scholarly journals Trajectory of brain maturation in adolescent individuals at familial risk of mood disorder

2019 ◽  
Author(s):  
Laura de Nooij ◽  
Mathew A. Harris ◽  
Emma L. Hawkins ◽  
Xueyi Shen ◽  
Toni-Kim Clarke ◽  
...  
Keyword(s):  
Mood Disorder ◽  
Longitudinal Research ◽  
Familial Risk ◽  
Structural Mri ◽  
Brain Maturation ◽  
History Of ◽  
The Difference ◽  
Prospective Longitudinal ◽  
Brain Age

AbstractBackgroundAccelerated biological ageing has been proposed as a mechanism underlying mood disorder, but has been predominantly studied cross-sectionally in adult populations. It remains unclear whether differential ageing/maturation trajectories emerge earlier in life, in particular during the neurodevelopmental period of adolescence, and whether they are associated with onset of mood disorder and/or presence of familial risk.MethodsParticipants were young individuals (16-25 years) from the prospective longitudinal Scottish Bipolar Family Study (SBFS) with and without family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, individual maturational trajectories were captured by the difference between predicted brain age and chronological age (brain-PAD) at baseline and two-year follow-up. Based on clinical assessment at follow-up, individuals were categorised into three groups: (i) controls who remained well (C-well,n=94), (ii) high familial risk who remained well (HR-well,n=73) and (iii) high familial risk who developed a mood disorder (HR-MD,n=38).ResultsResults showed no differences in brain-PAD between groups at baseline or follow-up. However, we found negative trajectories of brain-PAD for HR-MD versus C-well (β= −0.68 years,p<.001) and versus HR-well (β= −0.38 years,p=.01), and for HR-well versus C-well (β= −0.30 years,p=.03).ConclusionsThese findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain maturation trajectory. However, without significantly differential status of brain maturation at follow-up, extended longitudinal research will need to show whether this marks the emergence of maturational lag.

scholarly journals Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder

2019 ◽  
Vol 4 ◽  
pp. 206
Author(s):  
Laura de Nooij ◽  
Mathew A. Harris ◽  
Emma L. Hawkins ◽  
Toni-Kim Clarke ◽  
Xueyi Shen ◽  
...  
Keyword(s):  
Mood Disorder ◽  
Brain Structure ◽  
Longitudinal Research ◽  
Familial Risk ◽  
Age Difference ◽  
Age Related ◽  
Brain Ageing ◽  
Prospective Longitudinal ◽  
Brain Age

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain ageing. Currently, it remains unclear whether young individuals show differential brain structure ageing trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well (β = -0.60, pcorrected < 0.001) and HR-well (β = -0.36, pcorrected = 0.02), with a potential intermediate trajectory for HR-well (β = -0.24 years, pcorrected = 0.06).   Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure ageing trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

scholarly journals Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder from the Scottish Bipolar Family Study

2020 ◽  
Vol 4 ◽  
pp. 206
Author(s):  
Laura de Nooij ◽  
Mathew A. Harris ◽  
Emma L. Hawkins ◽  
Toni-Kim Clarke ◽  
Xueyi Shen ◽  
...  
Keyword(s):  
Mood Disorder ◽  
Brain Structure ◽  
Family Study ◽  
Familial Risk ◽  
Age Difference ◽  
Age Related ◽  
Brain Ageing ◽  
Prospective Longitudinal ◽  
Brain Age

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain ageing. Currently, it remains unclear whether young individuals show differential brain structure aging trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well (β = -0.60, pcorrected < 0.001) and HR-well (β = -0.36, pcorrected = 0.02), with a potential intermediate trajectory for HR-well (β = -0.24 years, pcorrected = 0.06).   Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure aging trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

scholarly journals Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder from the Scottish Bipolar Family Study

2020 ◽  
Vol 4 ◽  
pp. 206
Author(s):  
Laura de Nooij ◽  
Mathew A. Harris ◽  
Emma L. Hawkins ◽  
Toni-Kim Clarke ◽  
Xueyi Shen ◽  
...  
Keyword(s):  
Mood Disorder ◽  
Brain Structure ◽  
Family Study ◽  
Brain Aging ◽  
Familial Risk ◽  
Age Difference ◽  
Age Related ◽  
Prospective Longitudinal ◽  
Brain Age

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain aging. Currently, it remains unclear whether young individuals show differential brain structure aging trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well (β = -0.60, pcorrected < 0.001) and HR-well (β = -0.36, pcorrected = 0.02), with a potential intermediate trajectory for HR-well (β = -0.24 years, pcorrected = 0.06).   Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure aging trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

Incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy

2019 ◽  
Vol 101-B (11) ◽  
pp. 1379-1384 ◽  
Author(s):  
Jin-Sung Park ◽  
Se-Jun Park ◽  
Chong-Suh Lee
Keyword(s):  
Surgical Treatment ◽  
Spinal Metastasis ◽  
Spinal Disease ◽  
Primary Malignancy ◽  
Initial Manifestation ◽  
Kaplan Meier ◽  
History Of ◽  
The Mean ◽  
The Difference

Aims This study aimed to evaluate the incidence and prognosis of patients with spinal metastasis as the initial manifestation of malignancy (SM-IMM). Patients and Methods We retrospectively reviewed the electronic medical records of 338 patients who underwent surgical treatment for metastatic spinal disease. The enrolled patients were divided into two groups. The SM-IMM group included patients with no history of malignancy whose site of primary malignancy was diagnosed after the identification of spinal metastasis. The other group included patients with a history of treatment for primary malignancy who then developed spinal metastasis (SM-DTM). The incidence of SM-IMM by site of primary malignancy was calculated. The difference between prognoses after surgical treatment for SM-IMM and SM-DTM was established. Results The median follow-up period was 11.5 months (interquartile range (IQR) 3.2 to 13.4) after surgical treatment. During the follow-up period, 264 patients died; 74 patients survived. The SM-IMM group consisted of 94 patients (27.8%). The site of primary malignancy in the SM-IMM group was lung in 35/103 patients (34.0%), liver in 8/45 patients (17.8%), kidney in 10/33 patients (30.3%), colorectum in 3/29 patients (10.3%), breast in 3/22 patients (13.6%), prostate in 3/10 patients (30%), thyroid in 4/8 patients (50%), and ‘other’ in 28/88 patients (31.8%). On Kaplan–Meier survival analysis, the SM-IMM group showed a significantly longer survival than the SM-DTM group (p = 0.013). The mean survival time was 23.0 months (95% confidence interval (CI) 15.5 to 30.5) in the SM-IMM group and 15.5 months (95% CI 11.8 to 19.2) in the SM-DTM group. Conclusion Of the 338 enrolled patients who underwent surgical treatment for spinal metastasis, 94 patients (27.8%) underwent surgical treatment for SM-IMM. The SM-IMM group had an acceptable prognosis with surgical treatment. Cite this article: Bone Joint J 2019;101-B:1379–1384.

scholarly journals The Natural History of Ossification of Yellow Ligament of the Thoracic Spine on MRI: A Population-Based Cohort Study

2020 ◽  
pp. 219256822090376 ◽  
Author(s):  
Chris Yuk Kwan Tang ◽  
Kenneth Man Chee Cheung ◽  
Dino Samartzis ◽  
Jason Pui Yin Cheung
Keyword(s):  
Cohort Study ◽  
Natural History ◽  
Thoracic Spine ◽  
Population Based ◽  
Close Monitoring ◽  
Level Of Evidence ◽  
Southern Chinese ◽  
History Of ◽  
Prospective Longitudinal

Purpose: To assess the natural history of ossification of yellow ligament (OYL) in the thoracic spine and determine risk factors for progression based on a longitudinal population-based cohort. Methods: A prospective, longitudinal cohort study was performed on a population-based cohort of Southern Chinese volunteers. T2-weighted magnetic resonance imaging (MRI) was used at baseline to identify any OYL and was verified with computed tomography. Follow-up MRI was performed 5 years later. Parameters under study included the size of OYL, levels of involvement, morphology (round, triangular, beak), whether it crossed the midline and any disc degeneration. Results: A total of 114 (6.1%) individuals were identified to have OYL at baseline out of the 1864 individuals. Size progression occurred predominantly at the lower thoracic region. Majority of the new OYL were also in the lower thoracic spine and was associated with higher body mass index (BMI). Smokers were associated with OYL size progression while patients with higher BMI tended to develop new OYL at follow-up. Progression commonly occurred at the lower thoracic levels and regression occurred mostly at the upper thoracic levels. Conclusions: This is the first population-based series addressing the natural history of OYL. Better understanding of the natural history of OYL may provide incentive to introduce preventive measures such as weight reduction and close monitoring for myelopathy development in those at-risk groups for progression. This is especially important for patients with lower thoracic OYL and who are smokers with higher BMI. Level of Evidence: 1 (prognostic study).

scholarly journals Clinical Characteristics in Early Childhood Associated with a Nevus-Prone Phenotype in Adults from Tropical Australia: Two Decades of Follow-Up of the Townsville Preschool Cohort Study

2020 ◽  
Vol 17 (22) ◽  
pp. 8680
Author(s):  
Ramez Barsoum ◽  
Simone L. Harrison
Keyword(s):  
Longitudinal Research ◽  
Sun Exposure ◽  
Cost Effective ◽  
Risk Groups ◽  
Melanoma Risk ◽  
Bottom Quartile ◽  
Targeted Screening ◽  
History Of ◽  
Tropical Australia

Having numerous melanocytic nevi increases melanoma risk. Few studies have enumerated nevi in children and re-examined them as adults. We aimed to determine if childhood nevus-counts predict nevus-prone adults, and further explore the relevance of host-factors and sun-exposure. Fifty-one Caucasian residents of Townsville (19.16° S, Queensland, Australia) had full-body nevus-counts aged 1–6 and 21–31 years-old. Sun-exposure was determined from questionnaires. Children in the upper-quartile of nevus-counts acquired nevi more rapidly than those in the bottom-quartile (13.3 versus 4.7 nevi/year; p < 0.0005). Children sunburnt before 7 years-old acquired more incident nevi by adulthood (238 versus 126, p = 0.003) particularly if sunburn was severe (321 versus 157.5, p = 0.003) or erythema occurred annually (380 versus 132, p = 0.008). Fair-skinned, freckled children with some nevi ≥ 3 mm, solar lentigines, or a family history of melanoma acquired more incident nevi than children without these attributes. Nevus-prone adults exhibit distinguishing features earlier in life (<7 years-old in Queensland) than has been shown previously. In addition to intervening with sun-protection counselling early enough to reduce risk, being able to reliably triage children into high- and low melanoma-risk groups may inform more efficacious and cost-effective targeted-screening in melanoma-prone populations. Further longitudinal research is needed to confirm that these attributes can reliably separate risk-groups.

The IPI Predicts Outcome in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Immunochemotherapy: A Report of the University of Iowa/Mayo Clinic SPORE

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1279-1279
Author(s):  
Thomas M. Habermann ◽  
B.K. Link ◽  
M.J. Maurer ◽  
J.E. Wooldridge ◽  
S.M. Geyer ◽  
...  
Keyword(s):  
Strong Predictor ◽  
Predictive Ability ◽  
B Cell Lymphoma ◽  
University Of Iowa ◽  
History Of ◽  
Observational Cohort ◽  
Factor Index ◽  
The Difference ◽  
The University

Abstract The International Prognostic Factor Index (IPI) predicts survival in DLBCL in patients treated with chemotherapy. The Revised IPI (R-IPI) has been reported to be a simpler and more accurate predictor of outcome in patients treated with immunochemotherapy (rituximab and anthracycline-based chemotherapy). We evaluated the predictive value of the IPI and the R-IPI in an observational cohort of unselected patients treated with R-CHOP. Consecutive, newly diagnosed patients age 18 years and older with DLBCL were prospectively offered enrollment into our Lymphoma SPORE Registry. Pathology was centrally reviewed, and composite lymphomas and history of concurrent or prior cancers were excluded. All patients were actively followed for progression free progression (PFS) and overall survival (OS). Here we report on patients enrolled from 9/2002 – 6/2006. 229 patients with a median age of 62 years (range 20–93) were evaluated. 56% were >60 years of age, 16% had a performance score ≥2, 54% had an elevated LDH, 19% had >1 extranodal site, and 51% were stage III/IV. During follow-up, there were 63 progressions (28%) and 45 deaths (20%), and the median follow-up time for living patients was 34 months (range 6–61 months). As shown in the table and figure, the IPI and R-IPI were predictive for both PFS and OS (all p<0.001). The predictive ability of the IPI as measured by 3-year concordance index was stronger for the IPI (0.71) compared to the R-IPI (0.67) and the bootstrap 95% confidence interval for the difference (0.01, 0.08) indicates that this difference was statistically significant. While all factors in the IPI were statistically significant (p<0.05) predictors of OS individually, when included in a multivariate model, an elevated LDH (HR=1.5; p = 0.32) and >1 extranodal sites (HR=1.0; p = 0.96) were no longer significant; similar results were obtained for PFS. The IPI remains a strong predictor of PFS and OS in the immunochemotherapy era. Figure Figure Group % Pats 3 Y PFS HR 95% CI 3 Y OS HR 95% CI Standard IPI Low (0,1) 41% 87% 1.0 ref 93% 1.0 ref Low-Int (2) 22% 62% 3.1 (1.4, 6.8) 74% 4.2 (1.6, 11.1) High-Int (3) 21% 60% 3.1 (1.4, 6.8) 77% 3.4 (1.2, 9.7) High (4,5) 15% 39% 7.2 (3.4, 15.2) 47% 10.2 (4.0, 26.5) R-IPI Very good (0) 11% 96% 1.0 ref 100% 1.0 ref Good (1,2) 53% 74% 6.2 (0.8, 46.0) 84% - - Poor (3–5) 36% 52% 13.5 (1.8, 98.9) 65% - -

scholarly journals Prospective longitudinal voxel-based morphometry study of major depressive disorder in young individuals at high familial risk

2016 ◽  
Vol 46 (11) ◽  
pp. 2351-2361 ◽  
Author(s):  
T. Nickson ◽  
S. W. Y. Chan ◽  
M. Papmeyer ◽  
L. Romaniuk ◽  
A. Macdonald ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
High Risk ◽  
Depressive Disorder ◽  
Mood Disorder ◽  
Childhood Trauma ◽  
Familial Risk ◽  
Voxel Based Morphometry ◽  
Major Depressive ◽  
Potential Biomarker ◽  
Prospective Longitudinal

BackgroundPrevious neuroimaging studies indicate abnormalities in cortico-limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel-based morphometry to examine the trajectory of these abnormalities during early stages of illness development.MethodUnaffected individuals (16–25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls (‘low risk’, n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures.ResultsSignificant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub-diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline.ConclusionsThese longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures.

scholarly journals History of childbirths relates to region-specific brain aging patterns in middle and older-aged women

2020 ◽  
Author(s):  
Ann-Marie G. de Lange ◽  
Claudia Barth ◽  
Tobias Kaufmann ◽  
Melis Anatürk ◽  
Sana Suri ◽  
...  
Keyword(s):  
Brain Aging ◽  
Reward System ◽  
Regional Brain ◽  
Pregnancy And Postpartum ◽  
Maternal Brain ◽  
History Of ◽  
Novel Applications ◽  
Prospective Longitudinal ◽  
Brain Age ◽  
Age Prediction

AbstractPregnancy involves maternal brain adaptations, but little is known about how parity influences women’s brain aging trajectories later in life. In this study, we replicated previous findings showing less apparent brain aging in women with a history of childbirths, and identified regional brain aging patterns linked to parity in 19,787 middle and older-aged women. Using novel applications of brain-age prediction methods, we found that a higher number of previous childbirths was linked to less apparent brain aging in striatal and limbic regions. The strongest effect was found in the accumbens – a key region in the mesolimbic reward system, which plays an important role in maternal behavior. While only prospective longitudinal studies would be conclusive, our findings indicate that subcortical brain modulations during pregnancy and postpartum may be traceable decades after childbirth.

scholarly journals Brain 5-HT1A Receptor PET Binding, Cortisol Responses to Stress, and the Familial Transmission of Suicidal Behavior

2021 ◽  
Author(s):  
Nadine M Melhem ◽  
Yongqi Zhong ◽  
Jeffrey M Miller ◽  
Francesca Zanderigo ◽  
R Todd Ogden ◽  
...  
Keyword(s):  
High Risk ◽  
Mood Disorder ◽  
Receptor Binding ◽  
Suicidal Behavior ◽  
Social Stress ◽  
Familial Risk ◽  
Group Differences ◽  
Degree Relative ◽  
History Of ◽  
Cortisol Responses

Abstract Background The serotonin 1A (5-HT1A) receptor has been implicated in depression and suicidal behavior. Lower resting cortisol levels are associated with higher 5-HT1A receptor binding, and both differentiate suicide attempters with depression. However, it is not clear whether 5-HT1A receptor binding and cortisol responses to stress are related to familial risk and resilience for suicidal behavior. Methods [ 11C]CUMI-101 PET imaging to quantify regional brain 5-HT1A receptor binding was conducted in individuals considered to be at high-risk for mood disorder or suicidal behavior on the basis of having a first or second degree relative(s) with an early onset mood disorder and history of suicidal behavior. These high-risk subjects were subdivided into: high-risk resilient having no mood disorder or suicidal behavior (HR-R, n=29); high-risk with mood disorder and no suicidal behavior history (HR-MOOD n=31); and high-risk with mood disorder and suicidal behavior (HR-SA/MOOD, n=25). Groups were compared to healthy volunteers without a family history of mood disorder or suicidal behavior (HV, n=34). Participants underwent the Trier Social Stress Task (TSST). All subjects were free from psychotropic medications at the time of the TSST and PET scanning. Results We observed no group differences in 5-HT1A receptor binding considering all regions simultaneously, nor did we observe heterogeneity of the effect of group across regions. These results were similar across outcome measures (BPND for all subjects and BPp in a subset of the sample), and definitions of regions of interest (ROIs; standard or serotonin system-specific ROIs). We also found no group differences on TSST outcomes. Within HR-SA/MOOD, lower BPp binding [β=-0.084, Standard Error or SE=0.038, p=0.048] and higher cortisol reactivity to stress [β=9.25, 95% CI (3.27,15.23), p=0.004] were associated with higher lethality attempts. There were no significant relationships between 5-HT1A binding and cortisol outcomes. Conclusions 5-HT1A receptor binding in ROIs was not linked to familial risk or resilience protecting against suicidal behavior or mood disorder although it may be related to lethality of suicide attempt. Future studies are needed to better understand the biological mechanisms implicated in familial risk for suicidal behavior and how HPA axis function influences such risk.

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