Background. The number of antidepressant drugs available in the market has grown rapidly in the last few years. The present paper underlines some of the pre-clinical and clinical problems that call close attention from the regulatory authorities when approving new drugs.

Methods. We present here a review of the literature.

Results. A wide heterogeneity in the action of the various antidepressants precludes any single theory about the pathogenesis and therapy of depression. Antidepressant activity, in fact, may be achieved by acting on a number of different monoaminergic mechanisms. The variety in the neurochemical effects of antidepressants is not reflected in clinical trials, which tend to stereotypy. In many cases clinical trials aim at demonstrating equivalence rather than differences in efficacy. Regulatory authorities should, therefore, pay attention in accepting the equivalence of effects of a new drug in relation to a reference one: most clinical trials of new antidepressant drugs do not have the power to detect clinically relevant differences.

Conclusions. Unconventional new pre-clinical tests are needed to generate antidepressants with a different mechanism of action. Clinical studies are needed to promote objective comparative evaluation of the cost, benefits and toxic effects of new antidepressants.

Background. Compliance with referral for out-patient aftercare of psychiatric emergency patients is limited. This study investigated the efficacy of a combination of several referral strategies (fixed appointment, involvement of the family, presence of the aftercare person, motivational counselling) in increasing referral and treatment compliance of patients referred to the psychiatric emergency department of three general hospitals.

Methods. A randomized controlled design was used to assess the effect of this experimental condition on referral compliance and on continuation of aftercare treatment.

Results. A significant beneficial effect on compliance with the referral was found in two hospitals and a near-significant effect in the third. After 3 months of aftercare, the influence of the experimental procedure on adherence to therapy was still significant in two hospitals, but not in the third.

Conclusions. Helping the patient to attend an initial appointment can be achieved by a combination of practical and organizational arrangements.

Background. The aims of the present study were to examine serum activities of peptidases, i.e. prolyl endopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV), in patients with fibromyalgia and to examine the effects of subchronic treatment with sertraline on these variables.

Method. Serum PEP and DPP IV activity were measured in 28 normal volunteers and 21 fibromyalgia patients, classified according to the American College of Rheumatology criteria. Tenderness at tender points was evaluated by means of dolorimetry. Fibromyalgia patients had repeated measurements of serum PEP and DPP IV both before and after repeated administration of sertraline or placebo for 12 weeks.

Results. Patients with fibromyalgia had significantly lower serum PEP activity than normal volunteers. There were significantly negative correlations between serum PEP activity and severity of pressure hyperalgesia and the non-somatic, cognitive symptoms of the Hamilton Depression Rating Scale. Fibromyalgia patients with severe pressure hyperalgesia had significantly lower PEP activity than normal controls and fibromyalgia patients with less severe hyperalgesia. Fibromyalgia patients with severe non-somatic depressive symptoms had significantly lower serum PEP activity than normal volunteers. There were no significant changes in serum DPP IV activity in fibromyalgia. There were no significant effects of repeated administration of sertraline on serum PEP and DPP IV activity in patients with fibromyalgia.

Conclusions. The results show that fibromyalgia, and aberrant pain perception and depressive symptoms in fibromyalgia are related to lower serum PEP activity. It is hypothesized that lower serum PEP activity may play a role in the biophysiology of fibromyalgia through diminished inactivation of algesic and depression-related peptides.

Background. Previous studies of oculomotor dysfunction in schizophrenia have tended to concentrate on abnormalities of smooth pursuit eye tracking in chronic medicated patients. We report the results of a study of smooth pursuit, reflexive and antisaccade performance in drug naive and antipsychotic treated first-episode schizophrenic patients.

Methods. Smooth pursuit and saccadic eye movements were recorded in 36 first-episode schizophrenic patients and 36 controls matched for age and estimated IQ. The schizophrenic patients were divided into drug-naive (N=17) and antipsychotic treated groups (N=19).

Results. Smooth pursuit velocity gain was significantly lower than controls only in the drug-naive patients. The treated patients did not differ significantly from either the controls or the untreated group. In an antisaccade paradigm both treated and drug-naive schizophrenic patients demonstrated an increased number of errors, but only drug-naive patients also demonstrated an increased latency in initiating correct antisaccades.

Conclusions. These impairments are unlikely to be due to a generalized deficit in oculomotor function in the schizophrenic groups, as there were no differences between the groups in saccadic metrics on a reflexive saccade task. The results show that both smooth pursuit and saccadic abnormalities are present at the onset of schizophrenia and are integral to the disorder.

Background. We examined a group of subjects at familial risk of depression and explored the relationship between the perceptions of parents and a history of depression. We also investigated: (a) whether any difference in perceived parenting found between those with and without a past history of depression was an artefact of the depression; and (b) whether the relationship between parenting and depression was explained by neuroticism.

Method. We took a sample of first-degree relatives selected from a family study in depression and subdivided them by their history of mental illness on the SADS-L, into those: (a) without a history of mental illness (N=43); and (b) those who had fully recovered from an episode of RDC major depression (N=34). We compared the perceptions of parenting, as measured by the Parental Bonding Instrument (PBI), in these two groups having adjusted for the effect of neuroticism and subsyndromal depressive symptoms. We also had informants report on parenting of their siblings, the latter being subdivided into those with and without a past history of depression.

Results. Relatives with a past history of depression showed lower care scores for both mother and father combined compared with the never ill relatives. The presence of a history of depression was associated with a non-significant reduction in the self-report care scores compared to the siblings report. Vulnerable personality (as measured by high neuroticism) and low perceived care were both found to exert independent effects in discriminating between the scores of relatives with and without a history of depression and there was no interaction between them.

Conclusion. This study confirmed that low perceived parental care was associated with a past history of depression, that it was not entirely an artefact of having been depressed, and suggested that this association was partially independent of neuroticism.

Background. In the past it has been postulated that dysphoric emotions may be related to positive and/or negative symptoms in schizophrenia. The results of several recent studies have suggested that composite dysphoria indices are more strongly related to positive than negative symptoms. In the current study we use part correlation techniques to examine the possible unique contributions of two aspects of dysphoria – depression and anxiety – to three syndromes of symptoms (reality distortion, disorganization and psychomotor poverty) within schizophrenia.

Methods. Data were obtained from 60 patients with a DSM-III-R diagnosis of schizophrenia. Symptoms of schizophrenia were assessed using the SAPS and SANS and dysphoria was assessed using both self-report (BDI and BAI) and observer ratings (HRSD and HARS). Assessment of schizophrenia symptoms and ratings of depression and anxiety were completed by different observers. In addition, drug induced extrapyramidal side effects were rated.

Results. Part correlations showed that unique aspects of anxiety (particularly physiological arousal) were correlated with reality distortion while unique aspects of depression (including psychomotor slowing and loss of social interest) were related to psychomotor poverty. At least part of the latter relationship may be due to extrapyramidal side effects of neuroleptic medication.

Conclusions. Although there is considerable overlap between anxiety and depression, it appears that the unique arousing or activating aspects of anxiety are related to the experience of reality distortion symptoms in schizophrenia and the unique slowing and withdrawal aspects of depression are particularly related to psychomotor poverty. Possible reasons for these relationships are discussed.

Background. The gatekeeper function of the general practitioner (GP) in the pathway to specialized psychiatric services was investigated in this study, which is part of the Nordic Comparative Study on Sectorized Psychiatry. The question addressed in this paper is whether different sociodemographic and clinical factors as well as factors related to service utilization are associated with referral from the GP compared with self-referrals (including referrals from relatives).

Methods. The study comprised a total of 1413 consecutive patients, admitted during 1 year to five psychiatric centres in four Nordic countries. The centres included in this study were those that accepted non-medical referrals. Only new patients (not in contact with the service for at least 18 months) were included.

Results. Increasing age was the only sociodemographic factor significantly associated with referral by the GP. The clinical factors (psychosis, being totally new to psychiatry and being in need of in-patient treatment) and some treatment characteristics (planned out-patient treatment and involuntary in-patient treatment), were all significantly associated with referral by the GP. Some indication was found that self-referred patients have shorter episodes of care.

Conclusions. The findings were remarkably stable across the different centres indicating a general pattern. This study extends previous work on the role of GPs in the pathway to specialized psychiatric services and indicates that the GP has an important gatekeeper function for the most disabled patients.

Background. Self-report instruments assessing the DSM personality disorders are characterized by overdiagnosis due to their emphasis on the measurement of personality traits rather than the impairment and distress associated with the criteria.

Methods. The ADP-IV, a Dutch questionnaire, introduces an alternative assessment method: each test item assesses ‘Trait’ as well as ‘Distress/impairment’ characteristics of a DSM-IV criterion. This item format allows dimensional as well as categorical diagnostic evaluations. The present study explores the validity of the ADP-IV in a sample of 659 subjects of the Flemish population.

Results. The dimensional personality disorder subscales, measuring Trait characteristics, are internally consistent and display a good concurrent validity with the Wisconsin Personality Disorders Inventory. Factor analysis at the item-level resulted in 11 orthogonal factors, describing personality dimensions such as psychopathy, social anxiety and avoidance, negative affect and self-image. Factor analysis at the subscale-level identified two basic dimensions, reflecting hostile (DSM-IV Cluster B) and anxious (DSM-IV Cluster C) interpersonal attitudes. Categorical ADP-IV diagnoses are obtained using scoring algorithms, which emphasize the Trait or the Distress concepts in the diagnostic evaluation. Prevalences of ADP-IV diagnoses of any personality disorder according to these algorithms vary between 2·28 and 20·64%.

Conclusions. Although further research in clinical samples is required, the present results support the validity of the ADP-IV and the potential of the measurement of trait and distress characteristics as a method for assessing personality pathology.

Background. Attachment theory posits links between early experiences with parents, adult relationships and adult mental health, but does not specify whether these are independent, mediating, or moderating effects.

Methods. Associations of parent's behaviour on the Parental Bonding Instrument, adult attachment styles and three dimensions of mental health were investigated in a large sample of women and men.

Results. Men and women with secure styles recalled higher levels of care from both parents than those with fearful styles. Maternal and paternal control were more consistent predictors of increased distress for men than for women. Fearful and preoccupied adult styles were associated with higher levels of distress in both men and women. While adult styles had few mediating effects on the association of parental behaviour and mental health, interactions between the fearful style and parental variables suggested that this form of insecurity sometimes accentuated the impact of high parental care or low paternal control on mental health in both men and women; among women, however, the secure style seemed to buffer somewhat the negative effect of high parental control.

Conclusion. Although the amount of variance explained by either parental behaviour or adult styles was modest, patterns of moderating effects of adult styles on associations between parental behaviour and mental health suggested that both continuity and discontinuity principles can be applied to understanding these links.

Background. Research on the subject of insight has been hampered by difficulties in definition and reliable measurement.

Methods. We compared several rating scales to measure insight on a group of 33 psychotic patients as well as assessing patients' psychopathology, clinical characteristics and cognitive functioning.

Results. Most currently used scales showed a high degree of inter-correlation. Measures of insight related strongly to the presence of delusions; grandiosity (inversely), and depression (positively). Higher insight scores correlated with indices of treatment compliance and inversely with substance abuse. Measures of pre-morbid IQ and impaired executive functioning, including the Wisconsin Card Sorting Test were not associated with poor insight.

Conclusions. The study highlights aspects of psychopathology and clinical variables particularly related to insight and supports the continued use of standardized scales in further research in this area.

Background. Empirical evidence indicates that manipulations of attention may facilitate changes in cognition and stress symptoms in emotional disorder.

Methods. The present study reports the effects of Attention Training (ATT) in a brief case series of three patients with primary hypochondriasis using an A–B–A design.

Results. ATT produced clinically significant improvements in self-reported measures of affect, and illness-related behaviour and cognition. Treatment gains were maintained at 6 months follow-up assessments. Measures of body-focused attention indicated that the ATT procedure acted on attentional processes as intended.

Conclusions. The present case series extends the effects of ATT to problems of hypochondriasis. A number of studies now suggest that ATT is associated with a reduction in anxiety and negative beliefs across disorders of panic, social phobia and hypochondriasis. Controlled clinical trials are now required to establish firmly the effects of ATT as a component of cognitive therapy.

Background. Deterioration in school achievement may pre-date adult mental disorders. We studied the association between compulsory school performance and later onset hospital-treated psychiatric morbidity experienced by the Northern Finland 1966 Birth Cohort (N=11017) in adult life.

Methods. School performance was operationalized in two ways: school class level (in normal, i.e. age-appropriate class v. not in normal class, i.e. class below age level or in special school) at the age of 14, and marks for individual school subjects at the age of 16. School class level was ascertained by postal questionnaire and school marks from national application register. These were linked to data on psychiatric morbidity from the National Finnish Hospital Discharge Register. By the end of 1994 (between ages 16 and 28 years), a total of 383 subjects had psychiatric illness. DSM-III-R diagnoses were grouped into three categories: schizophrenia; other psychoses; and non-psychotic disorders. The remaining population with no psychiatric hospitalization served as a single comparison group. School class level and values of school marks in the three diagnostic categories were each compared with this comparison group, stratified by sex.

Results. In the comparison group 6·8% of boys and 3·4% of girls were not in their normal class. In all the diagnosis groups the proportions of those not in normal class were from 2 to 8 times higher than in the comparison group. A majority of those not in normal class and having psychiatric diagnosis were intellectually subnormal (IQ<85). Among adolescents who later developed non-psychotic disorders, means of school marks were lower (P<0·05, adjusted for social class and place of residence) than in the comparison group. Lower marks were not found in categories schizophrenia or other psychoses. Logistic regression analysis confirmed these findings after adjustment for confounding factors.

Conclusions. Not being in the normal class at age 14 predicted future hospital-treated disorders, but low school marks at age 16 predicted only non-psychotic disorders. These findings may be an early manifestation of the disorders themselves, or a marker of vulnerability or other risk factors. The mechanisms may differ between diagnoses.

Background. Few data are available regarding the impact of improved depression treatment on daily functioning and disability.

Methods. In two studies of more intensive depression treatment in primary care, patients initiating antidepressant treatment were randomly assigned to either usual care or to a collaborative management programme including patient education, on-site mental health treatment, adjustment of antidepressant medication, behavioural activation and monitoring of medication adherence. Assessments at baseline as well as 4 and 7 months included several measures of impairment, daily functioning and disability[ratio ]self-rated overall health, number of bodily pains, number of somatization symptoms, changes in work due to health, reduction in leisure activities due to health, number of disability days and number of restricted activity days.

Results. Average data from the 4- and 7-month assessments in both studies, intervention patients reported fewer somatic symptoms (OR 0·68, 95% CI 0·46, 0·99) and more favourable overall health (OR 0·50, 95% CI 0·28, 0·91). While intervention patients fared better on other measures of functional impairment and disability, none of these differences reached statistical significance.

Conclusions. More effective acute-phase depression treatment reduced somatic distress and improved self-rated overall health. The absence of a significant intervention effect on other disability measures may reflect the brief treatment and follow-up period and the influence of other individual and environmental factors on disability.

Background. A sentence verification task was developed to investigate semantic memory in schizophrenia.

Methods. The test consisted of three types of sentence (true, unlikely and nonsense) and seven different types of content (neutral, persecutory, grandiose, political, religious, relationships and somatic) representing common delusional themes present in schizophrenic patients. Sixty-three schizophrenic patients and 66 matched control subjects were asked to make true/false judgements to 143 sentences.

Results. Overall accuracy was similar across the two groups; sentences with some emotional themes and sentences of the unlikely type produced the most violations. Significant differences between the two subject groups were found specifically on nonsense sentences with persecutory and religious themes. Patients made significantly more incorrect responses (acceptance) to nonsense sentences that had an emotional content congruent with their delusional beliefs, past or present, and also on unlikely sentences (incorrect rejections) whose content was not congruent with their delusions. Further analysis of response bias in the patients showed, overall, that there were more incorrect rejections (a reflection of the large number of unlikely sentence errors) and more incorrect responses to sentences congruent with patients delusions. Furthermore, analysis of those patients currently experiencing delusions revealed more incorrect responses to sentences congruent with their delusional ideas compared with patients not currently deluded.

Conclusions. These findings are indicative of cognitive bias in schizophrenia towards certain emotional themes that may underlie illogical semantic connections and delusions.

Background. Cognitive models suggest that auditory hallucinations are experienced when mental events are misattributed to an external source; therefore, this study was designed to examine attributional biases in patients experiencing auditory hallucinations. The study also examined the role of metacognitive beliefs in the experience of auditory hallucinations, as some theories have implicated metacognition in the development and maintenance of auditory hallucinations.

Methods. Fifteen participants with a diagnosis of schizophrenia experiencing auditory hallucinations were compared with 15 non-hallucinating schizophrenics and 15 non-psychiatric control subjects on several measures, including an immediate source monitoring task and a questionnaire assessing metacognitive beliefs.

Results. Results indicated that patients experiencing hallucinations exhibited the predicted bias towards misattributing internal events to an external source, as measured by ratings of internality of responses in a word association task. All groups had lower perceived levels of internality and control for emotionally salient words, which provides further evidence for the importance of emotional content in hallucinations. Patients experiencing hallucinations were found to score higher than the other two groups on metacognitive beliefs about uncontrollability and danger and positive beliefs about worry. In addition, a logistic regression analysis showed that beliefs about uncontrollability and danger were predictive of whether subjects experienced auditory hallucinations or not.

Conclusions. These results offer considerable support to cognitive bias models of auditory hallucinations, particularly those that implicate metacognition.

Background. Various studies from Australia, Canada and the United States have shown significant rank correlations between the suicide rates of immigrants and those of their country of birth (COB). This study compares the rank ordering of age standardized suicide rates of immigrants in Australia for two periods, 1961–70 and 1979–90: (a) between each period; and (b) with their COB for each period.

Methods. Data were obtained from the World Health Organization Annual Statistics and from the Australian Bureau of Statistics. Comparisons were made for 11 countries from England and Wales, Ireland and Europe, for which there was a sufficiently large number of immigrant suicides to warrant statistical analysis.

Results. The data showed considerable heterogeneity in rates of immigrants from various countries, with increased rates in Australia compared with their COB. There were consistently significant Spearman rank correlations between the rates after immigration and those in their COB for each period, and between rates in the two periods for both immigrants and for their COB, despite increases in suicide rates, and considerable socio-economic demographic changes between the various countries over that time span.

Conclusions. The findings are used to argue two conclusions: (i) the important influence of pre-migrant social and cultural experiences in subsequent suicide rates in immigrants in their host country; and (ii) to support the case for the reliability of using international suicide data for comparative epidemiological research.

Background. Abnormalities of brain serotonin (5-HT) transmission have been implicated in the pathophysiology of bulimia nervosa (BN), but no conclusive data have yet been provided. The purpose of this study was to assess 5-HT transmission via the measurement of the prolactin (PRL) response to the specific 5-HT releasing agent d-fenfluramine (d-FEN) in both patients with BN and comparison subjects.

Methods. According to a double-blind placebo-controlled design, plasma PRL response to d-FEN was measured in 14 drug-free bulimics and 14 matched healthy controls. In both patients and controls, eating-related psychopathology, depressive and obsessive–compulsive symptoms, and aggressiveness were measured by rating scales.

Results. Baseline plasma levels of PRL and 17β-oestradiol were significantly reduced in bulimic patients, whereas basal plasma levels of cortisol did not significantly differ from healthy controls. PRL response to d-FEN was not different between patients and controls as groups, but it was significantly blunted in bulimics with high frequency bingeing ([ges ]2 binge episodes per day; N=7) as compared to both those with low frequency bingeing ([les ]1 binge episode per day; N=7) and matched controls. A significant negative correlation emerged between the frequency of binge episodes and the hormone response to d-FEN. Moreover, although patients scored higher than healthy subjects on rating scales assessing depressive and obsessive–compulsive symptoms and aggressiveness, no significant correlation was found between these measures and the PRL response to d-FEN.

Conclusions. These results support the idea that serotonin transmission is impaired in bulimic patients with frequent binge episodes.

Background. There is little research that examines demographic, clinical and treatment factors associated with changes in physical symptoms, psychiatric symptoms and functional outcome in patients with somatized depression or anxiety in primary care.

Method. Factors associated with the outcome of psychologized or somatized depression or anxiety were derived from the literature. These factors were tested individually for their effects on changes in physical symptoms, psychiatric symptoms and functional outcome between baseline consultation with the general practitioner and 1 or 3 months later in 215 patients with somatized depression or anxiety. Individual factors associated with a particular outcome, demographic, DSM-IV diagnosis and treatment variables were entered into a multiple regression analysis.

Results. Factors associated with a better outcome on all three types of outcome measure were the absence of generalized anxiety disorder and/or simple or social phobias, absence of physical pathology, and the prescription of fewer drugs, especially hypnotics or benzodiazepines. In addition, a better psychiatric symptom outcome was associated with the patients' perceived satisfaction with the general practitioner's understanding or explanation of the patient's problems. A better functional outcome was associated with having a job, less distress over physical symptoms, not receiving invalidity benefit and no referral to hospital.

Conclusion. There are clinical and demographic factors associated with all types of short-term outcome in patients with somatized depression or anxiety but there are additional factors that are associated only with either psychiatric or functional outcome.

Background. Personality is an important determinant of suicidal behaviour. However, it has been studied little in relation to suicidal behaviour in depression.

Methods. Depressed patients who had attempted suicide (N=41) were compared with depressed patients who had never attempted suicide (N=56) and normal controls (N=56) for their scores on three personality questionnaires.

Results. Introversion was the only personality dimension where the post hoc test showed a different pattern between the two groups of depressed patients in their relation to controls. In particular, only depressed patients who had attempted suicide had significantly lower introversion scores than controls.

Conclusion. The personality dimension of introversion may be a risk factor for suicidal behaviour in depression.

Background. The validity of the concept of seasonal affective disorder and the causal link to lack of daylight in winter is controversial. There is a need for investigations in large samples of the general population at different latitudes and within general research contexts to avoid selective response bias and sensitization of the population.

Methods. During a study of health effects of the air pollution from Russia in a small community at 70° north, a self-administered questionnaire was filled in by 3736 inhabitants, 60·8% of the total population between 18 and 69 years. Three questions concerned depression, sleeping problems and other problems related to the two contrasting seasons with regard to daylight.

Results. Twenty-seven per cent reported to have some kind of problem in the dark period. Most frequently reported were sleeping problems during winter, in 19·9% of women and 11·2% of men. Self-reported depression in winter was found in 11·1% of women and 4·8%% of men. Sleeping problems increased with age, while depression was most often reported by middle-aged people. The only other reported problem in winter was fatigue. The adjusted relative risk (RR) for winter depression in women compared to men was 2·5 (95% confidence interval: 1·9–3·2). Very few had problems in summer.

Conclusions. In the high north, one-third of the women and one-fifth of the men experience problems with sleep, mood or energy related to season. The prevalence of self-reported depression was surprisingly low in winter considering the lack of daylight.