STRUCTURAL AND FUNCTIONAL CONNECTIVITY IN POSTTRAUMATIC STRESS DISORDER: ASSOCIATIONS WITH FKBP5.
paper
Cited
Public
- Authors
- Fani, Negar; King, Tricia Z; Shin, Jaemin; Srivastava, Amita; Brewster, Ryan C; Jovanovic, Tanja; Bradley, Bekh; Ressler, Kerry J
- Year
- 2016
- Journal
- Depression and anxiety
- PMID
- 27038411
- DOI
- 10.1002/da.22483
- PMCID
- PMC4983452
BACKGROUND: The integrity of connections between the hippocampus and the anterior cingulate cortex (ACC) is critical for adaptive cognitive and emotional processing; these connections may be compromised in posttraumatic stress disorder (PTSD). However, there is a lack of PTSD research that combines structural and functional connectivity data, and no studies have examined whether abnormal ACC-hippocampal connectivity is associated with genetic variability, particularly for polymorphisms of a gene that has been previously associated with PTSD, FKBP5. This was the goal of the present study. METHODS: Fifty-four women with and without PTSD underwent diffusion tensor imaging and resting-state MRI. Probabilistic tractography was used to examine ACC-hippocampal structural connectivity; mean fractional anisotropy (FA) values were extracted from connectivity streamlines, which represent the cingulum bundle. Genotype data were collected for a single nucleotide polymorphism (SNP) of FKBP5, rs1360780. RESULTS: Participants with PTSD demonstrated poorer structural connectivity (lower cingulum FA) compared to traumatized controls (F1, 50 = 6.77, P < .05). An interaction of FKBP5 genotype and diagnostic group was also observed (F1, 37 = 4.52, P = .04), indicating lower cingulum FA in carriers of two risk alleles for this SNP, compared to other diagnostic and genotype groups. Carriers of two FKBP5 risk alleles also demonstrated poorer hippocampus-ACC connectivity at rest (P < .05). When cingulum FA was used a regressor in a brain-wide, seed-based regression analysis, significant associations were found between the hippocampus and dorsal regions of the ACC (P < .05). CONCLUSIONS: Individuals with PTSD demonstrated compromised structural connectivity of the hippocampus-ACC pathway. Altered hippocampus-ACC connectivity may represent a highly salient intermediate neural phenotype for PTSD.
Example probabilistic tracts of the cingulum.
Participants with two copies of the (T) risk allele for an FKBP5 polymorphism (rs1360780) and a diagnosis of PTSD demonstrate poorer cingulum connectivity compared to the other genotype and diagnostic groups.
When cingulum FA was used as a regressor in a whole-brain, seed-based analysis, the hippocampus demonstrated significant functional connectivity to dorsal regions of the anterior cingulate, exclusively (p<.05, FWE corrected across the whole brain). Left panel depicts atlas-based ACC mask; right panel depicts regions of ACC activation corresponding with hippocampal activation (unmasked image).
1–20 of 26
Next →
| Name | Type |
|---|---|
| ACC | anatomy |
| African-Americans | cohort |
| age | phenotype |
| Agencourt DNAdvance extraction kit local | drug |
| alcohol dependence | phenotype |
| amygdala | anatomy |
| anterior cingulate cortex | anatomy |
| anxious psychopathology local | phenotype |
| bipolar disorder | phenotype |
| CAPS subscale scores local | phenotype |
| CC/CT genotype local | variant |
| childhood trauma | phenotype |
| cingulum | anatomy |
| cingulum FA local | phenotype |
| contextual memory local | phenotype |
| controls | cohort |
| corpus callosum | anatomy |
| dementia | phenotype |
| depression | phenotype |
| depressive symptoms | phenotype |
| DNA | drug |
| dorsolateral prefrontal cortex | anatomy |
| entorhinal cortex | anatomy |
| extinction learning local | phenotype |
| fear-potentiated startle response | phenotype |
| Fkbp5 | gene |
| FKBP5 CC genotype local | variant |
| FKBP5 CT genotype local | variant |
| FKBP5 risk allele local | variant |
| FKBP5 TT genotype | variant |
| Fornix | anatomy |
| fractional anisotropy | phenotype |
| gel electrophoresis local | drug |
| glucocorticoids | drug |
| Harvard-Oxford Subcortical Structural Atlas local | anatomy |
| head injury with loss of consciousness >5 minutes local | phenotype |
| hippocampal functional connectivity local | phenotype |
| hippocampal-prefrontal connectivity local | anatomy |
| hippocampal-prefrontal pathway local | anatomy |
| hippocampus | anatomy |
| hippocampus-ACC functional connectivity local | phenotype |
| iPlex reagents local | drug |
| MassARRAY system local | drug |
| medial prefrontal cortex | anatomy |
| MNI space local | anatomy |
| mood disorders | phenotype |
| NanoDrop2000 local | drug |
| neurological illness local | phenotype |
| Oragene vials local | drug |
| parahippocampal gyrus | anatomy |
| parietal cortex | anatomy |
| participants | cohort |
| PC FA values local | phenotype |
| physical abuse | phenotype |
| Post-Traumatic Stress Disorder | phenotype |
| prefrontal cortex | anatomy |
| pregnancy | phenotype |
| psychosis | phenotype |
| psychotropic medication | drug |
| PTSD+ local | cohort |
| PTSD group local | cohort |
| Quantity One software local | drug |
| reinforcement learning | phenotype |
| Resting state connectivity local | phenotype |
| rs1360780 | variant |
| saliva | drug |
| schizophrenia | phenotype |
| Sequenom | drug |
| Study cohort (30 participants) local | cohort |
| substance use | phenotype |
| supplementary motor areas local | anatomy |
| TaqMan assay | drug |
| TaqMan Genotyping Master Mix | drug |
| Taqman GTXpress Master Mix local | drug |
| Taqman SNP Genotyping Assays | drug |
| Taqman ViiA7 Real-Time PCR system local | drug |
| Total trauma exposure local | phenotype |
| trauma | phenotype |
| trauma-exposed control group local | cohort |
| trauma exposure | phenotype |
| TT genotype | variant |
| white matter | anatomy |
| working memory | phenotype |
No uploaded files.
Not in any collection.
In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features. | 2023 | 37232664 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Use of Single Prolonged Stress to Model Post-traumatic Stress Disorder in Rodents: What We Found and Where to Next? | Ding K et al. | — | 2026 | → |
| Childhood Adversity Is Associated With Longitudinal White Matter Changes After Adulthood Trauma. | Tianyi Li et al. | — | 2025 | → |
| Epitranscriptomic Analysis of the Ventral Hippocampus in a Mouse Model of Post-Traumatic Stress Disorder Following Deep Brain Stimulation Treatment of the Basolateral Amygdala. | Ma M et al. | — | 2025 | → |
| <i>FKBP5/</i>FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies. | Liu Y et al. | — | 2025 | → |
| Obsessive-compulsive symptoms as a unique presentation of complex posttraumatic stress disorder in Southeast Asia: a case report. | Albert A et al. | — | 2025 | → |
| The rs1360780 Variant of <i>FKBP5</i>: Genetic Variation, Epigenetic Regulation, and Behavioral Phenotypes. | Arancibia M et al. | — | 2025 | → |
| A systematic review on the bidirectional relationship between trauma-related psychopathology and reproductive aging. | Arnold AR et al. | — | 2024 | → |
| Cognitive training and brain stimulation in patients with cognitive impairment: a randomized controlled trial. | Antonenko D et al. | — | 2024 | → |
| Neural underpinnings of a two-phase memory suppression process in the neural response to self-related and observed perspective views. | Song X et al. | — | 2024 | → |
| White matter correlates of dissociation in a diverse sample of trauma-exposed women. | Kondas A et al. | — | 2024 | → |
| Early Social Adversity, Altered Brain Functional Connectivity, and Mental Health. | Holz NE et al. | — | 2023 | → |
| Microstructural and functional plasticity following repeated brain stimulation during cognitive training in older adults. | Antonenko D et al. | — | 2023 | → |
| Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features. | Kamarajan C et al. | — | 2023 | → |
| Structural equation modeling of treatment-related changes in neural connectivity for youth with PTSD. | Garrett AS et al. | — | 2023 | → |
| Acute Posttraumatic Symptoms Are Associated With Multimodal Neuroimaging Structural Covariance Patterns: A Possible Role for the Neural Substrates of Visual Processing in Posttraumatic Stress Disorder. | Harnett NG et al. | — | 2022 | → |
| Adiponectin gene polymorphisms and posttraumatic stress disorder symptoms among female rape survivors: an exploratory study. | Vuong E et al. | — | 2022 | → |
| FKBP51 modulates hippocampal size and function in post-translational regulation of Parkin. | Qiu B et al. | — | 2022 | → |
| FKBP5 intron 7 methylation is associated with higher anxiety proneness and smaller right thalamus volume in adolescents. | Womersley JS et al. | — | 2022 | → |
| Mapping structural covariance networks in children and adolescents with post-traumatic stress disorder after earthquake. | Mo X et al. | — | 2022 | → |
| Prefrontal cortex, amygdala, and threat processing: implications for PTSD. | Alexandra Kredlow M et al. | — | 2022 | → |
| Racial Discrimination and White Matter Microstructure in Trauma-Exposed Black Women. | Fani N et al. | — | 2022 | → |
| Stress-related cognitive style is related to volumetric change of the hippocampus and FK506 binding protein 5 polymorphism in post-traumatic stress disorder. | Yun JY et al. | — | 2022 | → |
| Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium. | Dennis EL et al. | — | 2021 | → |
| Computational analysis of deleterious single nucleotide polymorphisms in catechol O-Methyltransferase conferring risk to post-traumatic stress disorder. | Chitrala KN et al. | — | 2021 | → |
| MicroRNAs as biomarker and novel therapeutic target for posttraumatic stress disorder in Veterans. | Gupta S et al. | — | 2021 | → |
| Multimodal structural neuroimaging markers of risk and recovery from posttrauma anhedonia: A prospective investigation. | Harnett NG et al. | — | 2021 | → |
| The role of childhood trauma, HPA axis reactivity and FKBP5 genotype on cognition in healthy individuals. | Ferrer A et al. | — | 2021 | → |
| White matter microstructure in trauma-exposed children: Associations with pubertal stage. | Fani N et al. | — | 2021 | → |
| Amygdala functional connectivity in the acute aftermath of trauma prospectively predicts severity of posttraumatic stress symptoms. | Belleau EL et al. | — | 2020 | → |
| Childhood maltreatment experiences are associated with altered diffusion in occipito-temporal white matter pathways. | Olson EA et al. | — | 2020 | → |
| FKBP5 and early life stress affect the hippocampus by an age-dependent mechanism. | Criado-Marrero M et al. | — | 2020 | → |
| FKBP5-associated miRNA signature as a putative biomarker for PTSD in recently traumatized individuals. | Kang HJ et al. | — | 2020 | → |
| FKBP5 haplotypes and PTSD modulate the resting-state brain activity in Han Chinese adults who lost their only child. | Qi R et al. | — | 2020 | → |
| FKBP5 methylation predicts functional network architecture of the rostral anterior cingulate cortex. | Muehlhan M et al. | — | 2020 | → |
| Genetic and Neuroimaging Approaches to Understanding Post-Traumatic Stress Disorder. | Nisar S et al. | — | 2020 | → |
| Hypothalamic-pituitary-adrenal axis-related genes and cognition in major mood disorders and schizophrenia: a systematic review. | Ferrer A et al. | — | 2020 | → |
| Impacts of FKBP5 variants on large-scale brain network connectivity in healthy adults. | Zhang H et al. | — | 2020 | → |
| Mild traumatic brain injury impacts associations between limbic system microstructure and post-traumatic stress disorder symptomatology. | Sydnor VJ et al. | — | 2020 | → |
| Nervous and Endocrine System Dysfunction in Posttraumatic Stress Disorder: An Overview and Consideration of Sex as a Biological Variable. | Seligowski AV et al. | — | 2020 | → |
| PTSD-related neuroimaging abnormalities in brain function, structure, and biochemistry. | Harnett NG et al. | — | 2020 | → |
| Rethinking post-traumatic stress disorder - A predictive processing perspective. | Kube T et al. | — | 2020 | → |
| White matter microstructure varies with post-traumatic stress severity following medical trauma. | Harnett NG et al. | — | 2020 | → |
| Adaptive Identification of Cortical and Subcortical Imaging Markers of Early Life Stress and Posttraumatic Stress Disorder. | Salminen LE et al. | — | 2019 | → |
| Altered White Matter Microstructural Organization in Post-Traumatic Stress Disorder across 3,049 Adults: Results from the PGC-ENIGMA PTSD Consortium | Dennis EL et al. | — | 2019 | — |
| Attentional control abnormalities in posttraumatic stress disorder: Functional, behavioral, and structural correlates. | Fani N et al. | — | 2019 | → |
| Cognitive and neural facets of dissociation in a traumatized population. | Fani N et al. | — | 2019 | → |
| Convergent neurobiological predictors of mood and anxiety symptoms and treatment response. | Jabbi M et al. | — | 2019 | → |
| Early Life Stress and High FKBP5 Interact to Increase Anxiety-Like Symptoms through Altered AKT Signaling in the Dorsal Hippocampus. | Criado-Marrero M et al. | — | 2019 | → |
| Frontal Lobe Circuitry in Posttraumatic Stress Disorder. | Selemon LD et al. | — | 2019 | → |
| Structural connectivity and risk for anhedonia after trauma: A prospective study and replication. | Fani N et al. | — | 2019 | → |
| Altered anterior cingulate cortex to hippocampus effective connectivity in response to drug cues in men with cocaine use disorder. | Ma L et al. | — | 2018 | → |
| A Network-Based Neurobiological Model of PTSD: Evidence From Structural and Functional Neuroimaging Studies. | Akiki TJ et al. | — | 2017 | → |
| Brain structural connectivity and context-dependent extinction memory. | Hermann A et al. | — | 2017 | → |
| Dissecting the molecular mechanisms of gene x environment interactions: implications for diagnosis and treatment of stress-related psychiatric disorders. | Binder EB | — | 2017 | → |
| Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery. | Savulich G et al. | — | 2017 | → |
| FKBP5 polymorphisms influence pre-learning stress-induced alterations of learning and memory. | Zoladz PR et al. | — | 2017 | → |
| Gene × Environment Interactions: From Molecular Mechanisms to Behavior. | Halldorsdottir T et al. | — | 2017 | → |
| Persistent amygdala novelty response is associated with less anterior cingulum integrity in trauma-exposed women. | Yoon SA et al. | — | 2017 | → |
| PTSD in Court II: Risk factors, endophenotypes, and biological underpinnings in PTSD. | Young G | — | 2017 | → |
| The FKBP51 Glucocorticoid Receptor Co-Chaperone: Regulation, Function, and Implications in Health and Disease. | Fries GR et al. | — | 2017 | → |
| The evolution of the molecular response to stress and its relevance to trauma and stressor-related disorders. | Watson IPB et al. | — | 2016 | → |