Toward defining schizophrenia as a more useful clinical concept.

Delineating schizophrenia remains elusive despite considerable interest and study for more than a century. During this time, a variety of terms and defining features have been ascribed to the construct. The predominant contemporary construct, for which substantial limitations persist, has changed little in the past 30 years. With the approaching arrival of the DSM-V, interest in the nosology of schizophrenia has rebounded. Recent publications have focused principally on the following: integrating dimensional approaches to diagnosis, subtypes of schizophrenia, endophenotypes, and identifying those at early risk as part of a staging process. Some have even suggested replacing the term. Although an etiopathic diagnosis remains out of reach, contemporary research is marching down several distinct paths toward defining schizophrenia as a construct of greater clinical utility.

Progressive structural brain abnormalities and their relationship to clinical outcome: a longitudinal magnetic resonance imaging study early in schizophrenia.

BACKGROUND: Many studies have shown that structural brain abnormalities in schizophrenia are already present by the time of index evaluation of first-episode patients. However, whether these abnormalities progressively worsen during the subsequent course of the disorder remains unresolved. METHODS: To study the longitudinal progression of structural brain abnormalities, high-resolution multispectral magnetic resonance images obtained on 73 recent-onset schizophrenic patients and 23 controls were analyzed using state-of-the-art, well-validated, and highly reliable neuroimaging tools. The mean duration between initial and follow-up MRIs was 3 years. Repeated-measures analysis of covariance was carried out to determine (1) whether brain volume changes differed between patients and controls and (2) the significance of regional brain changes on functional outcome in schizophrenia. RESULTS: We found accelerated enlargement in cortical sulcal cerebrospinal fluid spaces early in the course of schizophrenia. Instead of the usual trajectory of volume enlargement, patients showed progressive reduction in frontal lobe white matter volume. A reciprocal increase in frontal lobe cerebrospinal fluid volume also occurred at a more rapid rate in patients than in controls. In keeping with most of our a priori hypotheses, patients with poor outcome had greater lateral ventricular enlargement over time than patients with good outcome. Progressive decrement in frontal lobe white matter volume and enlargement in frontal lobe cerebrospinal fluid volume were associated with greater negative symptom severity. Reductions in frontal lobe gray and white matter volumes correlated with poorer executive functioning. CONCLUSIONS: There are ongoing changes in the brains of schizophrenic patients during the initial years after diagnosis despite ongoing antipsychotic drug treatment. These progressive changes seem to be most evident in the frontal lobes and to correlate with functional impairment. Disruptions in neurodevelopment or neural plasticity may act alone or in combination to bring about these progressive brain deficits in schizophrenia.

Effects of smoking marijuana on brain perfusion and cognition.

The effects of smoking marijuana on regional cerebral blood flow (rCBF) and cognitive performance were assessed in 12 recreational users in a double-blinded, placebo-controlled study. PET with [(15)Oxygen]-labeled water ([(15)O]H(2)O) was used to measure rCBF before and after smoking of marijuana and placebo cigarettes, as subjects repeatedly performed an auditory attention task. Smoking marijuana resulted in intoxication, as assessed by a behavioral rating scale, but did not significantly alter mean behavioral performance on the attention task. Heart rate and blood pressure increased dramatically following smoking of marijuana but not placebo cigarettes. However, mean global CBF did not change significantly. Increased rCBF was observed in orbital and mesial frontal lobes, insula, temporal poles, anterior cingulate, as well as in the cerebellum. The increases in rCBF in anterior brain regions were predominantly in "paralimbic" regions and may be related to marijuana's mood-related effects. Reduced rCBF was observed in temporal lobe auditory regions, in visual cortex, and in brain regions that may be part of an attentional network (parietal lobe, frontal lobe and thalamus). These rCBF decreases may be the neural basis of perceptual and cognitive alterations that occur with acute marijuana intoxication. There was no significant rCBF change in the nucleus accumbens or other reward-related brain regions, nor in basal ganglia or hippocampus, which have a high density of cannabinoid receptors.

Validity of symptom assessment in psychotic disorders: information variance across different sources of history.

BACKGROUND: Factors such as poor insight, amotivation, suspiciousness, disorganized speech and attentional problems may interfere with the ability of acutely ill individuals with psychotic disorders to provide a valid account of their symptoms. This study was designed to determine the degree to which history provided by such subjects is consistent with that obtained from other sources. METHOD: Fifty-five subjects presenting with psychotic disorders were multiply evaluated with a semi structured interview, the Comprehensive Assessment of Symptoms and History (CASH), which includes the Scales for the Assessment of Negative and Positive symptoms (SANS and SAPS). One interviewer assessed the severity of the patient's symptoms in the previous month based solely on information provided by the patient. A second rater made symptom ratings based on information obtained from a "best informant". Following this, a consensus rating was established based on an extensive evaluation and review of all sources of information. An item-by-item comparison of the three sets of symptom ratings was then quantified by paired t-tests, simple and multiple correlations. RESULTS: Positive and negative symptoms ratings based on the subjects' report were significantly lower than the corresponding consensus ratings. However, those based on the informants' report did not differ from consensus ratings for negative symptoms. Information obtained from subjects and from informants together accounted for a majority of the variance of the consensus ratings. CONCLUSIONS: These findings demonstrate that assessment limited to patients' own reports are likely to underestimate psychopathology in acutely ill patients with psychotic disorders. Obtaining corroborative history from a family member may substantially improve the validity of the assessment of negative symptoms.

Psychiatric prescribing trends and practices in Iowa's prisons.

In response to rising pharmacy costs in the Iowa Department of Corrections prison system, a retrospective analysis of psychiatric drug use and expenditures was performed for fiscal years 1990 through 2000. Population-adjusted changes in use and expenditures over time were analyzed in aggregate and by drug class. Expenditures for psychiatric drugs increased 28-fold from $7,974 in 1990 to $381,893 in 2000, or from $291 to $8,138 per 100 inmates, while use increased fivefold. The use of antipsychotics remained relatively constant, but expenditures increased ninefold. In contrast, both use of and expenditures for antidepressants increased tremendously, from $215 to $1,929 per 100 inmates.

Diagnosing schizophrenia circa 2005: how and why?

Since the introduction of the third edition of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition in 1980, schizophrenia has been widely diagnosed with good to excellent levels of reliability. This is no small feat, as prior to the 1970s the reliability of this diagnosis over time and place was very poor. Although there have been some changes in the diagnostic algorithm for schizophrenia with subsequent revisions of the Diagnostic and Statistical Manual of Mental Disorders, there has been little change in the overall classification scheme. However, there has also been relatively little movement toward enhancing the validity of this diagnosis. Although there is broad consensus that what we now call schizophrenia is probably very heterogeneous with respect to underlying etiology and pathophysiology, attempts to identify more valid subtypes or dimensions have not progressed to the point that they are likely to be incorporated into diagnostic systems any time soon. The limited progress in defining more valid disease categories has increasingly important clinical implications as the field moves more and more to treatment by preset algorithms that are typically driven by diagnosis.

Older offenders, substance abuse, and treatment.

OBJECTIVE: The adoption of more stringent truth-in-sentencing laws and the aging of the United States population in general has led to an increase in the proportion of prison inmates age 55 years and older. Recent judicial rulings require prisoners to receive adequate medical and mental health care. Care for substance abuse is often included to reduce recidivism. However, little systematic research has been conducted on the mental health and substance abuse treatment needs of older prisoners. METHODS: The authors examined age differences in substance abuse history provided by 10,952 offenders as part of their orientation and evaluation on entry into prison. Trained substance abuse counselors interviewed each offender and recorded data in an institutional database. RESULTS: Seventy-one percent of older inmates reported a substance abuse problem. When compared with younger inmates, older offenders were more likely to abuse alcohol only. Those older inmates with abuse problems had used substances for over 40 years, yet more than one-third had never received treatment. CONCLUSION: Like younger inmates, most older offenders would benefit from substance abuse treatment. The treatment may need to be tailored to age and lack of previous treatment experience and should be sensitive to this high-risk group's additional medical needs.

Insomnia as a predictor for symptom worsening following antipsychotic withdrawal in schizophrenia.

Sleep disturbances have been associated with schizophrenia, and are an especially prominent feature during the prodrome preceding psychotic relapse. In this study, we examined the changes in sleep quality following withdrawal of antipsychotic treatment, as well as the predictive value of sleep disturbances on symptom exacerbation. One hundred twenty-two patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder underwent a 3-week medication wash-out prior to neuroimaging studies. Sleep quality was rated using items on the Hamilton Rating Scale for Depression (HAM-D), while symptom severity was measured using the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). Sleep quality deteriorated progressively following antipsychotic discontinuation. Total insomnia score prior to antipsychotic withdrawal had a significant effect on the severity of psychotic symptoms at the last weekly assessment, while baseline terminal insomnia had a significant effect on disorganized symptoms at the end of the medication-free period. These findings were independent of baseline symptom severity. Our findings suggest that schizophrenia patients with sleep disturbances are at a greater risk for worsening of positive symptoms after antipsychotic discontinuation. The implications of these findings in research and clinical settings are discussed.

Cerebral blood flow changes associated with Schneiderian first-rank symptoms in schizophrenia.

The authors examined the severity of Schneiderian first-rank symptoms in relation to regional cerebral blood flow (rCBF) with the use of PET. Eighty-seven schizophrenic patients were imaged during an eyes-closed condition during which they were instructed to relax and not perform any specific task (random episodic silent thought, or REST). Schneiderian symptoms were rated by using structured assessment instruments. The Schneiderian score of the patients was positively correlated with rCBF in right superior parietal cortex and negatively correlated with rCBF in left posterior cingulate gyrus and in left lingual gyrus. The results of this study demonstrate a cerebral pattern of activation related to Schneiderian symptoms and reinforce the hypothesis of an involvement of cortical areas that mediate space and body representation in such phenomena.

Coercion and informed consent in research involving prisoners.

Prison-based research has been limited due to concern that prisoners may represent a vulnerable population secondary to possible coercion and limited capacity for voluntary informed consent. This study was designed to assess decisional capacity and susceptibility to coercion in prison research subjects. Subjects were 30 mentally ill prisoners and 30 healthy controls. The groups were compared on ability to provide informed consent to a hypothetical drug trial, susceptibility to possible coercion, neuropsychological functioning, and psychiatric symptoms. Results indicated that all controls and all but one of the prisoners demonstrated adequate capacity to consent to the hypothetical drug trial. However, when decisional capacity was measured quantitatively, prisoners performed significantly worse regarding two aspects of this ability. Regarding possible coercion, prisoners' main reasons for participating in research included avoiding boredom, meeting someone new, appearing cooperative in hopes of being treated better, and helping society. Neuropsychological functioning was strongly positively correlated with decisional capacity and negatively correlated with susceptibility to possible coercion, whereas psychiatric symptoms were only weakly correlated with these variables. In conclusion, a very high percentage of particularly vulnerable, mentally ill prisoners demonstrated adequate capacity to consent to research. Lower scores on a quantitative measure of decisional capacity suggest that extra care should be taken during the consent process when working with these subjects. The reasons prisoners gave for participating in our research indicated that the prison setting may have influenced their decision to participate, but that they were not actually coerced into doing so. Despite serious past incidents, ethicists will need to consider the possibility that prisoners have become an overprotected population.