Sleep measures as a predictor of suicidal ideation among high-risk adolescents.

Suicide is the second leading cause of death among youth aged 15-24 years. Identifying modifiable risk factors relevant to adolescents is crucial for suicide prevention. Sleep patterns have been linked to suicidality in adults, but lack sufficient study in youth. This ecological momentary assessment (EMA) study aimed to explore the relationship between objectively and subjectively measured sleep characteristics and next-day suicidal ideation in high-risk youth. We included 29 adolescents (12-18 years old) admitted to the inpatient psychiatric ward post-suicide attempt or due to suicidal intent within the previous month. We conducted objective (actigraphy) and subjective (sleep diary) sleep pattern assessments over ten consecutive days. Daily suicidal ideation was evaluated using a questionnaire based on the validated C-SSRS interview. A significant positive association was observed between sleep onset latency (SOL) and expressing a "death wish" the following day (OR = 1.06, 95% CI [1-1.11], p = .04), with each minute of longer SOL increased the risk for a death wish the following day by 6%. In addition, a marginally significant negative association was observed between total sleep time (TST) and expressing a "death wish" the following day (OR = 0.57, 95% CI [0.3-1.11], p = 0.1), with each one-hour decrease in objectively measured TST increasing the odds of a death wish by 43%. Our study highlights the interplay between sleep patterns and suicidal ideation, with SOL and TST playing a significant role that may function as proximal risk factors for suicidality and as a target for intervention while treating suicidal youth.

Decreased mononuclear cell NR3C1 SKA2 and FKPB5 expression levels among adult survivors of suicide bombing terror attacks in childhood are associated with the development of PTSD.

Life threatening trauma and the development of PTSD during childhood, may each associate with transcriptional perturbation of immune cell glucocorticoid reactivity, yet their separable longer term contributions are less clear. The current study compared resting mononuclear cell gene expression levels of the nuclear receptor, subfamily 3, member 1 (NR3C1) coding the glucocorticoid receptor, its trans-activator spindle and kinetochore-associated protein 2 (SKA2), and its co-chaperon FKBP prolyl isomerase 5 (FKBP5), between a cohort of young adults first seen at the Hadassah Emergency Department (ED) after surviving a suicide bombing terror attack during childhood, and followed longitudinally over the years, and matched healthy controls not exposed to life threatening trauma. While significant reductions in mononuclear cell gene expression levels were observed among young adults for all three transcripts following early trauma exposure, the development of subsequent PTSD beyond trauma exposure, accounted for a small but significant portion of the variance in each of the three transcripts. Long-term perturbation in the expression of immune cell glucocorticoid response transcripts persists among young adults who develop PTSD following life threatening trauma exposure in childhood, denoting chronic dysregulation of immune stress reactivity.

Resting mononuclear cell NR3C1 and SKA2 expression levels predict blunted cortisol reactivity to combat training stress among elite army cadets exposed to childhood adversity.

Childhood adversity (CA) may alter reactivity to stress throughout life, increasing risk for psychiatric and medical morbidity, yet long-term correlates of milder CA levels among high functioning healthy adolescents are less studied. The current study examined the prevalence and impact of CA exposure among a cohort of healthy motivated elite parachute unit volunteers, prospectively assessed at rest and at the height of an intensive combat-simulation exposure. We found significantly reduced gene expression levels in resting mononuclear cell nuclear receptor, subfamily 3, member 1 (NR3C1), and its transactivator spindle and kinetochore-associated protein 2 (SKA2), that predict blunted cortisol reactivity to combat-simulation stress among CA exposed adolescents. Long-term alterations in endocrine immune indices, subjective distress, and executive functions persist among healthy high functioning adolescents following milder CA exposure, and may promote resilience or vulnerability to later real-life combat exposure.

Longitudinal course and risk factors associated with psychosis in bipolar youths.

OBJECTIVES: To compare the longitudinal clinical course of youths with bipolar disorder (BD) spectrum with lifetime (past, intake, and/or follow-up) psychosis (BDP+) to youths with BD without lifetime psychosis (BDP-). Also, to identify risk factors associated with increased risk of first onset of psychosis during prospective follow-up. METHOD: Bipolar disorder youths (BDP+ = 137, BDP- = 233), aged 7-17 years old, were followed on average every 7 months for 11.7 years and were evaluated using standardized instruments. Data were analyzed using linear and generalized linear models for the full sample, as well as for youths who developed first period of psychosis (n = 55). RESULTS: After adjusting for confounders, BDP+ youths with one, and in particular ≥2 lifetime psychotic episodes, had higher rates and more severe mood and anxiety symptoms, higher rates of suicidality, psychiatric hospitalizations, and sexual/physical abuse, and poorer psychosocial functioning than BDP- youths. Even before the first onset of psychosis during follow-up, BDP+ youths showed more psychopathology and had more family history of psychiatric illness than those who never developed psychosis. First-onset psychosis was associated with low socioeconomic status (SES), living with one parent, bipolar disorder type one and type two, comorbid anxiety, history of hospitalizations, and family history of mania and suicidality. CONCLUSION: BDP+ is associated with poor prognosis and worse clinical picture, even before the onset of psychosis, indicating the need for prompt identification and treatment of these youths. Studies aimed to treat acute symptoms of psychosis, as well as prevent the onset of psychosis, including risk factors amenable to change, are warranted.

Elevated salivary uric acid levels among adolescents with eating disorders.

OBJECTIVE: Uric acid (UA) is increasingly recognized as having important physiological roles and associated with several peripheral and central pathophysiological outcomes, and might play a role in eating disorders (ED) pathogenesis. We investigated whether UA levels are altered among adolescents with ED. METHODS: Morning salivary UA concentrations were compared between adolescents referred to treatment at the Herman Dana Center receiving a DSM-V diagnosis of an ED and matched healthy controls. RESULTS: Salivary UA was significantly elevated among ED compared with control values (ED mean 3.9 ± 1.2 mg/dl, control mean 2.9 ± 1.9 mg/dl, t = - 3.13 df = 81, p = 0.003). DISCUSSION: Salivary UA is elevated among adolescents with ED. Further studies are required to replicate and extend this finding and evaluate its generalizability as a state or trait marker as regards ED subtypes, other body fluids (plasma and cerebrospinal fluid), and recovery or premorbid stages, as well as its putative mechanistic relevance to ED. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Cortisol response to stress as a predictor for suicidal ideation in youth.

OBJECTIVE: To examine the association between cortisol response to stress and suicidal ideation (SI) cross-sectionally and longitudinally in our sample of bereaved and non-bereaved youth. METHODS: The sample included 114 youth bereaved by sudden parental death and 109 non-bereaved controls, mean age of 12.3 (SD = 3.6), evaluated at four time-points over an average follow-up period of 7 years. The Trier Social Stress Test (TSST) was conducted on average 6 years after bereavement. We used latent class analyses to examine the trajectories of SI over follow-up and up to the time of the TSST and compare them on cortisol measures. We examined whether cortisol measures predicted future SI at 18.5 months on average after the TSST. RESULTS: Bereavement was associated with higher cortisol reactivity after controlling for covariates [ß = 0.96, 95% CI (0.28, 1.65), p < 0.01, d = 0.41]. Cortisol reactivity to stress was higher in those belonging to the high SI trajectory [ß = 1.23, 95% CI (0.41, 2.06), p = 0.004, d = 0.23] compared to the low SI trajectory. Higher baseline cortisol showed small to medium effect size in predicting future SI [ß = 2.34, 95% CI (0.17, 4.51), p = 0.03, d = 0.38]. CONCLUSION: The persistence of SI is associated with higher cortisol reactivity to stress, and higher baseline cortisol may predict future SI. These results emphasize the importance of HPA-axis activity in youth exposed to major stressors, and those with SI. More research is needed to further clarify biological mechanisms linking SI and behavior, bereavement, and HPA axis response to stress, to better identify at-risk subjects for targeted prevention and intervention efforts.

A Longitudinal Study of Family Functioning in Offspring of Parents Diagnosed With Bipolar Disorder.

OBJECTIVE: To compare the longitudinal course of family functioning in offspring of parents with bipolar disorder (BD), offspring of parents with non-BD psychopathology, and offspring of healthy control (HC) parents. METHOD: Offspring of parents with BD (256 parents and 481 offspring), parents without BD (82 parents and 162 offspring), and HC parents (88 parents and 175 offspring) 7 to 18 years of age at intake, from the Bipolar Offspring Study (BIOS), were followed for an average of 4.3 years. Family functioning was evaluated using the child- and parent-reported Family Adaptability and Cohesion Scale-II and the Conflict Behavior Questionnaire. The data were analyzed using multivariate multilevel regression, generalized linear estimating equation models, and path analysis. RESULTS: Families of parents with BD and parents with non-BD psychopathology showed lower cohesion and adaptability and higher conflict compared with HC families. There were no significant differences in cohesion and adaptability between families of parents with psychopathology. The effect of parental psychopathology on family functioning was mediated by parental psychosocial functioning and, to a lesser extent, offspring disorders. In all 3 groups, parent-reported family conflict was significantly higher than child-reported conflict. Across groups, family cohesion decreased over follow-up, whereas conflict increased. CONCLUSION: Any parental psychopathology predicted family impairment. These results were influenced by the offspring's age and were mediated by parental psychosocial functioning and, to a lesser degree, by offspring psychopathology. These findings emphasize the need to routinely assess family functioning in addition to psychopathology and provide appropriate interventions to parents and offspring.

Long-Term Immune Alterations Accompanying Chronic Posttraumatic Stress Disorder following Exposure to Suicide Bomb Terror Incidents during Childhood.

BACKGROUND AND AIM: Long-term immune alterations have been proposed to play a mechanistic role in posttraumatic stress disorder (PTSD) as well as in its associated increase in medical morbidity and mortality. Better characterization of altered immune function may help identify diagnostic and prognostic biomarkers and potentially targets for preventive intervention. METHODS: As part of an ongoing study, we conducted a preliminary case-control comparison of resting immune inflammatory profiles between terror victims treated in childhood at the emergency department over the previous decade, who developed chronic PTSD upon long-term follow-up, and healthy controls. RESULTS: Our preliminary results in a subsample of this ongoing study support and extend elevated resting levels of granulocyte colony-stimulating factor, interleukin-4, and regulated on activation, normal T cell expressed and secreted in childhood onset chronic PTSD. CONCLUSION: Chronic immune alterations may participate in inflammatory activation and signal to the CNS through the neurovascular unit, as well as modulate the neuroendocrine axis. Better characterization and understanding of these preliminary findings may point to diagnostic and prognostic biomarkers and potentially elucidate mechanistic involvement of immune activation in PTSD.