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1.
Artículo en Inglés | MEDLINE | ID: mdl-38641208

RESUMEN

BACKGROUND: Borderline personality disorder (BPD) is the prototypical disorder of emotion dysregulation. We have previously shown that patients with BPD are impaired in their capacity to engage cognitive reappraisal, a frequently employed adaptive emotion regulation strategy. METHODS: Here, we report on the efficacy of longitudinal training in cognitive reappraisal to enhance emotion regulation in patients with BPD. Specifically, the training targeted psychological distancing, a reappraisal tactic whereby negative stimuli are viewed dispassionately as though experienced by an objective, impartial observer. At each of 5 sessions over 2 weeks, 22 participants with BPD (14 female) and 22 healthy control participants (13 female) received training in psychological distancing and then completed a widely used picture-based reappraisal task. Self-reported negative affect ratings and functional magnetic resonance imaging data were acquired at the first and fifth sessions. In addition to behavioral analyses, we performed whole-brain pattern expression analyses using independently defined patterns for negative affect and cognitive reappraisal implementation for each session. RESULTS: Patients with BPD showed a decrease in negative affect pattern expression following reappraisal training, reflecting a normalization in neural activity. However, they did not show significant change in behavioral self-reports. CONCLUSIONS: To our knowledge, this study represents the first longitudinal functional magnetic resonance imaging examination of task-based cognitive reappraisal training. Using a brief, proof-of-concept design, the results suggest a potential role for reappraisal training in the treatment of patients with BPD.


Asunto(s)
Trastorno de Personalidad Limítrofe , Encéfalo , Regulación Emocional , Imagen por Resonancia Magnética , Humanos , Trastorno de Personalidad Limítrofe/fisiopatología , Femenino , Regulación Emocional/fisiología , Adulto , Masculino , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Adulto Joven , Cognición/fisiología , Terapia Cognitivo-Conductual/métodos
2.
Psychiatry Res ; 322: 115132, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36841053

RESUMEN

This study compared demographic and clinical features in a sample of 384 participants: healthy controls (HC; n = 166) and individuals with schizotypal personality disorder (SPD) with (n = 50) and without (n = 168) suicidal ideation (SI) to examine specific risk factors for suicidality in SPD. Compared to the non-SI group, the SI group showed significantly greater severity of depression, aggression, impulsivity, affective lability, schizotypal features, poorer social adjustment, and had fewer social contacts. Individuals in the SI group were also more likely to have a history of a suicide attempt and comorbid borderline personality disorder in comparison to the non-SI group. Logistic regression analysis indicated that severity of depression and the number of social contacts drove the difference between the SI and non-SI groups. Compared with both SPD subgroups, the HC group was significantly less depressed, aggressive, impulsive, affectively labile, had fewer schizotypal features, was better socially adjusted, and had more social contacts. This study indicates that overall, the SI group is a more severely impaired group of individuals with SPD compared to the non-SI group. Better educating medical professionals about the diagnosis and management of SPD and its associations with suicidality is warranted.


Asunto(s)
Trastorno de la Personalidad Esquizotípica , Ideación Suicida , Humanos , Intento de Suicidio/psicología , Agresión/psicología , Conducta Impulsiva
3.
Personal Disord ; 14(4): 441-451, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36136792

RESUMEN

Recent initiatives in the empirically based classification of psychopathology, namely, the Hierarchical Taxonomy of Psychopathology (HiTOP), have made significant strides in addressing the limitations of traditional taxonomies (i.e., Diagnostic and Statistical Manual of Mental Disorders, International Classification of Diseases). The current study aimed to extend this work by helping to clarify the lower order structure of an understudied dimension of psychopathology-antagonism (i.e., HiTOP antagonistic externalizing spectrum)-a core feature of many externalizing disorders and related to important outcomes such as interpersonal problems, childhood conduct problems, and incarceration. We examined the hierarchical structure of several measures of antagonistic externalizing features across both self-report and clinical interview ratings for 2,279 community participants with a diverse range of personality pathology (~75% with a personality disorder) and antagonistic behaviors (~30% with intermittent explosive disorder). Exploratory structural equation modeling was used to account for the shared variance between variables within self-report and interview methods. Results revealed an optimal lower order structure consisting of six factors labeled Antisociality, Anger, Hostility, Narcissism, Mistrust, and Attention Seeking. Factor scores yielded expected relations with self-report and interview ratings of psychopathology, personality, and childhood trauma. Implications for future research in classification and treatment of psychopathology are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Hostilidad , Trastornos Mentales , Humanos , Psicopatología , Trastornos Mentales/terapia , Trastornos de la Personalidad/diagnóstico , Personalidad
4.
Psychopharmacology (Berl) ; 240(2): 361-371, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36640190

RESUMEN

RATIONALE: Characterizing the neuroanatomical basis of serotonergic abnormalities in severe, chronic, impulsive aggression will allow for rational treatment selection, development of novel therapeutics, and biomarkers to identify at-risk individuals. OBJECTIVES: The aim of this study is to identify associations between regional serotonin transporter (5-HTT) availability and trait and state aggression, as well as response to the anti-aggressive effects of fluoxetine. METHODS: We examined 5-HTT availability using positron emission tomography (PET) imaging with [11C]DASB in personality disordered patients with current physical intermittent explosive disorder (IED; n = 18), and healthy comparison participants (HC; n = 11), in the anterior cingulate cortex (ACC), amygdala (AMY), ventral striatum (VST), and midbrain (MID). After PET imaging, IED patients were treated with fluoxetine 20 mg daily (n = 9) or placebo (n = 6) for 12 weeks. Trait and state aggression, trait callousness, and childhood trauma were assessed. RESULTS: In IED patients, trait aggression was positively associated with [11C]DASB binding in the ACC and VST; covarying for trait callousness and childhood trauma enhanced these correlations. Baseline state aggression was positively correlated with ACC [11C]DASB in IED patients. Greater baseline VST [11C]DASB binding predicted greater decreases in state aggression with fluoxetine treatment. CONCLUSIONS: Consistent with prior reports, ACC 5-HTT is related to trait aggression, and adjusting for factors related to proactive (callousness) and reactive (childhood trauma) aggression subtypes further resolves this relationship. Novel findings of the study include a better understanding of the association between regional 5-HTT availability and state aggression, and the involvement of VST 5-HTT with trait aggression, and with the anti-aggressive effects of fluoxetine.


Asunto(s)
Fluoxetina , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Humanos , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Trastornos de la Personalidad , Agresión , Tomografía de Emisión de Positrones , Personalidad
5.
Biol Psychiatry ; 92(7): 573-582, 2022 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-35717211

RESUMEN

BACKGROUND: Borderline personality disorder (BPD) is characterized by greater intensity of reactions to unpleasant emotional cues and a slower-than-normal return of these responses to baseline. Habituation is defined as decreased response to repeated stimulation. Affect-modulated startle (AMS), a translational psychophysiological approach, is mediated by the amygdala and used to study emotion processing in both humans and animals. This is the first study to examine the specificity of habituation anomalies in BPD during passive emotional and neutral picture processing. METHODS: A total of 90 participants were studied: patients with BPD (n = 35), patients with schizotypal personality disorder (n = 26; included as a psychopathological comparison group), and healthy control subjects (n = 29). Participants received rigorous clinical assessments, and patients were unmedicated. AMS was examined during a series of intermixed unpleasant, neutral, and pleasant pictures. RESULTS: Compared with the other groups, patients with BPD showed greater overall AMS during unpleasant pictures and prolonged habituation of startle amplitude during unpleasant pictures from early to later trials. The groups did not differ in AMS during neutral or pleasant pictures or self-reported picture valence. Among the patients with BPD, prolonged habituation to unpleasant pictures was associated with greater symptom severity and suicidal/self-harming behavior. CONCLUSIONS: These findings 1) indicate that abnormal processing of and habituation to unpleasant pictures is observed in BPD but not schizotypal personality disorder, suggesting that these deficits are not simply characteristics of personality disorders in general; 2) are consistent with studies showing deficient amygdala habituation to unpleasant pictures in BPD; and 3) have significant implications for clinical assessment and treatment of BPD, e.g., alternative therapies for BPD such as gradual exposure to unpleasant emotional stimuli or amygdala neurofeedback may aid habituation deficits.


Asunto(s)
Trastorno de Personalidad Limítrofe , Habituación Psicofisiológica , Amígdala del Cerebelo , Trastorno de Personalidad Limítrofe/psicología , Emociones/fisiología , Humanos , Trastornos de la Personalidad , Reflejo de Sobresalto/fisiología
6.
J Pers Disord ; 35(Suppl A): 114-131, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33650890

RESUMEN

Long-standing theories of borderline personality disorder (BPD) suggest that symptoms develop at least in part from childhood adversity. Emotion dysregulation may meaningfully mediate these effects. The current study examined three factors related to emotion dysregulation-alexithymia, affective lability, and impulsivity-as potential mediators of the relation between childhood adversity and BPD diagnosis in 101 individuals with BPD and 95 healthy controls. Path analysis compared three distinct models informed by the literature. Results supported a complex mediation model wherein (a) alexithymia partially mediated the relation of childhood adversity to affective lability and impulsivity; (b) affective lability mediated the relation of childhood adversity to BPD diagnosis; and (c) affective lability and impulsivity mediated the relation of alexithymia to BPD diagnosis. Findings suggest that affective lability and alexithymia are key to understanding the relationship between childhood adversity and BPD. Interventions specifically targeting affective lability, impulsivity, and alexithymia may be particularly useful for this population.


Asunto(s)
Experiencias Adversas de la Infancia , Trastorno de Personalidad Limítrofe , Síntomas Afectivos , Trastorno de Personalidad Limítrofe/diagnóstico , Emociones , Humanos , Conducta Impulsiva
7.
J Interpers Violence ; 35(23-24): 6067-6082, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-29294890

RESUMEN

The current study investigates the relationship between intimate partner violence (IPV), childhood trauma, trait anxiety, depression, and anxious attachment in college students. Ninety-three male and 161 female undergraduate students at Fairfield University, ranging in age from 17 to 23, with a mean age of 18.8 years, participated. Participants completed five self-report inventories: The Conflict in Adolescent Dating Relationships Inventory (CADRI), the Childhood Trauma Questionnaire (CTQ), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), and the Adult Attachment Scale (AAS). IPV perpetration in college dating relationships was related to childhood emotional and physical abuse, emotional and physical neglect, and trait anxiety. IPV victimization in college dating relationships was related to childhood emotional and physical abuse, childhood emotional and physical neglect, and an anxious attachment style. IPV perpetration and victimization were also significantly correlated with one another. Subscale analyses suggest that childhood emotional abuse was related to being both the perpetrator and victim of verbal or emotional abuse in dating relationships. Childhood physical abuse, physical neglect, and emotional abuse were related to both perpetration and victimization of physical IPV. Threatening behavior perpetration in dating relationships was related to childhood emotional abuse, emotional neglect, physical abuse, and physical neglect; however, being the victim of threatening behavior was only related to childhood emotional abuse, physical neglect, and emotional neglect, not childhood physical abuse. These results support the relationship between childhood trauma and dating violence in college students. They also support a role for anxiety in IPV, although trait anxiety was related to perpetration and an anxious attachment style was correlated with IPV victimization. In addition, they suggest that different experiences of childhood trauma may relate to different aspects of IPV in college dating relationships.


Asunto(s)
Víctimas de Crimen , Violencia de Pareja , Adolescente , Adulto , Ansiedad/epidemiología , Femenino , Humanos , Masculino , Abuso Físico , Estudiantes
8.
Psychopharmacology (Berl) ; 237(9): 2649-2659, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32572588

RESUMEN

RATIONALE: Previous research has suggested that schizotypal personality disorder (SPD), a condition that shares clinical and cognitive features with schizophrenia, may be associated with elevated striatal dopamine functioning; however, there are no published studies of dopamine release within subregions of the striatum in SPD. OBJECTIVES: To characterize dopamine release capacity in striatal subregions and its relation to clinical and cognitive features in SPD. METHODS: We used positron emission tomography with [11C]raclopride and an amphetamine challenge to measure dopamine D2-receptor availability (binding potential, BPND), and its percent change post-amphetamine (∆BPND) to index amphetamine-induced dopamine release, in subregions of the striatum in 16 SPD and 16 healthy control participants. SPD participants were evaluated with measures of schizotypal symptom severity and working memory. RESULTS: There were no significant group differences in BPND or ∆BPND in any striatal subregion or whole striatum. Among SPD participants, cognitive-perceptual symptoms were associated at trend level with ∆BPND in the ventral striatum, and disorganized symptoms were significantly negatively related to ∆BPND in several striatal subregions. CONCLUSIONS: In contrast to previous findings, SPD was not associated with elevated striatal dopamine release. However, in SPD, there was a moderate positive association between ventral striatal dopamine release and severity of cognitive-perceptual symptoms, and negative associations between striatal dopamine release and severity of disorganized symptoms. Future larger scale investigations that allow for the separate examination of subgroups of participants based on clinical presentation will be valuable in further elucidating striatal DA functioning in SPD.


Asunto(s)
Anfetamina/farmacología , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Inhibidores de Captación de Dopamina/farmacología , Dopamina/metabolismo , Trastorno de la Personalidad Esquizotípica/metabolismo , Adolescente , Adulto , Cuerpo Estriado/diagnóstico por imagen , Femenino , Humanos , Masculino , Memoria a Corto Plazo/efectos de los fármacos , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Racloprida , Receptores de Dopamina D2/metabolismo , Trastorno de la Personalidad Esquizotípica/diagnóstico por imagen , Trastorno de la Personalidad Esquizotípica/psicología , Adulto Joven
9.
Psychiatry Res Neuroimaging ; 293: 110988, 2019 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-31655369

RESUMEN

Neuroimaging may predict response to cognitive remediation therapy and social skills training (CRT + SST) in schizophrenia. Identifying biological predictors of response is crucial for treatment decision making given not all patients respond to such interventions. Nineteen veterans with schizophrenia enrolled in an 8-week trial of CRT + SST. Ten participants completed diffusion tensor imaging (DTI) at baseline. Baseline fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and overall average FA predicted improvements in visual-spatial working memory, and social cognition, respectively. Neuroimaging may be useful in identifying therapeutic targets in schizophrenia.


Asunto(s)
Remediación Cognitiva , Esquizofrenia/terapia , Habilidades Sociales , Anisotropía , Imagen de Difusión Tensora , Estudios de Factibilidad , Femenino , Humanos , Memoria a Corto Plazo/fisiología , Red Nerviosa , Proyectos Piloto , Esquizofrenia/diagnóstico por imagen , Veteranos , Sustancia Blanca
10.
Am J Psychiatry ; 176(4): 307-314, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30654644

RESUMEN

OBJECTIVE: Impaired cognition is a hallmark of schizophrenia spectrum disorders, including schizotypal personality disorder, and it is the best predictor of functional outcome. Cognitive remediation therapy has demonstrated efficacy for improving cognition, augmenting other rehabilitation efforts in schizophrenia, and effecting gains in real-world functioning. Pharmacological augmentation of cognitive remediation has been attempted, but the effects of augmentation on combined therapies, such as cognitive remediation and social skills training, have not been studied. METHODS: Twenty-eight participants with schizotypal personality disorder enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of guanfacine plus cognitive remediation and social skills training (15 guanfacine, 13 placebo). Cognition was assessed with the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB), social cognition with the Movie for the Assessment of Social Cognition (MASC), and functional capacity with the University of California San Diego Performance-Based Skills Assessment (UPSA). RESULTS: A statistically significant pre- versus posttreatment effect was observed for MCCB speed of processing, verbal learning, and visual learning and UPSA total score. A significant time-by-medication (guanfacine, placebo) interaction was observed for MCCB reasoning and problem solving and UPSA total score; the time-by-treatment interaction approached significance for MASC hypomentalizing errors. CONCLUSIONS: Both guanfacine and cognitive remediation plus social skills training were well tolerated, with no side effects or dropouts. Participants treated with cognitive remediation, social skills training, and guanfacine demonstrated statistically significant improvements in reasoning and problem solving, as well as in functional capacity and possibly social cognition, compared with those treated with cognitive remediation, social skills training, and placebo. Cognitive remediation plus social skills training may be an appropriate intervention for individuals with schizotypal personality disorder, and guanfacine appears to be a promising pharmaceutical augmentation to this psychosocial intervention.


Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Remediación Cognitiva/métodos , Guanfacina/uso terapéutico , Trastorno de la Personalidad Esquizotípica/terapia , Habilidades Sociales , Adulto , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas
11.
Psychiatry Res ; 279: 353-357, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31101379

RESUMEN

Despite considerable phenomentological differences between borderline personality disorder (BPD) and schizotypal personality disorder (SPD), research increasingly provides evidence that some BPD symptoms overlap with SPD symptoms (e.g., disturbed cognitions). We examined the cingulate, a brain region implicated in the pathophysiology of both disorders, to determine similarities/differences between the groups, and similarities/differences from healthy controls (HC's). 3T structural and diffusion tensor magnetic resonance imaging scans were acquired in BPD (n = 27), SPD (n = 32), HC's (n = 34). Results revealed that BPD patients exhibited significantly lower FA in posterior cingulate white matter compared to HC's (p = 0.04), but SPD patients did not.


Asunto(s)
Imagen de Difusión Tensora/métodos , Giro del Cíngulo/diagnóstico por imagen , Trastorno de la Personalidad Esquizotípica/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adolescente , Adulto , Anisotropía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastorno de la Personalidad Esquizotípica/psicología , Adulto Joven
12.
Schizophr Res ; 209: 263-268, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30635257

RESUMEN

Given the common use of self-report questionnaires to assess schizotypy in personality pathology and schizophrenia research, it is important to determine the concordance between self-report and clinician ratings. 250 individuals with schizotypal personality disorder (SPD) and 116 community controls (CTR) were assessed on schizotypal traits using a clinical interview, the Structured Interview for DSM-IV Personality disorders (SIDP), and a self-report questionnaire, the Schizotypal Personality Questionnaire (SPQ). Ordinal logistic regressions examined concordance between self-reported and clinician-rated scores in CTR and SPD separately. Analyses of variance examined how the SPQ performed on differentiating between CTR with low schizotypy, CTR with high schizotypy, and SPD. For both CTR and SPD, higher SPQ subscale scores were significantly associated with higher clinician ratings on the respective SIDP items for the Ideas of Reference, Magical Thinking, Unusual Perceptual Experience, Suspiciousness, and Social Anxiety items, but not the Odd Speech or Limited Affect items. Higher SPQ subscale scores for Odd Behavior and Lack of Close Friends were significantly associated with the clinician-rated SIDP item scores in CTR but not SPD. CTR with low schizotypy scored lower on all SPQ subscales than CTR with high schizotypy, who did not differ from SPD. Self-report ratings are concordant with clinician ratings for positive schizotypal traits, whereas certain disorganization and interpersonal traits are not, particularly for individuals with SPD. The SPQ can differentiate between high and low schizotypy controls, but not between high schizotypy controls and individuals with SPD. Assessment of schizotypal traits should include both self-report questionnaires and clinician ratings.


Asunto(s)
Manual Diagnóstico y Estadístico de los Trastornos Mentales , Escalas de Valoración Psiquiátrica/normas , Trastorno de la Personalidad Esquizotípica/diagnóstico , Trastorno de la Personalidad Esquizotípica/fisiopatología , Autoinforme/normas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
13.
Schizophr Res ; 106(1): 50-8, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18053687

RESUMEN

Cognitive dysfunction is a common feature of schizophrenia and deficits are present before the onset of psychosis, and are moderate to severe by the time of the first episode. Controversy exists over the course of cognitive dysfunction after the first episode. This study examined age-associated differences in performance on clinical neuropsychological (NP) and information processing tasks in a sample of geriatric community living schizophrenia patients (n=172). Compared to healthy control subjects (n=70), people with schizophrenia did not differ on NP tests across age groups but showed evidence for age-associated cognitive worsening on the more complex components of an information-processing test. Age-related changes in cognitive function in schizophrenia may be a function of both the course of illness and the processing demands of the cognitive measure of interest. Tests with fixed difficulty, such as clinical NP tests, may differ in their sensitivity from tests for which parametric difficulty manipulations can be performed.


Asunto(s)
Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Procesos Mentales , Esquizofrenia/epidemiología , Factores de Edad , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
14.
J Abnorm Psychol ; 117(2): 342-54, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-18489210

RESUMEN

Working memory abnormalities, which are particularly pronounced on context processing tasks, appear relatively specific to schizophrenia spectrum illnesses compared with other psychotic disorders. However, the specificity of context processing deficits to schizotypal personality disorder (SPD), a prototype of schizophrenia, has not been studied. The authors administered 3 versions of the modified AX Continuous Performance Test and an N-back working memory test to 63 individuals with SPD and 25 with other personality disorders, as well as 42 healthy controls. For the AX Continuous Performance Test standard and degraded versions, there was a significant Trial Type x Delay x Group interaction, as SPDs made significantly more errors reflecting poor maintenance of context and fewer errors reflecting good maintenance of context. SPDs also demonstrated poor performance on the N-back, especially at the 2-back condition. Context processing errors and N-back accuracy scores were related to disorganization symptoms. These findings, which are quite similar to those previously reported in patients with schizophrenia, suggest that context processing deficits are specific to the schizophrenia spectrum and are not a reflection of overall psychopathology.


Asunto(s)
Memoria a Corto Plazo , Pruebas Neuropsicológicas , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Trastorno de la Personalidad Esquizotípica/psicología , Adulto , Atención , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Formación de Concepto , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/psicología , Desempeño Psicomotor , Trastorno de la Personalidad Esquizotípica/diagnóstico , Aprendizaje Seriado
15.
Biol Psychiatry ; 61(10): 1157-60, 2007 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-16950221

RESUMEN

BACKGROUND: The signature of impaired cognition in people with schizotypal personality disorder (SPD) may be centrally related to working memory impairments. Guanfacine, an alpha2A agonist that acts post-synaptically in the prefrontal cortex (PFC), has shown potential for reducing working memory limitations in other populations. This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD. METHODS: 29 individuals with SPD entered into a 4-week, randomized parallel-design, double-blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week open-label extension. A modified version of the AX-Continuous Performance Test (AX-CPT) was administered. On this task, evidence of intact context processing includes few BX errors (false cue, correct probe) and higher levels of AY errors (correct cue, false probe). RESULTS: At the end of double-blind treatment, participants treated with guanfacine demonstrated a significant reduction in BX errors and a small but significant increase in AY errors, a pattern that was not seen in the participants treated with placebo. CONCLUSIONS: SPD participants improved in their context processing toward a normal response bias, making fewer BX and more AY errors, after being treated with guanfacine.


Asunto(s)
Agonistas alfa-Adrenérgicos/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Guanfacina/uso terapéutico , Memoria a Corto Plazo/efectos de los fármacos , Trastorno de la Personalidad Esquizotípica/tratamiento farmacológico , Adulto , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tiempo de Reacción/efectos de los fármacos , Trastorno de la Personalidad Esquizotípica/diagnóstico , Trastorno de la Personalidad Esquizotípica/psicología
16.
Schizophr Res ; 89(1-3): 330-8, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16982175

RESUMEN

BACKGROUND: Neuropsychological (NP) performance is a consistent correlate of everyday functioning in schizophrenia, but it is unclear whether relationships between individual NP ability areas and domains of everyday functioning are general or specific. Assessments of real-world everyday functioning may be influenced by environmental and social factors (e.g., social security, disability status, opportunities and restrictions in living situations). This study examined the specificity of the relationships between different NP abilities and performance-based measures of social and living skills. METHODS: 181 ambulatory older (age>50) patients with schizophrenia were examined with NP tests measuring episodic and working memory, executive functioning, verbal fluency, and processing speed. All subjects performed tasks examining social (Social Skills Performance Assessment: SSPA) and everyday living (UCSD Performance Based Skills Assessment: UPSA) skills. RESULTS: Using canonical analysis, the NP variables were used to predict the functional capacity measures. The analysis found that 37% of the variance in the functional capacity and NP measures was shared, X(2) (54)=106.29, p<.001. Two canonical roots described the cognitive variables and the roots were differentially associated with everyday living and social skills. The root loading on processing speed, episodic memory, and executive functions were associated with UPSA scores, while the root loading on working and episodic memory and verbal fluency were associated most strongly with social competence. IMPLICATIONS: Social and everyday living skills deficits in patients with schizophrenia may reflect generally independent domains of functional outcome, linked through cognitive performance. The data suggest that somewhat different cognitive processes are associated with these two domains of functional capacity, although there appears to be some overlap, which may be due to the nature of the NP tests employed.


Asunto(s)
Actividades Cotidianas/clasificación , Pruebas Neuropsicológicas , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Recuerdo Mental , Escala del Estado Mental , Persona de Mediana Edad , Lenguaje del Esquizofrénico , Ajuste Social , Estadística como Asunto
17.
Arch Clin Neuropsychol ; 22(1): 109-16, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17161580

RESUMEN

Verbal episodic memory deficits, a well-established feature of the schizophrenia spectrum, have also been found in individuals with schizotypal personality disorder (SPD), although visual-spatial episodic memory has proven harder to examine. To address this, we administered the Visual Object Learning Test (VOLT), a measure of visual-spatial learning and memory, as well as the California Verbal Learning Test (CVLT) and a verbal working memory test, to 50 individuals with SPD, 19 with other personality disorders (OPD), and 17 healthy volunteers. Compared to both other groups, individuals with SPD learned verbal and visual-spatial information at a reduced rate and recalled fewer words and objects after a long delay. Verbal working memory performance eliminated diagnostic differences in these episodic memory domains. These findings suggest that it is possible to detect both auditory and visual processing episodic memory abnormalities in the spectrum and that these deficits are uniformly a function of verbal working memory impairments.


Asunto(s)
Memoria a Corto Plazo/fisiología , Psicología del Esquizofrénico , Trastorno de la Personalidad Esquizotípica/fisiopatología , Percepción Espacial/fisiología , Adulto , Análisis de Varianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos
18.
Drugs ; 66(11): 1465-73, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16906778

RESUMEN

Cognitive dysfunction is a core feature of schizophrenia as deficits that are present in the majority of patients with schizophrenia frequently precede the onset of other symptoms and persist even after other symptoms have been effectively treated. The use of atypical antipsychotics has produced some small improvements, although the need for adjunctive treatment specifically targeting cognitive dysfunction is gaining widespread acceptance. Animal models and some small clinical trials have yielded results that are promising but not definitive. Psychosocial interventions have also met with some success in ameliorating some cognitive limitations. The mixed results of pharmacological interventions are most likely to be as a result of a combination of methodological flaws of many studies, poor outcome measures, dose administration effects and problems with the agents themselves.


Asunto(s)
Antipsicóticos/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Esquizofrenia/complicaciones , Trastornos del Conocimiento/complicaciones , Humanos
19.
Neuropsychopharmacology ; 40(2): 446-53, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25074637

RESUMEN

Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D1 receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n=16) who met the criteria for cognitive impairment (ie, scoring below the 25th percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and that clinical data implicate as being associated with prefrontal D1 availability: (1) the Paced Auditory Serial Addition Test (PASAT); and (2) the N-back test (ratio of 2-back:0-back scores). Study procedures occurred over four consecutive days, with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen's d=1.14). Performance on the N-back ratio was also significantly improved; however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side effects were mild to moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, eg, co-administered normal saline. Although preliminary, these findings lend further clinical support to the potential of D1 receptor agonists to treat schizophrenia-spectrum working memory impairments. These data suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery.


Asunto(s)
Agonistas de Dopamina/uso terapéutico , Trastornos de la Memoria/tratamiento farmacológico , Memoria a Corto Plazo/efectos de los fármacos , Fenantridinas/uso terapéutico , Receptores de Dopamina D1/agonistas , Trastorno de la Personalidad Esquizotípica/tratamiento farmacológico , Adulto , Agonistas de Dopamina/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Trastornos de la Memoria/fisiopatología , Memoria a Corto Plazo/fisiología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fenantridinas/efectos adversos , Receptores de Dopamina D1/metabolismo , Trastorno de la Personalidad Esquizotípica/fisiopatología , Trastorno de la Personalidad Esquizotípica/psicología , Aprendizaje Verbal/efectos de los fármacos , Aprendizaje Verbal/fisiología , Adulto Joven
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