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1.
Mol Psychiatry ; 28(9): 3851-3855, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37845495

ABSTRACT

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.


Subject(s)
Stress Disorders, Post-Traumatic , Suicide , Humans , Young Adult , Chromosomal Proteins, Non-Histone , Glucocorticoids , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Stress Disorders, Post-Traumatic/genetics , Stress Disorders, Post-Traumatic/metabolism , Child
2.
Biol Psychiatry ; 94(6): 492-500, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37031779

ABSTRACT

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is characterized by affective, cognitive, and physical symptoms, suggesting alterations at the brain network level. Women with PMDD demonstrate aberrant discrimination of facial emotions during the luteal phase of the menstrual cycle and altered reactivity to emotional stimuli. However, previous studies assessing emotional task-related brain reactivity using region-of-interest or whole-brain analysis have reported conflicting findings. Therefore, we utilized both region-of-interest task-reactivity and seed-voxel functional connectivity (FC) approaches to test for differences in the default mode network, salience network, and central executive network between women with PMDD and control participants during an emotional-processing task that yields an optimal setup for investigating brain network changes in PMDD. METHODS: Twenty-four women with PMDD and 27 control participants were classified according to the Daily Record of Severity of Problems. Participants underwent functional magnetic resonance imaging scans while completing the emotional face-matching task during the midfollicular and late-luteal phases of their menstrual cycle. RESULTS: No significant between-group differences in brain reactivity were found using region-of-interest analysis. In the FC analysis, a main effect of diagnosis was found showing decreased default mode network connectivity, increased salience network connectivity, and decreased central executive network connectivity in women with PMDD compared with control participants. A significant interaction between menstrual cycle phase and diagnosis was found in the central executive network for right posterior parietal cortex and left inferior lateral occipital cortex connectivity. A post hoc analysis revealed stronger FC during the midfollicular than the late-luteal phase of PMDD. CONCLUSIONS: Aberrant FC in the 3 brain networks involved in PMDD may indicate vulnerability to experience affective and cognitive symptoms of the disorder.


Subject(s)
Premenstrual Dysphoric Disorder , Female , Humans , Premenstrual Dysphoric Disorder/diagnostic imaging , Brain/diagnostic imaging , Menstrual Cycle , Emotions , Luteal Phase
3.
Harefuah ; 161(4): 210-214, 2022 Apr.
Article in Hebrew | MEDLINE | ID: mdl-35466603

ABSTRACT

INTRODUCTION: Safety planning is a short-term therapeutic intervention aimed at enhancing the resources that suicidal individuals harness when dealing with imminent and future suicidal crises. Structured as a six-step action plan, the Safety Planning Intervention (SPI) includes identifying early signs of an emerging suicidal crisis, improving internal coping strategies and the ability to engage relevant social and therapeutic relationships, and removing dangerous means for suicide. The program can be applied in multiple settings, including emergency rooms and outpatient clinics. Studies examining this mode of intervention have demonstrated that it is highly effective in lowering suicidal behavior. Accompanied by a brief case vignette, we will outline key principles underlying safety planning, compare it to other available interventions and discuss remaining questions that warrant future assessment.


Subject(s)
Suicide Prevention , Adaptation, Psychological , Emergency Service, Hospital , Humans , Suicidal Ideation
4.
Mol Psychiatry ; 26(11): 6680-6687, 2021 11.
Article in English | MEDLINE | ID: mdl-33981010

ABSTRACT

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.


Subject(s)
Adverse Childhood Experiences , Military Personnel , Adolescent , Chromosomal Proteins, Non-Histone/metabolism , Humans , Hydrocortisone/metabolism , Receptors, Glucocorticoid/genetics , Receptors, Glucocorticoid/metabolism , Stress, Psychological/metabolism
5.
Psychol Serv ; 18(3): 377-388, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32105121

ABSTRACT

Suicide rates within the U.S. military are elevated. The interpersonal theory of suicide, supported within military samples, suggests that social disconnectedness confers risk for suicide. Autism spectrum disorder (ASD) is characterized by symptoms-difficulties in social communication/interaction (SCI) and restricted and repetitive behaviors (RRBs)-that contribute to social disconnectedness. To our knowledge, no study has examined ASD-related traits and suicide risk among active duty U.S. military service members. Participants included 292 active duty U.S. military service members (M [SD] age = 28.67 [7.40] years, 68.5% male, 78.1% White). The Autism Spectrum Quotient, Repetitive Behaviours Questionnaire-2 for Adults, Self-Injurious Thoughts and Behaviors Interview-Short Form, and Interpersonal Needs Questionnaire assessed for SCI difficulties, RRBs, suicidal symptoms, and interpersonal theory of suicide constructs (i.e., perceived burdensomeness, thwarted belongingness), respectively. Elevated levels of SCI difficulties and RRBs were associated with increased odds of reporting suicidal thoughts and behaviors occurring since joining the military, controlling for the number of years of service and suicidal symptoms occurring prior to joining the military. Perceived burdensomeness and thwarted belongingness statistically accounted for the relationship between ASD-related traits and suicidal ideation occurring since joining the military; a rival mediator, emotion dysregulation, was not a significant mediator. Among active duty U.S. military service members, greater ASD-related traits were associated with an increased likelihood of reporting suicidal thoughts and behaviors occurring since joining the military. Clinical efforts targeting perceived burdensomeness and thwarted belongingness might reduce suicide risk among military service members with elevated ASD-related traits. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Military Personnel , Suicide , Adult , Autism Spectrum Disorder/epidemiology , Female , Humans , Interpersonal Relations , Male , Psychological Theory , Risk Factors , Suicidal Ideation
6.
Hum Brain Mapp ; 42(3): 615-625, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33125770

ABSTRACT

Adverse childhood experiences (ACEs) have been acknowledged as risk factors for increased mental health complications in adulthood, specifically increasing susceptibility to developing psychopathology upon exposure to trauma. Yet, little is known regarding the impact of mild ACEs on highly functioning population. In this study forty participants were selected from a group of 366 highly selected military parachute trainees using the self-report "childhood trauma questionnaire," and classified into two groups of 20 each, with and without ACEs. Behavioral measurements were obtained before and at the peak of an intensive combat training period, including anxiety, depression and executive function assessment. Functional MRI including a negative emotional face perception task was conducted at the first time point. Psychometric and cognitive measurements revealed higher levels of anxiety and depressive symptoms, and more difficulties in executive functioning in the ACE group at baseline. Slower reaction time to emotional faces presentation was found in the ACE group. Lower activation in response to negative emotional faces stimuli was found in this group in bilateral secondary visual areas, left anterior insula, left parietal cortex and left primary motor and sensory regions. In contrast, higher activation in the ACE group was found in the right ventral lateral prefrontal cortex (Vlpfc). No significant differences between groups were detected in the amygdala. To conclude, mild adverse childhood experiences produce long-term sequela on psychological wellbeing and neurocircuitry even in high functioning population. Brain regions modulated by childhood trauma may instigate avoidance mechanisms dampening the emotional and cognitive effects of intensive stress.


Subject(s)
Adverse Childhood Experiences , Amygdala/physiology , Cerebral Cortex/physiology , Emotions/physiology , Executive Function/physiology , Facial Recognition/physiology , Military Personnel , Adolescent , Adult , Amygdala/diagnostic imaging , Anxiety/diagnostic imaging , Anxiety/physiopathology , Cerebral Cortex/diagnostic imaging , Depression/diagnostic imaging , Depression/physiopathology , Facial Expression , Functional Neuroimaging , Humans , Magnetic Resonance Imaging , Male , Young Adult
7.
Harefuah ; 159(7): 483-485, 2020 Jul.
Article in Hebrew | MEDLINE | ID: mdl-32720764

ABSTRACT

INTRODUCTION: Antidepressant treatment may have some adverse clinical effects. One main effect is a switch to mania or to an affective episode with mixed features. This case report describes a young woman who developed a manic episode with mixed features, a couple of weeks following Selective Serotonin Reuptake Inhibitor (SSRI) initiation. During the episode she made a serious suicide attempt. This case report highlights the significance of clinical follow-up after antidepressant initiation.


Subject(s)
Antidepressive Agents/therapeutic use , Bipolar Disorder , Military Personnel , Female , Humans , Selective Serotonin Reuptake Inhibitors , Suicide, Attempted
8.
Am J Med ; 121(10): 909-15, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18823863

ABSTRACT

BACKGROUND: Since the introduction of troponin for the diagnosis of myocardial infarction, several studies have shown additional conditions in which troponin is elevated, including sepsis. The objective of this study was to determine the incidence of an elevated troponin in patients with bacteremia and its significance. METHODS: This was a prospective, noninterventional study. Patients with a positive blood culture were included. Cardiac troponin I (cTnI) was determined within 4 days of blood culture. A repeat electrocardiogram was obtained in a sample of patients with elevated cTnI and in patients with a negative troponin test. Demographic, clinical, and microbiological data were obtained for all patients. RESULTS: A total of 159 bacteremic patients were included. Positive cTnI was detected in 69 patients (43%). Elevated cTnI was associated with a number of underlying diseases, hospitalization ward, severity of the systemic inflammatory condition, and kidney function (P<.05-.001). A repeat electrocardiogram was performed in 39 patients with a positive cTnI and in 28 patients with a negative cTnI. Two of 39 patients (5%) in the positive cTnI group had ischemic changes and 2 patients (5%) had nonspecific changes, whereas only 1 patient (4%) with a negative cTnI had nonspecific changes. Bivariate analysis revealed a statistically significant association for positive cTnI and mortality; however, on multivariate analysis this was no longer significant. CONCLUSION: Forty-three percent of bacteremic patients had an elevated cTnI. Risk factors for elevated cTnI were severity of the underlying infection, renal function, and underlying cardiac disease. Increased cTnI was found to be a dependent risk factor and a surrogate marker for death.


Subject(s)
Bacteremia/blood , Troponin I/blood , Acute Coronary Syndrome , Adult , Aged , Aged, 80 and over , Bacteremia/microbiology , Bacteremia/mortality , Biomarkers/blood , Electrocardiography , Female , Humans , Israel/epidemiology , Male , Middle Aged , Prognosis , Prospective Studies
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