Major depression, 5HTTLPR genotype, suicide and antidepressant influences on thalamic volume

Young, Kimball; Bonkale, Willy L.; Holcomb, Leigh A.; Hicks, Paul B.; German, Dwight C.

doi:10.1192/bjp.bp.107.039180

Cited by 66 publications

(40 citation statements)

References 27 publications

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“…42 Previous research has shown that functional and histological abnormalities in the thalamus are involved in the pathophysiology of depression and suicidal behaviours. 43 The present study also showed that depressed patients without a history of suicidal behaviour had decreased fibres in frontothalamic pathways passing to specific prefrontal regions and to the thalamus relative to healthy controls. In patients with a history of suicide attempts, we observed a more severe reduction in these pathways in the OFC and thalamus than in depressed patients without a history of suicide attempts.…”

Section: 38supporting

confidence: 49%

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

103

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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: 38supporting

confidence: 49%

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

103

View full text Add to dashboard Cite

show abstract

“…Although reduced thalamic volume was reported in adult women with MDD (Kim et al 2008), this may be the first report of such deficits during early-onset depression. Interestingly, a postmortem study in depressed adults reported an increase in the number of neurons in the mediodorsal and anteroventral/anteromedial nuclei of the thalamus that connect subcortical limbic system structures (such as the amygdala) with the prefrontal and cingulate cortices (Young et al 2004). Furthermore, an association between history of antidepressant use and reduction in the volume of various thalamic nuclei in depressed subjects (Young et al 2008) suggests a potential antidepressant effect on the thalamus.…”

Section: Shad Et Almentioning

confidence: 99%

“…Interestingly, a postmortem study in depressed adults reported an increase in the number of neurons in the mediodorsal and anteroventral/anteromedial nuclei of the thalamus that connect subcortical limbic system structures (such as the amygdala) with the prefrontal and cingulate cortices (Young et al 2004). Furthermore, an association between history of antidepressant use and reduction in the volume of various thalamic nuclei in depressed subjects (Young et al 2008) suggests a potential antidepressant effect on the thalamus. In the current study, most of the depressed participants were never exposed to psychotropic agents and in the small subgroup (18%) that had ever been exposed to antidepressant agents, the duration of exposure was relatively brief ( < 2 months) and also not in close proximity to the MRI study.…”

Section: Shad Et Almentioning

confidence: 99%

Gray Matter Differences Between Healthy and Depressed Adolescents: A Voxel-Based Morphometry Study

Shad

Muddasani

Rao

2012

Journal of Child and Adolescent Psychopharmacology

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Background: Major depressive disorder (MDD) frequently begins during adolescence and is associated with significant morbidity and mortality. However, little is known about the neurobiology of adolescent depression. A better understanding of the neurobiology will be helpful in developing more effective preventive and treatment interventions for this highly disabling illness. Methods: Using a voxel-based morphometric method, the study compared gray matter and white matter volumes in 22 adolescents with MDD and 22 age-and gender-matched normal controls. Results: Compared with controls, depressed adolescents had smaller gray matter volume in the frontal lobe and caudate nucleus bilaterally and right superior and middle temporal gyri. However, the groups did not differ significantly on white matter volume. Conclusions: These findings in depressed adolescents are consistent with the previous findings of gray matter abnormalities in frontolimbic areas and the striatum in depressed adults and suggest the presence of these structural changes at the onset of depressive illness.

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“…Likewise, we exclude cell number estimates based upon cell counts without guard zones needed to eliminate the confounding of neurons lost when tissue sections are cut. It is important to note that some of the included studies provided very limited details regarding the stereological methods employed; however, these (Mileaf and Byne, 2012; Young et al, 2008) were included as the terminology used suggested that they met our criteria.…”

Section: Introductionmentioning

confidence: 99%

Postmortem structural studies of the thalamus in schizophrenia

Dorph‐Petersen

Lewis

2017

Schizophrenia Research

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In this review, we seek to answer the following question: Do findings in the current literature support the idea that thalamo-cortical dysfunction in schizophrenia is due to structural abnormalities in the thalamus? We base our review on the existing literature of design-unbiased stereological studies of the postmortem thalamus from subjects with schizophrenia. Thus, all reported results are based upon the use of unbiased principles of sampling to determine volume and/or total cell numbers of thalamus or its constituent nuclei. We found 28 such papers covering 26 studies. In a series of tables we list all positive and negative findings from the total thalamus, the mediodorsal, pulvinar and anterior nuclei, as well as less frequently studied thalamic regions. Only four studies examined the entire thalamus and the results were inconsistent. We found largely consistent evidence for structural changes (reduced volume and cell numbers) in the pulvinar located in the posterior thalamus. In contrast, findings in the mediodorsal thalamic nucleus are inconsistent, with the largest and most recent studies generally failing to support earlier reports of a lower number of neurons in schizophrenia. Thus, the current findings of stereological studies of the thalamus in schizophrenia support the idea that thalamo-cortical dysfunction in schizophrenia might be attributable, at least in part, to structural alterations in the pulvinar that could impair thalamic inputs to higher order cortical association areas in the frontal and parietal lobes. However, more studies are needed before robust conclusions can be drawn.

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Major depression, 5HTTLPR genotype, suicide and antidepressant influences on thalamic volume

Abstract: The 5HTTLPR genetic variation may affect behaviour and psychiatric conditions, in part, by altering the anatomy of the thalamus.

Cited by 66 publications

References 27 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

Gray Matter Differences Between Healthy and Depressed Adolescents: A Voxel-Based Morphometry Study

Postmortem structural studies of the thalamus in schizophrenia

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