RESUMEN
We report our experience with high resolution microarray analysis in infants and young children with developmental disability and/or aberrant behavior enrolled at the Centro Ann Sullivan del Peru in Lima, Peru, a low income country. Buccal cells were collected with cotton swabs from 233 participants for later DNA isolation and identification of copy number variation (deletions/duplications) and regions of homozygosity (ROH) for estimating consanguinity status in 15 infants and young children (12 males, 3 females; mean age ± SD = 28.1 m ± 7.9 m; age range 14 m-41 m) randomly selected for microarray analysis. An adequate DNA yield was found in about one-half of the enrolled participants. Ten participants showed deletions or duplications containing candidate genes reported to impact behavior or cognitive development. Five children had ROHs which could have harbored recessive gene alleles contributing to their clinical presentation. The coefficient of inbreeding was calculated and three participants showed first-second cousin relationships, indicating consanguinity. Our preliminary study showed that DNA isolated from buccal cells using cotton swabs was suboptimal, but yet in a subset of participants the yield was adequate for high resolution microarray analysis and several genes were found that impact development and behavior and ROHs identified to determine consanguinity status.
RESUMEN
Before the 1990s, research on the early identification and prevention of severe behavior disorders (SBDs), such as aggression, self-injury, and stereotyped behavior, among young children with intellectual and developmental disabilities (IDD), was mostly done with children 3 years or older. More recent work suggests that signs of SBDs may occur as early as 6 months in some infants. The present study combined a cross-sectional and longitudinal approach to examine SBDs in 180 young children aged 4-48 months recruited through mass screening, then receiving an interdisciplinary evaluation and six-month follow-ups for one year. Twelve potential risk factors related to SBDs were examined. Eight of these risk factors, including age, gender, diagnosis, intellectual and communication levels, visual impairment, parent education, family income, were differentially related to scores for Aggression, SIB, and Stereotyped Behavior subscales on the Behavior Problems Inventory (BPI-01) at initial interdisciplinary evaluation. BPI-01 scores decreased over the year for 57% of the children and increased for 43%. The amount of decrease on each BPI-01 subscale varied with age, gender, and diagnosis.
Asunto(s)
Agresión/psicología , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/psicología , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/psicología , Conducta Autodestructiva/diagnóstico , Conducta Autodestructiva/psicología , Conducta Estereotipada , Trastorno Autístico/diagnóstico , Trastorno Autístico/psicología , Preescolar , Conducta Cooperativa , Síndrome de Down/diagnóstico , Síndrome de Down/psicología , Femenino , Humanos , Lactante , Comunicación Interdisciplinaria , Estudios Longitudinales , Masculino , Tamizaje Masivo , Determinación de la Personalidad/estadística & datos numéricos , Psicometría , Factores de RiesgoRESUMEN
Severe problem behaviors, like aggression, self-injury, and repetitive behaviors, in people with intellectual and developmental disabilities often appear during early development and may persist without early intervention. The frequencies of self-injurious behavior, aggression, tantrums, property destruction and stereotyped behavior among 17 infants and toddlers at risk for developmental delays and severe behavior problems were assessed using two methods: 1) direct observation of responses during 10 s partial interval recording during analogue functional analysis and 2) the Behavior Problem Inventory-01 (BPI-01; Rojahn et al, 2001), an informant rating scale. Analogue functional analysis results suggested that the most common function for problem behavior was automatic reinforcement, followed by negative reinforcement in the form of escape from demands. Agreement across the two types of measurement systems as to occurrence of the behaviors reported on the BPI-01 and direct observations during analogue functional analyses was greater than 75% across aggression, self-injury, and stereotyped behavior. Agreement at a more molecular level of the ranking of the most commonly occurring specific behaviors was considerably lower. Results are discussed in terms of future research on identifying conditions that set the occasion for high levels of agreement between indirect and direct measurement systems for severe behavior problems.
RESUMEN
The Parental Concerns Questionnaire (PCQ) was designed as a parent-interview screening instrument for young children with developmental concerns at risk for potentially severe behavior problems (SBDs). Parents of 262 young children (4 to 48 months) answered to the 15 dichotomous PCQ items interviewed by trained staff. Cluster analysis for items revealed three item clusters, which we labeled Developmental/Social (8 items), Biomedical (3 items), and Behavior Problems (3 items). This paper discussed primarily the Behavior Problems cluster, with items referring to self-injurious, aggressive, and destructive behaviors. Parents' concerns about behavior problems were high, with item-endorsements of the Behavior Problems cluster ranging from 41.8 % to 68.8 %. The Behavior Problems cluster was significantly correlated with all three subscales of the Behavior Problems Inventory (BPI-01), with select subscales of the Aberrant Behavior Checklist (ABC), and with the Repetitive Behavior Scale-Revised (RBS-R) providing some evidence for concurrent validity. Sensitivity and specificity data were computed for the three PCQ items as well as for the cluster score in comparison with the BPI-01, ABC, and RBS-R showing strong sensitivity. The PCQ Behavior Problems cluster is a useful screening checklist with high sensitivity for potential SBDs in young children at-risk for developmental delays.
RESUMEN
Behavior disorders, such as self-injurious, stereotypic, and aggressive behavior are common among individuals with intellectual or developmental disabilities. While we have learned much about those behaviors over the past few decades, longitudinal research that looks at developmental trajectory has been rare. This study was designed to examine the trajectory of these three forms of severe behavior disorders over a one year time period. The behaviors were measured on two dimensions: frequency of occurrence and severity. Participants were 160 infants and toddlers at risk for developmental delays in Lima, Peru. Using structural equation modeling, we found that the frequency of self-injury and stereotypic behavior and the severity of aggressive behavior remained stable over the 12-month period. Uni-directional structural models fit the data best for self-injurious and aggressive behavior (with frequency being a leading indicator of future severity of self-injury and severity being a leading indicator of future frequency for aggression). For stereotypic behavior, a cross-lagged autoregressive model fit the data best, with both dimensions of frequency and severity involved as leading indicators of each other. These models did not vary significantly across diagnostic groups, suggesting that toddlers exhibiting behavior disorders may be assisted with interventions that target the specific frequencies or severities of behaviors, regardless of diagnostic category.
Asunto(s)
Agresión/fisiología , Trastornos Generalizados del Desarrollo Infantil/fisiopatología , Discapacidades del Desarrollo/fisiopatología , Síndrome de Down/fisiopatología , Discapacidad Intelectual/fisiopatología , Conducta Autodestructiva/fisiopatología , Conducta Estereotipada/fisiología , Trastornos de la Conducta Infantil/complicaciones , Trastornos de la Conducta Infantil/fisiopatología , Trastornos Generalizados del Desarrollo Infantil/complicaciones , Preescolar , Estudios de Cohortes , Discapacidades del Desarrollo/complicaciones , Progresión de la Enfermedad , Síndrome de Down/complicaciones , Femenino , Humanos , Lactante , Discapacidad Intelectual/complicaciones , Estudios Longitudinales , Masculino , Modelos Estadísticos , Análisis de Regresión , Riesgo , Conducta Autodestructiva/complicaciones , Índice de Severidad de la Enfermedad , Trastorno de Movimiento Estereotipado/complicaciones , Trastorno de Movimiento Estereotipado/fisiopatologíaRESUMEN
Reliable and valid assessment of aberrant behaviors is essential in empirically verifying prevention and intervention for individuals with intellectual or developmental disabilities (IDD). Few instruments exist which assess behavior problems in infants. The current longitudinal study examined the performance of three behavior-rating scales for individuals with IDD that have been proven psychometrically sound in older populations: the Aberrant Behavior Checklist (ABC), the Behavior Problems Inventory (BPI-01), and the Repetitive Behavior Scale - Revised (RBS-R). Data were analyzed for 180 between six and 36 months old children at risk for IDD. Internal consistency (Cronbach's α) across the subscales of the three instruments was variable. Test-retest reliability of the three BPI-01 subscales ranged from .68 to .77 for frequency ratings and from .65 to .80 for severity ratings (intraclass correlation coefficients). Using a multitrait-multimethod matrix approach high levels of convergent and discriminant validity across the three instruments was found. As anticipated, there was considerable overlap in the information produced by the three instruments; however, each behavior-rating instrument also contributed unique information. Our findings support using all three scales in conjunction if possible.
Asunto(s)
Agresión/psicología , Conducta Infantil/psicología , Discapacidades del Desarrollo/psicología , Conducta del Lactante/psicología , Discapacidad Intelectual/psicología , Conducta Estereotipada , Lista de Verificación/provisión & distribución , Preescolar , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/epidemiología , Femenino , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/epidemiología , Masculino , Inventario de Personalidad , Reproducibilidad de los Resultados , Factores de Riesgo , Conducta Autodestructiva/diagnóstico , Conducta Autodestructiva/epidemiología , Conducta Autodestructiva/psicología , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
We report a 32-month-old female of Peruvian ethnicity identified with a rare 20q13.2-q13.33 deletion using microarray analysis. She presented with intellectual disability, absent speech, hypotonia, pre- and post-natal growth retardation and an abnormal face with a unilateral cleft lip. Clinical features and genetic findings with the loss of 30 genes, including GNAS, MC3R, CDH4 and TFAP2C, are described in relationship to the very few cases of 20q13 deletion reported in the literature. Deletion of this region may play an important role in neurodevelopment and function and in causing specific craniofacial features.
RESUMEN
There is a very substantial literature over the past 50 years on the advantages of early detection and intervention on the cognitive, communicative, and social-emotional development of infants and toddlers at risk for developmental delay due to premature birth or social disadvantage. Most of these studies excluded children with severe delays or other predisposing conditions, such as genetic or brain disorders. Many studies of children with biological or socio-developmental risk suggest that behavior disorders appear as early as three years and persist into adulthood if not effectively treated. By contrast, little is known about the infants and toddlers with established risk for severe delays, who make up a significant proportion of the population with dual diagnoses later in life.In the past decade, there has been a growing interest in early detection and intervention with children aged birth to three years, e.g. the P.L.99-457, Part C Birth-Three population, who may have disabilities and severe behavior problems, e.g. aggression, self-injury, and repetitive stereotyped behaviors. The available research is scattered in the behavior analytic literature, in the child development literature, as well as in the child mental health and psychiatry literature, the developmental disability literature, the animal modeling literature, and the genetics literature. The goal of this introductory overview is to integrate these literatures, by cross-referencing members of these various groups who have worked in this field, in order to provide the reader with an integrated picture of what is known and of future directions that need more research.
RESUMEN
INTRODUCTION: Severe behavior problems among people with intellectual and developmental disabilities (IDD) are a major barrier to integration in the community. Recent research suggests that these behaviors often begin very early in life and might be prevented by early identification and intervention (Rojahn, Schroeder, & Hoch, 2008). The current paper presents a method of mass screening for early signs of severe behavior problems among infants and toddlers in Peru. METHODS: A Parental Concerns Questionnaire (PCQ) which asks 15 questions, each related to a risk factor for severe behavior problems, based on past research on IDD, was used by veteran parents to interview 341 new parents who had been solicited by TV, radio, and public service announcements across the country. Of these, 262 were recruited and enrolled in a longitudinal study in which they will be followed for 12 months, to see if at-risk children actually will develop severe behavior problems. An extensive initial interdisciplinary evaluation was given to each child. Consumer satisfaction questionnaires were given to the parents as to their attitude toward the screening method. RESULTS: Data from the Interdisciplinary Evaluations of the sample suggest a very high hit rate (96%) by the screening instrument (PCQ). Consumer satisfaction was 98%, suggesting that the method was tolerated well by parents. DISCUSSION: The PCQ is a brief and efficient method to screen infants and toddlers at risk for severe behavior problems. The data also suggest that parents suspect these problems at a very early age. Early intervention thus seems a feasible strategy to intervene before these problems become deeply ingrained as children develop.
RESUMEN
A combination of behavioral and medication-based interventions has been the most effective form of treatment for reducing problem behavior in individuals with intellectual and developmental disabilities. Evaluating the 2 types of interventions in combination and separately may require that researchers adapt methods traditionally used to evaluate drug interventions for individuals without disabilities. Some methodological difficulties that arise when evaluating drug treatments with this population include the withholding of treatment from control groups, identifying large homogeneous samples of participants, predicting individual clinical responsiveness, and many others. The purpose of this article is to summarize the methodological problems that arise when studying drug-behavior interactions among people with intellectual and developmental disabilities and to suggest alternative methods that may ameliorate these issues.
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Terapia Conductista , Discapacidades del Desarrollo/psicología , Discapacidades del Desarrollo/terapia , Discapacidad Intelectual/psicología , Discapacidad Intelectual/terapia , Psicotrópicos/uso terapéutico , Terapia Conductista/métodos , Niño , Terapia Combinada/métodos , Discapacidades del Desarrollo/tratamiento farmacológico , Humanos , Discapacidad Intelectual/tratamiento farmacológico , Proyectos de Investigación , Resultado del TratamientoRESUMEN
We retrospectively reviewed clinic charts of 21 children and adolescents with developmental disabilities including autism spectrum disorders (ASD) treated consecutively with aripiprazole (ARI) for irritability and severe challenging behaviors. Data extracted include age, sex, and race; level of intellectual disability (ID); Diagnostic and Statistical Manual-IV diagnoses including comorbidity, ARI dosage, and treatment duration; other psychoactive medications and Clinical Global Impressions-Improvement (CGI-I) at baseline and end point; weight; height; and side effects. Body mass index (BMI) z scores are compared with Centers for Disease Control norms. Eleven boys and 10 girls with ID and/or ASD ages 8 to 18 years (mean age 13.4 years) received ARI; mean dose was 8.4 mg/day (range 2.5 to 15); average duration was 60.6 weeks (7 to 132). Eleven of 21 patients (52%) met CGI-I response of ≤ 2. ARI was well tolerated, including together with stimulants, divalproex, or less commonly other medications. Mean BMI was 23.8 ± 5.9 at baseline and 24.2 ± 5.2 at end. Mean BMI z score increase was 0.06 ± 0.67. Four individuals (19%) manifested early intolerable weight gain. In this long-term clinical sample, ARI was effective in 52% and well tolerated. ARI was mostly weight neutral; early weight gain was intolerable in 19%. Larger long-term outcome studies are warranted in this population.
RESUMEN
Risperidone has shown safety and efficacy for aggressive and destructive behaviors in short-term studies. This longer-duration study includes a broad sample. Forty subjects, aged 8-56 years (mean=22), all with mental retardation and 36 with autism spectrum disorders participated in this 22-week crossover study, with 24 weeks of open maintenance thereafter. Of 40 subjects, 23 (57.5%) responded fully (50% decrease in Aberrant Behavior Checklist-Community Irritability subscale score), while 35 subjects (87.5%) showed a 25% decrease. Gender, mood disorder, and antiseizure medications did not alter response. Increased appetite and weight gain were common. Low dose risperidone was effective for aggressive behavior in persons with MR. More long-term studies are needed, incorporating weight control interventions.
Asunto(s)
Agresión/psicología , Antipsicóticos/efectos adversos , Trastorno Autístico/epidemiología , Trastorno Autístico/psicología , Discapacidad Intelectual/psicología , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/epidemiología , Risperidona/efectos adversos , Aumento de Peso/efectos de los fármacos , Adolescente , Adulto , Antipsicóticos/uso terapéutico , Niño , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Discapacidad Intelectual/epidemiología , Masculino , Persona de Mediana Edad , Risperidona/uso terapéuticoRESUMEN
OBJECTIVE: Risperidone is widely prescribed for aggression and self-injury in children, adolescents, and adults with mental retardation (MR) and pervasive developmental disorders (PDD). Risperidone elevates prolactin more than other atypical antipsychotic medications. Females may show greater prolactin elevation than males. METHOD: In this relatively long-term study of risperidone efficacy and safety for aggression and self-injury in children, adolescents, and adults with MR and PDDs, serum prolactin was measured in a 21-subject subset during the course of a double-blind, placebo-controlled trial. Prolactin was measured in ng/mL at baseline, once during acute treatment, and once during maintenance. RESULTS: In children and adolescents (n=10), mean age of 12.5 years, prolactin increased from mean 13.2+/-8.6 at baseline to 31.0+/-11.6 acutely and remained elevated at 37.9+/-10.4 in maintenance. In adults, mean age of 35.3 years, prolactin increased more markedly from 11.6+/-7.4 baseline (n=11) to 93.3+/-54.2 acutely but decreased to 67.8+/-62.9 in maintenance (n=7). Prolactin remained significantly elevated above normal in all subjects for at least 26 weeks. Mean prolactin of adult females, while similar to that of adult males at baseline, was 2.2 times male levels acutely and 3.7 times greater in maintenance. CONCLUSION: In this small subset, mean prolactin elevation persisted for at least 26 weeks. In adults, females showed significantly greater elevations than males.
Asunto(s)
Antipsicóticos/efectos adversos , Trastornos Generalizados del Desarrollo Infantil/tratamiento farmacológico , Hiperprolactinemia/inducido químicamente , Discapacidad Intelectual/tratamiento farmacológico , Risperidona/efectos adversos , Adolescente , Adulto , Factores de Edad , Antipsicóticos/uso terapéutico , Niño , Trastornos Generalizados del Desarrollo Infantil/sangre , Trastornos Generalizados del Desarrollo Infantil/psicología , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Humanos , Hiperprolactinemia/sangre , Discapacidad Intelectual/sangre , Discapacidad Intelectual/psicología , Cuidados a Largo Plazo , Prolactina/sangre , Estudios Prospectivos , Risperidona/uso terapéutico , Factores Sexuales , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to study valproate efficacy and safety for aggression in children and adolescents with pervasive developmental disorders (PDD). METHODS: In this prospective double-blind, placebo-controlled study, 30 subjects (20 boys, 10 girls) 6-20 years of age with PDD and significant aggression were randomized and received treatment with valproate (VPA) or placebo (PBO) for 8 weeks as outpatients. Mean VPA trough blood levels were 75.5 mcg/mL at week 4 and 77.8 mcg/mL at week 8. RESULTS: No treatment difference was observed statistically between VPA and PBO groups. The Aberrant Behavior Checklist--Community Scale (ABC-C) Irritability subscale was the primary outcome measure (p = 0.65), and CGI--Improvement (p = 0.16) and OAS (p = 0.96) were secondary outcome measures. Increased appetite and skin rash were significant side effects. Only 1 subject was dropped from the study owing to side effects, notably a spreading skin rash, which then resolved spontaneously. Two subjects receiving VPA developed increased serum ammonia levels, one with an associated parent report of slurred speech and mild cognitive slowing. Poststudy, of 16 VPA and PBO subjects receiving VPA, 10 subjects demonstrated sustained response, 4 of whom later attempted taper, with significant relapse of aggression. CONCLUSION: The present negative findings cannot be viewed as conclusive, partly owing to the large placebo response, subject heterogeneity, and size of the groups. Larger studies are needed to expand upon these findings.
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Agresión/efectos de los fármacos , Anticonvulsivantes/uso terapéutico , Trastornos Generalizados del Desarrollo Infantil/tratamiento farmacológico , Trastornos Generalizados del Desarrollo Infantil/psicología , Ácido Valproico/uso terapéutico , Adolescente , Adulto , Agresión/psicología , Anticonvulsivantes/efectos adversos , Niño , Método Doble Ciego , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Ácido Valproico/efectos adversos , Aumento de Peso/efectos de los fármacosRESUMEN
Aggression is a common and costly problem in youth with developmental disabilities. Rating scales that accurately capture and measure subtypes of aggression phenomenology, frequency and severity are urgently needed, in both clinical practice and research. The authors studied the Overt Aggression Scale (OAS) in a preliminary sample of eight outpatients who participated in an ongoing placebo-controlled study of valproate for aggression in autism. Subjects' OAS aggression scores showed significant correlation with the already validated retrospectively rated Aberrant Behavior Checklist Community Scale irritability subscale. Further study of the OAS in outpatients with aggression and developmental disabilities is warranted.
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Agresión/psicología , Atención Ambulatoria , Trastorno Autístico/psicología , Escalas de Valoración Psiquiátrica , Adolescente , Adulto , Agresión/efectos de los fármacos , Atención Ambulatoria/estadística & datos numéricos , Trastorno Autístico/diagnóstico , Trastorno Autístico/tratamiento farmacológico , Niño , Método Doble Ciego , Femenino , Humanos , Masculino , Estudios Retrospectivos , Ácido Valproico/uso terapéuticoRESUMEN
Functional analyses were conducted during a double-blind, placebo-controlled study of the atypical antipsychotic medication risperidone with 13 individuals. Risperidone was effective in reducing destructive behavior (compared to placebo) for 10 participants. For 7 of these responders, an undifferentiated pattern of responding occurred across their baseline functional analysis conditions (i.e., a similar rate of responding across conditions), and risperidone treatment produced nonspecific reductions of their destructive behavior across functional analysis conditions. For the remaining 3 responders, a differentiated pattern of responding occurred across their baseline functional analysis conditions (i.e., an elevated rate of responding occurred in a specific condition), and risperidone treatment produced function-specific reductions of their destructive behavior.
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Agresión/efectos de los fármacos , Antipsicóticos/uso terapéutico , Discapacidades del Desarrollo/tratamiento farmacológico , Risperidona/uso terapéutico , Conducta Autodestructiva/prevención & control , Adulto , Niño , Discapacidades del Desarrollo/complicaciones , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Conducta Autodestructiva/complicacionesRESUMEN
The atypical antipsychotic medication risperidone was evaluated using a double-blind, placebo-controlled design in the treatment of destructive behavior in two individuals with autism. Pre-medication functional analyses indicated that destructive behavior was maintained by escape from demands, attention, or access to tangible items. For both individuals, destructive behavior during the demand condition was significantly reduced during the medication phases, whereas destructive behavior continued to occur to obtain tangible items (Reggie) and attention (Sean). In addition, there appeared to be a differential effect of the medication on self-injurious behavior (SIB) versus aggression for Sean. Results of the study demonstrate how functional analysis may provide information on those conditions and behaviors that are most likely to be affected by a specific medication.
Asunto(s)
Antipsicóticos/uso terapéutico , Trastorno Autístico/tratamiento farmacológico , Risperidona/uso terapéutico , Adulto , Agresión/efectos de los fármacos , Antipsicóticos/administración & dosificación , Déficit de la Atención y Trastornos de Conducta Disruptiva/tratamiento farmacológico , Trastorno Autístico/fisiopatología , Niño , Humanos , Masculino , Risperidona/administración & dosificación , Conducta Autodestructiva/tratamiento farmacológico , Conducta Autodestructiva/fisiopatologíaRESUMEN
Effects of two doses of risperidone on the performance of a matching task under tangible reinforcement and nonreinforcement conditions were measured in a woman with mental retardation. In both conditions, time to complete the task increased and response rates decreased under two doses of risperidone. Accuracy was generally unchanged. These changes were much smaller in the tangible reinforcement condition; thus, reinforcement seemed to protect performance from the rate-decreasing effects of risperidone.
Asunto(s)
Antipsicóticos/efectos adversos , Atención/efectos de los fármacos , Trastorno Autístico/tratamiento farmacológico , Terapia Conductista/métodos , Trastorno Bipolar/tratamiento farmacológico , Aprendizaje Discriminativo/efectos de los fármacos , Trastornos Disruptivos, del Control de Impulso y de la Conducta/tratamiento farmacológico , Discapacidad Intelectual/tratamiento farmacológico , Risperidona/efectos adversos , Adulto , Antipsicóticos/uso terapéutico , Trastorno Autístico/psicología , Trastorno Bipolar/psicología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/psicología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Discapacidad Intelectual/psicología , Reconocimiento Visual de Modelos/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Esquema de Refuerzo , Risperidona/uso terapéutico , Régimen de RecompensaRESUMEN
Fixed-ratio discrimination (FRD) training session-accuracy curves were constructed using first-order, nonlinear regression and probit analyses to determine maximal (asymptotic) accuracy and the number of sessions required to reach half-maximal accuracy. Increased FRD difficulty (reductions in the differences between the 2 fixed-ratio values to be discriminated) and a training parameter change each increased the number of sessions required to reach half-maximal accuracy and decreased maximal FRD accuracy (i.e., session-accuracy curves were shifted down and to the right) regardless of analysis procedure. These findings indicate that the above manipulations induced mixed competitive-noncompetitive inhibition of the rate of FRD learning. Microencephalic rats were more sensitive to increases in FRD difficulty, whereas control rats were more sensitive to the training parameter change.