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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.

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.

Objective: This study identified the prevalence of and relationship between mood disorders and multimorbidity in middle-aged and older veterans. Method: Cross-sectional data were obtained from veterans who received primary care services at VA Pittsburgh Healthcare System from January 2007 to December 2011 ( n = 34,786). Results: Most veterans had three or more organ systems with chronic disease (95.3%), of which 4.1% had a depressive disorder, 2.5% had an anxiety disorder, and 0.7% had co-occurring depression and anxiety. The odds of having a mood disorder increased with each additional organ system with chronic disease, with odds being the greatest in those with 10 to 13 organ systems with chronic disease. Younger age, female gender, non-married marital status, and having a service connected disability were also significant predictors of having a mood disorder. Discussion: These findings suggest a need to integrate mental health assessment and treatment in chronic health care management for veterans.

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.

Importance Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. Objective To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. Design, Setting, and Participants From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). Main Outcomes and Measures The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C 16 ] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C 16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Results Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. Trial Registration clinicaltrials.gov Identifier:NCT01421342

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.

We conducted a review of recent studies of appointment attendance in patients with schizophrenia. Appointment attendance is identified as an important issue, but the amount of attention addressing it is limited. Rates of missed appointments in the studies reviewed range from 20 to 67%. The transition from inpatient to outpatient care appears to be a time of higher rates of missed appointments. Correlates of missed appointments vary greatly across studies, with the most consistent relationship found between increased levels of psychopathology and decreased appointment attendance. Review of the limited literature on the relationship between missed appointments and suicide in patients with schizophrenia reveals an increase in mental health contacts prior to and following suicidal behaviors. Interventional studies demonstrate that appointment attendance can be improved. Psychoeducation and appointment reminders show promise in improving attendance. Future research on appointment attendance is likely to be fac...

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.

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.

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.

Corticotropin-releasing factor (CRF) is produced in the hypothalamic paraventricular nucleus (PVN) in response to stress and stimulates the release of adrenocorticotropic hormone in the corticotrophs. Estrogens acting centrally are able to modulate the stress responses. In fact, direct estrogenic regulation of CRF gene expression has been demonstrated in various tissues. However, the mechanisms responsible for the actions of estrogens on CRF regulation in the PVN remain undetermined. We investigated whether estradiol (E2) contributes to the regulation of CRF gene and promoter activity in hypothalamic 4B cells. Furthermore, the involvement of E2 in the regulation of interleukin (IL)-6 and its role in hypothalamic 4B cells was explored. We demonstrated the dominant expression of estrogen receptor type beta (ERbeta) and found that a physiologically relevant dose of E2 and an ERbeta agonist stimulated CRF gene transcription in hypothalamic 4B cells. E2 stimulated IL-6 transcriptional activity via ERbeta, and subsequently the levels of IL-6 mRNA and protein. We also found that treatment with IL-6 significantly reduced cell viability. Thus, these data suggest the important effects of E2 on the regulation of CRF gene and IL-6 production via ERbeta in hypothalamic 4B cells.

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).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.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.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 WileySons, Ltd.

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.

Corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) are the two major regulatory peptides in the hypothalamic–pituitary–adrenal axis. CRF, produced in the hypothalamic paraventricular nucleus (PVN) in response to stress, is secreted into the pituitary portal circulation, resulting in the release of adrenocorticotropic hormone from the anterior pituitary. AVP is synthesized in the PVN and supraoptic nucleus by various stressors. Hypothalamic 4B cells coexpress CRF and AVP. In 4B cells transfected with either a CRF or an AVP promoter-luciferase construct, forskolin increased the transcriptional activity of CRF or AVP. In the present study, we tried to determine whether pituitary adenylate cyclase-activating polypeptide (PACAP) regulates both CRF and AVP genes in the hypothalamic cells, because receptors for PACAP were expressed in the hypothalamic cells. PACAP stimulated activity of both CRF and AVP promoter via protein kinase A pathway. PACAP stimulated interleukin (IL)-6 promoter activity and the levels of IL-6 mRNA and protein. IL-6 stimulated activity of both CRF and AVP promoter in a dose-dependent manner. Finally, we found that the stimulatory effects of PACAP on both activities were significantly inhibited by treatment with anti-IL-6 monoclonal antibody. These data suggest that PACAP is involved in regulating the synthesis of IL-6 mRNA and IL-6 protein, and that the increase in endogenous IL-6 also contributes to stimulate the expression of both CRF and AVP genes. Taken together, these findings indicate that PACAP stimulates the transcription of CRF, AVP, and IL-6 genes in hypothalamic 4B cells.

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.

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.

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.

Treating older patients with neurodegenerative disorders involves numerous challenges. The older patient population is expected to increase appreciably in the coming years; thus, there will be increasing numbers of these individuals requiring treatment. As a result, the appropriate choice of psychopharmacologic agents becomes an important decision in treating older patients with atypical antipsychotics. The atypical antipsychotic medications are replacing the high-potency conventional antipsychotics in the long-term care setting because of the lower risks of side effects. For instance, atypical antipsychotics have lower rates of extrapyramidal side effects and tardive dyskinesia. Double-blind placebo-controlled trials examining the use of risperidone and olanzapine have been published and indicate that both agents safely and effectively reduce agitation symptoms in long-term care patients with neurodegenerative disorders. For instance, based on these studies, the doses that appear efficacious in treating behavioral agitation in dementia are 0.5 to 1.5 mg per day of risperidone and 5 to 10 mg per day of olanzapine. In addition, there are open-label studies examining the use of quetiapine, which suggest that this agent is also safe and efficacious in patients with dementia. Doses used range approximately from 25 to 350 mg per day. Very few studies are available examining the newest atypical antipsychotics, ziprasidone and aripiprazole, in patients with neurodegenerative disorders. These studies do suggest that ziprasidone and aripiprazole are worth further study in the long-term care setting.

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.

Studies involving regulation of corticotropin-releasing hormone (CRH) in vitro have been used to validate findings obtained in vivo and more importantly have been used as model systems to better understand signalling mechanisms responsible for the expression of the CRH gene and peptide. Many in vitro studies examining CRH have utilized hypothalamic tissue while a few have focused on the amygdala. Clonal cell lines have also been utilized as models of central nervous system CRH neurons. Stimuli that have been implicated in regulating hypothalamic CRH regulation in vitro include protein kinase A (PKA) and protein kinase C (PKC) activators, glucocorticoids, biogenic amines, cytokines and the gaseous neurotransmitters. Amygdalar CRH levels in vitro are affected by some of the same stimuli that regulate hypothalamic CRH; however there is evidence supporting differential regulation of CRH in these two brain regions by some of the same stimuli. Only a few studies in aggregate have investigated signal transduction mechanisms and these studies have focused on PKA- and glucocorticoid-mediated changes in CRH expression. Thus, much more investigative work in better understanding CRH regulation in vitro is needed.

Corticotropin-releasing hormone (CRH) is a 41 amino acid neuropeptide which plays an important role in the stress response in the hypothalamus. We describe the development of an immortalized hypothalamic cell line which expresses CRH. We hypothesized that this cell line would possess the relevant characteristics of parvocellular CRH-expressing neurones such as glucocorticoid receptor (GR) expression and vasopressin (VP) coexpression. For production of hypothalamic cells, embryonic day 19 rat pup hypothalami were dissected and dissociated into tissue culture dishes. They were immortalized by retrovirus-mediated transfer of the SV40 large T antigen gene at 3 days of culture and then screened for expression of CRH following dilution cloning. One cell line was chosen (IVB) which exhibited CRH-like immunoreactivity (CRH-LI) and expressed CRH, VP and CRH1 receptor RNA via the reverse transcriptase-polymerase chain reaction. In addition, the cell line expressed the neuronal marker, microtubule-associated protein-2. We verified that the CRH-LI from IVB cell lysates coeluted with CRH standard via reversed-phase high-performance liquid chromatography (HPLC). Furthermore, oxidation of the lysate converted its HPLC profile to that identical with oxidized CRH standard. In addition, IVB cells exhibited high affinity binding to CRH. Incubation of IVB cells with CRH lead to increases in cAMP levels and protein kinase A activity in a concentration-dependent manner. Incubation of IVB cells with CRH also resulted in increases in phospho-cyclic-AMP response element binding protein (CREB) immunostaining as detected by immunocytochemical analysis. Finally, CRH treatment of IVB cell lines has been linked to CREB-mediated gene expression as determined via the PathDetect CREB trans-reporting system. The characteristics of IVB cells, such as CRH and VP coexpression, GR expression and a biologically active CRH-R1-mediated signalling pathway, suggest that this neuronal cell line may serve as model of parvocellular CRH neurones.