Neuropsychological deficit in newly diagnosed patients with schizophrenia or schizophreniform disorder.

Forty-six patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time were compared with 21 healthy volunteers on neuropsychological tests reflecting prefrontal and left respectively right hemisphere function. The patients with schizophrenia or schizophreniform disorder had a poorer performance on neuropsychological tests (such as Wisconsin Card Sorting) compared with healthy volunteers. Both left and right hemisphere seemed to be involved. Especially poor performance was found on somewhat complicated tests requiring ability of analysis, abstraction and memory, thus indicating dysfunction of prefrontal and temporohippocampal regions. Signs of sulcal enlargement and size of lateral ventricles on computed tomographic scan correlated with poor test performance on some tests both in patients and in healthy volunteers. No correlations were found between performance on neuropsychological test and negative symptoms.

Relationship between brain structure and function in disorders of the schizophrenic spectrum: single positron emission computerized tomography, computerized tomography and psychopathology of first episodes.

Fifty newly diagnosed, briefly treated or drug-naive patients with schizophrenia or schizophreniform disorder were examined by psychopathology scales for positive (SAPS), negative (SANS) and overall psychotic symptoms (PSE and BPRS). CT-scan and regional cerebral blood flow (rCBF) measurement by 99mTc-HMPAO SPECT during rest and mental activation by Wisconsin Card Sorting Test was performed as well. Twenty-five age-matched normal healthy volunteers served as controls. Thought disorders and fundamental symptoms correlated positively with relatively high, though subnormal prefrontal (PFC) rCBF and high rCBF in temporal cortex; positive symptoms correlated positively with high rCBF in the striatum and temporal cortex during activation. Negative symptoms correlated with high prefrontal rCBF. The patients had sulcal enlargement and smaller brain volume compared with the healthy volunteers. There were no signs of ventricular enlargement. Neither total negative symptoms, thought disorder nor fundamental symptoms correlated with any CT measurements. Total positive symptoms correlated negatively with the size of the temporal horns. The relatively high rCBF in PFC and temporal cortex of cases with pronounced positive and negative symptoms and thought disorder may imply that an aberrant cortical network has to be active to express a malattuned clinical output. The striatal hyperfunction mainly in productive cases may be a secondary phenomenon and more pronounced in cases where no signs of subcortical atrophy has (yet?) ensued.

Computerised tomography in newly diagnosed schizophrenia and schizophreniform disorder. A controlled blind study.

Patients with newly diagnosed schizophrenia (n = 27) or schizophreniform disorder (n = 22) and 24 healthy volunteers were investigated by CT scan, the investigators being blind to subject status. The patients had never received medication or had been treated only briefly with neuroleptics. The patients had significantly smaller brain volume and brain length than the controls. The patients had greater sulcal enlargement in the case of both Sylvian and interhemispheric fissures and surface sulci in the frontal and parietal regions. The sulcal enlargement was more pronounced in male patients and on the left hemisphere. The study revealed no enlargement of the lateral ventricles and only a trend towards enlargement of the third ventricle in the patients. The findings were not explained by substance abuse or level of education.

The St. Hans Rating Scale for extrapyramidal syndromes: reliability and validity.

The St. Hans Rating Scale (SHRS) is a multidimensional rating scale for the evaluation of neuroleptic-induced hyperkinesia, parkinsonism, akathisia and dystonia. This scale and the Abnormal Involuntary Movement Scale (AIMS) were tested by 7 raters (2 experienced, 2 less experienced and 3 totally inexperienced) in 30 psychiatric patients with tardive dyskinesia (TD). The test was performed 3 times in the same patients: 1) live evaluation during a video recording, 2) evaluation 2 weeks later from the videotape, and 3) evaluation after another 2 weeks from the same videotape. The intrarater reliability was high in the experienced group (0.91-0.96 for SHRS hyperkinesia scale, 0.80-0.84 for AIMS, and 0.82-0.97 for SHRS total parkinsonism). No significant changes occurred from live to video evaluation. The interrater reliability coefficient for the experienced group was also high: 0.89-0.95 for the SHRS hyperkinesia scale, 0.76-0.85 for the AIMS scale and 0.95-0.98 for the SHRS parkinsonism scale. The less experienced and the inexperienced raters had coefficients for intra- and interrater reliability that were 0.10 and 0.20 lower, respectively. The SHRS parkinsonism scale had a high construct validity, as determined by the homogeneity coefficients of Cronbach (0.82) and Loevinger (0.43). The corresponding coefficients for the hyperkinesia scales were low, in agreement with the individual distribution of TD (only about 50% present extremity dyskinesia and less than 25% facial, head and trunk dyskinesia, independent of the severity of the syndrome). Finally, convergent validity was found between the SHRS hyperkinesia scale and AIMS and divergent validity between all of the other scales.(ABSTRACT TRUNCATED AT 250 WORDS)

Kidney functioning during lithium treatment: a prospective study of patients treated with lithium for up to ten years.

A cohort of 53 patients with affective disorders who originally carried through renal functional tests before start of prophylactic lithium treatment were followed up prospectively after an average period of 8.5 years (range 7-10 years). Ten patients who had continued lithium treatment were re-examined. In this subgroup, the glomerular function was unaffected by the treatment, whereas the average urine volume increased during lithium treatment (NS). Polyuria and low renal concentrating abilities were also found before start of treatment and these findings underline the importance of access to renal baseline information prior to lithium treatment.

Lithium: long-term effects on the kidney. A prospective follow-up study ten years after kidney biopsy.

Forty-six patients with recurrent affective disorders, who began prophylactic treatment with lithium an average of 20 years previously, were followed up prospectively after a ten-year observation period to assess renal function. Nineteen patients had maintained lithium therapy, and eight patients had died. Tubular function was almost unchanged and patients who had continued lithium had not shown increasing urine volumes, but patients who had received lithium in a single daily dosage at night had a significantly lower urinary output than those on a multiple-dosage schedule. The GFR decreased significantly, but the decline was essentially dependent on increasing age, except in two patients who had developed renal insufficiency. Renal function during chronic lithium treatment is related to age, lithium intoxication episodes, pre-existing renal disease, and treatment schedule rather than to duration of prophylactic lithium therapy.

Effect of intravenous injection of biperiden and clonazepam in dystonia.

The acute effect of intravenous injections of biperiden and clonazepam was investigated in 14 patients with various forms of dystonia (segmental dystonia, 2; generalized dystonia, 6; and Meige's syndrome, 6). Eleven patients had primary dystonia, and 3 patients had a secondary form of dystonia. Doses of 5 mg of biperiden reduced dystonia when evaluated by total scores, global scores, and subjective scores. Two patients had marked side effects in the form of dizziness. Doses of 1 mg of clonazepam significantly reduced total scores and subjective scores, but the reduction in global score was insignificant. No patient had marked side effects following injection with clonazepam. These results correspond with earlier investigations of the long-term effects of anticholinergics and benzodiazepines. It is concluded that in some cases, intravenous injections can be used as a test for evaluating both effects and side effects of antidystonic medication prior to the institution of oral treatment. Long-term intravenous treatment might be considered in individual cases.

Locked-in syndrome following cervical manipulation.

A case of locked-in syndrome following cervical manipulation in a 36-year-old woman is described. The patient had always been healthy but was born with polydactyly on one hand and had 2 mentally retarded children with progressive leucoencephalopathia. Because of pain in the neck the patient was treated with cervical manipulation, during which she became ill and developed a locked-in syndrome, where she was awake but mutistic and totally paralyzed. Following intensive training the patient became able to perform rocking movements with the head, which were used to activate an electronic system for communication. MR scanning 3 months after admission exhibited a sharply demarcated triangular area stretching through most of the pons, which was compatible with a recent infarction.

Effects of citalopram, a specific serotonin uptake inhibitor, in tardive dyskinesia and parkinsonism.

Serotonin (5-HT) has been proposed to exert an inhibitory effect on central dopamine activity, so increased brain 5-HT would be expected to reduce tardive dyskinesia (TD). Therefore a new antidepressant, a selective 5-HT uptake inhibitor, citalopram, was evaluated in 13 psychiatric patients with TD, 11 of whom also had neuroleptic-induced parkinsonism. Drug effects during active treatment (20-40 mg/day for 3 weeks) and pre- and posttreatment placebo periods were scored blindly from videotapes recorded weekly. TD, parkinsonism, and eyeblinking rates were unchanged. Psychiatric symptoms showed no significant changes, and no side effects were reported. The data suggest that increasing 5-HT activity by 5-HT uptake inhibitors has no significant beneficial effect in TD, but citalopram may be advantageous in the treatment of depressed patients who also have TD, as this drug does not aggravate TD as do tricyclic antidepressants.

Effects of serotonergic and anticholinergic drugs in haloperidol-induced dystonia in Cebus monkeys.

In rodents, serotonin (5-HT) antagonists counteract behavioral and biochemical effects of neuroleptic drugs. Therefore, we have studied the effect of different 5-HT drugs and one anticholinergic drug in acute dystonia in five cebus monkeys chronically treated with haloperidol. Acute dystonia induced by subcutaneous injections of haloperidol was slightly reduced by the 5-HT antagonist methysergide (4.0 mg/kg), while mianserin, ketanserin, and ritanserin (R 55 667; a new selective and potent 5-HT receptor blocker) had no effect. This was contrasted by the marked antidystonic effect of the anticholinergic drug biperiden (0.05-1.0 mg/kg). The 5-HT agonist citalopram, a specific 5-HT uptake inhibitor, had no significant effect. It is concluded that 5-HT antagonists have no useful effect in neuroleptic-induced dystonia.

Effects of apomorphine and haloperidol on "spontaneous" stereotyped licking behaviour in the Cebus monkey.

Three recently arrived drug naive Cebus apella monkeys with "spontaneous" stereotyped oral movements were treated with apomorphine and haloperidol using a wide dose range. Low doses of apomorphine (0.05-0.1 mg/kg) suppressed the oral stereotypies without affecting normal behaviour such as grooming and scratching. Higher doses of apomorphine (0.25-1.0 mg/kg) and haloperidol (0.01-0.1 mg/kg) also decreased or abolished the oral stereotypies, but induced generalized stereotypies (apomorphine) or dystonia/parkinsonism (haloperidol), suppressing normal behaviour. The findings indicate that dopamine is involved in these presumably stress-induced (not drug-induced) stereotypies.

Effect of a cholinomimetic drug (RS 86) in tardive dyskinesia and drug-related parkinsonism.

RS 86, a specific muscarinic agonist, was evaluated in a blind, placebo-controlled, single-dose trial in 10 psychiatric patients with stable tardive dyskinesia (TD). RS 86, 0.5-4 mg orally, produced no significant effects in TD, although 4 mg caused a minimal aggravation in parkinsonism. Side effects of the highest dose (4 mg) included hypersalivation (eight patients), nausea (6), sweating (3), and vomiting (3). It is concluded that treatment with RS 86 and probably other cholinomimetics has no or only limited beneficial effect in TD.