Adding the opioid antagonist naltrexone to relapse prevention therapy for patients with amphetamine dependence resulted in more negative urine samples (65%) than did placebo (48%). Jayaram-Lindström et al. (p. 1442) randomly assigned 80 patients to naltrexone or placebo for 12 weeks in addition to weekly individual treatment with a psychologist. Urine samples were collected twice a week. In addition to the objective evidence of greater abstinence in the patients receiving naltrexone, subjective reports indicated less craving. Naltrexone’s effects may be explained by the influence of mu-opioid receptors on the neurotransmission of dopamine, the primary mediator of amphetamine’s effects.

Two widely used second-generation antipsychotic drugs were not superior to a first-generation antipsychotic in treating 116 patients ages 8–19 with schizophrenia, schizoaffective disorder, or schizophreniform disorder. Over 8 weeks, 50% of those taking the first-generation antipsychotic molindone were ”much“ or ”very much“ improved, compared to 46% of the risperidone group and 34% of the olanzapine group. Sikich et al. (p. 1420) also examined adverse effects. These included an 18% rate of akathisia in the molindone group, despite prophylactic benztropine. The youth taking olanzapine gained an average of 6.1 kg, and those taking risperidone gained 3.6 kg. The olanzapine group also had significant increases in cholesterol, low-density lipoprotein, insulin, and liver transaminases. The olanzapine treatment arm was discontinued part way through the study because of concerns about these adverse effects. Findling et al. (p. 1432) compared a different second-generation antipsychotic, aripiprazole, with placebo for treating adolescents with schizophrenia. Both 10 and 30 mg/day of aripiprazole produced greater decreases than placebo in the total score on the Positive and Negative Syndrome Scale at week 6. The difference for the 30-mg dose was evident at week 1. The most common adverse events linked to aripiprazole were extrapyramidal disorder, somnolence, and tremor. Low prolactin levels were found in 34% and 26% of the 10- and 30-mg/day aripiprazole groups, respectively, compared to 8% of the placebo group. An editorial by Dr. Randal Ross on p. 1369focuses on issues unique to children and adolescents with schizophrenia.

Depression following bereavement appears to be largely similar to depression related to other life events. In a large twin study, Kendler et al. (CME, p. 1449) did find several differences between 82 people with bereavement-related depression and 224 with depression linked to other stressful life events. Those with bereavement had less neuroticism, greater tiredness and loss of interest, and fewer guilt feelings. However, the two groups shared episode duration and severity, frequency of impairment, number of prior episodes, age at onset, comorbid disorders, and risk of major depression in co-twins. The extensive similarities raise questions about excluding bereavement-related depression from the diagnosis of major depression, as in DSM-IV. Dr. Mario Maj discusses the diagnostic issues in an editorial on p. 1373.

The negative effects of stress on cognitive functioning may be amplified by the ε4 allele of the gene for apolipoprotein E (APOE), which is associated with Alzheimer’s disease. Lee et al. (p. 1456) used salivary cortisol level as the measure of stress in their analysis of data on a population-based sample of 962 people ages 50 to 70. High cortisol was associated with worse cognitive ability, and this effect was greater among respondents with an ε4 allele. Those with two ε4 alleles were particularly susceptible, although the effect of genotype on cognitive function was less than the effect of the genotype-cortisol interaction. The influence of the interaction extended to six of the seven cognitive domains studied. In an editorial on p. 1376, Dr. Guerry Peavy integrates these findings with results from other studies.