Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.

PURPOSE: To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS). PATIENTS AND METHODS: Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing. RESULTS: Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens. CONCLUSIONS: In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder.

The people seen by Sydney psychiatrists.

A one-in-six sample of psychiatrists practising in Sydney was asked to provide details of patients seen in the previous five working days. The averaged workload of the 49 psychiatrists showed that they spent a third of their time with patients with psychotic illnesses, a third with patients with neurotic conditions and most of the remainder on patients troubled by personality disorders. Sixty-one per cent of the patients were female and the median age of the patients was 39 years. Psychotherapy was the most commonly used primary treatment for the neuroses and personality disorders, but drugs were used most frequently for the psychoses.

Motor neuronal control of tail-directed and head-directed siphon responses in Aplysia californica.

1. Cutaneous stimulation of opposite ends of the body causes qualitatively different siphon responses: tail stimulation causes flaring and backward bending (the siphon T response), whereas head stimulation causes constriction and slight anterior bending (the siphon H response). This paper characterizes the motor neuronal control of siphon T and siphon H responses. 2. The siphon response to tail nerve (p9) shock in a semi-intact preparation was indistinguishable from the siphon T response in intact or parapodectomized animals. Similarly, the siphon response to head nerve (c2) shock in this preparation was indistinguishable from the siphon H response in intact or parapodectomized animals. 3. Central siphon motor neurons (SMNs) were found to cause a wider variety of movements than previously reported. The movements produced by the LFSB cells strongly resemble the flaring response of the siphon to tail or tail nerve stimulation. The movements produced by RDS and LDS1 resemble components of the constricting response of the siphon to head or head nerve stimulation. 4. Among central SMNs, the LFSB cells show the strongest activation by posterior stimulation, whereas RDS and LDS1 show the strongest activation by anterior stimulation. The LFSA cells, which produce much weaker siphon constriction, are only activated slightly by posterior stimulation and are inhibited by anterior stimulation. Peripheral SMNs are inhibited by stimulation of head and tail nerves, and thus their activity does not directly contribute to siphon T and H responses. 5. Artificially activating central SMNs with the pattern of activity previously exhibited after tail or head nerve stimulation indicated the sufficiency of the LFSB cells for the siphon T response, and of RDS and LDS1 for the siphon H response. 6. Dramatic behavioral deficits produced by hyperpolarizing the LFSB cells during tail nerve stimulation, or by hyperpolarizing RDS and LDS1 during head nerve stimulation, indicated the necessity of these cells for the expression of directed siphon responses to tail or head stimulation, respectively. 7. Because of their apparent necessity and sufficiency for directional siphon responses to anterior and posterior stimulation, these few cells provide well-defined vantage points for studying neural mechanisms underlying the motor control and transformation of siphon responses. The four LFSB cells offer a special advantage for cellular analysis because they form a homogeneous functional unit in which any sampled LFSB cell can be used as a precise monitor of the total motor output underlying the siphon T response.(ABSTRACT TRUNCATED AT 400 WORDS)

The synapse between LE sensory neurons and gill motoneurons makes only a small contribution to the Aplysia gill-withdrawal reflex.

The monosynaptic connection between the mechano-sensory neurons in the LE cluster and gill motoneurons has been extensively studied and used as a model for the gill-withdrawal reflex and its behavioural plasticity. In an attempt to evaluate the contribution of this synapse to the behaviour, we used voltage-sensitive dye recording to determine the number of activated LE neurons and the number of spikes made by each neuron in response to a light touch. In five preparations, light touch activated a median of five sensory cells with a median of 1.6 spikes per cell. From a comparison of the sizes of the motoneuron synaptic potentials elicited by LE spikes and elicited by a light siphon touch, we estimate that the LE sensory neurons contribute approximately 5% of the motoneuron synaptic potential in response to this touch. This result casts doubt on the validity of using this synaptic connection as a model for gill-withdrawal behaviour. Siphon nerve recordings reveal the existence of short-latency, low-threshold neurons that may provide much of the sensory input in response to a light touch.

Delayed-type hypersensitivity skin testing: normal values in the Australian population.

In our human psychoimmunological studies we have utilized a standardized assessment kit, the cell-mediated immunity (CMI) Multitest system, for determining delayed-type hypersensitivity (DTH) skin responses to a panel of ubiquitous antigens. Although the kit had been assessed in large populations of healthy controls in the U.S.A. and Europe, few data were available with regard to normative values in the Australian population. There are cogent reasons to suspect that results for the test will vary depending on geographical location, age cohort, compliance with specific immunization schedules and rates of natural exposure to certain diseases in differing populations. Most of our patient cohorts have a preponderance of female subjects and most standardization had been conducted in males. We tested medically and psychologically healthy males (n = 66) and females (n = 53). The percentage of positive responses to individual antigens was similar to other Australian studies but lower than that reported internationally. The mean number of positive responses was 3.7 for men and 2.8 for women, while the mean induration diameter was 17.5 mm for men and 12.2 mm for women. Three per cent of men and 5.6% of women were anergic (no positive responses), while a further 10.6% of men and 9.4% of women fell into the "hypoergic" category. These results, and those from other studies, indicate that the pattern of response to the CMI Multitest differs in healthy Australians. Therefore, researchers need to exercise caution when selecting patient and control samples (controlling for exposure factors), applying the test, reporting results (i.e. including all relevant parameters-with an emphasis on dimensional rather than categorical scores) and when designating subjects as having "impaired" responses.

Biochemical correlates of in vivo cell-mediated immune dysfunction in patients with depression: a preliminary report.

We have previously demonstrated that at least 50% of patients with melancholia have impaired cell-mediated immunity (CMI) as assessed by delayed-type hypersensitivity (DTH) skin responses to a standardized battery of antigens. Hypercortisolaemia and increased circulating catecholamines both occur in patients with severe depressive disorders and each has been proposed as a possible mediator of observed immune abnormalities in patients with mood disorders. As part of a larger study, we collected 24 h urine samples from 28 patients with major depression and measured concentrations of urinary free cortisol (UFC), the noradrenaline metabolite dihydroxyphenylglycol (DHPG), adrenaline, and the dopamine metabolite DOPAC. CMI multitest skin testing revealed a reduced or absent response in 54% of subjects. Those with reduced DTH skin responses demonstrated increased urinary adrenaline (P < 0.02), with trends toward increased UFC (P = 0.052) and increased DHPG (P = 0.06). These differences could not be attributed to differences in age or depression severity. Correlational analyses demonstrated inverse associations between the extent of DTH responsiveness and 24 h levels of urinary adrenaline and DHPG, with similar trends evident for UFC and DOPAC. These results suggest that both circulating catecholamines and cortisol may play roles in the reduction of CMI in patients with severe depression.

Impaired in vivo immune responses in patients with melancholia.

Previous attempts to establish a relationship between impaired cell-mediated immunity (CMI) and major mood disorders have been limited by a failure to explore the relevance of depressive subcategories or to assess CMI by in vivo methods. In this case-control study CMI was assessed in 57 patients with major depression (31 with melancholic, 26 with non-melancholic disorders), and in age- and sex-matched controls by both in vitro and in vivo immunological techniques. Compared with control subjects and patients with non-melancholic depression, patients with melancholia demonstrated reduced in vivo CMI as assessed by delayed-type hypersensitivity (DTH) skin responses. Although increasing age, severity of depression, hospital admission for treatment, and reported weight loss are correlates of melancholia, none of these factors alone, or in combination, accounted for the differences in DTH responses observed between the two depressive subtypes. These data suggest that impaired CMI in vivo may be limited to those with melancholic disorders. At this stage the factors which account for this effect are unclear.

Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression.

The chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder. Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non-melancholic, non-psychotic) as well as healthy control subjects. Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P less than 0.05 for each analysis). Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS.