A double FDG/PET study of the effects of scopolamine in older adults.

Two consecutive positron emission scans were done in one session using a double injection method of [18F]2-fluoro-2-deoxyglucose administration to examine the effects of the antimuscarinic drug scopolamine on cerebral glucose metabolism in ten older adults. Scopolamine causes temporary memory impairment, and its effects have been used to model aspects of the cognitive impairment that occur in Alzheimer's disease (AD). Cortical metabolic rates of patients with AD have been reported to be depressed, especially in parietal, temporal, and frontal association areas. After scopolamine administration to the elderly volunteers, absolute and normalized glucose metabolic rates were depressed in prefrontal and occipital regions and increased in parietal-occipital cortical regions and a left middle temporal region. These changes in the older volunteers are generally not consistent with changes seen in AD. We conclude that deficits in muscarinic system function may contribute to some but not all of the hypometabolic changes seen in AD patients.

Cerebral glucose metabolism in adults with attention deficit hyperactivity disorder after chronic stimulant treatment.

OBJECTIVE: The authors examined the effects of chronic stimulant treatment on cerebral glucose metabolism in adults diagnosed with attention deficit hyperactivity disorder (ADHD), who were studied by means of positron emission tomography (PET) with [18F]fluorodeoxyglucose as the tracer. METHOD: Each subject received two PET scans, the first before drug treatment and the second after treatment with daily oral doses, individually titrated for clinical effect, of either methylphenidate (N = 19) or d-amphetamine (N = 18) for a minimum of 6 weeks. The subjects completed behavioral self-report measures before and at the end of the medication period. RESULTS: Neither stimulant medication changed global, or whole-brain, metabolism, although both drugs increased systolic blood pressure. Metabolism in only two of the 60 brain regions sampled was changed by methylphenidate, while d-amphetamine exhibited no effect on regional metabolism. Both drugs were associated with significant improvement in behavior, as evidenced by improved ratings for restlessness and ability to maintain attention. CONCLUSIONS: While the present study does not demonstrate any robust metabolic effects of chronic stimulant treatment, the behavioral data strongly indicate that methylphenidate and d-amphetamine are effective agents for the treatment of adults with ADHD.

A review of the postconcussion syndrome.

OBJECTIVE: This review will focus on aspects of the postconcussion syndrome (PCS), including accompanying symptomatology, neuropsychological changes, brain imaging studies and treatment. METHOD: In each topic area, those research studies resulting in the most interpretable data are reported. Since there is little research in some aspects of the PCS, some studies of limited merit are described, with their limitations outlined, in lieu of not reporting any study. The section on psychopharmacology largely consists of opinions of recognized clinicians, since there is almost no research on the psychopharmacology of PCS. RESULTS: Mild traumatic brain injury is a relatively frequent occurrence which often results in the postconcussion syndrome (PCS), consisting of complaints of irritability, fatigue, headache, difficulty concentrating, dizziness, and memory problems. Anxiety and depression are also frequently present, especially later in its course. Although the PCS has often been thought to reflect a psychological response to injury, there is considerable recent evidence to suggest that it is primarily a physiologic disturbance. For most individuals, treatment consists primarily of education of the patient and his/her family, along with supportive counseling regarding emerging problems at work or at home. A subgroup of patients, however, may require psychopharmacologic intervention. CONCLUSION: More research is needed in all aspects of PCS, especially its neurophysiology and pharmacologic treatment. Relationships between neurophysiological changes and behavioral and neuropsychological changes are unknown. New imaging techniques, such as single-photon emission tomography, and positron emission tomography will likely play an important role in understanding the physiology of this disorder.

Intermittent vs maintenance medication in schizophrenia. Two-year results.

This is a 2-year, double-blind, placebo-controlled study of 101 patients, evaluating the relative efficacy of intermittent medication (given only when the patient shows early signs of relapse) compared with moderate doses of maintenance medication for stable schizophrenic outpatients. Patients were dropped from the study if they had three prodromal episodes in 1 year or if an episode lasted more than 9 weeks. Fourteen percent of patients given maintenance treatment were dropped from the study compared with 46% of intermittently treated patients. Relapse rates were 16% for patients given maintenance treatment and 30% for intermittently treated patients, a nonsignificant difference. Intermittently treated patients were receiving significantly less medication, but there were no differences found in drug side effects. There appears to be no advantage in using the intermittent approach, but we found that the use of an early intervention strategy reduced the relapse and rehospitalization rates for these patients.

Plasma phenylethylamine and phenylalanine in chronic schizophrenic patients.

The hypothesis that phenylethylamine (PEA) is an endogenous psychotogen in schizophrenics, particularly those with the paranoid subtype, has been previously studied by measuring PEA levels in urine and cerebrospinal fluid (CSF) of schizophrenic patients. However, plasma PEA may more accurately reflect simultaneous alterations of PEA in many organ systems, as might occur in a genetic disorder of PEA metabolism. No study to date has examined phenylalanine (Phe), which is thought to be a precursor of PEA, in the same patients who had PEA measured. In this study, we measure both plasma PEA and Phe in 17 drug-free schizophrenic patients and 17 matched controls. Plasma PEA in normal controls was found to be lower by three orders of magnitude compared to normal controls from previous studies--a finding that has not previously been reported. PEA was significantly lower in those schizophrenic patients who had a Research Diagnostic Criteria diagnosis of paranoid schizophrenia. PEA did not differ between patients and controls, and the correlation between plasma Phe and PEA was not significant.

Dihydropteridine reductase in schizophrenic patients.

The activity of the enzyme dihydropteridine reductase (DHPR) has been recently found to be one of the factors controlling the rate of synthesis of dopamine, norepinephrine, and serotonin, thought to be involved in the etiology of schizophrenia. Several lines of evidence suggest that peripheral and brain DHPR enzymes may be identical. In addition, peripheral DHPR activity has been hypothesized to be important in determining the level of phenylethylamine, a putative psychotogen that is produced peripherally and crosses the blood-brain barrier. Since DHPR activity has never been investigated in schizophrenic patients, we measured the whole blood activity in 20 schizophrenic patients and 20 matched controls. There was no difference between the groups in DHPR activity.

Recovery from schizophrenic psychosis.

Knowledge of changes in patients' symptoms during hospitalization is crucial in planning treatment for acute psychotic exacerbation of chronic schizophrenia. Biweekly assessment of symptoms in 44 schizophrenic patients during the first 4 weeks of hospitalization showed that rapid recovery from psychotic symptoms occurred early in hospitalization; recovery from depression and anxiety was less complete. The rapid recovery in the first few weeks of hospital treatment supports the use of brief hospitalization for psychotic relapse. It is important to focus follow-up treatment on patients' relative lack of recovery in the hospital from depression and anxiety.

Intermittent medication for stable schizophrenic outpatients: an alternative to maintenance medication.

Because of neuroleptics' potential long-term side effects, the authors conducted a pilot study of an alternative to maintenance medication for stable schizophrenic outpatients. The doses of 19 patients were gradually reduced to zero over 8 weeks, and medication was then given only when a patient experienced early signs of relapse. The patients attended weekly group therapy and were closely monitored for prodromal signs, especially at times of stress; significant others helped observe patients. Five patients experienced increased symptoms during the drug washout period and were dropped from the study; of the remaining 14, 10 remained stable on the intermittent medication protocol.

Estimating the local prevalence of persons needing community support programs.

As Community Support Programs for the chronically mentally ill expand, it becomes increasingly important to determine the number of individuals qualifying for these services. Although national prevalence data are currently available, they have only limited usefulness for program planning at state and local levels. Given the distinctive circumstances affecting each community's chronically ill population, their number, and their need for services, the authors propose identifying a patient cohort that approximates the local prevalence of persons needing Community Support Programs by using one of three methods. The first method identifies persons who have been hospitalized previously and who currently require outpatient psychiatric care. The second identifies persons previously hospitalized who require another hospitalization during a specified period of time. And, the third method identifies persons who are currently in outpatient treatment with a diagnosis of schizophrenia. choice of method depends on definition of chronic mental illness, type of data available, local treatment philosophies, and health care system structure.

Prolonged depersonalization after marijuana use.

The author describes four cases of prolonged depersonalization that occurred months after marijuana use. Each occurred in the setting of a stressful life event. Depersonalization is a common experience during acute intoxication with marijuana, and these cases suggest that after the patients had experienced depersonalization, external stressors and intrapsychic factors may have contributed to its continued use as a defense mechanism.