18F-Fallypride binding potential in patients with schizophrenia compared to healthy controls

Abstract

Background Molecular imaging of dopaminergic parameters has contributed to the dopamine hypothesis of schizophrenia, expanding our understanding of pathophysiology, clinical phenomenology and treatment. Our aim in this study was to compare 18F-fallypride binding potential BPND in a group of patients with schizophrenia-spectrum illness vs. controls, with a particular focus on the cortex and thalamus. Methods We acquired 18F-fallypride positron emission tomography images on 33 patients with schizophrenia spectrum disorder (28 with schizophrenia; 5 with schizoaffective disorder) and 18 normal controls. Twenty-four patients were absolutely neuroleptic naïve and nine were previously medicated, although only four had a lifetime neuroleptic exposure of greater than two weeks. Parametric images of 18F-fallypride BPND were calculated to compare binding across subjects. Results Decreased BPND was observed in the medial dorsal nucleus of the thalamus, prefrontal cortex, lateral temporal lobe and primary auditory cortex. These findings were most marked in subjects who had never previously received medication. Conclusions The regions with decreased BPND tend to match brain regions previously reported to show alterations in metabolic activity and blood flow and areas associated with the symptoms of schizophrenia.

Alterations in cortical and extrastriatal subcortical dopamine function in schizophrenia: systematic review and meta-analysis of imaging studies

“…For the meta-analysis of thalamic D 2 /D 3 receptors some studies reported results of overlapping samples, in which case the study with the largest sample was selected for inclusion. Thus, Buchsbaum et al 33 was excluded as there was sample overlap with Lehrer et al 34 Also there was sample overlap between Yasuno et al, 35 Yasuno et al 36 and Suhara et al 37 Only Suhara et al 37 was included as the thalamic region used was closest to that of other studies in the available literature. For Talvik et al 38 and Talvik et al 39 there appeared to be sample overlap.…”

“…However, the random-effects approach to meta-analysis we used is relatively robust to heterogeneity. 34 Implications and future directions An updated version of the dopamine hypothesis proposes that negative and cognitive symptoms of schizophrenia are secondary to cortical hypodopaminergia, whereas psychotic symptoms are secondary to subcortical hyperdopaminergia. 7,8 In the past two decades consistent in vivo evidence has accrued for subcortical hyperdopaminergia, with a large effect size elevation in striatal dopamine synthesis and release in schizophrenia 9 and potentially sufficient specificity to be a biomarker.…”

Pathway-Specific Dopamine Abnormalities in Schizophrenia

“…Of the nine studies in thalamus (16, 84–87, 94–97), only one ((94), which overlaps with (98)) found lower D 2 in SZ, and meta-analysis (88) was negative. Likewise, no differences were found in globus pallidus (97), amygdala (16, 86, 87), entorhinal cortex (16, 86) or hippocampus (84, 86, 87).…”

Paternal age effect: Replication in schizophrenia with intriguing dissociation between bipolar with and without psychosis

“…Endophenotypic markers associated with dopaminergic function are an intriguing area for study. Analysis of existing PET data using high‐affinity dopamine receptor ligands, such as with 18F‐fallypride [Lehrer et al, ] or 11C‐FLB‐457 [Talvik et al, ] may indicate variations in binding anomalies or ligand distribution (cortical, thalamic, striatal) as a function of paternal age, possibly identifying pathophysiologic or neurodevelopmental aspects characteristic of illness related to paternal age. Analysis of large existing prepulse inhibition datasets [Swerdlow et al, ] with respect to paternal age could also clarify phenotypic features associated with this risk factor.…”