Biomedical subjects
Publications and source records attributed to F K Judd.
Recently, much research interest has been directed to demonstrating a possible biological basis to obsessive compulsive disorder. In particular, dysregulation in brain serotonin is suggested to be important. Two cases are described in which fenfluramine, a presynaptic 5 HT-releasing agent and 5HT-reuptake inhibitor was used to augment clomipramine treatment for OCD.
Panic disorder is characterized by unexpected, unprovoked attacks of cognitive symptoms (e.g., dread, fear) and physical symptoms (e.g., palpitations, trembling, shortness of breath). It is the most common anxiety disorder seen in clinical practice. Pharmacotherapy has been shown to be effective in controlling symptoms of panic disorder, although potential disadvantages (e.g., adverse drug reactions, withdrawal syndrome, dependency) must be carefully assessed and balanced against the advantages. Current data indicate that for panic disorder, benzodiazepines prescribed for more than a 6-month period are as effective as other forms of pharmacotherapy, i.e., monoamine oxidase inhibitors and tricyclic antidepressants. Generally, doses of benzodiazepines used for the treatment of panic are higher compared to those used for generalized anxiety disorder.
Previous analysis of affection status in parents and siblings of 117 probands with panic disorder by a log-linear model for binary pedigree data found a common concordance across biological first-degree relatives and no spouse association [Hopper JL, Judd FK, Derrick PL, Burrows GD: Genet Epidemiol 4:33-41, 1987]. In this paper the data were reanalyzed using a regressive logistic model that modelled both vertical transmission and a shared sibship environment. Ascertainment correction was made by a) an "ascertainment assumption-free" procedure, following Ewens and Shute [Theor Pop Biol 30:388-412, 1986] and compared with b) complete ascertainment and c) single ascertainment. Under every scheme there was evidence for vertical transmission from parents to offspring. Inclusion of a sibship environment gave an improved fit, suggesting that vertical transmission alone may not be sufficient to explain the familial aggregation observed in these families. The effects of an affected parent, of the postulated environmental factor (present for all siblings if it was present for one sibling), and of the prevalence of the rare environmental factor were estimated and found to be roughly similar under the different schemes. Model predictions of lifetime prevalence were consistent with other population-based studies. Under the same assumption-free method, standard errors approximately doubled and computation time increased compared with the other ascertainment schemes that made specific, although not necessarily correct, assumptions. The regressive logistic model used less computation time and gave greater insight into the pattern of familial aggregation than did the previous modelling.
An increasing body of evidence suggests that benzodiazepines--which have long been considered the drugs of choice in the treatment of various anxiety disorders due to their relative lack of side effects, lack of adverse drug reaction, their safety, and increased efficacy over other agents--are effective in the treatment of panic disorders. Originally, the benzodiazepines were believed to be devoid of dependence-inducing properties, even at high doses. Recent evidence, however, suggests that discontinuation of both high and normal doses of both short- and long-acting benzodiazepines generally results in similar withdrawal symptoms, including anxiety and sleep and perceptual disturbances. This article presents a brief review of benzodiazepine withdrawal, with an emphasis on the discontinuation of these drugs following treatment of panic disorders. In particular, short-acting and long-acting drugs may present different features following long-term treatment and withdrawal. Preliminary results from a study comparing alprazolam and diazepam are presented to illustrate this point in contrast to expectations: the problems associated with withdrawal of both agents were comparable.
Platelet [3H]LSD binding was measured in 15 patients with panic attacks and 15 controls. The mean (+/- SD) Bmax values of the patients (14.1 +/- 6.3 fmol/mg protein) and of the controls (18.5 +/- 4.7 fmol/mg protein) were significantly different (P less than 0.05, Mann-Whitney U-test). Mean (+/- SD) values of Kd for the patients (0.55 +/- 0.34 nM) and for the controls (0.51 +/- 0.12 nM) were not significantly different (P greater than 0.1, Mann-Whitney U-test). The results are discussed in terms of a serotonergic hypothesis of the aetiology of panic disorders.
Nocturnal plasma melatonin concentrations were measured in seven patients with panic disorder and eight healthy control subjects. The five patients who had never received psychotropic medication had significantly greater melatonin concentrations from 4:00 a.m. to 7:00 a.m. than the control subjects. In addition it is possible that a phase delay occurred in these unmedicated patients. The findings are discussed in terms of previous studies showing increased melatonin in manic patients and the effect of intense stress on melatonin synthesis. The two patients who had been medication free for only 1 week showed a decreased melatonin rhythm, which is consistent with previous findings in medicated patients.
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Depression is a common disorder. While depressive symptoms are often transient and may be regarded as normal, 10 per cent of the population suffers depressive symptoms of sufficient severity and duration to be diagnosed as suffering a depressive illness.
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Platelet serotonin uptake was measured in 29 patients with DSM-III panic disorder or agoraphobia with panic attacks and compared to values obtained in 23 controls. Both the affinity constant (Km) and the maximal rate of uptake (Vmax) were determined in a buffered medium using 14C-serotonin. Patients and controls did not differ significantly with respect to age or Km values. A statistically significant difference was observed for Vmax (mean +/- SD = 65 +/- 22 pmol/10(8) platelet/min in patients vs. 44 +/- 13 pmol/10(8) platelets/min in controls). This finding suggests an overactivity of peripheral serotonergic function in panic disorder, which may also imply a similar dysfunction centrally.
Platelet serotonin uptake and platelet serotonin concentrations were measured in 17 patients (5 males, 12 females) with panic attacks and 15 controls (8 males, 7 females). Higher Vmax values were found in the patient group compared with controls (65 +/- 7 vs. 47 +/- 3 pmol/10(8) platelets/min; p less than 0.05) while the affinity constant Km was not significantly different (0.6 +/- 0.1 vs. 0.5 +/- 0.1 microM). Platelet serotonin concentrations were not significantly different between the two groups (38 +/- 4 vs. 41 +/- 4 ng/10(8) platelets). These results confirm our earlier finding of increased serotonin uptake in patients with panic attacks and suggest that platelet serotonin levels are normal.
Clobazam, a 1-5 benzodiazepine with anxiolytic properties, was evaluated in the treatment of patients with DSM-III panic disorder or agoraphobia with panic attacks. In this open clinical trial, 10 of the 15 patients completed 8 weeks of treatment. Six of the 10 completers (60%) were responders (75% reduction in the number of panic attacks from baseline) at the end of 8 weeks. Of the responders so defined, 5 of the 6 were panic free. At the end of week 8 the average dose for the responders to medication was 50 +/- 17 (S.D.) mg per day. Clobazam was well tolerated at the doses used with the few side-effects recorded as mild to moderate. The study suggests that further placebo-controlled studies are warranted to evaluate clobazam's potential antipanic effect.
In a systematic prospective study of 71 patients with acute spinal cord injury carried out in the acute and rehabilitation phases of treatment, 14 patients meeting the DSM-III criteria for major depressive disorder were identified. A further 13 patients had transient periods of depressed mood, while the majority of patients showed no clear evidence of depression. The BDI was found to be valid in this group of patients.
Acquired Immunodeficiency Syndrome (AIDS) has received much publicity and medical attention. Interest has focused on education, epidemiology, treatment and prevention of the syndrome. This paper raises other issues for consideration, including problems associated with HIV testing, confidentiality, informed consent and the dilemmas facing those involved in the treatment of patients suffering from HIV infection.
The revision of psychiatric diagnostic criteria by DSM-III has emphasised the central importance of panic attacks for the diagnosis of anxiety disorders. Since the introduction of this classification, there has been a re-evaluation of the role of major neurotransmitters as causal factors in anxiety disorders. The evidence for serotonergic hyperactivity in panic disorders is supported by the efficacy of specific serotonin reuptake blockers and 5HT2 receptor antagonists in the treatment of the condition. In addition neuroanatomical studies and positron-emission transaxial tomographic scanning are also consistent with a key role for serotonin in panic disorder. Clinical evidence of serotonin dysfunction has been sought using the blood platelet, a putative model of central serotonergic neurons. Studies of 3H-imipramine binding in platelets are equivocal, but most find no difference between patients and controls. On the other hand platelet serotonin uptake is significantly elevated in panic patients compared to controls. The reasons for the difference between two reputed markers of presynaptic serotonergic function is explored. The prolactin response to intravenous tryptophan administration is regarded as a functional correlate of central serotonergic neurons. Panic disorder patients and controls were not different in one study using this test. Serotonin concentrations in panic patients may be abnormal compared with appropriate controls. Replication of these preliminary data are necessary to confirm serotonergic dysfunction and to elucidate the interaction with other neurotransmitters, with clear implications for pharmacotherapy.
Family aggregations for panic disorder as defined by the American Psychiatric Association's DSM-III classification were examined at the Austin Hospital in Victoria, Australia, covering 636 individuals. The results were consistent with the common genetic relatedness of parents to offspring and of sibling pairs, but also consistent with other factors common to the family. The family data alone were not sufficient to draw conclusions about the cause of aggregation.
Melatonin is a major endocrine product of the pineal gland. It is produced at night when noradrenaline acts on beta-adrenergic receptors to stimulate enzymes which catalyse the formation of melatonin from serotonin. It is believed by some that nocturnal melatonin levels reflect beta-receptor function. The melatonin rhythm is also thought to be an indication of circadian rhythmicity. The nocturnal production of melatonin was studied in patients with depression and panic disorder and in control subjects. Midnight concentrations of melatonin in eleven depressed patients were significantly lower than 18 control subjects (27.1 +/- 5.1 pg/ml compared with 51.6 +/- 4.1 pg/ml; p less than 0.02, t-test). These data support previous reports of reduced melatonin synthesis in depressive illness. In the first report of patients with panic disorders, significantly lower midnight levels of melatonin were found compared with controls (28.4 +/- 6.4 pg/ml versus 51.6 +/- 4.1 pg/ml, p less than 0.02, t-test). In subsequent investigations this finding was confirmed, measuring melatonin levels over the initial phase of synthesis (i.e. 20h00 to 24h00). In these samples the melatonin rhythm also seemed to be delayed. These findings are discussed in terms of beta-receptor function and circadian rhythm alterations in affective disorders.
The development of a liaison psychiatry service to the Austin Hospital Spinal Injuries Unit highlighted the need for a psychosocial approach to patients rehabilitation. Increasingly we recognised that psychological factors influenced the course of the patient's acute illness and rehabilitation; this led to the formation of a psychosocial group under the leadership of the liaison psychiatrist. Membership of this group includes the liaison psychiatrist, psychiatry registrar, clinical psychologist, social workers, visiting nurse, chaplains and the rehabilitation registrar. The psychosocial approach advocates the consideration of psychosocial management in all aspects of patient care. In this paper we describe the structure and function of the psychosocial team in the management of patients in the Spinal Injuries Unit at the Austin Hospital.