Philip Morris

Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study.

BACKGROUND This study examined cerebral function in posttraumatic stress disorder (PTSD) during the updating of working memory to trauma-neutral, verbal information. METHODS Ten PTSD and matched control subjects completed a visuoverbal target detection task involving continuous updating (Variable target condition) or no updating (Fixed target condition) of target identity, with updating activity estimated by condition comparison. RESULTS Normal updating activity using this paradigm involved bilateral activation of the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe. The PTSD group lacked this activation in the left hemisphere and was significantly different from control subjects in this regard, but showed additional activation in the superior parietal lobe, bilaterally. CONCLUSIONS The pattern of parietal activation suggests a dependence on visuospatial coding for working memory representation of trauma-neutral, verbal information. Group differences in the relative involvement of the DLPFC indicate less dependence in PTSD on the executive role normally attributed to the left DLPFC for monitoring and manipulation of working memory content in posterior regions of the brain.

The relationship between the perception of social support and post-stroke depression in hospitalized patients.

In our study we examined the relationship between the perceived adequacy of social support and post-stroke depression in 76 hospitalized Australian patients. Social support or the perception of its lack, particularly from a spouse care-giver, was associated significantly with both the presence and severity of depressive disorder. Furthermore, depressed patients who perceived their support to be inadequate had a longer duration of depressive illness than depressed patients who perceived their support in a more favorable light. We conclude that following stroke, perception of social support from key relationships may mediate the emotional response to this life crisis. The implications of these findings are discussed.

Abnormal Functional Connectivity in Posttraumatic Stress Disorder

This study investigated the efficacy of a combined multivariate/resampling procedure for the analysis of PET activation studies. The covariance-based multivariate analysis was used to investigate distributed brain systems in posttraumatic stress disorder (PTSD) patients and matched controls during performance of a working memory task. The results were compared to univariate results obtained in an earlier study. We also examined whether the PTSD patients demonstrated a breakdown in functional connectivity that may be associated with working memory difficulties often experienced by these patients. A resampling procedure was used specifically to test the reliability of measured between-group effects, to avoid mistaken inference on the basis of random intersubject differences. Significant and reproducible differences in network connectivity were obtained for the two groups. The functional connectivity pattern of the patient group was characterized by relatively more activation in the bilateral inferior parietal lobes and the left precentral gyrus than the control group, and less activation in the inferior medial frontal lobe, bilateral middle frontal gyri and right inferior temporal gyrus. The resampling procedure provided direct evidence that working memory updating was abnormal in PTSD patients relative to matched controls. This work focuses on the need to identify extended brain networks (in addition to regionally specific changes) for the full characterization of brain responses in neuroimaging experiments. Our multivariate analysis explicitly measures the reliability of the patterns of functional connectivity we obtain and demonstrates the potential of such analyses for the study of brain network dysfunction in psychopathology.

The Relationship Between Risk Factors for Affective Disorder and Poststroke Depression in Hospitalised Stroke Patients

The influence of psychiatric risk factors on the development of depression following stroke was examined in 88 patients undergoing inpatient rehabilitation. In this sample, 34 patients (38%) had a diagnosis of major or minor depression. Older age and a personal or family history of affective or anxiety disorder were associated significantly with major depression. Minor depression was more common among males and those patients with greater physical disability. Severity of depressive symptoms was associated with a personal or family history of affective or anxiety disorder and higher pre-stroke personality neuroticism. We conclude that certain psychiatric risk factors for affective disorder are strongly associated with poststroke depression. The implications of these findings for anticipating and managing poststroke depression are discussed.

Intramuscular olanzapine and intramuscular haloperidol in acute schizophrenia: Antipsychotic efficacy and extrapyramidal safety during the first 24 hours of treatment

Objective: To determine the antipsychotic efficacy and extrapyramidal safety of intramuscular (IM) olanzapine and IM haloperidol during the first 24 hours of treatment of acute schizophrenia. Method: Patients (n = 311) with acute schizophrenia were randomly allocated (2:2:1) to receive IM olanzapine (10.0 mg, n = 131), IM haloperidol (7.5 mg, n = 126), or IM placebo (n = 54). Results: After the first injection, IM olanzapine was comparable to IM haloperidol and superior to IM placebo for reducing mean change scores from baseline on the Brief Psychiatric Rating Scale (BRPS) Positive at 2 hours (–2.9 olanzapine, −2.7 haloperidol, and −1.5 placebo) and 24 hours (–2.8 olanzapine, −3.2 haloperidol, and −1.3 placebo); the BPRS Total at 2 hours (–14.2 olanzapine, −13.1 haloperidol, and −7.1 placebo) and 24 hours (–12.8 olanzapine, −12.9 haloperidol, and −6.2 placebo); and the Clinical Global Impressions (CGI) scale at 24 hours (–0.5 olanzapine, −0.5 haloperidol, and −0.1 placebo). Patients treated with IM olanzapine had significantly fewer incidences of treatment-emergent parkinsonism (4.3% olanzapine vs 13.3% haloperidol, P = 0.036), but not akathisia (1.1% olanzapine vs 6.5% haloperidol, P = 0.065), than did patients treated with IM haloperidol; they also required significantly less anticholinergic treatment (4.6% olanzapine vs 20.6% haloperidol, P < 0.001). Mean extrapyramidal symptoms (EPS) safety scores improved significantly from baseline during IM olanzapine treatment, compared with a general worsening during IM haloperidol treatment (Simpson–Angus Scale total score mean change: −0.61 olanzapine vs 0.70 haloperidol; P < 0.001; Barnes Akathisia Scale global score mean change:−0.27 olanzapine vs 0.01 haloperidol; P < 0.05). Conclusion: IM olanzapine was comparable to IM haloperidol for reducing the symptoms of acute schizophrenia during the first 24 hours of treatment, the efficacy of both being evident within 2 hours after the first injection. In general, more EPS were observed during treatment with IM haloperidol than with IM olanzapine.

Are there two depressive syndromes after stroke

The objective of this study was to describe the clinical characteristics of minor depression after stroke and to compare this disorder with poststroke major depression and the nondepressed state. Ninety-four stroke inpatients were examined 8 weeks after stroke and reexamined 15 months later. Twenty-one (22%) of the 94 patients suffered from minor depression, 14 (15%) suffered from major depression, and 59 (63%) were not depressed. Minor depressed patients were twice as symptomatic as nondepressed patients but were only half as symptomatic as major depressed patients. Minor depressed patients were more likely than nondepressed patients to have a previous history of stroke and were more physically disabled. They were less likely than major depressed patients to have a family history of affective disorder. Depression symptom severity was associated with greater physical disability among minor but not major depressed patients. Fewer minor than major depressed patients were depressed at 15 months. These findings suggest that poststroke major and minor depression may be different depressive syndromes. Some cases of minor depression may be construed as an adjustment reaction to stroke disability.

Blunted growth hormone response to clonidine in post-traumatic stress disorder

Hyperactivity of the sympathetic and noradrenergic systems is thought to be a feature of post-traumatic stress disorder (PTSD). Assessment of noradrenergic receptor function can be undertaken by measuring the growth hormone (GH) response to the alpha2-agonist clonidine. The aim of this study was to examine whether subjects with combat-related PTSD (with or without co-morbid depression) have a blunted growth hormone response to clonidine, compared to a combat-exposed control group. Twenty-three Vietnam veterans suffering from PTSD alone, 27 suffering from PTSD and co-morbid depression, and 32 veteran controls with no psychiatric illness were administered 1.5 microg/kg clonidine i.v. Plasma growth hormone was measured every 20 min for 120 min. The growth hormone response to clonidine was significantly blunted in the non-depressed PTSD group compared to both the depressed PTSD group and the control group as measured by peak growth hormone, delta growth hormone and AUC growth hormone. Subjects with PTSD and no co-morbid depressive illness show a blunted growth hormone response to clonidine. This suggests that post-synaptic alpha2-receptors are subsensitive. This finding is consistent with other studies showing increased noradrenergic activity in PTSD.

Open Trial of Interpersonal Psychotherapy for Chronic Post Traumatic Stress Disorder

Objective: The aim of this study was to investigate the feasibility of adapting group-based interpersonal psychotherapy (IPT-G) for patients with chronic post traumatic stress disorder (PTSD). Methods: Thirteen subjects with DSM-IV-defined PTSD, with symptom duration greater than 12 months, entered the study, an 8-week treatment programme conducted in a clinical setting using IPT-G modified for the treatment of PTSD. Data obtained were analysed qualitatively and quantitatively. Results: All 13 subjects completed the treatment programme and showed significant improvement in social functioning, general wellbeing and depressive symptoms. Treatment completers demonstrated a moderate reduction in the avoidant symptom cluster of PTSD. These improvements appeared stable at 3-month follow-up. Benefits appeared to be associated with perceived intra-therapy progress in resolving identified IPT problem areas. Qualitative analysis found that themes of ‘reconnection’ and ‘interpersonal efficacy’ were core parts of the experience of the treatment. Conclusion: IPT-G modified for PTSD appears to be of modest symptomatic benefit, but may lead to improvement in social functioning, general psychological wellbeing and enhanced interpersonal functioning. Further studies are indicated.

Platelet paroxetine binding in post-traumatic stress disorder

Sixty-two subjects, 45 with post-traumatic stress disorder (PTSD) and 17 healthy control subjects, were examined in a study of serotonin function measured by [3H]paroxetine binding to platelet membranes. Subjects were selected from male combat exposed veterans. The mean (+/- S.D.) Kd was 0.078 +/- 0.045 nM for the PTSD patient group and 0.064 +/- 0.037 nM for the control group. The mean Bmax was 934 + 238 fmol/mg protein for the PTSD patient group and 1011 +/- 363 fmol/mg protein for the control group. There was no significant difference between the groups for either Kd or Bmax before or after controlling for season of sampling. There were no significant differences between subjects with current PTSD and those with PTSD in the past, or between PTSD subjects with or without concurrent major depressive disorder. This study finds no relationship between PTSD, major depressive disorder and peripheral serotonin function measured by [3H]paroxetine binding to blood platelets.

Blunted prolactin response to d-fenfluramine in post-stroke major depression

BACKGROUND This study investigated whether patients suffering from post-stroke depressive disorder had a similar disturbance in central serotonergic function to that described in non-brain injured depressed patients. METHODS Twenty-three depressed patients (nine major, 14 minor) and 38 non-depressed patients were examined 4-8 weeks post-stroke with a structured interview, rating scales and MRI brain scans. Patients were administered 30 mg D-fenfluramine orally and plasma prolactin and D-fenfluramine concentrations were measured for 6 h post-dose. RESULTS The prolactin response was significantly blunted in major depression compared to minor depression and non-depressed patients as measured by both delta prolactin and area under the prolactin versus time curve. There was no significant relationship between prolactin response and lesion lateralization or any of the measured clinical characteristics. LIMITATIONS The major limitation of the study is the relatively small number in each depressive group. CONCLUSIONS Patients suffering from major depression in the post-stroke period have a blunted prolactin response to D-fenfluramine. This indicates a serotonergic abnormality consistent with that found in major depression where neurological disease is not present.