Using iterative random forest to find geospatial environmental and Sociodemographic predictors of suicide attempts

IntroductionDespite a recent global decrease in suicide rates, death by suicide has increased in the United States. It is therefore imperative to identify the risk factors associated with suicide attempts to combat this growing epidemic. In this study, we aim to identify potential risk factors of suicide attempt using geospatial features in an Artificial intelligence framework.MethodsWe use iterative Random Forest, an explainable artificial intelligence method, to predict suicide attempts using data from the Million Veteran Program. This cohort incorporated 405,540 patients with 391,409 controls and 14,131 attempts. Our predictive model incorporates multiple climatic features at ZIP-code-level geospatial resolution. We additionally consider demographic features from the American Community Survey as well as the number of firearms and alcohol vendors per 10,000 people to assess the contributions of proximal environment, access to means, and restraint decrease to suicide attempts. In total 1,784 features were included in the predictive model.ResultsOur results show that geographic areas with higher concentrations of married males living with spouses are predictive of lower rates of suicide attempts, whereas geographic areas where males are more likely to live alone and to rent housing are predictive of higher rates of suicide attempts. We also identified climatic features that were associated with suicide attempt risk by age group. Additionally, we observed that firearms and alcohol vendors were associated with increased risk for suicide attempts irrespective of the age group examined, but that their effects were small in comparison to the top features.DiscussionTaken together, our findings highlight the importance of social determinants and environmental factors in understanding suicide risk among veterans

PET studies of the serotonin system in relation to behavioral phenotypes in psychiatry

Behavioral phenotypes beyond core symptoms of diagnoses have become an area of high interest in psychiatric research. All major psychiatric diagnoses are associated with deficits in cognitive function, including impairments in social abilities, which contribute to great suffering and have a negative impact on the everyday life. Aberrations in the central serotonin system has been demonstrated in several psychiatric disorders. However, treatment targeting cognitive impairment is lacking due to limited understanding of neurobiological mechanisms in psychiatry. The overall aim of this thesis is to investigate associations between cognitive ability and serotonin transporter and serotonin receptor 5- HT1B in major depressive disorder (MDD), autism spectrum disorder (ASD) and in nonpsychiatric control subjects. In Study I, ten patients with MDD were examined with cognitive tests and positron emission tomography (PET) and the radioligand [11C]AZ10419369 binding to 5-HT1B receptor before and after Internet-based cognitive behavioral therapy (ICBT) and for comparison with ten matched control subjects. The results showed improvements in verbal fluency from baseline to follow-up in the patient group. Correlations were found between improvement in verbal fluency and changes in 5-HT1B binding in ventral striatum and amygdala as well as between cognitive flexibility and dorsal brainstem, amygdala and hippocampus. In the control group when controlled for age and education level, an association between visuo-constructive memory and 5-HT1B availability in dorsal brainstem was demonstrated. The finding implicates a positive association between improvement in executive function and change in 5-HT1B binding in the MDD group. Study II investigated cognitive performance and the serotonin transporter (5-HTT) availability with PET and the radioligand [11C]MADAM in fifteen adults with ASD and fifteen matched control subjects. Analyses revealed lower 5-HTT availability in several brain regions in the ASD group compared to the controls. Also, positive associations between social cognition and 5-HTT binding were demonstrated. These results are in line with the hypothesis of lower brain 5-HTT binding in individuals with ASD, and further supports the theory of serotonin involvement in ASD neurodevelopment. In Study III, cognitive ability and 5-HT1B receptor binding with PET and the radioligand [11C]AZ10419369 were examined in 43 healthy control subjects. Our aim were to replicate parts of Study I as well as explore if other cognitive domains were associated with 5-HT1B. The findings between visuo-constructive performance and 5-HT1B receptor binding in the dorsal brainstem from Study I could not be replicated. Exploratory analyses when not controlled for age, revealed positive associations between visuo-constructive memory and 5-HT1B binding in several brain regions as well as negative correlations between 5-HT1B binding in numerous brain regions and cognitive flexibility and reaction time. When controlling for age effects, negative correlations between reaction time and 5-HT1B availability remained. Since a negative correlation between reaction time and amount of errors was found, implying faster reaction time and poorer impulse inhibition, these findings suggest that 5-HT1B receptors are involved in impulsive behavior. In Study IV, we investigated autism-related cognitive functions and the serotonin transporter (5-HTT) as well as serotonin receptor 5-HT1B with PET and the radioligands [11C]MADAM and [11C]AZ10419369 in a sample of healthy participants. In the 5-HTT sample, positive correlations between social cognition and standardized 5-HTT binding in striatum and putamen, as well as a negative correlation between social cognition and standardized 5-HTT binding in brainstem, were demonstrated. In the 5-HT1B sample, a significant correlation between central coherence and 5-HT1B binding in thalamus was found, but after controlling for age effects the correlation did not remain significant. The results of 5-HT1B binding in autism-like cognition do not support an association. Together with our finding of brain 5-HTT binding in relation to social-cognitive ability in neurotypical controls, and previous literature of individuals with ASD, a neurobiological and behavioral phenotype continuously distributed in the population is suggested for social ability

Long term isolation in Antarctica - shifts in nocturnal heart rate variability indicating modulated regulation of the autonomic nervous system

Ein 14-monatiger Aufenthalt in der Antarktis an der Forschungsstation Neumayer III ist für das Team der Überwinternden eine Herausforderung an Psyche und Physis. Soziale Isolation, Reizdeprivation, Leben in einem künstlichen abgeschlossenen Habitat, lebensfeindliche Umgebung, sowie der durch Polarnacht und Polartag alterierte circadiane Rhythmus bedeuten erheblichen Stress für die Überwinternden. Diese Studie untersucht erstmals, ob eine stressbedingte Veränderung der sympathovagalen Balance anhand von Veränderungen der nächtlichen Herzfrequenzvariabilität während einer langfristigen antarktischen Überwinterungskampagne beobachtet werden kann. Insgesamt dreizehn Testpersonen zeichneten jeweils während der Isolationsphasen 2017 und 2018 von Februar bis Oktober monatlich ein 24h EKG auf. Im Rahmen dieser Studie erfolgt die Analyse von Faktoren der Herzfrequenzvariabilität der Zeit- und Frequenzdomäne. Störungsarme Aufzeichnungen der Herzfrequenzvariabilität wurden während der Nachtstunden von 00:00 – 06:00 Uhr erfasst. Es zeigen sich aufschlussreiche Veränderungen der autonomen Regulation über die Isolationsphase der Überwinterung. So nahm die Dauer einer elektrischen Herzaktion, als wichtiger Indikator für Fitness und Wohlbefinden gegen Ende der Polarnacht deutlich ab. Kohärent hierzu veränderte sich die autonome Regulation des Herzens über den Beobachtungszeitraum. Die Faktoren pNN50 und rMSSD, als Parameter des Einflusses des parasympathischen Nervensystems (Resilienz, Erholungsfähigkeit, Regenerationsfähigkeit), erreichten am Ende der Polarnacht ihren Minimalwert. Der Faktor SDNN unterschritt klinisch etablierte Grenzwerte als Zeichen eines erhöhten kardiovaskulären Morbiditätsrsisikos. Zudem verschob sich das Verhältnis LF/HF, als Indikator der sympathovagalen Balance, mit Zunahme der sympathischen Aktivität unter Abnahme des Parasympathikustonus. Die Studie belegt wegweisend, dass während der Isolationsphase der Überwinterung die sympathovagale Balance mit fortschreitender Isolationsdauer durch sympathischen Einfluss dominiert wird und zum Teil gravierende Veränderungen der Regulation des autonomen Nervensystems beobachtet werden können.A 14-month stay in the Antarctic at Neumayer III research station is challenging to psyche and physis of the wintering team. Social isolation, deprivation, containment, hos-tile environment and altered circadian rhythm cause considerable stress for those who winter over. This study enquires whether a stress-induced alteration of the sympathovagal balance is revealed by shifts in nocturnal heart rate variability (HRV) during a long-term Antarctic wintering campaign. Thirteen test persons in total recorded a monthly 24-hour ECG during the isolation phase from February to October 2017 and 2018 respectively. This study targets the analysis of representative factors of time and frequency domain of HRV. Reliable recordings of HRV were observed during night hours from 00:00-06:00 UTC, which revealed the modulation of autonomous regulation over the isolation period. The duration of an electrical heart action decreased significantly towards the end of the polar night. Furthermore, a change in autonomous regulation of the heart could be ob-served. Parameters that represent the influence of the parasympathetic nervous system (resilience, ability to recover, regenerative capacity), such as pNN50 and rMSSD reached their minimum value at the end of the polar night. Time domain factor SDNN even decreased below clinically established limits as a sign of an increased risk of cardiovascular morbidity. Frequency domain factor LF/HF as an indicator of sympathovagal balance shifted with a gradual increase in sympathetic activity at the expense of parasympathetic activity. The study holds evidence that during the isolation period of the winter over campaign sympathovagal balance gets more dominated by sympathetic influence and partially severe changes in the regulation of the autonomic nervous system take place

The Impact of Sunlight Variation on Depressive Symptoms Following Treatment for Major Depressive Disorder

Introduction: Seasonal variation in sunlight has been implicated in the pathogenesis and maintenance of major depressive disorder (MDD), but has not yet been evaluated as a potential moderator of recovery. Given the high rate of recurrence following treatment for depression, there is a need to identify risk factors that contribute to poor long-term prognosis. The present study seeks to examine the relationship between seasonal sunlight and follow-up outcomes for MDD treatment. Methods: A secondary analysis was conducted on data collected by the NIMH Treatment of Depression Collaborative Research Program. Follow-up data were available from 159 participants who completed the acute treatment phase of the study, which consisted of cognitive behavior therapy (CBT), interpersonal therapy, imipramine, or placebo administered for 16 weeks. Depressive symptom severity, recovery status, and categorical ratings of symptomatology were then measured on four occasions during the 18-month follow-up period. Treatment site-specific sunlight data were collected from the NREL National Solar Radiation Data Base. Multilevel modeling was used to estimate seasonal differences for all outcomes. Results: Sunlight intensity at the time of patient assessment was significantly inversely associated with the severity of depressive symptoms, and the strength of this relationship decreased over the follow-up period. At the baseline (treatment termination) assessment, a one standard deviation increase in sunlight intensity predicted a 1.83-point reduction on the Hamilton Rating Scale for Depression. Symptom severity was significantly greater during winter sunlight conditions (versus summer) at both the baseline assessment and at the 6-month follow-up. At the baseline assessment, the effect of winter-versus-summer sunlight was substantial, equivalent to approximately 4.5 points on the HRSD; the effect was reduced to just over two HRSD points at the 6-month assessment. Exploratory analyses revealed that significant seasonal-typical differences in symptom severity were limited to participants who had been assigned to the CBT and placebo conditions. Sunlight was not significantly associated with recovery status or categorical ratings of symptomatology. Conclusion: Sunlight intensity was inversely associated with depressive symptom severity following psychotherapy, pharmacotherapy, or placebo treatment for depression. This effect persisted for six months post-treatment. Completing treatment during winter-typical sunlight conditions was associated with substantially higher levels of residual depressive symptoms—particularly for participants receiving CBT. Such adverse effects of relative sunlight deprivation could, in turn, increase the risk of negative long-term clinical outcomes, and prolonged or adjuvant treatments for light-deficient patients may be warranted

Measuring sociogenic, behavioral, and environmental impacts on circadian and rest-activity rhythms in healthy and pathological populations using actigraphy

Few biological systems are as ubiquitous as the circadian rhythm, a distributed yet inter-connected “system of systems” that coordinates the timing of physiological processes via a self-regulating, flexible network present at every level of biological organization, from cells to cities. Its functional role as the interface between time-dependent internal processes and external environmental cues exposes the circadian rhythm to disruption if these drift out of synchrony. This is especially common in industrialized human societies, where the abun-dance of resources – in combination with the fact that anthropogenic calendars have largely supplanted the sun as the primary determinant of our daily cycles of rest, activity, and sleep – disrupts the circadian rhythm’s ability to synchronize biological processes with each other and the geophysical solar day. Humans are now beholden to two increasingly disconnected clocks, and the ever-accelerating curve of human progress suggests our biological and so-cial times will only grow more disconnected. Longitudinal “out-of-clinic” monitoring is an ecologically valid alternative to well-controlled laboratory studies that can provide insight into how human circadian and behav-ioral rhythms exist in day-to-day life, and so has great potential to provide contextual data for translating chronobiological science into clinical intervention. However, methodological diversity, inconsistent terminology, insufficient reporting, and the sheer number of potential factors has slowed progress. Herein is presented scientific work focused on detecting and quantifying some of these factors, particularly “sociogenic” determinants such as the seven-day week. Through rhythmometric analysis of longitudinal in-home actigraphy, weekly be-havioral patterns were observed in both young adult males (n = 24, mean age = 23.46 years) and older adults with Parkinson’s disease (n = 13 [7 male], mean age = 60.62 years, mean Hoehn & Yahr Stage = 2.31) that evince a seven-day “circaseptan” rhythm of circadi-an and sleep disruption. This is hypothesized to be dependent upon the seven-day calendar week, particularly the regular and abrupt shifts in timing between work and rest days. These perturbations vary by chronotype in young adults, and by disease severity in Parkin-son’s disease. Collectively, these results contribute to the growing evidence that our daily rhythms are shaped by sociogenic factors in addition to well-documented environmental and biological mechanisms. Moreover, the study of these subtle infradian patterns presents serious – yet surmountable – methodological challenges that must be overcome in order to accurately monitor, quantify, analyze, report, and apply findings from observational studies of naturalistic human behavior to scientific and clinical problems