Although calcification of the basal ganglia is a relatively common and asymptomatic finding on cranial computed tomography, familial idiopathic calcification of the basal ganglia (ICBG) is a rare disorder with neurological and behavioural manifestations. Attention has recently been drawn to the frequency with which cases are diagnosed as schizophrenic (Cummings et al. 1983; Lowenthal, 1986; Davison, 1987). We report a family in which a mother and son have ICBG, but while the son has a paranoid schizophrenia and intellectual deterioration, the mother shows no psychiatric illness. A review of the relevant literature suggests that psychosis is not as common as usually supposed, and may only be coincidentally associated with familial ICBG. Moreover, we find little convincing evidence that familial ICBG is an independent entity; instead, and in agreement with earlier authorities (Bruyn et al. 1964), we argue that published accounts and our own cases provide evidence that the condition is related to pseudo-hypoparathyroidism (PHP) and, therefore, may be due to a defect in a guanine nucleotide binding protein.

Three hundred and twenty-six consecutively admitted patients with functional psychotic illnesses to which no diagnostic classification had been applied were followed up after 2·5 years. They were examined in social, clinical and psychological terms and the CATEGO programme and DSM-III criteria were applied to data concerning the index episode to derive diagnostic classifications. The deterioration in occupational functioning and the hospital careers of patients with diagnostic classifications of schizophrenia were worse than those in the other groups and positive and negative features were also more severe in patients with a classification of schizophrenia. By contrast, no differences in psychological test performance were found between the groups based upon diagnostic classification. Impaired psychological test performance was found and it was strongly related to concurrent mental state abnormalities, particularly negative symptoms. It is concluded that the diagnostic classifications used were of limited value in predicting outcome in functional psychosis.

Seven (21%) of 34 patients with a severe DSM-III diagnosis of major depression had red-cell folate levels below 150 ng/ml. This subgroup with folate deficiency had significantly lower CSF 5-hydroxyindoleacetic acid (5HIAA) compared to neurological controls. For all depressed patients red-cell folate was significantly correlated with CSF 5HIAA and homovanillic acid (HVA). CSF tetrahydrobiopterin (BH4) was significantly correlated with CSF 5HIAA and HVA and red-cell folate. Our observations provide further evidence of the links between folate, biopterin and monoamine metabolism in depression.

The distribution of cholecystokinin binding sites has been visualized and quantified by quantitative autoradiography in the human hippocampus from post-mortem brains of 11 controls and 11 schizophrenics. CCK receptors were localized to subiculum and parahippocampal gyrus. In the cortical areas there was a particularly dense lamination of receptors.

In the schizophrenic material a similar overall pattern was seen, but there were significant losses of receptors in CA1 subiculum and cortex. These findings confirm the distribution of CCK receptors in the retrohippocampal areas in man and also provide further support for earlier homogenate studies which have also shown a loss of CCK binding sites in schizophrenia. This effect was localized primarily to parahippocampal gyrus suggesting that CCK plays some role in the genesis of developmental abnormalities in this region.

The question of the relationship between anxiety and depression remains to be solved. The fact that clinical pictures show substantial overlap makes it difficult, using conventional instruments, to distinguish between the co-occurrence of anxiety and depression and overlap in definitions and measurement of the two syndromes. This calls for the construction of scales which exclude symptoms common to both syndromes and incorporate symptoms specific only to anxiety or only to depression; i.e. scales with maximum discriminant validity. This article describes the construction of two such scales based on PSE symptoms; a prototypical anxiety scale and a prototypical depression scale. In a sample of 134 non-psychotic psychiatric out-patients these scales show good reliability and validity, both as a measure of severity and as a screening device. Compared to the Hamilton anxiety and depression scales (HARS and HRSD), the correlation between the prototypical anxiety and depression scales is low.

Depressive symptoms have been reported in patients with mild to moderate Alzheimer's disease (AD). Recent evidence suggests that a noradrenergic deficit originating from neuronal degeneration in brainstem nuclei may represent an organic correlate of these disturbances. We examined the neuropathological changes in the locus coeruleus (LC), substantia nigra (SN), basal nucleus of Meynert and cortex of 52 patients (12 male, 40 female, mean age 83·2 ± 6·4 years) with pathologically verified AD. Fourteen patients (1 male, 13 female) showed signs of depression. The majority of these patients suffered from severe physical disability or sensory impairment and developed persistent delusions, but had less cognitive impairment. Neuronal counts in the LC were significantly lower than in the 38 patients without depression (36·9 ± 14 ·0; 51·4 ± 28·0 neuromelaninpigmented cells per section per nucleus; F = 3·4, df = 1, 50, P = 0·04). Neuron counts were higher in the basal nucleus of Meynert in depressed AD patients and there were no differences of the neuron numbers in the SN. Depression (main effect; F = 4·5, P = 0·04) contributed significantly to the variance of neuronal counts in the LC, even when covarying for gender, age of onset, cognitive impairment and cortical Alzheimer pathology. The observed disproportionate loss of noradrenergic and cholinergic neurons in the LC and basal nucleus of Meynert may represent an important organic substrate of depression in AD.

Several studies have reported a suppressed immune function (e.g. blast transformation) during depression. In an attempt to define the cellular basis of the reported immune disorders, the present study investigates the leukocyte cell subset profile of minor, simple major, and melancholic depressives, versus normal controls. We have counted the number of white blood cells (WBC) lymphocytes, monocytes, and granulocytes, while the number of lymphocyte (sub)populations has been identified by phenotype, using monoclonal antibody staining in conjunction with flow cytometry. The following cell surface antigens were determined: CD3+ (pan T), CD19+ (pan B), CD4+ (T helper/inducer), CD8+ (T suppressor/cytotoxic), CD4+CD45RA (T-memory cells), CD4+CD45RA+ (T-virgin cells), surface Ig, class II MHC HLA-DR, and CD25+ (IL-2 receptor). By means of pattern recognition methods, we established distinct immunological changes in minor and simple major depressed and in melancholic patients, setting them apart from the reference population. Depression, per se, is characterized by a higher number of WBC, monocytes, class II MHC HLA-DR, and memory T cells. Minor and simple major depressives exhibited an increased T helper/suppressor ratio. Increased numbers of IL-2 receptor bearing cells are a hallmark for major depression. Melancholics showed an increased number of pan T, pan B and T suppressor/cytotoxic cells. It was concluded that the established immune cell profile of depressed patients may point towards the existence of a systemic immune activation during that illness.

The schizophrenic patient's early psychological response to neuroleptic treatment has been demonstrated to be a significant predictor of treatment response. The validity of the construct of subjective response is evaluated by comparison of two measures. Fifty-five recently admitted and unmedicated schizophrenic patients were randomly allocated to chlorpromazine or haloperidol. Subjective responses at 24 and 48 hours as assessed by two different scales, the Van Putten & May scale and the self-administered Drug Attitude Inventory, were strongly correlated with outcome at three weeks. Early emergence of extrapyramidal symptoms was not related to subjective response, but dysphoric patients had a greater incidence of EPS by the end of treatment than did non-dysphoric patients. The two measures showed high concordance in identification of early drug dysphoria.

Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P < 0·05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P < 0·05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.

The aim of the study is to provide (i) a standardized procedure for a Cancellation Test of Digits, designed to assess in the visual modality selective attention deficits in patients with Alzheimer's disease, and (ii) a detailed analysis of how patients cope with it.

Age-, education-, and sex-adjusted normative scores earned by 352 healthy controls are set forth, as well as data yielded by the Digit Cancellation Test in 74 Alzheimer patients, in 26 patients with a CT-assessed frontal lobe lesion and in a group of 24 healthy subjects urged to perform the task with a shortened time-constraint. Findings include discriminant power of Alzheimer patients versus healthy controls, sensitivity to cognitive evolution of the dementing process and analysis of errors. Attention data failed to supply psychometric support for the posterior-to-anterior algorithm of progressive cortical encroachment of Alzheimer's disease suggested by PET-findings.

Emphasis is put on methodological aspects of neuropsychological research on Alzheimer patients and on the analysis of processing components of the tests employed. Results are discussed in the light of the relationships between psychometric assessments and related functions, and underlying neuronal degeneration.

Theorists have extrapolated the cholinergic supersensitivity theory of affective disorder from a convincing and broad spectrum of clinical observation and research. This hypothesis is tested using a neuroendocrine probe approach with the challenge drug pyridostigmine, an indirect cholinergic agent thought to release growth hormone (GH) by decreasing inhibitory somatostatin tone. The consequent increments in plasma GH were considered to reflect central acetylcholine responsivity. Fifty-four volunteers were tested: 27 DSM-III-R major depressives (18 women and 9 men) and 27 age- and sex-matched healthy controls. Subjects were cannulated at 9.00 h following an overnight fast and two baseline samples were taken at 15 min intervals. Pyridostigmine 120 mg was administered orally and thereafter samples were taken at the time points +60, +90, +120 and +180 min. GH responses were significantly greater in depressives than controls and this effect was more marked for men than women. These results support the proposal that muscarinic upregulation and/or supersensitivity is associated with depression.

Schizophrenic subjects performed significantly worse on neuropsychological tests of frontal lobe function but not on tests of non-frontal lobe function when compared to a matched group of normal subjects. Correlations expected between frontal lobe neuropsychological test performance and negative symptoms were not found.

Ten healthy male subjects were treated for three weeks with (+)oxaprotiline, a selective inhibitor of noradrenaline (NA) uptake and with (−)oxaprotiline which does not inhibit NA uptake. Plasma melatonin concentrations were measured throughout the night at 0, 1, 7 and 21 days and were higher during treatment with (+)oxaprotiline than with (−)oxaprotiline for the entire three weeks of treatment. Since NA stimulates the production and secretion of melatonin, these results are consistent with a sustained increase in noradrenergic activity within the pineal, during 21 days of treatment with an effective NA uptake inhibitor.

Using the Scale for the Assessment of Negative Symptoms (SANS), affective blunting, alogia, and attentional impairment were assessed in 30 manic patients with chronic impairment of inter-episode instrumental functioning and 85 chronic schizophrenic patients. The schizophrenic patients had markedly higher ratings on all three negative symptom dimensions. When negative symptoms were examined categorically, no manic patient was rated to show prominent affective flattening or alogia. This relative specificity may not apply to attentional impairment which was rated as prominent in 17% of the manic patients and in 55% of the schizophrenic patients.

A genetic analysis of the co-occurrence of bulimia and major depression (MD) was performed on 1033 female twin pairs obtained from a population based register. Personal interviews were conducted and clinical diagnoses made according to DSM-III-R criteria.

Additive genes, but not family environment, are found to play an important aetiological role in both bulimia and MD. The genetic liabilities of the two disorders are correlated 0·456. While unique environmental factors account for around half of the variation in liability to both bulimia and MD, these risk factors appear to be unrelated, i.e., each disorder has its own set of unique environmental risk factors. Thus, the genetic liability of bulimia and MD is neither highly specific nor entirely nonspecific. There is some genetic correlation between the two disorders as well as some genetic and environmental risk factors unique to each disorder. Limitations and directions for future research are discussed.

The National Adult Reading Test (NART) is widely used in clinical and research settings to estimate pre-morbid intellectual levels. The validity of the NART in estimating pre-morbid ability in Alcoholic Korsakoff Syndrome (AKS) is examined in the present study. Twenty AKS subjects were compared with 40 healthy controls. The validity of the NART as a pre-morbid measure in AKS was examined using four methods. AKS subjects made more NART errors than controls, had lower NART predicted IQ than demographically predicted IQ, made more NART errors than predicted by demographic variables and demonstrated NART performance which correlated with degree of memory impairment. It is concluded that NART performance is detrimentally affected by the AKS and that estimating pre-morbid intellectual level in Korsakoff's psychosis using the NART may be invalid. Furthermore, it is postulated that the impaired ability to pronounce correctly irregular words in AKS may reflect a failure in cognitive ‘error checking’ which may represent a consequence of frontal lobe dysfunction.

More than a decade ago, a series of retrospective studies examined the concordance between proliferating definitions of severe psychiatric disorder. The European response has been a polydiagnostic one, which has attempted to maintain interest in a broad range of psychiatric phenomena in the psychoses. In North America a more convergent approach has emerged, resulting in a series of operational definitions evolving from one another, and a correspondingly limited capacity to allow alternative perspectives to co-exist. The present study uses a prospective design as well as recent improvements in the clinical validity of psychopathology assessment to re-evaluate the relationships between competing concepts of psychotic illness in a broad sample (N = 176) of recent-onset psychotic patients. In the schizophrenic group, concordance was predictably highest among recent North American ‘cousins’, and lowest among various historical concepts. There was a moderately high concordance between selected schizoaffective and atypical psychosis definitions, indicating that this component is an important area for further studies of descriptive validity. These interrelationships may be used as a starting point to explore latent classes underlying the phenomena of functional psychosis.

The aim of the study was to compare the clinical features and predisposing characteristics of patients with an early onset of bulimia nervosa with those with a more typical onset. Twenty-three cases of early onset bulimia nervosa (onset age 15 or below) were compared with 23 sex- and class-matched cases of typical onset (onset age 17 to 21) using a retrospective case–control design. No difference was found in eating symptomatology between the two groups. Deliberate self-harm was more frequent in the early onset group, and there was a trend towards more depression among their relatives. Inadequate parental control occurred more often in the early onset group, but other indicators of intrafamilial disturbance did not differ in the two groups. There was also a trend for the early onset group to be exposed to more cultural stress as a result of family migration. Early onset patients were found to have a higher loading on risk factors than typical onset patients.

Neuropsychological tests of frontal lobe functions were undertaken in 46 chronic schizophrenic patients who were also rated for movement disorders. Tardive dyskinesia was found to have significant associations with most of these psychological tests. The possible mechanisms are discussed within the context of known neostriatal psychological functions.

Recent reports have suggested that brain stem and cortical Lewy body formation may identify a neurodegenerative disorder in elderly demented individuals which accounts for up to 20% of cases of senile dementia coming to autopsy. Retrospective analysis of case notes of 21 autopsy patients with neuropathologically proven senile dementia of Lewy body type (SDLT) and 37 cases with neuropathologically proven Alzheimer's disease (AD) identified a characteristic clinical syndrome in SDLT. Fluctuating cognitive impairment; psychotic features including visual and auditory hallucinations, and paranoid delusions; depressive symptoms; falling and unexplained losses of consciousness were all seen significantly more often than in AD.

Over half of the SDLT patients in this series who were given neuroleptics in standard dose showed acute and often irreversible adverse reactions indicative of a neuroleptic sensitivity syndrome. The survival time of drug treated patients was reduced by 50%.

Operational criteria to aid in the clinical distinction between SDLT and AD patients are proposed and hypotheses regarding possible aetiology and treatment discussed.