The effects upon regional brain function of infusing either saline or clonidine (1·5μg/kg) has been examined in 18 patients with alcoholic Korsakoff's psychosis using 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO or 99mTc-Exametazime) and Single Photon Emission Tomography (SPET or SPECT). The hypothesis tested was that frontal lobe function would be increased by adrenoceptor stimulation. This was confirmed by an increase in the uptake of 99mTc-Exametazime into anterior cingulate regions of the frontal lobes. Patients were scanned before and after saline or clonidine infusion during performance of a verbal fluency task. There was a significantly increased performance of verbal fluency in patients given clonidine. This effect was variable and could not be unequivocably distinguished from increases in performance in the saline treated group. Nevertheless, the increase in neuropsychological performance was also correlated with increased function in left dorsolateral frontal cortex within the clonidine treated group. An exploratory examination of other brain areas suggested that relative increases in posterior cingulate cortex and changes in the symmetry of function within the thalamus may also be produced by acute infusion of clonidine in Korsakoff patients. The findings support the idea that adrenergic mechanisms may modulate cognitive performance by actions on attentional systems within the brain. These appear to be located primarily within limbic cortex. It is, of course, notable that this can occur in patients with profound and disabling amnesia.

The rate of DSM-III schizotypal personality traits was evaluated in three groups of adolescent offspring (ages 15–21), defined by the psychiatric diagnosis of their parents. Parental diagnoses included schizophrenic disorder (40 adolescents), affective disorder (35 adolescents), and ‘no psychiatric disorder’ (normal controls) parents (82 adolescents). The presence of the eight component features of schizotypal personality disorder was assessed from video-taped semi-structured psychiatric interviews, subsequently rated by trained psychiatrists, blind to the parental psychiatric status of the subjects. The effect of age, sex, and social class on the pattern of prevalence results was examined.

The expected specificity of DSM-III schizotypal personality traits to schizophrenia was not supported by the prevalence pattern of the traits. Rates of 2 or more, 3 or more, and 4 or more schizotypal personality features were highest in the parental psychiatric groups. The rates of schizotypal personality traits in adolescent offspring of affective disorder parents were as high as those previously reported for relatives of schizophrenic disorder probands.

Plasma amitriptyline and nortriptyline concentrations were measured in a group of five adult subjects who each received two different dosage regimes of amitriptyline (Tryptizol) for 14 day periods—namely, 25 mg three times daily and 75 mg once nightly. Mean steady-state plasma concentrations during the two dosage regimes were in close accord. The daily variation in drugplasma concentrations were only minimal during the thrice daily dosage regime but during the once nightly dosage regime there was an average decline in total drug plasma concentrations (amitriptyline plus nortriptyline) of about 30%. It was concluded that antidepressant medication with amitriptyline using a single nightly dose schedule might be more reliably taken by patients without there being any significant reduction in therapeutic efficacy.

Urinary excretion of neopterins and biopterins was measured in 23 patients with severe depression before and after receiving electroconvulsive therapy (ECT) and 26 healthy control subjects. Patients with psychotic depression and those responding to ECT had neopterin:biopterin (N:B) ratio significantly higher than controls before commencing ECT and positive therapeutic response was associated with reduction of N:B ratio towards control values. As a raised N:B ratio implies failure to convert neopterin to biopterin it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive disorders. The N:B ratio may be a marker for certain depressive subtypes and response to ECT.

Background. Conflicting results have been reported in previous association studies of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR), seasonal affective disorder (SAD) and seasonality (seasonal variations in mood and behaviour). The aim of this study was to test for association in new case–control and population-based materials, and to perform a combined analysis of all published studies of 5-HTTLPR and SAD.

Method. One hundred and forty-seven new SAD cases and 115 controls were genotyped for 5-HTTLPR and in total 464 patients and 414 controls were included in the pooled analysis. In addition, 226 individuals selected for unusually high or low seasonality scores from a population based material and 46 patients with non-seasonal depression were analysed. Different genetic models were tested and seasonality was analysed both as a qualitative (high v. low) and as a quantitative trait in the different sample sets.

Results. No association between 5-HTTLPR and SAD was found in the new case–control material, in the combined analysis of all samples, or when only including 316 patients with controls (N=298) selected for low seasonality. A difference was detected between the population based high and low seasonality groups, when assuming a recessive effect of the short allele (20% and 10% short allele homozygotes, respectively, OR (95% CI): 2·24 (1·03–4·91)). Quantitative analysis of seasonality revealed no association with 5-HTTLPR in any sample set.

Conclusions. These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.

Background. Depression is a highly prevalent, often recurring or persistent disorder. The majority of patients are initially seen and treated in primary care. Effective treatments are available, but possibilities for providing adequate follow-up care are often limited in this setting. This study assesses the effectiveness of primary-care-based enhanced treatment modalities on short-term patient outcomes.

Method. In a randomized controlled trial we evaluated a psycho-educational self-management intervention. We included 267 adult patients meeting criteria for a DSM-IV diagnosis of major depressive disorder, assessed by a structured psychiatric interview. Patients were randomly assigned to: the Depression Recurrence Prevention (DRP) program (n=112); a combination of the DRP program with psychiatric consultation (PC+DRP, n=39); a combination with brief cognitive behavior therapy (CBT+DRP, n=44); and care as usual (CAU, n=72). Follow-up assessments were made at 3 months (response 90%) and 6 months (85%).

Results. Patient acceptance of enhanced care was good. The mean duration of the index episode was 11 weeks (S.D.=9·78) and similar in CAU and enhanced care. Recovery rate after 6 months was 67% overall; 17% of all participants remained depressed for the entire 6-month period.

Conclusion. Enhanced care did not result in better short-term outcomes. We found no evidence that the DRP program was more effective than CAU and no indications for added beneficial effects of either the psychiatric evaluation or the CBT treatment to the basic format of the DRP program. Observed depression treatment rates in CAU were high.

Background. It is not known if a subject's characteristic level of self-rated depression symptoms index their genetic or environmental liability to major depressive disorder when measurement error and other occasion-specific influences are taken into account.

Method. Monozygotic (N = 408) and dizygotic (N = 295) adult female twin pairs from a population-based registry were surveyed twice with an average follow-up interval of 61 months. At each occasion subjects completed a structured clinical interview (SCID) to assess lifetime history of major depression and the subject-rated Symptom Check List (SCL) to assess current level of depressive symptomatology. A bivariate measurement model was used to estimate the genetic and environmental correlations between liability to reliably diagnosed lifetime history of major depression and the characteristic or temporally stable SCL depression score.

Results. The genetic and non-familial environmental correlation between liability to reliably diagnosed major depression and the characteristic level of SCL depression symptoms (and the proportion of variance shared between measures) is +0·70 and +0·24 respectively.

Conclusions. When allowance is made for diagnostic unreliability and temporal fluctuations in the level of subject-rated symptoms, 70% of the variance in genetic risk factors and 24% of the variance in environmental risk factors is shared by a diagnosis of lifetime major depression and total SCL depression symptom score. SCL depression scores may therefore be a useful screening measure for many of the genetic risk factors which influence liability to major depression.

The question addressed to in this paper is whether severely mentally ill patients are treated differently in a community mental health service without the back-up of a mental hospital (South-Verona, Italy) compared with an institution-based system in which mental hospitals, although highly modernized, are still predominant (Groningen, The Netherlands). Using the psychiatric case-registers in both areas, the patterns of care in 2 years of follow-up of schizophrenic patients were constructed. Survival analysis was used to analyse in-, day- and out-patient episodes of care. Three-quarters of the Groningen and half of the South-Verona patients experienced at least one episode of hospitalization; 20% of the Groningen and 5% of the South-Verona patients were long-stay patients at the end of the observation period. The South-Verona patients had more episodes of in-patient and especially of day-patient and out-patient care. Cox's regression showed that the duration of episodes controlled for the history of events and sociodemographic characteristics, was significantly shorter in South-Verona. One of the main conclusion was that hospitalizations for the severely mental ill are also needed in a community-based system of care, supporting the assumption of a ‘bed-rock’ of mental illness. However, the South-Verona community mental health service seems to be able to reduce the duration of hospitalizations considerably.

Background. Despite the need for rational allocation of resources and cooperation between different treatment settings, clinical differences in patients with major depressive disorder (MDD) between primary and psychiatric care remain obscure. We investigated these differences in representative patient populations from primary care versus secondary level psychiatric care in the city of Vantaa, Finland.

Method. We compared MDD patients from primary care in the Vantaa Primary Care Depression Study (PC-VDS) (n=79) with psychiatric out-patients (n=223) and in-patients (n=46) in the Vantaa Depression Study (VDS). DSM-IV diagnoses were assigned by the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I in PC-VDS) or Schedules for Clinical Assessment in Neuropsychiatry (SCAN in VDS), and SCID-II interviews. Comparable information was collected on depression severity, Axis I and II co-morbidity, suicidal behaviour, preceding clinical course, and attitudes towards and pathways to treatment.

Results. Prevalence of psychotic subtype and severity of depression were highest among in-patients, but otherwise few clinical differences between psychiatric and primary care patients were detected. Suicide attempts, alcohol dependence, and cluster A personality disorder were associated with treatment in psychiatric care, whereas cluster B personality disorder was associated with primary care treatment. Patients' choice of the initial point of contact for current depressive symptoms seemed to be independent of prior clinical history or attitude towards treatment.

Conclusions. Severe, suicidal and psychotic depression cluster in psychiatric in-patient settings, as expected. However, MDD patients in primary care or psychiatric out-patient settings may not differ markedly in their clinical characteristics. This apparent blurring of boundaries between treatment settings calls for enhanced cooperation between settings, and clearer and more structured division of labour.

Background. The question of whether unipolar clinical depression differs categorically from limited depressive complaints has important implications for the disorder's assessment, treatment and research. This crucial issue has proven difficult to resolve, in part because many studies to date have relied on self-report measures or on clinically homogeneous samples. We therefore applied Meehl's taxometric method to a large, clinically heterogeneous sample, and examined the latent structure of depressive episodes using both self-report and structured clinical interview data.

Method. Data were derived from the Oregon Adolescent Depression Project, a large longitudinal community study. All analyses involved more than 1400 participants. MAXEIG (MAXimum EIGenvalue) and base rate estimation were performed separately for Beck Depression Inventory (BDI) items and for DSM-IV-based major depressive episode (MDE) symptoms.

Results. MAXEIG analyses of the BDI and MDE indicator sets appeared to converge on a taxonic structure for unipolar depression. Base rate estimates overall implied a latent depressive episode class that occurs more frequently than diagnosable MDEs but less frequently than persistent depressed or anhedonic mood.

Conclusions. These findings provide tentative support for a categorical conceptualization and make it very clear that the continuity controversy regarding unipolar depression has not yet been decided in favor of dimensionality. To reconcile the conflicting reports to date, several data analytic and sampling issues need to be explored systematically.

A comparative study of diabetics with autonomic neuropathy (N = 13) as against non-neuropathic diabetics (N = 16) and healthy control persons (N = 20) was carried out with respect to heart rate both at rest and under stress, frequency of cardiac arrhythmias in a 24-h ECG and accuracy of heartbeat and arrhythmia perception. In the subjects with diabetic autonomic neuropathy, the spontaneous variability and stress-induced reactivity of the heart rate as well as the number of tachycardic episodes were reduced, whereas the frequency of ventricular extrasystoles was somewhat increased. Impaired heartbeat perception and a complete loss of perception of arrhythmias as a consequence of neuropathic deafferentation could be demonstrated. Cardiac perception disorders also play a vital role in other clinical problems, e.g. silent myocardial infarction and lack of awareness of hypoglycaemia in diabetes mellitus.