Absence of neuropsychologic deficits in patients receiving long-term treatment with alprazolam-XR for panic disorder.

Studies to date on the effects of benzodiazepines on neuropsychologic function have yielded conflicting data with respect to the type, severity, and duration of deficits that may be induced by these agents. As part of a placebo-controlled trial of alprazolam-XR (extended release) administered in combination with cognitive-behavioral therapy in patients with panic disorder, a battery of tests was used to measure neuropsychologic function. Thirty-eight outpatients were randomly assigned to receive either alprazolam-XR or placebo. Dosages were titrated up so that the alprazolam group (N = 18) received a mean dose of 4 mg/day (reduced in two patients because of sedative side effects). Neuropsychologic function after 6 weeks of therapy at the target dosage was compared with baseline assessments in each group. Both groups showed a statistically significant improvement from baseline to repeated assessments on measures of attention, executive functioning, psychomotor speed, and visual memory (p < 0.001); these gains were attributed to a practice effect. No significant changes were noted in measures of learning, verbal memory, or reaction time, and neither group showed any deterioration from baseline to retesting in any aspect of neuropsychologic function. These findings call into question the assumption that long-term benzodiazepine therapy produces significant neuropsychologic deficit in patients with diagnosed anxiety disorders.

Stability and course of neuropsychological deficits in schizophrenia.

BACKGROUND: Neuropsychological deficits in schizophrenia appear to predate clinical symptoms of the disease and become more pronounced at illness onset, but controversy exists about whether and when further neuropsychological progression may occur. OBJECTIVE: To identify and characterize any subset of patients who evidenced progressive neuropsychological impairment, we compared the longitudinal stability of neuropsychological functioning in schizophrenic outpatients and normal comparison subjects. METHODS: One hundred forty-two schizophrenic outpatients and 206 normal comparison subjects were given annually scheduled comprehensive neuropsychological evaluations during an average of 3 years (range, 6 months to 10 years). Clinically and demographically defined subgroups were compared, and test-retest norms were used to identify individual patients who showed unusual worsening over time. RESULTS: The schizophrenic group was neuropsychologically more impaired than the normal comparison subjects but showed comparable test-retest reliability and comparable neuropsychological stability over both short (mean, 1.6 years) and long (mean, 5 years) follow-up periods. No significant differences in neuropsychological change were found between schizophrenic subgroups defined by current age, age at onset of illness, baseline level of neuropsychological impairment, improvement or worsening of clinical symptoms, and occurrence of incident tardive dyskinesia. Norms for change also failed to show neuropsychological progression in individuals with schizophrenia. CONCLUSIONS: Neuropsychological impairment in ambulatory persons with schizophrenia appears to remain stable, regardless of baseline characteristics and changes in clinical state. Our results may not be generalizable to the minority of institutionalized poor-outcome patients.

Norms for letter and category fluency: demographic corrections for age, education, and ethnicity.

Letter and category fluency tasks are used to assess semantic knowledge, retrieval ability, and executive functioning. They appear to be useful in detecting different types of dementia, but accurate detection of neuropsychological impairment relies on appropriate normative data. Multiple regression analysis was used to develop demographically corrected norms for letter and category fluency in 768 normal adults. T-score equations were developed on a base subsample of 403, and crossvalidated on a separate subsample (n = 365). Participants ranged in age from 20 years to 101 years; in educational level from 0 to 20 years; 55% were Caucasian and 45% were African American. Together, age, education, and ethnicity were significant predictors of letter and category fluency performance, accounting for 15% and 25% of variance, respectively. Formulas and tables for converting raw fluency scores to demographically corrected T scores are presented.

Use of oral reading to estimate premorbid intellectual and neuropsychological functioning.

Judgment of neuropsychological decline is typically made by comparing a patient's current cognitive performance to data from demographically similar normal individuals. Even within narrowly defined demographic categories, however, there is variability in level of performance, approximating the normal curve. The present study explored the degree to which oral reading scores on the American National Adult Reading Test (ANART) could more accurately predict a person's test performance relative to other demographically similar individuals. In a sample of 141 neurologically healthy participants, the ANART added modestly to the precision of WAIS-R Verbal and Full Scale IQ and Learning score predictions, beyond that achieved by demographics alone; however, ANART score did not significantly improve estimation of Performance IQ, Average Impairment Rating, or Memory score. Use of the ANART tended to improve demographic predictions primarily with "outlier" participants whose oral reading skills were relatively poor. For Verbal IQ, ANART helped with participants who had both poor ANART and relatively high education. Oral reading can be useful for estimating premorbid verbal intelligence and learning in combination with demographic variables, but it does not appear to improve estimates of other neurocognitive abilities.

A neuropsychological study of panic disorder: negative findings.

BACKGROUND: Gray (1982) proposed that the septo-hippocampal system, which plays an important role in learning and memory, may partially mediate anxiety. Thus, patients with anxiety disorders may manifest neurocognitive performance deficits. We hypothesized that patients with panic disorder would demonstrate learning and memory deficits relative to normal comparison subjects. METHOD: Comprehensive neuropsychological batteries were administered to 69 panic disorder subjects and 19 normal volunteers. RESULTS: There were no significant group differences in any neuropsychological performance domain including learning, memory, attention, visuospatial functioning, and psychomotor speed. Multiple regression conducted to evaluate the contribution of clinical symptoms to neuropsychological impairment within the panic disorder sample revealed that anxiety severity did not affect neuropsychological test performance. LIMITATIONS: Most patients had mild or moderate, rather than severe, panic disorder. CONCLUSION: Neuropsychological dysfunction was not associated with panic disorder.

Medical comorbidity in schizophrenia.

The extent and consequences of medical comorbidity in patients with schizophrenia are generally underrecognized. Patients with comorbid conditions are usually excluded from research studies, although they probably represent the majority of individuals with schizophrenia. Elderly patients are especially likely to have comorbid disorders. In this article, we review selected literature on medical comorbidity in schizophrenia, including physical illnesses, substance use, cognitive impairment, sensory deficits, and iatrogenic comorbidity. Data from the University of California, San Diego Clinical Research Center on late-life psychosis are also presented. Older schizophrenia patients report fewer comorbid physical illnesses than healthy comparison subjects, but their illnesses tend to be more severe. These results suggest that schizophrenia patients may receive less than adequate health care. Substance abuse is more common in patients with schizophrenia than in the general population and may exacerbate psychiatric symptoms in these patients. Although generalized cognitive impairment is associated with schizophrenia, the main contributors to dementia in older patients are more likely to be comorbid neurological and other physical disorders, substance abuse, and medication side effects. Iatrogenic comorbidity results primarily from the use of neuroleptic (e.g., tardive dyskinesia) and anticholinergic (e.g., confusion) medications. Clinical and research recommendations are made for management of comorbidity in schizophrenia.

Environmental events surrounding natural recovery from alcohol-related problems.

Environmental events influence relapse and recovery patterns in treated alcoholics, and the present study investigated the role of events in recoveries achieved without treatment. Subjects were 21 abstinent and 18 active problem drinkers; none had received treatment, and recovered subjects had abstained an average of 6 years. During structured interviews, event occurrences were assessed during a 3-year period that began 2 years before the attainment of abstinence by recovered subjects and were compared with event occurrences during a matched 3-year interval for active drinkers, which equated the groups on the length of recall. Collaterals verified subjects' reports of their drinking practices, events and absence of treatment. Recovered subjects showed (1) heightened health concerns and a relatively stable work situation during the year preceding initial abstinence, (2) a reduction in health events following resolution and (3) a decrease in legal events and total negative events across the 3 years surrounding resolution. Although qualified by the relatively small sample and the retrospective, correlational design, these findings suggest that (1) changes in several areas of functioning evolve over time to motivate initial abstinence and to maintain continued resolution, and (2) variables that motivate initial behavior change differ somewhat from those that maintain it.

Help-seeking and recovery by problem drinkers: characteristics of drinkers who attended Alcoholics Anonymous or formal treatment or who recovered without assistance.

Most problem drinkers do not seek formal treatment, yet some achieve problem resolution without it. This research investigated variables related to help-seeking and to long-term drinking outcomes in a 3 x 2 factorial design, using 126 problem drinkers who varied in their help-seeking history (no assistance, A.A. only, or treatment plus A.A.) and current drinking status (abstinent more than 6 months or engaging in problem drinking). Dependent variables included alcohol-related negative consequences, dependence symptoms, drinking patterns, other drug use, and demographic characteristics. Formal treatment utilization was associated with greater psychosocial dysfunction, especially in interpersonal relationships, and with greater nonprescribed drug use. Alcohol dependence levels were not related to help-seeking, but higher levels were associated with an abstinent drinking status. Abstinent subjects also showed some evidence of greater social stability, but demographic variables, including gender, did not otherwise differentiate the groups. These findings suggest that help-seeking and attainment of abstinence are somewhat independent processes, but that both relate more to the functional consequences of problem drinking than to stable drinker characteristics.

Adequacy of recall of drinking patterns and event occurrences associated with natural recovery from alcohol problems.

The adequacy of recall of drinking and events surrounding natural recovery from alcohol problems was investigated with 21 abstinent and 18 active untreated problem drinkers. During structured interviews, drinking was assessed for 6 years, and events were assessed for 1 year; both assessment periods ended about 6 years before data collection, which corresponded with the beginning of sobriety for abstinent subjects. The accuracy of subject reports of both variable classes was evaluated through comparisons with collateral reports, and the reliability of drinking reports was evaluated by reinterviewing a subset of subjects about 2 months after the first assessment. Reliability was generally high for subjects' drinking reports. Subject-collateral agreements were significant for drinking and event variables that collaterals could readily observe, but not for variables that were less observable. Current drinking status and the length of recall did not influence reporting accuracy. With some qualifications, these findings support the use of structured recall procedures to investigate drinking patterns and environmental circumstances related to natural recovery and highlight limitations in the use of collaterals as a verification method.

Environmental influences on relapse in substance use disorders.

Characteristics of the posttreatment environment have been implicated in relapse and recovery in substance use disorders. We summarize these findings and describe how different models of relapse interpret the data and diverge in their representations and measurement operations of environmental variables. The advantages and limitations of common measures of the posttreatment environment are discussed using research on life events and relapse as an example. An alternative approach to representing covariation over time between environmental characteristics and substance use that is derived from an application of behavioral theories of choice to relapse is presented.