Lawrence J. Whalley

Selective effects of ECT on hypothalamic—pituitary activity

The hypothesis that ECT produces selective effects on hypothalamic-pituitary activity was investigated by determining the effect of ECT on pituitary hormone release in nine depressed patients. After ECT there were massive and rapid increases in the plasma concentrations of nicotine- and oestrogen-stimulated neurophysin (NSN and ESN), prolactin (PRL) and adrenocorticotropin (ACTH), smaller increases in plasma luteinizing hormone (LH) and cortisol, a significant decrease in plasma growth hormone (GH) concentration but no change in plasma thyrotropin (TSH). There was significant attenuation of PRL responses with repeated ECT. The hormonal responses to ECT cannot simply be attributed to stress, since a similar pattern of increases in plasma hormone concentrations did not occur in psychologically normal patients in whom plasma hormone concentrations were measured during induction of anaesthesia and abdominal incision for cholecystectomy. Analysis of these hormonal responses in terms of the knowledge available on the neurotransmitter control of pituitary hormone release suggests that some of these hormonal responses to ECT may be mediated by the activation of serotonergic neurones, while others are probably due to direct stimulation of the neuroendocrine neurones themselves.

Treatment outcome, seizure duration, and the neurophysin response to ECT

Serum concentrations of immunoreactive neurophysin (IRN) and vasopressin-associated neurophysin (hNpI) were measured before and after the first treatment in a course of electroencephalographically monitored electroconvulsive therapy (ECT) given to 19 depressed patients. The difference (DIFF) between the serum concentrations of IRN and hNpI is equivalent to the concentration of oxytocin-associated neurophysin. Before ECT the six patients who had a good outcome at 2 months after the course of ECT had a mean serum IRN concentration one-half (p less than 0.05) and a mean serum DIFF concentration one-third (p less than 0.05) that of the 13 patients who had a poor outcome. The increase in serum DIFF concentration (but not IRN or hNpI) after the first ECT correlated with the improvement on the Hamilton Rating Scale for Depression (r = -0.73, p less than 0.005) and the Montgomery and Asberg Depression Rating Scale (r = -0.49, p less than 0.05). The peak percentage increase in serum DIFF concentrations after ECT was 4 times greater (p less than 0.001) in the good outcome group than in the poor outcome group. None of the neurophysin responses to ECT correlated with electroencephalogram-measured seizure duration.

Mood, cognition and cortisol: their temporal relationships during recovery from depressive illness

Single-case methodology, using cross-lagged panel correlations, was applied to study the order of change in mood, cognition and cortisol concentration in eight in-patients with a diagnosis of major, endogenous depression. Daily measures included: two visual analogue scales measuring depressed mood and general feeling of unwellness; cortisol concentration in saliva (sampled four times a day) and in 24-h urine; two cognitive scales, the Automatic Thoughts Questionnaire and the Cognitive Style Test. The results relating to the temporal relationship between biological and psychological data were ambiguous as the pattern of change was inconsistent among individuals. Group data indicated that changes in feeling unwell preceded changes in early evening salivary cortisol and changes in negative automatic thoughts preceded changes in day and early evening salivary cortisol. Psychological variables and cortisol concentrations were generally negatively correlated within individuals indicating that over the short recovery period improving mood and cognition were associated with increasing levels of cortisol. A more consistent pattern of precedence of change was obtained for mood and cognition: negative cognitive style predicted changes in both mood measures and feeling unwell predicted changes in negative automatic thoughts.

Choline uptake in patients with Alzheimer pre-senile dementia.

Serum and CSF choline levels were measured in 12 patients with pre-senile Alzheimers disease before and 1 hour after administration of 1.5 g choline chloride or 25 g lecithin granules. Serum choline levels were increased threefold and CSF choline levels by 72%. CSF choline levels in the untreated Alzheimer patients did not differ significantly from age-matched controls. In 35 neurological controls, CSF choline levels increased with age (R = 0.64, p less than 0.001). Choline influx into erythrocytes from 10 male and 10 female Alzheimer patients did not differ significantly from 40 male and 43 female controls. Choline influx into erythrocytes was not related to age or sex, although the range of values was greater (p less than 0.05) in females than in males. Our results indicate that there is no impairment of choline transport into CSF or erythrocytes in patients with pre-senile Alzheimers disease.

Survival in Presenile Alzheimer's and Multi-lnfarct Dementias

Duration of survival in patients who had died of presenile Alzheimers disease (AD) or presenile multi-infarct dementia (MID) in 13 mental hospitals in Scotland are described and contrasted. The duration of survival was significantly longer from symptom onset to death in AD (mean 7.4 years) than in MID (mean 5.8 years). Most of this difference was accounted for by a longer duration between symptom onset and presentation to hospital care in AD (mean 3.2 years) than in MID (mean 2.4 years). Age at onset and gender did not influence survival duration in AD or MID.

Luteinizing hormone responses to luteinizing hormone releasing hormone (LHRH) in acute mania and the effects of lithium on LHRH and thyrotrophin releasing hormone tests in volunteers

The endocrine responses to Luteinizing Hormone Releasing Hormone (LHRH) of eight drug-free males with mania were determined. Basal levels of Luteinizing Hormone (LH) and the plasma levels following injection of LHRH were elevated in patients compared with controls; Follicle Stimulating Hormone (FSH) and testosterone were not different. Elevated levels of LH have been described previously in recovered manic patients and have been suggested to be state-independent features of mania. In order to clarify the status of this finding, the effects of lithium administration upon hormone responses to LHRH in six male volunteers were also investigated, together with the effects upon Thyrotrophin Releasing Hormone (TRH) stimulation of Thyroid Stimulating Hormone (TSH) and prolactin release. Lithium increased the basal levels of LH and levels after injection of LHRH without effect upon FSH and testosterone. Lithium also increased basal and TRH stimulated release of TSH and basal prolactin levels. Lithium was without effect upon prolactin responses to TRH. The results are discussed in relation to current information on the mechanism of lithiums action. The implications for neuroendocrine work on recovered patients taking lithium are also explored.

Effects of seizure duration on serum TSH concentration after ECT

Serum thyroid stimulating hormone (TSH) concentrations were measured by a sensitive immunoradiometric assay in 14 patients immediately before and after the first treatment of a course of electroconvulsive therapy (ECT). There was a close correlation (r = +0.70, p less than 0.01) between the increase in TSH concentration 15 min after ECT and the duration of seizure activity as measured by EEG. This observation may help clarify previous contradictory findings on the effects of ECT on TSH concentrations. There was no correlation between the increase in serum TSH concentration and the extent of recovery from depressive illness.

Sulpiride treatment of acute mania with a comparison of the effects on plasma hormone concentrations of lithium and sulpiride treatment

Sulpiride, in this open study of acute manic patients, had a clear antimanic action with all eight patients responding to sulpiride treatment without the need for other antipsychotic drugs. Plasma prolactin concentrations were increased and oestrogen-stimulated neurophysin concentrations decreased by sulpiride but were unchanged by lithium treatment, whereas TSH concentrations showed a rapid increase following the introduction of lithium therapy.

Plasma cortisol concentrations in the functional psychoses and Alzheimer Type Dementia: A neuroendocrine day approach in drug-free patients

We have investigated the plasma concentration of cortisol in psychotic patients classified according to Feighners criteria as either depressed, manic, schizophrenic or unclassified, and in 8 patients with Alzheimers Type Dementia. The patients had been free of either neuroleptic or antidepressant drugs for at least 3 months before the study. Blood sampling was carried out by way of a neuroendrocrine day approach in which venous samples were taken at 07:00, 07:30 and 08:00 h; 15:00, 15:30 and 16:00 h; and 23:00, 23:30 and 24:00 h. This approach permits determination of circadian pattern of hormone release and allows for pulsatile hormone release. These preliminary results showed that, contrary to expectation, neither the mean concentrations nor the circadian pattern of plasma cortisol concentrations in patients with depression differed significantly from those in any other group.

Repeated ECT and prolactin release in depressed patients.

Whereas sham electroconvulsive therapy (ECT) increases the blood concentration of prolactin (PRL) up to two-fold after 15 m~n, real ECT increases PRL concentration several fold (Deakin et al 1983). Sequential study of the effects of electrode placement has established that bilateral ECT releases 25% (Swartz and Abrams 1984)-50% (Papakostos et al 1986) more PRL than does unilateral ECT which may demonstrate a greater hypothalan,ic-stimulating effect of bilateral ECT (Swartz and Abrams 1984). Electroencephalographic (EEG) study of the relationship between the length of cerebral seizure activity and PRL release has been inconclusive (Abrams and Swartz 198~b; Robin et at .~985), as has been the study of the relationship betw~,~ :, PRL release and recovery from depression (Deakin et al 1983; Abrams and Swartz 1985a). It has been suggested that the study of pituitary hormone release over a course of ECT may provide important information about alterations in central monoaminergic transmission in depressed patients. (Whalley et al 1982; Aperia et al 1985). The major role of the hypothalamus in the regulation of PRL release is inhibitory through the tuberoinfundibular dopaminergic system. A PRL releasing factor, such as thyrotropin releasing hormor ~ or vasoactive intestinal l~eptide, may be involved in stimulating PRL release and this may involve serotonin (5HT) (Leong et al 1983). After ECT, PRL release has been reported to be significantly reduced later on in a course of treatment for depression as compared to the first treatment (Deakin et al 1983; Abrams and Swartz 1985a; Aperia et al 1985; Cooper et al 1989), suggesting an increase in the responsiveness of post-synapuc dopamine receptors (Abrams and Swartz 1985a; Aperia et al 1985). This finding has not always been confirmed (Whalley et al 1982; Linnoila et al 1984; Haskett et al 1985). The intake of neuroleptic drugs increases both basal and ECl-induced PRL release (Swartz 1985a; Aperia et a! 1985), but only one report concerned depressed patients free of neuroleptic drugs in the 2 weeks before ECT (Abrams and Swartz 1985a). O~:r aim was to study PRL release over a course of ECT in depressed patients who had not takeL, neuroleptic drugs during their index illness. ECT was monitored by 6-channel EEG because the ~gpatial distribution of epileptic seizures in hum,ms influences PRL release in that generalized se~ :ures release more PRL than focal seizures (Spc.ding et al 1986).