Rachel Yehuda

Childhood trauma and risk for PTSD:relationship to intergenerational effects of trauma, parental PTSD and cortisol excretion

Among the adverse mental health consequences of childhood trauma is the risk related to the development of posttraumatic stress disorder (PTSD) in adulthood. Other risk factors for PTSD. including parental trauma exposure and parental PTSD, can also contribute to the experience of child trauma. We examined associations between childhood trauma and PTSD in 51 adult children of Holocaust survivors and 41 comparison subjects. in consideration of parental trauma exposure and parental PTSD. We also examined these variables in relation to 24-hr urinary cortisol levels. Adult offspring of Holocaust survivors showed significantly higher levels of self-reported childhood trauma, particularly emotional abuse and neglect. relative to comparison subjects. The difference was largely attributable to parental PTSD. Self-reported childhood trauma was also related to severity of PTSD in subjects, and emotional abuse was significantly associated with 24-hr mean urinary cortisol secretion. We conclude that the experience of childhood trauma may be an important factor in the transmission of PTSD from parent to child.

Behavioral and endocrine response to cholecystokinin tetrapeptide in patients with posttraumatic stress disorder

BACKGROUNDnGiven the relationship between posttraumatic stress disorder (PTSD) and panic, it was of interest to examine whether panic provoking agents affect PTSD symptoms. We therefore investigated the behavioral and endocrine response of PTSD patients to the panicogen cholecystokinin tetrapeptide (CCK-4).nnnMETHODSnEight patients with PTSD (DSM-IV) received 50 micrograms CCK-4 intravenously in a placebo-controlled, double-blind balanced design. Provocation of panic, anxiety, and flashbacks was assessed. Plasma adrenocorticotropin (ACTH) and cortisol levels after CCK-4 were measured and compared to healthy subjects matched for age, gender, and provoked symptoms.nnnRESULTSnDespite significant effects of CCK-4 on anxiety and panic symptoms, no significant provocation of flashbacks emerged. CCK-4-induced panic symptoms showed an inverse correlation to trait dissociation. The ACTH response after CCK-4 was significantly lower in PTSD patients than in controls. Cortisol was similarly increased in both groups after CCK-4, but PTSD patients showed a more rapid decrease of stimulated cortisol concentrations.nnnCONCLUSIONSnPanic symptoms or heightened anxiety are not necessarily conditioned stimuli for the provocation of posttraumatic flashbacks. Further studies in PTSD with different panicogens should be controlled for the potential interference of trait dissociation. Our hormone data show further evidence for a corticotropin-releasing hormone (CRH) overdrive and enhanced negative glucocorticoid feedback in PTSD patients.

Circadian Regulation of Basal Cortisol Levels in Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a psychiatric condition that can occur following exposure to trauma. Because the hypothalamic-pituitary-adrenal (HPA) axis is a major hormonal system mediating the stress response, and has been found to be altered in response to a variety of acute and chronic stressors, it has been hypothesized that fundamental changes in the HPA axis would be relevant to the pathophysiology of PTSD. There is now converging evidence suggesting that PTSD patients show HPA axis alterations that are substantially different from those that have been described in stress and major depression. For example, in s ~ m e , l ~ but not all studies4 basal 24-hr urinary excretion of cortisol was lower in PTSD compared with normal and depressed patients. Furthermore, in contrast to the “nonsuppression” of cortisol observed in major depression, cortisol levels following dexamethasone (DEX) were lower (i.e., more suppressed) in combat veterans with PTSD than in normals.sd It has also been observed that combat veterans with PTSD exhibit a larger number of cytosolic glucocorticoid receptors (GR) on circulating lymphocytes compared to other psychiatric groups such as bipolar mania, panic disorder, schizophrenia, and major depre~sion.~ Combat veterans with PTSD also appear to have a larger number of GR than combat veterans who do not meet criteria PTSD6 and normal control^.^^^ Veterans who do not meet criteria for PTSD were found to have a larger number of GR than normals? Although the larger number of cytosolic GR in PTSD may simply reflect the lower circulating levels of cortisol, it is also possible that some long-lasting alterations in GR binding parameters result from exposure to traumatic events, and/or the subsequent development of PTSD. Based on the above data, we have hypothesized that HPA axis alterations in chronic PTSD appear to reflect an enhanced negative feedback at one or more sites along the axis? In this model, chronic increases in the release of CRF would lead to an altered responsivity of the pituitary, as evidenced by the blunted ACTH response to CRF previously observed.* However, because of a primary alteration in GR responsivity, there would be a stronger negative feedback resulting in attenuated baseline ACTH and cortisol levels as well as an enhanced responsivity to DEX. According to this model it would be expected that some target tissue of the HPA axis might be unusually responsive or sensitized. Recently, in order to further explore the enhanced sensitivity of the HPA axis in PTSD, we conducted a chronobiological analysis to elucidate the intrinsic regulatory

Screening for Depression and Suicidality in Patients With Cardiovascular Illnesses

The American Heart Association (AHA) and the American Psychiatric Association jointly recommend screening for depression in cardiology clinics. This includes screening for suicidality. It is not known how frequently patients disclose suicidal thinking (ideation) in this setting, and what proportion of those will turn out to have suicidal intent. Patients were screened for depression using a protocol identical to the one endorsed by the AHA in a cardiology community clinic in Elmhurst (Queens, New York). Depression was assessed using the Patient Health Questionnaire. Reports of suicidal ideation were immediately evaluated by a mental health professional. We determined the degree to which suicidal ideation was identified, the proportion of patients with suicidal intent of those reporting suicidal ideation, and the relation between depression and suicidal ideation in this setting. One thousand three patients were screened; 886 had complete Patient Health Questionnaire data. Of those, 12% (109 patients) expressed suicidal ideation. Four of those were hospitalized for suicidal intent (0.45% of all screened patients). Suicidal ideation and depression were correlated (point biserial correlation coefficient 0.478). In conclusion, suicidal ideation can and will be identified using the AHA depression screening recommendations, but only a very small fraction (0.45%) of screened patients will turn out to have suicidal intent. Discovery and stabilization of suicidal patients is an important benefit of the screening, but the fact that >12% of all screened patients will need to be immediately evaluated for suicidal intent has important implications for resource allocation to screening programs.

Longitudinal course of salivary cortisol in post-traumatic stress disorder

Objective: In chronic post‐traumatic stress disorder (PTSD) lowered cortisol secretion and hypersuppression to dexamethasone has been described repeatedly. However, so far no longitudinal data on the natural course or on the effect of therapy are available.

Relationship between 3-Methoxy-4-Hydroxyphenylglycol and Homovanillic Acid in Saliva and Plasma of Healthy Volunteers

Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels may reflect changes in central noradrenergic and dopaminergic activity, respectively. The relationship between MHPG and HVA in saliva and plasma was investigated to evaluate the utility of salivary metabolite measurement as a relatively noninvasive and useful alternative to plasma analysis. MHPG and HVA in saliva and plasma, collected concurrently, from 12 healthy volunteers, were measured by high-performance liquid chromatography. Concentration of free MHPG in saliva correlated significantly with plasma free MHPG. Salivary free MHPG was significantly higher than in plasma. Enzymatic hydrolysis of conjugated MHPG corroborated other work that plasma free MHPG, MHPG-glucuronide, and MHPG-sulfate were in roughly equal proportions. Unpredictably, in saliva, free MHPG was greater than 80% of the total. Salivary and plasma free HVA concentrations also correlated significantly, but salivary HVA levels were significantly lower than in plasma. Conjugated HVA was consistently less than 10% of total both in saliva and plasma. These findings suggest that salivary MHPG and HVA can reflect plasma metabolite levels. Although local factors may influence their formation and concentration in saliva, large changes in plasma free MHPG or HVA could be reflected by parallel changes in saliva.

Assessment of Posttraumatic Stress Symptoms in Children who are Medically Ill and Children Presenting to a Child Trauma Program

Abstract:u2002 To test the utility of the UCLA posttraumatic stress disorder (PTSD) Index for DSM‐IV (U‐PTSD‐I)© for predicting PTSD diagnosis in children with and without medical illnesses. The U‐PTSD‐I and a standard psychiatric interview were administered to medically ill children (n= 76) and children who experienced other traumatic events (n= 31). We found U‐PTSD‐Is sensitivity and specificity was better in the nonmedical illness cohort. Only intrusion symptoms were significantly associated with the diagnosis of PTSD in the medically ill. In conclusion, the U‐PTSD‐I performs better among general trauma versus medically ill patients. Intrusion symptoms should be focused on when assessing PTSD in medically ill children.

Exercise Reinforcement, Stress, and β-endorphins: An Initial Examination of Exercise in Anabolic-Androgenic Steroid Dependence

BACKGROUNDnAnabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer.nnnMETHODnSixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, β-endorphin samples, and measures of mood, compulsive exercise, and body image.nnnRESULTSnBetween group differences indicated that on-cycle AAS users had the highest β-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest β-endorphin levels. Exercise value was positively correlated with β-endorphin and symptoms of AAS dependence.nnnCONCLUSIONnThe HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.

267. Trauma in personality disorder — serotonin — HPA interactions

includeneuroendocrine measures,as wellas cerebrospinal fluid(CSF)and postmortembraintissuestudies.The currentpresentationwill focuson a seriesof expxhnentsconductedoverthepastseveralyearsutilizinganimal modelsofearlyuntowardlifeevents,matemalseparationor stressfuliving conditions. In thesestudies,ratsamseparatedfromtheirmothersforvarious periodseartyin life(e.g.,days2-20),forvaryingperiodsofdrne.Asadults, HPAaxisrespoosesto stressamrneas~ as is CRFneuronalactivity,the latterby measurement of CRFin tissue,portrdblood,CSF,CRFmRNA expression,and CRF receptorbinding,as well as plasma ACf’Hand corticostcrone concentrations. Complimentary experimentswereconducted in non-humanprimates,bonnetmacaquesin collaborationwith COplan, GormsnandRosenblmn. In all of theseexperiments, earlymaternalseparationpmdueed,inadults,a hyperactiveHPAaxisstrrzssrqxrnae andindices of CRFneuronslhyperactivityincludinginereaaedCRFmRNAexpression in hypothalamicand extrabypothalamic brainregions,increasedCSFand portalbloodCRP, and alteredCRF receptorbinding.Bonnetmacaques raisedinanunfavorable, unpredictablenvironment earlyin lifeexhibitedas adultsincreasedCSFCRFconcentmtions, similarto that observedin the maternallydeprivedratsanddepressedhumans. Intheratstudies,theindices of CRF neumnalhyperacdvityare reversedby chronictreatmentwith paroxetine,a clinicallyeffectiveSSIUantidepressant. ‘I%da@ taken together,suggesthatCRPnerrronal hyperactivity, maybeaconscquenceof earlylife stressorsandmaycontributeto majordepression. Thesefindings supportthe development of CRFreceptorantagonistsas novelarrtidcpresssnts.sllp~rted byMI-IMH-42088, MH50113andDA08705-02.