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Figures
- Fig. 1
(A) A photomicrograph showing anti-muscarinic M1 receptor antibody immunolabelled cells in Brodmann area 9 (arrows highlighting CHRM+ neurons). (B) An adjacent tissue section that was treated identically but not exposed to the anti-muscarinic M1 receptor antibody. (C) Levels (mean ± SEM) of [3H]pirenzepine binding to Brodmann area 9 for the cases included in this study that were part of a larger published cohort.17 (D–G) Levels (mean ± SEM) of CHRM1+ neurons, total neurons and total glia in (D) layer III and (E) layer V in Brodmann area 9 and (F) layer III and (G) layer V in Brodmann area 17 from people with schizophrenia, a subgroup of people with MRDS and people with schizophrenia who did not have that deficit (non-MRDS). a = p < 0.05, b = p < 0.01, c = p < 0.001, d = p < 0.0001. CHRM+ = muscarinic M1 receptor–positive; MRDS = muscarinic receptor deficit form of schizophrenia; SEM = standard error of the mean.
- Fig. 2
(A) A photomicrograph showing antimuscarinic M1 receptor antibody immunolabelled cells in the medial dorsal nucleus (arrows highlighting examples of CHRM+ neurons). (B–F) Levels (mean ± SEM) of CHRM1+ neurons, total neurons and total glia in (B) the medial dorsal nucleus, (C) the polymorphic layer of the dentate gyrus, (D) CA1, (E) CA2 and (F) CA3 from people with schizophrenia, a subgroup of people with MRDS and people with schizophrenia who did not have that deficit (non-MRDS). a = p < 0.05. CA = cornu ammonis; CHRM1+ = muscarinic M1 receptor–positive; MRDS = muscarinic receptor deficit form of schizophrenia; SEM = standard error of the mean.
Tables
- Table 1
Demographic, antipsychotic treatment, anticholinergic drug treatment and central nervous system collection characteristics
Cortex and thalamus; mean ± SEM* Hippocampus; mean ± SEM* Characteristic Controls (n = 12) Schizophrenia (n = 24) p value Non-MRDS (n = 12) MRDS (n = 12) p value F2,33 Controls (n = 5) Schizophrenia (n = 13) p value Non-MRDS (n = 7) MRDS (n = 6) p value F2,15 Sex, M/F, n 9/3 18/6 > 0.99 9/3 9/3 > 0.99 — 4/1 9/4 > 0.99 5/2 4/2 0.88 — Age, yr 48 ± 5.5 48 ± 3.4 0.95 48 ± 4.4 49 ± 5.3 0.99 0.007 29 ± 4.3 49 ± 4.2 0.02 47 ± 5.2 51 ± 7.3 0.06 3.05 PMI, h 46 ± 4.4 39 ± 2.5 0.09 39 ± 3.7 40 ± 3.5 0.2 1.5 45 ± 7 37 ± 3.9 0.33 37 ± 4.8 39 ± 7 0.62 0.48 pH 6.34 ± 0.09 6.27 ± 0.04 0.15 6.31 ± 0.05 6.22 ± 0.06 0.23 1.53 6.21 ± 0.12 6.29 ± 0.05 0.5 6.32 ± 0.07 6.25 ± 0.07 0.67 0.41 Suicide,† Y/N, n 0/12 7/17 — 3/9 4/8 0.99 — — 4/9 — 2/5 2/4 0.99 — DI, yr — 20.5 ± 3.1 — 21 ± 3.7 20 ± 5.2 0.98 — — 20 ± 4.1 — 19 ± 4.5 21 ± 7.6 0.93 — FRADD‡ — 542 ± 109 — 638 ± 172 446 ± 136 0.39 — — 718 ± 183 — 783 ± 265 640 ± 275 0.71 — Anticholinergic drug exposure,§ 0/12 11/13 — 5/7 6/6 > 0.99 — 0/5 6/7 — 2/5 4/2 0.29 — DI = duration of illness; F = female; FRADD = final recorded antipsychotic drug dose; M = male; MRDS = muscarinic receptor deficit form of schizophrenia; PMI = postmortem interval; SEM = standard error of the mean.
↵* Unless otherwise indicated.
↵† Listed as cause of death by coroner.
↵‡ Shown as mg chlorpromazine equivalents per day.
↵§ Recorded exposure anywhere in case history.
- Table 2
The effect of sex and suicide (schizophrenia only) on levels of muscarinic receptor–positive neurons, total neurons and total glia in Brodmann areas 9 and 17, medial dorsal nucleus and regions of the hippocampus*
Sex Suicide Region Layer Male Female t d.f. p value Suicide Non-suicide t d.f. p value BA9 Layer III CHRM1+ neurons 841 ± 77 680 ± 158 1.00 34 0.32 510 ± 116 697 ± 81 1.28 22 0.21 Total neurons 1392 ± 70 1604 ± 37 1.70 34 0.10 1407 ± 117 1422 ± 98 0.09 22 0.93 Total glia 2187 ± 156 2438 ± 103 0.89 34 0.37 2008 ± 267 2290 ± 214 0.75 22 0.46 Layer V CHRM1+ neurons 1016 ± 98 882 ± 175 0.68 34 0.50 624 ± 151 817 ± 99 1.06 22 0.30 Total neurons 1541 ± 58 1566 ± 73 0.22 34 0.82 1407 ± 70 1525 ± 59 1.14 22 0.27 Total glia 2172 ± 136 2391 ± 80 0.91 34 0.36 2191 ± 263 2152 ± 161 0.13 22 0.90 BA17 Layer III CHRM1+ neurons 805 ± 101 543 ± 137 1.35 34 0.18 578 ± 200 547 ± 80 0.17 22 0.86 Total neurons 1701 ± 87 1629 ± 91 0.45 34 0.66 1590 ± 257 1662 ± 96 0.75 22 0.74 Total glia 2355 ± 166 2671 ± 114 1.06 34 0.30 2135 ± 396 2421 ± 197 0.72 22 0.48 Layer V CHRM1+ neurons 473 ± 83 354 ± 109 0.75 34 0.45 335 ± 73 254 ± 34 0.26 22 0.26 Total neurons 1312 ± 64 1192 ± 64 1.02 34 0.32 1320 ± 158 1197 ± 66 0.86 22 0.40 Total glia 2297 ± 64 2896 ± 191 1.96 34 0.06 2180 ± 453 2471 ± 192 0.7 22 0.49 MDN CHRM1+ neurons 478 ± 45 454 ± 45 0.58 34 0.56 374 ± 21 502 ± 23 3.33 22 0.003 Total neurons 596 ± 30 544 ± 52 0.88 34 0.39 477 ± 34 619 ± 37 2.26 22 0.03 Total glia 2777 ± 170 2847 ± 266 0.22 34 0.83 2438 ± 331 3054 ± 2303 1.47 22 0.15 Hippocampus CA3 CHRM1+ neurons 193 ± 33 155 ± 52 0.62 16 0.540 213 ± 72 132 ± 32 1.20 11 0.25 Total neurons 350 ± 12 379 ± 14 1.33 16 0.200 363 ± 20 349 ± 13 0.59 11 0.56 Total glia 1477 ± 56 1315 ± 185 1.13 16 0.270 1416 ± 180 1396 ± 95 0.11 11 0.91 CA2 CHRM1+ neurons 153 ± 35 179 ± 63 0.37 16 0.720 151 ± 36 129 ± 40 0.33 11 0.75 Total neurons 441 ± 37 534 ± 37 2.84 16 0.010 452 ± 35 465 ± 29 0.27 11 0.79 Total glia 1647 ± 52 1462 ± 154 1.48 16 0.160 1584 ± 176 1581 ± 85 0.01 11 0.99 CA1 CHRM1+ neurons 44 ± 8.1 27 ± 12 1.12 16 0.280 36 ± 16 33 ± 8.9 0.17 11 0.86 Total neurons 384 ± 15 442 ± 23 4.53 16 0.0003 440 ± 13 410 ± 21 0.38 11 0.39 Total glia 1096 ± 46 959 ± 90 0.16 16 0.160 1057 ± 81 1100 ± 66 0.38 11 0.71 Poly CHRM1+ neurons 116 ± 20 117 ± 39 0.01 16 0.990 110 ± 45 94 ± 22 0.36 11 0.72 Total neurons 210 ± 11 272 ± 16 2.96 16 0.009 223 ± 28 237 ± 17 0.43 11 0.68 Total glia 1579 ± 66 1393 ± 112 3.19 16 0.006 1576 ± 159 1467 ± 72 0.73 11 0.48 BA = Brodmann area; CA = cornu ammonis; CHRM1+ = muscarinic M1 receptor–positive; MDN = medial dorsal nucleus; poly = polymorphic layer of the dentate gyrus; SEM = standard error of the mean.
↵* All data listed as mean ± SEM of cells per mm3 × 10−2.
- Table 3
Levels of CHRM1+ neurons, total neurons and total glia in layers III and V in Brodmann areas 9 and 17 from people with schizophrenia who had or had not been prescribed anticholinergic medication in life
Cortical region Cortical layer Anticholinergic, mean ± SEM (n = 11) No anticholinergic, mean ± SEM (n = 13) t* p value BA9 III CHRM1+ neurons 586 ± 119 683 ± 81 0.70 0.49 Total neurons 1437 ± 126 1403 ± 97 0.22 0.83 Total glia 2421 ± 246 2055 ± 229 1.07 0.30 V CHRM1+ neurons 616 ± 134 863 ± 101 1.50 0.15 Total neurons 1497 ± 64 1486 ± 68 0.12 0.91 Total glia 2264 ± 176 2092 ± 195 0.62 0.54 BA17 III CHRM1+ neurons 429 ± 53 664 ± 133 1.53 0.14 Total neurons 1655 ± 124 1629 ± 152 0.13 0.90 Total glia 2458 ± 227 2235 ± 272 0.62 0.54 V CHRM1+ neurons 236 ± 32 314 ± 52 1.22 0.24 Total neurons 1201 ± 85 1259 ± 98 0.44 0.66 Total glia 2531 ± 249 2263 ± 274 0.71 0.48 BA = Brodmann area; CHRM1+ = muscarinic M1 receptor–positive; SEM = standard error of the mean.
↵* Degrees of freedom = 22.
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