Background The concept that early intervention with antipsychotic medications improves the long-term course of schizophrenia is discussed.

Method This report reviews the literature concerning early intervention with antipsychotic medications for people with firstepisodes, and how it affects long-term morbidity. It also studies the effects of discontinuing antipsychotic medications on relapse for people with first episodes.

Results Early intervention with antipsychotic medications appears to decrease the long-term morbidity of schizophrenia.

Conclusions Early intervention with antipsychotic medications should be encouraged for people experiencing their first episode of schizophrenia. This report proposes that studying the various phases of subject response to treatment can be helpful in elucidating when antipsychotic medications should be tapered or withdrawn.

We describe a case of marked increases in serum creatine phosphokinase (CPK) associated with a dramatic exacerbation of tardive dyskinesia (TD). Chart review of eight additional patients with severe TD revealed three cases with mild CPK elevations. These cases suggest that TD, especially when accompanied by dystonia, may be associated with pathology of striated muscle.

We have recently demonstrated that some patients with atypical bipolar affective disorders, characterized by psychotic manias and depressions, have fluctuating and episodic high urinary phenylethlamine (PEA) excretion. We treated a 30 year old woman, who has this disorder, with 200 mg/24 hours of carbidopa. Her psychosis was ameliorated and the urinary PEA output stabilized to a low normal level. Upon withdrawal of carbidopa her psychosis worsened and improved again when carbidopa treatment was reinstated. Carbidopa did not affect the duration or severity of the patient's mood cycles.

Spontaneous eye blink rates, psychiatric symptoms and response to neuroleptic medication may all be mediated by dopamine. Fixed doses of haloperidol, a dopamine blocking agent, were administered for six weeks to 17 chronic schizophrenic patients who had been previously withdrawn from all medications. The change in blink rates caused by haloperidol corresponded to a change in the thought disturbance syndrome which measures positive symptoms (r =.48, P <.05). The relationship was particularly clear in patients with normal cerebral ventricles (r =.74, P <.01).

Immunoglobulins, IgG, IgA and IgM were quantified in cerebrospinal fluid (CSF) and plasma from chronic schizophrenic patients and controls using an immunofluorescent antibody technique. A generalized reduction in immunoglobulin levels was observed in the schizophrenic patients compared with controls. While this study supports other reports of abnormal immune functioning in schizophrenia, it failed to replicate previous findings of elevations in CSF IgG and elevations in serum IgA. The aetiology and significance of these findings are hypothesized but remain elusive.

The frequency of HLA-A2 was examined in 32 black and 22 white schizophrenic patients separated into two groups according to whether they had normal or reversed cerebral hemispheric asymmetries as determined by computed tomography. The black patients with reversed asymmetry had a significantly greater frequency of HLA-A2 as compared to black patients with normal asymmetry and a black normal control group. There were no significant differences for any other A, B or C antigens. These findings also held when only the 22 black patients without evidence of brain atrophy were studied. The results for the white patients were in the same direction but did not reach statistical significance. These findings suggest that, at least for black schizophrenic patients, reversed cerebral asymmetry is associated with an increased frequency of HLA-A2.

A survey of 14 published studies found no consistent association between specific HLA antigens and schizophrenia. Since these studies lacked diagnostic or biological criteria, an investigation was undertaken using recognized diagnostic criteria and CT scan findings. Typing for HLA antigens at loci A, B and C was carried out on 130 patients. Among 92 black schizophrenic patients there was an increase of HLA-A2 which remained significant even after correcting for the number of antigens studied. When the patients for whom CT scans were available were divided according to the presence or absence of evidence of brain atrophy, there was an increase of A2 in the black schizophrenic patients without evidence of atrophy, which remained significant after multiplying by the number of antigens studied. However, there was no significant increase of A2 in those with evidence of atrophy. Similar trends held for the white population but they failed to reach significance. The need for HLA studies on biologically defined groups of schizophrenic patients is stressed.

Small but statistically significant increases in serum total calcium and serum inorganic phosphorus coincided with repeated onsets of psychotic agitation or mania in nine psychotic in-patients experiencing rapid cycles of illness. These increases were not accompanied by changes in magnesium or other constituents, which might suggest non-specific haemoconcentration. Similar increases in calcium or phosphorus were not present in patients without the same cycles of psychotic illness. The observed increases could neither be simulated nor altered by stress or activity, and it remains unclear whether they might be accounted for by dietary changes, sleep disruption, circadian phase shifts or by endocrine alterations.