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Biomedical subjects

J M Gorman

Publications and source records attributed to J M Gorman.

At least 91 records · Page 5Linked to original sources

Hemodynamic response to respiratory challenges in panic disorder.

This study compares the hemodynamic response to panic disorder subjects with that of normal controls during respiratory challenges. Panic patients meeting DSM-IIIR criteria for panic disorder and normal controls were challenged with room air hyperventilation, 5% CO2 breathing, and 7% CO2 breathing. Measurements of pulse and blood pressure were taken at resting baseline and before and at the end of each respiratory challenge. Panic attack to each challenge was determined by using raters blinded to subject diagnosis and each subject's self-rating of panic. Significantly larger systolic and diastolic blood pressure increases were found in patients who panicked with room air hyperventilation than nonpanicking patients or normal controls. No significant blood pressure differences were found with 7% or 5% CO2 challenges, but higher pulse rates were found in the patient group. It may be possible that panic with room air hyperventilation causes a significant increase in systolic and diastolic blood pressure, or that a subgroup of panic disorder patients has a hyperactive vascular response to hypocapnia. These patients panic with room air hyperventilation and develop greater vasoconstriction and/or increased blood pressure response.

Administration, Inhalation↗

Psychoneuroendocrinology of anxiety disorders.

This article focuses on neuroendocrine measures in anxiety disorders and their relationships to neurotransmitter and neuroendocrine function. In particular, the hypothalamic-pituitary-somatotropin and the hypothalamic-pituitary-adrenal (HPA) axes are emphasized, and a role for extrahypothalamic corticotropin releasing factor is proposed. Additional neuroactive hormones are also considered. A nonhuman primate model of anxiety is discussed in terms of its neuroendocrine relevance. And, throughout, a hypothetical functional-anatomic model for anxiety and panic is proposed using the findings of cognitive neuroscience fear research. Finally, an effort is made to synthesize existing psychoneuroendocrinologic data into a current conceptualization of the pathophysiology of anxiety disorders.

Adrenal Cortex Hormones↗

Psychopathologic domains and insight in schizophrenia.

The earlier conceptualization of positive and negative symptom topologies for schizophrenia has given way to more complex models that propose three-and-four dimensions of psychopathology. These constructs may relate to neurobiologic heterogeneity and discrete symptom clusters have been shown to have distinct anatomical and cognitive correlates. Insight is an excellent example and the understanding of insight at psychopathologic and cognitive levels has facilitated new approaches to treatment and enhanced medication compliance.

Attitude to Health↗

Word recognition, discrimination accuracy, and decision bias in schizophrenia: association with positive symptomatology and depressive symptomatology.

The purpose of this experiment was to replicate and extend to a memory task Bentall and Slade's (1985) finding that hallucinations in schizophrenic patients were linked to a liberal decision bias. A word recognition task was administered to 40 schizophrenic patients and 40 normal controls that yielded two indices of performance: an index of discrimination accuracy (Pr) and one of decision bias (Br). Patients obtained a lower Pr than controls, whereas Br was similar in both groups. In patients, Br was selectively correlated with positive symptomatology: the more the positive symptoms, the more liberal the bias. In particular, there was a specific correlation between decision bias and hallucinations. Conversely, Pr was inversely correlated with severity of depression, but not with either positive or negative symptoms. Thus, positive symptomatology may be linked more to difficulties in distinguishing between representations of internal versus external events than to deficits in encoding external events.

Adult↗

Pretreatment attrition in a comparative treatment outcome study on panic disorder.

OBJECTIVE: Whereas the fact of attrition during the course of treatment is well documented, little is known about the factors that affect sample selection before the beginning of a study ("pretreatment attrition"). The present study reports on the degree and sources of pretreatment attrition at two sites of a multicenter study on panic disorder that compared treatment outcomes for imipramine and cognitive behavior therapy. METHOD: Data were collected at two clinical research sites, one with a pharmacological treatment orientation (N = 420) and one with a psychosocial treatment orientation (N = 208). RESULTS: The main source of pretreatment attrition was participant refusal. At both research sites, eligible patients most often refused participation because they were either unwilling to start treatment with imipramine (30.6% and 47.4%, respectively) or discontinue their current medication (22.6% and 35.1%, respectively). CONCLUSIONS: Results from comparative treatment outcome studies are limited not only to people who meet the study criteria but also to those who are willing to begin a medication treatment and discontinue their current medication.

Adolescent↗

Efficient allocation of patients to treatment cells in clinical trials with more than two treatment conditions.

OBJECTIVE: Clinical trials generally allocate patients to equal-sized treatment groups. The authors propose that it may be more efficient to allocate unequal proportions of the total sample size to treatments when more than two treatments are being compared. METHOD: This proposal is illustrated with two examples. One involved a comparison of three treatments and used a dichotomous categorical outcome. The other involved comparison of three treatments and used a continuous measure. RESULTS: In both examples, a considerable increase in efficiency was realized by reducing the number of patients assigned to the placebo cell. CONCLUSIONS: Unequal allocation of patients to treatments should be considered when more than two groups are compared.

Antidepressive Agents↗

Cerebral glucose metabolism in women with panic disorder.

OBJECTIVE: This study was undertaken to clarify earlier inconsistent findings in brain metabolic topography in panic disorder patients at rest. METHOD: Positron emission tomography (PET) with [18F]fluorodeoxyglucose was used to determine cerebral metabolic activity in six female patients with a DSM-III-R diagnosis of panic disorder and in six healthy female volunteers. All patients with panic disorder were medication free and were sensitive to lactate infusion. RESULTS: A significant increase in glucose metabolism was found in the left hippocampus and parahippocampal area of the panic disorder subjects in comparison with that found in the healthy subjects. In addition, a significant decrease in metabolism was found in the right inferior parietal and right superior temporal brain regions of the panic disorder subjects in comparison with that of the normal subjects. There was no significant correlation between scores for the severity of panic disorder or for the severity of lactate-induced panic attack and the quantified PET abnormality. CONCLUSIONS: These data provide further support for the hypothesis of an abnormal brain metabolism in the hippocampal and parahippocampal area in individuals with panic disorder and also suggest other areas of aberrant brain metabolism in this disorder.

Adult↗

Sexual risk behavior changes among HIV+ and HIV-female injecting drug users over 4 years.

This paper examines the sexual risk behavior of female injecting drug users who participated in a 4 year longitudinal study. Both HIV+ and HIV- women showed increases in monogamy, decreases in the frequency of unprotected vaginal/anal sex, and decreases in a risk index score throughout the study. HIV+ women had fewer occasions of unprotected sex than HIV-. However, a substantial proportion of the sample continued to engage in unprotected sex. Among the HIV+ women, depressed mood was significantly related to abstinence and to fewer occasions of unprotected sex, but CD4, medical symptoms, neurological impairment, and memory test performance were not associated with sexual risk behavior.

Adult↗

Low-dose venlafaxine treatment in panic disorder.

Venlafaxine, a structurally novel antidepressant that combines mechanisms of action of both the cyclic antidepressants and SSRIs, may be effective in the treatment of panic disorder. Thirteen patients with DSM-IV panic disorder with or without agoraphobia participated in an open-label, fixed-flexible dose treatment study with venlafaxine. All patients who completed the 10-week trial exhibited statistically significant decreases in scores on anxiety symptoms as well as complete cessation of panic attacks at an effective mean daily dose of 47 mg per day. Venlafaxine was well tolerated in all completers. Venlafaxine may be an effective antipanic agent, even at lower than typical antidepressant dosages.

Adult↗

Effects of panic disorder treatments on personality disorder characteristics.

Ninety-three patients with panic disorder and mild or no agoraphobia were treated for their panic disorder by using either 11 sessions of individual cognitive-behavior therapy or imipramine. Before and after treatment, their panic disorder symptomatology was assessed, and a self-report measure was administered to measure personality disorder characteristics [Klein et al., 1990: Wisconsin Personality Disorders Inventory]. In addition, some patients received this personality assessment again after six monthly maintenance sessions. Both treatments were equally effective in reducing panic disorder symptomatology, and both treatments had a positive influence on personality disorder characteristics. Personality disorder characteristics did not predict treatment outcome in either group. The implications of the findings for the assessment of personality and the treatment of panic disorder are discussed.

Adolescent↗

Effect of antipanic treatment on response to carbon dioxide.

BACKGROUND: Disordered breathing among patients with panic disorder, including hyperventilation during attacks and increased anxiogenic response to carbon dioxide (CO2) inhalation, is well established. We wished to assess whether there is a change in the physiological response to CO2 after patients have undergone antipanic therapy with either tricyclic antidepressants or cognitive behavioral therapy (CBT). METHODS: Twenty-nine patients with panic disorder underwent baseline CO2 sensitivity testing using the traditional Read rebreathing method and then received either antidepressant treatment (n = 21) or CBT (n = 8). After completing treatment, CO2 testing was repeated. A comparison sample of 14 normal volunteers also had two CO2 sensitivity tests, separated by an average of 21.6 (SD = 8.8) weeks. RESULTS: Using a liberal standard, in which all CO2 sensitivity tests whose correlations between minute ventilation and end-tidal CO2 were at least .75 were used, patients, but not controls, demonstrated a significant reduction in CO2 sensitivity between the first and second test. Using a more conservative .90 correlation standard reduced the sample size available and resulted in trend reduction in patients but no significant change in controls. There was a suggestion that the change was most pronounced in treatment responders, although the number of patient nonresponders is extremely small in this sample. CONCLUSIONS: These data indicate that treatment reduces CO2 sensitivity in patients with panic disorder. We speculate that manipulation of the serotonergic and noradrenergic neurotransmission systems, both known to play a role in the control of respiration, may have a specific effect in reducing respiratory hyperactivity in panic disorder.

Administration, Inhalation↗

Psychopathology in male and female HIV-positive and negative injecting drug users: longitudinal course over 3 years.

OBJECTIVE: To evaluate the impact of HIV illness on psychiatric and psychosocial functioning over 3 years in a sample of male and female HIV-positive injecting drug users (IDU), with a comparison group of HIV-negative male and female IDU. DESIGN: As part of a multidisciplinary study, 121 men (69 HIV-positive, 52 HIV-negative) and 66 women (36 HIV-positive, 30 HIV-negative) were evaluated semiannually for seven visits. Attrition, unrelated to sex or serostatus, was 33%. RESULTS: At baseline, rates of major depression and dysthymia ranged from 15% (HIV-negative men) to 33% (HIV-positive men and HIV-negative women). Global impairment was in the range found in psychiatric patients (mean Global Assessment of Functioning scores, 46-51). Higher levels of social support and less social conflict were independently associated with decreased distress and improved global functioning among both men and women. For both HIV-positive groups, degree of improvement over time was related to degree to HIV progression: those who remained healthier in terms of CD4 count and illness stage showed more improvement. HIV-seronegative status was associated with less distress for men but not for women. Overall, women reported higher levels of psychiatric distress than men. CONCLUSIONS: High rates of psychopathology were found in this IDU cohort, independent of HIV status and sex. Although rates of psychopathology, injecting drug use and distress declined slightly during the study, they remained elevated; accordingly, psychiatric services are indicated for this population.

Cohort Studies↗

Clinical improvement with fluoxetine therapy and noradrenergic function in patients with panic disorder.

BACKGROUND: Central noradrenergic (NA) dysregulation has provided a major theoretical framework for understanding the pathogenesis of panic disorder (PD). Using clonidine, an alpha 2-adrenergic receptor agonist, as a probe of NA function, we investigated the hypothesis that the antipanic efficacy of the selective serotonin reuptake inhibitors may be associated with normalization of a putatively dysregulated NA system. METHODS: We report further analyses on data from 17 subjects with PD and 16 healthy volunteers who underwent measurement of the plasma NA metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) immediately before and after oral clonidine administration. Thirteen patients with PD were rechallenged after 12 weeks during open fluoxetine hydrochloride treatment using the same clonidine paradigm; 13 healthy volunteers were rechallenged at 12 weeks, not having received treatment between challenges. RESULTS: Patients with PD, compared with healthy volunteers, have markedly elevated plasma MHPG volatility during the first clonidine challenge. Volatility describes the magnitude of within-subject plasma MHPG oscillatory activity as assessed by the root of the mean square successive difference. A greater degree of clinical global improvement was predicted by a greater magnitude of basal MHPG reduction with fluoxetine treatment. Antipanic response to fluoxetine was accompanied by a significant decrease of MHPG volatility to volunteer levels. Volunteer MHPG volatility remained unchanged from the first to second clonidine challenge. CONCLUSIONS: Further evidence is provided for the hypothesis of NA dysregulation in PD as reflected by elevations of within-subjects plasma MHPG volatility during clonidine challenge. Effective selective serotonin reuptake inhibitor-antipanic treatment in this clinical sample was paralleled by normalization of dysregulated NA function.

Adult↗

Effects of clozapine on plasma catecholamines and relation to treatment response in schizophrenia: a within-subject comparison with haloperidol.

We conducted a within-subject comparison of the effects of clozapine and haloperidol on plasma levels of neurotransmitters and metabolites, and related changes in specific plasma neurochemicals with clozapine response. The subjects were 14 inpatients with schizophrenia or schzoaffective disorder, who were refractory to haloperidol and at least one other typical antipsychotic medication. Subjects underwent, in the following order: a 6-week "fixed, flexible dose" haloperidol trial, followed by a 2-4 week medication-free phase, and a 6-week clozapine trial. Plasma levels of norepinephrine (NE), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), and objective clinical ratings of total, positive, negative, and depressive symptoms were obtained at the end of each phase. As expected, we found a substantial increase of plasma NE with clozapine but not with haloperidol. However, the increase in NE was not associated with improvement in total or positive symptomatology. There was some evidence for an association between improvement in negative symptoms and increased HVA on clozapine, as well as diminished HVA during the medication-free phase. The implications of these data for understanding the mechanisms of action of clozapine are discussed.

Aged↗

Mechanisms underlying memory impairment in schizophrenia.

BACKGROUND: The purpose of this experiment was to investigate mechanisms underlying commonly-observed verbal memory impairments in schizophrenia, and especially the hypothesized encoding deficit. METHODS: A verbal memory task was administered to 38 patients with schizophrenia and 38 normal controls. Three functions involved in long-term memory-encoding, early phase of storage, retrieval-were investigated. First, non-organizable lists were compared to semantically-organizable lists in a free recall task, in order to vary encoding conditions. Superficial encoding (measured by a 'sequence' index) and deep encoding (measured by a categorization index) were assessed. Secondly, early storage was investigated by varying the delay between learning and recall. Lastly, cues were provided for organizable lists (semantic cues) and non-organizable lists (recognition sheet), in order to vary retrieval conditions. RESULTS: An analysis of variance revealed an interaction between type of list (organizable, non-organizable) and group, showing that patients used organization less than controls. A further analysis showed that deep encoding was impaired. Also, although the propensity to use superficial encoding was unimpaired, its efficiency was less. The analysis of variance revealed no interaction with delay or with either type of cue. A correlation was found between deep processing and memory performance in both groups. CONCLUSIONS: A major deficit in encoding appeared in the patient group, with a lesser use of deep encoding and a lesser efficiency of superficial encoding. On the other hand, the early phase of storage and the retrieval function seemed unaffected. Overall memory performance appeared to be related to the depth of encoding.

Adult↗

Discrimination accuracy and decision biases in different types of reality monitoring in schizophrenia.

A reality monitoring task was administered to 31 schizophrenic patients and 31 normal controls. Twenty-four items were produced, either orally by the experimenter, orally by the subjects, or seen as pictures. Subjects were later read a list of 48 items and were asked to indicate if each item was new, self-generated, experimenter-generated, or presented as a picture. Results showed that schizophrenic patients were impaired in discriminating old items from new, with a higher bias than controls toward reporting new items as if they were old (false alarms). In addition, patients were impaired in discriminating self-generated items from externally generated items, with a higher bias than controls toward attributing self-generated items to an external source. Lastly, they were significantly impaired in discriminating the modality (auditory versus visual) in which the event was presented. The bias toward remembering orally produced items as pictures was correlated with positive symptomatology and was significantly higher than controls in patients with high levels of positive symptoms. This suggests that mental imagery may play a role in positive symptomatology. These results demonstrate the relevance of studying decision biases along with discrimination performance for the understanding of the mechanisms of reality monitoring impairment in schizophrenia.

Adult↗

Clinical correlates of memory in schizophrenia: differential links between depression, positive and negative symptoms, and two types of memory impairment.

OBJECTIVE: This study investigated clinical correlates of memory impairment in schizophrenic patients. In particular, the authors hypothesized that depressive symptoms would be linked to memory efficiency, as found in other clinical populations. In addition, they tested Frith's pathophysiological model predicting links between negative symptoms and failure to respond, as well as between positive symptoms and production of erroneous responses. METHOD: Thirty-one patients were given several memory tasks: long-term free recall of nonorganizable and organizable lists in immediate and delayed conditions, recognition in immediate and delayed conditions, implicit memory (stem completion task), and short-term memory (digit span). Superficial encoding of information was also assessed by the ability to recall the items sequentially; deep encoding was assessed by the ability to organize the items according to their semantic properties. Two types of memory measures were individualized: measures reflecting memory efficiency and measures reflecting production of erroneous memory responses (intrusions, perseverations, false alarms). RESULTS: Consistent correlations appeared between severity of depressive symptoms and measures reflecting deep but not superficial encoding; none, however, was correlated with negative symptoms. Two of the three types of erroneous memory responses were positively linked to positive symptoms. CONCLUSIONS: Efficiency of memory processes relying on deep encoding seemed linked to depressive symptoms. In addition, the two distinct types of impairment predicted by Frith's model were found. The expected link of one with positive symptoms was verified, but the link of the other with negative symptoms was not.

Adult↗