducing cardiac complications of psychiatric disorders. References [1] S´evoz C, Nosjean A, Callera J-C, Machado BH, Hamon M, Laguzzi R, 1996, Stimulation of serotonin3 receptors in the NTS inhibits the cardiac Bezold-Jarisch reflex response. Am J Physiol 271, H80−87. [2] Callera J-C, S´evoz C, Laguzzi R, Machado BH, 1997, Microinjections of serotonin3 receptor agonist into the NTS of unanaesthetized rats inhibits the bradycardia evoked by activation of the baro- and chemoreflexes. J Autonom Nerv Syst 63, 127–136.
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S.23.02 Neuropsychological deficits in vascular brain disease M. van Zandvoort1 ° , G.M.S. Nys2 , E.H.F. Haan3 . 1 University Utrecht, Department of experimental Psychology/ Neurology, Utrecht, The Netherlands; 2 Ghent University Hospital, Laboratory for Neuropsychology, Ghent, Belgium; 3 Utrecht University, Department of Experimental Psychology/ Neurology, Utrecht, The Netherlands A cerebrovascular stroke is the number one cause of invalidity in the Western world in which neuropsychological deficits are often the most devastating consequences. In more than 70% of the stroke patients cognitive dysfunctions are present in the long term and hamper daily activities and negatively affect outcome. This even holds for supra and infratentorial single lacunar infarcts in for instance the brainstem that can induce persistent cognitive problems associated with (diffuse) neuronal derangement at distance from the actual lesion [1]. The complex character of the cognitive repercussions of stroke can be best harnessed by employing modern neuropsychological assessment procedures. The cognitive profile in the early stage after a stroke provides a strong prognostic marker for long term outcome which tend to exceed used medical prognostic models [2]. However, not only stroke but already disease of the cerebrovascular vasculature as for instance in diabetes or hypertension can affect cognition and as such form a risk factor for long term dependency and the development of vascular dementia and emotional disturbances (most often depression). In a recent review we conclude that the cognitive and emotional outcome is dependent on a combination of three factors, that is focal damage, diffuse neuronal dysfunction and patients variables such as age, gender and comorbidity [3]. Methods of lesion overlap (structural MRI), fMRI and TMS in combination with neuropsychological examination provide more insight into the underlying cause of the neuropsychological deficits and offer both diagnostic and therapeutic implications for the nearby future. References [1] van Zandvoort MJE, et al, 2005, Cognitive deficits and changes in neurometabolites after a lacunar infarct. J Neurol 252, 183–190. [2] Nys GMS, et al, 2006, The prognostic value of domain-specific cognitive abilities in acute first-ever stroke. Neurology 64, 821–827. [3] de Haan, et al, 2006, Cognitive functioning following stroke and vascular cognitive impairments. Curr Opin Neurol 19, 559–564.
S.23.03 ACE gene polymorphisms and depression: relation to cardiovascular disease T.C. Baghai1 ° , S. Haefner1 , C. Born1 , D. Eser1 , C. Schuele1 , P. Zill1 , G. Bedarida2 , C. von Schacky2 , R. Rupprecht1 , B. Bondy1 . 1 University of Munich, Psychiatry and Psychotherapy, Munich, Germany; 2 University of Munich, Preventive Cardiology, Munich, Germany Major depressive disorder (MDD) has been associated with cardiovascular disorders (CVD) and mortality. An enhanced hypothalamic–pituitary–adrenal (HPA)-axis activity and inflammatory processes have been associated with both disorders. Angiotensin-converting-enzyme (ACE) is assumed to influence the activity of the HPA system. The ACE gene, which is associated with CVD, is therefore a promising candidate gene for affective disorders. We investigated the genetic association between ACE gene polymorphisms and the susceptibility for MDD in two independent case-control samples together with the genetic association