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.

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

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

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. However, it is not clear whether 5-HT1A receptor binding and cortisol responses to stress are related to risk and resilience for suicidal behavior. [11C]CUMI-101 PET imaging to quantify regional brain 5-HT1A receptor binding was conducted in high-risk individuals, having a first or second degree relative(s) with an early onset mood disorder and history of suicidal behavior, and subdivided into: high-risk resilient having no mood disorder or suicidal behavior (HR-R, n=29); high-risk with mood disorder (HR-MOOD n=31); and high-risk with mood disorder and suicidal behavior (HR-SA/MOOD, n=25). Groups were compared to healthy volunteers (HV, n=34). Participants underwent the Trier Social Stress Task (TSST). 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 and BPp in a subset of the sample), and definitions of regions of interest (ROIs; standard or serotonin-specific ROIs). We also found no group differences on TSST outcomes. Within HR-SA/MOOD, lower BPp binding [=-0.084, Standard Error or SE=0.038, p=0.048] and higher cortisol reactivity to stress [=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. In conclusion, 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.

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 Differences in neural and cognitive response to emotional faces in middle-aged dizygotic twins at familial risk of depression

2017 ◽  
Vol 47 (13) ◽  
pp. 2345-2357 ◽  
Author(s):  
K. W. Miskowiak ◽  
A. M. B. Svendsen ◽  
C. J. Harmer ◽  
R. Elliott ◽  
J. Macoveanu ◽  
...  
Keyword(s):  
High Risk ◽  
Face Processing ◽  
Familial Risk ◽  
Risk Groups ◽  
Low Risk ◽  
Middle Aged ◽  
Emotional Faces ◽  
Dizygotic Twins ◽  
History Of ◽  
History Of Depression

BackgroundNegative bias and aberrant neural processing of emotional faces are trait-marks of depression but findings in healthy high-risk groups are conflicting.MethodsHealthy middle-aged dizygotic twins (N = 42) underwent functional magnetic resonance imaging (fMRI): 22 twins had a co-twin history of depression (high-risk) and 20 were without co-twin history of depression (low-risk). During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping.ResultsUnexpectedly, high-risk twins showed reduced fear vigilance and lower recognition of fear and happiness relative to low-risk twins. During face processing in the scanner, high-risk twins displayed distinct negative functional coupling between the amygdala and ventral prefrontal cortex and pregenual anterior cingulate. This was accompanied by greater fear-specific fronto-temporal response and reduced fronto-occipital response to all emotional faces relative to baseline. The risk groups showed no differences in mood, subjective state or coping.ConclusionsLess susceptibility to fearful faces and negative cortico-limbic coupling during emotional face processing may reflect neurocognitive compensatory mechanisms in middle-aged dizygotic twins who remain healthy despite their familial risk of depression.

scholarly journals Ventral prefrontal serotonin 1A receptor binding: neural marker of resilience in individuals with high familial risk for mood disorder and suicidal behavior?

2021 ◽  
Author(s):  
Spiro Pantazatos ◽  
Nadine M. Melhem ◽  
David Brent ◽  
Francesca Zanderigo ◽  
Elizabeth Bartlett ◽  
...  
Keyword(s):  
Suicide Attempt ◽  
Mood Disorder ◽  
Mood Disorders ◽  
Suicidal Behavior ◽  
Univariate Analysis ◽  
Familial Risk ◽  
Temporal Cortex ◽  
Binding Potential ◽  
Serotonin 1A Receptor ◽  
Total N

BACKGROUND: Mood disorders and suicidality have moderate heritability and are associated with altered corticolimbic serotonin 1A receptor (5-HT1A) binding potential. However, it is unclear whether these alterations reflect heritable risk or resilience markers, compensatory mechanisms, or illness-related changes as 5-HT1A binding has never been reported in unaffected high risk individuals (HR) who have passed through the age of greatest risk for psychopathology onset. METHODS: PET imaging quantified brain 5-HT1A binding potential BPND using [11C]CUMI-101 in healthy volunteers (HV) and three groups with one or more relatives with early-onset mood disorder and suicide attempt: 1. HR individuals; 2. HR individuals with a lifetime mood disorder (HR-MOOD); and 3. HR-MOOD individuals with lifetime history of suicide attempt (HR-MOOD/SA). Two additional studies included HV, individuals with low familial risk and current mood disorder (MOOD) and MOOD with lifetime suicide attempt (MOOD/SA) to identify differences persisting across independent cohorts (total N=185: 59 HV, 23 HR, 64 HR-MOOD or MOOD, and 39 HR-MOOD/SA or MOOD/SA). Univariate analysis tested for regional differences and multivoxel pattern analysis (MVPA) tested whether 5-HT1A BPND could distinguish HV, HR, HR-MOOD and HR-MOOD/SA. RESULTS: Low ventral prefrontal 5-HT1A BPND in lifetime MOOD/SA vs. HV and HR was consistently observed across study populations. MVPA distinguished HV from HR-MOOD/SA with informative regions in ventral prefrontal and temporal cortex (peak out-of-sample area under the ROC curve=0.74, p<0.001 corrected). MOOD alone groups did not consistently differ from HV groups. CONCLUSIONS: Low ventral prefrontal 5-HT1A BPND may reflect suicide-related pathology. Further studies are needed to determine if higher ventral prefrontal 5-HT1A BPND may confer resilience for developing suicidal behavior in the context of mood disorders. If so, it could be a potential suicide prevention target.

The Relationship Between Prior Suicidal Behavior and Mortality Among Individuals in Community Corrections

Crisis ◽  
2013 ◽  
Vol 34 (6) ◽  
pp. 428-433 ◽  
Author(s):  
C. Brendan Clark ◽  
Matthew C. Waesche ◽  
Peter S. Hendricks ◽  
Cheryl B. McCullumsmith ◽  
Nicole Redmond ◽  
...  
Keyword(s):  
Suicide Attempt ◽  
Suicidal Behavior ◽  
Social Stress ◽  
Substance Dependence ◽  
Past History ◽  
Community Corrections ◽  
Multiple Risk Factors ◽  
Cox Proportional Hazard ◽  
Risk Of Mortality ◽  
History Of

Background: Individuals under community corrections have multiple risk factors for mortality including exposure to a criminal environment, drug use, social stress, and a lack of medical care that predispose them to accidents, homicides, medical morbidities, and suicide. The literature suggests that prior suicidal behavior may be a particularly potent risk factor for mortality among individuals in the criminal justice system. Aims: This study looked to extend the link between history of a suicide attempt and future mortality in a community corrections population. Method: Using an archival dataset (N = 18,260) collected from 2002 to 2007 of individuals being monitored under community corrections supervision for an average of 217 days (SD = 268), we examined the association between past history of a suicide attempt and mortality. Results: A Cox Proportional Hazard Model controlling for age, race, gender, and substance dependence indicated that past history of a suicide attempt was independently associated with time to mortality, and demonstrated the second greatest effect after gender. Conclusion: These data suggest the need for a greater focus on screening and preventive services, particularly for individuals with a history of suicidal behavior, so as to reduce the risk of mortality in community corrections populations.

scholarly journals Familial Risks between Pernicious Anemia and Other Autoimmune Diseases in the Population of Sweden

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Xinjun Li ◽  
Hauke Thomsen ◽  
Kristina Sundquist ◽  
Jan Sundquist ◽  
Asta Försti ◽  
...  
Keyword(s):  
Pernicious Anemia ◽  
Genetic Background ◽  
Familial Risk ◽  
Population Level ◽  
Population Register ◽  
Degree Relative ◽  
Autoimmune Polyglandular Syndrome ◽  
Population Prevalence ◽  
History Of ◽  
Offspring Generation

Background. Pernicious anemia (PA) is an autoimmune disease (AID) which is caused by lack of vitamin B12 (cobalamin) due to its impaired uptake. PA is a multifactorial disease which is associated with a number of other AID comorbidities and which is manifested as part of autoimmune polyglandular syndrome. Due to the shortage of family studies on PA, we planned to address the problem by assessing familial risks for concordant PA between family members and for discordant PA in families of other AID patients. Methods. We collected data on patients diagnosed with AIDs from the Swedish hospitals and family data from a population register. We calculated standardized incidence ratios (SIRs) in families for concordant and discordant risks. Results. The number of PA patients in the offspring generation (for which the familial risk was calculated) was 7701; 278 (3.6%) patients had a family history of PA. The population prevalence of PA was 0.9/1000. The familial risk for PA was 3.88 when any first-degree relative was the proband, equal for men and women. The familial risk was two times higher between siblings than between offspring and parents which may be due to complex genetic background. Associations of PA with 14 discordant AIDs were significant; these included some AIDs that have previously been described as comorbidities in PA patients and several yet unreported associations, including rheumatoid arthritis and other AIDs. Conclusions. The familial risks for PA were high suggesting multifactorial genetic etiology. The results call for further population-level studies to unravel mechanisms of familial PA which may help to understand the etiology of this disease.

scholarly journals Multilevel assessment of the neurobiological threat system in depressed adolescents: Interplay between the limbic system and hypothalamic–pituitary–adrenal axis

2014 ◽  
Vol 26 (4pt2) ◽  
pp. 1321-1335 ◽  
Author(s):  
Bonnie Klimes-Dougan ◽  
Lynn E. Eberly ◽  
Melinda Westlund Schreiner ◽  
Patrick Kurkiewicz ◽  
Alaa Houri ◽  
...  
Keyword(s):  
Social Stress ◽  
Group Differences ◽  
Threat Detection ◽  
Amygdala Activation ◽  
Stress Task ◽  
Cortisol Responses ◽  
Amygdala Volume ◽  
Cortisol Levels ◽  
Assessment Strategies ◽  
The Brain

AbstractIntegrative, multilevel approaches investigating neurobiological systems relevant to threat detection promise to advance understanding of the pathophysiology of major depressive disorder (MDD). In this study we considered key neuronal and hormonal systems in adolescents with MDD and healthy controls (HC). The goals of this study were to identify group differences and to examine the association of neuronal and hormonal systems. MDD and HC adolescents (N = 79) aged 12–19 years were enrolled. Key brain measures included amygdala volume and amygdala activation to an emotion face-viewing task. Key hormone measures included cortisol levels during a social stress task and during the brain scan. MDD and HC adolescents showed group differences on amygdala functioning and patterns of cortisol levels. Amygdala activation in response to emotional stimuli was positively associated with cortisol responses. In addition, amygdala volume was correlated with cortisol responses, but the pattern differed in depressed versus healthy adolescents, most notably for unmedicated MDD adolescents. The findings highlight the value of using multilevel assessment strategies to enhance understanding of pathophysiology of adolescent MDD, particularly regarding how closely related biological threat systems function together while undergoing significant developmental shifts.

scholarly journals Differential Impact of Child Sexual Abuse and Family History of Suicidal Behavior in High-Risk Suicidal Patients

2019 ◽  
Vol 24 (sup2) ◽  
pp. S251-S263
Author(s):  
Leandro N. Grendas ◽  
Sasha M. Rojas ◽  
Demián E. Rodante ◽  
Soledad Puppo ◽  
Patricia Vidjen ◽  
...  
Keyword(s):  
Sexual Abuse ◽  
Family History ◽  
High Risk ◽  
Child Sexual Abuse ◽  
Suicidal Behavior ◽  
Differential Impact ◽  
History Of ◽  
Suicidal Patients

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.

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