Faculty Bibliography

OBJECTIVE: There is limited evidence suggesting a link between posttraumatic stress disorder (PTSD) and Attention-Deficit/ Hyperactivity Disorder (ADHD). This study examined the association between PTSD and ADHD using retrospective and current clinical evaluations. METHOD: Twenty-five male veterans with PTSD and 22 male veterans with panic disorder were evaluated for ADHD. The data was analyzed using chi-square and student's t-tests. RESULTS: Thirty-six percent of participants with PTSD and 9% of participants with panic disorder met criteria for childhood ADHD. Twenty-eight percent of participants with PTSD and 5% of participants with panic disorder met criteria for current ADHD. CONCLUSIONS: There appears to be a significant association of PTSD with ADHD. ADHD or common predisposing factors may increase the vulnerability for developing PTSD

Prepulse inhibition (PPI) represents an attenuation of the startle reflex following the presentation of a weak prepulse at brief intervals prior to the startle eliciting pulse. It has been shown that increases in striatal dopamine levels decrease PPI; because dopamine release is sensitive to estrogen, it is likely that PPI varies across the menstrual cycle. Cross-sectional studies looking at estrogen effects suggest that this may be true. In this study, we compare effects of menstrual phase on PPI in a between-group design (men, follicular phase women, and luteal phase women) as well as a within-subjects design (women across the two phases). The study found a between-group as well as a within-subjects effect of phase on PPI. PPI in follicular phase women did not differ significantly from PPI in men. However, PPI was reduced in luteal women compared to follicular women. These data provide evidence that ovarian hormones affect sensorimotor gating

A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted

Studies of the acoustic startle response and of its inhibition by the presentation of a non-startling preliminary stimulus (prepulse inhibition, PPI) have revealed deficits in PPI in schizophrenic subjects compared to healthy controls. Animal studies indicate that atypical antipsychotics improve PPI deficits induced by NMDA antagonists more consistently than typical antipsychotics. The effect of medication status on PPI in schizophrenia is unresolved in the literature. In the current study the effects on PPI of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol were compared to the unmedicated state in subjects with schizophrenia. In a between-group design, 11 schizophrenic subjects on olanzapine, 16 subjects on haloperidol, and 14 subjects who were on no medication received acoustic startle testing with PPI determination. ANOVAs revealed no significant differences in startle to pulse alone stimuli, habituation of startle, or PPI between the olanzapine, haloperidol and unmedicated groups. These 41 subjects with schizophrenia were compared to a group of 21 historical healthy controls and found to have reduced PPI. These data do not indicate a preferential effect of olanzapine compared to haloperidol on sensorimotor gating in schizophrenia. The results are consistent with the hypothesis that PPI impairments are relatively stable across treatment conditions

Quantitative electroencephalographic (qEEG) profiles were studied in cocaine dependent patients in response to cocaine cue exposure. Using neurometric analytical methods, the spectral power of each primary bandwidth was computed and topographically mapped. Additional measures of cue-reactivity included cocaine craving, anxiety and related subjective ratings, and physiological measures of skin conductance, skin temperature, heart rate, and plasma cortisol and HVA levels. Twenty-four crack cocaine-dependent subjects were tested for their response to tactile, visual and audio cues related to crack cocaine or neutral items. All measures were analyzed for significant difference by comparing cocaine versus neutral cue conditions. An increase in cocaine craving, anxiety and related subjective ratings, elevated plasma cortisol levels, and a decrease in skin temperature, were induced by cocaine cue exposure. Distinct qEEG profiles were found during the paraphernalia handling and video viewing (eyes-open), and guided imagery (eyes-closed), phases of cocaine cue exposure. During paraphernalia handling and video viewing, there was an increase in beta activity accompanied by a drop in delta power in the frontal cortex, and an increase in beta mean frequency in the occipital cortex. In contrast, during guided imagery there was an increase in theta and delta power in the frontal cortex, and an increase in beta power in the occipital cortex. Correlation analyses revealed that cue-induced anxiety during paraphernalia handling and video viewing was associated with reduced high frequency and enhanced low frequency EEG activity. These findings demonstrated that EEG activation during cue-induced cocaine craving may be topographically mapped and subsequently analyzed for functional relevance

RATIONALE: The acoustic startle response is inhibited when the startling stimulus is preceded by a weaker non-startling acoustic stimulus. This phenomenon, termed prepulse inhibition of acoustic startle (PPI), is impaired in schizophrenics compared to normal controls. To date, there is conflicting evidence regarding whether PPI impairments improve with antipsychotic treatment. OBJECTIVES: To examine the effect of medication status on PPI in schizophrenic subjects. METHODS: First, we performed acoustic startle testing on 16 schizophrenic subjects when they were acutely decompensated off medication and later after they were stabilized on antipsychotic treatment. Second, in a between-group design, we tested 21 schizophrenic subjects off medication, 16 subjects on atypical neuroleptics, and 27 subjects on typical neuroleptics. RESULTS: In both the test-retest study and the between-group study, ANOVAs revealed no significant changes in startle to pulse alone stimuli, habituation of startle to pulse alone stimuli, PPI, latency to response onset, or latency to response peak between the treatment conditions. CONCLUSIONS: Our results do not support the hypothesis that impaired sensorimotor gating in schizophrenia improves with antipsychotic treatment. Rather, impaired gating persists despite symptomatic improvement on medication

OBJECTIVE: The purpose of this study was test the hypothesis that abnormalities of inferior frontal white matter are related to the negative symptoms of schizophrenia. METHOD: Fractional anisotropy of white matter tracts in the prefrontal area of 10 schizophrenic patients was determined by diffusion tensor imaging. Patients were also assessed for severity of negative symptoms by using the Schedule for the Assessment of Negative Symptoms (SANS). RESULTS: Inferior frontal white matter fractional anisotropy was significantly inversely correlated with the SANS global ratings of negative symptoms. CONCLUSIONS: These data, while preliminary, suggest that impaired white matter integrity in the inferior frontal region may be associated with the severity of negative symptoms in schizophrenia