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

  1. EM: electron microscopy. GS: glutamine synthetase. MAP-2: microtubule-associated protein 2. OFC: orbitofrontal cortex. pGFAP: phosphorylated glial fibrillary acidic protein. SMI32: antibody against neurofilament proteins, labelling corticocortical projection neurons.
  2. For other abbreviations see earlier Tables, and text.
  3. aNoted as being non-significant when Bonferroni-corrected.
  4. bPercent differences in medians.
  5. cNoted as being non-significant after Abercrombie correction.