Negative symptoms in schizophrenia: considerations for clinical trials

There is little agreement about the methodology of clinical trials of antipsychotic drugs in patients with negative symptoms. A literature review revealed wide variation in experimental design, rating scales and study duration. This reflects differing views as to the definition and response to treatment of negative symptoms. Some degree of standardization would improve comparability of studies and aid the development of new compounds. Patients included in such studies should have displayed negative symptoms for at least 6 months. Depressive symptoms, positive schizophrenic symptoms and extrapyramidal signs may all influence or be confused with negative symptoms and may respond to treatment; they should be at a low level at baseline and should be measured during the study period. Studies should last at least 8 weeks. Several scales are available for measuring negative symptoms and are reviewed; a global impression score should be used additionally.     

The debit balance of present day stress research.

Stress often precedes psychiatric disorders. This holds particularly for the group of mood disorders. A crucial question is whether stress is an epiphenomenon or a decisive factor in the causation of (certain forms of) mood disorder. Certainty about this question can only be obtained when it can be demonstrated that stress phenomena may induce changes in brain functioning similar to the ones supposedly associated with (certain forms of) depression. Since the phenomenology of stress syndromes, as well as their emotional intensity, are highly variable, careful diagnosis is a first requirement. In studies into the significance of stress in the occurrence of depression this degree of finesse has not been achieved. The major shortcomings are discussed. Those should be systematically addressed to provide this type of research with the necessary acuity     

Scleral dellen in strabismus surgery

This communication highlights scleral dellen as an unusual complication of strabismus surgery in a 55-year-old hypertensive male. The clinical significance, differential diagnosis and management of this condition has been discussed.     

About the centrality of mood lowering in mood disorders : Plenary Lecture ECNP Congress, Monte Carlo, October 1991

5-HT disturbances in depression (as exemplified by lowered CSF 5-HIAA) are not syndrome specific but related to components of the depressive syndrome, specifically to increased anxiety and aggression. These 5-HT disturbances are probably core pathogenetic processes not derivative features. I hypothesized that in this subtype of depression, i.e. in “5-HT related depression”, the key psychopathological disturbances are dysregulation of anxiety and aggression, while mood lowering is a “by-product”. Based on this hypothesis it was predicted that agents which ameliorate anxiety and/or aggression via harmonization of 5-HTergic transmission will, in addition, exert overall antidepressant effect in “5-HT related depression”. The study of the relative “weight” of the various psychopathological components of depression is a basic exercise in understanding the nature of that condition and could, as such, greatly facilitate the goal-directed search for new and innovative antidepressants.     

Serotonin receptor sensitivity and aggression

This study investigated the relationship between increased serotonin (5-hydroxytryptamine, 5HT) receptor sensitivity and human aggression. A low oral dose of meta-chlorophenylpiperazine (MCPP), a postsynaptic 5HT receptor agonist, was administered in a placebo-controlled design to depressed (n = 22) and panic disorder (n = 20) patients classified with or without signs of outwardly directed aggression, patients with a history of suicide attempts (inwardly directed aggression) (n = 11), and normal controls (n = 19). Hormones under 5HT control were measured at 30-min intervals. Results were as follows: (1) MCPP did not induce or reduce anger, (2) patients with outwardly directed aggression did not have significantly greater MCPP-induced cortisol or prolactin release than did patients without signs of outwardly directed aggression, (3) patients with a history of suicide attempts did not have significantly greater MCPP-induced cortisol or prolactin release than did normal controls, and (4) MCPP-induced hormone release was unrelated to measures of aggression.     

Hazards of smoking

A strong association exists between cigarette smoking and several diseases namely, cancer of the lung, bronchitis and emphysema, cancer of the larynx, oral cavity and oesophagus, gastric and duodenal ulcers, Crohn's disease, cancer of the bladder, coronary artery disease, macrocytosis, polycythaemia, leukaemia, etc. This is due to the harmful constituents of cigarette and other modalities smoking. Smokers not only harm themselves but also harm those around. Foetal malformations, abortions, stillbirths, prematurity and low birth weight are common in smoker mothers. These are the effects of passive smoking. There is no safer cigarette in the market even by lowering its harmful constituents. Mass education about the hazards of smoking with emphasis on complete stoppage of smoking is the only way to prevent its rising incidence.     

The effects of systemic morphine on behavior and EEG in newborn rats.

Early studies suggested that newborn animals are far more susceptible to the convulsant effect of systemic morphine than adult animals. The present study reassessed morphine's (0, 6, 12.5, 25, 50, 100 and 300 mg/kg) toxic effects, making use of electroencephalographic (EEG) recordings, behavioral observations and the specific opiate antagonist naloxone in immature rats (postnatal days 1, 3, 6, 12 and 24). Although morphine had opiate-specific effects (such as inhibition of activity at low doses), non-specific effects (such as hyperactivity) elicited by the highest doses, predominated in the 3 youngest age groups. At day 12 high doses of morphine first produced Straub tail and catatonia. At this age morphine produced EEG spikes that were not reversed by naloxone. Only at day 24 were electrographic spikes temporarily inhibited by naloxone. Behavioral convulsions were never observed, at any age. These findings indicate that morphine is less toxic in newborns than suggested previously.