RESUMO
A total of 34 consecutive patients with dissociative identity disorder or dissociative disorder not otherwise specified were evaluated using the Turkish version of the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D). They were compared with a matched control group composed of 34 patients who had a nondissociative psychiatric disorder. Interrater reliability was evaluated by 3 clinicians who assessed videotaped interviews conducted with 5 dissociative and 5 nondissociative patients. All subjects who were previously diagnosed by clinicians as having a dissociative disorder were identified as positive, and all subjects who were previously diagnosed as not having a dissociative disorder were identified as negative. The scores of the main symptom clusters and the total score of the SCID-D differentiated dissociative patients from the nondissociative group. There were strong correlations between the SCID-D and the Dissociative Experiences Scale total and subscale scores. These results are promising for the validity and reliability of the Turkish version of the SCID-D. However, as the present study was conducted on a predominantly female sample with very severe dissociation, these findings should not be generalized to male patients, to dissociative disorders other than dissociative identity disorder, or to broader clinical or nonclinical populations.
Assuntos
Comparação Transcultural , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos Dissociativos/diagnóstico , Transtornos Dissociativos/psicologia , Entrevista Psicológica , Adulto , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Psicometria/estatística & dados numéricos , Valores de Referência , Reprodutibilidade dos Testes , Tradução , Turquia , Adulto JovemRESUMO
Nitric oxide (NO) has been implicated to play a role in the pathogenesis of many neuropsychiatric disorders. NO level was found high in acute manic inpatients. In this study, we aimed to assess NO level and activity of the antioxidant enzyme, superoxide dismutase (SOD), in euthymic bipolar patients. Twenty-seven patients with bipolar disorder (BD) in euthymic phase, and 20 healthy volunteers were included in this study. A semi-structured form was used to note social, demographic and clinical parameters of the patients. NO level and SOD activity were studied in the serum samples obtained from the patients and controls. The mean serum NO level in BD was significantly higher than in controls. Mean serum SOD activity was found to be elevated in patients with BD compared to controls. Total number of the manic episodes correlated with NO levels, but not with SOD activity. In conclusion, the number of manic episodes is positively associated with NO levels. NO and SOD appear to have a pathophysiological role in BD, especially in Type I euthymic phase, and may be considered an available trait marker for BD.
Assuntos
Transtorno Bipolar , Óxido Nítrico/sangue , Superóxido Dismutase/sangue , Adolescente , Adulto , Idoso , Antioxidantes/fisiologia , Transtorno Bipolar/sangue , Transtorno Bipolar/fisiopatologia , Transtorno Bipolar/psicologia , Demografia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Seguimentos , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Índice de Gravidade de Doença , Fatores de TempoRESUMO
Reactive oxygen species (ROS) have been suggested to play an important role in physiopathology of schizophrenia. The major intracellular antioxidant enzymes, copper-zinc superoxide dismutase in the cytoplasm and manganese superoxide dismutase (Mn-SOD) in the mitochondria, rapidly and specifically reduce superoxide radicals to hydrogen peroxide. Polymorphisms in the genes encoding antioxidant enzymes should therefore result in predisposition to schizophrenia. The present study was performed to assess whether there is a genetic association between a functional polymorphism (Ala-9Val) in the human Mn-SOD gene in schizophrenic patients (n=153) and healthy controls (n=196) using a PCR/RFLP method. Significant differences in the genotypic distribution between schizophrenics and controls were observed. Genotypic distribution with 14 (9.2%) Ala/Ala, 106 (69.3%) Ala/Val and 33 (21.6%) Val/Val subjects in schizophrenia was different from those of controls with 46 (23.5%), 83 (42.3%) and 67 (34.2%), respectively (p<0.0001). When the patients with schizophrenia were divided into the subgroups as disorganized, paranoid and residual, there was a significant difference in genotypic distribution among the subgroups (chi2=11.35, df=4, p=0.023). This association between -9Ala Mn-SOD allele and schizophrenia suggests that -9Ala variant may have a contribution in the physiopathogenesis of schizophrenia. Further investigations are warranted in larger populations with other susceptible genes that might be associated with schizophrenia.
Assuntos
Polimorfismo Genético/genética , Esquizofrenia/enzimologia , Esquizofrenia/genética , Superóxido Dismutase/genética , Adulto , Alelos , Substituição de Aminoácidos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Encéfalo/enzimologia , Discinesia Induzida por Medicamentos/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esquizofrenia/tratamento farmacológicoRESUMO
Evidence is accumulating for a possible role of nitric oxide (NO) in schizophrenia. Adrenomedullin (AM) induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of NO. AM immune reactivity is present in the brain consistent with a role as neurotransmitter. We aimed to examine plasma levels of nitrite (a metabolite of NO) and AM in schizophrenic patients. Eighty-two patients with schizophrenia and 21 healthy control subjects were included in this study. DSM-IV diagnosis of chronic schizophrenia was established on the basis of independent structured clinical interviews and review of records by two qualified psychiatrists which included the Brief Psychiatric Rating Scale (BPRS), The Scale for the Assessment of Negative Symptoms (SANS) and The Scale for the Assessment of Positive Symptoms (SAPS). Total nitrite and AM have been studied in plasma. The mean values of plasma nitrite and AM levels in schizophrenic group were significantly higher than control values, respectively (P=0.03, P<0.0001). AM levels of schizophrenic patients were three fold higher than controls. In correlation analyses, there were statistically significant positive correlations between AM level and SAPS-delusion subscale (r=0.27, P=0.04); SAPS-bizarre behavior subscale (r=0.28, P=0.03) and SAPS-total (r=0.36, P=0.005). There is no correlation between total nitrite and AM levels (r=0.11, P=0.31). Both NO and AM may have a pathophysiological role in schizophrenia, and clinically symptomatology and prognosis of schizophrenia. This subject needs further study including treatment response and subtypes of schizophrenia.
Assuntos
Encéfalo/fisiopatologia , Óxido Nítrico/sangue , Peptídeos/sangue , Esquizofrenia/sangue , Esquizofrenia/fisiopatologia , Adolescente , Adrenomedulina , Adulto , Encéfalo/metabolismo , Escalas de Graduação Psiquiátrica Breve , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
BACKGROUND: There is evidence that oxygen free radicals play an important role in the pathophysiology of many neuropsychiatric disorders. Although it has not been investigated yet, several recent studies proposed that nitric oxide (NO) and other parameters related to oxidative stress may have a pathophysiological role in autism. METHODS: We assessed the changes in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and thiobarbituric acid-reactive substances (TBARS) levels in plasma as well as NO levels in red blood cells (RBC) in patients with autism (n=27) compared to age- and sex-matched normal controls (n=30). RESULTS: In the autistic group, increased RBC NO levels (p<0.0001) and plasma GSH-Px activity (p<0.0001) and unchanged plasma TBARS levels and SOD activity were detected. CONCLUSIONS: These findings indicate a possible role of increased oxidative stress and altered enzymatic antioxidants, both of which may be relevant to the pathophysiology of autism.
Assuntos
Transtorno Autístico/sangue , Glutationa Peroxidase/sangue , Óxido Nítrico/sangue , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Transtorno Autístico/enzimologia , Criança , Pré-Escolar , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Estresse OxidativoRESUMO
A number of essential trace elements play a major role in various metabolic pathways. Selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) are essential trace elements that have been studied in many diseases, including autoimmune, neurological, and psychiatric disorders. However, the findings of previous research on the status of trace elements in patients with schizophrenia have been controversial. We studied these elements in patients with a DSM-IV diagnosis of schizophrenia and compared them with sex- and age-matched healthy controls. Plasma Cu concentrations were significantly higher (p < 0.01) and Mn and Fe concentrations were lower (p < 0.05 and p < 0.05, respectively) in schizophrenic patients than in controls. Se and Zn concentrations and protein levels did not differ between patients and healthy controls. These observations suggest that alterations in essential trace elements Mn, Cu, and Fe may play a role in the pathogenesis of schizophrenia. However, findings from trace element levels in schizophrenia show a variety of results that are difficult to interpret.
Assuntos
Esquizofrenia/sangue , Oligoelementos/sangue , Adulto , Cobre/sangue , Cobre/metabolismo , Feminino , Humanos , Ferro/sangue , Ferro/metabolismo , Masculino , Manganês/sangue , Manganês/metabolismo , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Esquizofrenia/fisiopatologia , Selênio/sangue , Selênio/metabolismo , Zinco/sangue , Zinco/metabolismoRESUMO
Several studies have examined the relationship between dissociation and alexithymia. In this study, the objective was to investigate whether there was a relationship between alexithymia, dissociation and state and trait anxiety in psychiatric outpatients. The evaluations of psychiatric outpatients (n=154) were based on the Toronto Alexithymia Scale, the Dissociative Experiences Scale and the State and Trait Anxiety Index. The data were analyzed using chi2 test and multiple covariance analyses. Subjects with alexithymia (46.8%) were significantly less educated and showed higher state and trait anxiety. The mean Toronto Alexithymia Scale total score of the female and male patients was similar. The mean Dissociative Experiences Scale score of the study group was 10.8 (sd=9.8, ranged 0 to 45). A multivariate analysis of covariance showed that state and trait anxiety was a significant covariant for the Toronto Alexithymia Scale-Difficulty Identifying Feelings subscale. Only the trait anxiety was a significant covariant for the Toronto Alexithymia Scale-Difficulty Expressing Feelings subscale. The overall main effect of dissociation was not significant on the Toronto Alexithymia Scale total and subscales. These data suggest that dissociation is fundamentally a different construct from alexithymia, while state and trait anxiety are closely related to alexithymia.
Assuntos
Sintomas Afetivos/etnologia , Ansiedade/etnologia , Transtornos Dissociativos/etnologia , Adulto , Sintomas Afetivos/diagnóstico , Ansiedade/diagnóstico , Transtornos Dissociativos/diagnóstico , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/etnologia , Transtornos Mentais/reabilitação , Inquéritos e Questionários , TurquiaRESUMO
Acute oedema of the uvula is relatively rare, and often idiopathic. There are only a few cases reported up to date. This is the first case of oedema in the uvula that occurred during lithium treatment of a patient with bipolar-I manic disorder.
RESUMO
OBJECTIVE: In the present study, we aimed to investigate whether nitric oxide (NO) levels and activities of xanthine oxidase (XO), superoxide dismutase (SOD), and adenosine deaminase (ADA) are associated with Panic disorder (PD) as well as impact of psychopharmacological treatments on NO, SOD, ADA, and XO levels in PD. METHOD: In this study, 32 patients and 20 healthy controls were included. The serum levels of NO, XO, SOD, and ADA were measured in the patients and controls. The patients were treated with antidepressant. RESULTS: ADA and XO levels of the patients were significantly higher than the controls. SOD levels of the patients were significantly lower than the controls but the difference was not statistically significant. Although NO levels of the patients were higher than the controls, the difference was not statistically significant. There was no correlation between PAS and the parameters studied (SOD, ADA, XO, and NO) of the patients. After 8 weeks of antidepressant treatment, ADA and SOD activities were increased whereas NO and XO levels decreased significantly. CONCLUSION: ADA, XO activity may have a pathophysiological role in PD, and prognosis of PD. Activity of these enzymes may be used to monitor effects of the antidepressant treatment.
Assuntos
Adenosina/sangue , Antidepressivos/administração & dosagem , Óxido Nítrico/sangue , Transtorno de Pânico/sangue , Superóxido Dismutase/sangue , Xantina Oxidase/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/tratamento farmacológico , Análise Espectral/métodosRESUMO
Lamotrigine is a novel mood stabiliser as well as an anti-epileptic drug that has already been used for the prevention of convulsions. Despite several known side effects, hepatic dysfunction related to the drug has not been widely reported. A few cases have been observed in neurological, especially paediatric patients, but not in psychiatric patients. We report a case of cholestatis which occurred 6 weeks after starting lamotrigine therapy and which resolved after discontinuation, during the acute phase of disease. To the best of our knowledge, this is the first case of lamotrigine associated with cholestasis reported in patients with bipolar disorder.
RESUMO
The aim of our study was to determine the frequency of dissociative disorders (DDs) among inpatients with conversion disorder (CD) in a university clinic settled in Eastern Turkey. During a period of 24 months, 59 consecutively admitted adult CD patients were screened with the Dissociative Experience Scale (DES). Patients who scored above 30 (DDs group) did not differ by age or gender from a group of inpatients who scored below 10 on the scale (comparison group). All patients in the two groups were then interviewed in a blind manner using the Dissociative Disorders Interview Schedule (DDIS) and Structured Interview for DSM-IV Dissociative Disorders (SCID-D). According to the SCID-D, 18 of 59 patients (30.5%) received a diagnosis of dissociative disorder; nine of these 18 patients (50%) were diagnosed as having dissociative identity disorder, eight (44.4%) were diagnosed as having dissociative disorder not otherwise specified (NOS), and one (5.6%) was diagnosed as having dissociative amnesia. Accordingly to the DDIS, borderline personality disorder was frequent in the DDs group, and all of the patients in the DDs group reported sexual abuse and neglect during childhood, latency, or adolescence. A high proportion of CD patients have significant dissociative pathology. The proper diagnosis of these patients has important implications for their clinical course.
Assuntos
Transtorno Conversivo/etnologia , Transtorno Conversivo/reabilitação , Transtornos Dissociativos/etnologia , Transtornos Dissociativos/reabilitação , Adolescente , Adulto , Transtorno da Personalidade Borderline/diagnóstico , Transtorno da Personalidade Borderline/epidemiologia , Transtorno Conversivo/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos Dissociativos/diagnóstico , Feminino , Hospitalização , Hospitais Psiquiátricos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Turquia/epidemiologiaRESUMO
The Adolescent Dissociative Experiences Scale (A-DES) is designed to measure dissociation in adolescents. The present study aimed to assess the reliability, validity, and psychometric characteristics of the Turkish version of the A-DES. The Turkish version of the A-DES was administered to 20 patients with a dissociative disorder, 24 patients with post-traumatic stress disorder (PTSD), 31 patients with anxiety disorder, 31 patients with mood disorder, 24 patients with attention deficit-hyperactivity disorder (ADHD), and 201 non-clinical participants. The internal consistency and the test-retest correlation of the A-DES were excellent. The mean total score of A-DES was 6.2 in dissociative disorder, 3.9 in PTSD, 2.1 in anxiety disorder, 2.4 in mood disorder, 2.5 in ADHD groups and 2.4 in non-clinical participants. There was a statistically significant difference between dissociative patients and other diagnostic groups on the A-DES total score. The good psychometric characteristics of the A-DES among Turkish participants support its cross-cultural validity.
Assuntos
Psiquiatria do Adolescente , Transtornos Dissociativos/diagnóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Escalas de Graduação Psiquiátrica/normas , Adolescente , Transtornos de Ansiedade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Feminino , Humanos , Masculino , Transtornos do Humor/diagnóstico , Reprodutibilidade dos Testes , Turquia/etnologiaRESUMO
There is a reciprocal regulation of arginase and nitric oxide synthase (NOS) in L-arginine-metabolizing pathways. Nitric oxide (NO) may be involved in some psychiatric disorders like schizophrenia, depression and bipolar affective disorder (BPAD). To our knowledge, there is no study in the literature in which the role of arginase, an important part of the arginine regulatory system affecting NOS activity, was investigated in BPAD. This study aims to investigate arginase, manganese (Mn) and total nitrite levels (a metabolite of NO) and their relationship to the arginine-NO pathway in patients with BPAD. Arginase activities, Mn and total nitrite levels were measured in plasma from forty-three patients with BPAD (Type one) and thirty-one healthy control subjects. Plasma arginase activities and Mn were found to be significantly lower and total nitrite level higher in patients with BPAD compared with controls. Our results suggest that the arginine-NO pathway is involved in the pathogenesis of BPAD.
Assuntos
Arginina/sangue , Transtorno Bipolar/sangue , Óxido Nítrico/sangue , Adulto , Análise de Variância , Estudos de Casos e Controles , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Manganês/sangue , Pessoa de Meia-Idade , Nitritos/sangue , Fatores SexuaisRESUMO
The purpose of this study was to evaluate the relationship between attention deficit hyperactivity disorder (ADHD) and polymorphism of the two regions of the 5-HTT gene [variable number of tandem repeats (VNTR) and 5-HTTLRR] in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 71 patients with ADHD and 128 healthy controls. The 5-HTTLPR S/S genotype was significantly lower in the patients than in the controls (p = 0.018). Homozygous and heterozygous L variant predominated in the ADHD group. But the VNTR STin2.12/12 genotype was significantly less found in the patients than in the controls (p = 0.001). There was no significant difference between the frequency of the short (S), long, 10, and 12 alleles of both groups. The lack of an S/S variant of 5-HTTLPR polymorphism of the STin2.12/12 variant of VNTR polymorphism appears to be associated with an increased risk of ADHD.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas de Transporte/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso/genética , Polimorfismo Genético , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase , Serotonina/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina , Sequências de Repetição em Tandem , TurquiaRESUMO
A questionnaire consisting of items about abuse, neglect, self-mutilation and suicide attempt and the Turkish Version of the Dissociative Experiences Scale were given to 862 high school students. The rates of suicide attempt and self-mutilative behaviors were 10.1% and 21.4%, respectively. Abused or neglected groups (34.3%) had 7.6-fold higher suicide attempts and 2.7-fold higher self-mutilation behaviours. The logistic regression model showed that each type of trauma and dissociation contributed to suicide attempts and self-mutilation, but dissociation was the most powerful. Suicidal and self-destructive adolescents should precisely be evaluated for abuse, neglect and dissociation in clinical practice.
Assuntos
Maus-Tratos Infantis/estatística & dados numéricos , Transtornos Dissociativos/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Estudantes/estatística & dados numéricos , Tentativa de Suicídio/estatística & dados numéricos , Adolescente , Adulto , Criança , Maus-Tratos Infantis/psicologia , Transtornos Dissociativos/psicologia , Feminino , Humanos , Masculino , Análise de Regressão , Comportamento Autodestrutivo/psicologia , Estudantes/psicologia , Tentativa de Suicídio/psicologia , Inquéritos e QuestionáriosRESUMO
Several studies indicate that nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. Adrenomedullin (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. We hypothesized that NO and AM activities have been affected in autistic patients and aimed to examine these molecules. Twenty-six autistic patients and 22 healthy control subjects were included in this study. AM and total nitrite (a metabolite of NO) levels have been measured in plasma. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31). Certainly, this subject needs much further research investigating autistic patients in earlier periods of life and with subtypes of the disorder.
Assuntos
Transtorno Autístico/metabolismo , Óxido Nítrico/metabolismo , Peptídeos/sangue , Vasodilatadores/metabolismo , Adrenomedulina , Transtorno Autístico/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Nitritos/sangueRESUMO
Nitric oxide (NO) has been implicated to play a role in the pathogenesis of depressive disorders. Adrenomedullin (AM) induces vasorelaxation by activating adenylate cyclase and also by stimulating the release of NO. AM immune reactivity is present in the brain, consistent with a role as neurotransmitter. Therefore, it is suggested that these two molecules may play a role together in the brain. We aimed to examine AM and NO in bipolar affective disorder (BPAD). Forty-four patients with BPAD and 21 healthy control subjects were included in this study. DSM-IV diagnosis of bipolar affective disorder (type I, manic episodes) was independently established by two psychiatrists and the Turkish version of the Bech-Rafaelson Mania Scale was administered. Also, a semistructured form was used to ascertain several sociodemographic and clinical variables of the patients. AM and NO were studied in plasma. The mean value of plasma NO levels in the BPAD group of 46.58 +/- 13.97 micromol/l was significantly higher than that of controls (31.81 +/- 8.14 micromol/l) (z = -4.15, p = 0.000). Mean plasma AM levels were found to be increased in patients with BPAD (35.13 +/- 5.26 pmol/l) compared to controls (16.22 +/- 3.02 pmol/l) (z = -6.16, p = 0.000). AM levels of BPAD patients were approximately 2-fold higher than controls. AM levels were positively correlated with the duration of hospitalization for the current episode and negatively correlated with the total duration of illness. Both NO and AM may have a pathophysiological role in BPAD (type I, manic episodes) and the clinical symptomatology and prognosis of BPAD.
Assuntos
Transtorno Bipolar/etiologia , Proteínas de Drosophila , Óxido Nítrico/sangue , Peptídeos/sangue , Proteínas de Ligação a RNA , Adrenomedulina , Adulto , Biomarcadores/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Proteínas de Insetos/metabolismo , Masculino , Índice de Gravidade de DoençaRESUMO
The reciprocal regulation of arginase and nitric oxide synthase (NOS) in L-arginine-metabolizing pathways has been demonstrated. There are various evidences of the role of the nitric oxide (NO) in several neuropsychiatric disorders including schizophrenia. However, there is no study which has investigated the role of arginase as an important part of the arginine regulatory system affecting NOS activity in schizophrenia. This study aims to investigate arginase, manganese (Mn) and total nitrite levels (a metabolite of NO) and their relationship to the arginine-NO pathway in patients with schizophrenia. Arginase activities, Mn and total nitrite levels were measured in plasma from 46 patients with schizophrenia and 32 healthy control subjects. Plasma arginase activities and Mn were found to be significantly lower and total nitrite level higher in patients with schizophrenia compared with controls. Our results suggest that the arginine-NO pathway is involved in the pathogenesis of schizophrenia.