Severe Behavioral Symptoms Research Articles

Measuring Impairment in Children with Attention-Deficit Hyperactivity Disorder

Typically, ADHD is diagnosed by collecting information on the presence and severity of behavioral symptoms specified in the Diagnostic and Statistical Manual of Mental Disorders (DSM; American Psychiatric Association, 1994), such as “often fidgets with hands or feet or squirms in seat.” Clinicians typically measure the occurrence of these symptoms using structured or semi–structured interviews, and by having parents and teachers complete standardized rating scales. Based on the information gathered, if a child has six or more inattentive symptoms, and/or six or more hyperactive/impulsive symptoms endorsed, he or she may meet criteria for ADHD.

Risperidone, haloperidol, and olanzapine for the treatment of behavioral disturbances in nursing home patients: A retrospective analysis

Objective This retrospective chart review assessed the efficacy and tolerability of risperidone, haloperidol, and olanzapine for the treatment of behavioral disturbances in nursing home patients with a psychiatric disorder. Methods A review of ~10,000 patient charts from 61 nursing homes in New Jersey identified 202 patients treated for 1 to 12 months with risperidone (n = 105), haloperidol (n = 77), or olanzapine (n = 20). The primary target symptoms were behavioral (hitting, screaming, pacing) and psychiatric (hallucinations, paranoia, delusions). Improvement in frequency and severity of behavioral symptoms was measured based on physicians' progress notes, psychiatric consultation reports, and nurses' summaries and behavioral monitoring forms. Results The most common diagnosis was dementia (n = 123), followed by schizophrenia (n = 32) and organic psychosis (n = 19). Among patients with dementia, behavioral symptoms improved in 55 of 65 (85%) patients treated with risperidone (1.1 mg/d), 18 of 42 (43%) treated with haloperidol (1.1 mg/d), and 7 of 16 (44%) treated with olanzapine (6.7 mg/d). Overall improvement in the target behavioral symptoms was seen in more patients treated with risperidone (80%) than in those treated with haloperidol (53%) or olanzapine (50%). Adverse effects were seen in 27 of 105 (26%) risperidone-treated patients, 26 of 77 (34%) haloperidol-treated patients, and 13 of 20 (65%) olanzapine-treated patients. Conclusions The apparent efficacy of risperidone in treating behavioral disturbances in these patients, and its more favorable safety profile, support its use as first-line therapy when antipsychotic medication is necessary.

Drug treatment in dementia

Significant recent advances have been made in the drug treatment of both cognitive and noncognitive symptoms of dementia. Further studies on the acetylcholinesterase inhibitors donepezil and rivastigmine have confirmed their role in the treatment of patients with mild-to-moderate Alzheimer's disease. Despite encouraging preclinical data, recent clinical trials on the use of oestrogen in Alzheimer's disease have demonstrated no apparent treatment effect. Studies on the use of risperidone in institutionalized patients with severe dementia and behavioural symptoms have helped to clarify the potential benefits and likely limitations of such treatment. Unfortunately, there is not yet convincing evidence from human trials of drugs with clinically significant disease-modifying effects. Curr Opin Psychiatry 13:415-421. (C) 2000 Lippincott Williams & Wilkins.

Smith-Magenis Syndrome Diagnosed at Birth

Most cases of Smith-Magenis Syndrome are diagnosed in children with self-destructive behaviors, disturbed sleep patterns, dysmorphic features, speech delay, and mental retardation. We report the detection of an interstitial deletion of the short arm of chromosome 17 at band p11.2 in a newborn infant with mild dysmorphic features. She was born at 39 gestational weeks and chromosome analysis was performed within the first 24 hours after birth due to the findings of prominent forehead, mild midface hypoplasia, small nose, and anteverted nostrils. Cytogenetic analyses in metaphases (450 bands) and prometaphases (750 bands) revealed the presence of an interstitial deletion 17p11.2. The microdeletion for the Smith-Magenis region was confirmed with fluorescence “in situ” hybridization (FISH) studies using the dual color Vysis probe and the ONCOR probe. Chromosome studies and FISH studies are pending on the parents. The diagnosis of an interstitial deletion 17p11.2 in a newborn infant offers the opportunity to provide early intervention and behavior management of the severe developmental and behavioral symptoms described in this syndrome. It also raises the question on whether or not this microdeletion may be present in children with dysmorphic features who are not diagnosed because they have milder clinical manifestations of this syndrome.

The use of clozapine in an individual with moderate intellectual disability, aggressive behaviour and resistant psychosis

AbstractThe case of a 32 year old man with moderate intellectual disability, severe behavioural problems and psychotic symptoms is described. Having tried various traditional antipsychotics he was commenced on clozapine with a marked improvement in symptoms. Clozapine is a useful drug for the treatment of schizophrenia in the intellectually disabled who are refractory to the conventional antipsychotics. It improves aggressive and self-injurious behaviour which may be in addition to its antipsychotic effect.

Noncognitive disturbances in Alzheimer's disease: frequency, longitudinal course, and relationship to cognitive symptoms.

To investigate the frequency and longitudinal course of symptoms of depression, agitation, and psychosis in a longitudinally studied sample of patients with Alzheimer's disease (AD). Longitudinal study of AD patients with follow-up assessments at 6-month intervals for an average of more than 3 years. Alzheimer's Disease Research Center of the Mount Sinai Medical Center and the Bronx VA Medical Center, New York. A total of 153 AD patients. Blessed Test of Information, Memory and Concentration (BIMC) and the Alzheimer's Disease Assessment Scale cognitive (ADAS-Cog) and noncognitive (ADAS-NC) subscales. At entry into the study, more than 90% of patients had a behavioral disturbance that was rated as mild or worse on one of the 10 ADAS noncognitive items; and 40% had at least one rating that was moderate or severe. Correlational analyses indicated that, with the exception of the two mood-related items, noncognitive symptoms on the ADAS were not highly correlated with one another. Only one of the noncognitive items, concentration, was strongly correlated with the severity of cognitive impairment. On average, patients showed progressively worse cognitive functioning over time as measured both by the ADAS-Cog and the BIMC. The mean severity of noncognitive symptoms did not change during the course of a 5-year follow up. The severity of behavioral disturbance at any one evaluation was negatively correlated with change in behavior during the next 6 months and was not correlated with cognitive decline. Mild behavioral disturbances are common, whereas moderate to severe behavioral symptoms are less frequent in this population of AD patients. Disturbances in mood and manifestations of agitation and psychotic symptoms are not closely related to one another and show little progressive worsening over time. Rather, they tend to be episodic such that increasing severity at one time is usually followed by improvement later. Concentration problems are a manifestation of cognitive dysfunction rather than behavioral disturbance in AD. Implications of these results for treatment of noncognitive disturbances in AD are discussed.

THE BEHAVIOR PATHOLOGY IN ALZHEIMER'S DISEASE RATING SCALE (BEHAVE-AD): RELIABILITY AND ANALYSIS OF SYMPTOM CATEGORY SCORES

The interrater reliability of the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), a psychiatric rating scale especially designed for the evaluation of behavioral disturbances in dementia patients, was studied in both English-speaking US patients and a French-speaking elderly patient population from France. Additionally, the quantitative relationship between severity of Alzheimer's disease (AD) and mean scores on each of the BEHAVE-AD categories and mean total BEHAVE-AD score was determined in a separate study of 140 patients diagnosed as having probable AD. In both reliability studies significant correlations were obtained for all BEHAVE-AD symptom category scores and for mean total BEHAVE-AD scores. Analysis of BEHAVE-AD scores as a function of disease severity demonstrated a non-linear relationship between severity of behavioral symptoms and the global and cognitive advance of AD. Moreover, score analysis of the BEHAVE-AD indicates that these behavioral disturbances become most severe in the moderate and moderately severe stages of the illness. The results of these studies provide support for the reliability of the BEHAVE-AD. Additionally, the BEHAVE-AD provides basic knowledge about the nature and severity of the behavioral symptoms in AD. The latter information may be useful for the development of appropriate and effective psychopharmacologic intervention strategies for these difficult to manage behaviors. Furthermore, these results have implications for the methodology of pharmacologic trials of putative cognitive-enhancer compounds in AD.

Pharmacologic treatment of noncognitive symptoms of dementia.

Cognitive deterioration in dementia includes many changes besides memory disturbances, including agitation, delusions, hallucinations, anxiety, irritability, and aggressiveness. Antipsychotic drugs are often used to control behavioral symptoms, but their benefits are limited. Depression, which is common in dementia, is often associated with anxiety. Selective serotonin reuptake inhibitors (SSRIs) improve mood and reduce anxiety while causing few side effects; they are also useful in managing irritability. Thus, the SSRIs should be considered the agents of choice for treating noncognitive symptoms associated with dementia. Neuroleptics should be used exclusively in patients with severe behavioral or psychotic symptoms, and only those agents without anticholinergic effects should be administered. Neuroleptics can be coadministered with SSRIs in patients who are extremely aggressive. Anxiolytics may also be effective for shortterm use. Future studies of drugs to treat the noncognitive symptoms of dementia should be placebo controlled and should evaluate the effects of those drugs on cognitive function.

Acute MPTP treatment produces no changes in mitochondrial complex activities and indices of oxidative damage in the common marmoset ex vivo one week after exposure to the toxin

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to cause a Parkinsonian syndrome in man and non-human primates. Hypotheses concerning the pathogenetic mechanisms of MPTP toxicity on nigro-striatal dopaminergic neurons relate to impairment of mitochondrial function and oxidative stress. However, surprisingly few primate studies addressed these issues ex vivo. Thus, the present study assessed the enzyme activities of the respiratory chain, GSH/GSSG and ubiquinol/ubiquinone content in the MPTP primate model (common marmoset, Callithrix jacchus; 2 mg MPTP-hydrochloride/kg body wt were injected subcutaneously (s.c.) on four consecutive days; animals were sacrificed 7 days after last MPTP exposure). Activities of respiratory chain enzymes were measured in crude homogenates of the caudate nucleus, because the probable toxic metabolite of MPTP, MPP +, is transported into dopaminergic neurons via the dopamine uptake system in striatal synapses and mitochondria are concentrated in axonal terminals. Since MPP + can damage membranes of axonal terminals of nigro-striatal neurons we measured GSH/GSSG contents in the putamen and ubiquinol/ubiquinone concentrations in the substantia nigra and putamen as indices of oxidative damage. At the time of sacrifice MPTP-induced deficits comprised severe behavioural Parkinsonian symptoms, profound depletion of striatal dopamine and its major metabolites as well as pronounced loss of nigro-striatal neurons. Despite these severe lesions, acute MPTP treatment had no effect on any of the enzymes of the respiratory chain in the caudate nucleus and indices of oxidative damage in both the substantia nigra and putamen. These results suggest that factors other than mitochondrial impairment and/or oxidative stress may be involved in MPTP neurotoxicity in primates. Alternatively, early compensatory mechanisms and/or transient effects could account for the reported results and will be discussed.

Socio-cultural determinants of psychiatric symptomatology in James Bay Cree children and adolescents.

To examine the type of psychiatric disorders found in 100 Cree children living in a Native community in northern Quebec. Standardized semi-structured interviews were given to all children and their caregivers, collecting 24 items of information. 51% of the children did not qualify for a DSM-III-R diagnosis but their frequently severe behavioural symptoms could be categorized by using 5 types of socio-cultural disturbances. There were also significant correlations between parental educational level, including length of time spent away from home, and the number of stress factors the children had been exposed to. There is a need to develop a diagnostic classification for child psychiatric disorders for aboriginal children.

The adolescent behavior checklist: Normative data and sensitivity and specificity of a screening tool for diagnosable psychiatric disorders in adolescents with mental retardation and other developmental disabilities

Individuals with mental retardation are almost twice as likely to demonstrate severe behavioral problems or symptoms of mental illness as are nonmentally retarded individuals. At present, however, the ability to diagnose a mental disorder in an individual with mental retardation is difficult, and instruments are needed to help facilitate this process. The Adolescent Behavior Checklist was developed with this purpose in mind. This self-report scale is used to assess the likelihood that an adolescent with mild mental retardation or borderline intelligence has a diagnosable mental illness. The 86-item yes\ o self-report scale renders scores on eight subscales derived from DSM III-R. The checklist has been found to have good criterion and congruent validity and good test-retest reliability. Data regarding interrater reliability and the sensitivity and specificity of the scale are presented, as are implications for future research.

Long-Term Prognosis after Left Tuberothalamic Infarction: A Study of 7 Cases

The long-term prognosis after left tuberothalamic infarction was studied in a selected group of 7 patients who had memory disturbances sufficiently severe to warrant neuropsychological consultation and rehabilitation. The mean age of the patients was 46.7 ± 5.6 years and the mean follow-up time 22.3 ± 15.0 months. At the acute stage 4 patients had dysphasia, 1 hemiparesis, and 1 vertical gaze paresis. These improved well. All 7 had memory disturbances, which remained the dominant disability. Four patients had severe behavioral symptoms (psychosis, depression, anxiety) at the acute stage. The most common residual behavioral symptoms were inactivity and depression. At the end of rehabilitation (mean 15.4 months) clear residual disturbances in verbal memory and learning were still observed. These prevented return to work in all but 1 case. No case of true dementia was found.

Antipsychotics

Many demented patients experience psychotic or other severe behavioral symptoms some time during the course of their illness. Neuroleptics are among the most widely prescribed medications for the management of these symptoms. The nine placebo-controlled studies published to date on the use of neuroleptics in the treatment of patients with dementia are reviewed with a focus on therapeutic response and adverse effects. The studies suggest that for some patients neuroleptics are useful in treating the psychotic and agitated behavior, but not the intellectual impairment associated with dementia. Also, there is a risk of side effects such as tardive dyskinesia.

“In vivo” visualization by positron emission tomography of the progressive striatal dopamine receptor damage occuring in MPTP-intoxicated non-human primates

Intravenous administration of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) leads to the progressive development of a model of Parkinson's disease in the primate. The development of damage occuring in the striatal area during MPTP-treatment was followed “in vivo” in a baboon by positron emission tomography (PET). Spiperone labelled with a positron emitter 76Br ( 76Br-BSP) was used for the quantitative “in vivo” imaging of D 2 dopamine receptors. The decrease in the striatal binding of 76Br-BSP measured “in vivo”, after three series of MPTP injections, paralleled the increase in the severity of behavioral symptoms seen immediately after administration of the neurotoxin. At the end of the MPTP-treatment when neurological symptoms were the most important, a 36 % decrease in the 76Br-BSP specific binding was measured. Between the series of MPTP injections a partial recovery in the quantitative measurement of the 76Br-BSP specific binding occuring in the striatum was well correlated with the disappearance of the neurological syndrome. Post-mortem histological and biochemical studies in nigro-striatal anatomical structures of MPTP-intoxicated primates compared with control animals showed a 80 % loss of neuronal cell bodies in the substantia nigra compacta and a 42 % decrease in the density (Bmax) of D 2 receptors (in vitro 3H-spiperone binding). All these results showed that the use of PET and 76Br-BSP allow to follow in a noninvasive way both the degenerative processes and the subsequent partial recovery which occur in dopaminergic striatal receptor function during MPTP-treatment.

EFFECTS OF STRONTIUM ON THE EMBRYONIC DEVELOPMENT OFAPLYSIA CALIFORNICA

Strontium is required in defined media for the development of normal shells and statoliths in the opisthobranch gastropod, Aplysia californica Cooper, 1863. Embryos grown in artificial seawater without strontium chloride become larvae with normally appearing soft tissue but with deformed shells and statocysts that lack the statolith granule. Shell and statolith formation is sensitive to concentration differences as small as one part per million strontium in the artificial seawater. Pulse experiments indicate a critical period of exposure for the requirement beginning at Day 4, (72 h after oviposition) and lasting no longer than 24 h. Animals exposed to artificial seawater containing 8 parts per million strontium only during this critical period develop normally. Conversely, animals immersed in artificial seawater lacking strontium during this same period, but exposed to the element during the rest of the 10-day embryonic phase, exhibit anomalous shells and statocysts. The effects are only marginally reversible if strontium is presented after Day 5. Strontium is also essential for the normal development of locomotory behavior. Animals that have been deprived of strontium swim erratically, spinning in tight circles. The pathogenesis of this behavioral disorder is explained by the lack of strontium during embryonic development which causes the major structural anomalies at the larval stage. The absence of the statolith results in a defective organ of balance which in turn causes the severe behavioral symptoms. A similar strontium effect in other molluscs, including Hermissenda crassicornis (Eschscholtz, 1831), is also documented.

Comparison of the ultrastructural myopathy induced by anticholinesterase agents at the end plates of rat soleus and extensor muscles

Rats were treated with single subcutaneous injections of the irreversible AChE inhibitors, sarin (90 to 100 μg/kg) or soman (55 μg/kg), and with chronic doses of the reversible carbamate inhibitor, pyridostigmine. In surviving animals with severe behavioral symptoms, we examined the end-plate regions of the slow-twitch soleus and the fast-twitch extensor digitorum longus muscles, using the electron microscope. Within 30 min, sarin administration caused a recognizable subjunctional myopathy. The progress of morphologic damage was followed for 7 days, during which time the occurrence of damage diminished. The initial swelling of subjunctional organelles and vacuole generation progressed to the point where nerve terminals and attached postjunctional folds were lifted away from the muscle surface. This appeared to be caused by a combination of enlarging vacuoles and insertion of Schwann and macrophage cells into the lesions, and was followed by degeneration of the postjunctional folds. A new component of anti-AChE myopathy was recognized: progressive swelling of chromatin in subjunctional muscle nuclei. The soleus muscle was considerably more sensitive to these effects than the extensor muscle. Soman had a much less prominent ultrastructural effect on the muscle end plates. Chronic pyridostigmine treatment had effects similar to those of a single sarin injection on the soleus as well as a pronounced effect on the extensor muscle.

Short-Term Effect of Thioridazine Tablets Versus Suspension on Emotionally Disturbed/Retarded Children

A 10-week study was conducted in four phases comparing the short-term efficacy of thioridazine tablets and thioridazine suspension for decreasing severe behavioral symptoms of psychotic retarded children. Behavioral observations were conducted in the classroom before and after medication, both during structured activity and during free play. Thioridazine was dispensed in phases I and III in tablet form and in phases II and IV in suspension, in the same amount of milligrams per subject throughout all four phases. Across all four phases the difference between the effects of thioridazine tablet and suspension was nonsignificant. On short-term observation both forms of thioridazine proved to be effective in reducing aggression, disruptive tantrumming, self-abuse, stereotype self-stimulation, and pica eating. The cumulative average symptom reduction was 27.4% within 35 minutes following medication intake.

CLASSIFICATION OF HYPERACTIVE CHILDREN

Numerical taxonomy was used in an attempt to identify subgroups in a sample of children labelled as hyperactive. In each of two analyses of Conners' questionnaire data (supplied by parents and by teachers), two classes were obtained, apparently differentiated on the basis of rated severity of behavioural symptoms. No aetiologically important differentiating attributes emerged. There was poor agreement between the two data sources. particularly in the classification of the more disordered group; and, over all, teachers perceived the children as less deviant than did parents. Comparison with earlier studies indicated the similarity in behavioural symptoms between this sample and those from other countries. However, the obtained data argued against the existence of a pure hyperactive disorder, since there was virtually no differentiation between conduct problems and items relating more specifically to hyperactivity. Hyperactivity as a diagnostic category appears to have little meaning either aetiologically, or descriptively, or prescriptively.

CLASSIFICATION OF HYPERACTIVE CHILDREN

Numerical taxonomy was used in an attempt to identify subgroups in a sample of children labelled as hyperactive. In each of two analyses of Conners' questionnaire data (supplied by parents and by teachers), two classes were obtained, apparently differentiated on the basis of rated severity of behavioural symptoms. No aetiologically important differentiating attributes emerged. There was poor agreement between the two data sources. particularly in the classification of the more disordered group; and, over all, teachers perceived the children as less deviant than did parents. Comparison with earlier studies indicated the similarity in behavioural symptoms between this sample and those from other countries. However, the obtained data argued against the existence of a pure hyperactive disorder, since there was virtually no differentiation between conduct problems and items relating more specifically to hyperactivity. Hyperactivity as a diagnostic category appears to have little meaning either aetiologically, or descriptively, or prescriptively.

Severity of behavioral symptoms in schizophrenia.

Severity of behavioral symptoms in schizophrenia.