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Carroll BJ, Iranmanesh A, Keenan DM, Cassidy F, Wilson WH, Veldhuis JD. Pathophysiology of hypercortisolism in depression: pituitary and adrenal responses to low glucocorticoid feedback. Objective: To test three theories of hypercortisolemia in depression–hypothalamic overdrive, impaired glucocorticoid feedback, or autonomous cortisol production. Method: We applied an overnight low-cortisol feedback strategy by administering metyrapone to hypercortisolemic depressed in-patients and control subjects. Results: Under metyrapone, the increases of plasma adrenocorticotropic hormone (ACTH) concentrations and of basal and pulsatile ACTH secretion were not exaggerated in hypercortisolemic depressed patients compared with control subjects. ACTH approximate entropy (ApEn) did not differ at baseline or under metyrapone. Thus, neither hypothalamic overdrive nor irregular ACTH secretion was seen. We did not detect impaired cortisol feedback: the ACTH response was not reduced, and ApEn measures that are sensitive to feedback changes were comparable in both groups. Metyrapone disrupted cortisol secretory regularity in depressed and control subjects. On the baseline day, basal cortisol secretion was significantly increased and was highly irregular (high ApEn), and ACTH-cortisol cross-ApEn was markedly elevated in high-cortisol patients. Conclusion: Classical feed-forward overdrive and impaired feedback theories of hypercortisolemia in depression were not supported. Depressive hypercortisolemia may result from alternative pathophysiological mechanisms involving irregular basal hypersecretion of cortisol, associated with adrenal enlargement, possibly through splanchnic sympathetic activation of the adrenal cortex.

The effect of fluoxetine (FLU) in posttraumatic stress disorder was studied in a one-year trial. Subjects received open-label treatment for 6 months, followed by double-blind randomized treatment with FLU or placebo (PBO) for 6 months. Rates of relapse were compared using the Clinical Global Impressions of Improvement. One hundred twenty-three subjects entered open-label treatment, of whom 114 returned at least once. Sixty-two subjects were randomized to receive FLU or PBO, of whom 57 returned at least once and were analyzed. The dose of FLU ranged from 10 to 60 mg/d; at randomization, mean doses were 48.6 and 42.1 mg for FLU and PBO groups. Rates of relapse were 22% for FLU versus 50% for PBO (P = 0.02), and time to relapse on FLU was longer than for PBO (P = 0.02, log-rank statistic). The odds ratio for relapse on PBO relative to FLU was 3.50. No significant differences were found on other measures. Fluoxetine was well tolerated during double-blind treatment.

We examined the test-retest reliabilities of reported and objective measures of smoking, and the intercorrelations among these measures, in acutely psychotic patients with schizophrenia to determine whether severe psychiatric illness affects the utility of these variables. All measures demonstrated good test-retest reliability. Objective measures of smoking were consistently intercorrelated and should be the preferred outcome measures in studies testing strategies to reduce smoking.

While several studies are available on the immediate effects of marijuana and its active ingredient tetrahydrocannabinol (THC) on regional cerebral blood flow (rCBF), we examined the effects of intravenous infusion of THC on rCBF and behavior over a 120-min. period using positron emission tomography. Indices of rCBF, intoxication and physiology were measured at baseline and 30, 60, 90 and 120 min. after a 20-min. intravenous infusion of 0.15 or 0.25 mg/min. of THC, or placebo given to 47 subjects. The rCBF remained increased up to 120 min. after the high-dose THC infusion. Significant increases were seen in global perfusion and in the frontal, insular and anterior cingulate regions. Changes were greater in the right hemisphere. After the high dose, cerebellar flow was increased at both 30 and 60 min. The anterioposterior ratio of cortical rCBF increased in both hemispheres, and remained significantly greater than in the placebo condition until 120 min. in the right hemisphere. Intoxication peaked at 30 min. and remained elevated at 120 min. THC had significant effects on global CBF and rCBF, and feeling intoxicated accounted for changes in rCBF better than plasma level of THC.

Objective: Although activation of an immune response during major depressive episodes has been reported, less is known about changes during manic and mixed bipolar episodes. Method: Albumin and leukocyte levels were compared between subjects in manic and mixed bipolar episodes. Neutrophil, lymphocyte and monocyte levels were compared between the two groups. Results: Albumin levels were lower in mixed manic subjects as opposed to pure manic subjects and in the combined groups levels were lower in females than in males. Leukocyte levels were higher in mixed manic patients compare with pure manic patients. Both neutrophil and monocyte levels were higher in the mixed manic patients but lymphocyte levels were no different. Conclusion: Leukocytosis and hypoalbuminemia during mixed manic states suggest immune activation in mixed mania similar to depression. This finding also tends to support the recognition of mixed mania as a distinct bipolar state.

While large numbers of studies are available on anxiety and cerebral blood flow (CBF), little is known about their relationship to extracranial (forehead) flow. The participants were 24 generalized anxiety disorder (GAD) patients and 26 normal volunteers. A randomized, between groups, repeated measures design was used to evaluate changes in cerebral blood flow. Measurements of CBF, forehead skin perfusion and ratings of anxiety and physiologic indices were made under resting conditions and during anxiety induction with epinephrine or saline infusions, given under double-blind conditions while subjects inhaled room air or 5% CO2. These subjects were divided into three groups; those with decreased anxiety, those with mild anxiety, and those with more severe anxiety increase. Subjects with severe anxiety showed least hypercarbic CBF increase (indicating cerebral vasoconstriction) and maximal increase in forehead skin perfusion. Those with minimal anxiety had most hypercarbic cerebral vasodilation and least increase in forehead skin perfusion. Forehead skin perfusion correlated positively with anxiety levels, and negatively with hypercarbic cerebral vasodilation. In animals, sympathetic activation limits hypercapnic cerebral vasodilation. Thus, the restricted hypercapnic cerebral vasodilation during severe anxiety may be mediated through cervical sympathetic fibers which innervate cerebral vessels.

Nearly 90% of schizophrenics smoke cigarettes, considerably higher than the general population's rate of 25%. There is some indication that schizophrenics may smoke as a form of self-medication. Nicotine has a variety of pharmacologic effects that may both counteract some of the cognitive deficits of schizophrenia and counteract some of the adverse side effects of antipsychotic drugs. In the current study, we assessed the interactions of haloperidol and nicotine on cognitive performance of a group of schizophrenics. These patients were in a double-blind study, randomly assigning them to low, moderate, and high dose levels of haloperidol. The subjects, all smokers, came to the laboratory on four different mornings after overnight deprivation from cigarettes. In a double-blind fashion, they were administered placebo, low (7 mg/day), medium (14 mg/day), or high (21 mg/day) dose nicotine skin patches. Three hours after administration of the skin patch, the subjects were given a computerized cognitive test battery including: simple reaction time, complex reaction time (spatial rotation), delayed matching to sample, the Sternberg memory test, and the Conners continuous performance test (CPT). With the placebo nicotine patch, there was a haloperidol dose-related impairment in delayed matching to sample choice accuracy and an increase in response time on the complex reaction time task. Nicotine caused a dose-related reversal of the haloperidol-induced impairments in memory performance and complex reaction time. In the CPT, nicotine reduced the variability in response that is associated with attentional deficit. These results demonstrate the effects of nicotine in reversing some of the adverse side effects of haloperidol and improving cognitive performance in schizophrenia.

We administered a series of 12 brief vignettes depicting examples of positive, negative, and manic psychopathology in everyday language to 21 patients with schizophrenia and 20 patients with mania. We asked patients to rate, first, how similar they were to the individual depicted in each vignette, and, second, the degree to which the experiences or behaviors depicted in each vignette reflected mental illness. Psychiatrists also rated how similar each patient was to each vignette. At admission, patients with schizophrenia rated themselves as significantly less similar to the positive symptom vignettes than the psychiatrists rated them. Patients with mania did not differ from the psychiatrist in rating their similarity to the vignettes, but they strongly denied that the vignettes reflected mental illness.

OBJECTIVE This paper is intended to help American clinicians and investigators further their understanding of the clinical use of clozapine by reviewing experience with the drug in Russia, where it was introduced 17 years before it became available in the United States. METHODS Key articles on clozapine from the Russian clinical research literature were reviewed by the first two authors, former Russian clinical investigators. The third author comments briefly about the implications of this work from a contemporary American perspective. FINDINGS AND CONCLUSIONS The review found that although clozapine was not widely distributed in Russia, it was investigated at several large psychiatric research institutions and hospitals. It was not reserved for neuroleptic-resistant disorders but instead was used with some success as a first-line treatment in acute disorders. Although no controlled clinical trials were conducted, results of long-term outcome studies of treatment-resistant schizophrenia were largely in agreement with those of controlled trials and clinical follow-up studies in the U.S. The studies found short-term gains for previously refractory patients as well as improvements in social functioning that continued for extended periods in some cases. Russian investigators described clozapine as an effective antipsychotic agent that lacked the extrapyramidal side effects of other neuroleptics.

State hospitals provide essential services to many of society's most ill and needy individuals. As the next century approaches, state hospitals can best fulfil their missions by developing as high-quality neuropsychiatric/rehabilitation institutes, as opposed to custodial care centers. Highly skilled professionals whose education has included the special knowledge and skill pertinent to state hospitals are central to this development. Although “training units” in state hospitals have existed in many locales, a specific curriculum is often lacking. This article describes the curriculum for psychiatric residents who rotate through the Professional Education Unit at Dammasch State Hospital, as part of the Oregon Public Psychiatry Training Program. The curriculum is described by exploration of the individual learning contract, known as the “Educational Plan,” which guides each resident's work.

Training has been a longstanding and fruitful area of collaboration between the public and academic sectors. Graduate medical education for psychiatry residents is one example. This paper reviews the history of Oregon's public psychiatry training program and highlights factors contributing to its success.

OBJECTIVE: The authors examined differences in the prevalence of psychiatric disorders in individuals who did or did not have alcoholic parents. METHOD: They used data from the National Institute of Mental Health Epidemiologic Catchment Area project, specifically from the Piedmont of North Carolina. Prevalence of psychiatric disorders was estimated in 408 ECA participants who reported problem drinking in their mother, their father, or both and in 1,477 age- and sex-matched subjects who did not report having alcoholic parents. RESULTS: The adult children of alcoholics showed significantly higher current (6-month) prevalence rates of simple phobia and agoraphobia and lifetime rates of dysthymia, generalized anxiety disorder, panic disorder, simple phobia, and agoraphobia. Adult children of alcoholics also had significantly more antisocial symptoms. Male children of alcoholics had higher rates of alcohol and drug abuse and reported more antisocial symptoms than did female children of alcoholics. Male children of alcoholics had a significantly higher rate of lifetime diagnoses of alcohol and drug abuse than men who were not children of alcoholics. More female children of alcoholics had generalized anxiety disorder than women who were not children of alcoholics. Both male and female children of alcoholics had significantly more antisocial symptoms than their matched comparison subjects. Sons of alcoholic fathers had a higher rate of substance abuse and more antisocial symptoms than did daughters of alcoholic fathers. Daughters of alcoholic fathers had a higher rate of generalized anxiety disorder. CONCLUSIONS: These data on adult children of alcoholics in a large community sample add to a literature based mainly on descriptive material or studies of smaller samples. Language: en

Psychological and physiological indices were monitored before and 120 minutes after smoking high- and low-potency marijuana cigarettes and a placebo cigarette in 35 physically and psychiatrically healthy normal volunteers during three separate visits to the laboratory. The psychological indices monitored consisted of temporal disintegration, depersonalization, and mood states. The psychological indices were cerebral blood flow, pulse, respiration, and end tidal carbon dioxide and carbon monoxide. Marijuana smoking, but not placebo smoking, was associated with significant temporal disintegration and depersonalization. The changes were most marked 30 minutes after smoking the high-potency cigarettes. Eighty-six percent of the subjects reported at least some temporal disintegration after high-potency marijuana. After marijuana smoking, there was also a significant increase in cerebral blood flow, respiration, pulse rate, and systolic blood pressure. Temporal disintegration was found to be most closel...

Case reports of clozapine treatment for refractory schizophrenia have focused on instances of marked therapeutic response, raising the expectation of dramatic “cures” and the emptying of state hospital wards. However, in clinical practice, a spectrum of response is found. This article reports four cases of varying levels of response to clinical treatment with clozapine in a state hospital, and discusses the implications of this spectrum for clinical and administrative decision makers.

Marijuana is known to cause symptoms suggestive of orthostatic hypotension such as dizziness and fainting during upright posture. We examined changes in cerebral blood velocity (CBV) and peripheral circulation during upright posture after smoking marijuana in 10 right-handed male subjects with a previous history of exposure to marijuana. The participants were physically and mentally healthy and drug-free for a minimum of 3 months before the experiment. Middle cerebral artery CBV, blood pressure and pulse rate were recorded during reclining position and standing, before and after smoking a high-potency marijuana cigarette or a placebo cigarette administered during 2 separate visits to the laboratory. The participants were questioned about dizziness during the upright position. Six of 10 subjects reported moderate to severe dizziness during standing after marijuana but not placebo. Subjects who experienced severe dizziness during standing showed marked decreases in blood pressure and CBV. Those who reported moderate dizziness showed reduction in CBV but not blood pressure. Subjects who reported mild dizziness after marijuana and after placebo smoking showed minimal changes in blood pressure and CBV. Cerebral ischemia during upright position after marijuana smoking may be caused by hypotension and impaired cerebral autoregulation.

In 1989, the Public Psychiatry Training Program of the Oregon Health Sciences University Department of Psychiatry and Dammasch State Hospital opened a collaborative Professional Education Unit with the author as Director. This article describes the Unit's structure and programs, as an example of successful state/university collaboration and a possible model for other training programs in public psychiatry.

In the normal brain, cerebral blood flow (CBF) and function are closely coupled. Thus, changes in brain function associated with drug-induced anxiety reduction should be accompanied by parallel CBF changes. Benzodiazepines such as diazepam have been reported to reduce CBF. It is unclear, however, if this CBF decrease is specifically a function of the anti-anxiety property of the drug. To examine the relationship between drug-induced anxiety reduction and CBF changes more closely, i.v. injections of an established anxiolytic agent and an experimental anti-anxiety drug were given to patients with generalized anxiety disorder. CBF and anxiety levels were measured before and 30 min after i.v. administration of diazepam (0.12 mg/kg), ondansetron (0.24 mg/kg), and normal saline during separate visits to the laboratory. The order of drug administration was randomized, and the injections were given under double-blind conditions. Diazepam but not ondansetron or saline reduced anxiety. Global CBF reduction was seen after diazepam, but no changes were found following the other two experimental conditions. The CBF values were adjusted for test-retest changes in carbon dioxide levels. Postdiazepam decreases in CBF and anxiety levels did not correlate.

Comprehensive treatment programs for individuals with schizophrenia usually include a variety of groups, many of which have concrete tasks as a focus: medication management, social skills training, meal preparation, etc. These groups can simultaneously serve more general rehabilitative purposes if leaders apply principles of group leadership which recognize the neuropathological substrate of schizophrenia and which take into account the specific interpersonal characteristics and needs of individuals who have the illness. This paper presents a framework for leading task-oriented groups for individuals with schizophrenia and give examples from a medication group in a psychosocial rehabilitation program.

The relationship between anxiety and cerebral blood flow (CBF) is of considerable clinical and research significance. Although a considerable amount of information is available on mechanisms through which anxiety may influence CBF, this topic has not received much attention in psychiatry. Earlier techniques for the measurement of CBF were cumbersome and invasive. With the advent of noninvasive techniques, study of CBF in psychiatric disorders, including anxiety, became easier, and a number of such studies have been conducted. In this article the literature on psychophysiological and clinical aspects of changes in CBF associated with anxiety is reviewed.

Caffeine is believed to induce anxiety in normal people and anxiety disorder patients and panic attacks in panic disorder patients. The drug is also known to reduce cerebral blood flow (CBF). Findings suggesting an anxiety-related cerebral vasoconstrictive factor have been reported. We examined the relationship between changes in anxiety and CBF induced by intravenously injecting 250 mg of caffeine (comparable to 2 cups of coffee) in 8 patients with generalized anxiety disorder, 9 patients with panic disorder and 9 normal controls. CBF measurements were also obtained before and after an injection of normal saline in another group of 9 normal volunteers. The anxiety disorder patients did not show any evidence of increase in anxiety and panic after caffeine. Both patients and controls who received caffeine but not normal controls who received saline showed significant CBF decrease. The CBF changes were unrelated to changes in mood, autonomic activity and carbon dioxide levels.

Objective: The mechanisms mediating hypercortisolemia in depression remain controversial. Adopting the biomarker strategy, we studied adrenocorticotropin (ACTH) and cortisol dynamics in hypercortisolemic and non-hypercortisolemic depressed in-patients, and in normal volunteers. Method: Deconvolution analysis of 24-h pulsatile secretion, approximate entropy (ApEn) estimation of secretory regularity, cross-ApEn quantitation of forward and reverse ACTH-cortisol synchrony, and cosine regression of 24-h rhythmicity. Results: Hypercortisolemia was strongly associated with melancholic and psychotic depressive subtypes. Hypercortisolemic patients had elevated ACTH and cortisol secretion, mediated chiefly by increased burst masses. Basal ACTH secretion was increased, ACTH half-life was reduced, and mean 24-h ACTH concentration was normal. Cortisol secretion was increased in a highly irregular pattern (high ApEn), with high ACTH -> cortisol cross-ApEn (impaired feedforward coupling). Cortisol-mediated feedback on the secretory pattern of ACTH was normal. Hypercortisolemic depressed patients had normal programming of the central hypothalamo-pituitary-adrenal (HPA) axis pulse generator: ACTH pulse frequency, cortisol pulse frequency, circadian acrophases, and ApEn of ACTH secretion were normal. Responsiveness of the adrenal cortex to endogenous ACTH was normal. Non-hypercortisolemic patients resembled hypercortisolemic patients on ACTH regulatory parameters but had low total cortisol secretion. Conclusion: Increased ACTH secretion occurs in depressed in-patients regardless of cortisolemic status, confirming central HPA axis overdrive in severe depression. Depressive hypercortisolemia results from an additional change in the adrenal cortex that causes ACTH-independent, disorderly basal cortisol release, a sign of physiological stress in melancholic/psychotic depression.

We applied nicotine 21 mg and matching placebo transdermal patches to thirty haloperidol-treated patients with schizophrenia who smoked. Clinical assessments of bradykinesia-rigidity were lower during nicotine patch administration than during placebo patch administration.

Introduction: Schizophrenia patients, particularly those with specific types of hallucinations and delusions, may have a deficit in monitoring the generation of thought. This deficit, termed autonoetic agnosia, may result in the conclusion that self-generated thoughts come from an external source. Methods: This study assessed autonoetic agnosia in 29 schizophrenic patients and 19 controls by applying a recently developed technique from cognitive science: multinomial modeling of source-monitoring data. Results: Schizophrenic patients demonstrated deficits in monitoring the source of self-generated information, yet performed similarly to controls in monitoring the source of visual and auditory information. Schizophrenic patients with specific “target” symptoms such as auditory hallucinations and thought insertion had greater deficits than other patients in recognizing self-generated information. Conclusion: This study offers partial support for the notion that schizophrenic patients manifest autonoetic agnosia.

The focus of this report is on the possible role that the age of first use of marijuana may play on brain morphology and function.Magnetic resonance imaging (MRI) and positron emission tomography (PET) were utilized to study 57 subjects. Brain volume measures (whole brain, gray matter, white matter and lateral ventricle volumes), global cerebral blood flow (CBF) and body size were evaluated.There are three primary findings related to age of first use of marijuana. Subjects who started using marijuana before age 17, compared to those who started later, had smaller whole brain and percent cortical gray matter and larger percent white matter volumes. Functionally, males who started using marijuana before 17 had significantly higher CBF than other males. Both males and females who started younger were physically smaller in height and weight, with the effects being greater in males.These findings suggest that the age at which exposure to marijuana begins is important. Early adolescence may be a critical period for effects that are not present when exposure begins later. These results are discussed in light of reported effects of marijuana on gonadal and pituitary hormones.

Objective The aim of this study was to examine the relationship between depersonalization induced by tetrahydrocannabinol (THC), and regional brain activation. Method Cerebral blood flow (CBF) was measured by means of positron emission tomography (PET) in 59 normal right-handed volunteers before and following intravenous infusions of THC. Results After THC, CBF showed a global increase which was more marked in the right hemisphere, frontal lobes and anterior cingulate. Conclusion Regression analyses showed positive correlations between the right frontal and anterior cingulate and depersonalization.

Regional cerebral blood flow (CBF) was measured with the 133xenon inhalation technique in 27 patients with schizophrenia of less than 5 years' duration and in 27 patients with schizophrenia of more than 12 years' duration, under resting conditions. Similar measurements were also performed in 54 normal control subjects matched for age and sex. Patients with schizophrenia of long duration had lower anteroposterior gradients of CBF than patients with schizophrenia of short duration and matched control subjects. Covarying out age and end-tidal levels of CO2 did not alter the results.

There is evidence that familial factors serve as determinants of risk for post-traumatic stress disorder (PTSD), especially familial anxiety. This study investigates the relationship between chronic PTSD and family psychiatric morbidity. The sample was drawn from 81 female rape survivors with or without lifetime PTSD, 31 major depressive disorder controls, 20 anxiety disorder controls and 39 healthy controls. First-degree family members were directly interviewed (n = 285) and diagnoses assigned of major depressive, anxiety and alcohol or substance use disorder. Information was also available by family history for 639 relatives. In the directly interviewed sample, no consistently increased morbidity risk was observed for anxiety, PTSD, or alcohol/substance abuse in the rape survivor groups, but there was an increase in depression relative to the anxiety in healthy control groups. When comorbid depression in rape survivor probands was taken into account post hoc, an increased risk for depression was noted in family members of PTSD probands with depression, but not in relatives of PTSD probands without lifetime depression. Among rape survivor probands with non-comorbid PTSD, rates by history of familial anxiety and depression were negligible. In a logistic regression analysis, individual vulnerability to depression served as an independent predictor of chronic PTSD, along with specific trauma-related variables. In the family history group, results were consistent with those obtained from the directly interviewed group. Our findings clearly support the view that PTSD following rape is associated with familial vulnerability to major depression, which may thus serve as a risk factor for developing PTSD. The exact nature of this predisposition calls for further inquiry and there is a need to expand this study to include other PTSD populations. PTSD may on occasion represent a form of depression which is induced and/or modified neurobiologically and phenomenologically by extreme stress. Our findings may be a reflection of the sample composition, the current conceptualization of PTSD, or be related to study limitations.

Objective : This study sought to determine the relationships between serum clozapine levels and therapeutic response. Method : Fifty-six inpatients who met the DSM-III-R criteria for chronic schizophrenia and who had not responded to extended treatment with classical antipsychotics were randomly assigned to 12 weeks of double-blind treatment with clozapine at one of three serum level ranges : low (50-150 ng/ml), medium (200-300 ng/ml), or high (350-450 ng/ml). Baseline clinical assessments were completed before the patients' regular antipsychotic and anticholinergic drugs were discontinued. During clozapine treatment, serum levels were ascertained weekly to allow adjustment of clozapine doses so as to maintain each patient near the midpoint of his or her assigned serum level range. Clinical assessments were completed after 6 and 12 weeks of treatment. Results : The analyses of the results of treatments supported the superior efficacy of the 200-300 ng/ml and 350-450 ng/ml serum clozapine level ranges over the 50-150 ng/ml range, with no advantage for 350-450 ng/ml over 200-300 ng/ml. Sleepiness increased with increasing serum levels. Conclusions : Serum clozapine levels per unit of daily dose were at the lower end of the range noted in previous reports, possibly reflecting the current study's dosing schedules of twice or three times a day, the 11- to 13-hour postdose sampling time, and the moderate doses given. Serum clozapine levels, if interpreted in relation to daily clozapine dosing schedules, postdose sampling time, and total daily dose, may help to guide dosing to provide adequate opportunities for therapeutic response and to limit certain side effects of clozapine treatment.

Objective To characterize better the length of time required for the onset of improvement during clozapine treatment for refractory schizophrenia, the author reanalyzed data from a naturalistic outcome study. Method Medical records of 100 adults sequentially treated with clozapine in a state hospital were reviewed through 18 months. A priori criteria were used to categorize change in a measure of global social functioning. Results Of 73 patients who met the criteria for at least some improvement during clozapine treatment, 55 demonstrated initial improvement within 6 months, and the remainder demonstrated improvement by month 11. Response at 3 months was significantly correlated with outcome at 18 months. Conclusions Gross social improvement as measured in this study is likely to lag behind more sensitive indicators of clinical response. This study supports the notion that initial response to clozapine occurs within the first few months of treatment.

In 62 individuals recovering from substance abuse, materialism and spiritualism and cognitive patterns were quantified, before (retrospectively) and after recovery with the Mathew Materialism Spiritualism Scale (MMSS) and a Cognitive Patterns Questionnaire (CPQ). MMSS was also administered once to 61 general controls. Recovering individuals showed highly significant prerecovery to postrecovery increases in spirituality on most subscales of MMSS and changes in cognitive patterns. Sixteen controls who met the criteria for alcoholism on the Michigan Alcoholism Screening Test (MAST-positive) were separated from the others. Prerecovery MMSS scores did not differentiate the recovering individuals from MAST-positive controls. However, the prerecovery MMSS scores obtained by recovering individuals were significantly lower than the scores obtained by the MAST-negative controls. On the other hand, after recovery, recovering individuals showed higher MMSS spirituality scores in comparison to MAST-positive controls. The only MMSS item that differentiated recovering individuals after recovery from MAST-negative controls was mysticism with the recovering group obtaining higher scores.

We report an exploratory study examining the interrelationships among common sense, insight into psychosis, and performance on a battery of neuropsychological tests in 32 patients with schizophrenia evaluated at the time of discharge from involuntary hospitalization at a State psychiatric hospital. Common sense, as measured by the Social Knowledge Questionnaire, was associated with better performance across tests measuring parietal lobe functioning and vocabulary. In addition, patients with more common sense were more likely to say that they were ill and needed treatment. A global measure of insight, the Insight and Treatment Attitudes Questionnaire (ITAQ), was related to performance on a test of left parietal lobe function. However, the responses to the ITAQ item that may best reflect current awareness of mental illness in patients at the time of discharge ("After you are discharged, is it possible you may have mental problems again?") were related to performance on tests of the functioning of the prefrontal lobes and the right and left parietal lobes. These results add to the growing evidence that some of the deficits in awareness of illness among patients with schizophrenia are related to the neuropsychological dysfunction commonly seen in patients with this disorder.

OBJECTIVE The atypical antipsychotic medication clozapine is an effective treatment for refractory psychosis; however, the efficacy of clozapine when used in public mental health programs has yet to be fully characterized. This study assessed the outcome of clozapine treatment in a state hospital. METHODS The medical records of the first 100 patients to receive clozapine in a state hospital, from six months before clozapine treatment through 18 months of treatment, were reviewed. RESULTS The patients had chronic psychotic disorders that had responded poorly to treatment with conventional antipsychotic medication. Eighteen months after beginning clozapine, 45 patients were much improved, and 18 were somewhat improved. All except one of the improved patients were continuing clozapine treatment. Forty patients were living in community settings, 59 remained hospitalized, and one had died of an illness unrelated to clozapine. Violent episodes in the hospital decreased during the first six months of clozapine treatment. Thirteen patients had one or two seizures while taking clozapine, 12 of whom successfully continued clozapine treatment. One patient developed agranulocytosis, and one developed leucopenia; each recovered fully after clozapine treatment was discontinued. CONCLUSIONS Clozapine was an effective treatment for refractory psychotic disorders when given as a part of routine state hospital treatment.

To evaluate the sensitivity of a computerized cognitive-neuromotor test battery in assessing the effects of marijuana (Δ-9-tetrahydrocannabinol [THC]), we conducted a study of 10 healthy male volunteers who were experienced marijuana smokers. After extensive training on the performance tasks, each subject was tested on three separate days after smoking a cigarette containing either 1.75% THC, 3.55% THC, or placebo according to a randomized double-blind repeated measures design. Testing was carried out before smoking and 30, 90, and 150 minutes after smoking the cigarette. Of the five tasks employed, the digit-symbol substitution test with memory and the reaction time task were the measures most sensitive to effects of marijuana. We examined the usefulness of the coefficient of variation and effect size as indices of sensitivity to be used across different types of tasks.

Objective and method This paper reviews acute and chronic effects of drugs of abuse on cerebral blood flow (CBF) and metabolism and their clinical significance. The most important source of information for the review is human research reports published in refereed journals. A few animal studies, book chapters, and abstracts that are especially relevant are also included. Results In humans, ethanol in small doses produces cerebral vasodilation; higher doses induce cerebral vasoconstriction. Chronic alcoholism is associated with reduced CBF and cerebral metabolism. Sedatives and antianxiety drugs lead to global reduction in CBF and cerebral metabolism. Caffeine, even in small doses, is a potent cerebral vasoconstrictor. Cerebral vasodilation is seen immediately after cigarette smoking, but chronic smokers show global reduction in CBF. Changes in CBF after marijuana smoking are variable; both increases and decreases are seen. Chronic marijuana smoking, however, seems to reduce CBF. Most inhalants and solvents are vasodilators; chronic abuse is accompanied by a decrease in CBF. A number of drugs of abuse, including ethanol, amphetamines, cocaine, nicotine, and caffeine-phenylpropanolamine combinations, increase the risk for stroke. Reduction in CBF associated with chronic use of ethanol, nicotine, inhalants, and solvents is at least partially reversible upon abstinence. Conclusions Topics for future research include regional brain function, which mediates drug-induced mood changes (euphoria); CBF concomitants of psychological and physiological characteristics that increase addiction potential; changes in CBF that accompany withdrawal syndromes; mechanisms responsible for drug-induced stroke; and effects of functional and organic complications on CBF.

Comparing Crow's schizophrenia model with the defect state and Huber's basic symptoms shows that this model is an oversimplification of the complex reality of schizophrenic outcomes. The concept of negative symptoms is undermined by several factors, such as differing definitions, other confounding cross-sectional variables (e.g., akinesia and depression), short follow-ups and lack of confirmation by factorial analysis. The longitudinal concept of a defect state, which has been used in long-term follow-up studies, includes enduring symptoms currently classified as positive and negative. Huber's conceptualization of basic symptoms describes prodromal and enduring residual symptoms of schizophrenia associated with structural brain abnormalities. The overlap and lack of equivalence of these concepts and the limited empirical evidence does not allow firm conclusions. New longitudinal studies using clinical, psychosocial, and neuropsychological measures are needed to understand the natural history and etiology of the defect state.

Carbon dioxide (CO2) is a potent cerebrovasodilator; even mild changes in CO2 are associated with marked changes in cerebral blood flow (CBF). We measured CBF before and after 5% CO2, inhalation in 19 medicated patients with schizophrenia and 16 normal volunteers. Another group of 16 volunteers had 2 CBF measurements under resting conditions. Although both patients and controls showed marked CBF increase during CO2 inhalation, the CBF response was significantly less in the patients. Change in CBF per mm of CO2 was lower in the patients. The second group of controls did not show significant differences between the 2 resting CBF measurements.