Eugene S. Paykel

Residual symptoms after partial remission : an important outcome in depression

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.

Emotional bias and inhibitory control processes in mania and depression

BACKGROUND Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. The disinhibited behaviour characteristic of mania and evidence that subgenual prefrontal cortex is differentially activated in mania and depression both suggest that dissociable deficits will emerge on tasks that require inhibitory control and are subserved by ventromedial prefrontal cortex. METHODS Manic patients and controls undertook computerized neuropsychological tests of memory and planning ability. In addition, manic and depressed patients were directly compared with controls on a novel affective shifting task that requires inhibitory control over different components of cognitive and emotional processing. RESULTS Manic patients were impaired on tests of memory and planning. Importantly, affective shifting performance of manic patients differed from that of depressed patients. Manic patients were impaired in their ability to inhibit behavioural responses and focus attention, but depressed patients were impaired in their ability to shift the focus of attention. Depressed patients exhibited an affective bias for negative stimuli, and we believe this to be the first demonstration of an affective bias for positive stimuli in manic patients. CONCLUSIONS Observed impairments on tests of memory and planning suggest a global pathology for mania consistent with previous profiles for this disorder and similar to established profiles for depression. The results on the affective shifting task demonstrate the presence of mood-congruent bias and dissociable components of inhibitory control in mania and depression. Against a background of memory and planning impairments in the two groups, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.

Life events and affective disorders.

Objective:  To summarize research in life events and affective disorders

Cognitive impairment in remission in bipolar affective disorder.

BACKGROUND Although the traditional view of bipolar affective disorder is that the majority of patients have full remission between episodes, recent evidence suggests that residual cognitive deficits are present. The aim of this study was to determine whether memory and executive deficits were present in a well-defined clinically remitted group of patients. METHODS This was a case-control study of bipolar patients in remission (N = 18). Subjects had to fulfil stringent clinical criteria for inclusion into the study and had to have been in remission for at least 4 months. Subjects also had no history of substance dependence. The cognitive battery examined memory and executive function. RESULTS Patients in excellent clinical remission and who reported good social adaptation showed imipairment on tests of visuospatial recognition memory. Accuracy on four tests of executive function was not impaired in patients in remission compared with controls, although response latency on these executive tests was still impaired. CONCLUSIONS As our group and others have shown, patients with mania and unipolar depression show generalized impairment on tests of memory and executive function. In comparison, this study has demonstrated that patients in remission show a relatively specific impairment in memory with recovery of accuracy measures on executive function task. The increased response latency on the executive tasks suggests a possible small residual impairment. These findings suggest that in netIroanatomical terms, more posterior cortical function (temporal lobe) has not improved but there is at least some recovery of frontal lobe function in remission.

Size and burden of depressive disorders in Europe

We review epidemiological studies of depression in Europe. Community surveys are essential. Methodological differences in survey methods, instruments, nuances in language and translation limit comparability, but consistent findings are emerging. Western European countries show 1 year prevalence of major depression of around 5%, with two-fold variation, probably methodological, and higher prevalences in women, the middle-aged, less privileged groups, and those experiencing social adversity. There is high comorbidity with other psychiatric and physical disorders. Depression is a major cause of disability. Incidence has been less studied and lifetime incidence is not clear, with longitudinal studies required. There is pressing need for prevalence studies from Eastern Europe. The considerable differences in health care systems among European countries may impact on proportions of depressives receiving treatment and its adequacy, particularly in the key area of primary care, and require further study. There is a need for public health programmes aimed at improving treatment, reducing rates and consequences of depressive disorders.

Abnormal response to negative feedback in unipolar depression: evidence for a diagnosis specific impairment

OBJECTIVES To assess in further detail the specific form of motivational impairment influencing neuropsychological performance in depression—oversensitivity to perceived failure. The present study considers two questions: firstly whether this is specific to depression and secondly how the effect relates to clinical features. METHODS Unipolar depressed patients and matched controls were assessed on two neuropsychological tests giving explicit performance feedback. The data were analysed in two separate studies to consider the questions above. The first study considered the specificity of the effect to depressed patients, using data on the same tests collected from other patient groups. The second study was a longitudinal assessment of the depressed patients on clinical recovery to determine whether the effect is specific to the depressed state. RESULTS The effect was not seen in non-depressed patient groups, either neurological or psychiatric groups. The longitudinal study showed a residual abnormal response to negative feedback on clinical recovery. CONCLUSIONS Abnormal response to negative feedback is specific to a primary diagnosis of depression and may be a trait rather than a state factor of the disorder. These results are discussed in relation to the putative neuropathology of depression and also to cognitive and behavioural accounts of the disorder. The findings presented here have important implications for establishing a link between mood and cognition in unipolar depression.

Remission and relapse in major depression: a two-year prospective follow-up study.

This paper reports the course with respect to remission and relapse of a cohort of predominantly in-patient RDC major depressive subjects, who were followed at 3-monthly intervals to remission and for up to 15 months thereafter. Remission was comparatively rapid with 70% of subjects remitting within 6 months. Only 6% failed to do so by 15 months. However, 40% relapsed over the subsequent 15 months, with all the relapses occurring in the first 10 months. Greater severity of the depression and longer duration of the illness predicted a longer time to remission. Greater initial severity of depression also predicted relapse. Subjects with a worse outcome had not received less adequate treatment than the remainder. Our results confirm the comparatively poor outcome subsequent to remission that has been reported in recent literature, in spite of the availability of modern methods of treatment. The clustering of relapses in the first 10 months gives some support to the distinction between relapse and later recurrence.

Urban–rural mental health differences in Great Britain: findings from the National Morbidity Survey

Studies of urban-rural differences in prevalence of non-psychotic mental disorder have not given consistent findings. Such differences have received relatively little study in Great Britain. Data from 9777 subjects in the Household Survey of the National Morbidity Survey of Great Britain were analysed for differences between urban, semi-rural, and rural areas. Psychiatric morbidity was assessed by scores on the Revised Clinical Interview Schedule (CIS-R), together with alcohol dependence, drug dependence, and receipt of treatment from general practitioners. Associations with other characteristics were examined by logistic regression. Urban subjects had higher rates than rural of CIS-R morbidity, alcohol dependence, and drug dependence, with semi-rural subjects intermediate. Urban subjects also tended to be members of more deprived social groups, with more adverse living circumstances and greater life stress--factors themselves associated with disorder. Urban-rural differences in alcohol and drug dependence were no longer significant after adjustment for these factors by logistic regression, and differences on CIS-R morbidity were considerably reduced. There were no differences in treatment. There are considerable British urban-rural differences in mental health, which may largely be attributable to more adverse urban social environments.

Residual symptoms at remission from depression: impact on long-term outcome.

BACKGROUND Although residual symptoms after remission from depression are common and predict early relapse, little is known about the impact of residual symptoms on longer-term clinical course of depression or social functioning. METHODS Sixty severe recurrent depressives, who remitted from an index episode of depression with residual symptoms or below residual symptomatology, were followed-up at 8-10 years. Subjects underwent detailed longitudinal interviewing on course of depression, treatment and socioecomonic functioning over follow-up. RESULTS Long-term follow-up data was obtained on all living subjects and 55 (95%) were interviewed. The residual symptoms group spent more time with depressive symptoms over follow-up but not at full criteria for major depression and showed greater impairment in longitudinal and follow-up social adjustment. No significant differences were found between the two groups in percentage recurring long-term, mean number of recurrences, readmissions, chronic episodes or clinical global outcome criteria. LIMITATIONS Long-term clinical and social outcomes were assessed by a single retrospective longitudinal interview. CONCLUSIONS Patients who remit from depression with residual symptomatology continue to have more depressive symptoms and impaired social functioning long-term and may need more aggressive treatment.

Staging of Cytoskeletal and β-Amyloid Changes in Human Isocortex Reveals Biphasic Synaptic Protein Response during Progression of Alzheimer’s Disease

We have examined the relationships between dementia, loss of synaptic proteins, changes in the cytoskeleton, and deposition of beta-amyloid plaques in the neocortex in a clinicopathologically staged epidemiological cohort using a combination of biochemical and morphometric techniques. We report that loss of synaptic proteins is a late-stage phenomenon, occurring only at Braak stages 5 and 6, or at moderate to severe clinical grades of dementia. Loss of synaptic proteins was seen only after the emergence of the full spectrum of tau and beta-amyloid pathology in the neocortex at stage 4, but not in the presence of beta-amyloid plaques alone. Contrary to previous studies, we report increases in the levels of synaptophysin, syntaxin, and SNAP-25 at stage 3 and of alpha-synuclein and MAP2 at stage 4. Minimal and mild clinical grades of dementia were associated with either unchanged or elevated levels of synaptic proteins in the neocortex. Progressive aggregation of paired helical filament (PHF)-tau protein could be detected biochemically from stage 2 onwards, and this was earliest change relative to the normal aging background defined by Braak stage 1 that we were able to detect in the neocortex. These results are consistent with the possibility that failure of axonal transport associated with early aggregation of tau protein elicits a transient adaptive synaptic response to partial de-afferentation that may be mediated by trophic factors. This early abnormality in cytoskeletal function may contribute directly to the earliest clinically detectable stages of dementia.