The effect of antipsychotic medications on acoustic startle latency in schizophrenia.

Prepulse inhibition of the acoustic startle reflex (PPI) is extensively studied as a biomarker of schizophrenia (SCZ); however, antipsychotic medication can confound the measure. Latency, the time between the startling stimulus and the reflexive eye blink, provides an index of neural processing speed and is 90% heritable. SCZ subjects have slower latency than controls (CON). This study examined the effects of antipsychotic medication on startle latency. 108 CON and 132 SCZ subjects in three medication subgroups (94 on second-generation antipsychotics (SGA), 25 on first-generation antipsychotics (FGA), 13 unmedicated (NoMed)) were tested on a standard acoustic startle paradigm designed to measure startle magnitude, PPI, and latency. Latency was slower in SCZ compared to CON subjects (p=0.005). Latency did not differ between the three SCZ medication groups. When CON were added to that model, both the NoMed subjects (p=0.04) and the SGA subjects (p=0.003) were slower than CON subjects. For PPI, CON did not differ from SCZ analyzed as a single group. When SCZ subjects were divided into medication groups, PPI was lower in NoMed subjects than the CON group (p=0.03), the SGA group (p=0.02) and the FGA group (p=0.05). SCZ subjects on any medication did not differ from CON. Thus, latency was partially normalized by antipsychotic medication, but this did not obscure the slower latency in SCZ compared to CON. Therefore latency is both trait and state related, whereas medication normalized PPI and obscured any difference between SCZ and CON.

Declarative memory and WCST-64 performance in subjects with schizophrenia and healthy controls.

The Wisconsin Card Sorting Test (WCST) is a set-switching task used extensively to study impaired executive functioning in schizophrenia. Declarative memory deficits have also been associated with schizophrenia and may affect WCST performance because continued correct responding depends on remembering the outcome of previous responses. This study examined whether performance in visual and verbal declarative memory tasks were associated with WCST performance. Subjects comprised 30 patients with schizophrenia or schizoaffective disorder (SCZ) and 30 demographically matched healthy controls (CON) who were tested on the WCST, the Benton Visual Retention Test (BVRT), the California Verbal Learning Test (CVLT), and the Continuous Performance Test (CPT). SCZ subjects showed significant correlations between visual and verbal declarative memory and performance on the WCST-64 that were in the hypothesized direction such that worse memory performance was associated with worse performance on the WCST. CON subjects did not show a significant relationship between visual or verbal memory and WCST-64 performance. Fisher's r to z transformations indicated that the associations between declarative memory and WCST-64 performance in the SCZ subjects differed significantly from those of CON subjects. The findings suggest that interpretations of WCST-64 scores for subjects with schizophrenia should be considered in light of their declarative memory functioning.

El trastorno de estrés postraumático puede asociarse a un deterioro de la inhibición del temor: relación con la gravedad de los síntomas / Posttraumatic stress disorder may be associated with impaired fear inhibition: Relation to symptom severity

Uno de los problemas clave que se plantean en el trastorno de estrés postraumático (TEPT) es la incapacidad de inhibir el temor, incluso estando en unas condiciones seguras. Los fundamentos neurales que subyacen en el temor son clínicamente relevantes pero no se conocen bien. En este estudio se evaluó la potenciación y la inhibición del temor con el empleo del sobresalto potenciado por el temor en un procedimiento de discriminación condicionada (AX+/BX–). Nuestra hipótesis fue que los pacientes con TEPT mostrarían una potenciación del temor normal, pero con un deterioro de su inhibición. Se estudió a 28 voluntarios sanos y 27 pacientes con TEPT (14 con síntomas actuales bajos, 13 con síntomas actuales altos) a los que se presentó un conjunto de luces de colores (ensayos AX) emparejadas con chorros de aire aversivos en la garganta, y una serie diferente de luces (ensayos BX) presentadas sin chorros de aire. A continuación se les presentaron conjuntamente A y B (ensayos AB) con objeto de determinar si B inhibía la potenciación del temor que se producía con A. Todos los grupos mostraron una potenciación clara del temor, por cuanto la magnitud del sobresalto fue significativamente mayor en los ensayos AX que en los ensayos con ruido solo. Sin embargo, el grupo de TEPT de síntomas altos no mostró una inhibición del temor: estos pacientes mostraban una potenciación del temor en los ensayos AB significativamente superior a la de los controles y a la de los pacientes con TEPT de síntomas bajos (AU)

One of the central problems in posttraumatic stress disorder (PTSD) is the inability to suppress fear even under safe conditions. The neural underpinnings of fear are clinically relevant but poorly understood. This study assessed fear potentiation and fear inhibition using fear-potentiated startle in a conditional discrimination procedure (AX+/BX–). We hypothesized that patients with PTSD would show normal fear potentiation and impaired fear inhibition. Subjects comprised 28 healthy volunteers and 27 PTSD patients (14 with low current symptoms, 13 with high current symptoms) who were presented with one set of colored lights (AX trials) paired with aversive air blasts to the throat, and a different series of lights (BX trials) presented without air blasts. We then presented A and B together (AB trials) to see whether B would inhibit fear potentiation to A. All groups showed robust fear potentiation in that they had significantly greater startle magnitude on AX trials than on noise-alone trials. However, the highsymptom PTSD group did not show fear inhibition: these subjects had significantly greater fear potentiation on the AB trials than both the controls and the low-symptom PTSD patients (AU)

Pain management after Hurricane Katrina: outcomes of veterans enrolled in a New Orleans VA pain management program.

OBJECTIVE: To evaluate Hurricane Katrina's impact on patients with pre-existing chronic pain. Design. Review of literature about Hurricane Katrina and chronic pain or pain management and a qualitative interview of all identified patients enrolled in a behavioral pain management program. SETTING: Southeast Louisiana Veterans Healthcare System, Mental Health Service Line. SUBJECTS: In total, 42 of the 53 (79%) veterans enrolled in a chronic pain program prior to Hurricane Katrina were able to be contacted and evaluated with interviews and a review of their available medical records. OUTCOME MEASURES: Major impediments and facilitative factors in delivering pain management services were identified. CONCLUSIONS: Health care planning for large-scale emergencies must take into the need for prompt continuation of pain management services in patients with chronic pre-existing pain. Coordination between emergency clinics and pain management specialists, as well as the availability of electronic medical records, is an important factor in continuing established pain management services after a regional disaster.

Posttraumatic stress disorder may be associated with impaired fear inhibition: relation to symptom severity.

One of the central problems in posttraumatic stress disorder (PTSD) is the inability to suppress fear even under safe conditions. The neural underpinnings of fear are clinically relevant but poorly understood. This study assessed fear potentiation and fear inhibition using fear-potentiated startle in a conditional discrimination procedure (AX+/BX-). We hypothesized that patients with PTSD would show normal fear potentiation and impaired fear inhibition. Subjects comprised 28 healthy volunteers and 27 PTSD patients (14 with low current symptoms, 13 with high current symptoms) who were presented with one set of colored lights (AX trials) paired with aversive air blasts to the throat, and a different series of lights (BX trials) presented without air blasts. We then presented A and B together (AB trials) to see whether B would inhibit fear potentiation to A. All groups showed robust fear potentiation in that they had significantly greater startle magnitude on AX trials than on noise-alone trials. However, the high-symptom PTSD group did not show fear inhibition: these subjects had significantly greater fear potentiation on the AB trials than both the controls and the low-symptom PTSD patients.

Differences in startle reflex and prepulse inhibition in European-Americans and African-Americans.

The acoustic startle reflex and its modulation by a prepulse are psychophysiological phenomena that are commonly studied to evaluate various aspects of information processing. Recent reports in human populations suggest that subjects from disparate racial backgrounds may have significant differences in the startle response. To determine if this pattern could be observed in our subject population and whether it extended to prepulse inhibition (PPI), we evaluated baseline startle parameters and PPI in 53 African-Americans (AA) and 38 European-Americans (EA). In AA compared to EA, mean startle magnitude and probability of blink response were lower, with no difference in habituation. PPI was greater in AA than EA when groups were matched on baseline startle magnitude. These findings support the idea of racial differences in startle response. Implications for study design are highlighted, and possible environmental and genetic influences are considered.

Veterans seeking treatment for posttraumatic stress disorder: what about comorbid chronic pain?

Our primary aim was to document the rate of comorbidity of physician-diagnosed chronic pain conditions in veterans who were seeking treatment for posttraumatic stress disorder (PTSD). Chronic pain diagnoses (e.g., chronic low-back pain and osteoarthritis) were examined with retrospective chart review. Of the patients with PTSD, 66% had chronic pain diagnoses at pretreatment. These findings are consistent with previous studies that documented the high comorbidity of chronic pain and PTSD using samples of pain patients. Our secondary aim was to examine pain ratings before, during, and after PTSD treatment. Using data that were a part of clinical practice, we found that patients with more pain before treatment reported reductions in pain over the course of PTSD treatment and in the 4 months following treatment. While our results must be interpreted cautiously because of multiple confounding factors and the absence of experimental manipulation, they highlight the importance of PTSD and pain comorbidity.

Medication status affects the relationship of symptoms to prepulse inhibition of acoustic startle in schizophrenia.

Inhibition of the acoustic startle response by a smaller preliminary nonstartling stimulus is termed prepulse inhibition (PPI). Schizophrenia patients have impairments in PPI that may not fully normalize even when they are clinically stable on medication, particularly typical antipsychotics. There is evidence that more severe symptoms are associated with more severe PPI abnormalities, but the effect of antipsychotics on this relationship is not clear. Seventy-three male schizophrenia patients underwent acoustic startle and PPI testing. Symptom ratings were performed using the Brief Psychiatric Rating Scale (BPRS) and its subscales. Fifty-two subjects were treated with antipsychotic medication at time of testing; 21 were unmedicated. For all subjects, PPI was negatively correlated with the BPRS psychological discomfort subscale but not with BPRS total symptoms, BPRS positive symptoms or BPRS negative symptoms. For medicated subjects analyzed separately, there were no correlations with BPRS total scores or any subscales. For the unmedicated subjects analyzed separately, there were significant correlations of lower PPI with greater severity of BPRS total symptoms, positive symptoms and the psychological discomfort subscale. These data indicate that more severe symptoms are associated with lower PPI, but that medication status is an important factor in the relationship between symptom severity and sensorimotor gating.

Contingency awareness and fear inhibition in a human fear-potentiated startle paradigm.

Fear-potentiated startle is defined as an increase in the magnitude of the startle reflex in the presence of a stimulus that was previously paired with an aversive event. It has been proposed that a subject's awareness of the contingencies in the experiment may affect fear-potentiated startle. The authors adapted a conditional discrimination procedure (AX+/BX-), previously validated in animals, to a human fear-potentiated startle paradigm in 50 healthy volunteers. This paradigm allows for an assessment of fear-potentiated startle during threat conditions as well as inhibition of fear-potentiated startle during safety conditions. A response keypad was used to assess contingency awareness on a trial-by-trial basis. Both aware and unaware subjects showed fear-potentiated startle. However, awareness was related to stimulus discrimination and fear inhibition.

Fear potentiation and fear inhibition in a human fear-potentiated startle paradigm.

BACKGROUND: The inability to suppress excessive fear or anxiety is a significant clinical problem. In the laboratory, extinction is a preferred method for the study of fear inhibition; however, in this paradigm the same stimulus causes both elicitation (excitation) and inhibition of fear, making it difficult to know whether an experimental manipulation that affects extinction does so by affecting one or both of these processes. For this reason, we sought to develop a behavioral procedure in humans that would render a stimulus primarily inhibitory. METHODS: We adapted a conditional discrimination procedure (AX+/BX-), previously validated in animals, to a human fear-potentiated startle paradigm. Forty-one healthy volunteers were presented with one set of colored lights paired with the delivery of aversive airblasts to the throat (AX+) and a different series of lights presented without airblasts (BX-). RESULTS: Participants exhibited fear potentiation to AX+, discrimination between AX+ and BX-, and transfer of fear inhibition to A in an AB compound test but not in an AC compound test. CONCLUSIONS: We believe this procedure will advance clinical research on fear disorders, such as posttraumatic stress disorder and phobias, by providing an effective and relatively independent measure of fear potentiation and fear inhibition.