The subcortical dysfunction hypothesis of verbal learning and memory deficits in depression was evaluated by comparing the memory test profiles of unipolar depressives (n = 40) and bipolar depressives (n = 9) with those of patients with a prototypical subcortical dementia (Huntington's disease, HD), patients with a prototypical cortical dementia (Alzheimer's disease, AD), and normal controls. In a discriminant function analysis that well-differentiated the HD, AD, and normal subjects, it was found that 28.6% of the depressed patients were classified as HD patients (DEP-HD subjects), 49.0% were classified as normals (DEP-N subjects), none were classified as AD patients, and 22.4% were not well-classified. The DEP-HD group closely resembled the HD group on additional indices of verbal learning and memory, and differed from the DEP-N group, which strongly resembled the normal control group. DEP-N patients also performed significantly better than DEP-HD patients on a number of other neuropsychological tests (e.g., WAIS-R Digit Symbol, category fluency, Trail Making Test Part B). The findings provide support for the subcortical dysfunction hypothesis, but only for a subgroup of depressed patients. Implications for differentiating depressive "pseudodementia" from AD are discussed.

Arecholine (4 milligrams), a cholinergic agonist, and choline (10 grams), a precursor of acetylcholine, significantly enhanced serial learning in normal human subjects. The subjects received methscopolamine prior to both arecholine and placebo injections. Conversely, scopolamine (0.5 milligram), a cholinergic antagonist, impaired learning and this impairment was reversed by arecholine and choline and the impairment after scopolamine were inversely proportional to the subject's performance on placebo; that is, "poor" performers were more vulnerable to both the enhancing effect of cholinergic agonist and precursor and the impairment after cholinergic antagonist than "good" performers.

This paper reviews recent literature which suggests that sleep disturbance in members of the general population, whether or not they have ever had a formal psychiatric disorder, is a risk factor for the onset of a formal psychiatric diagnosis at a later time. Based upon the current literature, the strongest link is between subjective insomnia, lasting at least 2 weeks, and the later onset of depression. Less well‐established data suggest that lifetime reports of at least 2 weeks of insomnia, hypersomnia, or both hypersomnia and insomnia, are risk factors for the later development of depression, anxiety disorders or substance abuse. More tentatively, preliminary data suggest that increasing subjective sleep disturbance may signal a relapse in remitted depressed patients. Sleep disturbances are common manifestations of major depressive and anxiety disorders. Therefore, sleep complaints may be among the most robust prodromal symptoms reflecting partial depressive or anxiety disorders, which eventually declare themselves as full‐blown clinical episodes.

Western countries experienced a widespread cocaine epidemic during the 1980s, and the number of frequent users has not declined in this decade. A key factor in the development of this epidemic has been the introduction of "crack," an affordable form of cocaine that appears to be more addicting than the powder. Epidemiologic studies indicate a high incidence of polysubstance abuse among cocaine abusers and probable gender differences in patterns of abuse and response to treatment. An abstinence syndrome has been documented in outpatients after the acute cessation of cocaine; the symptoms perhaps depend on the presence of cues to evoke craving of cocaine and thus are not detected in inpatient settings. Cocaine is a psychostimulant drug that possesses euphorigenic and reinforcing properties. The fact that various animal species self-administer cocaine through the intravenous route provides a reliable animal model for the study of the molecular mechanism of cocaine action and for the characterization of the anatomical substrates responsible for the rewarding properties of the drug. A multisynaptic, allocorticolimbic-accumbens-pallidal circuitry has been identified that seems to play an important role. This pathway may also be part of the neuronal substrates that mediate the reinforcing properties of other classes of abused drugs and, perhaps, motivated behavior in general. Because of this potent reinforcing nature of cocaine in humans, the problem of designing effective therapy for its addiction has not been simply solved. Clinical treatments, guided by animal studies and designed for specific attack of symptoms of the abstinence syndrome, craving and anhedonia, have been tested. To date, only a few agents have proved effective in controlled trials (amantadine, bromocriptine, carbamazepine, and desipramine) and these have limitations of side effects or delayed onset of action. Agents that interact with specific subcomponents of the dopamine system or its connections offer promise for the development of successful agents to treat cocaine abuse and craving in humans.