With the first diagnosis of mania come questions about the future. Some answers are provided by the McLean-Harvard First-Episode Project, which tracks patients hospitalized for the first time with a manic or mixed episode of bipolar disorder. Tohen et al. (p. 2099) evaluated 166 patients 2 years after hospitalization. Almost all were recovered from manic and depressive syndromes and 72% were free of nearly all symptoms, but only 43% had regained their occupational and residential functioning. Relapses or recurrences had occurred in 40% of the patients, and another 19% had switched into a new phase of bipolar disorder, usually depression, without recovering from the initial episode. Type of medication did not significantly affect outcome, but use of most types dropped substantially over the 2 years. This realistic evaluation of clinical outcomes for mania suggests high rates of illness and dysfunction in the early years after first hospitalization. F1

A person’s stage of life, e.g., childhood or old age, can influence both the origins and outcomes of depression. Reinherz et al. (p. 2141) call our attention to the critical years between 18 and 26, when young people are navigating the transition from adolescence and have a high rate of major depression. Of 354 participants interviewed multiple times from kindergarten to early adulthood, 23% met criteria for depression between ages 18 and 26. The rates were similar for men and women, confirming previous results for this age group but deviating from the female predominance in depression overall. Of 12 familial and behavioral-emotional characteristics associated with depression, a violent family environment was the most influential. Other important predictors were low family cohesion, an older parent or larger family, and anxious or depressive symptoms during childhood. These salient predictors could be used to facilitate intervention in childhood and adolescence and thus avoid derailment of developmental progress and risk for later disabling disorder.

Auditory tones usually elicit an asymmetrical pattern of activation in the brain, but many patients with schizophrenia have either symmetrical activation or reversed asymmetry. Reite et al. (p. 2148) report that the brain responses to touch also display reversed asymmetry in schizophrenia. Tactile stimulation was provided by a tiny rubber bladder, which was attached to the index finger and inflated briefly every 4 seconds. In addition to reversed asymmetry in the primary somatosensory cortex, patients with schizophrenia had responses in the left hemisphere that were further forward and lower than those of healthy comparison subjects. The reasons for these differences are not apparent, but the possibilities include anatomical displacement, functional reorganization of the somatosensory cortex, and disrupted tactile input to the motor cortex.

Manfred Bleuler’s landmark study of schizophrenia outcome provided important data on recovery, but since its end in 1965, major changes in treatments and diagnostic criteria have occurred. Modestin et al. (p. 2202) have updated Bleuler’s findings by applying several sets of contemporary psychiatric diagnostic criteria to Bleuler’s original patients, for whom detailed, long-term records were available. For approximately 30% of the patients who met Bleuler’s diagnostic criteria for schizophrenia, the newer criteria pointed to other diagnoses, often schizoaffective disorder. In the remaining patients, schizophrenia was confirmed by the newer criteria. These patients were more homogeneous than those identified by Bleuler’s criteria; they showed more illness chronicity and less frequent recovery. Nevertheless, half had an episodic course, and 12%–15% recovered. In addition, the high rates of poor outcome, 27%–28%, occurred during the 1940s to 1960s, when treatments were limited.

They’re not saying that smoking is a good thing. But in a large, long-term study, Zammit et al. (p. 2216) found that subjects who smoked had a reduced likelihood of developing schizophrenia. The subjects were 50,087 men drafted into the Swedish army in 1969–1970; intake information included the number of cigarettes smoked per day. Hospitalizations for schizophrenia among these men through 1996 were determined from a national database. The risk of schizophrenia 5 or more years after conscription was only 60% as high for medium smokers as for nonsmokers, and the risk for heavy smokers was even lower, 40%. This effect did not extend to other psychoses. Nicotine and other components of tobacco smoke have neuroprotective effects in animals, and nicotine is known to affect dopamine and other neurotransmitters. Although these findings do not outweigh smoking’s harmful effects, they do emphasize particular molecular mechanisms in schizophrenia.

Taunton State Hospital, Massachusetts (p. 2098). F2

F3 for details.