Illness narratives and preferences for treatment among older veterans living with treatment-resistant depression and insomnia.

BACKGROUND: Despite the prevalence of comorbid late-life treatmentresistant depression (LLTRD) and insomnia in older adults, there is a gap in the literature describing patient factors, such as patients' beliefs about their illnesses and preferences for treatment, that can facilitate recovery. Therefore, we explored the perceptions and treatment preferences of older veterans with LLTRD and insomnia. METHODS: Semi-structured interviews were completed with 11 older veterans. A thematic analysis of the interviews was conducted. RESULTS: Four main themes were identified: 1. Insomnia and medical problems were considered to be significant contributors to depression, which was defined by low mood and anhedonia; 2. "Overthinking" was thought to be a cause of insomnia; 3. Participants' preference for psychotherapy was driven by their past experiences with therapy; and 4. Participants viewed patient education as a facilitator for compliance. CONCLUSIONS: Older veterans with LLTRD and insomnia have a preference for behavioral interventions. However, they lack knowledge about available treatment options, such as behavioral interventions for sleep that can improve both their sleep and mood while being a good fit with their illness narratives, such as "overthinking." There is a need for patient education, which should be offered early and often during treatment.

Brief behavioral treatment for insomnia in older adults with late-life treatment-resistant depression and insomnia: a pilot study.

OBJECTIVE: Brief Behavioral Treatment for Insomnia (BBTI) is an efficacious treatment of insomnia in older adults. Behavioral treatments for insomnia can also improve depression. However, it is unknown if BBTI is feasible or has an effect in patients with insomnia and late-life treatment resistant depression (LLTRD). The aims of this study were two-fold, to test: 1) the feasibility (defined by acceptability and retention rates) of BBTI and 2) the therapeutic potency of BBTI on symptoms of insomnia and depression. METHODS: Eleven older Veterans with LLTRD and insomnia were recruited in a randomized control trial to receive immediate (4-weeks of BBTI followed by 3-weeks of phone call check-ins and a final in-person 8-week assessment) or delayed (3-weeks of treatment as usual [wait-list control] followed by 4-weeks of BBTI and a final in-person 8-week assessment) BBTI. The primary outcome measures included the Patient Health Questionnaire (minus the sleep item) and the Insomnia Severity Index. RESULTS: BBTI was found to be feasible in older Veterans with insomnia and LLTRD; all participants recommended BBTI and retention rates were 90.9%. There was no difference in treatment effect between the immediate BBTI and delayed BBTI groups at week 4. After both groups (immediate and delayed) received BBTI, improvements were seen in both insomnia (d = 1.06) and depression (d = 0.54) scores. CONCLUSIONS: BBTI is a feasible treatment for insomnia in older adults with LLTRD. BBTI may be an effective adjunctive treatment for depression. Larger adequately-powered trials are required to confirm these preliminary findings.

Effect of insomnia treatments on depression: A systematic review and meta-analysis.

BACKGROUND: Insomnia is frequently co-morbid with depression, with a bidirectional relationship between these disorders. There is evidence that insomnia-specific interventions, such as cognitive behavioral therapy for insomnia, may lead to improvements in depression. The purpose of this systematic review and meta-analysis is to determine whether treatment of insomnia leads to improved depression outcomes in individuals with both insomnia and depression. METHODS: We conduct a systematic review and meta-analysis to explore the effect of treatment for insomnia disorder on depression in patients with both disorders. RESULTS: Three thousand eight hundred and fifteen studies were reviewed, and 23 studies met inclusion criteria. Although all of the studies suggested a positive clinical effect of insomnia treatment on depression outcomes, most of the results were not statistically significant. Although the interventions and populations were highly variable, the meta-analysis indicates moderate to large effect size (ES) improvement in depression as measured with the Hamilton Depression Rating Scale (ES = -1.29, 95%CI [-2.11, -0.47]) and Beck Depression Inventory (ES = -0.68, 95%CI [-1.29, -0.06]). CONCLUSIONS: These results support that treating insomnia in patients with depression has a positive effect on mood. Future trials are needed to identify the subtypes of patients whose depression improves during treatment with insomnia-specific interventions, and to identify the mechanisms by which treating insomnia improves mood.

Prevalence and Specificity of the Abnormal Niacin Response: A Potential Endophenotype Marker in Schizophrenia.

The skin flush response to niacin is abnormally blunted among a subset of patients with schizophrenia (SZ), preferentially associates with SZ compared to other mental illnesses, occurs frequently in nonpsychotic members of SZ-affected families, appears heritable, and shows evidence of genetic association. The niacin response abnormality (NRA) may prove to be a useful SZ endophenotype. Using a laser Doppler flowmeter, we undertook this study to estimate the prevalence of NRA in SZ (n = 70), bipolar disorder (BP, n = 59), and healthy control (HC, n = 87) groups, and to estimate its specificity for the illness. From the dose-response curves, we calculated the concentration of methylnicotinate required to elicit a half-maximal blood flow (MBF) response (EC50 value) and MBF value for each subject. The median log10EC50 of the SZ was above the third quartile of log10EC50 of either the HC or BP groups, whereas the MBF was significantly lower in the SZ than in the HC or BP groups. With a definition of NRA of having both EC50 above the ninetieth percentile of the control samples and MBF response below the sixtieth percentile for the control range, the NRA predicted SZ with 31% sensitivity and 97% specificity. Moreover, the NRA was not influenced by age, gender, race, and cigarette smoking. In summary, the NRA may define a SZ subtype with a clinically significant phospholipid signaling defect. Understanding its molecular origins may shed light on the pathophysiology of SZ and suggest new tools for its early diagnosis and treatment.

Adding antidepressants to antipsychotics for treatment of subsyndromal depressive symptoms in schizophrenia: Impact on positive and negative symptoms.

OBJECTIVES: It remains unclear how augmenting anti-psychotic medications with anti-depressants impacts primary positive and negative symptoms of schizophrenia. In this study, we used data collected from a randomized trial comparing citalopram to placebo for management of subsyndromal depression (SSD) in schizophrenia and schizoaffective disorder, to assess the effects of antidepressant augmentation on positive and negative symptoms. MATERIALS AND METHODS: Participants in this study conducted at the University of California, San Diego and the University of Cincinnati, were persons with schizophrenia or schizoaffective disorder aged 40 or older and who met study criteria for SSD. Patients were randomly assigned to flexible-dose treatment with citalopram or placebo augmentation of their current anti-psychotic medication. Analysis of covariance was used to compare changes in positive and negative syndrome scale (PANSS) scores between treatment groups. We also assessed mediating effects of improvement in depression and moderating effects of multiple factors on positive and negative symptoms. RESULTS: There was significant improvement in PANSS negative symptoms scores in the citalopram group, which was partially mediated by improvement in depressive symptoms. There was no effect on PANSS positive scores. CONCLUSIONS: In patients with schizophrenia/schizoaffective disorder, treating depressive symptoms with citalopram appears to carry the added benefit of improving negative symptoms.

Suicidal Ideation Associated with PCL Checklist-Ascertained PTSD among Veterans Treated for Substance Abuse.

This manuscript begins by reviewing the literature concerning the use of the SCID versus the PCL for diagnosing PTSD, and by reviewing the literature regarding the presence of suicidal ideation as a clinical correlate of PTSD. This manuscript then describes our recent study involving PTSD among Veterans, which assessed the presence of suicidal ideation as a clinical correlate of PTSD, as diagnosed by the SCID versus as diagnosed by the PCL. We hypothesized that the presence of suicidal ideation would be associated with a diagnosis of PTSD. Subjects were 101 Veterans recruited from VA behavioral health and substance use treatment clinics in the VA Pittsburgh Healthcare System. The study compared correlations of suicidal ideation with PTSD as determined with the PTSD Checklist versus the Structured Clinical Interview for DSM-IV, and utilized question 9 of the Beck Depression Inventory for assessing presence of SI. PTSD was diagnosed in 15 subjects using the SCID, and in 15 subjects using the PTSD Checklist. SI were reported by 16 subjects. The presence of SI was significantly associated with the diagnosis of PTSD on the PCL (chi-square=5.73, df=1, p=0.017) but not on the SCID (chi-square=0.08, df=1, p=0.773). These findings suggest that SI associated with the diagnosis of PTSD among Veterans are better ascertained by the PCL as compared to the more elaborate diagnostic algorithm used in the SCID. The current study finding raises the possibility that a less complicated diagnostic assessment instrument such as the PCL may be superior to the SCID, a more complicated instrument for diagnosing PTSD, at least in some populations.

Narrative evolution and assimilation of problematic experiences in a case of pharmacotherapy for schizophrenia.

This case study applied the assimilation model to examine the changing narrative of an outpatient with schizophrenia and symptoms of depression across a successful pharmacotherapy. The assimilation model describes how clients assimilate painful, problematic experiences. Therapeutic progress is understood to reflect increasing assimilation, measured by the Assimilation of Problematic Experiences Scale (APES). The authors used a 15-min semistructured interview (Problematic Experiences Questionnaire) to elicit narrative descriptions of the patient's problems and coping across five interviews throughout his 12-week treatment. They describe how the patient's narrative and APES ratings of his main problems by two clinicians changed in concert through treatment, explain these developments using assimilation concepts, and interpret the results in relation to assimilation and insight in schizophrenia.

Elderly patients with schizophrenia and depression: diagnosis and treatment.

BACKGROUND: The treatment of older patients with schizophrenia and depressive symptoms poses many challenges for clinicians. Current classifications of depressive symptoms in patients with schizophrenia include: Major Depressive Episodes that occur in patients with schizophrenia and are not classified as schizoaffective disorder, Schizoaffective Disorder, and Schizophrenia with subsyndromal depression in which depressive symptoms do not meet criteria for Major Depression. Research indicates that the presence of any of these depressive symptoms negatively impacts the lives of patients suffering from schizophrenia-spectrum disorders. PURPOSE: The purpose of this paper is to review the literature related to older patients with schizophrenia-spectrum disorders and co-occurring depressive symptoms, and to guide mental health professionals to better understand the diagnosis and treatment of depressive symptoms in patients with schizophrenia. CONCLUSIONS: The treatment of elderly patients with schizophrenia and depressive symptoms includes first reassessing the diagnosis to make sure symptoms are not due to a comorbid condition, metabolic problems or medications. If these are ruled out, pharmacological agents in combination with psychosocial interventions are important treatments for older patients with schizophrenia and depressive symptoms. A careful assessment of each patient is needed in order to determine which antipsychotic would be optimal for their care; second-generation antipsychotics are the most commonly used antipsychotics. Augmentation with an antidepressant medication can be helpful for the elderly patient with schizophrenia and depressive symptoms. More research with pharmacologic and psychosocial interventions is needed, however, to better understand how to treat this population of elderly patients.

Augmentation with citalopram for suicidal ideation in middle-aged and older outpatients with schizophrenia and schizoaffective disorder who have subthreshold depressive symptoms: a randomized controlled trial.

OBJECTIVE: To examine the effects of citalopram augmentation of antipsychotics on suicidal ideation in middle-aged and older people with schizophrenia and subthreshold depressive symptoms. METHOD: In this placebo-controlled trial conducted from September 1, 2001, to August 31, 2007, 198 outpatients > or = 40 years old with DSM-IV-diagnosed schizophrenia or schizoaffective disorder and subthreshold depressive symptoms were randomly assigned to flexible-dose citalopram (n = 104) or placebo (n = 94) augmentation of their antipsychotic for 12 weeks. Depression was measured with the Hamilton Depression Rating Scale (HDRS) and Calgary Depression Rating Scale (CDRS). Primary suicidal ideation measures were the Clinical Global Impressions-Severity of Suicide scale (CGI-SS) and the InterSePT Scale for Suicidal Thinking (ISST); secondary outcomes were the Scale for Suicidal Ideation (SSI), Beck Hopelessness Scale (BHS), HDRS item 3, and CDRS item 8. RESULTS: Compared to placebo, at the final visit, citalopram was associated with lower BHS scores (4.21 vs 4.98; P < .05) and lower likelihood of having suicidal ideation on the ISST (17.7% vs 38.7%; P < .005) and HDRS item 3 (14.4% vs 22.6%; P < .05). Among the 114 participants with no baseline suicidal ideation, there were no significant differences between citalopram and placebo regarding "emergent" ideation on either primary outcome. Among the 55 participants with baseline suicidal ideation, fewer treated with citalopram had endpoint ideation on the ISST (28.6% vs 66.7%; P < .05). Significantly more depression responders than nonresponders went from having baseline suicidal ideation to no suicidal ideation on both the ISST (75.0% vs 31.4%; P < .05) and CGI-SS (84.6% vs 31.3%; P < .05). CONCLUSIONS: Treatment-emergent suicidal ideation was no more common with citalopram than placebo. In participants with baseline suicidal ideation, citalopram reduced suicidal ideation, especially in those whose depressive symptoms responded to treatment.

Functional NPY variation as a factor in stress resilience and alcohol consumption in rhesus macaques.

CONTEXT: Neuropeptide Y (NPY) counters stress and is involved in neuroadaptations that drive escalated alcohol drinking in rodents. In humans, low NPY expression predicts amygdala response and emotional reactivity. Genetic variation that affects the NPY system could moderate stress resilience and susceptibility to alcohol dependence. OBJECTIVE: To determine whether functional NPY variation influences behavioral adaptation to stress and alcohol consumption in a nonhuman primate model of early adversity (peer rearing). DESIGN: We sequenced the rhesus macaque NPY locus (rhNPY) and performed in silico analysis to identify functional variants. We performed gel shift assays using nuclear extract from testes, brain, and hypothalamus. Levels of NPY in cerebrospinal fluid were measured by radioimmunoassay, and messenger RNA levels were assessed in the amygdala using real-time polymerase chain reaction. Animals were exposed to repeated social separation stress and tested for individual differences in alcohol consumption. Animals were genotyped for -1002 T > G, and the data were analyzed using analysis of variance. SETTING: National Institutes of Health Animal Center. Subjects Ninety-six rhesus macaques. Main Outcome Measure Behavior arousal during social separation stress and ethanol consumption. RESULTS: The G allele altered binding of regulatory proteins in all nuclear extracts tested, and -1002 T > G resulted in lower levels of NPY expression in the amygdala. Macaques exposed to adversity had lower cerebrospinal fluid NPY levels and exhibited higher levels of arousal during stress, but only as a function of the G allele. We also found that stress-exposed G allele carriers consumed more alcohol and exhibited an escalation in intake over cycles of alcohol availability and deprivation. CONCLUSIONS: Our results suggest a role for NPY promoter variation in the susceptibility to alcohol use disorders and point to NPY as a candidate for examining gene x environment interactions in humans.

Functional CRH variation increases stress-induced alcohol consumption in primates.

Corticotropin-releasing factor (CRF), encoded by the CRH gene, is a key integrator of stress responses, and, as such, CRH gene variation may contribute to individual differences in susceptibility to stress-related pathology. In rhesus macaques, a single nucleotide polymorphism (SNP) is found within the CRH promoter (-248C--> T). Here, we assessed whether this variant influenced stress responding and, because increased CRF system activity drives alcohol drinking in rodents, we examined whether it predicted voluntary alcohol consumption as a function of prior stress exposure. Using a hypothalamic nuclear extract, we showed that the -248 T allele resulted in increased DNA protein interactions relative to the C allele. In vitro, the T allele resulted in CRH promoter activity that was higher following both stimulation with forskolin and treatment with dexamethasone. Endocrine and behavioral responses to social separation stress (release of ACTH and cortisol, and suppression of environmental exploration, respectively) were higher among carriers of the T allele, particularly among those exposed to early adversity in the form of peer rearing. We also found that T allele carriers with a history of early life adversity consumed more alcohol in a limited-access paradigm. Our data suggest that CRH promoter variation that confers increased stress reactivity increases the risk for alcohol use disorders in stress-exposed individuals.

Citalopram augmentation for subsyndromal symptoms of depression in middle-aged and older outpatients with schizophrenia and schizoaffective disorder: a randomized controlled trial.

BACKGROUND: Subsyndromal symptoms of depression (SSD) in older outpatients with schizophrenia are common and clinically important. While many physicians prescribe antidepressants to patients with schizophrenia and schizoaffective disorder who have SSD, evidence for their effectiveness and safety has been meager. We describe a randomized placebo-controlled trial of citalopram in 198 patients. METHOD: Participants in this 2-site study, conducted from September 1, 2001, to August 31, 2007, were men and women with DSM-IV schizophrenia or schizoaffective disorder who were 40 years of age or older and who met study criteria for SSD. Patients were randomly assigned to flexible-dose treatment with citalopram or placebo augmentation of their current antipsychotic medication. Analysis of covariance was used to compare improvement in scores on the Hamilton Rating Scale for Depression and Calgary Depression Rating Scale between treatment groups; secondary efficacy analyses compared improvement in several other dimensions of schizophrenia. RESULTS: Augmentation with citalopram was significantly more effective than with placebo in improving depressive (p = .002) and negative (p = .049) symptoms, mental functioning (p = .000), and quality of life (p = .046). There were no significant differences between citalopram and placebo in suicidal ideation, positive symptoms, cognition, general medical health, physical functioning, or symptoms of movement disorders. No adverse events were more frequent in participants receiving citalopram than in those receiving placebo, and only 4 participants from each treatment group terminated early because of side effects. CONCLUSIONS: Subsyndromal symptoms of depression in middle aged and older patients with schizophrenia responded to treatment with citalopram with lessening of depressive symptoms and improved functioning and quality of life. It may be important for clinicians to identify and treat SSD in middle-aged and older patients with chronic schizophrenia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00047450.

Heterogeneity of neuroendocrine stress responses in aging rat strains.

Hyperactivity of the hypothalamo-pituitary-adrenocortical (HPA) axis is linked with age-related decrements in cognition and neuronal survival. However, the nature and extent of age-related HPA axis deficits vary considerably across and indeed, within strains. The current study was designed to assess variance in HPA axis function using two rodent models commonly used in aging studies: Fischer 344 (F344) and F344/Brown-Norway F1 hybrid rats (F344/BN). We examined both basal and stress-induced ACTH and corticosterone (CORT) release in two stress contexts thought to differ in intensity: novel environment ('mild') and restraint ('intense'). Variability of the data was tested with a modification of the Brown-Forsythe test of homoscedasticity. The results indicated that F344 rats exhibit greater peak HPA responses. Furthermore, in most cases variability was increased in aged rats relative to young and middle-aged rats of the same strain, indicative of the emergence of individual differences in stress responsivity amongst older rats. The results suggest that these older rat strains may be useful models to further assess individual differences in neuroendocrine aging.

Co-occurring depressive symptoms in the older patient with schizophrenia.

Clinicians treating older patients with schizophrenia are often challenged by patients presenting with both depressive and psychotic features. The presence of co-morbid depression impacts negatively on quality of life, functioning, overall psychopathology and the severity of co-morbid medical conditions. Depressive symptoms in patients with schizophrenia include major depressive episodes (MDEs) that do not meet criteria for schizoaffective disorder, MDEs that occur in the context of schizoaffective disorder and subthreshold depressive symptoms that do not meet criteria for MDE. Pharmacological treatment of patients with schizophrenia and depression involves augmenting antipsychotic medications with antidepressants. Recent surveys suggest that clinicians prescribe antidepressants to 30% of inpatients and 43% of outpatients with schizophrenia and depression at all ages. Recent trials addressing the efficacy of this practice have evaluated selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, fluvoxamine and citalopram. These trials have included only a small number of subjects and few older subjects participated; furthermore, the efficacy results have been mixed. Although no published controlled psychotherapeutic studies have specifically targeted major depression or depressive symptoms in older patients with schizophrenia, psychosocial interventions likely play a role in any comprehensive management plan in this population of patients.Our recommendations for treating the older patient with schizophrenia and major depression involve a stepwise approach. First, a careful diagnostic assessment to rule out medical or medication causes is important as well as checking whether patients are adherent to treatments. Clinicians should also consider switching patients to an atypical antipsychotic if they are not taking one already. In addition, dose optimization needs to be targeted towards depressive as well as positive and negative psychotic symptoms. If major depression persists, adding an SSRI is a reasonable next step; one needs to start with a low dose and then cautiously titrate upward to reduce depressive symptoms. If remission is not achieved after an adequate treatment duration (8-12 weeks) or with an adequate dose (similar to that used for major depression without schizophrenia), switching to another agent or adding augmenting therapy is recommended.We recommend treating an acute first episode of depression for at least 6-9 months and consideration of longer treatment for patients with residual symptoms, very severe or highly co-morbid major depression, ongoing episodes or recurrent episodes. Psychosocial interventions aimed at improving adherence, quality of life and function are also recommended. For patients with schizophrenia and subsyndromal depression, a similar approach is recommended.Psychosis accompanying major depression in patients without schizophrenia is common in elderly patients and is considered a primary mood disorder; for these reasons, it is an important syndrome to consider in the differential diagnosis of older patients with mood and thought disturbance. Treatment for this condition has involved electroconvulsive therapy (ECT) as well as combinations of antidepressant and antipsychotic medications. Recent evidence suggests that combination treatment may not be any more effective than antidepressant treatment alone and ECT may be more efficacious overall.

Effects of trauma-related audiovisual stimulation on cerebrospinal fluid norepinephrine and corticotropin-releasing hormone concentrations in post-traumatic stress disorder.

BACKGROUND: Although elevated concentrations of both corticotropin-releasing hormone (CRH) and norepinephrine are present in the cerebrospinal fluid (CSF) of patients with post-traumatic stress disorder (PTSD), the effects of exposure to traumatic stimuli on these stress-related hormones in CSF are unknown. METHODS: A randomized, within-subject, controlled, cross-over design was used, in which patients with war-related PTSD underwent 6-h continuous lumbar CSF withdrawal on two occasions per patient (6-9 weeks apart). During one session the patients watched a 1-h film containing combat footage (traumatic film) and in the other a 1-h film on how to oil paint (neutral film). At 10-min intervals, we quantified CRH and norepinephrine in CSF, and ACTH and cortisol in plasma, before, during, and after symptom provocation. Subjective anxiety and mood were monitored using 100-mm visual analog scales. Blood pressure and heart rate were obtained every 10min from a left leg monitor. RESULTS: Eight of 10 patients completed two CSF withdrawal procedures each. A major drop in mood and increases in anxiety and blood pressure occurred during the traumatic relative to the neutral videotape. CSF norepinephrine rose during the traumatic film relative to the neutral videotape; this rise directly correlated with magnitude of mood drop. In contrast, CSF CRH concentrations declined during the trauma-related audiovisual stimulus, both absolutely and relative to the neutral stimulus; the magnitude of CRH decline correlated with degree of subjective worsening of anxiety level and mood. Plasma cortisol concentrations were lower and ACTH levels similar during the stress compared with the neutral videotape. CONCLUSIONS: CSF concentrations of the stress hormones norepinephrine and CRH differentially change after exposure to 1h of trauma-related audiovisual stimulation in chronic, combat-related PTSD. While the CSF norepinephrine increase was postulated, the decline in CSF CRH levels is surprising and could be due to audiovisual stress-induced increased uptake of CSF CRH into brain tissue, increased CRH utilization, increased CRH degradation, or to an acute stress-related inhibition or suppression of CRH secretion.

Higher levels of basal serial CSF cortisol in combat veterans with posttraumatic stress disorder.

OBJECTIVE: Results of basal peripheral cortisol measures in posttraumatic stress disorder (PTSD) have been variable. The authors' goal was to measure CSF cortisol concentrations, which more accurately reflect brain glucocorticoid exposure, in subjects with or without PTSD. METHOD: CSF was withdrawn from a subarachnoid catheter and plasma from a venous catheter, both indwelling, over a 6-hour interval to determine hourly plasma ACTH and cortisol concentrations and hourly CSF cortisol levels in eight well-characterized combat veterans with PTSD and eight matched healthy volunteers. RESULTS: Mean CSF cortisol concentrations were significantly higher in the subjects with PTSD (3.18 ng/ml, SD=0.33) than in the normal volunteers (2.33 ng/ml, SD=0.50), largely due to higher CSF cortisol concentration nadirs. No group differences were observed in either plasma ACTH or peripheral (plasma or urinary free) cortisol. CSF corticotropin-releasing hormone and CSF cortisol concentrations were positively and significantly correlated. CONCLUSIONS: Despite normal peripheral cortisol indexes in the veterans with PTSD, their CNS exposure to cortisol was greater than that of normal comparison subjects.

Childhood trauma and personality disorder: positive correlation with adult CSF corticotropin-releasing factor concentrations.

OBJECTIVE: To test the hypothesis that early life trauma results in adult stress hormone alterations in individuals with personality disorders, the authors examined the relationship between history of childhood adversity and lumbar CSF corticotropin-releasing factor (CRF). METHOD: Participants were 20 otherwise healthy men who met DSM-IV criteria for personality disorders. CSF CRF was obtained by lumbar puncture, and childhood adversity was measured by the Childhood Trauma Questionnaire. Correlations were obtained between CSF CRF and the total score on the Childhood Trauma Questionnaire as well as scores on its four subscales. RESULTS: CSF CRF concentrations were positively correlated with the total score on the Childhood Trauma Questionnaire. Analysis of the subscales revealed that CSF CRF was correlated with emotional neglect. Correlations between CSF CRF level and physical and emotional abuse and with physical neglect were not statistically significant. CONCLUSIONS: Consistent with the hypothesis that the severity of early life stress is correlated with stress hormone abnormalities in adulthood, Childhood Trauma Questionnaire total scores and emotional neglect scores were significantly correlated with CSF CRF levels in individuals with personality disorders.

Stability of neuroendocrine and behavioral responsiveness in aging Fischer 344/Brown-Norway hybrid rats.

Aging in rodents and primates is accompanied by changes in hypothalamic-pituitary-adrenal (HPA) activity. We examined behavioral and neuroendocrine responses in 3, 15-, and 30-month-old F344/Brown-Norway rats. Basal corticosterone and ACTH levels did not differ with age, although ACTH responses, but not corticosterone responses to restraint stress, were significantly lower in the 30-month-old group relative to 3- and 15-month-old rats. Induction of c-fos mRNA in the paraventricular nucleus from restraint was not affected by age. Furthermore, there was an enhanced sensitivity to dexamethasone suppression in aged animals as evidenced by lesser ACTH and corticosterone release after dexamethasone administration. Evaluation of emotional behaviors in the forced swim test revealed no differences between the age groups. With fear conditioning, aged rats had decreased freeze times relative to middle-aged or young rats. Regression analysis revealed no significant correlations between the behavioral and HPA axis data in any group. Overall, the data suggest that an apparent decrease in pituitary drive is compensated for at the level of the adrenal, resulting in stable patterns of glucocorticoid secretion. The lack of a correlation between HPA axis measures and emotional as well as fear conditioning-related behaviors indicates that corticosteroid dysfunction may not predict age-related behavioral deficits in this aging model.

Effects of the vanilloid agonist olvanil and antagonist capsazepine on rat behaviors.

Vanilloid receptors (VR) are molecular integrators of painful chemical and physical stimuli. Olvanil is an agonist of the vanilloid receptor; capsazepine is a competitive VR antagonist. The authors were interested in investigated the effects of these compounds on anxiety-like behaviors in rats using the elevated plus maze. In addition, the authors examined the effects of olvanil on the Porsolt swim test. Doses of 0, 0.2, 1.0 and 5.0 mg/kg olvanil, respectively, yielded percent open arm entries at 5 min of 25+/-10.1, 19.3+/-7.1, 14.9+/-5.9 and 0+/-0. We demonstrated a drug effect by showing that the mean of the 0.2, 1 and 5 mg/kg doses was significantly lower than the 0 mg/kg dose at P<.05. In addition, the authors examined the effect of olvanil on the ability of rats to perform in the Porsolt swim test. Float time for rats was tested with 0.1 or 2 mg/kg olvanil and differences between the float times for the lower and higher doses were significant at P<.05. In addition, the effects of various doses of the vanilloid antagonist capsazepine was examined on elevated plus maze behavior. Doses of 0, 1, 5 and 10 mg/kg yielded percent time in the open arms at 5 min of 1.46+/-1.38, 15.05+/-10.42, 11.54+/-10.57, and 14.56+/-7.86. The mean of the 1, 5 and 10 mg/kg doses was significantly greater than the percent time in the open arms for the vehicle, consistent with a drug effect. The results suggest that the vanilloid agonists and antagonists may impact on behaviors involving anxiety and affect. However, it cannot be ruled that the findings could be due to nonspecific motor effect.