Cerebellar Volumes in Pediatric Maltreatment-Related Posttraumatic Stress Disorder

doi:10.1016/j.biopsych.2006.04.035

Biological Psychiatry

Volume 60, Issue 7, 1 October 2006, Pages 697-703

https://doi.org/10.1016/j.biopsych.2006.04.035 Get rights and content

Background

The results of previous studies suggest structural brain differences in pediatric maltreatment-related posttraumatic stress disorder (PTSD) However, posterior fossa volumes were not examined, despite the consensus that the cerebellum is important in emotional and cognitive development. We investigated the relationship between structural volumes of the cerebellum hemispheres, vermis, brainstem, and clinical variables in pediatric maltreatment-related PTSD.

Methods

Fifty-eight psychotropic-naïve maltreated children and adolescents with DSM-IV PTSD were compared with two groups of pediatric subjects who had no DSM-IV criteria A trauma histories: 1) 13 with pediatric generalized anxiety disorder, and 2) 98 healthy non-abused children and adolescents. Subjects underwent a comprehensive psychiatric assessment and an anatomical magnetic resonance image brain scan.

Results

Unadjusted means of the left, right, and total cerebellum were smaller in the PTSD group. The group differences remained significant in the left cerebellum, right cerebellum, and total cerebellum in the analyses adjusted for cerebral volume, sociodemographic, and IQ variables. Cerebellar volumes positively correlated with age of onset of the trauma that lead to PTSD and negatively correlated with the duration of the trauma that lead to PTSD. Cerebellar volumes were larger in boys versus girls, but there was no group × gender interaction. There were significant positive correlations between IQ measures and volumetric variables.

Conclusions

The results support cerebellar volume differences in maltreated children and adolescents with PTSD. Further studies are warranted.

Section snippets

Subjects

Fifty-eight psychotropic-naïve maltreated subjects with DSM-IV PTSD were compared with two groups of pediatric subjects who had no criteria A trauma histories, 13 subjects with GAD and 98 healthy non-abused subjects. The groups were similar in age, height, weight, and gender.

Clinical Evaluation

Subjects and their legal guardians were evaluated by a board certified child psychiatrist (Master Drug Data Base [M.D.D.B.]) with a detailed trauma interview as described (De Bellis 1997) and by a trained Master’s level

Volumetric Variables

Unadjusted means of brain stem, left and right cerebellum, and total cerebellum were smallest in the PTSD group [pons/brain stem: F(2,166)= 5.13, p = < .007; left cerebellum: F(2,166) = 10.57, p < .0001; right cerebellum: F(2,166) = 11.74, p < .0001; and total cerebellum: F(2,166) = 11.18, p < .0001]. Thus, there were significant group differences in the unadjusted means of all the volumetric variables except cerebellum vermis. Relative to the healthy comparison group, the intracranial volume

Discussion

Maltreated children and adolescents with PTSD had smaller posterior fossa volumes than non-maltreated subjects with GAD and healthy subjects. The findings of smaller left, right, and total cerebellar volumes persisted when controlling for gender, cerebral volumes, SES, and IQ. Cerebellar volumes positively correlated with age of onset of the trauma that lead to PTSD, so that the younger the child experienced trauma, the smaller the cerebellar volume. Cerebellar volumes negatively correlated

References (56)

C.M. Anderson et al.
Abnormal T2 relaxation time in the cerebellar vermis of adults sexually abused in childhood: Potential role of the vermis in stress-enhanced risk for drug abuse
Psychoneuroendocrinology
(2002)
O. Bonne et al.
Resting regional cerebral perfusion in recent posttraumatic stress disorder
Biol Psychiatry
(2003)
V.G. Carrion et al.
Diurnal salivary cortisol in pediatric posttraumatic stress disorder
Biol Psychiatry
(2002)
M.D. De Bellis et al.
A.E. Bennett Research Award. Developmental Traumatology Part I: Biological Stress Systems
Biol Psychiatry
(1999)
M.D. De Bellis et al.
A pilot study of amygdala volumes in pediatric generalized anxiety disorder
Biol Psychiatry
(2000)
M.D. De Bellis et al.
A.E. Bennett Research Award. Developmental Traumatology Part II: Brain Development
Biol Psychiatry
(1999)
M.D. De Bellis et al.
Superior temporal gyrus volumes in maltreated children and adolescents with PTSD
Biol Psychiatry
(2002)
M.D. De Bellis et al.
Brain structures in pediatric maltreatment-related PTSD: A sociodemographically matched study
Biol Psychiatry
(2002)
M.D. De Bellis et al.
Superior temporal gyrus volumes in Pediatric Generalized Anxiety Disorder
Biol Psychiatry
(2002)
M.D. De Bellis et al.
Sex differences in Brain Maturation in Maltreatment-Related Pediatric Posttraumatic Stress Disorder
Neurosci Biobehav Rev
(2003)

M. Driessen et al.

Posttraumatic stress disorder and fMRI activation patterns of traumatic memory in patients with borderline personality disorder

Biol Psychiatry

(2004)

S.A. Ferguson et al.

Neonatal dexamethasone on day 7 in rats causes mild hyperactivity and cerebellar stunting

Neurotoxicol Teratol

(1999)

M. Fernandez et al.

Brain function in a patient with torture related post-traumatic stress disorder before and after fluoxetine treatment: A positron emission tomography provocation study

Neurosci Lett

(2001)

J.A. Fiez

Cerebellar contributions to cognition

Neuron

(1996)

Y. Finkelstein et al.

Low-level lead-induced neurotoxicity in children: An update on central nervous system effects

Brain Res Brain Res Rev

(1998)

S. Frangou et al.

Mapping IQ and gray matter density in healthy young people

Neuroimage

(2004)

J. Kaufman et al.

Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): Initial reliability and validity data

J Am Acad Child Adolesc Psychiatry

(1997)

R. Lalonde

Cerebellar contributions to instrumental learning

Neurosci Biobehav Rev

(1994)

R. Lalonde et al.

Spatial learning in a Z-maze by cerebellar mutant mice

Physiol Behav

(1996)

J.S. March et al.

Posttraumatic symptomatology in children and adolescents after an industrial fire

J Am Acad Child Adolesc Psychiatry

(1997)

S. Miachon et al.

Isolation-induced changes in radioligand binding to benzo-diazepine binding sites

Neurosci Lett

(1990)

K. Nguon et al.

Sexual dimorphism in cerebellar structure, function, and response to environmental perturbations

Prog Brain Res

(2005)

M. Onofrj et al.

Non-dominant dorsal-prefrontal activation during chess problem solution evidenced by single photon emission computerized tomography (SPECT)

Neurosci Lett

(1995)

R. Pascual et al.

Early social isolation decreases the expression of calbindin D-28k in rat cerebellar Purkinje cells

Neurosci Lett

(1999)

O. Ramirez et al.

Sexual dimorphism in rat cerebrum and cerebellum: Different patterns of catalytically active creatine kinase isoenzymes during postnatal development and aging

Int J Dev Neurosci

(2002)

L. Reneman et al.

Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons

Lancet

(2001)

J.H. Rogers

Immunoreactivity for calretinin and other calcium-binding proteins in cerebellum

Neuroscience

(1989)

M.S. Scheeringa et al.

New findings on alternative criteria for PTSD in preschool children

J Am Acad Child Adolesc Psychiatry

(2003)

Cited by (199)

Brain structural change associated with Cognitive Behavioral Therapy in maltreated children
2024, Brain Research
Severely maltreatment child is a harmful social factor that can disrupt normal neurodevelopment. Two commonly reported effects of maltreatment are post-traumatic stress disorder (PTSD) symptoms and brain structural and functional alteration. While Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) is effectively used to reduce PTSD symptoms in maltreated children, yet, its impact on brain structural alterations has not been fully explored. This study investigated whether TF-CBT can attenuate alterations in brain structures associated with PTSD in middle childhood.
The study evaluated the longitudinal effects of Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) on post-traumatic stress disorder (PTSD) symptoms and gray matter volume (GMV) in two groups of children under 12 years old: maltreated children (MC) and healthy non– maltreatmentd children (HC). Structural magnetic resonance images T1 were obtained before and after TF-CBT in the MC group, while the HC group was scanned twice within the same time interval. Voxel-based morphometry (VBM) was used to analyze GMV changes over time.
After TF-CBT, maltreated children showed significantly reduced PTSD symptoms. Furthermore, a significant group-by-time interaction effect was observed in certain areas of the Left Temporal, Left Occipital, and bilateral Frontal Cortex, the Basal Ganglia and Cerebellum. These interaction effects were driven by a GMV decrease in the MC group compared to the HC group. GMV changes can be predicted with clinical improvement in the left Middle Temporal gyrus, left Precuneus, and Cerebellum.
Our results suggest that TF-CBT intervention in very young maltreated children may have an effect on gray matter. This evidence demonstrates the importance of timely intervention when neuroplasticity mechanisms may be activated.
Sleep, brain systems, and persistent stress in early adolescents during COVID-19: Insights from the ABCD study
2024, Journal of Affective Disorders
The first year of the COVID-19 pandemic constituted a major life stress event for many adolescents, associated with disrupted school, behaviors, social networks, and health concerns. However, pandemic-related stress was not equivalent for everyone and could have been influenced by pre-pandemic factors including brain structure and sleep, which both undergo substantial development during adolescence. Here, we analyzed clusters of perceived stress levels across the pandemic and determined developmentally relevant pre-pandemic risk factors in brain structure and sleep of persistently high stress during the first year of the COVID-19 pandemic.
We investigated longitudinal changes in perceived stress at six timepoints across the first year of the pandemic (May 2020–March 2021) in 5559 adolescents (50 % female; age range: 11–14 years) in the United States (U.S.) participating in the Adolescent Brain Cognitive Development (ABCD) study. In 3141 of these adolescents, we fitted machine learning models to identify the most important pre-pandemic predictors from structural MRI brain measures and self-reported sleep data that were associated with persistently high stress across the first year of the pandemic.
Patterns of perceived stress levels varied across the pandemic, with 5 % reporting persistently high stress. Our classifiers accurately detected persistently high stress (AUC > 0.7). Pre-pandemic brain structure, specifically cortical volume in temporal regions, and cortical thickness in multiple parietal and occipital regions, predicted persistent stress. Pre-pandemic sleep difficulties and short sleep duration were also strong predictors of persistent stress, along with more advanced pubertal stage.
Adolescents showed variable stress responses during the first year of the COVID-19 pandemic, and some reported persistently high stress across the whole first year. Vulnerability to persistent stress was evident in several brain structural and self-reported sleep measures, collected before the pandemic, suggesting the relevance of other pre-existing individual factors beyond pandemic-related factors, for persistently high stress responses.
Distinct gray matter abnormalities in children/adolescents and adults with history of childhood maltreatment
2023, Neuroscience and Biobehavioral Reviews
Gray matter (GM) abnormalities have been reported in both adults and children/adolescents with histories of childhood maltreatment (CM). A comparison of effects in youth and adulthood may be informative regarding life-span effects of CM. Voxel-wise meta-analyses of whole-brain voxel-based morphometry studies were conducted in all datasets and age-based subgroups respectively, followed by a quantitative comparison of the subgroups. Thirty VBM studies (31 datasets) were included. The pooled meta-analysis revealed increased GM in left supplementary motor area, and reduced GM in bilateral cingulate/paracingulate gyri, left occipital lobe, and right middle frontal gyrus in maltreated individuals compared to the controls. Maltreatment-exposed youth showed less GM in the cerebellum, and greater GM in bilateral middle cingulate/paracingulate gyri and bilateral visual cortex than maltreated adults. Opposite GM alterations in bilateral middle cingulate/paracingulate gyri were found in maltreatment-exposed adults (decreased) and children/adolescents (increased). Our findings demonstrate different patterns of GM changes in youth closer to maltreatment events than those seen later in life, suggesting detrimental effects of CM on the developmental trajectory of brain structure.
Gray matter differences in adults and children with posttraumatic stress disorder: A systematic review and meta-analysis of 113 studies and 11 meta-analyses
2023, Journal of Affective Disorders
In this systematic review and meta-analysis, we aimed to provide a comprehensive overview of gray matter alterations of adult- and underage patients with posttraumatic stress disorder (PTSD) in comparison to healthy trauma-exposed (TC) and non-exposed (HC) individuals.
We subdivided our groups into patients with PTSD after trauma exposure in adulthood (aa) or childhood (ac) as well as children with PTSD (cc). We identified 113 studies, including 6.800 participants in our review, which we divided into studies focusing on whole-brain and region-of-interest (ROI) analysis. We performed a coordinate-based meta-analysis on 14 studies in the group of aa-PTSD.
We and found lower gray matter volume in patients with PTSD (aa) in the medial frontal gyrus (PTSD<HC/TC) and Culmen/posterior cingulate cortex (PTSD<TC). Results from ROI-based studies mainly show alterations for patients with PTSD in the prefrontal cortex, hippocampus, anterior cingulate cortex, insula, corpus callosum, and amygdala.
Due to a limited number of studies reporting whole-brain results, the meta-analyses could only be performed in one subgroup and within this subgroup for a limited number of studies.
Our results are in line with psychobiological models of PTSD that associate the identified regions with brain circuits involved in context processing, threat detection and emotion regulation.
Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning
2023, Cell Reports
Multiple brain regions are engaged in classical fear conditioning. Despite evidence for cerebellar involvement in fear conditioning, the mechanisms by which cerebellar outputs modulate fear learning and memory remain unclear. We identify a population of deep cerebellar nucleus (DCN) neurons with monosynaptic glutamatergic projections to the lateral parabrachial nucleus (lPBN) (DCN^→lPBN neurons) in mice. While optogenetic suppression of DCN^→lPBN neurons impairs auditory fear memory, activation of DCN^→lPBN neurons elicits freezing behavior only after auditory fear conditioning. Moreover, auditory fear conditioning potentiates DCN-lPBN synapses, and subsequently, auditory cue activates lPBN neurons after fear conditioning. Furthermore, DCN^→lPBN neuron activation can replace the auditory cue but not footshock in fear conditioning. These findings demonstrate that cerebellar nuclei modulate auditory fear conditioning via transmitting conditioned stimuli signals to the lPBN. Collectively, our findings suggest that the DCN-lPBN circuit is a part of neuronal substrates within interconnected brain regions underscoring auditory fear memory.
The cerebellum and psychological trauma: A systematic review of neuroimaging studies
2022, Neurobiology of Stress
Citation Excerpt :
Importantly, in the second study, individuals with PTSD scored significantly higher in early adverse experiences compared to resilient controls, suggesting that a reduction in cerebellar volume might occur after early exposure to stressors. This is in line with several studies that found cerebellar reduction in maltreated children and adolescents (De Bellis and Kuchibhatla, 2006) and with a recent study that showed a significant reduction of gray matter volume in cerebellar lobules I-IV, V and VI in individuals that were exposed to early adversity (Van Dam et al., 2014). It has been suggested that cerebellar function might be particularly important during critical periods of development, regulating cortical circuitries related to the cognitive and social domains (Badura et al., 2018).
Psychological trauma is highly prevalent among psychiatric disorders, however, the relationship between trauma, neurobiology and psychopathology is not yet fully understood. The cerebellum has been recognized as a crucial structure for cognition and emotion, however, it has been relatively ignored in the literature of psychological trauma, as it is not considered as part of the traditional fear neuro-circuitry. The aim of this review is to investigate how psychological trauma affects the cerebellum and to make conclusive remarks on whether the cerebellum forms part of the trauma-affected brain circuitry. A total of 267 unique records were screened and 39 studies were included in the review. Structural cerebellar alterations and aberrant cerebellar activity and connectivity in trauma-exposed individuals were consistently reported across studies. Early-onset of adverse experiences was associated with cerebellar alterations in trauma-exposed individuals. Several studies reported alterations in connectivity between the cerebellum and nodes of large-brain networks, which are implicated in several psychiatric disorders, including the default mode network, the salience network and the central executive network. Also, trauma-exposed individuals showed altered resting state and task based cerebellar connectivity with cortical and subcortical structures that are involved in emotion and fear regulation. Our preferred interpretation of the results is through the lens of the Universal Cerebellar Transform, the hypothesis that the cerebellum, given its homogeneous cytoarchitecture, performs a common computation for motor, cognitive and emotional functions. Therefore, trauma-induced alterations in this computation might set the ground for a variety of psychiatric symptoms.

View all citing articles on Scopus

View full text

Original articleCerebellar Volumes in Pediatric Maltreatment-Related Posttraumatic Stress Disorder

Background

Methods

Results

Conclusions

Section snippets

Subjects

Clinical Evaluation

Volumetric Variables

Discussion

Psychoneuroendocrinology

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Biol Psychiatry

Neurosci Biobehav Rev

Biol Psychiatry

Neurotoxicol Teratol

Neurosci Lett

Neuron

Brain Res Brain Res Rev

Neuroimage

J Am Acad Child Adolesc Psychiatry

Neurosci Biobehav Rev

Physiol Behav

J Am Acad Child Adolesc Psychiatry

Neurosci Lett

Prog Brain Res

Neurosci Lett

Neurosci Lett

Int J Dev Neurosci

Lancet

Neuroscience

J Am Acad Child Adolesc Psychiatry

Original article
Cerebellar Volumes in Pediatric Maltreatment-Related Posttraumatic Stress Disorder