Canonical pathway enrichment analysis using Ingenuity.

<p><b>A</b> In the DLPFC. <b>B</b> In the ACC. <b>C</b> In the NAcc.</p

Demographic and physiological details for the subjects included in the qPCR validation sample (cohort 2).

<p>Mean±standard deviation values (SD) are presented. DLPFC: dorsolateral prefrontal cortex, ACC: anterior cingulate cortex, NAcc: nucleus accumbens, NA: not available.</p

Expression levels of 11 metallothionein probe sets corresponding to 9 gene as measured by microarrays (HG-U133Plus 2.0) in the ACC and NAcc of non-suicide (grey bars) and suicide (black bars) mood disorder subjects.

<p>Significant genes/probe sets are labeled by * (P<0.01) and # (P<0.05) signs.</p

qPCR Confirmation of decreased expression of metallothionein subfamilies 1 and 2.

<p>Significant differences are in bold for one tailed t-test confirming the direction of the change.</p

Mitochondrial polymorphisms were analyzed in PLINK for allelic association with 50,000 case-control permutations to obtain empirical p-values.

<p>The number of individuals with mtDNA alleles shown in the far right columns is from the Ingman mt database (URL <a href="http://www.genpat.uu.se/mtDB/" target="_blank">http://www.genpat.uu.se/mtDB/</a>). A preliminary odds-ratio was calculated by comparing the affected allele frequency to the Ingman database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004913#pone.0004913-Ingman1" target="_blank">[80]</a>. All case-control differences were either in the control region, or a synonymous substitution in the third position in coding regions.</p

Demographics of subjects from which DLPFC mtDNA was resequenced.

<p>All subjects had a rapid death and absence of prolonged hypoxia prior to death. An increased pH was found in MDD compared to the C group. Subjects with SZ died at younger age than C subjects. The Ct for extracted DNA was measured by qPCR for genomic DNA and was similar between groups.</p

The super haplogroup (U, K, UK) showed a shift in postmortem brain pH, and this finding was significant following permutation analysis.

<p>The histogram shows the frequency of the pH (bars) for the super haplogroup (red) compared to all other matrilineages (blue). The accumulated percentage (right y-axis) is shown as two lines with the super haplogroup (red line) and all other matrilineages (blue line). There were no subjects with a prolonged death, or agonal factors as rated according to the Hardy <i>et al.</i> scale <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004913#pone.0004913-Wester1" target="_blank">[98]</a>. PMI differences did not account for this significant effect, as PMI was equivalent between the super haplogroup and other haplogroups.</p

Transition/transversion bias calculation for mtDNA coding sequences shows difference between SZ and control group substitution.

*<p><i>R</i> = [A*G*<i>k₁</i>+T*C*<i>k₂</i>]/[(A+G)*(T+C)]. Codon positions included were 1st+2nd+3rd. All calculations were conducted in MEGA4 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004913#pone.0004913-Tamura1" target="_blank">[84]</a>.</p><p>This result is consistent with the increased synonymous substitution rate in SZ shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004913#pone-0004913-t004" target="_blank">Table 4</a>.</p

The haplogroup determination of mtDNA derived from DLPFC was condensed from Table 1 and showed that BD and SZ were over-represented in Pre HV haplogroup and MDD was over-represented in the “other” haplogroups.

<p>The chi-square for this table is (chi-square = 13.7 (6), p = 0.032).</p

The haplogroup determination of mtDNA derived from DLPFC showed 31 diverse haplogroups that could be reconstructed.

<p>The haplogroup determination of mtDNA derived from DLPFC showed 31 diverse haplogroups that could be reconstructed.</p