Dopamine receptor genetic variation, psychosis, and aggression in Alzheimer disease

OBJECTIVE: To examine if selected polymorphisms in the dopamine receptor genes DRD1, DRD2, DRD3, and DRD4 are associated with the presence of psychosis or aggressive behavior in patients with Alzheimer disease (AD). DESIGN: A cohort of patients with AD were longitudinally evaluated for behavioral symptoms and classified with regard to the presence of psychotic symptoms and physical aggression. SETTING: Alzheimer's Disease Research Center. PATIENTS: Two hundred seventy-five elderly outpatients diagnosed as having probable AD. RESULTS: Among white patients, psychosis and aggression were both significantly more frequent in DRD1 B2/B2 homozygotes (P < .02), while psychosis was significantly more frequent in DRD3 1/1 or 2/2 homozygotes (P < .05). The joint risk for psychosis due to the DRD1 and DRD3 polymorphisms exceeded the risks due to either locus alone, suggesting an interaction. Neither the DRD2 S311C polymorphism nor the presence of long alleles for the DRD4 exon III repeat sequence was associated with psychosis or aggression. CONCLUSIONS: Genetic variation in DRD1 and DRD3 genes may act to modify the course of AD, predisposing to the development of psychotic or aggressive symptoms. Confirmation in other samples of patients with AD is required.     

Phenomenologic comparison of the idiopathic psychosis of schizophrenia and drug-induced cocaine and phencyclidine psychoses: a retrospective study

Both stimulant-induced and phencyclidine (PCP)-induced psychoses have been proposed as models of the idiopathic psychosis of schizopherenia. In this two-part study, the phenomenology of the psychosis associated with a period of cocaine intoxication was evaluated retrospectively in 34 male crack cocaine-dependent patients without concomitant psychiatric disorder and then was compared with the psychosis of 16 actively psychotic schizophrenic men (without a history of drug or alcohol abuse in the past year). Certain First Rank Schneiderian Symptoms (FRSS) were more commonly observed in the schizophrenic patients (e.g., thought broadcasting, thought withdrawal) than in the cocaine addicts. In the second part of this study, we retrospectively examined the cocaine and PCP experiences of an additional 22 cocaine addicts who had a past history of separate periods of cocaine and PCP use. Overall, the frequency of FRSS recalled during periods of cocaine and PCP intoxication was similar. However, the psychosis related to cocaine intoxication was more associated with an intense suspiciousness and paranoia related to a fear of being discovered or harmed while using cocaine. PCP-induced psychosis was less associated with suspiciousness and more associated with delusions of physical power, altered sensations, and unusual experiences [e.g., out of body experiences, experiencing religious figures or events directly (e.g., being with Noah at the time of the Arc)]. As elements of both cocaine and PCP psychosis can be found in schizophrenia, a model integrating the mechanisms of several psychotogenic drugs may be more informative. Such an integrative model might better capture the heterogeneity of psychotic symptoms that can be seen in schizophrenia. Furthermore, different pharmacologic interventions (e.g., "anti-stimulant" versus "anti-PCP") might address different aspects of the positive symptom picture in schizophrenia.     

Movement abnormalities and the progression of prodromal symptomatology in adolescents at risk for psychotic disorders.

The link between movement abnormalities and psychotic disorders is presumed to reflect common neural mechanisms that influence both motor functions and vulnerability to psychosis. The prodromal period leading to psychotic disorders represents both a viable point for intervention and a developmental period that, if studied, could shed light on etiology; however, no published studies have examined the temporal progression of this link. A group with high levels of prodromal symptomatology (i.e., adolescents with schizotypal personality disorder [SPD]; n = 42) and both psychiatric controls (with other personality disorders or conduct disorder [OD]; n = 30) and nonpsychiatric controls ([NC]; n = 49) were recruited. Videotapes of structured psychiatric interviews were coded for movement abnormalities by raters blind to participants' diagnostic status, and follow-up assessments were conducted 1 year later. Controlling for psychotropic medications, the authors found that adolescents with SPD exhibited significantly more motor abnormalities in the face and upper body than did OD and NC controls. At baseline, movement abnormalities were positively correlated with the severity of positive, negative, and total prodromal symptoms. Within the SPD group, baseline movement abnormalities predicted symptom severity 1 year later. Movement abnormalities represent an early risk indicator that may be predictive of later symptom severity and potentially of psychosis onset. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Movement abnormalities predict conversion to Axis I psychosis among prodromal adolescents.

Evidence suggests that movement abnormalities are a precursor of psychosis. The link between movement abnormalities and psychotic disorders is presumed to reflect common neural mechanisms that influence both motor functions and vulnerability to psychosis. The authors coded movement abnormalities from videotapes of 40 adolescents at risk for psychosis (designated prodromal on the Structured Interview for Prodromal Symptoms; T. J. Miller et al., 2002). Following initial assessment, participants were evaluated for diagnostic status at 4 times annually. Ten participants converted to an Axis I psychosis (e.g., schizophrenia) over the 4-year period. Comparisons of converted and nonconverted participants at baseline indicated that the groups did not differ on demographic characteristics or levels of prodromal symptomatology, but those who converted exhibited significantly more movement abnormalities. Movement abnormalities and prodromal symptoms were strongly associated and logistic regression analyses indicated that abnormalities in the face and upper body regions were most predictive of conversion. Findings suggest that individuals with elevated movement abnormalities may represent a subgroup of prodromal adolescents who are at the highest risk for conversion. The implications for neural mechanisms and for identifying candidates for preventive intervention are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Implicit memory in Alzheimer's disease: A meta-analysis.

Meta-analysis was performed on 33 articles (36 experiments involving 564 Alzheimer's disease [AD] patients and 592 controls). Overall, AD patients were significantly impaired on implicit memory tests, r?=?.163 (a difference of .329 SDs from normal performance). They were impaired on nonverbal tests (e.g., fragmented pictures), word stem completion, classical conceptual tests (e.g, free association), and on word-based perceptual tests with long delays. However, they performed normally on word-based perceptual tests (e.g., perceptual identification of words) with short study test delays. They also performed normally on word stem completion if they were older than 75, possibly because their age-matched controls were also impaired. These results are neither qualified by study list length nor patient mental status. None of the theories in the field is compatible with the results. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neocortical Disconnectivity Disrupts Sensory Integration in Alzheimer's Disease.

The cortical pathology in Alzheimer's disease (AD) should lead to the loss of effective interaction between distinct neocortical areas. This study compared 2 conditions within a single sensory integration task that differed in the demands placed on effective cross-cortical interaction. AD patients were impaired in their ability to bind distinct visual features of a stimulus when this binding placed greater demands on cross-cortical interaction (i.e., motion and color) but were not impaired when this binding placed lesser demands on such interaction (i.e., motion and luminance). In contrast, neurologically intact individuals and patients with Huntington's disease were able to effectively bind features under both conditions. These results provide psychophysical support for the presence of functional disconnectivity in AD and demonstrate the utility of AD for investigating the neurocognitive substrates of sensory integration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exposure of nonmigratory pigeons to mancozeb: a sentinel model for humans

Pathologically asymmetrical P300 fields with right lateralized peaks were described in core schizophrenia as an expression of left-temporal functional deficits, while higher than normal amplitudes were found in cycloid psychosis. This latter finding appeared to be specific for cycloid psychosis and was explained by a generalized cerebral hyperarousal. Based on some psychopathological analogies with cycloid psychosis, and on the comparable pharmacological treatment of the acute episodes, a group of 19 manic patients was investigated immediately after remission and clinical stabilization of an episode. Patients with psychotic features were excluded to avoid overlaps with cycloid psychosis. Patients showed normal P300 amplitudes and no pathological asymmetries of the field, but more posterior positive areas compared to age- and sex-matched controls. This indicates that the neurophysiological changes underlying mania are different from both core schizophrenia and cycloid psychosis. Based on previous three-dimensional source location studies, this finding indicates that disinhibition due to reduced frontal lobe activity, and not hyperarousal, is the basic functional mechanism of manic disorders.     

Deterioration of generic knowledge in patients with Alzheimer's disease: evidence from the Number Information Test

Semantic memory for generic knowledge was assessed in patients with probable Alzheimer's disease (AD; n = 142) and elderly normal control (NC; n = 78) subjects using the Number Information Test (NIT), a test that consists of 24 general knowledge questions that require a single number for an answer (e.g., "How many days are in a year?"). The results showed that patients with AD were impaired, even in the mildest stage of dementia, and that this impairment grew as the severity of their dementia increased over time. In addition, patients with AD were highly consistent in the individual items they missed in subsequent test sessions conducted 1 or 2 years later. These results indicate that semantic memory for generic knowledge is impaired relatively early in AD, deteriorates throughout the course of the disease, and may be due to a loss of knowledge rather than to a retrieval deficit.     

Aging minds and twisting attitudes: An fMRI investigation of age differences in inhibiting prejudice.

Cognitive capacity is believed to decline with age, but it is not known whether this decline extends to tasks involving social cognition. In the current study, social neuroscience methodologies were used to examine the effects of age-related cognitive decline on older adults’ abilities to engage regulatory mechanisms (which are typically impaired by normal aging) to inhibit negative reactions to stigmatized individuals. Older and young adults were presented with images of stigmatized individuals (e.g., individuals with amputations, substance abusers) and of normal controls while they underwent functional magnetic resonance imaging. All participants were also given a battery of tests to assess their executive function capacity. Young adults showed more activity in areas associated with empathy (i.e., medial prefrontal cortex) than did older adults when viewing stigmatized faces. By contrast, older adults with relatively preserved levels of executive function had heightened activity in areas previously implicated in emotion regulation (i.e., lateral prefrontal cortex) as compared to other groups. These results suggest that although cognitive decline may interfere with older adults’ attitudes toward stigmatized individuals, older adults with relatively preserved cognitive function may utilize different strategies to compensate for these deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Use of exercise myocardial perfusion imaging to guide and assess the effectiveness of medical therapy in coronary artery vasospasm

A computed tomography (CT) scan of the head is often routine for patients with new-onset psychosis to rule out somatic causes. Charts of 127 such patients admitted to a major military medical center were examined. Most patients were young and otherwise in good health. Relationships were examined between CT scan findings and demographic variables, seizure history, neurological abnormalities, and discharge diagnosis. None of the 127 patients had an abnormal scan; four had incidental findings. Incidental findings were strongly associated with ethnic minority status but not with neurologic abnormalities, seizure history, or diagnosis. Findings suggest that routine CT scans for all newly psychotic military patients may not be warranted.     

Psychiatric aspects of temporal arteritis: a case report and review of the literature

Temporal arteritis may present with atypical manifestations that can hamper its diagnosis. We report a case presenting with predominantly psychiatric symptoms including psychotic features and affective symptoms both on a background of cognitive impairment. Such clear-cut psychotic symptoms have not been described previously in the literature. Corticosteroid treatment was followed by full remission of psychotic and affective symptoms; treatment with antipsychotic medication was unnecessary. Temporal arteritis should be considered in the differential diagnosis of psychosis and affective disorder in the elderly. The erythrocyte sedimentation rate is a valuable parameter in the assessment of old-age psychiatry patients presenting both with functional and neurologic disorders.     

Daily injections of fluoxetine induce dose-dependent desensitization of hypothalamic 5-HT1A receptors: reductions in neuroendocrine responses to 8-OH-DPAT and in levels of Gz and Gi proteins

BACKGROUND: Overall and left temporal scalp area reductions of P300 have been demonstrated in schizophrenia. P300 amplitude and topography in psychotic affective disorder, a crucial comparison in assessing the specificity of P300 abnormalities to schizophrenia, are not well studied. METHODS: P300 was recorded from 35 schizophrenic, 20 psychotic manic, and 30 control subjects. All were right-handed men. RESULTS: P300 was reduced in both psychotic groups relative to control subjects. Anteroposterior P300 topography differed between patient groups, with schizophrenic subjects showing posterior reduction and bipolar subjects showing anterior reduction. Schizophrenic subjects showed an abnormal asymmetry, with smaller P300 over the left temporal scalp site than the right. Both bipolar and control subjects showed a left greater than right asymmetry. CONCLUSIONS: Widespread auditory P300 reductions were present in schizophrenia and bipolar disorder with psychosis, but subtle topographic differences were present in the two diseases. Although unequivocal knowledge of neural generators cannot be derived from topography alone, differences in topography imply different generator configurations. Based on previous studies, the posterior P300 reductions in schizophrenia may reflect abnormalities of a generator located in the left superior temporal gyrus. The frontal reductions in bipolar psychosis may reflect abnormalities in a hypothetical frontal generator, consonant with reports of altered frontal lobe function in mania.     

Cognitive controls and psychopathology.

Studied 90 psychiatric inpatients (nonpsychotic, nonschizophrenic psychotic, schizophrenic) and 35 normal controls to (a) determine whether some of the traditional cognitive controls could be isolated in these patients and (b) evaluate whether various diagnostic groups differed from each other and from normals in terms of these congitive controls. Ss were administered a battery of cognitive control tasks (e.g., the Phillips Scale of Premorbid Adjustment, WAIS, and Rorschach tests). With age, socioeconomic status, and verbal IQ as covariates, the factor structure for the total group was similar to that reported in other studies of cognitive control organization in the normal population. Schizophrenic and other psychiatric patients were not characterized by distinctly different organizations of cognitive controls. Although patients showed specific areas of cognitive dysfunctions, these seemed to be related to degree of disorganization. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Color coded ultrasound--quantification of perfusion in a perfusion model

One patient with acute and transient functional psychosis was assessed repeatedly using a brief neuropsychological assessment during his recovery from the psychotic episode. The psychotic features of the patient were characterized by perplexed behavior, attentional disturbance and emotional turmoil. Characteristic findings, including impairment of attention tests, dysgraphia and constructional disturbances, were seen. Findings improved in accordance with recovery on a behavioral level. We discussed the similarity of neuropsychological and behavioral abnormalities of this patient and those of patients in an acute confusional state.     

Smooth-pursuit eye tracking in first-episode psychotic patients and their relatives.

In order to determine the specificity of smooth-pursuit eye tracking dysfunction to schizophrenia (SC) and the prevalences of dysfunction among functionally psychotic and normal individuals, the authors investigated pursuit tracking in a large sample of psychotic patients, normal Ss, and 1st-degree relatives (N?=?482). Ss were recruited as part of an epidemiological study of 1st-episode psychosis that used a broadly based referral network to identify all cases in a major metropolitan area over a 2.5-yr period. Ss received diagnoses of SC, schizophreniform disorder, psychotic mood disorder, and paranoid or other psychotic disorder based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-III). The distribution of tracking performance was bimodal for the SC Ss and their relatives, perhaps reflecting major gene action. Moreover, poor tracking ran in families. Pursuit tracking dysfunction was relatively specific to SC Ss and their relatives and occurred infrequently in other psychotic Ss and normal Ss. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Protein kinase C from rainbow trout brain: identification and characterization of three isozymes

This study examines the hypothesis that patients with frontal lobe lesions are impaired on tests of letter but not category fluency. This hypothesis was proposed by Moscovitch (1994), based on a series of cognitive studies with young, normal participants. A group of patients with lateral prefrontal lesions and age-matched controls were tested on 2 tests of verbal fluency, the FAS task and a category fluency task that used semantic categories as cues (e.g., animals). Patients with frontal lobe lesions generated fewer items than controls on both letter and category fluency. This effect did not interact with the type of fluency test, suggesting that the frontal lobes are more generally involved in verbal fluency. Moreover, this pattern of findings, along with previous results of impaired free recall and remote retrieval in this patient group, suggests that patients with frontal lobe lesions do not efficiently organize and develop retrieval strategies.     

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment.

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association of cerebral palsy with epilepsy

Fifty patients of various types of cerebral palsy were studied to find out an association between cerebral palsy, EEG abnormalities and development quotient. Seventy-six per cent patients had spastic cerebral palsy. Hypotonic cerebral palsy was the next common type (14%). Athetosis and ataxic forms were found to be rare (2% each). Epilepsy was associated with 56% patients. Clinical types of seizures observed were: Generalised tonic-clonic (43%), myoclonic (17.9%), generalised tonic (10.7%), partial simple (10.7%) and partial complex (17.9%). The incidence of seizures was highest in hypotonic type in which 85.7% had epilepsy. Mean developmental quotient of cerebral palsy patients was 34.9% with maximum retardation in hypotonic cerebral palsy (25.14%). Sixty per cent of patients had abnormal EEG, out of these hypotonic patients had maximum (70%) chances of EEG abnormality followed by spastic patients (55%). Developmental retardation was more severe statistically in the patients with abnormal EEG than normal EEG.     

Postperceptual effects and P300 latency

BACKGROUND: Structural and functional brain changes have been described in elderly patients with unipolar affective disorder. Changes appear to be more marked in patients with late-onset depression, but the reversibility of such changes after clinical recovery is not known. METHODS: Magnetic resonance imaging, electroencephalography (EEG), and cognitive tests were performed in 23 elderly patients (mean age 66.5 years) clinically recovered from major depression. Twelve had late-onset depression (first episode over 55 years of age); 11 had early onset (first episode before 50 years). EEG and cognitive testing were also performed on 15 control subjects. RESULTS: Patients with late-onset depression had larger third and lateral ventricles, increased ventricular-brain ratio, and greater frequency and severity of subcortical white matter lesions than those with early onset. There was no difference between early- and late-onset patients in EEG and cognitive measures, but compared with controls patients showed significant changes in EEG evoked potentials and increased slow-wave activity, slowed reaction times, and global impairments in cognitive function. CONCLUSIONS: These results suggest that structural changes are greater in patients with late-onset depression, and that EEG and cognitive impairments persist after recovery, regardless of age of onset of depression, and are independent of structural changes.     

Reading lexically without semantics: evidence from patients with probable Alzheimer's disease

Recent modifications of the lexical model of oral reading make the prediction that under conditions where sublexical reading processes alone cannot achieve the target pronunciation (i.e., when words have exceptional spellings or when sublexical processes are impaired), patients with severe semantic impairment should have more difficulty reading aloud semantically impaired words than semantically retained words. In a battery of lexical-semantic and reading tasks, two neurologically normal control subjects and two subjects with probable Alzheimer's disease (AD) and only moderate semantic impairment read aloud all words accurately. One AD subject with severe semantic impairment was impaired in word reading but demonstrated no difference in reading words with regular and exceptional spellings. Another AD subject with severe semantic impairment read aloud without error virtually all regular and exception words. Neither severely impaired AD subject demonstrated any relationship between oral reading accuracy and semantic knowledge of exception words. These findings support a model of word reading incorporating lexical, nonsemantic processes by which lexical orthographic input representations directly activate lexical phonological output representations without the necessity of semantic mediation.