Joan Jarman

Migraine and depression: Biological aspects

There is a considerable overlap in migraine and depression incidence, and both conditions may be associated with low levels of 5-hydroxytryptamine (5-HT). During a migraine attack there is evidence for low levels of platelet 5-HT and possibly also low Vmax for 5-HT uptake; both these findings are also associated with the depressed state. Both conditions can be treated by tricyclic and monoamine oxidase inhibiting antidepressants. However, there are also clear differences: migraine attacks are brief and self limiting. Part of the migraine cascade occurs outside the blood brain barrier, presumably involving blood vessels and, unlike depression, migraine attacks can be ameliorated by drugs which only act peripherally. In addition, migraine patients, especially males, often have permanently low levels of platelet monoamine oxidase activity, whereas patients with unipolar depression tend to have raised levels of this marker. This low enzyme activity may reflect part of the vulnerability to migraine, often associated in the prodromal phase with agitation or hyperactivity. Migraine may form part of a family of brief recurrent self-limiting disorders, which involve disturbances of both mood and monoamines; during the headache phase of the attack, the links with depression are most apparent.

Kinetics of platelet 5-hydroxytryptamine uptake in headache patients

Platelet 5-hydroxytryptamine (5-HT) uptake was measured in asymptomatic headache patients attending a specialist migraine clinic, and in hospital staff who did not suffer from regular or severe headache. Current levels of anxiety and depression were assessed in all subjects using the Hospital Anxiety and Depression (HAD) scale and their possible influence on the uptake kinetics taken into account during the analysis of results. The Michaelis-Menten constant (K m ) was significantly raised in common migraine and tension headache compared with controls (p < 0.001 and p < 0.01, respectively), but not in classical migraine or cluster headache. The increase remained significant after adjusting for differences in age, sex, presence of anxiety or depression (HAD sub-scale score 3 8), drug intake during the week before testing, time elapsed since last attack and time of assay (am or pm). No differences were observed between patients and controls in the maximal rate of uptake (V max) or platelet count, and previous reports of a reduction in V max in patients experiencing attack within 5 days prior to testing could not be confirmed. The cause and significance of an increased K m are not clear, but plasma factors acting as competitive inhibitors for the uptake site or an alteration in the configuration of the uptake site are possible explanations. If confirmed, the shared biochemical abnormality may suggest that common migraine and tension headache have a common pathogenesis.

Platelet monoamine oxidase-B activity in Parkinson's disease: a re-evaluation

SummaryAn increase in platelet monoamine oxidase (MAO) B activity in drug-free parkinsonians (n=6) compared with healthy controls (n=10) has been confirmed using both phenylethylamine (PEA) and dopamine as substrates, reaching statistical, significance in the case of PEA oxidising activity (p<0.05). Thus, certain reports of raised platelet MAO B activity towards PEA but decreased activity towards dopamine in parkinsonians, raising the possibility of the existence of an abnormal form of MAO B in this condition, cannot be supported.

Release of (14C)5-hydroxytryptamine from human platelets by red wine

Red wine, at a final dilution of 1/50, caused release of [14C]5-hydroxytryptamine (5-HT) from preloaded platelets, an effect which was not observed with any white wines or beers tested. Since 5-HT, is probably released from body stores during migraine attacks and red wine is known to provoke migraine episodes in susceptible individuals, release of 5-HT, possibly from central stores, could represent a plausible mechanism for its mode of action.

Platelet [3H]imipramine binding in migraine and tension headache in relation to depression.

Platelet [3H]imipramine binding was measured in 40 migrainous (7 classical and 33 common) and 17 tension headache patients and in 28 normal controls. A significant reduction in Bmax was found in migraine compared with controls (p less than 0.05) but not in tension headache. In migraine, there was no significant relationship between Bmax and depression or anxiety score on the self-rating Hospital Anxiety and Depression (HAD) Scale, suggesting that the reduction in Bmax is a concomitant of migraine itself rather than a manifestation of associated depression. Preliminary evaluation using the Schedule of Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) tended to confirm this conclusion.

Urinary output of endogenous monoamine oxidase inhibitor and isatin during acute migraine attacks

Urinary output of endogenous monoamine oxidase (MAO) inhibitory activity, was significantly raised in serial samples collected across a migraine attack compared with collections during attack-free periods and in healthy controls, which did not differ from each other. There was a highly significant correlation in output between isatin, a major fraction of the MAO inhibitory activity, and output of the MAO inhibitory activity itself. However, although there was a tendency towards increased isatin excretion during migraine attacks, it failed to reach statistical significance.