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PubMed1998

Neuropsychiatry and pituitary disease: an overview.

It has been recognized for some time that psychiatric symptoms, such as depression, anxiety, and behavioral alterations, may occur in patients who have pituitary disease. From other research focused on endocrine abnormalities seen in patients with psychiatric illness, it is understood that there is a significant interrelationship between the endocrine system and mental health. More recent research focusing on neural circuits in the brain and the impact of alterations in neurotransmission and neurohormonal modulation has shown that the prefrontal cortex can be affected by perturbations in functioning occurring in distant sites. Such is the situation with the hypothalamic-pituitary axis. Through its rich connections with other limbic structures, the hypothalamic-pituitary axis may affect the behavioral control exerted by the prefrontal cortex, causing mood and personality alterations. In the more severe cases, an apathy syndrome may develop which must be carefully differentiated from depression and other cognitive disorders. This report will review: (1) the neuroanatomical components that cause the behavioral changes observed in many patients with pituitary disease; (2) the current concept of apathy syndrome; (3) the differentiation of apathy syndrome from major depression; (4) the underlying neurobiology of apathy, and (5) potential treatments.

Depressive Disorder↗
PubMed2005

A prospective study of predictors of poststroke depression.

OBJECTIVE: To investigate the association between early depressive behavior after stroke onset and occurrence of poststroke depression (PSD) at 3- and 12-month follow-up evaluations. METHODS: The study prospectively included 273 patients with first-ever single uncomplicated ischemic stroke. In the stroke unit, nurses scored crying, overt sadness, and apathy daily using an observational method to include patients with comprehension deficits. The Barthel Index was used to assess disability. Follow-up evaluation at months 3 and 12 included psychiatric assessment based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. RESULTS: Crying (19.8%), overt sadness (50.5%), and apathy (47.6%) were observed. Of the patients observed crying, 4 showed pathologic crying, 19 emotionalism, and 12 catastrophic reactions. Crying and overt sadness, but not apathy, were associated with a subjective experience of depression (p < 0.05). Thirty of 52 (58%) patients observed crying, 12 of 19 (63%) patients with emotionalism, and 5 of 12 (41%) patients with catastrophic reactions developed PSD within the first year. Multiple logistic regression analysis showed that only severe functional disability (odds ratio [OR], 4.31; 95% CI, 2.41 to 7.69), crying behaviors (OR, 2.66; 95% CI, 1.35 to 5.27), and an age <68 years (OR, 2.32; 95% CI, 1.30 to 4.13) were (p < 0.05) predictors of late PSD development (13% of the variance). CONCLUSIONS: In the stroke unit, crying and overt sadness are more reliable indicators of depressed mood than apathy. In patients with first-ever stroke, crying behaviors soon after stroke, a younger age, and severe disability are predictors of poststroke depression occurrence within the first year after stroke onset.

Aged↗
PubMed2005

The course of neuropsychiatric symptoms in dementia. Part I: findings from the two-year longitudinal Maasbed study.

BACKGROUND: Although neuropsychiatric symptoms in dementia are common, there have been few large long-term prospective studies assessing the course of a broad range of neuropsychiatric symptoms in dementia. OBJECTIVES: To investigate the course of neuropsychiatric symptoms in patients with dementia, including data about prevalence, incidence and persistence. METHODS: One hundred and ninety-nine patients with dementia were assessed every six months for two-years, using the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms. RESULTS: Nearly all patients (95%) developed one or more neuropsychiatric symptoms in the two-year study period. Mood disorders were the most common problem. The severity of depression decreased, whereas the severity of apathy and aberrant motor behaviour increased during follow-up. The cumulative incidence was highest for hyperactive behaviours and apathy. Overall behavioral problems were relatively persistent, but most symptoms were intermittent, with apathy and aberrant motor behaviour being persistent for longer consecutive periods. CONCLUSIONS: Neuropsychiatric symptoms in dementia are a common and major problem. Different symptoms have their own specific course, most of the time show a intermittent course, but behavioural problems overall are chronically present. The data have implications for developing treatment strategies.

Aged↗
PubMed2005

Neuropsychiatric symptoms of dementia: cross-sectional analysis from a prospective, longitudinal Belgian study.

OBJECTIVE: Given the rather limited knowledge on profiles of neuropsychiatric symptoms (behavioural and psychological signs and symptoms of dementia, BPSD) in several degenerative dementias, we designed a prospective study of which we here present the baseline data. METHODS: Diagnosed according to strictly applied clinical diagnostic criteria, patients with probable Alzheimer's disease (AD) (n = 205), frontotemporal dementia (FTD) (n = 29), mixed dementia (MXD) (n = 39) and dementia with Lewy bodies (DLB) (n = 23) were included. All patients underwent a neuropsychological examination and behavioural assessment by means of a battery of scales (Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia). RESULTS: In AD and MXD, activity disturbances and aggressiveness occurred in more than 80% of the patients. With a prevalence of 70%, apathy was very common whereas delusions and hallucinations were rare in FTD patients. Frequently used behavioural assessment scales like the Behave-AD systematically underestimated BPSD in FTD whereas the MFS displayed high sensitivity for frontal lobe symptoms. Hallucinations discriminated DLB patients from other dementias. A high prevalence of disinhibition (65%) in DLB pointed to frontal lobe involvement. CONCLUSIONS: Behavioural assessment may help differentiating between different forms of dementia, further stressing the need for the development of new and more sensitive behavioural assessment scales. By means of the MFS, frontal lobe involvement was frequently observed in DLB. As 70% of FTD patients displayed apathy, prevalence was about two times higher compared to the other disease groups, meanwhile indicating that apathy is frequently observed in dementia, irrespective of its etiology.

Aged↗
PubMed2003

Behavioural disturbances in dementia patients and quality of the marital relationship.

OBJECTIVES: To investigate the relationship between behavioural problems in patients with dementia and changes in the marital relationship. METHODS: Fifty-three spouse caregivers of patients with dementia participated in the study. Questionnaires and interviews were used to examine caregiver perception of changes in the quality of their relationship. Behavioural disturbances in the patient were measured with the NeuroPsychiatric Inventory (NPI). RESULTS: Caregivers experienced a deterioration of their relationship, yet at the same time most felt closer to their spouse now than in the past. Regression analysis revealed that patient behavioural problems were, independent of patient cognitive status or functional impairment, associated with deterioration in the quality of the relationship between patient and caregiver. Patient apathy rather than depressive mood was associated with this deterioration. Apathy diminished the amount and reciprocity of interactions between partners. CONCLUSIONS: These results show that passive behaviour rather than excessive behaviour has most impact on the deterioration of the marital relationship. Intervention programmes should target relationship problems when problem behaviour, especially apathy, is present in patients with dementia.

Aged↗
PubMed2005

Differential impact of severity of drug use on frontal behavioral symptoms.

Increasing evidence indicates that substance abusers are impaired in cognitive-executive control tasks relying on different functional systems converging in the prefrontal cortex (PFC). Different PFC functional systems relevant to addiction have been described: the dorsolateral (DLC), orbitofrontal (OFC), and anterior cingulate (ACC) circuits. Each system is associated with different behavioral, cognitive, and emotional deficits, including apathy, disinhibition, and executive dysfunction. In this study, we examined the effects of severity of use of different drugs on apathy, disinhibition and executive dysfunction behavioral deficits as measured by the Frontal Systems Behavior Scale (FrSBe). The FrSBe, and a severity of substance use interview were administered to 32 poly-substance abusers. Multiple regression analyses showed that severity of cannabis use significantly predicted greater apathy and executive dysfunction behavior; and that severity of cocaine use significantly predicted greater disinhibition behavior. These results are consistent with previous studies using cognitive measures and support the notion that severity of substance use significantly affects behavioral symptoms associated with PFC systems functioning. These clinical symptoms should be specifically addressed during rehabilitation.

Adult↗
PubMed2004

Effects of recurrent major depressive disorder on behavior and cognitive function in female depressed patients.

Little is known about the effects of recurring depressive episodes on cognition and behavior. The objective of the study was to compare cognitive function and depression-related behavior between healthy female subjects and female outpatients with early-onset DSM-IV recurrent major depressive disorder and to investigate the effect of cumulative depressive duration. Neuropsychological tests and scales for apathy, anhedonia and psychomotor retardation were assessed in 23 female patients and 60 healthy age-matched female controls. Significantly higher levels of apathy, anhedonia and psychomotor retardation, and worse performance on tests of executive function were found in the patient group compared with the healthy controls. In the patient group, cumulative depression duration was not significantly correlated with cognitive function, apathy, anhedonia or psychomotor retardation. The deficits in executive function were not related to the actual level of depression. Mild executive dysfunction may be the effect of the illness process underlying recurrent depressive disorder. Repeated or extensive depressive episodes do not seem to additionally affect cognitive deficits or behavior in depressed patients.

Aged↗
PubMedDate not supplied

[Loss of motivation and frontal dysfunction. Role of the white matter change].

Since the recognition of white matter changes on computed tomography, researches were done to investigate a possible relation with ageing and cognition. This study examined whether computed tomography evidence of cerebrovascular disease in the form of white matter changes was associated with decreased implicit performance of frontal tests and with a loss of motivation in a group of 10 elderly volunteers with a mild cognitive impairment and in a group of 29 demented patients; 39 old patients (28 females: 82.4 +/- 7.1; 10 males: 75.5 +/- 11.3) cared in a psycho-geriatric day care hospital were enrolled for this essay. Motivation was evaluated with a specific scale: EAD. Patients were tested during the same period with MMSE for cognition, Cornell's scale for depression, Marin's scale for apathy. There were also assessed with a battery of frontal tests: BREF test. A brain scan was used to determinate the presence of leukoaraïosis. Table 1 give a description of the population according to the pathology. Cognitive disorder, but also apathy and loss motivation, frontal evaluation significantly differ in the two studied groups. The presence of a leukoaraïosis is associated with older people, a weaker cognitive status, a more important apathy or loss of motivation, and weaker results with frontal evaluation (table 2). Similar results were obtained considering only the frontal lesions (table 3). Age related changes of the white matter observed on computed tomography were associated with a decreased cognitive status. Leukoaraïosis is associated with loss of motivation and related with a poor results on frontal assessment. Loss of motivation is associated with certain frontal dysfunctions and with brain abnormal scan anomalies.

Aged↗
PubMed2002

Frontal Systems Behavior Scale in schizophrenia: relationships with psychiatric symptomatology, cognition and adaptive function.

Schizophrenia patients often exhibit impairments in executive functioning on formal testing and exhibit behaviors consistent with executive/frontal impairment in daily life. The Frontal Systems Behavior Scale (FrSBe) assesses behaviors associated with frontal lobe damage including executive dysfunction, apathy and disinhibition. We examined the reliability and validity of the FrSBe in 131 schizophrenia outpatients. Subjects were rated on the FrSBe and received symptom, cognitive and functional assessments. Statistical tests were corrected for multiple comparisons. The FrSBe was found to have good internal consistency and test-retest reliability. All three dimensions of the FrSBe (i.e. executive dysfunction, apathy and disinhibition) were significantly correlated with poor adaptive functioning as measured by the Social and Occupational Functioning Scale and the Functional Needs Assessment. In addition, differential relationships were found for apathy and disinhibition with symptoms as rated from the Brief Psychiatric Rating Scale and with cognitive variables including Trails B and verbal fluency scores. A multivariate analysis of variance examined differences on the FrSBe between patients and a group of 51 education-matched controls. Patients had significantly greater impairment on the FrSBe than controls. These differences were found for all FrSBe subscales. Results support the use of the FrSBe to characterize goal-directed behavior in schizophrenia patients.

Adaptation, Psychological↗
PubMed2002

Emotional and affective disturbances in patients with epilepsy.

We sought to assess whether epilepsy is associated with a higher risk of emotional reactions to frustrating stimuli, aggressive behavior, apathy, and depression, and whether these psychiatric patterns are specific to the epileptic condition. The study population consisted of referral patients 17 years and older with idiopathic or cryptogenic epilepsy (i.e., epilepsy not caused by a detectable brain lesion) without significant cognitive dysfunction. A first control was selected for each patient among patients with insulin-dependent diabetes and a second among normal blood donors. Aggressiveness in response to stressful stimuli was assessed with the Picture Frustration Study (PFS). Depression was tested by the Beck Depression Inventory. The Aggressive Behavior Scale (assessing irritability and rumination) and the Apathy Scale were also used. Odds Ratios (ORs) with 95% Confidence Intervals (95% CI) were used as the risk measure. Statistical analysis included between-group comparisons. In patients with epilepsy, the test scores were correlated to the main demographic (age, sex, education, marital status, and occupation) and clinical features (seizure types, disease duration, seizure control, and treatments). The sample included 55 patients with epilepsy, 56 diabetics, and 59 normal individuals. Patients with epilepsy and the two control groups had similar PFS scores and similar aggressiveness. Scores were also similar for the Aggressive Behavior and Apathy Scales, with similar numbers of individuals with aggressive conduct and excess rumination. Patients with epilepsy had higher depression scores. Moderate to severe depression was present in 9 cases (diabetes, 2; blood donors, 1) (P=0.004). Relative to blood donors, the OR for moderate to severe depression (95% CI) was 2.1 (0.1-61.7) for diabetes and 11.3 (1.4-247.8) for epilepsy. No significant correlation was detectable between test scores and patient and disease characteristics.

Journal Article↗
PubMed2005

Neuropsychiatric symptoms, functional impairment and executive ability in Thai patients with Alzheimer's disease.

BACKGROUND: Instrumental activities of daily living (IADL) depend on executive planning and procedural memory mediated by the frontal lobes. Planning and judgment are involved in clock drawing. Neuropsychiatric symptoms are also mediated by frontal lobes, and a relationship between ADL, clock drawing and neuropsychiatric symptoms was hypothesized. OBJECTIVE: To investigate the relationship between behavioral disturbances, ADL, and executive function. METHODS: Seventy-three Thai patients with Alzheimer's disease (AD) were evaluated. Neuropsychiatric symptoms and behaviors were assessed with the Nevropsychiatric Inventory (NPI). The Thai version of the Mini-mental State Examination (TMSE) was utilized as a global cognitive assessment. A clock-drawing test (CDT) and both category (animals) and letter (ko, so in Thai) verbal fluency were used as executive measures. Thai ADL scale, Barthel Index (BI), and Functional Assessment Questionnaire (FAQ) were ADL measures used in this study. RESULTS: There were statistically significant correlations between CDT and the frontally-mediated behaviors of agitation (r = -0.367), apathy (r = -0.273) and disinhibition (r = -0.247). Verbal fluency correlated with agitation (r = -0.341). There were significant correlations between Thai ADL scores and agitation (r = 0.350), apathy (r = 0.441), and disinhibition (r = 0.417). FAQ correlated with the same three behaviors. After controlling for TMSE, a significant correlation remained between Thai ADL scores and agitation (r = 0.291) and apathy (r = 0.342). CONCLUSIONS: We demonstrated correlations between ADL and behavioral changes in Thai elderly with AD. Our results emphasize the important relationships among behavioral changes and impaired ADL.

Aged↗
PubMed2006

Behavioral correlates of GABAergic disruption in Alzheimer's disease.

BACKGROUND: Losses of gamma-aminobutyric acid (GABA) have been variably demonstrated in Alzheimer's disease (AD) and may be related to the presence of behavioral and psychological symptoms of dementia (BPSD) in AD. Our objective was to assess the relationship between plasma GABA (pGABA) levels and specific BPSD in patients with severe AD. METHODS: pGABA levels and BPSD were measured in 14 institutionalized AD patients (8M/6F, mean age +/- S.D. = 85.6 +/- 4.5 years) with severe cognitive impairment (Mini-mental State Examination score = 4.5 +/- 4.6) and prominent behavioral disturbances (Neuropsychiatric Inventory (NPI) score = 33.4 +/- 23.6). RESULTS: pGABA was positively correlated with depression and apathy scores on the NPI and negatively correlated with age. Apathy and age were independent predictors of pGABA levels. CONCLUSIONS: The final stages of AD are associated with GABAergic changes, which may contribute to depression and apathy in AD.

Affect↗
PubMed2001

Toward individualized evidence-based medicine: five "N of 1" trials of methylphenidate in geriatric patients.

OBJECTIVES: To investigate the efficacy of methylphenidate in depressed or apathetic geriatric patients. DESIGN: Five "N of 1" trials (individual cross-over, double-blinded, randomized trials). SETTING: Department of Geriatrics, University Medical Center, Nijmegen, and two nursing homes in Nijmegen, the Netherlands. PARTICIPANTS: Patients suffered from depression due to a general medical condition (n = 2); depression resistant to antidepressive drugs (n = 1), chronic apathy due to mild and moderate severe dementia (n = 2). INTERVENTION: Methylphenidate (5 mg bid) and placebo (both for two subsequent days) in 5 weeks of randomized treatment blocks. MEASUREMENTS: Montgomery Asberg Depression Rating Scale (MADRS), Apathy Evaluation Scale (AES)-clinician, the AES-informant, Barthel index and a semiquantitative checklist of adverse effects. RESULTS: Among the three depressed patients, two showed significant improvement on the MADRS (P = .089 and P = .001; alpha = 0.10), one patient's apathy showed significant improvement on AES-clinician and -informant (P = .077 and P = .086). One apathetic patient's trial was stopped because AES could not be completed. None of the patients showed significant changes in the Barthel index. No side effects developed. CONCLUSION: "N of 1" trials are useful in evaluating efficacy of methylphenidate in depressed or apathetic geriatric patients. Single-patient trials can be a useful tool in pharmacotherapeutic decision-making in frail older subjects.

Aged↗
PubMed2005

Performance of clinical signs in poultry for the detection of outbreaks during the avian influenza A (H7N7) epidemic in The Netherlands in 2003.

The aim of this study was to make an inventory of the clinical signs of high-pathogenicity avian influenza (HPAI), to facilitate the development of an operational syndrome-reporting system (SRS) in The Netherlands as an early warning system for HPAI outbreaks. A total of 537 poultry flocks (240 infected and 297 non-infected) with a clinical suspicion of an infection with HPAI virus were investigated with respect to the clinical signs observed. Standardized reports were analysed with respect to observed clinical signs in the flocks. Various poultry types were distinguished. In infected commercial flocks with egg-producing chickens, the presence of increased mortality, apathy, coughing, reduction in normal vocalization, or pale eggs appeared to be overall the most sensitive indicators to detect a HPAI outbreak, matching a sensitivity of 99% with a specificity of 23%. In infected turkey flocks, the presence of apathy, decreased growth performance, reduction of normal vocalization, swollen sinuses, yawning, huddling, mucosal production from the beak, or lying down with an extended neck appeared to be overall the most sensitive indicators to detect a HPAI outbreak, matching a sensitivity of 100% with a specificity of 79%. In infected backyard/hobby flocks, increased mortality or swollen head appeared to be overall the most sensitive indicators of a HPAI outbreak, matching a sensitivity of 100% with a specificity of 26%. These results indicate that there is a solid basis for the choice of using increased mortality in the operational SRS in The Netherlands as an early warning system for HPAI outbreaks. The presence of apathy, specifically for turkeys, should be added to the SRS as an indicator.

Animals↗
PubMed2000

On the evolution of attachment-disordered behaviour.

Using an example of a goose which grew up in complete isolation, this article shows how escape behaviour increases through all its developmental steps by lack of a sufficient secure primary attachment object. If a gosling has no mother, its fear influences wide parts of its behaviour and blocks the capacity to approach another animal in order to form a new attachment. But the urge for attachment is still alive and provokes strong conflicts between this urge and fear. In these situations displacement activities and apathy occur--attachment-disordered behaviour. Under partly artificial circumstances, a change to 'normal' attachment behaviour took place by reduction of escape motivation, which enabled the goose to accept her brood. From this moment on the attachment-disordered behaviour, the displacement activity and the apathy disappeared. Implications to human behaviour are drawn--a comparison between displacement activity and neurotic symptoms, the state of apathy and personal disorder. A synthesis of ethological and psychoanalytical models concerning etiological and therapeutic aspects is discussed. Fear and attachment, not aggression and sexuality--our 'animal heritage'--are the primary factors which influence our development. The balance of fear and attachment is the basis for a healthy or unhealthy development of social relationships. This applies to social living animals as well as to humans.

Animals↗
PubMed1992

Morbidity and the growth of stunted and nonstunted children, and the effect of supplementation.

Children aged 9-24 mo were recruited by a survey of poor areas of Kingston, Jamaica. Stunted children were randomly assigned to supplementation or not. Weekly morbidity histories were taken for 2 y. Separate multiple regressions on each symptom for weight or length gain in 2-mo intervals showed significant reductions in weight gain with coughing, apathy, anorexia, diarrhea, and fever, ranging from -2.1 to -16.8 g/d ill. Apathy and diarrhea reduced gains in length (-0.26 and -0.20 mm/d ill). Significant reductions in linear growth with lower respiratory-tract infections (-0.16 mm/d ill) occurred only in nonsupplemented children. Growth over 4-mo intervals was reduced if diarrhea occurred in the first 2 mo of the interval but there were no long-term effects of apathy, fever, or anorexia. Some of the effects of morbidity on growth were therefore transient and morbidity is unlikely to be a major cause of growth retardation in this population.

Body Weight↗
PubMedDate not supplied

Mild cognitive impairment is associated with characteristic neuropsychiatric symptoms.

Mild cognitive impairment (MCI) has emerged as an identifiable condition and in many cases is a transitional state preceding diagnosable Alzheimer disease (AD). Neurobiological and neuroimaging characteristics of amnestic-type MCI have been investigated, but few comprehensive neuropsychiatric studies have been reported. The aim of this preliminary study was to define the neuropsychiatric features of the amnestic-type MCI and compare them with those of mild AD and normal controls. The Neuropsychiatric Inventory (NPI) was used to assess the neuropsychiatric symptoms in three age and education comparable groups, i.e., 28 MCI, 124 mild AD, and 50 normal subjects. Individual subscores of the 10 NPI symptoms and total NPI scores were compared between the MCI patients and the other 2 groups. The results of this preliminary investigation showed that MCI patients frequently manifested neuropsychiatric symptoms. The most common symptoms in the MCI group were dysphoria (39%), apathy (39%), irritability (29%), and anxiety (25%). There were significant differences in apathy, dysphoria, irritability, anxiety, agitation, and aberrant motor behavior between the MCI and control groups; in contrast, only delusions were significantly less common in MCI compared with mild AD. There was a significant difference between the MCI and control groups on total NPI scores (p = 0.001), but not between the MCI and mild AD groups (p = 0.304). Amnestic MCI is associated with significant neuropsychiatric symptoms, especially mood disturbances and apathy. Psychotic symptoms are significantly more common in the early stage of AD than in MCI. These results are derived from a limited clinical sample and require confirmation in longitudinal community-based investigations.

Affect↗
PubMed2006

Behavioral alterations and vascular dementia.

BACKGROUND: Vascular dementia is one of the most frequent forms of dementia, where behavioral and cognitive symptoms coexist. Negative signs, such as apathy, abulia, opposition, and agnosia, are badly tolerated and dramatically experienced by caregivers, even worse than the other signs of cognitive decline. REVIEW SUMMARY: We have studied 120 subjects affected by subcortical vascular dementia (group A) and 120 subjects suffering from multiinfarct dementia (group B) for 24 months. The main outcomes of the study were the global performance, the global behavioral symptoms, the caregiver stress, the depression status, and the insight in their clinical situation. CONCLUSIONS: Group A manifested a reduction of depression, agitation and suicidal ideation during follow-up, with a constant tendency to refer somatic pain, to exhibit anxiety, and an evident increase in apathy, cognitive abulia, social withdrawal, and loss of insight. On the contrary, group B showed a constant tendency to manifest depression, somatic pain, anxiety, agitation, cognitive abulia, social withdrawal, and suicide ideations; they manifested a decrease of apathy and an increase in delusions, hallucinations, craving for food, and loss of insight and awareness. Their behavioral alterations were stronger than those exhibited by group A, and that was reflected by an increment of caregivers' burden score. Even from a behavioral perspective, multiinfarct dementia is not the same as subcortical vascular dementia. This opinion must be taken into account to find more suitable and tailored therapy to specific pathologies and not to a single, generic entity.

Activities of Daily Living↗