Perfusion of the basolateral nucleus of the amygdala (BLA) is correlated with anxiety levels.

<p>Significant correlations were found between anxiety levels and perfusion of the left (A) and right (B) basolateral amygdala (BLA), as defined using anatomical regions-of-interest. These findings were then confirmed in a voxel-wise, whole brain regression analysis (C). In C, the BLA regions-of-interest are outlined in blue; the voxel-level display threshold is p<.005 (showing only clusters surviving whole-brain correction, see Methods). Clusters that showed cluster-wise significance (p<.05, whole brain corrected) are reported in the text and in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone-0097466-t002" target="_blank">Table 2</a>. R, right.</p

Perfusion of a distributed network of regions outside of the amygdala is also correlated with anxiety levels.

<p>A voxel-wise whole brain regression analysis revealed that, in addition to the basolateral amygdala (BLA), perfusion of the superior frontal gyri and posterior cingulate cortex (A), and anterior putamen (B), among other regions (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone-0097466-t002" target="_blank">Table 2</a>), were significantly correlated with anxiety levels. Whole-brain corrected results (see Methods) are displayed here using a voxel-level threshold of p<.005. Clusters that showed cluster-wise significance (p<.05, whole brain corrected) are reported in the text and in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone-0097466-t002" target="_blank">Table 2</a>. R, right; PCC, posterior cingulate cortex; SFG, superior frontal gyri.</p

Functional connectivity between the BLA and mPFC is inversely correlated with BLA perfusion and anxiety levels.

<p>An average map of basolateral amygdala (BLA) functional connectivity is shown in A. A whole-brain voxel-wise regression revealed that the strength of connectivity between the BLA and mPFC was negatively correlated with both: anxiety levels (B, C) and BLA perfusion (D, E). In A, B, and D, voxels with positive connectivity with the BLA (A) or showing positive correlations between their connectivity with the BLA and anxiety levels (B) or BLA perfusion (D) are shown in warm colors; voxels with negative correlations are shown in cool colors. The scatter plots in C and E are derived from the accompanying voxel-wise regression maps shown in B and D and are presented for the purpose of illustrating the range of values only. Data are displayed at a threshold of p<.05. The clusters indicated with arrows in B and D met a cluster-wise correction (FWE, p<.05) within the ventral mPFC. The peaks of the clusters in B (4, 2, −7) and D (2, 4, −4) were localized to the posterior-most portion of the SGC (with both clusters extending into the hypothalamus) using two independent atlases (the Talairach and Tournoux Stereotaxic Atlas <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-Tailarach1" target="_blank">[46]</a> and the Wake Forrest University (WFU) PickAtlas <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-Maldjian1" target="_blank">[47]</a>; see Methods). Prior work further supports this localization; previously reported sites that have been localized to the SGC (BA25), as well as an architectonic mapping of BA25 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-ngr1" target="_blank">[68]</a>, overlap with the two clusters reported here, with nearby peaks: 4, 2, −4 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-Mayberg3" target="_blank">[69]</a>; −2, 6, −6 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-Mayberg2" target="_blank">[8]</a>; −2, 8, −10 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-Mayberg4" target="_blank">[70]</a>; −3, 9, −6 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-Pizzagalli1" target="_blank">[71]</a>; −4, 9, −12 & 2, 11, −7 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-Kumano1" target="_blank">[72]</a>; 0, 8, −16 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone.0097466-Nahas1" target="_blank">[73]</a>. BLA, basolateral amygdala; FC, functional connectivity; Hy, hypothalamus; SGC, subgenual cingulate gyrus; mPFC, medial prefrontal cortex.</p

Basolateral amygdala functional connectivity.

<p>Areas of the brain showing significant functional connectivity with the basolateral amygdala (BLA) are listed. Clusters that are unshaded are those with positive functional coupling with the BLA, whereas clusters that are shaded grey are those showing negative functional coupling (inverse or anti-correlations) with the BLA (following global mean regression). Sites of connectivity within or abutting the BLA are not listed because of the difficulty of interpreting these findings. Also see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone-0097466-g003" target="_blank">Figure 3</a>. BA = Brodmann Area; Hemi = hemisphere; Tal = Talaraich coordinates.</p

Regions showing a correlation between perfusion and anxiety levels.

<p>Results of a whole-brain voxel-wise regression analysis of the regional cerebral blood flow (rCBF) data, using anxiety levels as a regressor, are listed. Sites which showed a significant positive correlation between rCBF and anxiety levels are listed below. Also, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097466#pone-0097466-g002" target="_blank">Figure 2</a>. BA = Brodmann Area; Hemi = hemisphere; Tal = Talaraich coordinates.</p

Genetic underpinnings of left superior temporal gyrus thickness in patients with schizophrenia

<div><p></p><p><i>Objectives.</i> Schizophrenia is a highly disabling psychiatric disorder with a heterogeneous phenotypic appearance. We aimed to further the understanding of some of the underlying genetics of schizophrenia, using left superior temporal gyrus (STG) grey matter thickness reduction as an endophenoptype in a genome-wide association (GWA) study. <i>Methods.</i> Structural magnetic resonance imaging (MRI) and genetic data of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia were used to analyse the interaction effects between 1,067,955 single nucleotide polymorphisms (SNPs) and disease status on left STG thickness in 126 healthy controls and 113 patients with schizophrenia. We next used a pathway approach to detect underlying pathophysiological pathways that may be related to schizophrenia. <i>Results.</i> No SNP by diagnosis interaction effect reached genome-wide significance (5 × 10^–8) in our GWA study, but 10 SNPs reached <i>P</i>-values less than 10^–6. The most prominent pathways included those involved in insulin, calcium, PI3K-Akt and MAPK signalling. <i>Conclusions.</i> Our strongest findings in the GWA study and pathway analysis point towards an involvement of glucose metabolism in left STG thickness reduction in patients with schizophrenia only. These results are in line with recently published studies, which showed an increased prevalence of psychosis among patients with metabolic syndrome-related illnesses including diabetes.</p></div