Apathy and depressed mood in acquired brain damage: relationship to lesion localization and psychophysiological reactivity

BACKGROUND: Apathy is a frequent neurobehavioural sequel in patients with acquired brain damage and it may seriously affect outcome of rehabilitation. METHODS: Patients with traumatic brain injury, cerebrovascular insults and hypoxic brain injury, categorized into four lesion localization groups: left hemisphere damage (LHD); right hemisphere damage (RHD); bilateral hemispheric damage (BHD); and subcortical damage (SCD) were assessed with the Apathy Evaluation Scale (AES) and Montgomery and Asberg Depression Rating Scale (MADRS). Heart rate and electrodermal activity were recorded in an experimental situation that exposed the patients to mental stressors in order to measure psychophysiological reactivity. RESULTS: Significant differences in level of apathy were found between diagnostic groups as well as between localization subgroups. SCD and RHD patients displayed most apathy. Factor analysis of MADRS revealed a three-factor solution; depressed mood, somatic symptoms and negative symptoms. Apathy was significantly correlated with negative symptoms in all localization subgroups, except among the BHD patients. Apathy was not correlated with depressed mood or somatic symptoms. Moreover, apathy was significantly correlated with heart rate reactivity, but not with electrodermal reactivity. CONCLUSION: Apathy is common, its severity depending on diagnosis and localization of lesion. Apathy and depression in brain damaged patients share common features, but may be differentiated. The significant relationship between apathy and heart rate may provide a psychophysiological correlation of the disengagement, lack of interest and absence of emotional responsivity typically seen in apathy. The results have implications for the theoretical understanding of apathy and related negative symptoms, and for rehabilitation practice.     

Decision strategies in neuropsychology III: The relationship among lateralized dysfunction, etiology and depression

The present study examines depression as a function of lateralized dysfunction and etiology. The proposed hypothesis is: patients with left hemisphere lesions would be depressed, whereas patients with right hemisphere lesions would not. A total of 61 patients (26 right hemisphere, 35 left hemisphere) having either a stroke, tumor, or penetrating head wound, completed the MMPI and were given a neuropsychological evaluation. Lesion localization was based on electroencephalography and neuroradiological procedures. A regression formula derived from the MMPI assessed depression. Two analyses were performed between: (i) right and left lesioned groups of mixed etiology and a control group, and (ii) right and left cerebrovascular lesioned groups and a control group. Potentially confounding factors, such as, diagnosis, demographic factors, degree of neuropsychological impairment, presence or absence of aphasia, and lesion localization were examined. Regardless of etiology, left and right lesioned patients did not significantly differ in their depression score, nor was either group considered depressed based on the criteria used in this study to measure depression.     

Brain structure and symptom dimension relationships in obsessive-compulsive disorder: a voxel-based morphometry study

BACKGROUND: Obsessive-compulsive disorder (OCD) is a clinically heterogenous disorder characterized by temporally stable symptom dimensions. Past inconsistent results from structural neuroimaging studies of OCD may have resulted from the effects of these specific symptom dimensions as well as other socio-demographic and clinical variables upon gray matter (GM) volume. METHODS: GM volume was measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based morphometry (VBM), controlling for age and total brain GM volume. Univariate and multivariate regression analyses were carried out between regions of GM difference and age, age of onset, medication load, OCD severity, depression severity, and separate symptom dimension scores. RESULTS: Significant GM volumetric differences in OCD patients relative to controls were found in dorsal cortical regions, including bilateral BA6, BA46, BA9 and right BA8 (controls>patients), and bilateral midbrain (patients>controls). Stepwise regression analyses revealed highly significant relationships between greater total OCD symptom severity and smaller GM volumes in dorsal cortical regions and larger GM volumes in bilateral midbrain. Greater age was independently associated with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes in right midbrain. Greater washing symptom severity was independently associated with smaller GM volume in right BA6, while there was a trend association between greater hoarding symptom severity and lower GM volume in left BA6. LIMITATIONS: The sample was relatively small to examine the relationship between symptom scores and GM volumes. Multiple patients were taking medication and had comorbid disorders. CONCLUSIONS: These analyses suggest dorsal prefrontal cortical and bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by the effects of total OCD symptom severity. The results regarding the relationship between GM volumes and symptom dimension scores require examination in larger samples.     

Gray matter reduction associated with psychopathology and cognitive dysfunction in unipolar depression: a voxel-based morphometry study

BACKGROUND: Functional neuroimaging studies on both cognitive processing and psychopathology in patients with major depression have reported several functionally aberrant brain areas within limbic-cortical circuits. However, less is known about the relationship between psychopathology, cognitive deficits and regional volume alterations in this patient population. METHODS: By means of voxel-based morphometry (VBM) and a standardized neuropsychological test battery, we examined 15 patients meeting DSM-IV criteria for major depression disorder and 14 healthy controls in order to investigate the relationship between affective symptoms, cognitive deficits and structural abnormalities. RESULTS: Patients with depression showed reduced gray matter concentration (GMC) in the left inferior temporal cortex (BA 20), the right orbitofrontal (BA 11) and the dorsolateral prefrontal cortex (BA 46). Reduced gray matter volume (GMV) was found in the left hippocampal gyrus, the cingulate gyrus (BA 24/32) and the thalamus. Structure-cognition correlation analyses revealed that decreased GMC of the right medial and inferior frontal gyrus was associated with both depressive psychopathology and worse executive performance as measured by the Wisconsin Card Sorting Test (WCST). Furthermore, depressive psychopathology and worse performance during the WCST were associated with decreased GMV of the hippocampus. Decreased GMV of the cingulate cortex was associated with worse executive performance. LIMITATIONS: Moderate illness severity, medication effects, and the relatively small patient sample size should be taken into consideration when reviewing the implications of these results. CONCLUSIONS: The volumetric results indicate that regional abnormalities in gray matter volume and concentration may be associated with both psychopathological changes and cognitive deficits in depression.     

Decreased working memory and processing speed mediate cognitive impairment in geriatric depression

BACKGROUND: While neuropsychological dysfunction is common in geriatric depression, not all aspects of cognition are equally affected. It has been suggested that depressed patients are impaired only in tasks that make heavy demands on processing resources and that a resource decrement therefore underlies the neuropsychological decrements seen in geriatric depression. The present study examined whether processing resources in the form of working memory and information processing speed are decreased in depression and whether a decrease in these resources actually mediates neuropsychological impairment. METHODS: Measures of processing resources were administered to elderly depressed patients prior to treatment and to age-matched controls. Patients whose depression remitted were retested as were the controls. Subjects also received neuropsychological tests of episodic memory and visuospatial performance. RESULTS: Depressed patients performed significantly worse on measures of both processing speed and working memory. While performance on these measures improved in patients whose depression remitted, the amount of improvement was no greater than that seen in the controls with repeat testing. Hierarchical regression analyses showed that depression explained a significant amount of variance on the neuropsychological tasks. However, if the variance associated with processing resources was removed first, depression no longer accounted for a significant amount of neuropsychological variance. CONCLUSIONS: Processing resources are decreased in elderly depressed patients and this decrease in resources appears to mediate impairments in several areas of neuropsychological functioning including episodic memory and visuospatial performance. The resource decrement persists after remission of the depression and thus may be a trait marker of geriatric depression.     

Depression with late onset is associated with right frontal lobe atrophy

BACKGROUND: The objective of this study was to determine whether older adults with first-ever onset of depression after age 60 years (late onset depression, LOD) have smaller frontal lobes than elderly patients with early-onset depression (EOD) and aged controls. METHOD: Twenty-seven subjects with LOD, 24 with EOD and 37 controls underwent volumetric MRI to determine right and left frontal lobe volumes and total brain volume. RESULTS: The right frontal volume of subjects with LOD was 8.0% and 5.6% smaller than that of patients with EOD (P < 0.01) and controls (NS) respectively. Volume of the left frontal lobe was not significantly different from EOD or controls. All analyses were adjusted for age, gender and total brain volume. Unlike controls and those with EOD, patients with LOD did not display a significant positive correlation between cognitive scores and total brain, left frontal or right frontal volumes. CONCLUSION: LOD is associated with right frontal lobe atrophy and loss of the correlation between cognitive performance and brain volume. This adds support to the fronto-striatal hypothesis of depression and suggests that structural brain changes have a particular role in cases of LOD.     

Sleep apnea in acute cerebrovascular diseases: final report on 128 patients

Although obstructive sleep apnea (OSA) appears to be a cardiovascular risk factor, its frequency in patients with transient ischemic attack (TIA) and stroke remains poorly known. We prospectively studied 128 patients (mean +/- SD age = 59 +/- 15 years) with stroke (n = 75) or TIA (n = 53). Assessment included body mass index (BMI); history of snoring and daytime sleepiness; cardiovascular risk factors and diseases; and severity of stroke (Scandinavian Stroke Scale = SSS). Polysomnography (PSG) was obtained in 80 subjects (group 1), a mean of 9 days (range, 1-71 days) after TIA or stroke. In 48 subjects (group 2), PSG was not available, refused, or inadequate. Groups 1 and 2 were similar with the exception of gender distribution. Clinical and PSG data were compared to those of 25 healthy controls matched for age, gender, and BMI. An apnea-hypopnea index (AHI) > 10 was found in 62.5% of subjects and 12.5% of controls. Between patients and controls there was a significant difference in AHI (mean [range]: 28 (0-140) vs 5 (0-24), p < 0.001), maximal apnea duration (mean + SD: 37 +/- 23 vs 23 +/- 13 seconds, p = 0.009), and minimal oxygen saturation (mean + SD: 82 +/- 10% vs 90 +/- 5%, p < 0.001). Conversely, frequency and severity of OSA were similar in stroke and TIA subjects. Multiple regression analysis identified age, BMI, diabetes, and SSS as independent predictors of AHI. Sleep apnea has a high frequency in patients with TIA and stroke, particularly in older patients with high BMI, diabetes, and severe stroke. These results may have implications for prevention, acute treatment, and rehabilitation of patients with acute cerebrovascular diseases.     

The neurobiology of depression in later-life: clinical, neuropsychological, neuroimaging and pathophysiological features

As the population ages, the economic and societal impacts of neurodegenerative and neuropsychiatric disorders are expected to rise sharply. Like dementia, late-life depressive disorders are common and are linked to increased disability, high healthcare utilisation, cognitive decline and premature mortality. Considerable heterogeneity in the clinical presentation of major depression across the life cycle may reflect unique pathophysiological pathways to illness; differentiating those with earlier onset who have grown older (early-onset depression), from those with illness onset after the age of 50 or 60 years (late-onset depression). The last two decades have witnessed significant advances in our understanding of the neurobiology of early- and late-onset depression, and has shown that disturbances of fronto-subcortical functioning are implicated. New biomedical models extend well beyond perturbations of traditional monoamine systems to include altered neurotrophins, endocrinologic and immunologic system dysfunction, inflammatory processes and gene expression alterations. This more recent research has highlighted that a range of illness-specific, neurodegenerative and vascular factors appear to contribute to the various phenotypic presentations. This review highlights the major features of late-life depression, with specific reference to its associated aetiological, clinical, cognitive, neuroimaging, neuropathological, inflammatory and genetic correlates. Data examining the efficacy of pharmacological, non-pharmacological and novel treatments for depression are discussed. Ultimately, future research must aim to evaluate whether basic biomedical knowledge can be successfully translated into enhanced health outcomes via the implementation of early intervention paradigms.     

Neuropsychological performance and dementia in depressed patients after 25-year follow-up: a controlled study

BACKGROUND: Previous research has yielded conflicting evidence regarding the long-term cognitive outcome of depression. Some studies have found evidence for a higher incidence of subsequent cognitive impairment or dementia, while others have refuted this. METHOD: Depression, neuropsychological performance, functional ability and clinical variables were assessed in a sample of patients who had been hospitalized for depression 25 years previously. RESULTS: Data were available on 71 depressed patients (10 of whom were deceased) and 50 surgical controls. No significant differences were found between depressed subjects and controls on any neuropsychological measure. Ten depressed patients but no controls were found to have dementia at follow-up (continuity corrected chi2 = 5.93, P < 0.01). Presence of dementia was predicted by older age at baseline. Vascular dementia was the most common type. CONCLUSIONS: We conclude that this study did not find evidence that early onset depression is a risk factor for Alzheimer's disease, but that for a small subgroup there appears to be a link with vascular dementia. Several plausible explanations for this link, such as lifestyle factors, require further investigation.     

脑血管病人的心理健康状况调查

脑血管病人常常会出现明显的心理改变 ,除认知功能受损外 ,抑郁、焦虑、恐怖、强迫、躯体化、精神病性等症状亦十分突出 ,这些改变严重影响病人的康复和预后 ,影响病人的生活质量 ,给家庭和社会带来沉重的负担。本文旨在探讨脑血管病人的这些心理改变特点 ,以便提供必要的临床干预和治疗。1　资料和方法1.1　病例组病例组选自哈尔滨医科大学附属二院神经科2 0 0 1年 10月至 2 0 0 2年 2月住院治疗的脑血管病病人 ,共计 6 0例。符合中华医学会第四届全国脑血管病学术会议各类脑血管病诊断要点 ,全部病例均否认曾经患过脑卒中 ,经CT或MRI确…     

Neuropsychological impairment after hemorrhagic stroke in basal ganglia.

We aimed to determine the severity and pattern of cognitive dysfunction in patients with basal ganglia (BG) hemorrhage within the first 6 months after stroke and to identify its clinical correlates. The study samples consisted of 30 patients with BG hemorrhage and 37 healthy controls. A comprehensive neuropsychological battery including tests of attention, memory, language, visuospatial function, and executive function was administered to all participants. Relative to healthy controls, BG patients performed significantly worse across different cognitive domains after controlling for age, sex, and education. 96.7% of patients displayed defective performance on at least three neuropsychological tests. Discriminant function analysis showed that visuospatial function and memory were the best predictors of group membership (patient/control), with an overall classification rate of 95.5%. Only side of stroke and admission Glasgow Coma Scale (GCS) score correlated significantly with some of the cognitive domains. The widespread pattern of cognitive deficits seen in BG patients provides evidence for the substantial involvement of the BG in many neuronal pathways connecting cortical and subcortical brain areas responsible for various cognitive functions.     

Treatment response in late-onset depression: relationship to neuropsychological, neuroradiological and vascular risk factors

BACKGROUND: Late-onset depressive disorder is associated with white matter lesions and neuropsychological deficits that in some studies are linked to a poorer outcome for depression. Some white matter lesions may be vascular in origin. This study investigated the relationship between response or non-response to antidepressant monotherapy and neuropsychological function, structural brain measures and vascular factors. METHOD: This was a case control study. Fifty patients with late-onset major depressive disorder (29 who were responders to antidepressant monotherapy and 21 who were not) were compared with 35 non-depressed control subjects. Measures included assessment of vascular risk factors, neuropsychological testing and a magnetic resonance imaging (MRI) scan. RESULTS: After adjustment for depressed mood and medication at evaluation, both patient groups had significantly more impairment compared to control subjects on verbal learning tasks involving immediate or delayed recall. Patients who did not respond to antidepressant monotherapy had significantly poorer performance than controls on tests involving visuospatial ability, language, word recognition and tests of executive function, whereas there were no differences between control subjects and responders. On two tests of executive function (verbal fluency and the Stroop test) non-responders scored significantly worse than responders. There were no significant group differences on MRI measures of atrophy or of white matter lesions apart from a higher periventricular hyperintensity score in non-responders compared to controls. There were no group differences on measures of vascular disease. CONCLUSION: The results lend support to the emerging evidence that resistance to treatment in late-onset depression may be associated with impaired executive function. Subtle cerebrovascular mechanisms may be involved.     

Executive dysfunction in medicated, remitted state of major depression

BACKGROUND: Past neuropsychological studies on depression have documented executive dysfunction and it has been reported that some dysfunction persists even after depressive symptoms disappear. Studies have shown a correlation between cerebrovascular lesions and executive dysfunction in depression among the elderly. The aim of the present study was to focus on executive functions in remitted major depressive disorder (MDD) patients, and to investigate whether remitted young and elderly patients show different patterns of executive dysfunction, and to ascertain the relationships with vascular lesions. METHODS: Subjects were 79 inpatients with MDD and 85 healthy controls. Each subject received Wisconsin Card Sorting Test (WCST), Stroop test, and Verbal Fluency Test (VFT) in a remitted state. Both the MDD and control groups were divided into young and elderly groups, and the performances between 4 groups were compared. RESULTS: For Stroop test, the scores of the MDD group were significantly lower than controls. In addition, as for VFT, the scores for the elderly MDD group were significantly lower than the other groups. Multiple regression analysis showed that VFT scores were affected by the presence of vascular lesions. CONCLUSIONS: The results of the present study demonstrated that executive dysfunction remained even in a remitted state in MDD patients, but the patterns of impairment were different between young and elderly patients. The results also suggested that vascular lesions affect executive dysfunction, particularly in elderly depressive patients.     

The prolactin response to buspirone in poststroke depression: a preliminary report

BACKGROUND: The issue of whether a serotonergic abnormality is involved in poststroke depression (PSD) was investigated in a sample of poststroke patients. METHODS: The severity of depression was assessed by Hamilton Rating Scale for Depression (HDRS). Buspirone was administered to 16 depressed poststroke (DPS), 10 non-depressed post-stroke (NDPS) patients, and 10 male healthy controls (HCs), to evaluate serotonin (5-HT) function. RESULTS: The prolactin (PRL) response was significantly blunted in DPS patients compared to HCs. There was no significant relationship between the severity of depression and lesion lateralization. Also, no significant differences in buspirone-induced PRL responses were found between DPS patients with right- and left-sided lesions. The severity of depression in DPS patients was not correlated with the time since stroke. CONCLUSIONS: Our results suggest that serotonergic dysfunction may involve in development of poststroke depression. LIMITATIONS: The relatively small sample size and the failure to adequately control for age are major limitations of this study.     

Right lower prefronto-parietal cortical dysfunction in akinetic catatonia: a combined study of neuropsychology and regional cerebral blood flow

BACKGROUND: Catatonia is a psychomotor syndrome that can be characterized by behavioural, affective and motor abnormalities. In order to reveal further underlying pathophysiological mechanisms of psychomotor disturbances in catatonia we investigated neuropsychological function and regional cerebral perfusion (r-CBF) in a combined study. METHODS: Ten catatonic patients were investigated with Tc-99mECD brain SPECT and compared with 10 psychiatric (similar age, sex, medication and underlying psychiatric diagnosis but without catatonic syndrome) and 20 healthy controls. Neuropsychological measures included tests for general intelligence, attention, executive functions and right parietal visual-spatial abilities. Correlational analyses were performed between neuropsychological measures, catatonic symptoms and r-CBF. RESULTS: Catatonic patients showed a significant decrease of r-CBF in right lower and middle prefrontal and parietal cortex compared with psychiatric and healthy controls as well as significantly poorer performance in visual-spatial abilities associated with right parietal function. Correlational analysis revealed significant correlations between visual-spatial abilities and right parietal r-CBF only in psychiatric and healthy controls but not in catatonic patients. In contrast, attentional measures correlated significantly with motor symptoms, visual-spatial abilities and right parietal r-CBF in catatonia only but not in psychiatric or in healthy controls. CONCLUSION: Findings are preliminary but suggest right lower prefronto-parietal cortical dysfunction in catatonia, which may be closely related to psychomotor disturbances.     

Comparison of cognitive impairment associated with major depression following stroke versus traumatic brain injury

Several studies have reported an association between cognitive impairment and major depression following stroke but failed to find a similar association among patients with traumatic brain injury (TBI). This study examined the hypothesis that age differences between stroke and TBI patients would account for the differences in the effect of major depression on cognitive function. We examined subjects' cognitive function using the Mini-Mental State Examination and compared findings among patients with stroke or TBI. Results indicated that stroke patients with major depression (N = 73) were significantly older and more cognitively impaired than similar TBI patients (N = 35), even after matching patients for lesion volume and years of education. After matching for age, however, there was no association of major depression with cognitive impairment in this relatively young stroke population. These findings support the hypothesis that age, presumably related to physiological response to brain injury, accounts for differences in the effect of major depression on cognitive function between stroke and TBI patients.     

Centrum semiovale white matter CT changes associated with normal ageing, Alzheimer's disease and late life depression with and without reversible dementia

A standardized, reliable means of assessing CT attenuation numbers in the centrum semiovale and surrounding grey matter was developed. This was applied to cranial CT scans of 60 normal controls (36 aged greater than 60 years), 25 elderly patients with major depression (14 of whom had the dementia syndrome of depression), and 10 patients with Alzheimer's disease (AD). Subjects received neuropsychological evaluation. Centrum semiovale (CSO) CT attenuation numbers decreased with increasing age for both white and grey matter. White matter attenuation values best discriminated elderly controls from the three patient groups. Both white and grey matter CSO attenuation values correlated with performance on a number of cognitive tasks.     

Neuropsychological correlates of methylphenidate treatment in adult ADHD with and without depression.

The purpose of this study was to characterize the neuropsychological profiles of adult patients with attention deficit hyperactivity disorder (ADHD) alone and ADHD with active comorbid depression, and to evaluate changes in the neuropsychological profile in these two groups following a trial of methylphenidate. Forty patients with ADHD were classified into two groups based on their affective status resulting in a group of 21 patients with ADHD alone and 19 patients with ADHD and active comorbid symptoms of depression (ADHD-D). All subjects received a comprehensive neuropsychological evaluation including measures of cognitive, motor and affective functioning before and after treatment. Fifteen normal controls were also assessed at a yoked time interval. At baseline, both patient groups showed impairment in verbal memory, motor and processing speed, visual scanning, and auditory and visual distractibility. Following treatment, both patient groups showed improvement across all neuropsychological measures while controls remained relatively stable over time. Improvement in neuropsychological test performance was not related to gender, affective status or referral source. Patients with active comorbid symptoms of depression show a similar neuropsychological profile and appear equally likely to benefit from methylphenidate intervention as patients with ADHD alone.     

A neuroendocrine study of serotonin function in depressed stroke patients compared to non depressed stroke patients and healthy controls.

OBJECTIVES: We employed a neuroendocrine challenge paradigm to study serotonergic abnormalities associated with poststroke depression. METHOD: Twelve depressed stroke patients (major depression N= 5, minor depression N = 7), 8 nondepressed stroke patients and 12 healthy volunteers completed a single-blind, placebo-controlled, challenge tests. Baseline cortisol (CORT) and prolactin (PRL) values, and these hormonal responses to 30 mg of oral d-FEN and placebo over a 4 hour period were measured in the three groups. RESULTS: There were intergroup differences for baseline adjusted PRL responses (change scores from baseline) to d-FEN (group effect F = 4.38, df = 2,29, p = 0.02) while these responses to placebo were comparable between groups (group effect F = 1.82, df = 2,29, p = 0.18). Peak PRL responses (post d-FEN maximal PRL change from baseline scores) in depressed stroke patients were significantly greater than in nondepressed patients (p = 0.005) but comparable to healthy normals (p = 0.47). However, these responses between major and minor depression were not significant (p = 0.34). There was a trend suggesting a negative correlation between peak PRL response and severity of depression (p = 0.056). Depressed patients were younger than the controls (p = 0.054). Also, the depressed group was more functionally impaired (p = 0.04) and more likely to have right-sided lesions (p = 0.009) compared with the nondepressed group. Differences in baseline adjusted PRL changes between depressed and nondepressed groups became non significant when the influence of laterality of lesions was covaried, whereas covariation of functional scores and age did not alter the significance. CORT responses did not show intergroup differences. LIMITATIONS: The study group was small and was heterogenous in lesion characteristics, time since stroke and type of depression. A fixed-order design was used in the challenge test paradigm. CONCLUSIONS: When laterality of stroke lesion was taken into account, depressed and nondepressed stroke patients did not differ in PRL responses to d-FEN.