Reduced striatal dopamine synthesis capacity in patients with schizophrenia during remission of positive symptoms

Avram, Mihai; Brandl, Felix; Cabello, Jörge; Leucht, Claudia; Scherr, Martin; Mustafa, Mona; Leucht, Stefan; Ziegler, Sibylle und Sorg, Christian (2019): Reduced striatal dopamine synthesis capacity in patients with schizophrenia during remission of positive symptoms. In: Brain, Bd. 142: S. 1813-1826

Abstract

While there is consistent evidence for increased presynaptic dopamine synthesis capacity in the striatum of patients with schizophrenia during psychosis, it is unclear whether this also holds for patients during psychotic remission. This study investigates whether striatal dopamine synthesis capacity is altered in patients with schizophrenia during symptomatic remission of positive symptoms, and whether potential alterations relate to symptoms other than positive, such as cognitive difficulties. Twenty-three patients with schizophrenia in symptomatic remission of positive symptoms according to Andreasen, and 24 healthy controls underwent F-18-DOPA-PET and behavioural-cognitive assessment. Imaging data were analysed with voxel-wise Patlak modelling with cerebellum as reference region, resulting in the influx constant k(i)(cer) reflecting dopamine synthesis capacity. For the whole striatum and its subdivisions (i.e. limbic, associative, and sensorimotor), averaged regional k(i)(cer) values were calculated, compared across groups, and correlated with behavioural-cognitive scores, including a mediation analysis. Patients had negative symptoms (Positive and Negative Syndrome Scale-negative 14.13 +/- 5.91) and cognitive difficulties, i.e. they performed worse than controls in Trail-Making-Test-B (TMT-B;P = 0.01). Furthermore, k(i)(cer) was reduced in patients for whole striatum (P = 0.004) and associative (P = 0.002) and sensorimotor subdivisions (P = 0.007). In patients, whole striatum k(i)(cer) was negatively correlated with TMT-B (rho = -0.42, P = 0.04;i.e. the lower striatal k(i)(cer), the worse the cognitive performance). Mediation analysis showed that striatal k(i)(cer) mediated the group difference in TMT-B. Results demonstrate that patients with schizophrenia in symptomatic remission of positive symptoms have decreased striatal dopamine synthesis capacity, which mediates the disorder's impact on cognitive difficulties. Data suggest that striatal dopamine dysfunction contributes to cognitive difficulties in schizophrenia.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0006-8950
• Sprache: Englisch