Cell Membrane Predictors of Response to Lithium Prophylaxis of Affective Disorders

Abstract

HLA antigens and RBC/plasma lithium ratio were studied in a sample of 49 patients, diagnosed as bipolar affective psychotics (n = 22), unipolar depressive psychotics (n = 18) and cycloid psychotics (n = 9), receiving prophylactic lithium for 1–4 years and maintained at lithium plasma levels of 0.6–1.2 mEq/1. Mean values of the ratio were found to be significantly higher in patients who responded to treatment when compared with non-responders, whereas the frequency of the HLA-A3 antigen was significantly higher in non-responders. The only 6 patients with a lithium ratio above the median and the absence of the HLA-A3 antigen coexistent with bipolarity and a family history of the illness were all good responders to treatment. Further research in this field will probably bring about the isolation of a subgroup of lithium-responsive patients with well-defined clinical and biological features. When patients were divided into two subgroups according to their lithium ratios (above and below the median), the HLA-A3 and Aw26 antigens were found to be significantly more frequent in those with ratios below the median. It can be hypothesized that these antigens disturb lithium transport in some way, leading to low lithium ratio values.

Prediction of affective psychoses response to lithium prophylaxis

“…3) platelet MA0 activity (by a radioenzymatic method, using tryptamine and beta-phenylethylamine as substrates (21), testing each patient while euthymic, at least twice during the follow-up period), and 4) HLA antigens (by the standard NIH microcytotoxicity test (9). Statistical significance of differences between responders and non-responders was evaluated by the Student's t test and the x 2 method with Yates' correction.…”

“…the occurrence of more than three affective episodes within 1 year), a history of alcoholism or drug abuse not associated with mood changes, and the presence of paranoid features in the clinical picture have been cited as clinical predictors of a poor response (3,4). Among biological variables, high values of the red blood celVplasma lithium ratio (5,6) and a significantly elevated potential difference across the rectal mucosa (7) have been found to be associated with a favourable response to prophylaxis, while the presence of the HLA-A3 antigen has been reported to be significantly more frequent in non-responsive patients (8,9). Finally, evidence has been claimed of higher mean scores on the Obsessional Scale of the Middlesex Hospital Questionnaire in lithium-responsive patients (10) and on the Neuroticism Scale of the Eysenck Personality Questionnaire in non-responders (1 1).…”

Biological predictors of lithium response in bipolar disorder

“…found that the frequency of HLA‐A3 antigen was significantly higher in lithium non‐responders 59 . This relationship between HLA‐A3 antigen and non‐response to prophylactic treatment by lithium was confirmed by other researchers 7,60 , 61 . However, subsequent studies could not replicate an association between affective disorder and HLA antigens 62–65 .…”

“…59 This relationship between HLA-A3 antigen and non-response to prophylactic treatment by lithium was confirmed by other researchers. 7,60,61 However, subsequent studies could not replicate an association between affective disorder and HLA antigens. [62][63][64][65] This questioned the possible relationship between lithium response and HLA.…”

High genetic loading of schizophrenia predicts poor response to lithium in patients with bipolar disorder: A polygenic score and cross-trait genetic analysis

“…Differences in cellular HLA surface protein composition between BPD patients who respond well to lithium and non-responders were first reported over 30 years ago in several studies. These reports noted that leukocyte HLA-A3 antigen reactivity was reported to be associated with poor lithium response, whereas the absence of HLA-A3 predicted a favorable response [58][59][60] . At the same time, in vitro experiments suggested that lithium binds to HLA antigens on cultured human leukocytes 61 .…”