• In a family study of 1,254 adult relatives of patients and controls, lifetime prevalences of major affective disorder (including schizoaffective) were 37%, 24%, 25%, 20% and 7% in relatives of probands with schizoaffective, bipolar I, bipolar II, and unipolar disease, and normal controls. These data were compatible with the different affective disorders representing thresholds on a continuum of underlying multifactorial vulnerability. In this model, schizoaffective illness represents greatest vulnerability, followed by bipolar I and bipolar II, then unipolar illnesses. Alcoholism, drug abuse, and sociopathy were not more frequent in relatives of patients v relatives of controls. Sex-related transmission of morbid risk was not present. Morbid risk was 74% to offspring of two ill parents, and 27% to offspring of one ill parent. Nationality and age at time of interview seem to be nongenetic factors that affect frequency of diagnosis.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=PSYCH&articleId=492887&pdfFileName=archpsyc_39_10_006.pdf

A Family Study of Schizoaffective, Bipolar I, Bipolar II, Unipolar, and Normal Control Probands

Drug craving, the desire to experience the effect(s) of a previously experienced psychoactive substance, has been hypothesized to contribute significantly to continued drug use and relapse after a period of abstinence in humans. In more theoretical terms, drug craving can be conceptualized within the framework of incentive motivational theories of behavior and be defined as the incentive motivation to self-administer a psychoactive substance. The incentive-motivational value of drugs is hypothesized to be determined by a continuous interaction between the hedonic rewarding properties of drugs (incentive) and the motivational state of the organism (organismic state). In drug-dependent individuals, the incentive-motivational value of drugs (i.e., drug craving) is greater compared to non-drug-dependent individuals due to the motivational state (i.e., withdrawal) developed with repeated drug administration. In this conceptual framework, animal models of drug craving would reflect two aspects of the incentive motivation to self-administer a psychoactive substance. One aspect would be the unconditioned incentive (reinforcing) value of the drug itself. The other aspect would be relatively independent of the direct (unconditioned) incentive value of the drug itself and could be reflected in the ability of previously neutral stimuli to acquire conditioned incentive properties that could elicit drug-seeking and drug-taking behavior. Animal models of drug craving that permit the investigation of the behavioral and neurobiological components of these two aspects of drug craving are reviewed and evaluated. The models reviewed are the progressive ratio, choice, extinction, conditioned reinforcement and second-order schedule paradigms. These animal models are evaluated according to two criteria that are established herein as necessary and sufficient criteria for the evaluation of animal models of human psychopathology: reliability and predictive validity. The development of animal models of drug craving will have heuristic value and allow a systematic investigation of the neurobiological mechanisms of craving.

Animal models of drug craving

• Interviews with patients and two resource persons were used to determine primary psychiatric diagnoses in 577 consecutive men entering an alcohol treatment program (ATP) at a veterans hospital. Twelve months later, about 95% of the sample were successfully followed up with a patient and resource person Interview to establish the clinical course over the year for the four most populous diagnostic subgroups. At intake into the treatment program, the 432 group 1 primary alcoholic men were older, had a later age at onset of alcoholism, demonstrated a lower intensity of drinking, had fewer antisocial problems, and used fewer categories of drugs than the 60 men in group 2 with primary drug abuse and the 40 men in group 3 with primary antisocial personality disorder. During the follow-up, men in groups 2 and 3 had a greater likelihood of drug use, more police and social problems, and demonstrated higher (more adverse) outcomes on a clinical outcome scale. The nine group 4 men with primary affective disorder at intake demonstrated an increased risk for past suicide attempts and psychiatric care and had a higher rate of affective disorder in first-degree family members. These findings underscore the importance of distinguishing between symptoms (eg, sadness or antisocial problems) and diagnoses and the need to establish primary and secondary labels in substance abusers.

The Clinical Implications of Primary Diagnostic Groups Among Alcoholics

Amphetamine-Induced Increases in Extracellular Dopamine, Drug Wanting, and Novelty Seeking: A PET/[11C]Raclopride Study in Healthy Men

Toward Constructing an Endophenotype Strategy for Bipolar Disorders

Behavioral, biochemical and neuroendocrine responses to amphetamine in normal twins and ‘well-state’ bipolar patients☆

The neurochemical specificity of physiological, biochemical, and psychological responses to dextroamphetamine was tested by pretreating volunteers with haloperidol (0.014 mg/kg IM), proparonol (0.1 mg/kg IV), thymoxamine (0.1 mg/kg IV), or placebo prior to 0.3 mg/kg IV amphetamine. Healthy volunteers (N=12) participated in the studies, but not all volunteers received each drug combination. Haloperidol prevented dextroamphetamine-induced behavioral excitation, but did not significantly affect plasma norepinephrine or pressor responses, whereas propranolol inhibited norepinephrine and pressor responses without influencing excitation or other behavioral responses. Thymoxamine did not affect any of the responses measured. None of the agents significantly affected plasma cortisol or growth hormone responses. The prolactin rise following dextroamphetamine was potentiated by haloperidol. The results are consistent with the hypothesis that behavioral excitation after dextroamphetamine occurs through a dopaminergic mechanism, and pressor responses through a noradrenergic mechanism.

Linda Kessler

Papers

Behavioral, biochemical and neuroendocrine responses to amphetamine in normal twins and ‘well-state’ bipolar patients☆

Separate mechanisms for behavioral, cardiovascular, and hormonal responses to dextroamphetamine in man

Genetic studies and biologic strategies in the affective disorders.

Pirbuterol trial as antidepressant.