Regional patterns and clinical correlates of basal ganglia morphology in non-medicated schizophrenia

Abstract

Although structural changes of the basal ganglia are widely implicated in schizophrenia, prior findings in chronically medicated patients show that these changes relate to particular antipsychotic treatments. In unmedicated schizophrenia, local alterations in morphological parameters and their relationships with clinical measures remain unknown. Novel surface-based anatomical modelling methods were applied to magnetic resonance imaging data to examine regional changes in the shape and volume of the caudate, the putamen and the nucleus accumbens in 21 patients (19 males/2 females; mean age=30.7+/-7.3) who were either antipsychotic-naïve or antipsychotic-free for at least 1 year and 21 healthy comparison subjects (19 males/2 females; mean age=31.1+/-8.2). Clinical relationships of striatal morphology were based on exploratory analyses. Left and right global putamen volumes were significantly smaller in patients than controls; no significant global volume effects were observed for the caudate and the nucleus accumbens. However, surface deformation mapping results showed localized volume changes prominent bilaterally in medial/lateral anterior regions of the caudate, as well as in anterior and midposterior regions of the putamen, pronounced on the medial surface. A significant positive correlation was observed between right anterior putamen surface contractions and affective flattening, a core negative symptom of schizophrenia. The diagnostic effects of local surface deformations mostly pronounced in the associative striatum, as well as the correlation between anterior putamen morphology and affective flattening in unmedicated schizophrenia suggest disease-specific neuroanatomical abnormalities and distinct cortical-striatal dysconnectivity patterns relevant to altered executive control, motor planning, along with abnormalities of emotional processing.

FIGURE 1

Uncorrected surface maps depicting striatal shape differences in schizophrenia subjects (N=21) and healthy comparison subjects (N=21). Pink-to-red shadings indicate regions of contractions of the striatal surfaces (caudate, putamen, nucleus accumbens) in schizophrenia patients versus controls. Blue-to-light-blue shadings display regions of expansion of the surfaces. For all statistical maps, the color bar encodes the probability values associated with the F (1, 37)=4,11, p<.05 and F(1, 37)=7.38, p<.01. Corrected p-values after permutation testing for the whole map: Caudate: right, P=0.026; left, P=0.010; Putamen: right, P=0.043; left, P=0.006; Nucleus accumbens: right, P=0.076; left, P=0.056. R=Right; L=Left.

FIGURE 2

Top: Uncorrected surface maps show relationships between the blunted affect score on the scale of negative symptoms of the PANSS and regional deformations of putamen surface indicated as pink-to-red shadings within unmedicated patients with schizophrenia (N=21). For all statistical maps, the color bar encodes the probability values for the observed effects. Regions of surface expansions were not observed in the above analysis. Corrected p-values after permutation testing for the whole map: right, P=0.041; left, P=0.072. Bottom: R-values are plotted onto the surface at each point of the putamen using a color code (purple/light-blue/light-green shadings) to produce an r-map, which displays the significance of the relationship corresponding to the probability values of the surface map (Top). R=Right; L=Left