Brain Structural Abnormalities in Posttraumatic Stress Disorder and Relations with Sleeping Problems


Literature (author; year)

PTSD (trauma; gender; N)

Control (trauma; gender; N)

Measure

Brain structures

Hippocampus (HC)

Amygdala

Prefrontal and cingulate cortices

Other brain regions

Abe et al. (2006)

Attack; mixed; 9

Trauma exposed; mixed; 16

DTI
  
FA increase in the left ACC
 
Baldacara et al. (2011)

Violence; mixed; 42

Trauma exposed; mixed; 42

Volume
   
Smaller left cerebellum and vermis

Bing et al. (2013)

MVA, mixed, 20

Healthy; mixed; 20

Thickness
  
Thinner in left mPFC, inferior frontal, ACC

Thinner in right superior temporal cortex

Bonne et al. (2001)

Unclear; mixed; 10

Trauma exposed; mixed; 27

Volume

No group difference and over time change

No group and overtime change
  
Bremner et al. (1995)

Combat; mixed; 26

Trauma-free; mixed; 22

Volume

Smaller right HC
   
Bremner et al. (1997)

Childhood abuse; mixed; 17

Trauma-free; mixed; 17

Volume

Smaller left HC

No difference
 
No difference in temporal lobe

Bremner et al. (2003)

Childhood abuse; F; 10

Childhood abuse; F; 12; trauma-free; F; 11

Volume

Smaller right and left HC in PTSD vs two control groups
   
Cardenas et al. (2011)

Veteran; M; 25

Trauma exposed; M; 22

Volume (DBM)
  
PTSD: non-PTSD: no difference

PTSD: non-PTSD: no difference

worsen PTSD: non-PTSD: decrease in dlPFC, ACC

worsen PTSD: non-PTSD: decrease in insula, anterior temporal lobe

Chao et al. (2012)

Combat; M; 21

Combat; M; 20

VBM
   
Lower density in left precentral, occipital, and right angular cortices

Chao et al. (2013)

Combat; mixed; current PTSD; 39, remitted PTSD; 34

Combat; mixed; 43, nonexposed; mixed; 75;

Volume

Smaller HC in current PTSD

No difference

Smaller caudal ACC in current PTSD

Smaller insula, corpus callosum, total brain volume in current PTSD

Chen et al. (2009)

Disaster; mixed; 12

Trauma exposed; mixed; 12

VBM
  
Lower density in left medial frontal gyrus

Lower density in bilateral insula

Chen et al. (2012)

Disaster; M; 10

Trauma exposed; M; 10, trauma-free; M; 20;

VBM
  
Lower density in left ACC in PTSD vs trauma-free control
 
Corbo et al. (2005)

Mixed trauma; mixed; 14

Trauma-free; mixed; 14

VBM
  
Lower density in right cingulate gyrus

Lower density in left insula

Depue et al. (2014)

Combat with PTSD+TBI; mixed; 16

Combat; mixed; 21

VBM volume
 
Decreased density and volume
  
Eckart et al. (2011)

Mixed civilian traumas; M; 20

Trauma exposed; M; 19

Volume, VBM
  
Smaller volume in left rostral middle frontal in PTSD and isthmus cingulate cortices in PTSD and trauma-exposed control

Smaller right volume in right inferior parietal cortex in PTSD and trauma-exposed control

Trauma-free; M; 13

Lower density in bilateral ACC, left isthmus cingulate cortices in PTSD and trauma-exposed control

Lower density in right inferior parietal cortex in PTSD and trauma-exposed control

Emdad et al. (2006)

Mixed; M; 23

Trauma-free; M; 17

VBM

Smaller bilateral HC
   
Volume

Lower density in right HC

Fani et al. (2012)

Interpersonal trauma; F; 25

Trauma exposed; F; 26

DTI
  
Lower FA in bilateral posterior cingulum

Lower FA in left superior longitudinal fasciculus, high FA in right lateral occipital cortex, uncorrected

Felmingham et al. (2009)

Civilian trauma; mixed; 21

Trauma exposed; mixed; 17

VBM

Lower density in bilateral HC
 
Lower density in bilateral rostral ACC, bilateral superior medial frontal cortex, left orbitofrontal gyrus

Lower density in left middle temporal gyrus and left supramarginal gyrus

Fennema-Notestine et al. (2002)

Intimate partner violence; F; 11

Trauma exposed; F; 11

Volume

No difference

No difference
  
Trauma-free; F; 17

Geuze et al. (2008)

Veteran; M; 25

Trauma exposed; M; 25

Cortical thickness
  
Thinner in bilateral superior, middle frontal, and left inferior frontal gyri

Thinner in left superior, temporal gyrus

Gilbertson et al. (2002)

Combat; monozygotic twins; M; 17

Trauma exposed; monozygotic twins; M; 23

Volume

Smaller HC in PTSD twin pairs than control twin pairs

No difference
  
Golier et al. (2005)

Holocaust; mixed; 14

Trauma-free; mixed; 20

Volume

No difference
  
Larger left lateral temporal lobe and bilateral superior temporal gyrus in two holocaust groups

Trauma-exposed; mixed; 13

Gurvits et al. (1996)

Combat; M; 7

Trauma exposed; M; 7

Volume

Smaller in bilateral HC in PTSD

No difference
 
CSF volume increased in PTSD and trauma-exposed groups

Trauma-free; M; 8

Hakamata et al. (2007)

Cancer; F; 14

Cancer; F; 100; healthy; F; 70

VBM
  
Smaller gray matter density in right orbitofrontal cortex
 
Hara et al. (2008)

Cancer; F; 15

Cancer; F; 15

Volume

No difference

No difference
  
Healthy; F; 15

Hedges et al. (2007)

Combat; M; 6

Trauma exposed; M; 5

Volume

No difference
  
Smaller right superior, middle, inferior temporal volume, fusiform and parahippocampus volume

Herringa et al. (2012)

Combat; mixed; 13;

Combat; mixed; 15;

VBM
  
Lower density in subgenual ACC and right middle frontal gyrus

Lower density in caudate, hypothalamus, left insula, middle temporal gyrus

Irle et al. (2009)

Childhood abuse; F; 10

Trauma-free; F; 25

Volume

Smaller bilateral HC

Smaller bilateral amygdala
  
Jatzko et al. (2006)

Disaster; mixed; 15

Trauma-free; mixed; 15

Volume

No difference
  
No difference in total brain volume, gray and white matter volume, and density

VBM

Kasai et al. (2008)

Combat; monozygotic twins; M; 18

Trauma exposed; monozygotic twins; M; 23

VBM

Lower density in right HC in PTSD
 
Lower density in pregenual ACC in PTSD

Lower density in bilateral insula in PTSD

Kim et al. (2006)

Disaster; mixed; 21

Trauma-free; mixed; 21

DTI
  
Lower FA in the left rostral, subgenual, dorsal ACC
 
Kitayama et al. (2006)

Abuse; mixed; 8

Trauma-free; mixed; 13

Volume
  
Smaller volume in right ACC
 
Kitayama et al. (2007)

Abuse; F; 9

Trauma-free; F; 9

Volume
   
Smaller posterior mid-body/total CC area ratio

Kuo et al. (2012)

Combat; mixed; 42

Trauma exposed; mixed; 45

Volume
 
Larger volume
  
Bossini et al. (2008)

Mixed trauma; mixed; 34

Trauma-free; mixed; 34

Volume

Smaller bilateral HC
  
Smaller brain gray matter volume, larger brain white matter volume, no difference in brain volume and CSF volume

Levitt et al. (2006)

Combat; monozygotic twins; M; 20

Trauma exposed; monozygotic twins; M; 23

Volume
   
No differences in vermis volume

Levy-Gigi et al. (2013)

Mixed trauma; mixed; 39

Traumatized; mixed; 31

Volume

Smaller bilateral HC; increased after CBT

No difference

Smaller volume in medial orbitofrontal cortex

No difference in total brain volume

Li et al. (2006)

Fire disaster; mixed; 12

Trauma exposed; mixed; 12

VBM

Lower density in left HC
   
Lindauer et al. (2005)

Mixed trauma; mixed 18

Trauma exposed; mixed; 14

Volume

Smaller HC, no change after treatment

No difference
 
Larger total and left parahippocampal gyrus

Lindauer et al. (2004)

Traumatized police officers; mixed; 14

Trauma exposed; mixed; 14

Volume

Smaller HC

No difference
 
No difference in parahippocampal gyrus, gray matter, white matter and CSF

Lindauer et al. (2006)

Traumatized police officers; mixed; 12

Trauma exposed; mixed; 12

Volume

Smaller bilateral HC
   
Lindemer et al. (2013)

Combat; mixed; 65

Combat; mixed; 39

Cortical thickness
   
Vertex based: thinner in bilateral postcentral and middle temporal; left fusiform; right precuneus, and inferior temporal

ROI based: thinner in right postcentral and left insula

Liu et al. (2012)

Disaster; M; 10

Trauma exposed; M; 10

Cortical thickness
  
Thinner in right inferior frontal cortex

Thinner in left precuneus and right parahippocampus

Lyoo et al. (2011)

Disaster; mixed; 30

Trauma-free; mixed; 36

Cortical thickness
  
Thicker in right dlPFC, left superior and inferior frontal cortices 1 year later
 
No difference 5 years later

May et al. (2004)

Combat; monozygotic twins; M; 20

Trauma exposed; monozygotic twins; M; 23

Volume
   
Greater cavum septum pellucidum in PTSD twins

Morey et al. (2012)

Military; mixed; 99

Trauma exposed; mixed; 101

Volume

Smaller left HC

Smaller bilateral amygdala
  
Nardo et al. (2010)

Occupational trauma; mixed; 21,

Trauma exposed; mixed; 22

VBM
 
Lower density in no treatment response PTSD (5 NR) than response PTSD (10 R)

Lower density in left PCC in PTSD than non-PTSD

Lower density in left precuneus, lingual, and posterior parahippocampal gyrus in PTSD than non-PTSD

Lower density in bilateral PCC and left middle and medial frontal gyri in NR than R

Lower density in left precentral, right anterior insula, and anterior parahippocampal gyrus in NR than R

Nardo et al. (2013)

Accident/assault mixed; 15

Trauma exposed; mixed; 17

VBM
  
Low density in right PFC, including superior, middle, and inferior frontal and rACC
 
Niedtfeld et al. (2013)

Abuse; F; 21

Trauma-free; F; 31

VBM

No difference

No difference

Greater density in dlPFC in borderline with PTSD

Greater density in left superior temporal gyrus in borderline with PTSD

Pavic et al. (2007)

Combat; mixed; 15

Trauma-free; mixed; 15

Volume

Smaller right HC in PTSD than control, smaller right HC than left HC in PTSD
   
Pitman et al. (2006)

Combat; monozygotic twins; M; 20

Trauma exposed; monozygotic twins; M; 24
 
Smaller HC in PTSD twin pairs
   
Rauch et al. (2003)

Combat; F; 9

Trauma exposed; F; 9

Volume
  
Smaller pregenual ACC, subcallosal cortex
 
Rocha-Rego et al. (2012)

Assault; mixed; 16

Trauma exposed; mixed; 16

VBM

No difference

No difference

Low density in pregenual ACC, premotor cortex
 
Rogers et al. (2009)

Attack; mixed; 9

Trauma exposed; mixed; 16

Volume

No difference

Smaller bilateral amygdala
  
VBM

Saar-Ashkenazy et al. (2014)

Civilian trauma; mixed; 20

Trauma-free; mixed; 17

Volume
   
Smaller corpus callosum, no difference in white matter and gray matter volume

Schuff et al. (2011)

Veterans; M; 17

Trauma exposed; M; 15

ASL, DTI
  
Lower FA in PFC, ACC and PCC

Higher rCBF in right parietal, superior temporal gyri

Starcevic et al. (2014)

Unclear; M; 49

Trauma exposed; M; 30

Volume

No difference

Smaller volume

No difference in PFC
 
Stein et al. (1997)

Childhood abuse; F; 21

Trauma-free; F; 21

Volume

Smaller left HC
   
Sui et al. (2010)

Sexual assault; F; 11

Trauma-free; F; 12

VBM

Lower density in right HC

Lower density in right amygdala

Higher density in right PCC

Higher density in left insula, cerebellum, including pyramis, uvula, declive, and nodule

Sui et al. (2010)

Sexual assault; F; 11

Trauma exposed; F; 8

VBM
  
Lower density in bilateral medial frontal and left middle frontal cortices, higher density in right PCC in PTSD

Lower density in left middle temporal and fusiform cortices in PTSD;

Trauma-free; F; 12

Higher density in right postcentral, bilateral precentral, and inferior parietal cortices in PTSD

Tan et al. (2013)

Mine disaster; M; 12

Symptom improved; M; 7

VBM
   
Lower gray matter density in right lingual gyrus in chronic PTSD vs symptom-improved group

Trauma exposed; M; 14

Right superior frontal and left superior parietal lobe in PTSD vs trauma control

Tavanti et al. (2012)

Mixed trauma; mixed; 25

Trauma-free; mixed; 25

Volume
  
Smaller bilateral frontal lobes

Smaller bilateral occipital lobes

VBM

Lower density in left frontal lobe

Lower density in right inferior temporal gyrus

Villarreal et al. (2002)

Mixed trauma; mixed; 12

Trauma-free; mixed; 10

Volume

Smaller bilateral HC
  
Volume reduction in white matter

Villarreal et al. (2004)

Mixed trauma; mixed; 12

Trauma-free; mixed; 10

Volume
   
Smaller corpus callosum total volume, and genu, mid-body, and isthmus subregional volume

Vythilingam et al. (2005)

Combat; mixed; 14

Trauma exposed; mixed; 23

Volume

Smaller bilateral head of HC in PTSD than civilians, smaller right HC in trauma-exposed veterans than civilians
   
Trauma-free; mixed; 22

Trauma-free civilians; mixed; 29

Wang et al. (2010)

Combat; M; 17

Trauma exposed; M; 19

Volume

Smaller HC and CA3/dentate gyrus subfield volumes
   
Weniger et al. (2008)

Childhood abuse; F; 10

Trauma-free; F; 25

Volume

Smaller HC in PTSD

Smaller amygdala in PTSD
  
Trauma exposed; F; 13

Wignall et al. (2004)

Accident; mixed; 15

Trauma-free; mixed; 11

Volume

Smaller right HC

No difference
 
Smaller brain volume

Woodward et al. (2009)

Combat; mixed; 50

Trauma exposed; mixed; 47

Volume, cortical thickness
  
Smaller volume in lateral OFC and pars orbitalis

Smaller volume in parahippocampus, superior temporal region

Thinner thickness in rostral and caudal ACC

Thinner thickness in superior temporal cortex

Woodward et al. (2006)

Combat; mixed; 51

Trauma exposed; mixed; 48

Volume
  
Smaller ACC volume
 
Woodward et al. (2007)

Combat; mixed; 51

Trauma exposed; mixed; 48

Volume
   
Smaller cranial and CSF volume

Yamasue et al. (2003)

Attack; mixed; 9

Trauma exposed; mixed; 16

VBM
  
Lower density in the left ACC
 
Yehuda et al. (2007)

Combat; M; 17

Trauma exposed; M; 16

Volume

No difference
   
Zhang et al. (2011)

Disaster; M; 17

Trauma-free; M; 28;

DTI
  
Decreased FA in ACC in PTSD vs GAD
 
Generalized anxiety disorder (GAD); M; 20

Increased FA in left superior frontal gyrus in PTSD vs trauma-free controls

Zhang et al. (2011)

Disaster; M; 10

Trauma exposed; M; 10

Volume, VBM

Smaller volume and lower density in left HC
  
Smaller volume and lower density in bilateral calcarine and left parahippocampus

Zandieh et al. (2016)

Torture; mixed; 9

Violent-free; mixed; 10

Volume

Smaller volume in left HC
   
Fani et al. (2016)

Mixed trauma; F: 13

Trauma exposed; F; 41

DTI
  
Decreased FA in ACC in PTSD
 
Luo et al. (2016)

Bereavement; mixed; 57

Trauma- xposed; mixed; 11

Volume

Left HC atrophy in PTSD and trauma-exposed group

No difference
  
trauma-free; mixed; 39

Li et al. (2016)

Earthquake; mixed; 67

Trauma exposed; mixed; 78

Cortical thickness, volume
   
Greater thickness in the right superior temporal gyrus, inferior parietal lobule, and left precuneus; reduced volume in the posterior corpus callosum

Helpman et al. (2016)

Mixed trauma; mixed; 25 (11 remitters; 14 non-remitters)

Trauma exposed; mixed; 25

Cortical thickness, volume
  
Left rACC thinning and reduced volume from pre- to posttreatment in remitters
 
Mueller et al. (2015)

Combat; M; 40

Trauma exposed; M; 45

Cortical thickness, volume
  
Cortical thinning in rACC

Cortical thinning in insula

Sun et al. (2015)

Traffic accidents; mixed; 15

Trauma exposed; mixed; 14

DTI
   
Decreased FA in commissural tracts connecting bilateral superior/middle frontal gyrus

Bierer et al. (2015)

Combat; M; 12

Trauma exposed; M; 8

DTI
  
Lower MD in the right cingulum bundle
 
Chalavi et al. (2015)

Interpersonal trauma; F; 33

Trauma exposed; F; 28

Volume

Smaller bilateral HC, especially bilateral subfield CA2-3, right CA4-DG, and left presubiculum
   



Table 12.2
Summary of structural MRI studies on pediatric PTSD
























































































































































































Literature

PTSD (trauma; gender; N)

Control (trauma; gender; N)

Measure

Brain structures

Hippocampus

Amygdala

Prefrontal and cingulate cortices

Other brain regions

Carrion et al. (2001)

Mixed trauma; mixed; 24

Trauma-free; mixed; 24

Volume

No difference

No differences
 
Smaller total brain and cerebral gray matter volumes

Carrion et al. (2009)

Interpersonal trauma; mixed; 24;

Trauma-free; mixed; 24

Volume
   
Larger volume in bilateral superior and inferior PFC

Smaller volume in the pons

VBM

Greater density in bilateral ventral PFC

De Bellis et al. (1999)

Maltreatment; mixed; 44

Trauma-free; mixed; 61

Volume

No difference

No difference

No difference

Smaller volume in cerebral, intracranial, and corpus callosum, larger volume in bilateral lateral ventricles and CSF

De Bellis et al. (2001)

Maltreatment; mixed; 9

Trauma-free; mixed; 9

Volume

No difference

No difference
 
No difference in temporal lobe

De Bellis et al. (2002)

Maltreatment; mixed; 28;

Trauma-free; mixed; 66;

Volume

No difference

No difference

Smaller total and white matter volume in PFC

Smaller cerebral and intracranial volume; right temporal, and corpus callosum volume; larger frontal lobe CSF and lateral ventricular volume

De Bellis et al. (2002)

Maltreatment; mixed; 43;

Trauma-free; mixed; 61

Volume
     
Larger cerebral volume and unadjusted gray matter volume in superior temporal gyrus (STG), smaller STG white matter volume

De Bellis et al. (2003)

Maltreatment; mixed; 61;

Trauma-free; mixed; 122

Volume
     
Larger prefrontal CSF volumes and smaller midsagittal corpus callosum in both boys and girls with PTSD; smaller cerebral, rostrum, and isthmus corpus callosum volumes; and greater lateral ventricular volume in boys with PTSD

De Bellis et al. (2006)

Maltreatment; mixed; 58

Trauma exposed with GAD; mixed; 13

Volume
     
Smaller brain stem volume and bilateral cerebellum volume in PTSD, larger cerebellar volume in PTSD boys

Trauma-free; mixed; 98

De Bellis et al. (2010)

Maltreatment; mixed; 49

Maltreatment; mixed; 49

Volume

No difference
     

Trauma-free; mixed; 118

Jackowski et al. (2008)

Maltreatment; mixed; 17

Trauma-free; mixed; 15

DTI
     
Lower FA in anterior and posterior mid-body corpus callosum regions

Richert et al. (2006)

Mixed trauma; mixed; 23

Trauma-free; mixed; 24

Volume
   
Larger gray matter volume in the middle and inferior ventral PFC
 

Tupler et al. (2006)

Maltreatment; mixed; 61

Trauma-free; mixed; 122

Volume

Larger bilateral HC
     

Ahmed et al. (2012)

Mixed trauma; mixed; 21

Trauma exposed; mixed; 32

VBM
   
Low density in right ACC

Low density in left insula, right precuneus

Thickness

Thinner thickness in insula

De Bellis et al. (2015)

Maltreatment; mixed; 38

Trauma exposed; mixed; 35

Volume
     
smaller cerebral and cerebellar total volume and gray matter volumes, smaller superior posterior brain regional gray matter volumes, larger white matter and CSF volumes in bilateral superior frontal-parietal region

Trauma-free; mixed; 59

DTI

lower AF in occipital region to corpus callosum

Morey et al. (2016)

Maltreatment; mixed; 32

Trauma exposed; mixed; 31

Volume

Large right HC in non-PTSD group vs PTSD and non-trauma control groups

Large left amygdala in non-PTSD group vs PTSD and non-trauma control groups

Smaller right vmPFC in PTSD group
 

Trauma-free; mixed; 57

Keding et al. (2015)

Mixed trauma; mixed; 27

Trauma-free; mixed; 27

VBM

No difference
 
Smaller gray matter volume in right anterior vmPFC

Reduced gray matter volume in bilateral fusiform gyrus and left occipital cortex



Hippocampus


Hippocampus is a temporal lobe structure implicated in learning and memory processing as well as in emotion processing, contextual processing, stress regulation, and more [11, 42, 119, 147]. PTSD symptoms had been also associated with deficits in memory function and negative emotion processing [11], implicating hippocampus in PTSD-related pathophysiology. Accordingly, abnormal activation of the hippocampus had been suggested by functional MRI studies of PTSD patients, as compared to trauma-exposed and healthy control subjects (reviewed by [80, 112]). Multiple structural MRI studies thus examined the hippocampal volume and VBM in diverse cohorts of adult PTSD patients including survivors of combat, physical/sexual abuse, disasters, and childhood maltreatment. The majority of volumetric studies reported smaller left, right, or bilateral hippocampal volumes in PTSD patients [710, 15, 17, 36, 47, 50, 57, 76, 8284, 88, 109, 111, 120, 127, 139, 140, 144, 146, 149, 157]. In contrast, a smaller but meaningful number of studies failed to find difference in hippocampal volume in PTSD [6, 40, 48, 52, 53, 59, 117, 126, 156]. The meta-analyses published to date in general confirm smaller hippocampal volume in PTSD patients [61, 78, 107, 125], and the most recent largest meta-analysis examining neuroimaging and clinical data from 1868 subjects across 16 cohorts confirmed the presence of smaller hippocampus in PTSD [87]. Studies of the size of the subdivisions of hippocampus suggest that the dentate gyrus and adjacent anterior hippocampus specifically might be smaller in PTSD patients [140, 143]. Furthermore, some studies had found that hippocampal volume is smaller in veterans with current PTSD as compared to veterans with remitted PTSD, potentially suggesting that the hippocampal volume may be associated with the presence of active PTSD symptoms [17]. In concert, VBM-based studies also reported decreased gray matter density in hippocampal regions in PTSD patients [36, 39, 62, 77, 129, 130].

These structural findings were met with substantial interest because the convergence of functional and structural MRI findings suggests that the hippocampus may play a role in PTSD development. With respect to the functional significance of the volumetric findings, several studies reported relationships between hippocampal volume and the severity of PTSD symptoms, especially reexperiencing or dissociative symptoms [8, 39, 47, 82, 83, 127, 134, 139, 140, 144]. Furthermore, it has been also reported that in PTSD veterans, a smaller right hippocampal volume was positively correlated with deficits in short-term verbal memory, suggesting that alterations of hippocampal structure may be related to the memory functions of PTSD patients [8]. Interestingly, more recent data suggested that these findings might be at least to some degree reversible, as some interventions may be able to alter the hippocampal volume of PTSD patients. For example, a SSRI treatment that increases hippocampal volume of PTSD patients also reduces PTSD symptoms and significantly improved verbal memory [137]. Similarly, cognitive behavioral therapy (CBT), which had been demonstrated as effective treatment for PTSD, also increased hippocampal and medial orbital frontal volume associated with the clinical symptom improvement in PTSD patient [76]. However, these relationships between reduction of hippocampal volume and memory function or PTSD symptoms have not been detected in other studies [40, 117, 143, 150]. Thus, existing findings linking the abnormalities of hippocampal structure to symptom levels in PTSD patients are yet to be firmly established, and additional work clarifying these relationships is needed. Further examination of these relationships carries promise to further advance current understanding of PTSD pathophysiology.

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Feb 25, 2018 | Posted by in PSYCHOLOGY | Comments Off on Brain Structural Abnormalities in Posttraumatic Stress Disorder and Relations with Sleeping Problems
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