Optimizing Scripted Dialogues for an e-Health Intervention for Suicidal Veterans with Major Depression.

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.

Using problem solving therapy to treat veterans with subsyndromal depression: a pilot study.

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 <24. Participants were randomized to receive one of two interventions--either PST-PC or an attention control condition consisting of dietary education (DIET)--each consisting of six to eight sessions within a 4-month period. RESULTS: Of 45 individuals randomized, 23 (11 PST-PC and 12 DIET) completed treatment. Using regression models in completers that examined outcomes at end of treatment while controlling for baseline scores, there were significant differences between treatment groups in SF-36 mental health component scores but not in depressive symptoms (as assessed with either the 17-item Hamilton Rating Scale for Depression or the Beck Depression Inventory), social problem solving skills, or physical health status (SF-36 physical health component score). CONCLUSIONS: These pilot study findings suggest that a six-to-eight session version of PST-PC may lead to improvements in mental health functioning in primary care veterans with subsyndromal depressive symptoms.

Development of telehealth dialogues for monitoring suicidal patients with schizophrenia: consumer feedback.

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.

Subsyndromal depression and anxiety in older adults: health related, functional, cognitive and diagnostic implications.

Subsyndromal depression in later life is common in primary care. Comorbid anxiety disorders could exacerbate the negative effect of subsyndromal depression on functioning, health-related quality of life, comorbidity and/or cognition. We examined anxiety disorders co-existing with subsyndromal depression in participants ≥ age 50 in an NIH trial of Problem Solving Therapy for Primary Care for indicated prevention of major depression. There were 247 participants, with Centers for Epidemiologic Studies - Depression scores ≥ 11. Participants could have multiple psychiatric diagnoses: 22% of the sample had no DSM IV diagnosis; 39% of the sample had only 1 DSM IV diagnosis; 28% had 2 diagnoses; 6% had 3 DSM IV diagnoses; 4% had 4 DSM IV diagnoses; and 1% had 5 diagnoses. Furthermore, 34% of participants had a current comorbid DSM IV diagnosis of a syndromal anxiety disorder. We hypothesized that those with subsyndromal depression, alone relative to those with co-existing anxiety disorders, would report better health-related quality of life, less disability, less medical comorbidity and less cognitive impairment. However, there were no differences in quality of life based on the SF 12 nor in disability based on Late Life Function and Disability Instrument scores. There were no differences in medical comorbidity based on the Cumulative Illness Scale-Geriatrics scale scores nor in cognitive function based on the Executive Interview (EXIT), Hopkins Verbal Learning Test-Revised and Mini-Mental Status Exam. Our findings suggest that about one third of participants 50 years and older with subsyndromal depression have comorbid anxiety disorders; however, this does not appear to be associated with worse quality of life, functioning, disability, cognitive function or medical comorbidity.

Post-traumatic stress disorder symptoms in emotionally distressed individuals referred for a depression prevention intervention: relationship to problem-solving skills.

OBJECTIVES: This study examined the 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 to 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. METHODS: We examined the rates of traumatic exposure, syndromal, and subthreshold PTSD. In those exposed to trauma, we performed a multiple linear regression to examine the effects of PTSD symptoms, depression symptoms, race, age, and gender on social problem-solving skills. RESULTS: Of the 244 participants, 64 (26.2%) reported a traumatic event; 6/234 (2.6%) had syndromal PTSD, and 14/234 (6.0%) had subthreshold PTSD. By way of regression analysis, higher PTSD symptom scores predicted poorer problem-solving skills. In addition, racial status (Caucasian vs. African American) predicted problem-solving skills; Caucasians exhibited lower levels of problem-solving skills. CONCLUSIONS: Individuals presenting with subsyndromal depressive symptoms may also have a history of traumatic exposure, subthreshold and syndromal PTSD. Thus, screening these individuals for PTSD symptoms is important and may inform clinical management decisions because problem-solving skills are lower in those with more severe PTSD symptoms (even after adjusting for race, age, gender, and depressive symptoms).

Development of a recovery manual for suicidal patients with schizophrenia: consumer feedback.

A recovery-oriented manual was developed for patients with schizophrenia and suicidality. It included psychoeducational information, vignettes, "workbook" sections and was reviewed by experts in suicidology, recovery, patient education, manual development and psychosocial interventions. The revised version was tested in 22 consumers with schizophrenia and a history of suicidality. Consumer-based focus groups yielded five key themes which were used to further refine the manual. A satisfaction survey indicated that 85% stated the manual was 'somewhat easy', 'easy' or 'very easy to read.' All stated it was 'very useful', 'useful' or 'somewhat useful. Thus, the manual appears to be acceptable and useful.

Glial glucocorticoid receptors in aged Fisher 344 (F344) and F344/Brown Norway rats.

Glucocorticoid receptors (GR) regulate glial function, and changes in astrocyte gene expression are implicated in age-related pathology. We evaluated changes in astroglial GR expression in two strains of rats--Fisher 344 (F344; 4, 12 and 24 months) and F344/Brown Norway strain (F344/BN; 4, 12 and 30 months). In both strains basal levels of corticosterone were higher in the oldest groups of rats. Age-related increases in GR (+) astrocytes but not the percent of astrocytes expressing GR were observed in the hippocampus CA1 region in F344 rats. Age-related decreases in CA1 GR (+) astrocytes and the percentage of GR (+) astrocytes were observed in the F344/BN strain only. Similar strain-specific changes were observed in the dentate gyrus. In the hypothalamic paraventricular nucleus: (1) F344 rats exhibited significant decreases in the overall number of glial profiles with age, (2) F344/BN rats exhibited decreases in the numbers of GR (+) astrocytes with aging and (3) the proportion of GR (+) astrocytes decreased in older F344/BN, but not F344 rats. Overall, the data demonstrate age- and strain-related alterations in GR astrocytic expression that may explain unique phenotypic differences in brain function observed in both strains.

Suicidality in middle aged and older patients with schizophrenia and depressive symptoms: relationship to functioning and Quality of Life.

BACKGROUND: Suicidality is a health concern in patients with schizophrenia. We examined the hypotheses: (1) Middle aged and older patients with schizophrenia, depressive symptoms and suicidality would exhibit worse quality of life and worse everyday functioning, social skills and medication management relative to those without suicidality; (2) higher levels of suicidality would be significantly associated with worse functioning, worse quality of life and older age. METHODS: We examined 146 outpatients with schizophrenia and depression. Patients were at least 40 years old and were diagnosed with schizophrenia or schizoaffective disorder and had two or more depressive symptoms based on DSM-IV criteria for major depression. We assessed suicidality with the Intersept Suicide Scale (ISS) and functioning with the UCSD Performance-based Skills Assessment (UPSA), Social Skills Performance Assessment (SSPA), and Medication Management Ability Assessment (MMAA). Quality of life was assessed with the Heinrichs Quality of Life Scale (QLS). RESULTS: The mean age of patients was 52.4+ 6.9 years. Subjects with suicidality (ISS scores > 0) had lower QLS scores compared to those without suicidality. However, there were no differences in UPSA, SSPA nor MMAA scores between the two groups. In addition, based on Spearman's rho correlational analysis, there were significant associations of QLS scores with ISS scores (r = - 0.236) and with MMAA "total errors" scores (r = 0.174). Logistic regression demonstrated that only QLS scores predicted suicidality. CONCLUSION: Thirty-six percent of our sample had at least mild degrees of suicidality. Lower quality of life appears to be an important predictor of suicidality.

Neurocognitive functioning in dually diagnosed middle aged and elderly patients with alcoholism and 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 > or = 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.

Aging associated changes in amygdalar corticotropin-releasing hormone (CRH) and CRH-binding protein in Fischer 344 rats.

Behavioral adaptation in aging may become impaired from abnormal expression of amygdalar corticotropin-releasing hormone (CRH) and/or CRH-binding protein (CRH-BP). In this study, we serially sectioned the amygdala in 4-, 12-, and 24-month-old Fischer 344 rats following perfusion with 4% paraformaldehyde. We determined the amount of CRH and CRH-BP containing cells as well as the density of fibers expressing CRH or CRH-BP utilizing densitometric methods. Images were digitized using Zeiss Axiovision software and densitometrically analyzed using Scion Image. Both sides were analyzed in sections cut at 30 mum thickness. Cell counts of CRH-BP containing cells in the basolateral and lateral nucleus of the amygdala were lower in 24-month-old rats vs. 4-month-old rats, respectively (mean cells/section +/- SE): 31 +/- 6 vs. 72 +/- 10 (n = 3; P < 0.05 via ANOVA and Fisher's PLSD). There was a trend for cell counts of CRH containing cells in the central nucleus of the amygdala to be lower in 24-month-old rats vs. 4-month-old rats, respectively 28 +/- 7 vs. 47 +/- 9 (n = 3; P = 0.07 via ANOVA). Densitometric analysis of the number of CRH-BP positive fibers revealed no age differences in CeA; however, with regards to CRH-positive fibers, both 4- and 12-month rats had greater CeA CRH immunoreactivity relative to 24-month-old rats (Ps < 0.05 via ANOVA and Fisher's PLSD). These changes may contribute to impaired adaptations to stress, cognitive decline, and other pathophysiological processes during aging.

The use of novel antipsychotics in the older patient with neurodegenerative disorders in the long-term care setting.

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.

In vitro regulation of corticotropin-releasing hormone.

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) expression and protein kinase A mediated CRH receptor signalling in an immortalized hypothalamic cell line.

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.

Citalopram augmentation of antipsychotic treatment in older schizophrenia patients.

BACKGROUND: Depressive symptoms are common in older patients with schizophrenia; yet, few studies have examined the usefulness of antidepressants in this population. OBJECTIVE: We conducted a 10-week single-blind trial of citalopram (20-40 mg/day) vs no citalopram augmentation in 19 middle-aged and elderly patients with schizophrenia hospitalized for more than six of the last 12 months. At study-entry, the patients had been on stable doses of antipsychotics for at least two weeks, and had a 17-item Hamilton Depression Rating (HAM-D) scale score of 12 or greater. Nine patients were randomly assigned to citalopram augmentation, and 10 to no augmentation of antipsychotics. RESULTS: Patients in both groups improved on positive and negative symptoms, but the citalopram group had significantly greater improvement in HAM-D and Clinical Global Impression Scale scores than the control group. There were no major side effects. CONCLUSION: Larger double-blind studies are needed to follow up on these preliminary findings.

CSF norepinephrine concentrations in posttraumatic stress disorder.

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

A double-blind, randomized, prospective evaluation of the efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder.

The relative efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder was studied. Sixty-two patients (29 depressed type; 33 bipolar type) entered a three-site, randomized, double-blind, 6-week trial of risperidone (up to 10 mg/day) or haloperidol (up to 20 mg/day). Trained raters assessed baseline, weekly, and end-of-study levels of psychopathology with the Positive and Negative Syndrome Scale (PANSS), the 24-item Hamilton Rating Scale for Depression (HAM-D-24) and the Clinician-Administered Rating Scale for Mania (CARS-M). The authors were unable to statistically distinguish between risperidone and haloperidol in the amelioration of psychotic and manic symptoms. In addition, there was no difference in worsening of mania between the two agents in either subgroup (i.e., depressed or bipolar subgroups). For the total PANSS, risperidone produced a mean decrease of 16 points from baseline compared with a 14-point decrease with haloperidol. For the total CARS-M scale, risperidone and haloperidol produced mean change scores of 5 and 8 points, respectively, and for the CARS-M Mania subscale, 3 and 7 points, respectively. Additionally, risperidone produced a mean decrease of 13 points from the baseline 24-item HAM-D, compared with an 8-point decrease with haloperidol. In those patients who had more severe depressive symptoms (i.e., HAM-D baseline score >20), risperidone produced at least a 50% mean improvement in 12 (75%) of 16 patients in comparison to 8 (38%) of 21 patients receiving haloperidol. Haloperidol produced significantly more extrapyramidal side effects and resulted in more dropouts caused by any side effect. There was no difference between risperidone and haloperidol in reducing both psychotic and manic symptoms in this group of patients with schizoaffective disorder. Risperidone did not demonstrate a propensity to precipitate mania and was better tolerated than haloperidol. In those subjects with higher baseline HAM-D scores (i.e., >20), risperidone produced a greater improvement in depressive symptoms than haloperidol.

Circulating human corticotropin-releasing factor-binding protein levels following cortisol infusions.

Corticotropin-releasing factor-binding protein (CRF-BP) is a 37 kDa protein present in the brain and plasma and is known to regulate the actions of CRF. It has been demonstrated that CRF-BP in the brain and the pituitary appears to be positively regulated by glucocorticoids. In this study, the effect of various doses of hydrocortisone infusions on plasma CRF-BP levels was assessed. Four groups of 10 age-matched males received a 100 min infusion of either placebo (saline), 40 microg/kg/h, 300 microg/kg/h or 600 microg/kg/h hydrocortisone. CRF-BP levels were measured via a LIRMA. In addition, levels of plasma ACTH and cortisol were measured by standard radioimmunoassay. As expected, plasma cortisol levels increased and plasma ACTH levels were suppressed following the infusion. When expressed as proportion of pre-infusion baseine, no significant changes in plasma CRF-BP levels were observed following the infusion for all hydrocortisone groups relative to the control group. However, a significant time-averaged positive correlation was found between CRF-BP and cortisol levels at low to moderate, but not high, cortisol levels. The data obtained in this study indicate that CRF binding protein levels within the time course examined may slightly appear to be affected in the peripheral circulation in response to pronounced, sustained hypercortisolemia.

Health-related quality of well-being in chronically hospitalized patients with schizophrenia: comparison with matched outpatients.

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.

The effect of feeding on cerebrospinal fluid corticotropin-releasing hormone levels in humans.

Corticotropin-releasing hormone (CRH) is a neuropeptide thought to play a role in appetite regulation. In this report, we used a serial cerebrospinal fluid (CSF) sampling technique to examine the relationship between CSF CRH, plasma ACTH and cortisol and perceptions of hunger and satiety in fasting and sated volunteers. CSF was withdrawn continuously from 11:00 AM to 5:00 PM via an indwelling subarachnoid catheter. Blood was withdrawn every 10 min via an antecubital vein catheter. Fed subjects received a meal at 1:00 PM. Subjects who were fed had lower post-prandial ratings on hunger scales and higher ratings on satiety scales. Fed subjects also had slightly lower levels of CSF CRH after feeding. Furthermore, fed subjects had higher ACTH and cortisol concentrations in the first 3 h; by the fourth h the opposite was true. Our findings do not support the hypothesis that CNS CRH is a central satiety factor in the human. Instead our findings of slightly diminished CSF CRH levels after feeding may be accounted for by the rises in glucocorticoids and their associated negative feedback effects on CNS CRH. Alternatively, our findings could also reflect changes in CRH levels associated with feeding in multiple brain areas and in the spinal cord with the net effect being in the negative direction.