The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates

Coplan, Jeremy D.; Abdallah, Chadi G.; Tang, Cheuk Y.; Mathew, Sanjay J.; Martı́nez, José M.; Hof, Patrick R.; Smith, Eric L.; Dwork, Andrew J.; Perera, Tarique D.; Pantol, Gustavo; Carpenter, David M.; Rosenblum, Leonard A.; Shungu, Dikoma C.; Gelernter, Joel; Kaffman, Arie; Jackowski, Andrea Parolin; Kaufman, Joan; Gorman, Jack M.

doi:10.1016/j.neulet.2010.06.012

Cited by 65 publications

(48 citation statements)

References 31 publications

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“…11 Abnormalities in the anterior limb of the internal capsule (ALIC) have also been identified in patients with depression, 12 and other data indicate that the ALIC is affected by early-life stress during development. 13 These studies have increased the understanding of possible anatomic and functional substrates for suicid al behaviour, but the specific neural circuits implicated in suicide risk remain to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Impaired frontothalamic circuitry in suicidal patients with depression revealed by diffusion tensor imaging at 3.0 T

Jia

Wang

Huang

et al. 2014

J Psychiatry Neurosci

104

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IntroductionSuicide is one of the leading causes of death in children and middle-aged individuals and represents a major public health problem throughout the world. Current trends suggest that about 1.5 million people will die by suicide in the year 2020.1 Major depressive disorder (MDD) is a highly prevalent, etiologically multifactorial and clinically heterogen eous disorder. The lifetime risk of suicide in patients with MDD is about 6%, which represents a 20-fold increase from the general population.2,3 Suicide attempts, defined as selfdestructive acts with some degree of intent to end one's life, are one of the strongest predictors of future suicidal acts. 4,5 Thus, suicide attempts represent an important intervention point for suicide prevention efforts, and in vivo studies of individuals who attempt suicide represent an important strategy for learning about the neurobiology of suicide.Conventional magnetic resonance imaging (MRI) studies have found white matter and grey matter hyperintensities and reduced orbitofrontal cortex grey matter volumes on scans of depressed patients with a history of suicide attempts.6-8 A functional MRI experiment revealed that suicidal patients were distinguished from nonsuicidal patients in their activation patterns in frontal, cingulate and cerebellar regions.9 A positron emission tomography study revealed localized prefrontal hypofunction and impaired responsivity of serotonergic systems to pharmaco logic al challenge that were proportional to the lethality of the suicide attempt in individuals with MDD. Background:The neurobiology of suicide is largely unknown. Studies of white matter tracts in patients with a history of suicidal behaviour have shown alteration in the left anterior limb of the internal capsule (ALIC). Our aim was to determine whether particular target fields of fibre projections through the ALIC are affected in depressed patients who recently attempted suicide. Methods: We studied patients with major depressive disorder (MDD) with and without a history of suicide attempts and healthy controls using diffusion tensor imaging (DTI) and deterministic tractography to generate fibre tract maps for each participant. Tract voxels were coded as being unique to the left ALIC. We compared the mean percentage of fibres projecting to relevant brain regions in the 3 groups using analysis of covariance. Results: We included 63 patients with MDD (23 with and 40 without a history of suicide attempts) and 46 controls in our study. Both groups of depressed patients had reduced fibre projections through the ALIC to the left medial frontal cortex, orbitofrontal cortex and thalamus. Those with a history of suicide attempts had greater abnormalities than those without suicide attempts in the left orbitofrontal cortex and thalamus. Limitations: Diffusion tensor imaging deterministic tracking is unable to distinguish between afferent and efferent pathways, limiting our ability to distinguish the directionality of altered fibre tracts. Conclusion: Frontothalamic loops passing throu...

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Section: Introductionmentioning

confidence: 99%

Impaired frontothalamic circuitry in suicidal patients with depression revealed by diffusion tensor imaging at 3.0 T

Jia

Wang

Huang

et al. 2014

J Psychiatry Neurosci

104

View full text Add to dashboard Cite

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“…VFD is an early-life stress paradigm in which infant bonnet macaques are reared by mothers undergoing an experimentally-induced “perception” of food uncertainty (Gorman et al, 2002). VFD and non-VFD mothers and infants differ on a number of behavioral and biological indices that persist throughout development, including disrupted measures of maternal-infant attachment (Andrews and Rosenblum, 1991), increased stress reactivity (Rosenblum et al, 2001), synchronized maternal-infant elevation of cerebrospinal fluid (CSF) concentrations of corticotropin releasing factor (CRF; Coplan et al, 2005), and reduced neuronal integrity (Mathew et al, 2003; Coplan et al, 2010b). …”

Section: Introductionmentioning

confidence: 99%

Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates

Jackowski

Perera

Abdallah

et al. 2011

Psychiatry Research: Neuroimaging

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102

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Male bonnet monkeys (Macaca radiata) were subjected to the Variable Foraging Demand (VFD) early stress paradigm as infants, MRI scans were completed an average of four years later, and behavioral assessments of anxiety and ex-vivo corpus callosum (CC) measurements were made when animals were fully matured. VFD rearing was associated with smaller CC size, CC measurements were found to correlate with fearful behavior in adulthood, and ex-vivo CC assessments showed high consistency with earlier MRI measures. Region of Interest (ROI) hippocampus and whole brain voxel- based morphometry assessments were also completed and VFD rearing was associated with reduced hippocampus and inferior and middle temporal gyri volumes. Animals were also characterized according to serotonin transporter genotype (5-HTTLPR), and the effect of genotype on imaging parameters was explored. The current findings highlight the importance of future research to better understand the effects of stress on brain development in multiple regions, including the corpus callosum, hippocampus, and other regions involved in emotion processing. Nonhuman primates provide a powerful model to unravel the mechanisms by which early stress and genetic makeup interact to produce long-term changes in brain development, stress reactivity, and risk for psychiatric disorders.

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“…These findings are consistent with neuroimaging studies demonstrating white matter abnormalities in the prefrontal cortex of asymptomatic high-risk individuals (42), first-onset unmediated individuals (43), and in individuals with chronic schizophrenia (44). However, white matter abnormalities are unlikely to be a specific marker for schizophrenia (84–90) and therefore additional work is needed to determine how these changes modify brain function and risk for psychopathology.…”

Section: The Opportunitymentioning

confidence: 99%

New Frontiers in Animal Research of Psychiatric Illness

Kaffman

Krystal

2011

Methods in Molecular Biology

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Alterations in neurodevelopment are thought to modify risk of numerous psychiatric disorders, including schizophrenia, autism, ADHD, mood and anxiety disorders, and substance abuse. However, little is known about the cellular and molecular changes that guide these neurodevelopmental changes and how they contribute to mental illness. In this review, we suggest that elucidating this process in humans requires the use of model organisms. Furthermore, we advocate that such translational work should focus on the role that genes and/or environmental factors play in the development of circuits that regulate specific physiological and behavioral outcomes in adulthood. This emphasis on circuit development, as a fundamental unit for understanding behavior, is distinct from current approaches of modeling psychiatric illnesses in animals in two important ways. First, it proposes to replace the diagnostic and statistical manual of mental disorders (DSM) diagnostic system with measurable endophenotypes as the basis for modeling human psychopathology in animals. We argue that a major difficulty in establishing valid animal models lies in their reliance on the DSM/International Classification of Diseases conceptual framework, and suggest that the Research Domain Criteria project, recently proposed by the NIMH, provides a more suitable system to model human psychopathology in animals. Second, this proposal emphasizes the developmental origin of many (though clearly not all) psychiatric illnesses, an issue that is often glossed over in current animal models of mental illness. We suggest that animal models are essential to elucidate the mechanisms by which neurodevelopmental changes program complex behavior in adulthood. A better understanding of this issue, in animals, is the key for defining human psychopathology, and the development of earlier and more effective interventions for mental illness.

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The role of early life stress in development of the anterior limb of the internal capsule in nonhuman primates

Cited by 65 publications

References 31 publications

Impaired frontothalamic circuitry in suicidal patients with depression revealed by diffusion tensor imaging at 3.0 T

Impaired frontothalamic circuitry in suicidal patients with depression revealed by diffusion tensor imaging at 3.0 T

Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates

New Frontiers in Animal Research of Psychiatric Illness

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