Despite its virtually universal acceptance as the gold standard in treating bipolar disorder, prescription rates for lithium have been decreasing recently. Although this observation is multifactorial, one obvious potential contributor is the side effect and toxicity burden associated with lithium. Additionally, side effect concerns assuredly play some role in lithium nonadherence. This paper summarizes the knowledge base on side effects and toxicity and suggests optimal management of these problems. Thirst and excessive urination, nausea and diarrhea and tremor are rather common side effects that are typically no more than annoying even though they are rather prevalent. A simple set of management strategies that involve the timing of the lithium dose, minimizing lithium levels within the therapeutic range and, in some situations, the prescription of side effect antidotes will minimize the side effect burden for patients. In contrast, weight gain and cognitive impairment from lithium tend to be more distressing to patients, more difficult to manage and more likely to be associated with lithium nonadherence. Lithium has adverse effects on the kidneys, thyroid gland and parathyroid glands, necessitating monitoring of these organ functions through periodic blood tests. In most cases, lithium-associated renal effects are relatively mild. A small but measurable percentage of lithium-treated patients will show progressive renal impairment. Infrequently, lithium will need to be discontinued because of the progressive renal insufficiency. Lithium-induced hypothyroidism is relatively common but easily diagnosed and treated. Hyperparathyroidism from lithium is a relatively more recently recognized phenomenon.

The Developmental Processes in Schizophrenic Disorders project is a longitudinal study of schizophrenic patients who have recently had a first episode of psychosis. The project focuses on discriminating characteristics of schizophrenic patients that are "stable vulnerability indicators," "mediating vulnerability factors," and "episode indicators" by comparing normal subjects to schizophrenic patients assessed in clinically remitted and psychotic states. A parallel project goal is to identify predictors of relapse, social and work impairment, and illness course among potential psychobiological vulnerability factors and environmental potentiating factors. Hypothesized vulnerability factors and potential environmental stressors are examined first under standardized maintenance antipsychotic medication conditions for at least 1 year. Patients showing stable remission of psychosis after 1 year of maintenance antipsychotic medication are invited to enter drug crossover and withdrawal protocols to determine the need for continuous antipsychotic medication. Vulnerability and stress factors are again assessed. A summary of results to date is presented. Deficits in early components of processing visual arrays and in sustained discrimination of successive ambiguous perceptual inputs are relatively stable across psychotic and clinically remitted states in the schizophrenic patients. Performance on a vigilance task demanding active, working memory also remains abnormal during clinical remission but covaries significantly with psychotic state and is a candidate for a mediating vulnerability factor. Autonomic activation level does not appear to be an enduring vulnerability factor, but it predicts the extent of short-term symptomatic recovery and may mediate the impact of stressors. Under conditions of standardized, injectable antipsychotic medication, independent stressful life events and highly critical attitudes toward the patient in the social environment predict relapse risk. Prospective data suggest that signs and symptoms prodromal to psychotic relapse may be present in about 60 percent of patients.

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Followed samples of unipolar and bipolar patients for a 6-month period, with independent assessment of symptoms and life events. Patients were initially categorized into subtypes using Beck's Sociotropy/Autonomy Scale, with the prediction that onset or exacerbation of symptoms, as well as more total symptoms, would occur for sociotropic individuals experiencing more negative interpersonal events than achievement events, and for autonomous-achievement patients experiencing more achievement events than interpersonal events. Results were confirmed for unipolars, indicating that the course of disorder was associated with the occurrence of personally meaningful life events, but not for bipolars. Further research is recommended to examine whether the effect is equally robust for both subtypes of unipolars, whether longer study duration may be required for bipolars, and whether a cognitive self-schema mechanism may account for the specific vulnerability to a subset of stressful events.

While the role of neurocognitive impairment in predicting functional outcome in chronic schizophrenia is now widely accepted, the results that have examined this relationship in the early phase of psychosis are surprisingly rather mixed. The predictive role of cognitive impairment early in the illness is of particular interest because interventions during this initial period may help to prevent the development of chronic disability. In a University of California, Los Angeles (UCLA) longitudinal study, we assessed schizophrenia patients with a recent first episode of psychosis using a neurocognitive battery at an initial clinically stabilized outpatient point and then followed them during continuous treatment over the next 9 months. Three orthogonal cognitive factors were derived through principal components analysis: working memory, attention and early perceptual processing, and verbal memory and processing speed. All patients were provided a combination of maintenance antipsychotic medication, case management, group skills training, and family education in a UCLA research clinic. A modified version of the Social Adjustment Scale was used to assess work outcome. Multiple regression analyses indicate that the combination of the 3 neurocognitive factors predicts 52% of the variance in return to work or school by 9 months after outpatient clinical stabilization. These data strongly support the critical role of neurocognitive factors in recovery of work functioning after an onset of schizophrenia. Cognitive remediation and other interventions targeting these early cognitive deficits are of major importance to attempts to prevent chronic disability.