The Relationship Between Frontostriatal Connectivity and Striatal Dopamine Function in Schizophrenia: An 18F-DOPA PET and Diffusion Tensor Imaging Study in Treatment Responsive and Resistant Patients
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC).Methods Twenty-four patients with schizophrenia and twelve HC underwent [<sup>18</sup>F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant K<sub>i</sub><sup>cer</sup>) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between K<sub>i</sub><sup>cer</sup> and FA in each group were evaluated using Spearman’s rho correlation coefficients.Results Non-TRS showed a negative correlation (r=-0.629, p=0.028) between connectivity of dorsolateral prefrontal cortex-associative striatum (DLPFC-AST) and dopamine synthesis capacity of associative striatum but this was not evident in TRS (r=-0.07, p=0.829) and HC (r=-0.277, p=0.384).Conclusion Our findings are consistent with the hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal cortex pathology localized to connectivity of DLPFC-AST in non-TRS, and also extend the hypothesis to suggest that different mechanisms underlie the pathophysiology of non-TRS and TRS.
Abstract
Objective Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC).Methods Twenty-four patients with schizophrenia and twelve HC underwent [<sup>18</sup>F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant K<sub>i</sub><sup>cer</sup>) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between K<sub>i</sub><sup>cer</sup> and FA in each group were evaluated using Spearman’s rho correlation coefficients.Results Non-TRS showed a negative correlation (r=-0.629, p=0.028) between connectivity of dorsolateral prefrontal cortex-associative striatum (DLPFC-AST) and dopamine synthesis capacity of associative striatum but this was not evident in TRS (r=-0.07, p=0.829) and HC (r=-0.277, p=0.384).Conclusion Our findings are consistent with the hypothesis of dysregulation of the striatal dopaminergic system being related to prefrontal cortex pathology localized to connectivity of DLPFC-AST in non-TRS, and also extend the hypothesis to suggest that different mechanisms underlie the pathophysiology of non-TRS and TRS.
참고문헌 (63)
- Delay J, "Therapeutic use in psychiatry of phenothiazine of central elective action (4560 RP)", Ann Med Psychol (Paris), 110, pp.112~117 (1952)
- Seeman P, "Antipsychotic drug doses and neuroleptic", dopamine receptors, 1976, pp.261, 717~719
- Seeman P, "Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons", Science, 188, pp.1217~1219 (1975)
- Creese I, "Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs", Science, 192, pp.481~483 (1976)
- McCutcheon RA, "Dopamine and glutamate in schizophrenia: biology, symptoms and treatment", World Psychiatry, 19, pp.15~33 (2020)
- Howes OD, "The nature of dopamine dysfunction in schizophrenia and what this means for treatment", Arch Gen Psychiatry, 69, pp.776~786 (2012)
- Lindenmayer JP, "Treatment refractory schizophrenia", Psychiatr Q, 71, pp.373~384 (2000)
- Demjaha A, "Dopamine synthesis capacity in patients with treatment-resistant schizophrenia", Am J Psychiatry, 169, pp.1203~1210 (2012)
- Jauhar S, "The relationship between cortical glutamate and striatal dopamine in first-episode psychosis: a cross-sectional multimodal PET and magnetic resonance spectroscopy imaging study", Lancet Psychiatry, 5, pp.816~823 (2018)
- DOPA PET study, "Neuropsychopharmacology", 2017, 941~950
- Howes OD, "A neurobiological hypothesis for the classification of schizophrenia: type A (hyperdopaminergic) and type B (normodopaminergic)", Br J Psychiatry, 205, pp.1~3 (2014)
- Jauhar S, "Determinants of treatment response in first-episode psychosis:an 18F-DOPA PET study", Mol Psychiatry, 24, pp.1502~1512 (2019)
- Howes OD, "The dopamine hypothesis of schizophrenia: version III--the final common pathway", Schizophr Bull, 35, pp.549~562 (2009)
- Davis KL, "Dopamine in schizophrenia:a review and reconceptualization", Am J Psychiatry, 148, pp.1474~1486 (1991)
- Deutch AY, "The regulation of subcortical dopamine systems by the prefrontal cortex: interactions of central dopamine systems and the pathogenesis of schizophrenia", J Neural Transm Suppl, 36, pp.61~89 (1992)
- Grace AA, "Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia", J Neural Transm Gen Sect, 91, pp.111~134 (1993)
- Weinberger DR, "Implications of normal brain development for the pathogenesis of schizophrenia", Arch Gen Psychiatry, 44, pp.660~669 (1987)
- Meyer-Lindenberg A, "Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia", Nat Neurosci, 5, pp.267~271 (2002)
- Kegeles LS, "Increased synaptic dopamine function in associative regions of the striatum in schizophrenia", Arch Gen Psychiatry, 67, pp.231~239 (2010)
- Fusar-Poli P, "Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis", Mol Psychiatry, 16, pp.67~75 (2011)
- McCutcheon R, "Defining the locus of dopaminergic dysfunction in schizophrenia: a meta-analysis and test of the mesolimbic hypothesis", Schizophr Bull, 44, pp.1301~1311 (2018)
- McCutcheon RA, "Schizophrenia, dopamine and the striatum: from biology to symptoms", Trends Neurosci, 42, pp.205~220 (2019)
- Goldman-Rakic PS, "Sensory-motor areas and aspects of cortical connectivity", pp.447~466 (1986), Springer
- Leroux E, "Abnormalities of fronto-subcortical pathways in schizophrenia and the differential impacts of antipsychotic treatment: a DTI-based tractography study", Psychiatry Res Neuroimaging, 280, pp.22~29 (2018)
- McCutcheon RA, "Schizophrenia-an overview", JAMA Psychiatry, 77, pp.201~210 (2020)
- Levitt JJ, "Reduced structural connectivity in frontostriatal white matter tracts in the associative loop in schizophrenia", Am J Psychiatry, 174, pp.1102~1111 (2017)
- D’Ambrosio E, "The relationship between grey matter volume and striatal dopamine function in psychosis: a multimodal 18F-DOPA PET and voxel-based morphometry study", Mol Psychiatry, 26, pp.1332~1345 (2021)
- DOPA PET and fMRI study, "Psychol Med", 2019, 2533~2542
- Alexander GE, "Functional architecture of basal ganglia circuits: neural substrates of parallel processing", Trends Neurosci, 13, pp.266~271 (1990)
- Howes OD, "Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology", Am J Psychiatry, 174, pp.216~229 (2017)
- First MB, "Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition" (2002), New York State Psychiatric Institute
- Andreasen NC, "Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs", Biol Psychiatry, 67, pp.255~262 (2010)
- Bai YM, "Equivalent switching dose from oral risperidone to risperidone longacting injection: a 48-week randomized, prospective, single-blind pharmacokinetic study", J Clin Psychiatry, 68, pp.1218~1225 (2007)
- Turkheimer FE, "Multiresolution analysis of emission tomography images in the wavelet domain", J Cereb Blood Flow Metab, 19, pp.1189~1208 (1999)
- -DOPA PET study, "Neuropsychopharmacology", 2014, 2397~2404
- fluorodopa study, "Arch Gen Psychiatry", 2004, 134~142
- Martinez D, "Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum", J Cereb Blood Flow Metab, 23, pp.285~300 (2003)
- Hammers A, "Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe", Hum Brain Mapp, 19, pp.224~247 (2003)
- Patlak CS, "Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations", J Cereb Blood Flow Metab, 5, pp.584~590 (1985)
- Behrens TE, "Probabilistic diffusion tractography with multiple fibre orientations: what can we gain?", Neuroimage, 34, pp.144~155 (2007)
- Fischl B, "FreeSurfer", Neuroimage, 62, pp.774~781 (2012)
- Desikan RS, "An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest", Neuroimage, 31, pp.968~980 (2006)
- Mather M, "The affective neuroscience of aging", Annu Rev Psychol, 67, pp.213~238 (2016)
- Nopoulos P, "Hyperactivity, impulsivity, and inattention in boys with cleft lip and palate: relationship to ventromedial prefrontal cortex morphology", J Neurodev Disord, 2, pp.235~242 (2010)
- Boes AD, "Right ventromedial prefrontal cortex: a neuroanatomical correlate of impulse control in boys", Soc Cogn Affect Neurosci, 4, pp.1~9 (2009)
- Kikinis Z, "Gray matter volume reduction in rostral middle frontal gyrus in patients with chronic schizophrenia", Schizophr Res, 123, pp.153~159 (2010)
- "This wiki page contains a historical archive of student questions and answers from various freesurfer courses"[URL]
- Pycock CJ, "Effect of lesion of cortical dopamine terminals on subcortical dopamine receptors in rats", Nature, 286, pp.74~76 (1980)
- Jaskiw GE, "Persistent elevations in dopamine and its metabolites in the nucleus accumbens after mild subchronic stress in rats with ibotenic acid lesions of the medial prefrontal cortex", Brain Res, 534, pp.321~323 (1990)
- Roberts AC, "6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin Card Sort Test: possible interactions with subcortical dopamine", J Neurosci, 14(5 Pt 1), pp.2531~2544 (1994)
- Braun AR, "Effects of ibotenic acid lesion of the medial prefrontal cortex on dopamine agonist-related behaviors in the rat", Pharmacol Biochem Behav, 46, pp.51~60 (1993)
- Flores G, "Enhanced amphetamine sensitivity and increased expression of dopamine D2 receptors in postpubertal rats after neonatal excitotoxic lesions of the medial prefrontal cortex", J Neurosci, 16, pp.7366~7375 (1996)
- Bertolino A, "The relationship between dorsolateral prefrontal neuronal N-acetylaspartate and evoked release of striatal dopamine in schizophrenia", Neuropsychopharmacology, 22, pp.125~132 (2000)
- Carletti F, "Alterations in white matter evident before the onset of psychosis", Schizophr Bull, 38, pp.1170~1179 (2012)
- Bloemen OJ, "White-matter markers for psychosis in a prospective ultra-high-risk cohort", Psychol Med, 40, pp.1297~1304 (2010)
- Brozoski TJ, "Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey", Science, 205, pp.929~932 (1979)
- Krabbe S, "Increased dopamine D2 receptor activity in the striatum alters the firing pattern of dopamine neurons in the ventral tegmental area", Proc Natl Acad Sci U S A, 112, pp.E1498~E1506 (2015)
- Simpson EH, "A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia", Neuron, 65, pp.585~596 (2010)
- Lin P, "Functional dysconnectivity of the limbic loop of frontostriatal circuits in firstepisode, treatment-naive schizophrenia", Hum Brain Mapp, 39, pp.747~757 (2018)
- White TP, "Dysfunctional striatal systems in treatment-resistant schizophrenia", Neuropsychopharmacology, 41, pp.1274~1285 (2016)
- McNabb CB, "Differences in white matter connectivity between treatment-resistant and treatmentresponsive subtypes of schizophrenia", Psychiatry Res Neuroimaging, 282, pp.47~54 (2018)
- Reis Marques T, "White matter integrity as a predictor of response to treatment in first episode psychosis", Brain, 137(Pt 1), pp.172~182 (2014)
- Ozcelik-Eroglu E, "Effect of clozapine on white matter integrity in patients with schizophrenia: a diffusion tensor imaging study", Psychiatry Res, 223, pp.226~235 (2014)