Bethlem Royal Hospital

Necropsy brain tissue from normal (control) patients and patients with depression and dementia was examined for activities of various cholinergic components, and these related to the degree of senile plaque formation and extent of intellectual impairment. Choline acetyltransferase and acetylcholinesterase activities decreased significantly as the mean plaque count rose, and in depressed and demented subjects the reduction in choline acetyltransferase activity correlated with the extent of intellectual impairment as measured by a memory information test; muscarinic cholinergic receptor binding activity remained unchanged with increasing senile plaque formation but butyrylcholinesterase activity increased. The results suggest a close relation between changes in the cholinergic system and Alzheimer's dementia, but the precise role of the system in this disease remains to be elucidated.

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

BACKGROUND: Unanswered questions from controlled studies of posttraumatic stress disorder concern the value of cognitive restructuring alone without prolonged exposure therapy and whether its combination with prolonged exposure is enhancing. METHODS: In a controlled study, 87 patients with posttraumatic stress disorder of at least 6 months' duration were randomly assigned to have 10 sessions of 1 of 4 treatments: prolonged exposure (imaginal and live) alone; cognitive restructuring alone; combined prolonged exposure and cognitive restructuring; or relaxation without prolonged exposure or cognitive restructuring. RESULTS: Integrity of audiotaped treatment sessions was satisfactory when rated by an assessor unaware of the treatment assignment. Seventy-seven patients completed treatment. The pattern of results was similar regardless of rater, statistical method, measure, occasion, and therapist. Exposure and cognitive restructuring, singly or combined, improved posttraumatic stress disorder markedly on a broad front. Gains continued to 6-month follow-up and were significantly greater than the moderate improvement from relaxation. CONCLUSION: Both prolonged exposure and cognitive restructuring were each therapeutic on their own, were not mutually enhancing when combined, and were each superior to relaxation.

Importance: Evidence of gut microbiota perturbations has accumulated for multiple psychiatric disorders, with microbiota signatures proposed as potential biomarkers. However, no attempts have been made to evaluate the specificity of these across the range of psychiatric conditions. Objective: To conduct an umbrella and updated meta-analysis of gut microbiota alterations in general adult psychiatric populations and perform a within- and between-diagnostic comparison. Data Sources: Cochrane Library, PubMed, PsycINFO, and Embase were searched up to February 2, 2021, for systematic reviews, meta-analyses, and original evidence. Study Selection: A total of 59 case-control studies evaluating diversity or abundance of gut microbes in adult populations with major depressive disorder, bipolar disorder, psychosis and schizophrenia, anorexia nervosa, anxiety, obsessive compulsive disorder, posttraumatic stress disorder, or attention-deficit/hyperactivity disorder were included. Data Extraction and Synthesis: Between-group comparisons of relative abundance of gut microbes and beta diversity indices were extracted and summarized qualitatively. Random-effects meta-analyses on standardized mean difference (SMD) were performed for alpha diversity indices. Main Outcomes and Measures: Alpha and beta diversity and relative abundance of gut microbes. Results: A total of 34 studies provided data and were included in alpha diversity meta-analyses (n = 1519 patients, n = 1429 control participants). Significant decrease in microbial richness in patients compared with control participants were found (observed species SMD = -0.26; 95% CI, -0.47 to -0.06; Chao1 SMD = -0.5; 95% CI, -0.79 to -0.21); however, this was consistently decreased only in bipolar disorder when individual diagnoses were examined. There was a small decrease in phylogenetic diversity (SMD = -0.24; 95% CI, -0.47 to -0.001) and no significant differences in Shannon and Simpson indices. Differences in beta diversity were consistently observed only for major depressive disorder and psychosis and schizophrenia. Regarding relative abundance, little evidence of disorder specificity was found. Instead, a transdiagnostic pattern of microbiota signatures was found. Depleted levels of Faecalibacterium and Coprococcus and enriched levels of Eggerthella were consistently shared between major depressive disorder, bipolar disorder, psychosis and schizophrenia, and anxiety, suggesting these disorders are characterized by a reduction of anti-inflammatory butyrate-producing bacteria, while pro-inflammatory genera are enriched. The confounding associations of region and medication were also evaluated. Conclusions and Relevance: This systematic review and meta-analysis found that gut microbiota perturbations were associated with a transdiagnostic pattern with a depletion of certain anti-inflammatory butyrate-producing bacteria and an enrichment of pro-inflammatory bacteria in patients with depression, bipolar disorder, schizophrenia, and anxiety.

BACKGROUND: This investigation sought to determine the prevalences of various psychopathologies in outstandingly creative individuals, and to test a hypothesis that the high prevalence of mental abnormalities reported in prominent living creative persons would not be found in those who had achieved and retained world status. METHOD: The family background, physical health, personality, psychosexuality and mental health of 291 famous men in science, thought, politics, and art were investigated. The membership of the six series of scientists and inventors, thinkers and scholars, statesmen and national leaders, painters and sculptors, composers, and of novelists and playwrights was determined by the availability of sufficiently adequate biographies. Extracted data were transformed into diagnoses in accordance with DSM-III-R criteria, when appropriate. RESULTS: All excelled not only by virtue of their abilities and originality, but also of their drive, perseverance, industry, and meticulousness. With a few exceptions, these men were emotionally warm, with a gift for friendship and sociability. Most had unusual personality characteristics and, in addition, minor 'neurotic' abnormalities were probably more common than in the general population. Severe personality deviations were unduly frequent only in the case of visual artists and writers. Functional psychoses were probably less frequent than psychiatric epidemiology would suggest, and they were entirely restricted to the affective varieties. Among other functional disorders, only depressive conditions, alcoholism, and, less reliably, psychosexual problems were more prevalent than expected in some professional categories, but strikingly so in writers. CONCLUSIONS: Similar findings have been reported for living artists and writers, and this suggests that certain pathological personality characteristics, as well as tendencies towards depression and alcoholism, are causally linked to some kinds of valuable creativity.

A cross-national randomised trial of alprazolam for chronic panic disorder with agoraphobia was run. Compared with previous trials it had three new features: an exposure therapy contrast group, a six-month treatment-free follow-up, and a low rate of early placebo drop-outs ('non-evaluables'). The dose of alprazolam was high (5 mg/day). The 154 patients had eight weeks of: alprazolam and exposure (combined treatment); or alprazolam and relaxation (a psychological placebo); or placebo and exposure; or placebo and relaxation (double placebo). Drug taper was from weeks 8 to 16. Follow-up was to week 43. Results were similar at both sites. Treatment integrity was good. All four treatment groups, including double placebo, improved well on panic throughout. On non-panic measures, by the end of treatment, both alprazolam and exposure were effective, but exposure had twice the effect size of alprazolam. During taper and follow-up, gains after alprazolam were lost, while gains after exposure were maintained. Combining alprazolam with exposure marginally enhanced gains during treatment, but impaired improvement thereafter. The new features put previous trails in a fresh light. By the end of treatment, though gains on alprazolam were largely as in previous studies, on phobias and disability they were half those with exposure. Relapse was usual after alprazolam was stopped, whereas gains persisted to six-month follow-up after exposure ceased. Panic improved as much with placebo as with alprazolam or exposure.

BACKGROUND: There is evidence to suggest that the broad discrepancy in the ratio of males to females with diagnosed ADHD is due, at least in part, to lack of recognition and/or referral bias in females. Studies suggest that females with ADHD present with differences in their profile of symptoms, comorbidity and associated functioning compared with males. This consensus aims to provide a better understanding of females with ADHD in order to improve recognition and referral. Comprehensive assessment and appropriate treatment is hoped to enhance longer-term clinical outcomes and patient wellbeing for females with ADHD. METHODS: The United Kingdom ADHD Partnership hosted a meeting of experts to discuss symptom presentation, triggers for referral, assessment, treatment and multi-agency liaison for females with ADHD across the lifespan. RESULTS: A consensus was reached offering practical guidance to support medical and mental health practitioners working with females with ADHD. The potential challenges of working with this patient group were identified, as well as specific barriers that may hinder recognition. These included symptomatic differences, gender biases, comorbidities and the compensatory strategies that may mask or overshadow underlying symptoms of ADHD. Furthermore, we determined the broader needs of these patients and considered how multi-agency liaison may provide the support to meet them. CONCLUSIONS: This practical approach based upon expert consensus will inform effective identification, treatment and support of girls and women with ADHD. It is important to move away from the prevalent perspective that ADHD is a behavioural disorder and attend to the more subtle and/or internalised presentation that is common in females. It is essential to adopt a lifespan model of care to support the complex transitions experienced by females that occur in parallel to change in clinical presentation and social circumstances. Treatment with pharmacological and psychological interventions is expected to have a positive impact leading to increased productivity, decreased resource utilization and most importantly, improved long-term outcomes for girls and women.

Forty chronic obsessive-compulsive ritualizers were randomly assigned to treatment with oral clomipramine or placebo for 8 months. During weeks 4 to 7 these two groups were each randomly split into treatment by relaxation or by exposure in vivo, and during weeks 7 to 10 all patients had exposure in vivo. Double blind assessments were made at weeks 4, 7, 10, 18, 36, 62 and 114. Results are reported to one year. Clomipramine produced significant improvement in rituals, mood and social adjustment, but only in those patients who initially had depressed mood. The clomipramine effect was maximum from weeks 10 to 18 and diminished thereafter. On stopping clomipramine patients often relapsed and improved again on restarting the drug. Relaxation produced little change. Exposure produced significant lasting improvement in rituals, but less change in mood; improvement generalized to social adjustment at follow-up. Clomipramine plus exposure had a slight additive but not interactional effect. Clomipramine enhanced compliance both with exposure and with relaxation. Clomipramine is useful for compulsive ritualizers with depressed mood, but may need continuation for over a year and combination with exposure in vivo. Exposure in vivo remains the treatment of choice for rituals without depressed mood.

Forty-one patients with anorexia nervosa, admitted to the Maudsley Hospital between 1959 and 1966, were followed up after a mean of 20 years. An assessment of general outcome (based on the Morgan-Russell scales) yielded three outcome categories: 'good' (n = 12), 'intermediate' (n = 13) and 'poor' (n = 15). Six patients (15%) had died from causes related to anorexia nervosa; at least 15% had developed bulimia nervosa. There was a general consistency between the follow-up at 20 years and that previously conducted five years after admission, although with a few individual patients there were serious prognostic errors at the earlier follow-up. A poorer outcome was associated with a later age of onset, a history of neurotic and personality disturbances, disturbed relationships in the family and a longer duration of illness.

BACKGROUND: High rates of comorbid alcohol and drug disorders have previously been found among individuals with severe mental illnesses such as schizophrenia and bipolar affective disorders. Clinical and social outcomes have been reported to be worse in this group and service costs greater than in individuals with severe mental illness only. These 'dual diagnosis' patients have mainly been investigated in the USA, and there has been very little research in Europe, where patterns of substance abuse may be different. METHOD: All patients with psychotic illnesses who had any contact with the mental health services in a geographically defined sector in South London over a specified period were studied. Individuals with problems related to alcohol or drugs were identified using standardised interviews with subjects and their keyworkers. Data on psychiatric service use during the previous 2 years were also obtained. RESULTS: One hundred and seventy-one subjects with psychotic illnesses were interviewed (response rate: 78.4%). The one-year prevalence rate for any substance problem was 36.3% (95% CI = 29.1-43.5), for alcohol problems it was 31.6% (95% CI = 24.6-38.5), and for drug problems 15.8% (95% CI = 10.3-21.3). Young male subjects were at higher risk of having substance problems. Patients with substance problems had spent almost twice as many days in hospital as those without such problems over the previous two years (difference = 26.3 days, 95% CI = 3.8-48.7). CONCLUSIONS: The prevalence of substance problems among people suffering from severe mental disorders is high, and seems to be associated with greater use of in-patient services. This is a significant clinical problem, with cost implications. Further investigation is needed for adequate service provision.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs.

The extent to which psychiatric disability after head injury depends upon the brain damage which has occurred remains a problem of considerable practical and theoretical interest. In 1904 Adolf Meyer saw the need for caution in approaching this question since there was “no direct measure of the damage of a concussion”; similarly in 1945 Denny-Brown saw that the most serious obstacles to better understanding still lay in the difficulty of obtaining a reliable estimate of the severity of injury to the brain and in the impossibility of differentiating clinically between simple skull fracture, laceration or contusion of the brain.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental syndrome with a high human and economic burden. The pathophysiology of ASD is largely unclear, thus hampering development of pharmacological treatments for the core symptoms of the disorder. Abnormalities in glutamate and GABA signaling have been hypothesized to underlie ASD symptoms, and may form a therapeutic target, but it is not known whether these abnormalities are recapitulated in humans with ASD, as well as in rodent models of the disorder. We used translational proton magnetic resonance spectroscopy ([1H]MRS) to compare glutamate and GABA levels in adult humans with ASD and in a panel of six diverse rodent ASD models, encompassing genetic and environmental etiologies. [1H]MRS was performed in the striatum and the medial prefrontal cortex, of the humans, mice, and rats in order to allow for direct cross-species comparisons in specific cortical and subcortical brain regions implicated in ASD. In humans with ASD, glutamate concentration was reduced in the striatum and this was correlated with the severity of social symptoms. GABA levels were not altered in either brain region. The reduction in striatal glutamate was recapitulated in mice prenatally exposed to valproate, and in mice and rats carrying Nlgn3 mutations, but not in rodent ASD models with other etiologies. Our findings suggest that glutamate/GABA abnormalities in the corticostriatal circuitry may be a key pathological mechanism in ASD; and may be linked to alterations in the neuroligin-neurexin signaling complex.

To date there has been no suitable scale for the self-assessment of irritability in the clinical situation. Existing scales have either included aspects of personality trait together with present state or they have been constructed on non-clinical populations. A self-assessment scale has been constructed which seeks to overcome such faults. Measures of depression and of anxiety are included, together with measures of outwardly directed irritability and inwardly directed irritability. This scale should be known as the Irritability, Depression, Anxiety--or IDA--Scale.

BACKGROUND: Evidence suggests that black, Asian and minority ethnic (BAME) groups have an increased risk of involuntary psychiatric care. However, to our knowledge, there is no published meta-analysis that brings together both international and UK literature and allows for comparison of the two. This study examined compulsory detention in BAME and migrant groups in the UK and internationally, and aimed to expand upon existing systematic reviews and meta-analyses of the rates of detention for BAME populations. METHODS: For this systematic review and meta-analysis, we searched five databases (PsychINFO, MEDLINE, Cochrane Controlled Register of Trials, Embase, and CINAHL) for quantitative studies comparing involuntary admission, readmission, and inpatient bed days between BAME or migrant groups and majority or native groups, published between inception and Dec 3, 2018. We extracted data on study characteristics, patient-level data on diagnosis, age, sex, ethnicity, marital status, and occupational status, and our outcomes of interest (involuntary admission to hospital, readmission to hospital, and inpatient bed days) for meta-analysis. We used a random-effects model to compare disparate outcome measures. We assessed explanations offered for the differences between minority and majority groups for the strength of the evidence supporting them. This study is prospectively registered with PROSPERO, number CRD42017078137. FINDINGS: Our search identified 9511 studies for title and abstract screening, from which we identified 296 potentially relevant full-text articles. Of these, 67 met the inclusion criteria and were reviewed in depth. We added four studies after reference and citation searches, meaning 71 studies in total were included. 1 953 135 participants were included in the studies. Black Caribbean patients were significantly more likely to be compulsorily admitted to hospital compared with those in white ethnic groups (odds ratio 2·53, 95% CI 2·03-3·16, p<0·0001). Black African patients also had significantly increased odds of being compulsorily admitted to hospital compared with white ethnic groups (2·27, 1·62-3·19, p<0·0001), as did, to a lesser extent, south Asian patients (1·33, 1·07-1·65, p=0·0091). Black Caribbean patients were also significantly more likely to be readmitted to hospital compared with white ethnic groups (2·30, 1·22-4·34, p=0·0102). Migrant groups were significantly more likely to be compulsorily admitted to hospital compared with native groups (1·50, 1·21-1·87, p=0·0003). The most common explanations for the increased risk of detainment in BAME populations included increased prevalence of psychosis, increased perceived risk of violence, increased police contact, absence of or mistrust of general practitioners, and ethnic disadvantages. INTERPRETATION: BAME and migrant groups are at a greater risk of psychiatric detention than are majority groups, although there is variation across ethnic groups. Attempts to explain increased detention in ethnic groups should avoid amalgamation and instead carry out culturally-specific, hypothesis-driven studies to examine the numerous contributors to varying rates of detention. FUNDING: University College London Hospitals National Institute for Health Research (NIHR) Biomedical Research Centre, NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, King's College London, and NIHR Collaboration for Leadership in Applied Health Research and Care North Thames at Bart's Health NHS Trust.

In the search for more effective methods of psychological treatment in anorexia nervosa, there are a number of controlled trials evaluating the efficacy of different forms of treatment. Previous studies have shown that family therapy is the superior treatment for patients with an early onset and short duration of illness. In order to assess the impact and the effective components of family therapy, we conducted a pilot trial in which consecutive referrals of anorexia nervosa patients were randomly assigned to one of two forms of family treatment: family therapy (conjoint family sessions) or family counselling (separate supportive sessions for the patient and counselling for the parents). Changes taking place within the patient and the family were evaluated at regular intervals, while within and between group comparisons were made. Although tentative, it was found that, in the short term, there were few differences in terms of symptomatic relief between the two treatment groups. © 1992 john Wiley & Sons, Inc.

Two hundred and three male remanded prisoners were interviewed with respect to their current offence, mental state, and social and psychiatric histories. All but nine of the sub-group of 121 psychotic men showed active symptoms at the time of committing a criminal offence; 20% of the actively ill psychotics were directly driven to offend by their psychotic symptoms, and a further 26% probably so. If some of the indirect consequences of the psychosis were taken into account, 82% of their offences were probably attributable to the illness. Among the normal and neurotic men, none claimed psychotic motives for offending, but motives suggesting high emotional arousal such as panic or retaliation triggered the greatest violence. Within the psychotic group, those driven to offend by their delusions were most likely to have been seriously violent, and psychotic symptoms probably accounted directly for most of the very violent behaviour.

Article Abstract Background: Reduced brain-derived neurotrophic factor (BDNF) levels have been reported in the serum and plasma of patients with psychosis. The aim of this cross-sectional case-control study was to investigate potential causes and consequences of reduced BDNF expression in these patients by examining the association between BDNF levels and measures of stress, inflammation, and hippocampal volume in first-episode psychosis. Method: Brain-derived neurotrophic factor, interleukin (IL)-6, and tumor necrosis factor (TNF)-α messenger RNA levels were measured in the leukocytes of 49 first-episode psychosis patients (DSM-IV criteria) and 30 healthy controls, all aged 18 to 65 years, recruited between January 2006 and December 2008. Patients were recruited from inpatient and outpatient units of the South London and Maudsley National Health Service Foundation Trust in London, United Kingdom, and the healthy controls were recruited from the same catchment area via advertisement and volunteer databases. In these same subjects, we measured salivary cortisol levels and collected information about psychosocial stressors (number of childhood traumas, number of recent stressors, and perceived stress). Finally, hippocampal volume was measured using brain magnetic resonance imaging in a subsample of 19 patients. Results: Patients had reduced BDNF (effect size, d = 1.3; P < .001) and increased IL-6 (effect size, d = 1.1; P < .001) and TNF-α (effect size, d = 1.7; P < .001) gene expression levels when compared with controls, as well as higher levels of psychosocial stressors. A linear regression analysis in patients showed that a history of childhood trauma and high levels of recent stressors predicted lower BDNF expression through an inflammation-mediated pathway (adjusted R2 = 0.23, P = .009). In turn, lower BDNF expression, increased IL-6 expression, and increased cortisol levels all significantly and independently predicted a smaller left hippocampal volume (adjusted R2 = 0.71, P < .001). Conclusions: Biological changes activated by stress represent a significant factor influencing brain structure and function in first-episode psychosis through an effect on BDNF. J Clin Psychiatry Submitted: November 25, 2010; accepted February 8, 2011. Online ahead of print: May 18, 2011 (doi:10.4088/JCP.10m06745). Corresponding author: Valeria Mondelli, MD, PhD, Sections of Perinatal Psychiatry & Stress, Psychiatry and Immunology (SPI-Laboratory), Centre for the Cellular Basis of Behaviour, The James Black Centre, Institute of Psychiatry, King's College London, 125 Coldharbour Lane, London SE5 9NU, United Kingdom (valeria.mondelli@kcl.ac.uk).

Since the long-term results of the treatment of elderly depressives admitted to the writer's care between 1949 and 1951 were communicated (1962), further experiences (e.g. Colwell and Post, 1959; Post, 1968) have confirmed that affective illnesses in late life are associated with much subsequent mental invalidism and needs for further treatment. It was hoped that these needs might be met by increased use of out-patient and community care as well as by the introduction of thymoleptic drugs. A follow-up investigation of a further consecutive series of depressives over the age of 60 receiving inpatient treatment from the same psychiatrist in the same hospital during the years 1966–67 was undertaken with the following aims in view: Firstly, it was intended to test the proposition that the less reluctant use of electro-convulsive therapy in old persons, as well as the introduction of antidepressant drugs and of more active after-care measures, had improved the long term outlook in the affective illnesses of late life. It was realized that a comparison of two series of patients separated from one another by some 15 years might be vitiated by differences between the samples other than those due to changed methods of treatment. It would, however, have been unethical to withhold the new forms of management from a control group.