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Biomedical subjects

J M Gorman

Publications and source records attributed to J M Gorman.

At least 55 records · Page 3Linked to original sources
PubMed2000

Positive symptomatology and source-monitoring failure in schizophrenia--an analysis of symptom-specific effects.

Recent research has suggested that certain positive symptoms in patients with schizophrenia are linked to self monitoring/reality-monitoring deficits. We wished to investigate the association between such deficits and three specific symptoms: hallucinations, delusions and thought disorganisation. Forty patients with schizophrenia and 40 normal controls were administered a source-monitoring task. Twenty-four items were produced, either verbally by the experimenter, or verbally by the subject, or presented as pictures. Then, subjects were read a recognition list including the produced target items mixed with distractors. They were required to recognise the target items and to remember their source of production. The pattern of memory deficits has previously been reported (Brébion, G., Smith, M., Gorman, J., Amador, X., 1997. Discrimination accuracy and decision biases in different types of reality monitoring in schizophrenia. Journal of Nervous and Mental Disease 185, 247-253). The current analyses focussed on the false recognition of distractors, and on the errors in the source attribution of the recognised target items. Results showed that higher hallucination scores were associated with an increased tendency towards false recognition of non-produced items. In addition, hallucinators were more prone than control subjects to misattribute to another source the items they had produced themselves. Furthermore, hallucinators and delusional patients were more prone than the other patients to report that spoken items had been presented as pictures. This latter finding suggests that both hallucinations and delusions are associated with confusion between imagined and perceived pictures. Our previous report stated that only one of the three investigated types of response bias was associated with global positive symptomatology. However, this finer-grained analysis revealed that the three of them were in fact associated with hallucinations and/or delusions. On the other hand, thought disorganisation appeared to be independent from these mechanisms.

Adult↗
PubMed2000

Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.

The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D(2) receptor. We measured in vivo occupancy of striatal D(2) receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D(2) receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D(2) receptor availability in patients with schizophrenia (19% +/- 11%) compared with control subjects (9% +/- 7%, P = 0.003). The increased occupancy of D(2) receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D(2) receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons.

Adult↗
PubMed2000

Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial.

CONTEXT: Panic disorder (PD) may be treated with drugs, psychosocial intervention, or both, but the relative and combined efficacies have not been evaluated in an unbiased fashion. OBJECTIVE: To evaluate whether drug and psychosocial therapies for PD are each more effective than placebo, whether one treatment is more effective than the other, and whether combined therapy is more effective than either therapy alone. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled clinical trial conducted in 4 anxiety research clinics from May 1991 to April 1998. PATIENTS: A total of 312 patients with PD were included in the analysis. INTERVENTIONS: Patients were randomly assigned to receive imipramine, up to 300 mg/d, only (n=83); cognitive-behavioral therapy (CBT) only (n=77); placebo only (n=24); CBT plus imipramine (n=65); or CBT plus placebo (n=63). Patients were treated weekly for 3 months (acute phase); responders were then seen monthly for 6 months (maintenance phase) and then followed up for 6 months after treatment discontinuation. MAIN OUTCOME MEASURES: Treatment response based on the Panic Disorder Severity Scale (PDSS) and the Clinical Global Impression Scale (CGI) by treatment group. RESULTS: Both imipramine and CBT were significantly superior to placebo for the acute treatment phase as assessed by the PDSS (response rates for the intent-to-treat [ITT] analysis, 45.8%, 48.7%, and 21.7%; P=.05 and P=.03, respectively), but were not significantly different for the CGI (48. 2%, 53.9%, and 37.5%, respectively). After 6 months of maintenance, imipramine and CBT were significantly more effective than placebo for both the PDSS (response rates, 37.8%, 39.5%, and 13.0%, respectively; P=.02 for both) and the CGI (37.8%, 42.1%, and 13.0%, respectively). Among responders, imipramine produced a response of higher quality. The acute response rate for the combined treatment was 60.3% for the PDSS and 64.1% for the CGI; neither was significantly different from the other groups. The 6-month maintenance response rate for combined therapy was 57.1% for the PDSS (P=.04 vs CBT alone and P=.03 vs imipramine alone) and 56.3% for the CGI (P=.03 vs imipramine alone), but not significantly better than CBT plus placebo in either analysis. Six months after treatment discontinuation, in the ITT analysis CGI response rates were 41.0% for CBT plus placebo, 31.9% for CBT alone, 19.7% for imipramine alone, 13% for placebo, and 26.3% for CBT combined with imipramine. CONCLUSIONS: Combining imipramine and CBT appeared to confer limited advantage acutely but more substantial advantage by the end of maintenance. Each treatment worked well immediately following treatment and during maintenance; CBT appeared durable in follow-up. JAMA. 2000;283:2529-2536

Adult↗
PubMed2000

Hippocampal pathology in schizophrenia: magnetic resonance imaging and spectroscopy studies.

The hippocampus is a site of previously reported structural and functional abnormalities in schizophrenia. We used magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) to measure gray matter volumes, the neuronal marker N-acetylaspartate (NAA), and the combination of glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA), designated Glx. Measurements were obtained of the medial temporal lobe, centered on the hippocampus, in 10 male patients with schizophrenia (3 neuroleptic-medicated and 7 medication-free), and 10 matched normal volunteers. MRI volumetric measurements and MRS data obtained with short echo time (TE=20 ms) one-dimensional STEAM chemical shift imaging (CSI) on a GE 1.5 Tesla Signa system were analyzed. A laterality index ¿(L-R)/(L+R) was generated from the ratio of Glx to choline-containing compounds (Cho) to test asymmetry changes. Reliability of the MRS measures was assessed with five test-retest studies of healthy volunteers and showed coefficients of variation (CV) in the range of 36-44% for the MRS ratios and standard deviations (S.D.) of 0.15-0.17 for the laterality indices. The Glx/Cho laterality index showed a relative right-sided excess in this region in the patients (-0.23+/-0.20) compared to the controls (+0.06+/-0.20), which was not confounded by tissue composition or placement variability of the MRS voxels. Hippocampal volume deficit and asymmetry were not significant, and other MRS measures showed no differences between patients and controls. The preliminary finding of a lateralized abnormality in Glx is consistent with postmortem findings of asymmetric neurochemical temporal lobe abnormalities in schizophrenia.

Adult↗
PubMed2000

Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group.

BACKGROUND: To examine the relationship between respiratory regulation and childhood anxiety disorders, this study considered the relationship between anxiety disorders and symptoms during carbon dioxide (CO(2)) exposure, CO(2) sensitivity in specific childhood anxiety disorders, and the relationship between symptomatic and physiological responses to CO(2). METHODS: Following procedures established in adults, 104 children (aged 9-17 years), including 25 from a previous study, underwent 5% CO(2) inhalation. The sample included 57 probands with an anxiety disorder (social phobia, generalized anxiety disorder, separation anxiety disorder, and panic disorder) and 47 nonill comparison subjects. Symptoms of anxiety were assessed before, during, and after CO(2) inhalation. RESULTS: All children tolerated the procedure well, experiencing transient or no increases in anxiety symptoms. Children with an anxiety disorder, particularly separation anxiety disorder, exhibited greater changes in somatic symptoms during inhalation of CO(2)-enriched air, relative to the comparison group. During CO(2) inhalation, symptom ratings were positively correlated with respiratory rate increases, as well as with levels of tidal volume, minute ventilation, end-tidal CO(2), and irregularity in respiratory rate during room-air breathing. CONCLUSIONS: Childhood anxiety disorders, particularly separation anxiety disorder, are associated with CO(2) hypersensitivity, as defined by symptom reports. Carbon dioxide hypersensitivity is associated with physiological changes similar to those found in panic disorder. These and other data suggest that certain childhood anxiety disorders may share pathophysiological features with adult panic disorder.

Adolescent↗
PubMed2000

Efficacy of venlafaxine in mixed depression-anxiety states.

Patients with depression almost always suffer from comorbid anxiety or anxiety disorder. It is commonly stated that comorbid depression and anxiety has a worse prognosis, even with adequate therapy, than depression alone. An accumulation of data now make clear that the antidepressants venlafaxine and venlafaxine XR are effective in reducing anxiety in patients with depression. Several of the studies supporting this are reviewed here. Venlafaxine and venlafaxine XR have also been shown to be effective in treating anxiety disorders and venlafaxine XR is presently the only antidepressant approved by the FDA for the specific treatment of generalized anxiety disorder. The effectiveness of venlafaxine in treating anxiety associated with depression and anxiety disorders supports theories implicating abnormal noradrenergic activity as a component of pathological anxiety.

Anxiety↗
PubMed2000

How study of respiratory physiology aided our understanding of abnormal brain function in panic disorder.

There is a substantial body of literature demonstrating that stimulation of respiration (hyperventilation) is a common event in panic disorder patients during panic attack episodes. Further, a number of abnormalities in respiration, such as enhanced CO2 sensitivity, have been detected in panic patients. This led some to posit that there is a fundamental abnormality in the physiological mechanisms that control breathing in panic disorder and that this abnormality is central to illness etiology. More recently, however, evidence has accumulated suggesting that respiratory physiology is normal in panic patients and that their tendency to hyperventilate and to react with panic to respiratory stimulants like CO2 represents the triggering of a hypersensitive fear network. The fear network anatomy is taken from preclinical studies that have identified the brain pathways that subserve the acquisition and maintenance of conditioned fear. Included are the amygdala and its brain stem projections, the hippocampus, and the medial prefrontal cortex. Although attempts to image this system in patients during panic attacks have been difficult, the theory that the fear network is operative and hyperactive in panic patients explains why both medication and psychosocial therapies are clearly effective. Studies of respiration in panic disorder are an excellent example of the way in which peripheral markers have guided researchers in developing a more complete picture of the neural events that occur in psychopathological states.

Arousal↗
PubMed2000

Heart rate variability in depressive and anxiety disorders.

Loss of normal autonomic nervous system control of heart rate and rhythm is an important risk factor for adverse cardiovascular events. After myocardial infarction, reduction in beat-to-beat heart rate variability, a measure of cardiac autonomic innervation by the brain, is a strong predictor of death. With loss of vagal innervation, as is noted in patients with severe neuropathy and in heart transplant recipients, there is loss of heart rate variability. It is speculated that decreased parasympathetic innervation exposes the heart to unopposed stimulation by sympathetic nerves. Individuals with high hostility scores and patients with anxiety or depressive disorders have low heart rate variability and may be at increased risk for cardiovascular death associated with coronary heart disease and arrhythmias. After myocardial infarction, depressed patients exhibit higher mortality rates compared with nondepressed patients. Men with "phobic anxiety," a construct that appears to overlap substantially with panic disorder, also have higher rates of sudden cardiac death and coronary artery disease than control populations. The reduction in autonomic nervous system control to the heart may be one link between psychopathology and heart disease. Although tricyclic antidepressants reduce heart rate variability, at least one study has suggested that, in patients with panic disorder, treatment with the selective serotonin reuptake inhibitor paroxetine normalizes heart rate variability. Hence there is potential for the treatment of psychiatric disorders to affect positively the development and course of cardiovascular disease.

Anxiety Disorders↗
PubMed2000

Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: a prospective birth cohort study.

We sought to examine the relationship between maternal exposure to adult respiratory infections and schizophrenia spectrum disorder (SSD) in the Prenatal Determinants of Schizophrenia (PDS) Study, a large birth cohort investigation. Previous work suggests that second trimester exposure to respiratory infection may be a risk factor for SSD. We therefore examined whether this class of infection was associated with adult SSD. For this purpose, we capitalized on several design advantages of the PDS Study, including a comprehensive, prospective data base on physician-diagnosed infections and a continuous followup in which diagnoses of SSD were made, in the majority, by face-to-face interview. Second trimester exposure to respiratory infections was associated with a significantly increased risk of SSD, adjusting for maternal smoking, education, and race (rate ratio [RR] = 2.13 [1.05-4.35], chi2 = 4.36, df= 1,p = 0.04); no associations were shown for first trimester and third trimester exposure to these respiratory infections. These findings support-and extend-previous studies suggesting that second trimester respiratory infections are risk factors for SSD. This study therefore has implications toward uncovering the etiology of schizophrenia and developing preventive strategies.

Adult↗
PubMed2000

Efficacy of open-label nefazodone treatment in patients with panic disorder.

Fifteen patients with panic disorder participated in a 12-week treatment trial with open-label nefazodone. Nefazodone was well-tolerated with minimal side effects; none of the patients reported sexual dysfunction, and only one patient experienced weight gain. Although the response rate was lower than that found with most other antipanic medications, given its favorable side effect profile, nefazodone may be a good alternative for patients apprehensive about potential adverse drug reactions.

Adult↗
PubMed2000

Neuroanatomical hypothesis of panic disorder, revised.

OBJECTIVE: In a 1989 article, the authors provided a hypothesis for the neuroanatomical basis of panic disorder that attempted to explain why both medication and cognitive behavioral psychotherapy are effective treatments. Here they revise that hypothesis to consider developments in the preclinical understanding of the neurobiology of fear and avoidance. METHOD: The authors review recent literature on the phenomenology, neurobiology, and treatment of panic disorder and impressive developments in documenting the neuroanatomy of conditioned fear in animals. RESULTS: There appears to be a remarkable similarity between the physiological and behavioral consequences of response to a conditioned fear stimulus and a panic attack. In animals, these responses are mediated by a "fear network" in the brain that is centered in the amygdala and involves its interaction with the hippocampus and medial prefrontal cortex. Projections from the amygdala to hypothalamic and brainstem sites explain many of the observed signs of conditioned fear responses. It is speculated that a similar network is involved in panic disorder. A convergence of evidence suggests that both heritable factors and stressful life events, particularly in early childhood, are responsible for the onset of panic disorder. CONCLUSIONS: Medications, particularly those that influence the serotonin system, are hypothesized to desensitize the fear network from the level of the amygdala through its projects to the hypothalamus and the brainstem. Effective psychosocial treatments may also reduce contextual fear and cognitive misattributions at the level of the prefrontal cortex and hippocampus. Neuroimaging studies should help clarify whether these hypotheses are correct.

Adult↗
PubMed2000

Relation of familial schizophrenia to negative symptoms but not to the deficit syndrome.

OBJECTIVE: Although a family history of schizophrenia has been associated with negative symptoms, family history is inconsistently related to the presence of the deficit syndrome. METHOD: The authors assessed family history and the deficit syndrome in 99 patients with DSM-III-R-diagnosed schizophrenia who were assessed during clinical treatment. Of these 99 patients, 45 were assessed both while antipsychotic free and during antipsychotic treatment to index their treatment response. RESULTS: Patients with (N=39) and without (N=60) a family history of schizophrenia had similar proportions of the deficit syndrome. Yet family history and deficit syndrome categorizations identified a group with greater negative symptoms on the Positive and Negative Syndrome Scale. Those with a family history had greater emotional withdrawal, poor rapport, and lack of spontaneity. Groups with and without the deficit syndrome similarly differed in these symptoms but also in affective blunting, motor retardation, and passive or apathetic social withdrawal. The study involving antipsychotic-free and antipsychotic treatment phases showed main medication effects explaining positive, psychopathology, depression, and activation symptoms but not negative symptoms. Only patients without a family history had improved negative symptoms with antipsychotic treatment. CONCLUSIONS: Patients with a family history of schizophrenia had greater and more treatment-resistant negative symptoms than those without a family history. They were not more likely to have the deficit syndrome. The group with a family history had more pathology only in negative symptoms related to psychosocial function. The stable negative symptoms specifically related to the genetic vulnerability to inherit schizophrenia might be those associated with psychosocial functioning.

Adaptation, Psychological↗
PubMed2000

Schizophrenia subgroups differing in dichotic listening laterality also differ in neurometabolism and symptomatology.

Schizophrenia patients vary in right ear advantage (REA) on dichotic listening tests for assessing left hemispheric dominance for language processing. The authors examined if patients with low REA differed from other patients in symptoms and in resting brain metabolism. SPECT was conducted during visual fixation for 9 healthy control subjects and 16 schizophrenia patients: 8 with normal and 8 with diminished REA. REA-diminished patients had greater positive symptoms and lower mental status scores (all P<0.05) and had right middle temporal gyrus hypermetabolism. Both schizophrenia groups had decreased right frontal and increased medial temporal lobe metabolism vs. control subjects. REA-diminished patients had right temporal lobe hypermetabolism under a resting condition (eyes open, visual fixation). Results suggest reduced right ear (left hemisphere) advantage for dichotic word perception in schizophrenia is related to a predisposition to overactivate right temporal lobe regions and to positive symptoms. In contrast, the prefrontal-medial temporal imbalance present in both patient groups may typify the schizophrenia syndrome.

Adult↗
PubMed2000

Difficulties in interpersonal relationships associated with personality disorders and axis I disorders: a community-based longitudinal investigation.

A longitudinal study was conducted to investigate the association between Axis I and Axis II psychiatric disorders, interpersonal relationships, and global functioning among men in the community. Structured clinical interviews assessing Axis I and Axis II psychiatric disorders, global assessments of functioning, and questionnaires assessing social support, social conflict, and loneliness were administered to a community sample of 95 HIV+ and 45 HIV- men. The questionnaires were readministered 1 year later. Results indicated that (a) Personality disorders (PDs) and unipolar depressive disorders were associated with loneliness, social conflict, and low levels of social support after HIV status was controlled statistically; (b) PDs were associated with interpersonal and global impairment after HIV status and co-occurring Axis I disorders were controlled statistically; (c) Axis I disorders were associated with global impairment, but were not associated with interpersonal difficulties after HIV status and PDs were controlled statistically; (d) PDs, but not Axis I disorders, predicted increases in social conflict and global impairment after HIV status was controlled statistically; (e) PDs continued to predict increases in global impairment after both Axis I disorders and HIV status were controlled statistically; and (f) HIV+ men reported more loneliness, less social support, and had a higher prevalence of substance use disorders than HIV- men. The present findings are of particular interest because they suggest that PDs are associated with loneliness, social conflict, and a lack of social support among men in the community, whether or not Axis I disorders are present.

Adult↗
PubMed2000

Noradrenergic approaches to antidepressant therapy.

A decade of remarkable research in neuroscience has given us a much more complete picture of how the central nervous system works and, in some instances, how the brain does not work when patients develop depression. Preclinical and clinical studies have shown that stimulation of the serotonergic system leads to noradrenergic effects and vice versa, confirming that the serotonin and norepinephrine systems are intimately connected in the central nervous system. Although medications that target the serotonergic neurotransmitter system have recently dominated antidepressant therapy, atypical antidepressants--with either mixed serotonergic and noradrenergic effects or exclusively noradrenergic effects--have been shown to be clinically efficacious medications. This increased understanding of the interrelationship between neurotransmitter systems has renewed interest in the role of neurotransmitters other than serotonin in the treatment of depression. With the introduction of reboxetine, a very selective norepinephrine reuptake inhibitor, researchers have had an opportunity to study the unique effects of norepinephrine in the etiology and treatment of depression. Ultimately, differences in neurotransmitter profiles may influence therapeutic potentials of antidepressants. For example, influencing norepinephrine may affect the expression of energy and interest, while influencing serotonin may affect impulse control and influencing dopamine may affect drive. Clinicians now have a range of antidepressants with variable neurotransmitter effects, different side effect profiles, and some interesting differences in functional utility in their armamentarium for treating depression.

Adrenergic Uptake Inhibitors↗
PubMed2000

Depression, psychomotor retardation, negative symptoms, and memory in schizophrenia.

OBJECTIVE: The purpose of this study was to examine the relations between depression, psychomotor retardation, and negative symptoms in schizophrenia as well as the specific contribution of each of these factors to memory impairment. BACKGROUND: It has been suggested that depression overlaps with negative symptomatology in schizophrenia. The relation between psychomotor retardation and negative symptomatology has been unclear. METHOD: The Hamilton Depression Rating Scale, The Positive and Negative Symptom Scale for Schizophrenia, and Scale for the Assessment of Negative Symptoms were used to assess depressive and negative symptomatology in a sample of patients with schizophrenia. Verbal memory performance was assessed by a free recall test. Two indices of processing speed were measured. Correlations among variables were computed. RESULTS: Depression score was correlated with the avolition item from the Scale for the Assessment of Negative Symptoms and with both measures of processing speed. Negative symptomatology was unrelated to processing speed. Memory performance was correlated with depression score, slowing of processing speed, and avolition. Its correlation with depression score and processing speed remained significant when the other factors were partialled out. CONCLUSIONS: Memory performance in schizophrenia may be affected by lack of motivation, psychomotor retardation, and depression. It is suggested that negative symptoms could be split between a volitional component linked to depression and cognitive efficiency and an emotional component unrelated to them.

Adult↗
PubMed1999

The noradrenergic system in pathological anxiety: a focus on panic with relevance to generalized anxiety and phobias.

Over the past three decades of psychiatric research, abnormalities in the noradrenergic system have been identified in particular anxiety disorders such as panic disorder. Simultaneously, neuroscience research on fear pathways and the stress response have delineated central functions for the noradrenergic system. This review focuses on the noradrenergic system in anxiety spectrum disorders such as panic disorder, generalized anxiety disorder, and phobias for the purpose of elucidating current conceptualizations of the pathophysiologies. Neuroanatomic pathways that are theoretically relevant in anxiogenesis are discussed and the implications for treatment reviewed.

Amygdala↗