Table 3 Studies of prefrontal cortex
From: The neuropathology of bipolar disorder: systematic review and meta-analysis
Study | Sample (Con/BD) | Sub-regions investigated | Stain | Parameters measured | Key significant findings in BD |
|---|---|---|---|---|---|
Guidotti et al. (2000) [23] | 15/15 | DLPFC (BA9), layer I | Nissl, reelin | Density of neurons | Density of reelin-positive neurons decreased (−28%). Overall neuronal density unchanged. |
Rajkowska et al. (2001) [24] | 11/10 | DLPFC (BA9), layers I, II, IIIa-c, IV, Va,b, VI | Nissl | Cortical and layer thickness. Density, size, and shape, of neurons and glia. | Sublayer IIIc thicker (16%). Decreased neuronal density in layer IIIa-c (−12–23%). Decreased density of pyramidal neurons in layers IIIa-c (20–32%) and Va (−27%). Decreased density of ‘medium-sized neurons’ (−35%). Decreased glial density in layer IIIc (−19%) and Vb (−12%). Glia enlarged in layer I ( + 9%) and IIIc ( + 7%). |
Uranova et al. (2001) [29] | 16/6 | Frontal pole (BA10), layer VI | EM | Oligodendroglial ultrastructure | Apoptosis and necrosis noted. No quantitative data presented. |
Webster et al. (2001) [30] | 15/15 | Middle frontal gyrus | pGFAP | Frequency and distribution of pGFAP-positive cells | Semi-quantitative study. No differences. |
Beasley et al. (2002a) [32] | 15/15 | DLPFC (BA9), layers I, II, III, IV, V/VI. | CB, CR, PV | Cortical thickness. Density of neurons. | Density of CB-neurons decreased in layers II (−22%) and III (−32%).a No other significant differences. |
Beasley et al. (2002b) [33] | 15/15 | DLPFC (BA9/46), white matter compartments I-V | MAP-2 | Density, size, and clustering of MAP-2-positive neurons. | No differences. |
Cotter et al. (2002b) [36] | 15/15 | DLPFC (BA9), layers I-VI | Nissl | Density, size, and clustering of neurons and glia. | Glial density reduced in layer VI (−7%).a,b Neuronal size decreased in layer III (−10%)a,b, V (−14%)band VI (−25%)b. No differences in cell density or clustering. |
Law and Harrison (2003) [41] | 15/15 | DLPFC (BA9), layers III and V | SMI32 | Density, size and shape of SMI32-positive neurons | No differences. |
Uranova et al. (2004) [44] | 15/15 | DLPFC (BA9), layer VI and white matter | Nissl | Cortical layer thickness. Density of oligodendroglia. | Decreased oligodendroglial density in layer VI (−29%). No difference in white matter. |
Cotter et al. (2005) [48] | 15/14 | Caudal OFC, layers I-VI | Nissl | Cortical layer thickness. Density and size of neurons and glia. | Decreased neuronal size in layer I (−21%)b and V (−20%)a,b. |
Toro et al. (2006) [52] | 15/15 | DLPFC (BA9) and OFC (BA11/47) | GFAP, GS | Immunoautoradiography. | Reduced GFAP signal in orbitofrontal cortex (−13%). No change in GS. |
Bielau et al. (2007) [55] | 19/11 | DLPFC and OFC | GAD | Density of GAD-positive neurons. | Increased density in OFC ( + 133%). |
Vostrikov et al. (2007) [58] | 15/15 | DLPFC (BA9), layer IIIa,b,c | Nissl | Size of pyramidal neurons. Density of perineuronal oligodendroglia. | Decreased pyramidal neuron size in layer IIIc (−4%). Fewer perineuronal oligodendroglia in layers IIIa (−29%), IIIb (−40%) and IIIc (−49%). |
Sakai et al. (2008) [62] | 5/5 | DLPFC (BA9), layers I, II, III, IV, V/VI | Nissl, CB, CR, PV | Density and size of neurons and glia. | Decreased neuronal density overall and in layer IV (−28%).c Increased density of ‘large’ CR-positive neurons in layer II ( + 209%). |
Cataldo et al. (2010) [67] | 10/10 | Prefrontal cortex | EM | Size of neuronal mitochondria. | Mitochondria smaller. |
Mosebach et al. (2013) [81] | 16/8 | DLPFC (BA9), grey and white matter | Nissl, olig1 | Density of oligodendroglia. | No differences. |
Hercher et al. (2014) [84] | 20/20 | DLPFC (BA9), white matter | Nissl, GFAP, Iba-1 | Density of cells. Size of nuclei. Clustering of cells. Area fraction occupied by GFAP- or Iba-1-positive cells. | Increased density of oligodendroglia (+17%). Decreased GFAP area fraction (−17%). Increased clustering of GFAP-positive astrocytes. No change in Iba-1. |
Konopaske et al. (2014) [85] | 19/9 | DLPFC (BA46), deep layer III pyramidal neurons | Golgi | Dendritic spine density. Spines per dendrite. Dendritic length. | Decreased spine density (−10%). Fewer spines per dendrite (−26%). Decreased dendritic length (−19%). |
Bernstein et al. (2015) [87] | 16/15 | DLPFC (BA9) | GS | Density of GS-positive astrocytes and GS-positive oligodendrocytes | No differences |