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.

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.

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.

Genetics of unipolar major depressive disorder.

Major depressive disorder (MDD) is a heterogeneous, highly prevalent, and moderately heritable disorder. A complex and diverse genetic-environmental interplay converges to set apart a significant minority that is susceptible to MDD, from among those who experience shorter lived and less recurrent intensive and incapacitating forms of sadness. The major technological advances of deciphering the human genome reference sequence and its common gene variations are beginning to allow cost effective genetic studies of unprecedented scale, applying increasingly denser genome wide mapping to increasingly larger case control samples. This effort is now at the initial stages of unraveling the genetic architecture of several complex phenotypes. Despite a tardy beginning, MDD genetic research is maturing from modest scale candidate gene association studies to include family-based linkage studies, and will soon allow genome wide case control association studies. Replicated risk conferring gene variants discovered so far exert a modest effect size that appears to contribute to overt phenotype expression in the context of a highly intricate concert of interrelated epigenetic and epistatic modifiers. The unraveling of additional previously unimplicated MDD risk conferring genes, that will throw light on molecular mechanisms mediating such susceptibilities, is necessary for progressing beyond current generation monoamine modulating antidepressant drugs. The review outlines basic concepts and current progress briefly overviews major replicated gene findings that to date mostly stem from hypotheses driven candidates, and ends with a discussion of current directives, including sample size and phenotype considerations and advancement of systematic studies of the functional significance of implicated gene variants, beyond their current exploratory stage.

Effect of triiodothyronine on 5-HT1A and 5-HT1B receptor expression in rat forebrain and on latency to feed in the novelty suppressed feeding test.

Thyroid hormones, particularly triiodothyronine (T3), have long been used for the treatment of depression, most frequently to enhance the therapeutic activity of other antidepressants. The purpose of this study was to evaluate possible underlying mechanisms for the antidepressant activity of T3. The effects of T3 20 microg/kg/d S.C. and fluoxetine 5mg/kg/d I.P. given alone or in combination for 7 days on the transcription rates of inhibitory serotonergic receptors (5-HT1A and 5-HT1B) were studied in different brain areas of male Sabra rats using real-time PCR. Significant effects of fluoxetine were found on the expression of 5-HT1B receptors in the frontal cortex and of T3 on the expression of 5-HT1A receptors in the amygdala and hippocampus and 5-HT1B receptors in the frontal and entorhinal cortices, the expression being reduced in all cases. An effect of the combination of T3 plus fluoxetine to reduce transcription was observed for 5-HT1A receptors, in the amygdala and dentate gyrus and for 5-HT1B receptors in the entorhinal cortex and anterior raphe nucleus. In the second experiment, the novelty suppressed feeding test (NFST) was used to examine the effects of fluoxetine 5mg/kg/d I.P. and T3 20 or 50 microg/kg/d, alone or in combination for 12 days, on latency to feed. Only the combinations of T3 (20 or 50 microg/kg/d) and fluoxetine (5mg/kg/d) yielded significant behavioral effects in this test. The results of our studies suggest that the mechanism underlying the antidepressant effect of T3 may involve a reduction in 5-HT1A and 5-HT1B receptor transcription rates.

Why do young women smoke? IV. Role of genetic variation in the dopamine transporter and lifetime traumatic experience.

Cigarette smoking is a complex behavior to which environmental, psychological, and genetic factors contribute. Applying a multifactorial model, we examined the role of genetic variation in the dopamine transporter (DAT1) in smoking initiation (SI) and nicotine dependence. The participants were female college students who had never smoked (n = 148) or had smoked daily for at least a year (n = 242). All participants provided extensive background information and completed a series of psychological instruments. Five SNPs were genotyped in the 3' and 5' regions of DAT1. Data were analyzed by logistic regression. The best fitting model for SI (P = 1.9 x 10(-17), Nagelkerke R2 = 0.33) revealed novelty seeking (OR = 1.14, P = 0.000004) and lifetime traumatic experience (OR = 2.3, P = 0.001) as risk factors and a DAT1_E15 + 274-DAT1_VNTR G-9 haplotype as protective (OR = 0.57, P = 0.03). In the model for nicotine dependence (P = 1.4 x 10(-8), Nagelkerke R2 = 0.27) novelty seeking was a risk factor (OR = 1.07, P = 0.03); the DAT1_E15+274-DAT1_VNTR G-9 haplotype (OR = 0.37, P = 0.001) and the interaction between trauma and a DAT1_E15 + 274-DAT1_VNTR C-9 haplotype (OR = 0.15, P = 0.01) were protective. Lifetime experience of trauma was associated with high nicotine dependence among non-carriers of the C-9 haplotype but not among carriers of this haplotype. These findings indicate that in the context of a multifactorial model, haplotypes in the 3' region of DAT1 influence the propensity of young women to initiate smoking as well as the severity of nicotine dependence once the habit is established. A haplotype in the 3' untranslated region of DAT1 modifies the effect of lifetime traumatic experience on the severity of nicotine dependence.