Background We aimed to review published work for the efficacy and safety of electroconvulsive therapy (ECT) with simulated ECT, ECT versus pharmacotherapy, and different forms of ECT for patients with depressive illness. Methods We designed a systematic overview and meta-analysis of randomised controlled trials and observational studies. We obtained data from the Cochrane Collaboration Depressive Anxiety and Neurosis and Schizophrenia Group Controlled trial registers, Cochrane Controlled Trials register, Biological Abstracts, CINAHL, EMBASE, LILACS, MEDLINE, PsycINFO, and SIGLE, reference lists, and specialist textbooks. Our main outcome measures were depressive symptoms, measures of cognitive function, and mortality. Findings Meta-analysis of data of short-term efficacy from randomised controlled trials was possible. Real ECT was significantly more effective than simulated ECT (six trials, 256 patients, standardised effect size [SES] -0.91, 95% CI-1.27 to -0.54). Treatment with ECT was significantly more effective than pharmacotherapy (18 trials, 1144 participants, SES -0.80, 95% CI-1.29 to -0.29). Bilateral ECT was more effective than unipolar ECT (22 trials, 1408 participants, SES -0.32, 95% CI-0.46 to -0.19). Interpretation ECT is an effective short-term treatment for depression, and is probably more effective than drug therapy. Bilateral ECT is moderately more effective than unilateral ECT, and high dose ECT is more effective than low dose.
The psychometric properties of the 28- and 30-item versions of the Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) are reported in a total of 434 (28-item) and 337 (30-item) adult out-patients with current major depressive disorder and 118 adult euthymic subjects (15 remitted depressed and 103 normal controls). Cronbach's alpha ranged from 0.92 to 0.94 for the total sample and from 0.76 to 0.82 for those with current depression. Item total correlations, as well as several tests of concurrent and discriminant validity are reported. Factor analysis revealed three dimensions (cognitive/mood, anxiety/arousal and vegetative) for each scale. Analysis of sensitivity to change in symptom severity in an open-label trial of fluoxetine (N = 58) showed that the IDS-C and IDS-SR were highly related to the 17-item Hamilton Rating Scale for Depression. Given the more complete item coverage, satisfactory psychometric properties, and high correlations with the above standard ratings, the 30-item IDS-C and IDS-SR can be used to evaluate depressive symptom severity. The availability of similar item content for clinician-rated and self-reported versions allows more direct evaluations of these two perspectives.
We first discuss current diagnostic issues concerning the classification of anorexia nervosa (AN) by reference to the proposed criteria of the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). We strongly welcome the changes in the latest revision of DSM-5 (update April 2012), which in our opinion partially solve the previously delineated classification problems. Nevertheless, we still miss a standard or reference(s) for the weight criterion including the delineation between a healthy and unhealthy underweight, a better operationalization of observable behaviors including symptoms of disordered eating, readily accessible cognitions and a better allowance for cross-cultural aspects in the proposed DSM-5 classification of AN. In the second part, we review the treatment recommendations of the NICE guidelines for AN, which overall are characterized by a lack of evidence. Nevertheless, NICE recommended an outpatient treatment setting based on one randomized controlled trial with many methodological limitations. A review of the current literature shows that (a) the optimal treatment setting (inpatient vs. outpatient treatment) still is a subject of debate, and (b) the evaluation of treatment costs in AN plays an important role within this discussion. In contrast to the German Guidelines for the Treatment of Eating Disorders, NICE does not offer any specific criteria for the clinician with regard to determining the adequate treatment setting.
Two previous epidemiological studies of autistic twins suggested that autism was predominantly genetically determined, although the findings with regard to a broader phenotype of cognitive, and possibly social, abnormalities were contradictory. Obstetric and perinatal hazards were also invoked as environmentally determined aetiological factors. The first British twin sample has been re-examined and a second total population sample of autistic twins recruited. In the combined sample 60% of monozygotic (MZ) pairs were concordant for autism versus no dizygotic (DZ) pairs; 92% of MZ pairs were concordant for a broader spectrum of related cognitive or social abnormalities versus 10% of DZ pairs. The findings indicate that autism is under a high degree of genetic control and suggest the involvement of multiple genetic loci. Obstetric hazards usually appear to be consequences of genetically influenced abnormal development, rather than independent aetiological factors. Few new cases had possible medical aetiologies, refuting claims that recognized disorders are common aetiological influences.
This paper draws attention to an important adverse outcome in depression, the occurrence of residual symptoms after partial remission. Among patients with definite major depression followed every 3 months to remission and thereafter, residual symptoms reaching 8 or more on the Hamilton Depression Scale 17-item total were present in 32% (19) of the 60 who remitted below major depression by 15 months. The pattern was of mild but typical depressive symptoms. Residual symptoms were more common in subjects with more severe initial illness, but were not related to any other predictors, including longer prior illness, dysthymia, or lower dose of drug treatment during the illness episode. There were weak associations with personality that might have been consequences of symptom presence. Residual symptoms were very strong predictors of subsequent early relapse, which occurred in 76% (13/17) of those with residual symptoms and 25% (10/40) of those without.
Mentalizing ability was studied in 46 symptomatic schizophrenic patients and 44 non-symptomatic controls. Subjects heard six stories and simultaneously were shown simple cartoon pictures depicting the action sequencing occurring in the stories. All the stories involved false belief or deception, so that it was necessary to infer the mental states of the characters in order to understand their behaviour. After each story, subjects were asked one memory/reality question (concerning an event in the story) and one question that depended on the ability to infer the mental state of one of the characters. Patients with paranoid delusions were impaired on the questions concerning mental states. Patients with behavioural signs (i.e, negative features or incoherence) were also impaired on the mental state questions, but this difficulty was associated with memory impairments. Patients with symptoms of passivity (e.g. delusions of control) and patients in remission did not differ from normal controls. These results are consistent with the hypothesis that certain of the positive symptoms of schizophrenia reflect an impairment in the ability to infer the mental states of others.
The CANTAB battery of neuropsychological tests was used to compare the performance of 28 patients with unipolar depression with that of 22 age and IQ matched controls. The patients were impaired on almost all tests studied with deficits in pattern and spatial recognition memory, matching to sample, spatial span, spatial working memory and planning. Most of the patients showed at least some impairment and deficits were seen across cognitive domains. An important finding was the detrimental effect of failure on subsequent performance; having solved one problem incorrectly, patients were far more likely than controls to fail the subsequent problem. Superimposed on the general deficits, there were also specific deficits in executive tasks characteristic of frontostriatal dysfunction and deficits in mnemonic tasks characteristic of temporal lobe dysfunction. This combination of a specific form of motivational deficit, resulting in oversensitivity to negative feedback, and superimposed specific neuropsychological deficits were correlated with severity of depression. The most significant correlations were seen between mnemonic deficits and clinical rating scores. Comparisons of the deficits seen in the depressed patients in this study with other patient groups assessed with the CANTAB neuropsychological battery, showed that one of the hypotheses of the neuropsychological deficits in depression, that of 'frontosubcortical' or 'frontostriatal' dysfunction, was not supported. These findings are discussed in relation to the likely neural substrates of depression.
The paper reports the profile of impairment across a variety of cognitive functions with special emphasis on tests sensitive to frontal lobe dysfunction, in 24 elderly depressed patients during and on recovery from mood disorder, compared with 15 age- and sex-matched controls. Traditional neuropsychological tests and a recently developed battery of computerized tests (CANTAB) were used. Impairments were found in the depressed group compared to controls and to themselves on recovery across all domains examined. The depressed group showed deficits on visuospatial recognition memory, attentional shifting at the extra-dimensional shift stage and in measures of both processing and motor speed without impaired accuracy in a visual search task. Impairments were also found on a planning task with disproportionately increased numbers of moves needed for more difficult problems and evidence of both slowed motor response and increased processing time once the task was commenced. Performance on recovery improved across all tasks. Comparisons were made with the performance of patients suffering from dementia of the Alzheimer type (DAT) and Parkinson's disease on similar tests. Response latencies in test performance were found to correlate with the number of episodes of depression suffered and with ventricular size on CT scan, as measured by computerized planimetry. On recovery, residual depression scores correlated with latency of test performance and with ventricular brain ratio. The results, thus, show that depression in the elderly is associated with a significant degree of deficit on tests sensitive to frontostriatal dysfunction. Some of the deficits appear specific to depression and some do not remit following clinical recovery. However, these impairments have to be interpreted in the context of a broad profile of cognitive deficit.
A comprehensive semi-structured questionnaire was administered to 100 psychotic patients who had experienced auditory hallucinations. The aim was to extend the phenomenology of the hallucination into areas of both form and content and also to guide future theoretical development. All subjects heard 'voices' talking to or about them. The location of the voice, its characteristics and the nature of address were described. Precipitants and alleviating factors plus the effect of the hallucinations on the sufferer were identified. Other hallucinatory experiences, thought insertion and insight were examined for their inter-relationships. A pattern emerged of increasing complexity of the auditory-verbal hallucination over time by a process of accretion, with the addition of more voices and extended dialogues, and more intimacy between subject and voice. Such evolution seemed to relate to the lessening of distress and improved coping. These findings should inform both neurological and cognitive accounts of the pathogenesis of auditory hallucinations in psychotic disorders.
Great advances have been made during the last 20 years in the development of structured and semi-structured interviews for use with psychiatric patients. However, in the field of child and adolescent psychiatry there have been weaknesses in the specification and definition of both symptoms and the psychosocial impairments resulting from psychiatric disorder. Furthermore, most of the available interviews for use with children have been tied to a single diagnostic system (DSM-III, DSM-III-R, or ICD-9). This has meant that symptom coverage has been limited and nosological comparisons have been inhibited. The Child and Adolescent Psychiatric Assessment (CAPA) represents an attempt to remedy some of these shortcomings. This paper outlines the principles adopted in the CAPA to improve the standardization, reliability and meaningfulness of symptom and diagnostic ratings. The CAPA is an interviewer-based diagnostic interview with versions for use with children and their parents, focused on symptoms occurring during the preceding 3 month period, adapted for assessments in both clinical and epidemiological research.
Data from four studies were used to assess the psychometric properties of the 26 IQCODE items. The items were assessed in terms of item-total correlations, test-retest reliabilities, correlations with indicators of current cognitive functioning and correlations with indicators of premorbid cognitive functioning. These data were used to develop a 16-item short form. The short form was cross-validated in a new sample using dementia/delirium diagnosis as the validity standard. It was found to perform as well as the long form.
The Structured Clinical Interview for DSM-III-R (SCID and SCID II) was administered to 105 eating disorder in-patients in order to examine rates of comorbid psychiatric disorders and the chronological sequence in which these disorders developed. Eighty-six patients, 81.9% of the sample, had Axis I diagnoses in addition to their eating disorder. Depression, anxiety and substance dependence were the most common comorbid diagnoses. Anorexic restrictors were significantly more likely than bulimics (all subtypes) to develop their eating disorder before other Axis I comorbid conditions. Personality disorders were common among the subjects; 69% met criteria for at least one personality disorder diagnosis. Of the 72 patients with personality disorders, 93% also had Axis I comorbidity. Patients with at least one personality disorder were significantly more likely to have an affective disorder or substance dependence than those with no personality disorder.
Many of the standardized interviews currently used in psychiatry require the interviewer to use expert psychiatric judgements in deciding upon the presence or absence of psychopathology. However, when case definitions are standardized it is customary for clinical judgements to be replaced with rules. The Clinical Interview Schedule was therefore revised, in order to increase standardization, and to make it suitable for use by 'lay' interviewers in assessing minor psychiatric disorder in community, general hospital, occupational and primary care research. Two reliability studies of the revised Clinical Interview Schedule (CIS-R) were conducted in primary health care clinics in London and Santiago, Chile. Both studies compared psychiatrically trained interviewer(s) with lay interviewer(s). Estimates of the reliability of the CIS-R compared favourably with the results of studies of other standardized interviews. In addition, the lay interviewers were as reliable as the psychiatrists and did not show any bias in their use of the CIS-R. Confirmatory factor analysis models were also used to estimate the reliabilities of the CIS-R and self-administered questionnaires and indicated that traditional measures of reliability are probably overestimates.
This paper is part of a series dealing with the role of life events in the onset of depressive disorders. Women who developed depression in a general population sample in Islington in North London are contrasted with a National Health Service-treated series of depressed patients in the same area. Findings among the latter confirm the importance of a severely threatening provoking event for onset among the majority of depressed women patients. The results for the two series are similar except for a small subgroup of patients characterized by a melancholic/psychotic condition with a prior episode. The severe events of importance have been recognized for some time by the traditional ratings of the Life Events and Difficulty Schedule (LEDS). However, the full descriptive material collected by the LEDS has been used to develop a new refined measure reflecting the likelihood of feelings of humiliation and being trapped following a severely threatening event, in addition to existing measures of loss or danger. The experience of humiliation and entrapment was important in provoking depression in both the patient and non-patient series. It proved to be associated with a far greater risk of depression than the experience of loss or danger without humiliation or entrapment.
We have previously described focal abnormalities of regional cerebral blood flow (rCBF) in the left dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex and angular gyrus in 40 patients with major depression. We now report on the patterns of change in rCBF in a subgroup of 25 of the same patients who were rescanned following clinical remission of depression. Fifteen patients were scanned when optimally matched for drug treatment (4) or drug free on both occasions (11). The other 10 patients were fully recovered but could not be matched for drug status for clinical and ethical reasons. In a paired comparison of the same patients when ill and following recovery it was evident that remission was associated with a significant increase in rCBF in the left DLPFC and medial prefrontal cortex including anterior cingulate. Increases in rCBF in the angular gyrus were not seen when the comparison of depressed and recovered scans was matched for medication. The previously described relationship between clinical symptoms and brain perfusion in the depressed state was no longer present in the recovered state; this supports the hypothesis of state relatedness. Thus, recovery from depression is associated with increases in rCBF in the same areas in which focal decreases in rCBF are described in the depressed state in comparison with normal controls.
We have previously reported focal abnormalities of regional cerebral blood flow (rCBF) in a group of 33 patients with major depression. This report, on an extended sample of 40 patients who demonstrated identical regional deficits to those previously described, examines the relationships between depressive symptoms and patterns of rCBF. Patients' symptom ratings were subjected to factor analysis, producing a three-factor solution. The scores for these three factors, which corresponded to recognizable dimensions of depressive illness, were then correlated with rCBF. The first factor had high loadings for anxiety and correlated positively with rCBF in the posterior cingulate cortex and inferior parietal lobule bilaterally. The second factor had high loadings for psychomotor retardation and depressed mood and correlated negatively with rCBF in the left dorsolateral prefrontal cortex and left angular gyrus. The third factor had a high loading for cognitive performance and correlated positively with rCBF in the left medial prefrontal cortex. These data indicate that symptomatic specificity may be ascribed to regional functional deficits in major depressive illness.
Using positron emission tomography( PET) and Oxygen-15, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P < 0-05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P < 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.
The clinical course and outcome of anorexia nervosa are presented in a 10-year follow-up study of 76 severely ill females with anorexia nervosa who met specific diagnostic criteria and had participated in a well-documented hospital treatment study. Information was obtained on 100% of the subjects. A comprehensive assessment was made in 93% of the living subjects in specific categories of weight, eating and weight control behaviours, menstrual function, anorexic attitudes, and psychological, sexual, social and vocational adjustment. Five subjects had died, which gives a crude mortality rate of 6.6%. Standardized mortality rates demonstrated an almost 13-fold increase in mortality in the anorexia nervosa subjects. Only eighteen (23.7%) were fully recovered. Sixty-four per cent developed binge-eating at some time during their illness, 57% at least weekly. Twenty-nine (41%) were still bulimic at follow-up. The high frequency and chronicity of the bulimic symptoms plus the high rate of weight relapse (42% during the first year after hospital treatment) suggest that intensive intervention is needed to help anorexics restore and maintain their weight within a normal range and to decrease abnormal eating and weight control behaviours.
Forty patients with obsessive-compulsive disorder (OCD) were compared to matched healthy controls on neuropsychological tests which are sensitive to frontal lobe dysfunction. On a computerized version of the Tower of London test of planning, the patients were no different from healthy controls in the accuracy of their solutions. However, when they made a mistake, they spent more time than the controls in generating alternative solutions or checking that the next move would be correct. The results suggest that OCD patients have a selective deficit in generating alternative strategies when they make a mistake. In a separate attentional set-shifting task, OCD patients were impaired in a simple discrimination learning task and showed a continuous cumulative increase in the number who failed at each stage of the task, including the crucial extra-dimensional set shifting stage. This suggests that OCD patients show deficits in both acquiring and maintaining cognitive sets. The cognitive deficits in OCD may be summarized as: (i) being easily distracted by other competing stimuli; (ii) excessive monitoring and checking of the response to ensure a mistake does not occur; and (iii) when a mistake does occur, being more rigid at setting aside the main goal and planning the necessary subgoals. Both studies support the evidence of fronto-striatal dysfunction in OCD and the results are discussed in terms of an impaired Supervisory Attentional System.
We analysed aggregate data from 25 studies linking Expressed Emotion (EE) and schizophrenia. We had access to original data sets from 17 studies, and used published data from the remainder. This provided us with 1346 cases from around the world. The association of EE with relapse was overwhelming, and was maintained whatever the geographical location. The predictive capacity of EE was virtually identical in men and women. While high contact with a high EE relative increased the risk of relapse, the opposite was true in low EE households. Medication and EE were independently related to relapse, and thus EE status has no bearing on the decision to prescribe. Our findings were confirmed using log-linear analysis.