Research Article
The functional neuroanatomy of schizophrenic subsyndromes
- G. D. HONEY, T. SHARMA, J. SUCKLING, V. GIAMPIETRO, W. SONI, S. C. R. WILLIAMS, E. T. BULLMORE
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- Published online by Cambridge University Press:
- 31 July 2003, pp. 1007-1018
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Background. There is considerable variability between patients in their expression of the diverse range of symptoms encompassed by the syndrome of schizophrenia, which may modulate functional activation to cognitive processing.
Method. Here we investigate associations between schizophrenic subsyndrome scores, identified by factor analysis, and experimentally controlled brain activation. Five factors were defined by rotated principal components analysis of PANSS rating scale measurements in 100 patients with schizophrenia. A subsample of 30 patients and a group of 27 comparison subjects were studied using functional magnetic resonance imaging (fMRI) during the performance of two periodically designed cognitive activation experiments: verbal working memory and psychomotor sequencing.
Results. Factor analysis replicated the five dimensions consistently reported. Within the patient group, power of activation by working memory was negatively associated with global symptom severity in left lingual and temporo-parietal cortices; negatively associated with positive subsyndrome scores in left inferior frontal and superior temporal cortices and basal ganglia; and positively associated with negative subsyndrome scores in lateral and medial premotor cortex. No relationship was observed between subsyndrome scores and functional activation during the motor task. Between-group comparisons demonstrated reduced power of response to the working memory task by patients in bilateral dorsolateral prefrontal and left pre- and post-central cortices.
Conclusions. In this study we observed task-specific modulation of functional response associated with symptom expression in schizophrenia. Our findings are compatible with previous empirical findings and theoretical conceptualization of human brain function, in terms of capacity constraints on activation in the face of competing demands from pathological and task-related cognitive activity.
Social phobia in the Australian National Survey of Mental Health and Well-Being (NSMHWB)
- L. LAMPE, T. SLADE, C. ISSAKIDIS, G. ANDREWS
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- Published online by Cambridge University Press:
- 13 May 2003, pp. 637-646
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Background. This article reports data on social phobia from the first large scale Australian epidemiological study. Prevalence rates, demographic correlates and co-morbidity in the sample that met criteria for social phobia are reported and gender differences examined.
Method. Data were obtained from a stratified sample of 10641 participants as part of the Australian National Survey of Mental Health and Well-Being (NSMHWB). A modified version of the Composite International Diagnostic Interview (CIDI) was used to determine the presence of social phobia, as well as other DSM-IV anxiety, affective and substance use disorders. The interview also screened for the presence of nine ICD-10 personality disorders, including anxious personality disorder, the equivalent of DSM-IV avoidant personality disorder (APD).
Results. The estimated 12 month prevalence of social phobia was 2·3%, lower than rates reported in several recent nationally representative epidemiological surveys and closer to those reported in the Epidemiological Catchment Area study (ECA) and other DSM-III studies. Considerable co-morbidity was identified. Data indicated that the co-morbidity with depression and alcohol abuse and dependence were generally subsequent to onset of social phobia and that the additional diagnosis of APD was associated with a greater burden of affective disorder. Social phobia most often preceded major depression, alcohol abuse and generalized anxiety disorder.
Conclusions. Social phobia is a highly prevalent, highly co-morbid disorder in the Australian community. Individuals with social phobia who also screen positively for APD appear to be at greater risk of co-morbidity with all surveyed disorders except alcohol abuse or dependence.
The genetic epidemiology of body attitudes, the attitudinal component of body image in women
- T. D. WADE, J. WILKINSON, D. BEN-TOVIM
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- Published online by Cambridge University Press:
- 30 October 2003, pp. 1395-1405
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Background. There were four purposes of the current study, including the investigation of the: (i) adequacy of a multidimensional measure of body image; (ii) genetic and environmental epidemiology of this measure; (iii) shared variance between genetic and environmental risk factors for body mass index (BMI) and body image; and (iv) Equal Environment Assumption (EEA) as it related to body attitudes.
Method. Six types of body attitudes, as measured by the Body Attitudes Questionnaire (BAQ) and reported by 894 complete female–female twin pairs (mean age 32·35 years, S.D.=41·8) from the Australian Twin Registry, were analysed.
Results. Confirmatory factor analysis of the BAQ supported the adequacy of the measure. Additive genetic and unique environmental influences best accounted for the variance of all six of the BAQ subscales. The relationship between BMI and body attitudes was primarily due to shared genes rather than environment but the majority of genetic and environmental effects on body attitudes were independent of BMI, with the exception of the Feeling Fat subscale, which shared 53% of its genetic risk factors with BMI. One violation of the EEA was suggested, namely similarity of childhood treatment influenced similarity on Lower Body Fatness subscale.
Conclusions. Findings support the notion that: (i) body image is a multidimensional concept; (ii) it is relatively independent of BMI; and (iii) both genetic and non-shared environment are influential determinants of body attitudes.
Does the level of family dysfunction moderate the impact of genetic factors on the personality trait of neuroticism?
- K. S. KENDLER, S. H. AGGEN, K. C. JACOBSON, M. C. NEALE
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- Published online by Cambridge University Press:
- 26 June 2003, pp. 817-825
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Background. While the family environment can directly influence later risk for psychopathology, dysfunction in the family of origin may also moderate the impact of genetic factors on liability for psychiatric disorders. Can a similar pattern be seen for the personality trait of Neuroticism (N) – which is a risk factor for many psychiatric conditions?
Method. Our sample of 957 complete female–female twin pairs from a population-based register had measures of self-reported N and multiple reporters (twin, co-twin, mother, father) for family dysfunction (FD). Statistical analysis was conducted by traditional regression analysis and a moderator structural equation twin model operationalized in the computer program Mx.
Results. Dividing the sample into quartiles based on increasing levels of FD, the mean of N increased substantially while correlations of N in monozygotic (MZ) and dizygotic (DZ) twins were relatively constant. Regression analyses did not suggest greater twin resemblance for N with increasing levels of FD. The best-fit structural equation model was the standard un-moderated model in which the proportion of variance in N due to genetic (39%) and unique environmental effects (61%) remained constant across values of FD.
Conclusions. Although a false-negative result due to limited power cannot be excluded, these analyses do not support the hypothesis that FD moderates the impact of genetic factors on levels of N.
Life events and early onset depression: cause or consequence?
- G. C. PATTON, C. COFFEY, M. POSTERINO, J. B. CARLIN, G. BOWES
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- Published online by Cambridge University Press:
- 25 September 2003, pp. 1203-1210
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Background. Adverse life events prior to episodes of depression are assumed to play a causal role. Earlier studies have, however, not adequately controlled for the potential confounding effects of previous depression.
Method. A two-phase study was nested within a six-wave population based cohort study of 1947 adolescents. Interviews at two assessment phases with the CIS-R and CIDI were used to generate ICD-10 diagnoses of depressive disorder. Life events with longer-term contextual threat were reported for the 6 months before first diagnosis and categorized on the basis of participant appraisal as negative and neutral/positive in effects. Previous depressive and anxiety symptoms were measured 6 months earlier.
Results. Pre-existing depressive and anxiety symptoms predicted later events, increasing three-fold the risks for both neutral/positive and negative events in females and increased seven-fold the risk of negative events in males. Life events in turn predicted the onset of depressive disorder independently of previous symptoms. Single negative events held an over five-fold elevated risk and multiple events an almost eight-fold higher risk. Personal threat and loss were associated with disorder in females but not males.
Conclusions. The findings are consistent with a causal role for life events in early episodes of depression. The association also reflects a reciprocal relationship in which earlier symptoms predict later events, perhaps as a result of an individual's attempts to change unfavourable social circumstances.
Fatigue in a community sample of twins
- P. F. SULLIVAN, P. KOVALENKO, T. P. YORK, C. A. PRESCOTT, K. S. KENDLER
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- Published online by Cambridge University Press:
- 14 February 2003, pp. 263-281
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Background. Fatigue is a complex symptom associated with many physiological, psychological and pathological processes. Its correlates and typology remain inadequately understood.
Method. These data were from two large, longitudinal twin studies. Trained interviewers enquired as to the presence of a [ges ]5 day period in the previous year of fatigue or tiredness that interfered with daily activities. A range of potential correlates was assessed in a structured interview: demography; health beliefs; the presence of nine physical disorders; mood, anxiety and addictive disorders; neuroticism and extraversion; recollections of parental rearing; and nine stressful life events. Statistical analyses included logistic regression, CART, MARS, latent class analysis and univariate twin modelling.
Results. Data were available for interfering fatigue (IF) on 7740 individual twins (prevalence 9·9% in the previous year). IF was significantly associated with 42 of 52 correlates (most strongly with major depression, generalized anxiety disorder, reported major health problems and neuroticism). Multivariate analyses demonstrated that IF is a highly complex construct with different sets of correlates in its subtypes. There were two broad clusters of correlates of IF: (a) major depression, generalized anxiety disorder and neuroticism; and (b) beliefs of ill health coexisting with alcoholism and stressful life events. Twin analyses were consistent with aetiological heterogeneity – genetic effects may be particularly important in women and shared environmental effects in men.
Conclusions. IF is a complex and common human symptom that is highly heterogeneous. More precise understanding of the determinants of IF may lead to a fuller understanding of more extreme conditions like chronic fatigue syndrome.
Factors associated with the wish to hasten death: a study of patients with terminal illness
- B. KELLY, P. BURNETT, D. PELUSI, S. BADGER, F. VARGHESE, M. ROBERTSON
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- Published online by Cambridge University Press:
- 23 December 2002, pp. 75-81
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Background. There is considerable debate regarding the clinical issues surrounding the wish to hasten death (WTHD) in the terminally ill. The clinical factors contributing to the WTHD need further investigation among the terminally ill in order to enhance understanding of the clinical assessment and treatment needs that underlie this problem. A more detailed understanding may assist with the development of appropriate therapeutic interventions.
Method. A sample of terminally ill cancer patients (N=256) recruited from an in-patient hospice unit, home palliative care service and a general hospital palliative care consulting service from Brisbane Australia between 1998–2001 completed a questionnaire assessing psychological (depression and anxiety), social (family relationship, social support, level of burden on others) and the impact of physical symptoms. The association between these factors and the WTHD was investigated.
Results. A high WTHD was reported by 14% of patients. A discriminant function analysis revealed that the following variables were associated with a high WTHD (P<0·001): higher levels of depressive symptoms, being admitted to an in-patient hospice setting, a greater perception of being a burden on others, lower family cohesion, lower levels of social support, higher levels of anxiety and greater impact of physical symptoms.
Conclusions. Psychological and social factors are related to a WTHD among terminally ill cancer patients. Greater attention needs to be paid to the assessment of psychological and social issues in order to provide appropriate therapeutic interventions for terminally ill patients.
Remission and recurrence of depression in the maintenance era: long-term outcome in a Cambridge cohort
- N. KENNEDY, R. ABBOTT, E. S. PAYKEL
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- Published online by Cambridge University Press:
- 26 June 2003, pp. 827-838
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Background. Long-term studies of severe depression have described high rates of non-recovery, recurrence, chronic incapacity and mortality. A more recent cohort was followed-up to ascertain whether the course had improved given developments in pharmacological and psychological treatments in the last 15 years.
Method. Subjects from a cohort of 70 mainly severe recurrent depressives originally recruited to a shorter follow-up study from 1990–1992 were followed-up after 8–11 years. Data included longitudinal information on course of depression and other psychiatric disorders, pharmacological and psychological treatment and social functioning during follow-up.
Results. Sixty-nine (99%) subjects were successfully followed-up, with 61 of 66 living subjects interviewed and detailed follow-up data obtained in total on 65. Sixty (92%) of 65 subjects recovered during follow-up, with two-thirds subsequently suffering a recurrence. Eleven (17%) suffered from an episode of chronic depression of at least 2 years duration during follow-up. Social function at follow-up was good and there were high levels of pharmacological and psychological treatment. Greater severity of illness was the most consistent predictor of poor outcome. Times to recovery and recurrence and recovery and recurrence rates were very similar to older studies.
Conclusions. The long-term outcome of depression still shows high recurrence rates and does not appear to have changed in the last 20 years.
Corpus callosum in first-episode patients with schizophrenia – a magnetic resonance imaging study
- S. BACHMANN, J. PANTEL, A. FLENDER, C. BOTTMER, M. ESSIG, J. SCHRÖDER
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- Published online by Cambridge University Press:
- 31 July 2003, pp. 1019-1027
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Background. Morphometric studies on the corpus callosum (CC) in schizophrenia have yielded contradictory results. The aim of the present study was to investigate magnetic resonance imaging (MRI) abnormalities of the CC in first-episode patients with schizophrenic psychoses.
Method. We assessed volumetric MRI in 31 patients with diagnoses of schizophrenia, schizophreniform or schizoaffective disorder (DSM-IV) and a maximum exposure to neuroleptics of 2 weeks. As a control group, 12 healthy age- and sex-matched individuals were included in the study. A whole body scanner at 1.5 Tesla was used to obtain 3D T1- and T2-weighted MR datasets. The data were evaluated semi-automatically (intracranial volume, total brain volume) and manually (CC) with the software NMRwin.
Results. Patients had smaller CC and CC subdivisions than controls. Schizophrenic and unaffected women exhibited larger total CC and rostral subdivisions than men in both groups. Handedness did not exert an influence.
Conclusions. Our findings are in line with other in vivo morphometric studies on the CC in schizophrenia. The larger CC area in women may reflect general gender-related differences in CC size as described in healthy individuals.
A brief behavioural treatment of chronic post-traumatic stress disorder in earthquake survivors: results from an open clinical trial
- M. BAŞOĞLU, M. LIVANOU, E. ŞALCIOĞLU, D. KALENDER
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- Published online by Cambridge University Press:
- 13 May 2003, pp. 647-654
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Background. Natural disasters such as earthquakes affect large numbers of people. Given the extent of the mental health problem following earthquakes, brief, effective and cost-effective treatment interventions are urgently needed. The present study examined whether cognitive-behavioural treatment could be shortened to a minimum number of sessions without undermining its effectiveness in post-traumatic stress disorder (PTSD).
Method. The study participants (N=231) were consecutive referrals to five project sites in the earthquake region in Turkey a mean of 13 months after the disaster. A modified behavioural treatment (BT) was used, which involved self-exposure instructions based on an enhancement of ‘sense of control’ rather than a habituation rationale and minimal cognitive interventions. The duration of treatment was variable, involving as many sessions as required for clinical improvement. Survival analysis was used to explore the minimum number of sessions required for clinical improvement, and multiple regression analysis to examine the predictors of outcome.
Results. The survivors received a mean of 4·3 sessions. Significant treatment effects and clinically meaningful effect sizes were noted on all measures. The treatment improved all PTSD and depression symptoms. The cumulative proportion of improved cases was 76% after one session and 88% after two sessions. No baseline variable predicted treatment outcome.
Conclusions. The modified BT appears to be promising as an effective one- or two-session intervention for earthquake survivors. It may be particularly useful in large-scale disasters as a cost-effective treatment that can be relatively easily disseminated to mass populations. Further research is needed to clarify the possible role of a treatment focus on sense of control in rapid recovery from traumatic stress.
Pre-morbid characteristics and co-morbidity of methamphetamine users with and without psychosis
- C.-K. CHEN, S.-K. LIN, P. C. SHAM, D. BALL, E.-W. LOH, C.-C. HSIAO, Y.-L. CHIANG, S.-C. REE, C.-H. LEE, R. M. MURRAY
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- Published online by Cambridge University Press:
- 30 October 2003, pp. 1407-1414
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Background. The long-term use of methamphetamine (MAMP) can result in psychosis but it is not clear why some individuals develop psychotic symptoms, while others use MAMP regularly over long periods and remain unscathed. We set out to characterize MAMP users and to examine the relationship of pre-morbid personality, pre-morbid social function and other psychiatric disorders to MAMP psychosis.
Method. Four hundred and forty-five amphetamine users were recruited from a psychiatric hospital and a detention centre in Taipei, and were assessed with the Diagnostic Interview for Genetic Studies (DIGS). Their parents were interviewed with the Premorbid Schizoid and Schizotypal Traits (PSST) and the Premorbid Social Adjustment (PSA) schedules. Pre-morbid characteristics and psychiatric co-morbidity were compared between the MAMP users with a lifetime diagnosis of MAMP psychosis and those without.
Results. The MAMP users with psychosis presented a clinical picture which mimicked the positive symptoms of schizophrenia: 85% had auditory hallucinations; 71% persecutory delusions; 63% delusions of reference. Compared with their non-psychotic counterparts, these MAMP users were younger at first MAMP use, used larger amounts of MAMP, had a significantly higher mean PSST score, and higher rates of major depressive disorder, alcohol dependence and antisocial personality disorder.
Conclusions. Earlier and larger use of MAMP was associated with increased risk of psychosis. Our data are also compatible with the view that pre-morbid schizoid/schizotypal personality predisposes MAMP users to develop psychosis, and that the greater the personality vulnerability, the longer the psychosis will persist.
Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance
- F. C. MURPHY, A. MICHAEL, T. W. ROBBINS, B. J. SAHAKIAN
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- Published online by Cambridge University Press:
- 09 April 2003, pp. 455-467
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Background. Recent evidence suggests that an abnormal response to performance feedback may contribute to the wide-ranging neuropsychological deficits typically associated with depressive illness. The present research sought to determine whether the inability of depressed patients to utilize performance feedback advantageously is equally true for accurate and misleading feedback.
Method. Patients with major depression and matched controls completed: (1) a visual discrimination and reversal task that featured intermittent and misleading negative feedback; and (2) feedback and no-feedback versions of a computerised test of spatial working memory. In the feedback version, negative feedback was accurate, highly informative, and could be used as a mnemonic aid.
Results. On the Probability Reversal task, depressed patients were impaired in their ability to maintain response set in the face of misleading negative feedback as shown by their increased tendency to switch responding to the ‘incorrect’ stimulus following negative reinforcement, relative to that of controls. Patients' ability to acquire and reverse the necessary visual discrimination was unimpaired. On the Spatial Working Memory task, depressed patients made significantly more between-search errors than controls on the most difficult trials, but their ability to use negative feedback to facilitate performance remained intact.
Conclusions. The present results suggest that feedback can have different effects in different contexts. Misleading, negative feedback appears to disrupt the performance of depressed patients, whereas negative but accurate feedback does not. These findings are considered in the context of recent studies on reinforcement systems and their associated neurobiological substrates.
Psychiatrists' attitudes to maintenance medication for patients with schizophrenia
- M. X. PATEL, V. NIKOLAOU, A. S. DAVID
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- Published online by Cambridge University Press:
- 23 December 2002, pp. 83-89
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Background. Maintenance antipsychotic medication is the mainstay of relapse prevention in patients with schizophrenia. Long acting depot antipsychotics were developed to promote treatment adherence and yet their utilization is variable, perhaps due to negative attitudes of both patients and psychiatrists. Recently, a shift away from depots has occurred, in favour of the newer atypical oral antipsychotics.
Method. This study investigated the current attitudes and knowledge concerning depots, with a newly designed questionnaire, in a cross-sectional postal survey of qualified psychiatrists working in south-east England.
Results. A substantial minority of psychiatrists believe that depots are old fashioned (40%), stigmatizing (48%) and are associated with more side-effects than typical oral antipsychotics (38%). Many believe that depots are as efficacious as oral medication (91%) but are less acceptable to patients (69%) and relatives (66%). A large majority consider depots enhance patient compliance (81%) and prevent relapse (94%). Psychiatrists would be persuaded to prescribe depots if they were associated with fewer side-effects, in patients where compliance is an issue, and if atypical depot antipsychotics were available, presumably because they would have a lower incidence of side-effects. Additionally, psychiatrists' knowledge about depots was positively associated with attitudes. More favourable patient-centred attitudes were reported by psychiatrists with higher depot use.
Conclusion. Practising psychiatrists have several strongly endorsed attitudes towards depot medication that are associated with knowledge and prescribing habits. By updating psychiatrists' knowledge about depots, in turn their attitudes may become more positive and prescribing practices may subsequently change.
Effect of neuroticism, response style and information processing on depression severity in a clinically depressed sample
- D. LAM, N. SMITH, S. CHECKLEY, F. RIJSDIJK, P. SHAM
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- Published online by Cambridge University Press:
- 09 April 2003, pp. 469-479
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Background. It is postulated that individuals who score high on neuroticism would ruminate when faced with stress. A ruminative response style to depression is associated with faulty attribution and higher dysfunctional beliefs, which in turn is associated with a higher level of depression and hopelessness. Distraction is associated with less severe depression. Evidence supporting these hypotheses mainly comes from a non-clinical population. Hence it is not clear if these theories apply to clinical depression.
Method. One hundred and nine out-patients suffering from unipolar major depressive disorder were recruited to test these theories, using model-fitting analysis technique.
Results. Certain rumination responses to depression were associated with higher levels of depression and hopelessness, faulty attribution and dysfunctional attitudes when gender and the level of depression were controlled. Principal component analysis of the Rumination Scale yielded four factors: ‘symptom-based rumination’, ‘isolation/introspection’, ‘self-blame’ and ‘analyse to understand’. Unlike the other factors, ‘analyse to understand’ did not correlate with the level of depression. Model fitting analysis, though not reflecting entirely the true model, captures most of the hypothesized relationships between important variables. Neuroticism was associated with stress. Rumination was associated with an increased level of dysfunctional beliefs and faulty attribution, which in turn was associated with increased severity of depression. Distraction, in contrast, was associated with lower levels of negative mood.
Conclusion. The results of our study support the importance of teaching depressed patients to manage their depressive symptoms by avoiding rumination about their symptoms and engaging in distracting and pleasurable activities.
Attributes of long-term heavy cannabis users: a case–control study
- A. J. GRUBER, H. G. POPE, J. I. HUDSON, D. YURGELUN-TODD
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- Published online by Cambridge University Press:
- 30 October 2003, pp. 1415-1422
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Background. Although cannabis is the most widely used illicit drug in the United States, few recent American studies have examined the attributes of long-term heavy cannabis users.
Method. Using a case–control design, we obtained psychological and demographic measures on 108 individuals, age 30–55, who had smoked cannabis a mean of 18000 times and a minimum of 5000 times in their lives. We compared these heavy users to 72 age-matched control subjects who had smoked at least once, but no more than 50 times in their lives.
Results. We found no significant differences between the two groups on reported levels of income and education in their families of origin. However, the heavy users themselves reported significantly lower educational attainment (P<0·001) and income (P=0·003) than the controls, even after adjustment for a large number of potentially confounding variables. When asked to rate the subjective effects of cannabis on their cognition, memory, career, social life, physical health and mental health, large majorities of heavy users (66–90%) reported a ‘negative effect’. On several measures of quality of life, heavy users also reported significantly lower levels of satisfaction than controls.
Conclusion. Both objective and self-report measures suggest numerous negative features associated with long-term heavy cannabis use. Thus, it seems important to understand why heavy users continue to smoke regularly for years, despite acknowledging these negative effects. Such an understanding may guide the development of strategies to treat cannabis dependence.
Predictors of outcome in a fatigued population in primary care following a randomized controlled trial
- T. CHALDER, E. GODFREY, L. RIDSDALE, M. KING, S. WESSELY
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- 14 February 2003, pp. 283-287
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Background. The objective of this study was to examine factors that predicted outcome in a chronically fatigued group of patients who were randomized to cognitive behaviour therapy or counselling in primary care.
Method. Illness perceptions, attributions, fatigue, disability and demographic variables were recorded at assessment and levels of fatigue and disability were measured at 6 months post randomization. Logistic regression was used to examine associations.
Results. Factors that predicted a poor outcome (four or more on the fatigue questionnaire) were: poor social adjustment at assessment; the patients self-report that they had never seen the GP for an emotional reason; a physical illness attribution; and, a long perceived future illness duration.
Conclusions. Patients who are more psychologically minded are more likely to improve with psychological treatments in primary care. General practitioners need to assess this before referring to an appropriate therapist.
Growth hormone responses to low-dose physostigmine administration: functional sex differences (sexual diergism) between major depressives and matched controls
- R. T. RUBIN, S. A. ABBASI, M. E. RHODES, R. K. CZAMBEL
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- Published online by Cambridge University Press:
- 13 May 2003, pp. 655-665
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Background. Considerable endocrine and non-endocrine evidence supports the hypothesis of increased cholinergic activity relative to noradrenergic activity in major depression. We previously reported functional sex differences (sexual diergism) in hypothalamo–pituitary–adrenal cortical (HPA) hormone responses to the administration of low-dose physostigmine (PHYSO), a cholinesterase inhibitor, in 12 female and eight male unipolar major depressives and 12 female and eight male individually matched control subjects. Because growth hormone (GH) secretion also is influenced by cholinergic mechanisms, we measured GH in the samples from this study.
Method. Subjects underwent four test sessions 5–7 days apart: PHYSO (8 μg/kg i.v.), arginine vasopressin (AVP) (0·08 U/kg i.m.), PHYSO+AVP and saline control. The AVP was administered as a second stimulus to HPA axis hormone secretion. PHYSO and AVP produced no side-effects in about half the subjects and predominantly mild side-effects in the other half, with no significant patient–control differences. Point biserial correlations between side-effects (absent or present) after PHYSO and the corresponding GH responses were non-significant in all groups.
Results. Afternoon baseline GH was significantly higher in the women than in the men, but it was not significantly different between the female or the male patients and their respective matched controls. AVP administration had no effect on GH. PHYSO administration acutely stimulated GH secretion, to a similar degree in the women and men. The depressed patients as a group had a significantly greater average post-PHYSO GH response than did their controls, with a trend toward a significant sex×diagnosis interaction: The female depressives had a significantly greater GH response than their female controls, whereas the male depressives had a similar GH response as their male controls.
Conclusions. These findings suggest sexual diergism (functional sex differences) in baseline and cholinergically stimulated plasma GH measures between major depressives and matched normal controls.
Subclassifications for mild cognitive impairment: prevalence and predictive validity
- A. BUSSE, J. BISCHKOPF, S. G. RIEDEL-HELLER, M. C. ANGERMEYER
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- Published online by Cambridge University Press:
- 31 July 2003, pp. 1029-1038
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Background. Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. Recently published results of the Current Concepts in MCI Conference suggested subclassifications for MCI (MCI-amnestic, MCI-multiple domains slightly impaired, MCI-single nonmemory domain) based on the recognized heterogeneity in the use of the term. These subclassifications have not been empirically validated to date.
Method. A community sample of 1045 dementia-free individuals aged 75 years and over was examined by neuropsychological testing in a three-wave longitudinal study. The prevalences and the predictive validities for the subclassifications of MCI and their modifications (original criteria except for the report of subjective decline in cognitive function) were determined.
Results. The prevalence was 1 to 15% depending on the subset employed. Subjects with a diagnosis of MCI progressed to dementia at a rate of 10 to 55% over 2·6 years, depending on the subset employed. MCI-amnestic achieved the highest positive predictive power (PPP). ROC curves of the subclassifications for MCI indicate that all but one subset for MCI failed to predict dementia (MCI-multiple domains slightly impaired-modified: AUC=0·585, P<0·01, 95% CI, 0·517–0·653). The use of modified criteria for MCI (original criteria except for the report of subjective decline in cognitive function) is associated with a higher diagnostic sensitivity but also with a reduction in diagnostic specificity and PPP.
Conclusions. Modified criteria should be applied if a concept for MCI with a high sensitivity is required and the original criteria (including subjective cognitive complaint) if a concept with high specificity and high PPP is required.
Primary anxiety disorders and the development of subsequent alcohol use disorders: a 4-year community study of adolescents and young adults
- P. ZIMMERMANN, H.-U. WITTCHEN, M. HÖFLER, H. PFISTER, R. C. KESSLER, R. LIEB
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- Published online by Cambridge University Press:
- 25 September 2003, pp. 1211-1222
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Background. Cross-sectional findings in community surveys of adults suggest that adolescent anxiety disorders are strong predictors of the subsequent onset of alcohol use, abuse and dependence. However, prospective data that follow a sample of adolescents into adulthood are needed to confirm these associations.
Method. Baseline and 4-year follow-up data from the EDSP-Study, a prospective community survey of 3021 (2548 at follow-up) adolescents and young adults aged 14 to 24 years at baseline carried out in Munich, were used. DSM-IV anxiety disorders, alcohol use and alcohol use disorders were assessed with the Munich-Composite-International-Diagnostic-Interview (M-CIDI). Multiple logistic regression analysis, controlling for age, gender, other mental disorders, substance use disorders and antisocial behaviour was used to study the associations of baseline anxiety disorders with the subsequent onset and course of alcohol use and alcohol disorders.
Results. Baseline social phobia significantly predicts the onsets of regular use and hazardous use and the persistence of dependence. Panic attacks significantly predict the onsets of hazardous use and abuse as well as the persistence of combined abuse/dependence. Panic disorder significantly predicts the persistence of combined abuse/dependence. Other anxiety disorders do not significantly predict any of the outcomes.
Conclusions. Panic and social phobia are predictors of subsequent alcohol problems among adolescents and young adults. Further studies are needed to investigate the underlying mechanisms and the potential value of targeted early treatment of primary panic and social phobia to prevent secondary alcohol use disorders.
Time to recurrence after recovery from major depressive episodes and its predictors
- T. KANAI, H. TAKEUCHI, T. A. FURUKAWA, R. YOSHIMURA, T. IMAIZUMI, T. KITAMURA, K. TAKAHASHI
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- Published online by Cambridge University Press:
- 26 June 2003, pp. 839-845
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Background. Depression is a remitting but recurring disease. However, there is a paucity of prospectively recorded data on the course of depression after recovery.
Method. A multi-centre prospective serial follow-up study of an inception cohort of hitherto untreated unipolar major depression (N=95) for 6 years. We report the time to recurrence after recovery from the index depressive episode and their predictors.
Results. The cumulative probability of remaining well without subthreshold symptoms was 57% (95% CI, 46 to 68%) at 1 year, 47% (95% CI, 36 to 58%) at 2 years and 35% (95% CI, 23 to 47%) at 5 years. The same without full relapse was 79% (95% CI, 70 to 88%) at 1 year, 70% (95% CI, 60 to 80%) at 2 years and 58% (95% CI, 46 to 70%) at 5 years. The median duration of well-interval from the end of the index episode to the beginning of the subthreshold episode was 19·0 months (95% CI, 2·4 to 35·7), and that to the end of the full episode was over 6 years. Residual symptoms at time of recovery predicted earlier recurrence.
Conclusions. The median length of the well-interval was much longer than previously reported in studies employing similar definitions but dealing with a more severe spectrum of patients. However, the sobering fact remains that less than half of the patients can expect to remain virtually symptom-free for 2 years or more after recovery from the depressive episode.