RESUMO
Known comorbidities for Attention-Deficit Hyperactivity Disorder (ADHD) include conduct problems, substance use disorder and gaming. Comorbidity with conduct problems may increase the risk for substance use disorder and gaming in individuals with ADHD. The aim of the study was to build a causal model of the relationships between ADHD and comorbid conduct problems, and alcohol, nicotine, and other substance use, and gaming habits, while accounting for age and sex. We used a state-of-the-art causal discovery algorithm to analyze a case-only sample of 362 ADHD-diagnosed individuals in the ages 12-24 years. We found that conduct problem severity mediates between ADHD severity and nicotine use, but not with more severe alcohol or substance use. More severe ADHD-inattentive symptoms lead to more severe gaming habits. Furthermore, our model suggests that ADHD severity has no influence on severity of alcohol or other drug use. Our findings suggest that ADHD severity is a risk factor for nicotine use, and that this effect is fully mediated by conduct problem severity. Finally, ADHD-inattentive severity was a risk factor for gaming, suggesting that gaming dependence has a different causal pathway than substance dependence and should be treated differently. By identifying these intervention points, our model can aid both researchers and clinicians.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno da Conduta/psicologia , Transtorno de Adição à Internet/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Jogos de Vídeo/psicologia , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Teorema de Bayes , Estudos de Casos e Controles , Criança , Pré-Escolar , Transtorno da Conduta/diagnóstico , Transtorno da Conduta/epidemiologia , Feminino , Humanos , Transtorno de Adição à Internet/diagnóstico , Transtorno de Adição à Internet/epidemiologia , Masculino , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Increased reaction time variability (RTV) on cognitive tasks requiring a speeded response is characteristic of several psychiatric disorders. In attention deficit hyperactivity disorder (ADHD), the association with RTV is strong phenotypically and genetically, yet high RTV is not a stable impairment but shows ADHD-sensitive improvement under certain conditions, such as those with rewards. The state regulation theory proposed that the RTV difference score, which captures change from baseline to a rewarded or fast condition, specifically measures 'state regulation'. By contrast, the interpretation of RTV baseline (slow, unrewarded) scores is debated. We aimed to investigate directly the degree of phenotypic and etiological overlap between RTV baseline and RTV difference scores. Method We conducted genetic model fitting analyses on go/no-go and fast task RTV data, across task conditions manipulating rewards and event rate, from a population-based twin sample (n=1314) and an ADHD and control sibling-pair sample (n=1265). RESULTS: Phenotypic and genetic/familial correlations were consistently high (0.72-0.98) between RTV baseline and difference scores, across tasks, manipulations and samples. By contrast, correlations were low between RTV in the manipulated condition and difference scores. A comparison across two different go/no-go task RTV difference scores (slow-fast/slow-incentive) showed high phenotypic and genetic/familial overlap (r = 0.75-0.83). CONCLUSIONS: Our finding that RTV difference scores measure largely the same etiological process as RTV under baseline condition supports theories emphasizing the malleability of the observed high RTV. Given the statistical shortcomings of difference scores, we recommend the use of RTV baseline scores for most analyses, including genetic analyses.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Tempo de Reação/genética , Gêmeos/genética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estudos de Casos e Controles , Criança , Feminino , Humanos , Inibição Psicológica , Masculino , Modelos Genéticos , Fenótipo , Tempo de Reação/fisiologia , Gêmeos/psicologia , Gêmeos Dizigóticos/genética , Gêmeos Dizigóticos/psicologia , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologiaRESUMO
BACKGROUND: Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ. METHOD: Multivariate familial models were run on data from 1265 individuals aged 6-18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice-delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI). RESULTS: Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41-0.71) and IQ (rF=-0.25 to -0.49). The association between ADHD and cognitive performance was largely independent (80-87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ. CONCLUSIONS: The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/psicologia , Inteligência/genética , Testes Neuropsicológicos/estatística & dados numéricos , Fenótipo , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Comportamento de Escolha , Transtornos Cognitivos/diagnóstico , Europa (Continente) , Feminino , Humanos , Inibição Psicológica , Controle Interno-Externo , Masculino , Análise Multivariada , Determinação da Personalidade/estatística & dados numéricos , Psicometria , Tempo de Reação/genética , RecompensaRESUMO
BACKGROUND: Oppositional defiant disorder (ODD) is frequently co-occurring with attention deficit hyperactivity disorder (ADHD) in children and adolescents. Because ODD is a precursor of later conduct disorder (CD) and affective disorders, early diagnostic identification is warranted. Furthermore, the predictability of three recently confirmed ODD dimensions (ODD-irritable, ODD-headstrong and ODD-hurtful) may assist clinical decision making. METHOD: Receiver-operating characteristic (ROC) analysis was used in order to test the diagnostic accuracy of the Conners' Parent Rating Scale revised (CPRS-R) and the parent version of the Strength and Difficulties Questionnaire (PSDQ) in the prediction of ODD in a transnational sample of 1093 subjects aged 5-17 years from the International Multicentre ADHD Genetics study. In a second step, the prediction of three ODD dimensions by the same parent rating scales was assessed by backward linear regression analyses. RESULTS: ROC analyses showed adequate diagnostic accuracy of the CPRS-R and the PSDQ in predicting ODD in this ADHD sample. Furthermore, the three-dimensional structure of ODD was confirmed by confirmatory factor analysis and the CPRS-R emotional lability scale significantly predicted the ODD irritable dimension. CONCLUSIONS: The PSDQ and the CPRS-R are both suitable screening instruments in the identification of ODD. The emotional lability scale of the CPRS-R is an adequate predictor of irritability in youth referred for ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/diagnóstico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/psicologia , Escalas de Graduação Psiquiátrica , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/complicações , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Poder Familiar , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Análise de RegressãoRESUMO
We [Hawi et al. (2005); Am J Hum Genet 77:958-965] reported paternal over-transmission of risk alleles in some ADHD-associated genes. This was particularly clear in the case of the DAT1 3'-UTR VNTR. In the current investigation, we analyzed three new sample comprising of 1,248 ADHD nuclear families to examine the allelic over-transmission of DAT1 in ADHD. The IMAGE sample, the largest of the three-replication samples, provides strong support for a parent of origin effect for allele 6 and the 10 repeat allele (intron 8 and 3'-UTR VNTR, respectively) of DAT1. In addition, a similar pattern of over-transmission of paternal risk haplotypes (constructed from the above alleles) was also observed. Some support is also derived from the two smaller samples although neither is independently significant. Although the mechanism driving the paternal over-transmission of the DAT risk alleles is not known, these finding provide further support for this phenomenon.
Assuntos
Alelos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Impressão Genômica , Haplótipos , Regiões 3' não Traduzidas , Humanos , Repetições MinissatélitesRESUMO
Replication is a key to resolving whether a reported genetic association represents a false positive finding or an actual genetic risk factor. In a previous study screening 51 candidate genes for association with ADHD in a multi-centre European sample (the IMAGE project), two single nucleotide polymorphisms (SNPs) within the norepinephrine transporter (SLC6A2) gene were found to be associated with attention deficit hyperactivity disorder (ADHD). The same SNP alleles were also reported to be associated with ADHD in a separate study from the Massachusetts General Hospital in the US. Using two independent samples of ADHD DSM-IV combined subtype trios we attempted to replicate the reported associations with SNPs rs11568324 and rs3785143 in SLC6A2. Significant association of the two markers was not observed in the two independent replication samples. However, across all four datasets the overall evidence of association with ADHD was significant (for SNP rs11568324 P = 0.0001; average odds ratio = 0.33; for SNP rs3785143 P = 0.008; average odds ratio = 1.3). The data were consistent for rs11568324, suggesting the existence of a rare allele conferring protection for ADHD within the SLC6A2 gene. Further investigations should focus on identifying the mechanisms underlying the protective effect.
Assuntos
Alelos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Predisposição Genética para Doença , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Frequência do Gene , Marcadores Genéticos , Genótipo , Heterozigoto , Humanos , Íntrons , Mães/estatística & dados numéricos , Estudos Multicêntricos como Assunto , Razão de Chances , Pais , Polimorfismo de Nucleotídeo Único , IrmãosRESUMO
Multiple studies have reported an association between attention deficit hyperactivity disorder (ADHD) and the 10-repeat allele of a variable number tandem repeat (VNTR) polymorphism in the 3'-untranslated region (3'UTR) of the dopamine transporter gene (DAT1). Yet, recent meta-analyses of available data find little or no evidence for this association; although there is strong evidence for heterogeneity between datasets. This pattern of findings could arise for several reasons including the presence of relatively rare risk alleles on common haplotype backgrounds or the functional interaction of two or more loci within the gene. We previously described the importance of a specific haplotype at the 3' end of DAT1, as well as the identification of associated single nucleotide polymorphisms (SNPs) within or close to 5' regulatory sequences. In this study we replicate the association of SNPs at the 5' end of the gene and identify a specific risk haplotype spanning the 5' and 3' markers. These findings indicate the presence of at least two loci associated with ADHD within the DAT1 gene and suggest that either additive or interaction effects of these two loci on the risk for ADHD. Overall these data provide further evidence that genetic variants of the dopamine transporter gene confer an increased risk for ADHD.
Assuntos
Regiões 5' não Traduzidas/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Heterogeneidade Genética , Variação Genética , Alelos , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Europa (Continente) , Frequência do Gene , Marcadores Genéticos , Haplótipos , Humanos , Desequilíbrio de Ligação , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fatores de Risco , População BrancaRESUMO
Several independent studies have reported association between serotonin transporter gene (SLC6A4) polymorphisms and attention deficit hyperactivity disorder (ADHD). Five studies found evidence for association between the long-allele of a 44-bp insertion/deletion polymorphism (5-HTTLPR) and ADHD. Another two studies corroborated this finding while a further six studies did not find such an association. For a second polymorphism within the gene, a variable number tandem repeat (VNTR) within intron 2, one study demonstrated that the 12/12 genotype was significantly less frequent in ADHD cases compared to controls, while a second study found that the 12-allele was preferentially transmitted to offspring affected with ADHD. To provide further clarification of the reported associations, we investigated the association of these two markers with ADHD in a sample of 1,020 families with 1,166 combined type ADHD cases for the International Multi-Centre ADHD Genetics project, using the Transmission Disequilibrium Test. Given the large body of work supporting the association of the promoter polymorphism and mood disorders, we further analyzed the group of subjects with ADHD plus mood disorder separately. No association was found between either of the two markers and ADHD in our large multisite study or with depression within the sample of ADHD cases.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Polimorfismo Genético/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Criança , Pré-Escolar , Depressão/genética , Saúde da Família , Predisposição Genética para Doença/genética , Humanos , Transtornos do Humor/genéticaRESUMO
As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 9/genética , Polimorfismo de Nucleotídeo Único , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Comorbidade , Europa (Continente)/epidemiologia , Europa (Continente)/etnologia , Feminino , Genótipo , Humanos , Israel/epidemiologia , Escore Lod , Masculino , Variações Dependentes do Observador , Índice de Gravidade de Doença , Irmãos , Estados Unidos/epidemiologia , População Branca/genéticaRESUMO
Common disorders of childhood and adolescence are attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD). For one to two cases in three diagnosed with ADHD the disorders may be comorbid. However, whether comorbid conduct problems (CP) represents a separate disorder or a severe form of ADHD remains controversial. We investigated familial recurrence patterns of the pure or comorbid condition in families with at least two children and one definite case of DSM-IV ADHDct (combined-type) as part of the International Multicentre ADHD Genetics Study (IMAGE). Using case diagnoses (PACS, parental account) and symptom ratings (Parent/Teacher Strengths and Difficulties [SDQ], and Conners Questionnaires [CPTRS]) we studied 1009 cases (241 with ADHDonly and 768 with ADHD + CP), and their 1591 siblings. CP was defined as > or =4 on the SDQ conduct-subscale, and T > or = 65, on Conners' oppositional-score. Multinomial logistic regression was used to ascertain recurrence risks of the pure and comorbid conditions in the siblings as predicted by the status of the cases. There was a higher relative risk to develop ADHD + CP for siblings of cases with ADHD + CP (RRR = 4.9; 95%CI: 2.59-9.41); p < 0.001) than with ADHDonly. Rates of ADHDonly in siblings of cases with ADHD + CP were lower but significant (RRR = 2.9; 95%CI: 1.6-5.3, p < 0.001). Children with ADHD + CP scored higher on the Conners ADHDct symptom-scales than those with ADHDonly. Our finding that ADHD + CP can represent a familial distinct subtype possibly with a distinct genetic etiology is consistent with a high risk for cosegregation. Further, ADHD + CP can be a more severe disorder than ADHDonly with symptoms stable from childhood through adolescence. The findings provide partial support for the ICD-10 distinction between hyperkinetic disorder (F90.0) and hyperkinetic conduct disorder (F90.1).
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno da Conduta/complicações , Transtorno da Conduta/epidemiologia , Saúde da Família , Adolescente , Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Comorbidade , Feminino , Humanos , Masculino , Análise Multivariada , Psicometria , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
Season of birth (SOB) has been associated with attention deficit hyperactivity disorder (ADHD) in two existing studies. One further study reported an interaction between SOB and genotypes of the dopamine D4 receptor (DRD4) gene. It is important that these findings are further investigated to confirm or refute the findings. In this study, we investigated the SOB association with ADHD in four independent samples collected for molecular genetic studies of ADHD and found a small but significant increase in summer births compared to a large population control dataset. We also observed a significant association with the 7-repeat allele of the DRD4 gene variable number tandem repeat polymorphism in exon three with probands born in the winter season, with no significant differential transmission of this allele between summer and winter seasons. Preferential transmission of the 2-repeat allele to ADHD probands occurred in those who were born during the summer season, but did not surpass significance for association, even though the difference in transmission between the two seasons was nominally significant. However, following adjustment for multiple testing of alleles none of the SOB effects remained significant. We conclude that the DRD4 7-repeat allele is associated with ADHD but there is no association or interaction with SOB for increased risk for ADHD. Our findings suggest that we can refute a possible effect of SOB for ADHD.
Assuntos
Alelos , Transtorno do Deficit de Atenção com Hiperatividade/genética , Parto , Receptores de Dopamina D4/genética , Estações do Ano , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Desequilíbrio de Ligação , MasculinoRESUMO
Mismatch negativity (MMN) is an event-related potential measure of auditory change detection. It is widely reported to be smaller in patients with schizophrenia and may not improve along with otherwise successful clinical treatment. The main aim of this report is to explore ways of measuring and presenting four features of frequency-deviant MMN dipole sources (dipole moment, peak latency, brain location and orientation) and to relate these to the processes of psychopathology and illness progression. Data from early onset patients (EOS) at the start of the illness in adolescence, and others who had their first break in adolescence 15 years ago (S-15Y) were compared with two groups of age-matched healthy controls (C-EOS, C-15Y). A four-source model fitted the MMN waveform recorded from all four groups, whether MMN amplitude was more (EOS) or less (S-15Y) reduced. The locations were in the left superior temporal and anterior cingulate gyri, right superior temporal and inferior/mid frontal cortices. Dipole latencies confirmed a bottom-up sequence of processing and dipole moments were larger in the temporal lobes and on the left. Patients showed small dipole location changes that were more marked in the S-15Y than the EOS group (more rostral for the left anterior cingulate, more caudal for the right mid-frontal dipole) consistent with illness progression. The modelling of MMN dipole sources on brain atlas and anatomical images suggests that there is a degree of dissociation during illness between small progressive anatomical changes and some functional recovery indexed by scalp recordings from patients with an onset in adolescence 15 years before compared to adolescents in their first episode.
Assuntos
Variação Contingente Negativa/fisiologia , Potenciais Evocados Auditivos/fisiologia , Lobo Frontal/fisiopatologia , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Lobo Temporal/fisiopatologia , Adolescente , Adulto , Atenção/fisiologia , Mapeamento Encefálico , Doença Crônica , Progressão da Doença , Dominância Cerebral/fisiologia , Eletroencefalografia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Valores de Referência , Esquizofrenia/fisiopatologia , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Given recent reports of differences between mismatch negativity (MMN) elicited by always novel sounds (novelty-elicited MMN) and that elicited by repeated rare deviants (conventional MMN), we investigated novelty-elicited MMN and P3a in patients with schizophrenia before and after a nonstandardized inpatient treatment. DESIGN: Electrophysiological and clinical assessment of patients on admission and discharge from hospital. Assessment of control subjects on 2 sessions. SETTING: Inpatient treatment in a psychiatric university hospital. SUBJECTS: 20 patients with schizophrenia and 21 healthy control subjects of similar age and sex. Selection of patients with first- to third-episode schizophrenia. OUTCOME MEASURES: Early and late component MMN amplitudes and latencies, P3a amplitudes and latencies, Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Extrapyramidal Symptom Scale (EPS), Abnormal Involuntary Movement Scale (AIMS) and chlorpromazine equivalents. RESULTS: In patients with schizophrenia, novelty-elicited MMN was unimpaired on admission, and there was a statistically significant reduction of the late MMN component with treatment. Improvements in symptom expression were associated with increased latencies of the early MMN component. CONCLUSION: Results indicate differences in information processing between conventional and novelty-elicited MMN. Some components of the novelty-elicited MMN might be more state dependent than those of the conventional MMN.
Assuntos
Nível de Alerta/fisiologia , Atenção/fisiologia , Variação Contingente Negativa/fisiologia , Esquizofrenia/fisiopatologia , Adulto , Antipsicóticos/uso terapêutico , Nível de Alerta/efeitos dos fármacos , Atenção/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/fisiopatologia , Variação Contingente Negativa/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Admissão do Paciente , Alta do Paciente , Escalas de Graduação Psiquiátrica , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Esquizofrenia/tratamento farmacológicoRESUMO
Measures of selective attention processing like latent inhibition (LI) and conditioned blocking (CB) are disturbed in some patients with schizophrenia. [LI is the delay in learning about the associations of a stimulus that has been associated with no event (versus de novo learning); CB is the delay in learning the associations of a stimulus-component when the other component has already started to acquire these associations.] We proposed: (1) to replicate the reported decreases of CB in patients without paranoid-hallucinatory symptoms; (2) to see if CB depends on the age of illness-onset and its duration, as reported for LI. We studied 101 young and old, acute and chronically ill patients with schizophrenia, of whom 62 learned a modified 'mouse-in-house' CB task, and compared them with 62 healthy controls matched for age, education and socio-economic background. CB was more evident in patients with a diagnosis of paranoid schizophrenia than other subtypes. An unusual persistence of high CB scores through testing was associated with productive symptoms (including positive thought disorder). Reduced CB related to the expression of (a) Schneider's first rank symptoms of ideas-of-reference and (b) to negative symptoms like poor rapport and poor attention. CB was less evident in the older patients and those with an earlier illness-onset. In contrast to the similar LI test of selective attention, CB is found in patients with paranoid schizophrenia and its expression is not related closely to illness duration. This implies that the two tests reflect the activity of different underlying processes. We suggest that reduced CB on initial test-trials in nonparanoid schizophrenia reflects the unusual persistence of controlled information processing strategies that would normally become automatic during conditioning. In contrast, continued CB during testing reflects an unusual persistence of automatic processing strategies.
Assuntos
Condicionamento Psicológico/fisiologia , Transtornos Psicóticos/diagnóstico , Esquizofrenia/fisiopatologia , Doença Aguda , Adulto , Fatores Etários , Doença Crônica , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Estudos Transversais , Feminino , Humanos , Aprendizagem/fisiologia , Masculino , Transtornos Psicóticos/fisiopatologia , Tempo de Reação , Psicologia do Esquizofrênico , Índice de Gravidade de Doença , Pensamento/fisiologiaRESUMO
Childhood conduct disorder (CD) may originate in a stressful upbringing, and be associated with unusual physical or sexual development and thyroid dysfunction. We therefore explored circulating levels of hormones from adrenal, gonadal and growth hormone axes associated with stress, aggression and development in 28 CD patients and 13 age-matched healthy children (10-18 years old). The CD group had higher levels of dehydroepiandrosterone sulphate (DHEA-S), corticotropin (ACTH) and free tri-iodothyronine (fT(3)) if under 14 years. There were no differences for gonadal hormones or maturity ratings which were not associated with aggression. Smaller physical measures in CD children correlated with DHEA-S and growth factors (e.g. insulin-like growth factor I) increased ACTH and fT(3) correlated with restless-impulsive ratings, and DHEA-S with 'disruptive behaviour'. Imbalances in the adrenal and growth axes may have neurotropic repercussions in development.
Assuntos
Hormônio Adrenocorticotrópico/sangue , Transtorno da Conduta/fisiopatologia , Sulfato de Desidroepiandrosterona/sangue , Adolescente , Agressão , Estudos de Casos e Controles , Criança , Hormônios Esteroides Gonadais/sangue , Substâncias de Crescimento/sangue , Humanos , Masculino , Estresse Psicológico , Hormônios Tireóideos/sangueRESUMO
Patients with schizophrenia show impairments of attention and neuropsychological performance, but the extent to which this is attributable to antipsychotic medication remains largely unexplored. We describe here the putative influence of the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), the antipsychotic serum concentration of dopamine (DA) D2-blocking activity and the approximated central dopamine D2-receptor occupancy (DA D2-occupancy), on conditioned blocking (CB) measures of attention and performance on a neuropsychological battery, in 108 patients with schizophrenia (compared with 62 healthy controls). Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid versus non-paranoid diagnosis, and in female versus male patients (independent of symptom severity). Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB in non-paranoid patients. Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance of the trail-making and picture completion tests (negative) and the block-design task (positive) showed the functional importance of DA-related activity. High estimates of central DA D2-occupancy were related to impaired verbal fluency but were associated with improved recall of stories, especially in paranoid patients. This, the first study of its kind, tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB, verbal fluency) and temporal lobe functions (verbal recall) as well as in some non-verbal abilities mediated more in the right hemisphere in patients with schizophrenia.
Assuntos
Antipsicóticos/efeitos adversos , Atenção/efeitos dos fármacos , Clorpromazina/efeitos adversos , Transtornos Cognitivos/etiologia , Lobo Frontal/efeitos dos fármacos , Receptores de Dopamina D2/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Comportamento Verbal/efeitos dos fármacos , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacologia , Estudos de Casos e Controles , Clorpromazina/administração & dosagem , Clorpromazina/farmacologia , Transtornos Cognitivos/patologia , Condicionamento Clássico , Relação Dose-Resposta a Droga , Feminino , Lobo Frontal/patologia , Lobo Frontal/fisiologia , Humanos , Masculino , Rememoração Mental , Transtornos Paranoides/fisiopatologia , Receptores de Dopamina D2/fisiologia , Esquizofrenia/patologia , Fatores Sexuais , Teste de Sequência Alfanumérica , Comportamento Verbal/fisiologiaRESUMO
Controversy exists on whether the constructs tested by paper/pencil and computerized continuous-performance tests (CPT) are similar, and the deficits recorded in children with attention-deficit/hyperactivity symptoms (ADHD) are comparable. Signal-detection measures were recorded on four such tests of 'sustained attention', with increasing working-memory requirements in healthy children (14; mean 10 years), and those with ADHD (14; mean 10 years) or a tic syndrome (TS, 11; mean 11 years). Clinical associations were sought from 24-h urinary measures of monoamine activity. The cancellation paper/pencil test revealed no group differences for errors or signal detection measures. On the CPT, ADHD children made more omission and commission errors than control subjects, but TS children made mostly omissions. This reflected the poor perceptual sensitivity (d-prime, d') for ADHD and conservative response criteria (beta) for TS children. This group difference extended to the CPTax, which was shown on a regression analysis to test for putative working-memory-related abilities as well as concentration. In all children, immediate response-feedback reduced omissions, and modestly improved d'. CPTax performance related negatively to dopamine metabolism in control subjects and to serotonin metabolism in the ADHD group. But comparisons between the metabolites in the ADHD group suggest that increased serotonin and decreased noradrenaline, with respect to dopamine metabolism, may detract from CPT performance in terms of d'. CPT tasks demonstrated a perceptual-based impairment in ADHD and response conservatism in TS patients independent of difficulty. Catecholamine activity was implicated in the promotion of perceptual processing in normal and ADHD children, but serotonin activity may contribute to poor CPTax (working-memory) performance in ADHD patients.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Atenção , Monoaminas Biogênicas/metabolismo , Síndrome de Tourette/diagnóstico , Síndrome de Tourette/metabolismo , Adolescente , Estudos de Casos e Controles , Criança , Dopamina/metabolismo , Feminino , Ácido Homovanílico/metabolismo , Humanos , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Metoxi-Hidroxifenilglicol/metabolismo , Testes Neuropsicológicos , Norepinefrina/metabolismo , Desempenho Psicomotor , Serotonina/metabolismoRESUMO
Dopamine agonists impair and antagonists normalize prepulse inhibition (PPI) of startle and gating of the P50 event-related potential (ERP), but the within-subject effect of treatment on impaired gating in schizophrenia has not been studied. We report the first results of a longitudinal study using PPI of ERPs as a measure of sensory gating in an auditory Go/NoGo discrimination. After admission and approximately 3 months later, at discharge, 15 patients with schizophrenia performed a discrimination between a 1.4 kHz target tone and an 0.8 kHz non-target tone with no prepulse, or with a prepulse at 100 ms or 500 ms before either tone. ERPs were recorded from 19 sites. Healthy subjects were studied twice, with 3 months between sessions. PPI of the P50 peak in the 100-ms condition was reduced in patients on admission. At discharge, decreased negative symptoms correlated with enhanced P50-PPI at frontocentral sites. After treatment increased N100-PPI at centrotemporal sites correlated with fewer positive symptoms. At frontal sites in the 100-ms condition, the initially small difference of non-target minus target P300 amplitudes increased as negative symptoms decreased. It is concluded that weak auditory prepulses interfere with early auditory stimulus processing (P50), channel selection (N100) and selective attention (P300). Gating of these stages of processing is impaired in psychotic patients and treatment tends to normalize gating in tandem with improvements of different types of symptoms.
Assuntos
Mapeamento Encefálico , Encéfalo/fisiopatologia , Potenciais Evocados/fisiologia , Esquizofrenia/fisiopatologia , Estimulação Acústica , Adolescente , Adulto , Eletroencefalografia , Feminino , Seguimentos , Humanos , Masculino , Psicologia do EsquizofrênicoRESUMO
1. Increased water intake and output is more common among psychiatric patients, especially those with schizophrenia, than in the general population. Animal studies suggest that polydipsia and polyuria derive, in part, from dopamine dysregulation. Stimulated by these observations this study sought to elucidate relationships among water homeostasis, monoamine metabolism, and electrolyte excretion in schizophrenic patients with and without paranoid hallucinatory symptoms (PH vs. NP), thought to reflect hyper- and hypo-dopaminergic states respectively, and to compare these with those shown by patients with obsessive compulsive disorder (OCD). 2. 24 hr-urine samples for electrolyte, monoamine and metabolite measures were taken from 14 schizophrenic patients with PH symptoms, 13 with predominantly nonparanoid (NP) symptoms, 11 OCD patients and 27 healthy controls (matched for age, weight and creatinine production). Water intake and serum electrolytes was sampled during psychological testing. 3. PH patients drank 2-3 times more than the others in a 3-4 hr test, yet 24 hr-urinary volumes were 75% larger in both PH and NP patients than in the two comparison groups. 4. Daily potassium excretion was a bit higher in PH patients, but concentrations of sodium, potassium and phosphate tended to be lower in PH and NP patients than in the others. 5. Positive associations of electrolyte with homovanillic acid excretion were consistent across groups and not directly related to medication. But associations of electrolyte excretion with noradrenergic activity in controls were absent in psychotic patients and associations with serotonin in OCD patients were absent in the other groups. 6. Increased water intake and output in PH patients along with the disturbed association with noradrenergic metabolism are consistent with altered autonomic activity in these patients. 7. The independence of measures of water homeostasis from dopaminergic medication indicates that the associations in clinically responding PH patients of polydipsia with DA function (decreased DA levels) may be pertinent to this subgroup but not to schizophrenia in general.
Assuntos
Dopamina/farmacologia , Comportamento de Ingestão de Líquido/fisiologia , Transtorno Obsessivo-Compulsivo/complicações , Poliúria/etiologia , Esquizofrenia/complicações , Adolescente , Adulto , Criança , Eletrólitos/urina , Feminino , Homeostase , Humanos , Concentração de Íons de Hidrogênio , Masculino , Transtorno Obsessivo-Compulsivo/fisiopatologia , Esquizofrenia/fisiopatologia , Equilíbrio HidroeletrolíticoRESUMO
Against a background of (a) increased drinking behavior in children with attention-deficit hyperactivity disorder (ADHD); (b) the parallel between some behaviors associated with ADHD and hypertension; (c) the use of the spontaneously hypertensive rat as a model for ADHD; and (d) similarities in the changes of neuropeptide Y (NPY) and catecholamine in studies of hypertension and drinking, NPY, catecholamines and electrolyte balance were compared in the plasma and urine of healthy children and those with ADHD. Drinking was monitored during 3 h of neuropsychological tests over 2 days in 14 ADHD and nine healthy children. Patients drank four times as much water and showed twice the levels of NPY found in controls. In controls there were positive and in patients there were negative relationships for NPY with drinking and restless behavior. Patients' plasma levels of norepinephrine (NE) and epinephrine were slightly elevated, but urinary levels of NE and the serotonin metabolite were markedly increased. Urinary excretion rates for sodium (not potassium), phosphate and especially calcium were decreased in patients even after covarying for less urine production in the ADHD group. NPY levels were inversely related to calcium excretion and drinking was inversely related to circulating sodium. Increases of drinking and circulating NPY in ADHD children and decreased electrolyte excretion may reflect a common disturbance in metabolic homeostasis.