In order to investigate the relationship between the immune apparatus and the hypothalamic–pituitary–adrenal (HPA)-axis activity in depressed patients, we measured in vitro lymphocyte responses to the mitogens Phytohaemagglutinin (PHA), Pokeweed (PWM) and Concanavalin A (Con A) and 8 a.m. baseline cortisol values in plasma, free cortisol excretion in 24 h urine (UFC), basal and post-dexamethasone βendorphin values. Major depressed patients with melancholia/psychotic features exhibited a significantly lower mitogen-induced blast transformation as compared to minor and simple major depressed patients. The lymphocyte responses to the three mitogens were significantly inversely related to baseline cortisol values and postdexamethasone β-endorphin values. The proliferative capacity of lymphocytes to stimulation with PHA and PWM was significantly and positively related to UFC excretion. Up to 45% of the variance in the immune responses to the mitogens was explained by the baseline cortisol, post-dexamethasone β-endorphin and UFC values.

This review of the literature suggests that antipsychotic drug response is determined by dopamine (DA) turnover and norepinephrine (NE) activity prior to treatment. The data suggest that NE modulates the DA system. Drug-free psychotic patients with relatively increased DA and NE activity, including release, are more likely to be treatment responsive, while patients who show evidence of enhanced DA and NE activity during treatment with antipsychotic drugs are likely to relapse soon after neuroleptic withdrawal. Basal release of DA and NE is decreased and associated with residual positive and negative symptoms. Improvement during neuroleptic treatment is associated with decreases in DA and NE phasic or stimulus induced release. The variable response to antipsychotic drugs is most likely to be a result of dysregulated DA and NE release, i.e. under state-dependent control, rather than evidence of a heterogeneous aetiology. Because catecholamines regulate gain, signal-to-noise ratio and gating in the brain, this model allows for environmental factors to interact with biochemical state and drug treatment. The author proposes that impaired homeostasis of NE and DA in schizophrenia causes instability in NE and DA neuronal firing and release, presumably related to mechanisms down-stream from the receptors, such as G proteins. This instability of catecholamine release may explain the observed variability in clinical states and drug response in schizophrenia.

The hypothesis is advanced that the psychological stance which patients adopt in response to cancer can, in some cases, influence the course of their disease. This hypothesis is examined in the light of the author's 15-year follow-up study of women with early breast cancer and of other pertinent studies. The available evidence supports the hypothesis in respect of certain earlystage non-metastatic cancers.

The T1 relaxation time of the basal ganglia (putamen, globus pallidus and head of caudate) and of the frontoparietal centrum semiovale was compared between 49 schizophrenic patients and 36 healthy controls. Previous reports of increased T1 time in the basal ganglia were not confirmed, and group differences were not detected within the white matter. Within patients T1 values could not be related to tardive dyskinesia or other clinical features. Normal variation seen in basal ganglia T1 times is described for the first time: lowest values occur in the globus pallidus and highest in the caudate, and values within the putamen increase rostrally.

The possible relationship between psychological responses among breast cancer patients and discase outcome continues to be an area of controversy and debate. Two parallel findings are reported separately in the literature: first, that emotional control is more common among women with breast cancer than in women with benign breast disease or in healthy controls and second, that a helpless attitude towards the disease is related to a poor prognosis.

These previously unrelated psychological responses are examined here in a group of women (N = 359) with early stage breast cancer, who were seen one to three months after diagnosis. The relationships between emotional control, adjustment to cancer and psychological morbidity were examined. Prevalence levels of 16 and 6% were observed for anxiety and depression respectively, which are lower than reported more generally in the literature. The results indicated a highly significant association between scores for the tendency to control emotional reactions and a fatalistic attitude toward cancer. A significant association was observed between anger control and a helpless attitude. Psychological morbidity was also linked to type of adjustment to cancer. The data are interpreted in terms of a process model of psychological responses which suggests that emotional control (an important component of the Type C behaviour pattern) fatalism, helplessness and psychological morbidity are linked.

A standardized, reliable means of assessing CT attenuation numbers in the centrum semiovale and surrounding grey matter was developed. This was applied to cranial CT scans of 60 normal controls (36 aged > 60 years), 25 elderly patients with major depression (14 of whom had the dementia syndrome of depression), and 10 patients with Alzheimer's disease (AD). Subjects received neuropsychological evaluation.

Centrum semiovale (CSO) CT attenuation numbers decreased with increasing age for both white and grey matter. White matter attenuation values best discriminated elderly controls from the three patient groups. Both white and grey matter CSO attenuation values correlated with performance on a number of cognitive tasks.

Despite increasing knowledge of the neurochemical bases of the action of the tricyclic drugs, little is known about the sequence of psychological effects which precede recovery in drug-responsive patients. This research was aimed at identifying the specific behavioural effects associated with the therapeutic action of amitriptyline in depression. The design involved measurement (post-hoc) of weekly changes in a severely depressed placebo-resistant group who recovered with drug treatment, compared with a group of similar patients treated for the equivalent four weeks, who showed minimal to no clinical response. The research strategy, in accordance with a dose–response paradigm, was to determine which of the early changes in emotion and behaviour found in treatment responders were systematically associated with plasma concentrations of amitriptyline or its major metabolite. Amitriptyline was found to act within seven days on the components of anxiety and on hostility in the responders, and on sleep disorder in all patients. After 12 to 14 days of treatment these effects increased, with improvements in other significant components distinguishing the responders from the non-responders. At the 12th to 14th treatment days when a steady state concentration of drug in plasma was approached, reductions in anxiety and hostility and in certain somatic components correlated significantly with plasma concentrations of amitriptyline. Implications of the findings for clarifying the specificity of clinical actions of the tricyclic drugs, and for understanding the psychobiological dynamics underlying rapid drug-induced recovery in depression, were explored.

The relationships between depression, anxiety and positive and negative symptoms of schizophrenia were examined in a study of 95 schizophrenic patients who were receiving out-patient care. Various measures of depression and anxiety showed a pattern of interrelationships which suggested that they were measuring a general state of dysphoria rather than separate dimensions of anxiety and depression. Dysphoria was found to be more reliably related to level of positive symptomatology than to negative symptoms.

Two hundred and sixty case reports of misidentification syndromes were evaluated. One hundred and seventy-four patients had a Capgras syndrome misidentifying other persons, 18 a Fregoli syndrome, 11 intermetamorphosis, 17 reduplicative paramnesia and the rest had other forms or combinations of mistaken identification. Schizophrenia (127 cases), mostly of paranoid type, affective disorder (29), and organic mental syndromes including dementia (46) were the most common diagnoses in patients who misidentified others or themselves. The patients with reduplicative paramnesia more frequently suffered from head trauma or cerebral infarction and showed more features of right hemisphere lesions on neuropsychological testing or CT scan than the patients with other misidentification syndromes. Forty-one case-reports implicated underlying medical conditions. Forty-six of the patients were reported to show violent behavioaur.

The misidentification of persons can be a manifestation of any organic or functional psychosis, but the misidentification of place is frequently associated with neurological diseases, predominantly of the right hemisphere. Misidentification syndromes show a great degree of overlap and do not represent distinctive syndromes nor can they be regarded as an expression of a particular disorder. These patients deserve special diagnostic and therapeutic attention because of the possible underlying disorders and their potentially dangerous behavioura.

We studied a series of twins systematically ascertained through 214 probands (84 monozygotic, 130 dizygotic) who had had one or more episodes of hospital-treated major depression. A variety of definitions of depression were applied to the co-twins all of which resulted in (a) markedly higher rates of disorder than are found in the general population, (b) significantly higher monozygotic than dizygotic concordance. The results of applying a simple additive model in which depression is considered as a threshold trait suggested that both genetic factors and shared family environment make substantial and significant contributions to the familiality of depression.

The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has been implicated in the pathophysiology of depression. Therefore, we examined cerebrospinal fluid (CSF) levels of GABA in depressed patients (N = 25) and normal controls (N = 20). There was no significant difference between the groups. However, among the depressed patients the subgroup of unipolar melancholic patients (N = 13) had significantly lower CSF levels of GABA than the rest of the depressed patients (N = 12). There was no significant difference for CSF levels of GABA between depressed patients who were (N = 14) or were not (N = 11) cortisol non-suppressors. It was of interest that among the controls there was a significant negative correlation between CSF levels of GABA and CSF levels of norepinephrine.

This study reports the cognitive abnormalities of a group of 58 patients with definite multiple sclerosis (MS). The psychometric functions measured were: ‘IQ deficit’, verbal and visual memory, abstracting ability, visual and auditory attention and naming ability. The presence of brain pathology was investigated using magnetic resonance imaging (MRI). A group of 46 physically disabled controls without significant brain disease was used for comparison. Normative MRI data were obtained from a groulp of 40 normal volunteers. The psychometric performance of the MS group was compared to the previously reported findings in patients with clinically isolated syndromes.

MS patients had widespread cognitive deficits sparing naming ability and affecting verbal memory less severely than other intellectual functions. The overall performance on psychometric tests was related to the severity of the MRI abnormalities and to the duration of the illness, but was not significantly influenced by the presence of psychiatric morbidity or the degree of physical disability. Patients with clinically isolated syndromes occupied an intermediate position between MS patients and disabled controls in terms cognitive and MRI abnormalities.

A whole population cohort of 157 patients with idiopathic Parkinsonism, most of whom had previously been clinically examined by Mutch (1986 a), were assessed to determine prevalence figures for dementia and examine the relationship between dementia, cognitive impairment and Parkinsonian signs. Dementia according to DSM-III-R criteria was diagnosed in 23·3% of all patients (95% confidence interval: 17·1 to 32·4%). Dementia and cognitive impairment were associated with overall measures of Parkinsonian impairment and rigidity, but not tremor, even after controlling for age, sex and education.

The psychiatric status of patients with chronic fatigue syndrome (N = 34) and muscle disease (N = 24) attending a general medical clinic was studied. Among fatigue patients 14 (41·2%) were cases and a further 9 (26·5%) were subcases of psychiatric disorder as defined by CATEGO. A variety of diagnoses was found. Significantly fewer of the muscle patients had a psychiatric disorder with 3 (12·5%) being cases and 1 (4%) a subcase. The relative risk of psychiatric disorder in patients with chronic fatigue syndrome compared to patients with muscle disease was 3·3:1.

This study examines data on self-report coping behaviour, life events and symptoms of anxiety and depression in a general population sample of 827 female twin pairs. Factor analysis identified three almost uncorrelated coping factors: turning to others; problem solving; and denial. Turning to others and problem solving were negatively and denial was positively related to levels of anxiety and depression. Turning to others and problem solving buffered the depressogenic and anxiogenic effects of stressful life events, while denial exacerbated the anxiogenic effects of life events. Structural equation model-fitting indicated that twin resemblance in turning to others and problem solving could be explained entirely by genetic factors with an estimated heritability of 30 and 31%, respectively. For denial, twin resemblance could be best explained by familial–environmental factors accounting for 19% of the total variation. Genes may affect the vulnerability to psychiatric disorders in part by influencing coping behaviour.

The performance of 47 patients with Parkinson's disease on a battery of tests of cognition, motor function, disability and mood was compared with the performance of 47 healthy control subjects who were matched to the patients on the basis of age, sex and pre-morbid IQ. An increased prevalence of impairment over a range of cognitive functions was observed in the Parkinson's disease patients as compared with their matched controls. The differences between the Parkinson's disease patients and controls could not be accounted for by factors such as depressed mood, effects of medication or motor impairment. Our findings are discussed in relation to the methodology of previous studies in this area and to the need for a comprehensive clinico-pathological longitudinal study.

Seventeen patients with Parkinson's disease which was markedly asymmetric and worse on the right side of the body (RHP) were compared with 13 patients whose signs were worse on the left (LHP). The two groups of patients were well matched for age, duration of symptoms, disability, overall severity of signs, and medication.

The mean scores on ratings of depression, using both a self-rating scale and semi-structured interview rating, were almost twice as great in the LHP group. The LHP group also had significantly more symptoms of anxiety. The prevalence of clinically significant psychopathology was increased about five fold in the LHP group compared with the RHP group.

There was a close correlation between anxiety and depressive symptoms. The depression experienced by the patients was ‘atypical’, with relatively little anhedonia and evidence of a negative view of self, and prominent symptoms of anxiety. The best predictor of symptoms of depression and anxiety was a measure of social support and stress. They also correlated with the overall severity of Parkinson's disease.

This study aimed to investigate the psychological characteristics of chronic fatigue syndrome (CFS: Holmes et al. 1988). A battery of psychometric instruments comprising the General Health Questionnaire (GHQ), the Beck Depression Inventory (BDI), the Minnesota Multiphasic Personality Inventory (MMPI) and the Lazarus Ways of Coping (WoC) inventory, was administered to a sample of clinically-defined CFS sufferers (N = 58), to a comparison group of chronic pain (CP) patients (N = 81) and to a group of healthy controls matched for sex and age with the CFS sample (N = 104). Considerable overlap was found between CFS and CP patients at the level of both physical and psychological symptoms. This raises the possibility that CFS sufferers are a sub-population of CP patients. However, while there was some commonality between CFS and CP patients in terms of personality traits, particularly the MMPI ‘neurotic triad’ (hypochondriasis, depression and hysteria), CFS patients showed more deviant personality traits reflecting raised levels on the first MMPI factor, emotionality. Moreover, results were not consistent with the raised emotionality being a reaction to the illness, but rather were consistent with the hypothesis that emotionality is a predisposing factor for CFS. The majority of CFS patients fell within four personality types, each characterized by the two highest MMPI scale scores. One type (N = 20) reported a lack of psychological symptoms or emotional disturbance contrary to the overall trend for the CFS sample. This group conformed to the ICD-10 classification of neurasthenia.

Data from the 1981 East Baltimore Mental Health Survey were used to examine the relationship between cognitive impairment and psychiatric diagnosis in an adult population. The Mini-Mental State Examination was administered to 3841 household respondents and a subset of 810 received psychiatric evaluations. Of the 810, 23% were found to be cognitively impaired. Over one-third of those with cognitive impairment, however, did not meet DSM-III criteria for a psychiatric diagnosis. Education, geographical background, race and neurological status were predictive of cognitive performance. There was no linear effect of age on cognitive performance with disease status and education controlled. In addition to their cognitive impairment these individuals, who ranged in age from 19 to 89, were found to have significant functional disabilities. Cognitive performance itself, along with physical and emptional health, predicted total functional disability.

Five operational methods for clinical diagnosis of mild dementia were compared to find out their diagnostic concordance when applied to a single group of seventy-five subjects. The clinical validity of the diagnoses was assessed in terms of their capacity to predict continued cognitive deterioration over three years after diagnosis and their capacity to reject the diagnostic influence of ‘non-dementia’ factors (that is, the cognitive consequences of depression, poor intellect, limited education and non-neurological physical illness). By all criteria of clinical validity the diagnostic methods for mild dementia performed poorly. Kappas measuring agreement between methods averaged only 0·15 and up to 57% of diagnostic deviance was explained by ‘non-dementia’ factors. Prediction of continued deterioration was poor, with a false positive rate which was too high for the diagnoses to be clinically usable. By no criterion of validity did the diagnostic methods exceed the performance of a clinician's judgement of the presence of pathological cognitive impairment or diagnosis by a cutpoint on the Mini-Mental State Examination.