EEG spectral abnormalities and psychosis as predictors of cognitive and functional decline in probable Alzheimer's disease

We examined whether either psychotic features (e.g., delusions and hallucinations) or EEG abnormalities are associated with more rapid progression of Alzheimer's disease (AD). AD patients with psychosis have exhibited more EEG abnormalities than those without psychosis, and both abnormal EEG and psychosis have been noted to be predictors of functional and cognitive decline in AD. Ninety-five probable AD patients participating in a longitudinal study of dementia had an EEG and a semistructured psychiatric interview at baseline. Using EEG spectral analysis, we classified records as normal/abnormal based on the parasagittal mean frequency. Patients with abnormal EEGs were more functionally (e.g., Blessed Rating Scale for activities of daily living) and cognitively (e.g., Mini-Mental State) impaired than patients with normal EEG. AD patients with psychosis were only more functionally impaired than patients without psychosis. A two-factor analysis showed no interaction between abnormal EEG and psychosis. In addition, using a Cox proportional hazard model adjusted for age and education, the presence of an abnormal EEG or psychotic symptom at study entry was associated with higher risk of reaching severe cognitive and functional impairment during follow-up. Neither abnormal EEG nor the presence of psychosis predicted death. These results indicate that both abnormal EEG and psychosis are independent predictors of disease progression but not of physical survival.     

5-HT2A and 5-HT2C receptor polymorphisms and psychopathology in late onset Alzheimer's disease

The psychopathology of Alzheimer's disease (AD) is varied and includes both behavioural and psychological symptoms. Behavioural and psychological symptoms are common and contribute to the difficulties experienced by carers. However, the mechanism whereby these symptoms occur in some individuals with AD is not understood. We hypothesized that common genetic polymorphisms in neurotransmitter systems are risk factors for these symptoms in the course of AD. A total of 211 subjects from a population-based prospective study of psychopathology within late-onset AD were genotyped for the 5-HT2A receptor polymorphism 102-T/C and the 5-HT2C receptor polymorphism Cys23Ser. Associations were found between the presence of the C102 allele and the presence of visual (Fisher's exact test, one-tailed, P = 0.003) and auditory hallucinations (Fisher's exact test, one-tailed, P = 0.004) and between the presence of the Ser23 allele and visual hallucinations (chi2 = 7.5, df = 1, P = 0.006) (P = 0.03, 0.04 and 0.06, respectively, after Bonferroni correction). In addition, there was an association between the Cys23Ser polymorphism and hyperphagia (chi2 = 6.7, df = 2, P = 0.03) (P = 0.3 after Bonferroni correction). We conclude that common 5-HT2A and 5-HT2C genetic polymorphisms previously showing only weak associations with psychotic illness are associated with psychotic symptoms in AD but are clinically silent until the onset of the neurodegenerative process.     

Elevated blood lead levels in children are associated with lower erythropoietin concentrations

PURPOSE: We investigated the incidence of well-directed violent behavior and suicide attempts in patients with temporal lobe epilepsy, with special attention to postictal psychosis. METHODS: We compared 57 episodes of postictal psychosis with 62 episodes of acute interictal (or alternative) psychosis and with 134 complex partial seizures. All patients were matched for age and for age at onset of seizures. RESULTS: The incidence of well-directed violent behavior against human beings was significantly higher (23%) during postictal psychotic episodes than during acute interictal episodes (5%) and postictal confusion (1%). Suicide attempts were also more frequent during postictal psychosis (7%) than during either acute interictal psychosis (2%) or postictal confusion (0%). CONCLUSIONS: Our study showed that well-directed violent and self-destructive behavior was not a feature of epileptic psychosis in general but a specific hallmark of postictal psychosis.     

Atrial adipofibrosis in a dog

Recent studies in healthy controls suggest an association between novelty-seeking (NS) and the dopamine D4 receptor (DRD4) gene. In this study, we further investigated the relationship between genes implicated in dopamine as well as serotonin neurotransmission and personality traits in bipolar (BP) disorder. Scores on the Tridimensional Personality Questionnaire were examined in 37 recovered Research Diagnostic Criteria-diagnosed BP patients genotyped for DRD3, DRD4, and serotonin 2A receptor (5HTR2a) polymorphisms. Carriers of DRD3 allele 1 showed significantly lower NS values compared to patients without this allele. Scores on NS and on harm-avoidance were not related to DRD4 or 5HTR2a polymorphisms. These preliminary results suggest a role for D3 receptor in NS expression in BP patients.     

True histiocytic lymphoma: is it an entity?

OBJECTIVE: Mania with psychotic features presenting following abrupt normalisation of thyroid function from severe Graves's disease is reported. CLINICAL PICTURE: A 33-year-old man with severe, untreated Graves's disease was treated aggressively, with rapid restoration of normal serum thyroid hormone levels. Symptoms of mania and psychosis then developed. TREATMENT: Time limited antipsychotic medication and continuing medical treatment. OUTCOME: There was resolution of psychiatric symptoms. CONCLUSIONS: The association of mania and psychosis with thyroid disease is rare, but aggressive medical treatment and rapid restoration of normal serum thyroid levels may increase the risk of the emergence of such symptoms.     

Association between dopamine receptor genes and migraine without aura in a Sardinian sample

BACKGROUND: Migraine seems to be caused by a combination of environmental and genetic factors. Clinical and pharmacologic evidence supports the hypothesis that dopaminergic transmission is involved in the pathogenesis of migraine. OBJECTIVE: The current report concerns a genetic study to test the involvement of genes for dopamine (DA) receptors D2 (DRD2), D3 (DRD3), and D4 (DRD4) in migraine without aura, particularly in a subgroup with enhanced DA sensitivity. METHODS: For the first time, a family-based association method--the Transmission Disequilibrium Test (TDT)--was used to examine an isolated population, such as Sardinians. We studied 50 nuclear families of patients affected by migraine without aura. The subgroup of dopaminergic migraineurs was selected based on the presence of both nausea and yawning immediately before or during the pain phase of migraine. RESULTS: No association was detected using the TDT between DRD3, DRD4, and migraine without aura either in the overall sample or in the subgroup. No difference was observed in DRD2 allelic distribution in the overall sample, although the allelic distribution at the DRD2 locus differed significantly in the subgroup of dopaminergic migraineurs (p = 0.004). Allele 1 of the TG dinucleotide intronic noncoding polymorphism of the DRD2 locus was the individual allele that appeared to be in disequilibrium with migraine without aura (p = 0.02). CONCLUSIONS: Our data suggest that a genetic approach could be useful in providing molecular support to the hypothesis that hypersensitivity of the dopaminergic system may represent the pathophysiologic basis of migraine, at least in a subgroup of patients.     

Codon usage in Taenia species

BACKGROUND: Evidence from family and twin studies suggests a genetic contribution to the etiology of anorexia nervosa. Different genes could contribute to the vulnerability to anorexia nervosa, but dopamine could be more specifically implicated in anorexia nervosa because of pharmacologic, endocrine, and neurobiological specificities. The dopamine receptor D3 (DRD3) may be of additional interest, since it is specifically located in the limbic area, an area implicated in reward and reinforcement behavior. METHODS: We performed an association study between 39 patients with severe (requiring hospitalization and with young age at onset) anorexia nervosa (DSM-III-R), and 42 controls, with the Bal I polymorphism in exon I of the DRD3 gene. RESULTS: There was no significant difference between patients with anorexia nervosa and controls in allele frequencies or genotype count. The association was still negative between subgroups separated according to family history of anorexia nervosa or comorbid mood disorders. CONCLUSIONS: Despite the fact that the number of patients tested is small, there is good evidence that the Bal I DRD3 polymorphism does not play a major role in the genetic component of anorexia nervosa. It would be useful to test polymorphisms of the other genes coding for dopamine receptors.     

Late incidence of cancer after metronidazole use: a matched metronidazole user/nonuser study

OBJECTIVE: To address clinical features of subacute postictal aggression, we examined aggressive behavior beginning hours to days after the acute confusional postictal period. METHODS: Six patients from our database of 1300 were assessed. Data was obtained from the patients, their family and caretakers, and medical records. One patient was studied with closed circuit video/EEG. RESULTS: There is clinical heterogeneity among these individuals with respect to etiology of epilepsy, age of onset, laterality, memory of adverse behaviors, and presence of psychosis. Several clinical features, including male gender, were common to all. The episodes of postictal aggression were not isolated events, but recurred repeatedly; the behaviors were uniquely stereotyped in each patient. Subacute postictal aggression was more likely after a cluster of seizures than after a single ictus. All patients had medically intractable epilepsy and were remorseful in the interictal period. CONCLUSIONS: Subacute postictal aggression, a rare phenomenon within the broad spectrum of epilepsy-related behaviors, appears to be a true clinical entity with several consistently observed manifestations.     

Psychiatric symptoms in patients with dementia predict the later development of behavioural abnormalities

BACKGROUND: Cross-sectional studies of non-cognitive symptoms in dementia show that patients with psychotic symptoms tend to have more disturbed behaviour. However, it is not known whether individuals who experience psychiatric symptoms early in dementia are more prone to develop behavioural problems later in the illness. METHOD: The behaviour of 86 community-dwelling subjects with dementia was intensively studied for 4 years or until death, using an informant interview which was administered every 4 months on a median of eight occasions. The extent to which psychiatric symptoms, age, sex and cognitive function predicted clinically significant physical aggression or motor hyperactivity was assessed. RESULTS: Physical aggression was predicted by sad appearance and motor hyperactivity was predicted by persecutory ideas. These associations were robust, remaining significant over 2, 3 and 4 years of follow-up and were independent of cognitive function, age, sex and duration of illness. CONCLUSIONS: There may be two distinct longitudinal syndromes of non-cognitive symptoms in dementia. This suggests that important aberrant behaviours in late dementia may share pathophysiological mechanisms with psychiatric symptoms in early dementia.     

Drug abuse and suicidal tendencies

Among the psychotic symptoms in juvenile drug-consumers one can find autonomous, i.e. drug-independent developments, whose connection with the drug-abuse is to be assessed in differing ways. A beginning psychosis can be modified in its actual symptoms by drug-consumption. On the other hand one must consider the manifestation of a latent psychosis or purely symptomatic psychosis, which, in its symptoms, can hardly be distinguished from schizophrenia. Finally drug-induced personality-changes can develop together with secondary psychotic symptoms. Psychotic symptoms are determined and influenced in a varying degree by drugs. Both after short drug-consumption and after a longer drug-anamnesis with polytoxicomanic symptoms psychotic syndromes can be discovered. Even the initial psychotic symptoms can hint at an adverse development and a bad prognosis. Sometimes the drug-experiences conceal the autonomous development of the psychosis, which, as a rule, shows predominantly schizophrenic symptoms. In addition to a quick change of the actual symptoms, acute states of confusion and depressive-suicidal syndromes, flash-back and horror-trip phenomena, closely connected with the psychotic experience, and a schizophrenic colouring of affective psychoses can be found as frequently drug-induced modifications of the psychotic symptoms. Furthermore one finds an increase of symptoms and of the psychotic episodes in the case of psychoses of the schizophrenic variety which have already begun. Grave personality changes with psychotic symptoms after chronic drug-abuse can cause differential-diagnostic difficulties.     

Risk of left ventricular dysfunction in patients with probable Alzheimer's disease with APOE*4 allele

OBJECTIVE: To examine the association between the APOE genotype and cardiovascular disease in Alzheimer's disease (AD) patients. DESIGN: Case register study of 100 consecutive referrals to a Memory Clinic where type of dementia and cardiovascular comorbidity were diagnosed and APOE genotype was determined. SETTING: The Memory Clinic, University Hospital Rotterdam Dijkzigt. PARTICIPANTS: One hundred Memory Clinic patients, 59 to 91 years of age, who attended the Memory Clinic in the period between January 1994 and March 1996. MEASUREMENTS: Relative risk of cardiovascular morbidity in probable AD, based on clinical and ECG findings. RESULTS: The diagnosis of probable AD was more frequent in APOE*4 allele-carrying AD patients. When comparing homozygotes for APOE*4 with homozygotes for APOE*3, a nine-fold increase in prevalence of cardiac ischemia on ECG was found in the former. When grouping parameters of left ventricular dysfunction, the prevalence was 7.2 (95% confidence interval 1.2-42.6) times greater in probable Alzheimer patients with APOE4/4. CONCLUSIONS: In patients with probable AD, APOE*4 is associated with cardiac disease indicative of left ventricular dysfunction.     

High J Pure Inversion Spectrum of ND3 in the v2 = 1 State

OBJECTIVE: The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients. METHOD: Twenty-eight actively psychotic inpatients, aged 20-60 years, who were under treatment with neuroleptic agents were selected for the study. Each was randomly assigned on a double-blind basis to receive either 5 mg i.m. of haloperidol (N=13) or 1 mg i.m. of flunitrazepam (N=15) during an aggressive event. Verbal and physical aggression was measured over time with the Overt Aggression Scale. Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale. RESULTS: Both flunitrazepam and haloperidol exhibited acute antiaggressive activity. This beneficial effect, as assessed by the Overt Aggression Scale, was obtained within 30 minutes. CONCLUSIONS: Intramuscular flunitrazepam may serve as a convenient, rapid, safe, and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric settings.     

Aggression and the EEG: A quantitative analysis.

80 male offenders (mean age 33.93 yrs) at a psychiatric security hospital completed scales of aggression and hostility and were rated on previous history of assaulative behavior. Two psychiatrists agreed that 45 Ss had personality disorders and 35 were psychotic. Low frequency analysis was employed to obtain measures of EEG abundance at rest, during repetitive auditory stimulation, and during the cold pressor test. Neither within the sample as a whole nor within personality disorders alone was any relation found between resting abundance and aggression. More aggressive Ss tended to have a higher dominant frequency at rest, less increase in theta during monotonous stimulation, and greater alpha reactivity to cold pressor stimulation. Results are not in accord with the view that a high prevalence of theta activity characterizes aggressive offenders. The evidence of greater cortical excitability in aggressive patients suggests that persistent aggression is associated with a dominance of the ergotropic system. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self- and other-directed aggression in child and adolescent psychiatric inpatients

OBJECTIVE: To examine self- and other-directed aggression in 89 children and adolescents on a psychiatric inpatient unit to determine ways in which aggressive and nonaggressive patients differ and to discover those factors associated with self-directed versus other-directed aggression. METHOD: Three types of data were collected: ongoing observations of aggressive behavior during hospitalization, Child Behavior Checklists completed by a parent or guardian at admission, and patient and family history data gathered from a retrospective chart review. RESULTS: Compared with nonaggressive patients, aggressive patients were more likely to have a history of antisocial behavior, to be victims of abuse or neglect, to have lived in a foster home, and to have had several primary caretakers. Both groups of aggressive patients engaged in three types of aggressive behavior with equal frequency and were strikingly similar on a host of other variables. Only the number of primary caretakers with whom a patient had lived discriminated self- from other-directed aggressive patients; patients who experienced frequent disruptions in caretaking were likely to engage in acts of self-injury during hospitalization. CONCLUSIONS: Whether a particular patient will engage in aggressive behavior during hospitalization can be accurately predicted from preadmission characteristics; however, the manner in which a patient is likely to aggress, i.e., toward others or self, is difficult to predict because of striking similarities between types of aggressive patients. Further investigations are needed to determine how self- and other-directed aggressive patients differ and to elucidate relationships between disrupted, unstable, or inadequate caretaking and aggression, particularly self-injury, in children and adolescents.     

Association study between the -141C Ins/Del and TaqI A polymorphisms of the dopamine D2 receptor gene and alcoholism

Dopamine D2 receptors have been implicated in the biology of alcohol preference. We examined the -141 C Ins/Del polymorphism in the promoter region of the dopamine D2 receptor gene (DRD2) and the DRD2 TaqI A polymorphisms in 209 Japanese alcoholics and 152 age- and sex-matched Japanese controls. The Ins allele was significantly increased in the alcoholics, compared with the controls (p < 0.002, odds ratio = 1.82). The TaqI A1 allele tended to be more frequent in the alcoholics than in the controls (p < 0.04). Linkage disequilibrium between these two polymorphisms was weak (a maximum delta value = 0.13). The -141 C Ins/Del polymorphism may affect the vulnerability for alcoholism presumably through different expression of DRD2 in the Japanese.     

Genetics of salivary protein polymorphisms

Human salivary PRPs are determined by six closely linked genes on chromosome 12p13.2. The many PRPs show complex electrophoretic patterns that differ between individuals and reflect numerous genetic polymorphisms. Frequent length and null polymorphisms are common among PRPs. Common themes emerge as a background for these PRP polymorphisms. First, posttranslational proteolysis occurs with double-banded patterns among acidic PRPs and the generation of numerous basic PRPs derived from precursor proteins. Specific mutations may interfere with proteolysis, preventing generation of double-banded acidic PRPs (as with the Pa protein) or of small basic PRPs from precursor proteins (as with Pm proteins). Second, single cysteine substitutions in PRPs (Pa from PRH1 and G1 8 from PRB3) may lead to disulfide bonded homodimers as well as heterodimers with salivary peroxidase. Third, frequent homologous and unequal crossing-over within the PRP gene cluster leads to frequent protein size-variants (intragenic events as with the G1 protein variants) and the generation of the PRB2/1 fusion gene (intergenic event) with deletion of the PRB1 coding region and absence of multiple PRB1 coded proteins (Ps, Pm, Pe) in PRB2/1 homozygotes. Fourth, null mutations may also be produced (as with PsO and G1 0) by single nucleotide changes.     

Psychotic masked depression or black mask for depression

We have used as depression criteria those of Pichot and Hassan, described during the Sint-Moritz Symposium in 1973 on masked depression. According to their clinical experience in Za?re and Senegal, the authors consider the possibility that the "bouffée délirante" (acute psychotic reaction), frequent in black Africa, is in fact a manifestation of depression. They remind the five criterias of Pichot and Hassan, i.e.: 1 degree evidence of depression symptoms; 2 degrees a background and a particular underlying personality; 3 degrees evolutional characteristics; 4 degrees familial antecedents and hereditary factors; 5 degrees the response to antidepressive treatment. They present ten cases of acute psychosis: five from Za?re and five from Senegal. These ten patients have been successfully treated with antidepressive drugs imipramine type, without any neuroleptic drugs; the outcome has always been a rapid remission. Some socio-cultural references are described; it permits to better comprehend the psychological frame of African people. An attempt to psychodynamically interpret the results ends the article.     

Polymorphisms in dopamine system genes are associated with individual differences in attention in infancy.

Knowledge about the functional status of the frontal cortex in infancy is limited. This study investigated the effects of polymorphisms in four dopamine system genes on performance in a task developed to assess such functioning, the Freeze-Frame task, at 9 months of age. Polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine D4 receptor (DRD4) genes are likely to impact directly on the functioning of the frontal cortex, whereas polymorphisms in the dopamine D2 receptor (DRD2) and dopamine transporter (DAT1) genes might influence frontal cortex functioning indirectly via strong frontostriatal connections. A significant effect of the COMT valine1??methionine (Val158Met) polymorphism was found. Infants with the Met/Met genotype were significantly less distractible than infants with the Val/Val genotype in Freeze-Frame trials presenting an engaging central stimulus. In addition, there was an interaction with the DAT1 3` variable number of tandem repeats polymorphism; the COMT effect was present only in infants who did not have two copies of the DAT1 10-repeat allele. These findings indicate that dopaminergic polymorphisms affect selective aspects of attention as early as infancy and further validate the Freeze-Frame task as a frontal cortex task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurotransmission-related genetic polymorphisms, negative affectivity traits, and gender predict tobacco abstinence symptoms across 44 days with and without nicotine patch.

Genetic and personality trait moderators of tobacco abstinence–symptom trajectories were assessed in a highly controlled study. Based on evidence suggesting their importance in stress reactivity and smoking, moderators studied were serotonin transporter gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) polymorphisms and personality traits related to negative affect (NA). Smokers were randomly assigned to quit smoking with nicotine or placebo patches. Financial incentives resulted in 80% verified abstinence across the 44-day study. Individuals with 1 or 2 short alleles of 5-HTTLPR (S carriers) experienced larger increases in NA symptoms than did those without a short allele. Nicotine replacement therapy (NRT) alleviated anxiety only in S carriers. NRT reduced NA to a greater extent in DRD2 A1 carriers than in A2A2 individuals during the 1st 2 weeks of treatment (when on the 21-mg patch); however, A1 carriers experienced a renewal of NA symptoms when switched to the 7-mg patch and when off the patch, while A2A2 individuals continued to benefit from NRT. The results suggest that the effects of genotype and treatment may vary across different durations of abstinence, treatment doses, and genotypes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)