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

Neuropsychiatry Research Program, Central Texas Veterans Health Care System and Texas A&M Health Science Center Department of Psychiatry and Behavioral Science, Temple, TX 76504, USA.
The British Journal of Psychiatry (Impact Factor: 7.99). 05/2008; 192(4):285-9. DOI: 10.1192/bjp.bp.107.039180
Source: PubMed


The 5HTTLPR genetic variant of the serotonin transporter gene (SERT or 5-HTT), which is comprised of a short (SERT-s) and a long (SERT-l) allele, is associated with major depressive disorder and post-traumatic brain disorder.
The present study sought to determine whether the total thalamus and major subregions are altered in size in major depressive disorder and in relation to the 5HTTLPR genotype.
We investigated the influence of 5HTTLPR genotype, psychiatric diagnosis, suicide and other clinical factors on the volume of the entire post-mortem thalamus.
Major depressive disorder, SERT-ss genotype and suicide emerged as independent factors contributing to an enlargement of the total thalamus. The majority of the volume enlargement associated with the SERT-ss genotype occurred in the pulvinar, whereas enlargement associated with major depressive disorder occurred in the limbic nuclei and in other regions of the thalamus. A history of antidepressant treatment was associated with reduced thalamic volume.
The 5HTTLPR genetic variation may affect behaviour and psychiatric conditions, in part, by altering the anatomy of the thalamus.

Download full-text


Available from: Dwight C German
  • Source
    • "The PCR primers and conditions were adapted from earlier studies, for COMT (Stacy et al., 2010), BDNF (Zeman et al., 2010), 5-HTT (STin2) (Hranilovic et al., 2000), and 5-HTTLPR (Young et al., 2008). The polymerase chain reaction products were visualized by running on a 2% agarose gel except for COMT with 8% polyacrylamide gel. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Suicide as a public health problem is studied worldwide and association of psychiatric and genetic risk factors for suicidal behavior are the point of discussion in studies across different ethnic groups. The present study is aimed at evaluating psychiatric and genetic traits among primary relatives of suicide completer families in an urban Indian population. Bi-variate analysis shows significant increase in major depression (PHQ and Hamilton), stress, panic disorder, somatoform disorder and suicide attemptamong primary compared to other relatives. Sib pair correlations also reveal significant results for major depression (Hamilton), stress, suicide attempt, intensity of suicide ideation and other anxiety syndrome. 5-HTTLPR, 5-HTT (Stin2) and COMT risk alleles are higher among primary relatives, though statistically insignificant. Backward conditional logistic regression analysis show only independent variable, Depression (Hamilton) made a unique statistically significant contribution to the model in primary relatives. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Jul 2015
  • Source
    • "Elderly suicide attempters showed reduced voxel counts in the putamen (Dombrovski et al. 2012). Moreover, the thalamus has similarly been implicated in a neuroimaging study (Benedetti et al. 2011) and in a volumetric post-mortem study (Young et al. 2008). Taken together, there is substantial evidence to suggest that several subcortical structures may be structurally altered in suicide attempters and completers, and may represent relevant biomarkers of suicidal behavior. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Previously, studies have demonstrated cortical impairments in those who complete or attempt suicide. Subcortical nuclei have less often been implicated in the suicidal vulnerability. In the present study, we investigated, with a specific design in a large population, variations in the volume of subcortical structures in patients with mood disorders who have attempted suicide. We recruited 253 participants: 73 suicide attempters with a past history of both mood disorders and suicidal act, 89 patient controls with a past history of mood disorders but no history of suicidal act, and 91 healthy controls. We collected 1.5 T magnetic resonance imaging data from the caudate, pallidum, putamen, nucleus accumbens, hippocampus, amygdala, ventral diencephalon, and thalamus. Surface-based morphometry (Freesurfer) analysis was used to comprehensively evaluate gray matter volumes. In comparison to controls, suicide attempters showed no difference in subcortical volumes when controlled for intracranial volume. However, within attempters negative correlations between the left (r = -0.35, p = 0.002), and right (r = -0.41, p < 0.0005) nucleus accumbens volumes and the lethality of the last suicidal act were found. Our study found no differences in the volume of eight subcortical nuclei between suicide attempters and controls, suggesting a lack of association between these regions and suicidal behavior in general. However, individual variations in nucleus accumbens structure and functioning may modulate the lethality of suicidal acts during a suicidal crisis. The known role of nucleus accumbens in action selection toward goals determined by the prefrontal cortex, decision-making or mental pain processing are hypothesized to be potential explanations.
    Full-text · Article · Mar 2015 · Brain Imaging and Behavior
  • Source
    • "Lesions in these thalamic nuclei induce symptoms similar to PFC dysfunction, including impairment of executive function, initiative, and attention [52], suggesting the thalamic nuclei and their cortical targets can act as functional units. Abnormalities in thalamic regions have been described in mood disorders [10] [22] and OCD [18] [20], based on post-mortem [5] [58] and in vivo anatomical and functional imaging techniques [14] [15]. Orexin inhibits HCN currents [29] and produces anxietylike responses in rats when injected in to the PVT, whereas inhibition of orexin attenuates anxiety [30] [43] [45] [53]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Hyperpolarization activated cyclic nucleotide-gated (HCN) potassium channels are implicated in the control of neuronal excitability and are expressed widely in the brain. HCN4 is expressed in brain regions relevant to mood and anxiety disorders including specific thalamic nuclei, the basolateral amygdala, and the midbrain dopamine system. We therefore examined the association of HCN4 with a group of mood and anxiety disorders. We genotyped nine tag SNPs in the HCN4 gene using Sequenom iPLEX Gold technology in 285 Caucasian patients with DSM-IV mood disorders and/or obsessive compulsive disorder and 384 Caucasian controls. HCN4 polymorphisms were analyzed using single marker and haplotype-based association methods. Three SNPs showed nominal association in our population (rs12905211, rs3859014, rs498005). SNP rs12905211 maintained significance after Bonferroni correction, with allele T and haplotype CTC overrepresented in cases. These findings suggest HCN4 as a genetic susceptibility factor for mood and anxiety disorders; however, these results will require replication using a larger sample.
    Full-text · Article · Jun 2011 · Neuroscience Letters
Show more