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Patients with schizophrenia have an elevated risk of suicidal behavior. We explored whether there were age differences in inpatients with schizophrenia admitted for suicidal behavior. We compared demographic/clinical characteristics of 76 inpatients aged 59 to those 60. All patients had a score greater 0 on items 4 (active suicidality) and/or 5 (passive suicidality) on the Beck Scale for Suicidal Ideation for inclusion. There were no significant group differences with respect to race, education, depressive symptoms or negative symptoms. There was evidence suggesting that hallucinations appear to be less prominent in the older group. Future studies will determine whether these age related differences are stable over time and could account for potential age differences in suicidal behavior in individuals with schizophrenia.

Objective To identify which specific depressive symptoms predict remission to aripiprazole augmentation in late-life treatment resistant depression. Methods This is a secondary analysis of data from a late-life treatment resistant depression trial examining the safety and efficacy of aripiprazole augmentation. Participants aged 60 and above were randomized to aripiprazole augmentation (N = 91) versus placebo (N = 90). The main outcome was depression remission. Clinical predictors included individual Montgomery-Asberg Depression Rating Scale (MADRS) item scores categorized as symptomatic (scores >2) or nonsymptomatic (scores ≤2). Results Three MADRS items predicted depression remission with aripiprazole augmentation: symptomatic scores on sleep disturbance and nonsymptomatic scores on apparent sadness and inability to feel. The 2-way and 3-way interaction terms of these MADRS items were not significant predictors of remission; therefore, the models' ability to predict remission was not improved by combining the significant MADRS items. Conclusions The identification of specific depressive symptoms, which can be clinically assessed, can be used to inform treatment decisions. Older adults with treatment resistant depression that present with sleep disturbances, lack of apparent sadness, or lack of inability to feel should be considered for aripiprazole augmentation.

Introduction Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging. Neuropsychiatric symptoms (NPS) in AD are a major cause of burden to patients, caregivers, and society and are near-universal at some point in the AD course. One of the most troubling of these symptoms is agitation (Agit-AD), typified by a variety of problem behaviors including combativeness, yelling, pacing, lack of cooperation with care, insomnia, and restlessness. There is a great need for better interventions that target Agit-AD, a major source of patient disability as well as caregiver burden and stress, particularly in the case of moderate to severe agitation. Dronabinol (Marinol®) is synthetic tetrahydrocannabinol (THC, one of the predominant biochemical constituents of cannabis), which produces anxiolytic, antidepressant, and anti-inflammatory effects and is FDA approved for anorexia and nausea. This pilot trial could open the door to "re-purposing" dronabinol as a novel and safe treatment for Agit-AD with significant public health impact. Methods THC-AD is a three-week placebo-controlled, double-blind, randomized clinical trial of dronabinol (10?mg QD) in 80 inpatients, assisted living facility (ALF), or nursing home residents with severe Agit-AD. Capsules of dronabinol contain 2.5?mg per dose (5?mg daily) during Week 1, then increase to 5?mg per dose (10?mg daily) for Weeks 2 and 3. The half-life of dronabinol is ∼4?hours, so study medication is administered BID at 08:00 and 14:00 to maximize daytime coverage for agitation and to minimize sundowning. Inclusionary criteria include a diagnosis of AD, severe agitation as determined by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), and being 60-95?years old, while exclusionary criteria include serious or unstable medical illness, seizure disorder, delirium, current use of lithium, and inability to swallow a pill. Primary outcomes include a change in the Pittsburgh Agitation Scale and NPI-C Agitation/Aggression subscales. Secondary outcomes include measures of agitation, cognition, sleep, and global functioning as determined by the following assessments: the NPI-C, Cohen Mansfield Agitation Inventory, Clinical Global Impression of Change, Activities of Daily Living, Mini-Mental State Examination (MMSE), Severe Impairment Battery (8 item), and subjective and observer-rated drug effects. Safety outcomes include monitoring for adverse events (AEs), weekly health assessments, EKG changes, incident delirium (Confusion Assessment Method), and changes in laboratory values. DNA specimens are collected to explore the possibility that cannabinoid receptor polymorphisms may affect response to dronabinol. Serum samples are collected to examine the association of peripheral markers of inflammation with agitation and response to dronabinol. Concomitant medications are limited to currently used antipsychotics, antidepressants, and benzodiazepines, as well as anticonvulsant therapy when not used for seizure disorder, with lorazepam 0.75?mg QD total daily allowed as rescue medication, and can be administered orally or intramuscularly. Additionally, PRN trazodone in doses up to 100?mg total daily dose are allowed for agitation and insomnia. Results We began recruitment in March, 2017 and have enrolled 27 out of 80 participants (mean age 76.96?years, 77.8% female, 85.2% Caucasian, mean total education completed 13.84?years, 55.6% family history of memory impairment). Study participants are significantly cognitively impaired (mean baseline MMSE of 6.69), agitated (mean NPI-C Agitation subtotal 15.19, mean NPI-C Aggression subtotal 6.48) and in reasonable overall health (General Medical Health Rating, 51.9% "good" and 40.7% "fair.") The pace of recruitment is behind initial projections due to a number of factors including adaptation of inpatient units to a culture of research, cost of study medication post clinical trial, difficulty swallowing over-encapsulated pills, prior or current treatment with dronabinol and patient acuity leading to protocol deviations. To meet our recruitment target, we are launching our trial at additional locations (including ALF and nursing homes) and we have expanded the inclusion criteria to increase the maximum age at study entry to 95?years. We have not encountered adverse events or regulatory issues that suggest a rationale to change our study protocol. Conclusions AD is a fatal disease which robs an individual of their memory and personality. Agitation is one of the most common behavioral manifestations of AD and is associated with greater caregiver burden and shorter time to institutionalization. Current treatments for Agit-AD have a plethora of safety limitations, and there is a particularly acute need for interventions for severe Agit-AD in advanced dementia. One important question for treatment development is whether Agit-AD represents a specific target for intervention or a nonspecific syndrome shared with many other diseases. This clinical trial may enable us to understand if targeting the cannabinoid system will be an effective approach to treat this public health issue. This research was funded by: National Institute of Aging, R01AG050515

Objective To explore middle-aged and older veterans' current disease-management practices, mental health treatment preferences, and challenges of living with multiple chronic health conditions (i.e., multimorbidity). Methods Semi-structured qualitative interviews and self-report measures were collected from 28 middle-aged and older (50 years of age or older) veterans with multimorbidity. Results Our sample of veterans with multimorbidity was, on average, mildly depressed and anxious with elevated stress and disability. Veterans acknowledged the interaction of physical and emotional symptoms, which caused greater difficulty with health care management and daily functioning. Veterans had many concerns regarding their physical and emotional health conditions, such as continued disease progression and the addition of other emotional and physical health complications. Veterans also identified specific self-care approaches for disease management (e.g., medication, healthy lifestyle practices, and psychological stress management techniques), as well as barriers to engaging in care (e.g., money, transportation, and stigma). Participants preferred a combination of medication, psychotherapy, and healthy lifestyle practices for mental health treatment. The majority of participants (88.5%) agreed that these mental health treatments would be beneficial to integrate into disease management for older veterans with multimorbidity. Lastly, veterans provided an array of recommendations for improving Veteran's Administration services and reducing mental health stigma. Conclusions These findings provide support for patient-centered approaches and integrated mental and physical health self-management in the Veteran's Administration for middle-aged and older veterans with multiple chronic conditions. Copyright © 2016 John Wiley & Sons, Ltd.

Veterans with schizophrenia admitted for suicidal ideation were recruited into a post-discharge program consisting of Intensive Case Monitoring (ICM) with daily monitoring with the Health Buddy (HB; experimental group) or ICM alone (control group). This study tested the feasibility of the telehealth monitoring intervention in this population. Secondly, we determined whether augmentation of ICM with our intervention for 3 months would result in a reduction in suicidal ideation. Twenty of 25 telehealth participants could set up the device. Monthly adherence for telehealth participants was > 80%. A qualitative analysis of endpoint surveys revealed that the majority of participants had positive responses. In both groups, there were improvements in Beck Scale for Suicidal Ideation (BSS) scores at endpoint relative to baseline. No group differences were present with survival analysis when using remission (i.e., BSS score = 0) as the outcome; however, in a subgroup with a history of suicide attempt, there was a trend (p = .093) for a higher rate of remission for those in the HB condition. In conclusion, telehealth monitoring for this population appears to be feasible for those who are able to start using the system. The pilot data obtained should help investigators design better telehealth interventions for this population.

This study tested the hypothesis that addition of telehealth to Intensive Case Monitoring (ICM) would reduce hospital admissions in Veterans with schizophrenia or schizoaffective disorder admitted for psychiatric care in response to suicidal behavior. Participants (n =51) were randomized to ICM or ICM plus telehealth monitoring. Telehealth participants responded to daily electronic queries about depression, suicidality, and medication adherence. Comparisons revealed that participants in the telehealth group had significantly less medical hospitalizations than the control group. This study found that telehealth augmentation is related to decreased number and length of medical hospitalizations in Veterans with schizophrenia and schizoaffective disorder.

Suicide is a public health concern in older adults. Recent cross sectional studies suggest that impairments in executive functioning, memory and attention are associated with suicidal ideation in older adults. It is unknown whether these neuropsychological features predict persistent suicidal ideation. We analyzed data from 468 individuals ≥ age 60 with major depression who received venlafaxine XR monotherapy for up to 16 weeks. We used latent class growth modeling to classify groups of individuals based on trajectories of suicidal ideation. We also examined whether cognitive dysfunction predicted suicidal ideation while controlling for time-dependent variables including depression severity, and age and education. The optimal model using a zero inflated Poisson link classified individuals into four groups, each with a distinct temporal trajectory of suicidal ideation: those with ‘minimal suicidal ideation’ across time points; those with ‘low suicidal ideation’; those with ‘rapidly decreasing suicidal ideation’; and those with ‘high and persistent suicidal ideation’. Participants in the ‘high and persistent suicidal ideation’ group had worse scores relative to those in the “rapidly decreasing suicidal ideation” group on the Color-Word ‘inhibition/switching’ subtest from the Delis–Kaplan Executive Function Scale, worse attention index scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and worse total RBANS index scores. These findings suggest that individuals with poorer ability to switch between inhibitory and non-inhibitory responses as well as worse attention and worse overall cognitive status are more likely to have persistently higher levels of suicidal ideation. Clinicaltrial.gov number NCT00892047 .

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.

A telehealth system was developed to monitor risk following hospitalization for suicidal ideation. We hypothesized that 3 months of telehealth monitoring will result in a greater reduction in suicidal ideation. Veterans with schizophrenia admitted with recent suicidal ideation and/or a suicidal attempt were recruited into a discharge program of VA Usual Care with daily Health Buddy© monitoring (HB) or Usual Care (UC) alone. Fifteen of 25 were randomized to HB and 10 received UC. Daily adherence in the use of the HB system during months 1-3 was, respectively, 86.9%, 86.3%, and 84.1%. There were significant improvements in Beck Scale for Suicide Ideation scores in HB participants. There were no changes in depressive symptoms. Telehealth monitoring for this population of patients appears to be feasible. Language: en

Four definitions of subthreshold posttraumatic stress disorder (PTSD) were compared in 815 veterans seen in Veterans Affairs Medical Center primary care clinics. We compared PTSD Checklist (PCL) scores and Short Form 36 (SF-36) scores between participants meeting criteria for one of the subthreshold PTSD definitions (based on Schnurr, Marshall, Blanchard, or Stein) to those with and without PTSD. Using regression, those meeting subthreshold criteria by any of the four definitions had lower mental and physical health functioning and higher PCL scores relative to those without PTSD; they also had higher mental health functioning and lower PCL scores relative to those with PTSD. With SF-36 physical functioning scores, only those meeting the Stein definition differed from the group with PTSD. Thus, these definitions appear to distinguish individuals who are qualitatively different from individuals with no PTSD or with PTSD and are nearly equivalent in their ability to discriminate individuals.

Objective Sleep disturbances are common in late life depression; however, changes in insomnia symptoms during antidepressant treatment need to be characterized further. The objective of this study was two-fold: 1) to describe longitudinal trajectories of insomnia symptoms in older adults receiving antidepressant treatment and 2) to examine whether baseline depressive symptoms were associated with trajectories of sleep over time. Methods Data was obtained from 680 older adults (aged ≥ 60) with major depression who participated in one of two protocolized open-label antidepressant treatment clinical trials (Maintenance Therapies in Late Life Depression [MTLD-3]; Incomplete Response in Late Life Depression: Getting to Remission [IRL-GRey]). Depression (total score minus sleep items) and sleep (sum of sleep items) outcomes were derived from the Hamilton Depression Rating Scale in the MLTD-3 and Montgomery-Asberg Depression Rating Scale in the IRL-GRey. Results Both datasets identified 5 possible trajectories of insomnia symptoms with about half of the older adults having clinically significant baseline sleep disturbances and minimal improvement following a course of antidepressant treatment (i.e., sub-optimal sleep trajectory). Furthermore, across both datasets, worse baseline depression severity was associated with sub-optimal sleep trajectories. Conclusion In older adults receiving antidepressant treatment, those with clinically significant baseline sleep disturbances and greater depression severity may require adjunctive sleep-focused treatment to ameliorate sleep symptoms.

Suicide is a health concern among Veterans with depression. We had previously reported on scripted dialogues adapted for an e-health system that engages at-risk veterans with schizophrenia. Here we report a further adaptation of the dialogues for Veterans with depression. Usability was assessed with nine outpatients with a history of major depression and suicidality. We noted that participants preferred greater specificity in the wording of questions. Topics that elicited an emotional response dealt with questions on suicide, social isolation and family relationships. Based on feedback, dialogues were revised for patients with depression. We also compared responses between those with depression and those with schizophrenia who were previously tested. The two groups shared similar themes. Also, individuals with a history of major depression had less trouble with vocabulary comprehension but were less willing to answer more questions daily.

The study objective was to assess the efficacy of problem-solving therapy for primary care (PST-PC) for preventing episodes of major depression and mitigating depressive symptoms of older black and white adults. The comparison group received dietary coaching.A total of 247 participants (90 blacks, 154 whites, and three Asians) with subsyndromal depressive symptoms were recruited into a randomized depression prevention trial that compared effects of individually delivered PST-PC and dietary coaching on time to major depressive episode and level of depressive symptoms (Beck Depression Inventory) over two years. Cumulative intervention time averaged 5.5-6.0 hours in each study arm.The two groups did not differ significantly in time to major depressive episodes, and incidence of such episodes was low (blacks, N=8, 9%; whites, N=13, 8%), compared with published rates of 20%-25% over one year among persons with subsyndromal symptoms and receiving care as usual. Participants also showed a mean decrease of 4 points in depressive symptoms, sustained over two years. Despite greater burden of depression risk factors among blacks, no significant differences from whites were found in the primary outcome.Both PST-PC and dietary coaching are potentially effective in protecting older black and white adults with subsyndromal depressive symptoms from developing episodes of major depression over two years. Absent a control for concurrent usual care, this conclusion is preliminary. If confirmed, both interventions hold promise as scalable, safe, nonstigmatizing interventions for delaying or preventing episodes of major depression in the nation's increasingly diverse older population.

Objective We conducted a pilot study comparing problem solving therapy for primary care (PST-PC) to a dietary education control condition in middle-aged and older veterans with symptoms of emotional distress and subsyndromal depression. Methods This was a two-site study at the VA Pittsburgh Healthcare System and Philadelphia VA Medical Center. Participants included veterans >50 years of age referred from primary care clinics who were eligible if they obtained a pre-screen score >11 on the Centers for Epidemiologic Studies Depression (CES-D) scale. Exclusions were a DSM-IV Major Depressive Episode within the past year, active substance abuse/dependence within 1 month, current antidepressant therapy, and a Mini mental status exam score

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.

Suicide is a health concern among individuals with schizophrenia. A telehealth system for monitoring suicidal patients with schizophrenia was developed using the Health Buddy©. The existing dialogues were improved using an expert panel; the new dialogues were tested in 10 consumers with schizophrenia and a history of suicidal behavior. Using qualitative editing, several themes emerged: (1) Certain topics elicited strong emotional responses; (2) There were concerns with confidentiality; (3) Some content was too vague and (4) There were problems with vocabulary and wording. The process yielded information for improving the intervention and demonstrated that the approach is feasible in this population.

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.

Background:This study compared sedative hypnotic use by type of mental health diagnosis and determined factors associated with use among older veterans (65+ years) with a newly reported mental health disorder.Methods:This study used data from veterans who received primary care services at VA Pittsburgh Healthcare System (VAPHS) from January 1, 2007 to December 31, 2011 (n= 879).Results:Sedative hypnotics were commonly used in older veterans within 12-months following a newly reported mental health disorder (19.9%), particularly amongst those with insomnia (41.7%). The number of newly reported mental health disorders was a significant factor associated with sedative hypnotic use, with the odds of use increasing by more than 200% in older adults with two newly reported disorders compared to those with one newly reported mental health disorder.Conclusions:Continued efforts are needed to improve provider and patient awareness of the risks associated with sedative hypnotic use in older adults, as well as to increase access to and receipt of non-pharmacological mental health treatments for this vulnerable population.

Objectives This study examined rates of syndromal and subthreshold Post Traumatic Stress Disorder (PTSD) and PTSD symptom scores in participants with symptoms of emotional distress, subsyndromal depression and a history of traumatic exposure. Participants had been referred for a study of an indicated depression prevention intervention using Problem-Solving Therapy in Primary Care. We hypothesized that higher severity of PTSD symptom scores would predict poorer problem solving skills. In addition, some reports have suggested that there are higher rates of PTSD in minority populations relative to Caucasians; thus we hypothesized that race would also predict problem solving skills in these individuals.

The management of suicide risk in patients with schizophrenia poses many challenges for clinicians. Compared with the general population, these patients have an 8.5-fold greater risk of suicide. This article reviews the literature dealing with the treatment of at-risk patients with schizophrenia. An integrated psychosocial and pharmacological approach to managing this population of patients is recommended. Although there is at least modest evidence suggesting that antipsychotic medications protect against suicidal risk, the evidence appears to be most favourable for second-generation antipsychotics, particularly clozapine, which is the only medication approved by the US FDA for preventing suicide in patients with schizophrenia. In addition, treating depressive symptoms in patients with schizophrenia is an important component of suicide risk reduction. While selective serotonin receptor inhibitors (SSRIs) ameliorate depressive symptoms in patients with schizophrenia, they also appear to attenuate suicidal thoughts. Further research is needed to more effectively personalize the treatment of suicidal thoughts and behaviours and the prevention of suicide in patients with schizophrenia.

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.

Background Subsyndromal symptoms of depression (SSD) in patients with schizophrenia are common and clinically important. SSRI's appear to be helpful in alleviating depressive symptoms in patients with schizophrenia who have SSD in patients age 40 and greater. It is not known whether SSRI's help improve functioning in this population. We hypothesized that treating this population with the SSRI citalopram would lead to improvements in social, mental and physical functioning as well as improvements in medication management and quality of life. Methods Participants were 198 adults ⩾ 40 years old with schizophrenia or schizoaffective disorder who met study criteria for subsyndromal depression based on having two or more of the nine DSM-IV symptoms of a major depressive episode, for at least 2 weeks, and a Hamilton depression rating scale (HAM-D 17) score ⩾ 8. Patients were randomly assigned to flexible-dose treatment with citalopram or placebo augmentation of their current antipsychotic medication(s) which was stable for 1 month. Subjects were assessed with the following functional scales at baseline and at the end of the 12-week trial: (1) social skills performance assessment (SSPA), (2) medication management ability assessment (MMAA), (3) mental and physical components of the medical outcomes study SF-12 Scale, and (4) the Heinrichs quality of life scale (QOLS). Analysis of covariance (ANCOVA) was used to compare differences between endpoint scores of the citalopram and placebo treated groups, controlling for site and baseline scores. ANCOVAs were also used to compare differences in the above endpoint scores in responders versus non-responders (responders = those with > 50% reduction in depressive symptoms). Results Overall, the citalopram group had significantly higher SSPA, mental functioning SF-12, and quality of life scale (QOLS) scores compared to the placebo group. There was no effect on MMAA or physical functioning SF-12 scores. Responders had significantly better endpoint mental SF-12 and QOLS scores compared to non-responders. Response to citalopram in terms of depressive symptoms mediated the effect of citalopram on mental functioning, but not on the quality of life. Conclusions Citalopram augmentation of antipsychotic treatment in middle aged and older patients with schizophrenia and subsyndromal depression appears to improve social and mental health functioning as well as quality of life. Thus it is important for clinicians to monitor these aspects of functioning when treating this population of patients with schizophrenia with SSRI agents. Copyright © 2009 John Wiley & Sons, Ltd.

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.

This study examines the prevalence and correlates of current suicidal ideation and past suicide attempts among patients aged 40 and older with schizophrenia spectrum disorders and concurrent depressive symptoms. Nearly half the sample (n = 132) reported having attempted suicide once or more in their lifetime; those who had attempted, exhibited greater depression and psychopathology. A regression analysis revealed that only past suicide attempts and hopelessness significantly accounted for the presence of current suicidal ideation. Surprisingly, current suicidal ideation did not differ by diagnosis, race/ethnicity, marital status, living situation, age, education, or severity of medical illness. Overall, suicidal ideation and the presence of past suicide attempts were remarkably prevalent, highlighting the need for continued clinical vigilance with this patient population. The impact of hopelessness and general psychopathology, as well as the insignificance of demographic characteristics and medical illness severity warrant further investigation.

Background Depressive symptoms are common in middle aged and older patients with schizophrenia. The authors hypothesized that worse functioning in these patients would be associated with worse psychopathology. Methods Outpatients with schizophrenia were ≥40 years old with subsyndromal depression and Hamilton Depression Rating Scale Scores of ≥8. Exclusions were dementia, two months of either mania or major depression or 1 month active substance abuse/dependence. The authors administered performance based functional assessments, the Positive and Negative Syndrome Scale of Schizophrenia [PANSS], and Calgary Depression Rating Scale. Results PANSS (−) scores were negatively correlated with the UCSD Performance Skills Based Assessment, Social Skills Performance Assessment and Medication Management Ability Assessment total error (MMAA) scores. Digit symbol scores served as a moderator of the relationship between MMAA and PANSS (−) scores. Conclusions Negative symptoms were associated with functioning. The relationship between negative symptoms and medication errors seem to weaken in subjects with quicker processing speed.

Objective The authors detail the public health need for depression prevention research and the decisions made in designing an experiment testing problem solving therapy as "indicated" preventive intervention for high-risk older adults with subsyndromal depression. Special attention is given to the recruitment of African Americans because of well-documented inequalities in mental health services and depression treatment outcomes between races. Methods A total of 306 subjects (half white, half African American) with scores of 16 or higher on the Center for Epidemiological Studies of Depression Scale, but with no history of major depressive disorder in the past 12 months, are being recruited and randomly assigned to either problem solving therapy-primary care or to a dietary education control condition. Time to, and rate of, incident episodes of major depressive disorder are to be modeled using survival analysis. Level of depressive symptoms will be analyzed via a mixed models approach. Results Twenty-two subjects have been recruited into the study, and to date eight have completed the randomly assigned intervention and postintervention assessment. Four of 22 have exited after developing major depressive episodes. None have complained about study procedures or demands. Implementation in a variety of community settings is going well. Conclusion The data collected to date support the feasibility of translating from epidemiology to RCT design and implementation of empirical depression prevention research in later life.

Summary 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 10 min 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 1 h 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.

Cerebrospinal fluid (CSF) neurohumors reflect central nervous system physiology in a way that peripheral indices can not. We reviewed clinical studies of CSF biogenic amines and neurohormones in alcohol misusers during various stages of withdrawal or abstinence and found them difficult to compare because of highly variable experimental methods, reliance on single time collections (lumbar punctures) that fail to control for potential stress-induced effects of the procedure, lack of control for tobacco use, and a paucity of non-alcoholmisusing controls. However, taken together, the data thus far show that a variety of neuroactive substances are reduced in concentration in the CSF of some alcohol misusers. Low CSF levels of corticotropinreleasing hormone, beta-endorphin, norepinephrine, diazepam-binding inhibitor, 5-hydroxyindoleacetic acid and somatostatin have all been reported. Whether the decreased CSF levels of these neurohormones and neurotransmitters are a cause or consequence of alcoholism has not been determined. In fact, further studies using serial or continuous CSF sampling techniques with homogeneous, better-characterized patients and normal volunteers are still needed to establish the precise CSF neurochemical abnormalities in alcohol misusers.

Objective The objectives are to delineate the nature of subsyndromal depressive symptoms (SSD) in midlife and older patients with schizophrenia and schizoaffective disorder by: 1) describing the relationship of SSD with a number of other clinical features; and 2) examining which specific depressive symptoms are increased in patients broadly defined as having SSD. Methods A total of 204 participants with schizophrenia or schizoaffective disorder and SSD who entered a federally funded intervention study at the University of California San Diego (UCSD) and University of Cincinnati were matched with schizophrenic and schizoaffective participants from the Geriatric Research Center at UCSD who had minimal or no depressive symptoms. The SSD and no depression groups were compared on a variety of clinical features including general psychopathology, positive and negative symptoms, medical and mental functioning, cognition, movement abnormalities, and specific depressive symptomatology. Results SSD was associated with increases in overall psychopathology; positive and negative symptoms; severity of general medical conditions; impaired physical and mental functioning; possibly more severe akathisia; and more depressive symptoms throughout the spectrum of symptom clusters measured by the Hamilton Depression Rating Scale, including anxiety and suicidality. Conclusions SSD in middle aged and older patients with schizophrenia is an important clinical dimension that appears to be associated with substantial morbidity and distress. The findings suggest that is important for clinicians to look for and assess subsyndromal depressive symptoms in patients with chronic schizophrenia.

Background Alcohol abuse and dependence have important clinical implications for managing patients with schizophrenia. Alcoholism in schizophrenia patients can interfere with the course and prognosis of the schizophrenic illness. Objective The purpose of the present study was to compare the cognitive status, symptom profile and quality of life of middle aged and older patients (>44 years old) with schizophrenia and alcohol abuse/dependence vs those without alcohol abuse/dependence. We initially hypothesized that more males in this age group with schizophrenia would exhibit alcoholism. We also examined the characteristics of the 45–54 year age group with those of the ≥ 55 year old group and hypothesized that comorbidity with alcohol would be associated with worse cognition and quality of life in later life. Methods Data were obtained from a database from the Center for Services and Interventions research at the University of California, San Diego. Patients had diagnoses of schizophrenia or schizoaffective disorder. Data collected included demographic characteristics, cognitive status (tested with the Mattis Dementia Rating Scale learning, the Figural and Story Memory Test of the Wechsler Memory Scale-Revised and the California Verbal Learning Test [CVLT]). In addition, patients had undergone psychopathologic assessment and were screened for quality of life using the Quality of Well Being scale. Results We demonstrated that the older aged patients with alcoholism had worse scores assessing cognition relative to the same aged group without alcoholism. In addition, they had worse cognitive scores relative to the younger group (45–54 year old) with alcoholism. There was no significant difference with regards to quality of life. In addition, more males than females exhibited alcoholism. Conclusion The results are consistent with the premise that the higher cognitive function in the younger schizophrenia patients with alcoholism appear to mask the effects of alcohol use on cognition at that age. However, for the older group of schizophrenia patients, the effects of alcohol use on neuropsychological functioning appear to be deleterious. Copyright © 2006 John Wiley & Sons, Ltd.

The elevated rate of suicide among patients with schizophrenia is well documented and thus frequently researched. The majority of research has focused solely on the identification of risk factors that predispose patients to attempt or commit suicide. This review serves to expand on the literature pertaining to suicide risk factors by additionally outlining how protective factors may shield against suicide within this unique patient population.A literature review of English-language publications pertaining to suicide among people with schizophrenia was completed using PsychINFO and MEDLINE databases between the years of 1960-2004 and 1950-2004 respectively. Special emphasis was given to studies of risk factors and protective factors for suicide.Commonly supported risk factors for suicide were identified: previous attempts, severity of illness, comorbidity, social isolation, temporal relationships, and demographic characteristics. Risk factors such as a history of violence, the presence of command hallucinations, and recent tragic loss were found to warrant future study. Social support, positive coping skills, life satisfaction, and resiliency emerged as protective factors that may mitigate suicide.Understanding why some patients wish to end their lives but also why some desire to live allows for more comprehensive suicide prevention.

SUMMARY Background The number of elderly combat veterans is steadily increasing in the US and estimates project that a notable percentage of these veterans experience symptoms of posttraumatic stress disorder (PTSD). Limited data exist specifically related to prevalence, assessment, and treatment of PTSD among the elderly veteran population. Objective This review summarizes the available research related to difficulties in assessment with the elderly American Armed Forces veteran population. In addition, both psychotherapeutic and pharmacological treatment interventions for PTSD are discussed. Methods A literature search was conducted using PsycINFO, Medline, and the National Center for PTSD’s PILOTS database. Results Evidence suggests that elderly veterans generally present more somatic symptoms of PTSD. Medical and psychological comorbodities, such as depression, substance abuse, or cognitive deficits can further complicate the assessment process. Cut-scores for existing instruments need to be further established with elderly veterans. Use of exposure therapies with the elderly has not been adequately researched and mixed results have been obtained for supportive therapy for treatment of PTSD. Controlled research investigating pharmacological interventions for PTSD with the elderly is also limited. Conclusion Evidence suggests that some psychotherapeutic and pharmacological interventions already utilized with younger individuals may be useful with the elderly veteran population. However, research indicates that modifications may be required for working with the elderly population and further research in the areas of assessment and treatment are necessary. Copyright # 2005 John Wiley & Sons, Ltd.

Antidepressant pharmacotherapy in elderly patients is challenging. The authors examined the use of citalopram to treat late-life minor depression. Ten men (mean age: 73±2 years) with DSM-IV Minor Depression were administered citalopram 20 mg/day. Efficacy was measured with the Geriatric Depression Scale (GDS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions of Severity (CGI-S) scales. Citalopram was well tolerated, and GDS, MADRS, and CGI-S scores decreased after 12 weeks. These findings indicate that citalopram is safe and effective in the treatment of late-life minor depression.

Quantifying the functional consequences of illness in terms of quality of life can enhance our understanding of both mental and physical disorders. However, little is known about the quality of life among older inpatients vs. outpatients with schizophrenia. We present the results of health-related quality of life assessments in 54 middle-aged and elderly long-term inpatients with schizophrenia and a demographically matched outpatient sample. Assessments were performed using the Quality of Well-Being (QWB) scale, along with standard measures of psychopathology and global cognitive impairment. Compared with outpatients, the inpatients had a significantly lower health-related quality of life, as measured by the QWB. In the inpatient and outpatient groups, higher levels of positive symptoms were associated with lower health-related quality of life. Health-related quality of life remained fairly stable among the inpatients who remained hospitalized over 6 months. In both inpatients and outpatients, baseline cognitive status and psychopathology predicted QWB scores at the 6-month follow-up. These findings further support the use of the QWB in severely mentally ill populations; implications for improving health-related quality of life among older patients with schizophrenia are discussed.

Despite evidence of hyperresponsive peripheral and central nervous system (CNS) noradrenergic activity in posttraumatic stress disorder (PTSD), direct measures of CNS norepinephrine in PTSD have been lacking. The goal of this study was to determine serial CSF norepinephrine levels in patients with PTSD.CSF samples were obtained serially over a 6-hour period in 11 male combat veterans with chronic PTSD and eight healthy men through an indwelling subarachnoid catheter. Thus the authors were able to determine hourly CSF norepinephrine concentrations under baseline (unstressed) conditions. Severity of the patients' PTSD symptoms was assessed with the Clinician-Administered PTSD Scale.CSF norepinephrine concentrations were significantly higher in the men with PTSD than in the healthy men. Moreover, CSF norepinephrine levels strongly and positively correlated with the severity of PTSD symptoms. Plasma norepinephrine concentrations showed no significant relationship with the severity of PTSD symptoms.These findings reveal the presence of greater CNS noradrenergic activity under baseline conditions in patients with chronic PTSD than in healthy subjects and directly link this pathophysiologic observation with the severity of the clinical posttraumatic stress syndrome.

Background: Little is known about the relationship between endogenous central nervous system (CNS) testosterone and any psychiatric syndrome. The goal of this study was to screen for potential abnormalities in CNS testosterone levels in patients with post-traumatic stress disorder (PTSD) and/or tobacco dependence. Methods: We sampled cerebrospinal fluid (CSF) via a subarachnoid catheter over six hours and determined hourly basal CSF concentrations of testosterone in 11 combat veterans with PTSD and 12 normal volunteers. Smokers were abstinent for 11–17 h. Testosterone in CSF and matching plasma samples was assayed by radioimmunoassay. Results: A factor analysis for effects of PTSD status, smoking status and sample time revealed significant effects of PTSD or smoking status, but not time, on CSF testosterone. CSF testosterone levels were lower in individuals with PTSD as compared with normal volunteers. When divided by smoking status, abstinent smokers had mean CSF testosterone levels higher than those of non-smokers. A similar analysis of plasma testosterone revealed no significant effects of any factor on plasma testosterone. Conclusions: These results indicate that CSF testosterone is significantly influenced by PTSD and smoking status. The exposure of the brain to altered levels of testosterone in smokers and patients with PTSD may have pathophysiologic significance in these conditions.

Depression is a common disorder in late life which can be successfully treated with antidepressant agents. Other disorders such as behavioural agitation associated with dementia may also be treated with antidepressants. In this review, we have examined the use of five serotonin-selective reuptake inhibitors in the treatment of late-life depression and related disorders in the elderly population. Medications examined include citalopram, fluoxetine, fluvoxamine, sertraline and paroxetine. Comparisons of these agents' efficacy in the elderly are made. In addition, comparisons of these agents' side effects, pharmacokinetics and potential for drug-drug interactions are also discussed.

The authors sought to carefully test, by using a technique of continuous CSF sampling, the hypothesis that basal elevations in CSF corticotropin-releasing hormone (CRH) concentrations exist in patients with posttraumatic stress disorder (PTSD). They also sought to assess the relationship among PTSD symptoms, adrenocortical activity, and CSF CRH levels.CSF was withdrawn by means of a flexible, indwelling subarachnoid catheter over a 6-hour period, and hourly CSF concentrations of CRH were determined for 11 well-characterized combat veterans with PTSD and 12 matched normal volunteers. Twenty-four-hour urinary-free cortisol excretion was also determined. PTSD and depressive symptoms were correlated with the neuroendocrine data.Mean CSF CRH levels were significantly greater in PTSD patients than in normal subjects (55.2 [SD = 16.4] versus 42.3 pg/ml [SD = 15.6]). No correlation was found between CSF CRH concentrations and PTSD symptoms. While there was no significant difference between groups in 24-hour urinary-free cortisol excretion, the correlation between 24-hour urinary-free cortisol excretion and PTSD symptoms was negative and significant.By using a serial CSF sampling technique, the authors found high basal CSF CRH concentrations and normal 24-hour urinary-free cortisol excretion in combat veterans with PTSD, a combination that appears to be unique among psychiatric conditions studied to date.

The authors evaluated the safety, tolerability, and efficacy of risperidone in 103 elderly patients (mean age, 71 years) with schizophrenia (75%) or schizoaffective disorder (25%). Using the Extrapyramidal Symptoms Rating Scale (ESRS), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression (CGI) scale, they conducted a prospective, open-label, 12-week trial in 14 psychiatric centers in the United States. Patients' symptoms were assessed at baseline and over a 12-week period. At endpoint, ESRS scores were significantly reduced, as were PANSS total and subscale scores. There were no clinically significant changes in electrocardiograms, laboratory test results, or vital signs. Risperidone was well tolerated and efficacious in elderly patients with schizophrenia or schizoaffective disorder.

Schizophrenia is a serious illness and one of the most expensive psychiatric disorders.It is anticipated that the number and proportion of older patients with schizophrenia will continue to increase. By 2025, it is anticipated that patients 55 and older with schizophrenia will comprise 25% of all patients with schizophrenia. This research symposium will include papers by investigators from various sites which present and discuss recent research in older patients with schizophrenia. Dr. Kasckow will serve as chair. The topics will range from research studies examining recent longitudinal data on outcome with respect to remission, community integration, cognition, depression and health; research examining the feasibility and potential effectiveness of using ecological momentary assessments with older adults with schizophrenia and other serious mental illnesses to allow clinicians to recognize early signs of of psychiatric distress; research examining inflammatory biomarkers in older patients with schizophrenia; and a review of the evidence base for psychopharmacologic treatment of older adults with schizophrenia. Dr. Carl Cohen will serve as the symposium discussant and will relate these findings towards treating this population. This session will important new advances in research pertaining to older patients with schizophrenia.

We used the technique of continuous cerebrospinal fluid (CSF) sampling to test the following hypotheses regarding CNS monoaminergic systems in depression:(1) absolute concentrations of the informational substances tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) are altered in the CNS of depressed patients (2) abnormal rhythms of tryptophan and/or 5-HIAA, or defective conversion of tryptophan to serotonin (5HT), exist in the CNS of depressed patients, and (3) the relationship between the CNS 5HT and norepinephrine (NE) systems is disrupted in depressed patients. We obtained 6-h concentration time series of tryptophan, 5-HIAA, NE, and 3-methoxy-4-hydroxyphenylglycol (MHPG) in the CSF of 10 patients with major depression and in 10 normal volunteers. No significant differences in CSF tryptophan, 5-HIAA, NE, or MHPG concentrations or rhythms were observed between normal volunteers and depressed patients. Neither were there differences in the mean tryptophan-to-serotonin ratio. However, a negative linear relationship was observed between mean concentrations of 5-HIAA and NE in the CSF of the normal volunteers (r = 0.916 [r2 = 0.839], df = 9, P < 0.001) while, in contrast, depressed patients showed no such relationship (r = +0.094 [r2 = 0.00877], df = 9, n.s.). Furthermore, the correlation coefficients expressing the relationship between CSF MHPG and CSF 5-HIAA within the normal and depressed groups were significantly different. These data support the hypothesis that a disturbance in the interaction between the serotonergic and noradrenergic systems can exist in depressive illness in the absence of any simple 5HT or NE deficit or surplus. Depression and Anxiety 6:89–94, 1997.© 1997 Wiley-Liss, Inc.

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.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.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.Despite normal peripheral cortisol indexes in the veterans with PTSD, their CNS exposure to cortisol was greater than that of normal comparison subjects.

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).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.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.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.