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Effects of cocaine administration on VTA cell activity in response to prefrontal cortex stimulation.

The repeated use of psychostimulants in humans has been associated with progressive enhancement of anxiety, panic attacks, and eventually paranoid psychosis. The appearance of such behaviors has been termed behavioral sensitization, which forms part of the basic pathological mechanisms involved in drug addiction. Psychostimulants act via a circuit involving the ventral tegmental area (VTA), prefrontal cortex (PFC), and nucleus accumbens. The PFC sends glutamatergic projections that activate dopaminergic neurons in the VTA. These projections provide an extremely important excitatory drive necessary for the development of sensitization. The effects of cocaine administration on the response of dopaminergic VTA cells to activation of the PFC have not been reported. Here the effects of acute cocaine administration on VTA cell response to PFC stimulation are examined. Statistical analysis of the changes in spontaneous activity and evoked response revealed a significant decrease in spontaneous activity at 1.0 mg/kg i.v. after cocaine treatment compared to baseline levels. The net effect was an increase in signal-to-noise ratio. Treatment with MK-801 at a dose of 2 mg/kg showed that the excitatory response was, at least partially, NMDA-mediated. Prazosin pretreatment (0.5 mg/kg i.p.) did not prevent a significant decrease in spontaneous activity brought about by cocaine (15 mg/kg, i.p.). Nonetheless, prazosin alone induced a significant decrease in the response to PFC stimulation when compared to baseline. In addition, iontophoretic application of norepinephrine (NE) onto VTA cells revealed that NE potentiated (19.2%), enhanced (26.9%), or suppressed (46.2%) the glutamate-evoked response in VTA cells. The results suggest that a possible role of cocaine in the process of sensitization might be to amplify the PFC-induced excitation at the VTA. Since the iontophoretic release of NE in almost half of the sampled cells produced similar effects to those of cocaine it may suggest a possible NE-mediated mechanism for cocaine actions.

Animals↗

Managers can drive their subordinates mad.

This article explores the phenomenon of "folie à deux"--an aberrant relationship between manager and subordinates that is characterized by shared delusions. Though most visible among public figures like Adolf Hitler, J. Edgar Hoover and Jim Jones, the problem also surfaces among private managers and their associates with dangerous implications for the firm. In folie à deux, the unusual behavior patterns of a manager in an isolated setting become mirrored by dependent subordinates, and the organization loses touch with its original goals and strategies. The author describes the dynamics of this phenomenon and details steps to remedy the situation. Once recognized, he suggests that the manager establish a trusting relationship with the instigator as a prelude to altering the behavior patterns, then transfer the subordinates and reorient the work climate so that independence and responsibility are encouraged. If the instigator is a powerful executive, the author suggests enlisting the support of a countervailing force, such as the government or a union, to guide the organization away from possible self-destructive adventures.

Administrative Personnel↗

Self-mutilation resulting in bacterial meningitis.

Self-mutilation and particularly self-destructive dermatoses are not usually life-threatening. This case involves a man who met the DSM-III R diagnostic criteria for delusional (paranoid) disorder, somatic type. His destructive behavior involving the face and scalp resulted in osteomyelitis and pneumococcal meningitis. He responded to treatment initially, but was later lost to follow-up. No similar case of self-mutilation has been reported.

Frontal Bone↗

Hypochondriasis and paranoia: similar delusional systems in an institutionalized geriatric population.

Hypochondriasis and paranoia are common psychopathologies of aging. The former may be secondary to depression or organic brain syndrome, whereas the latter may be secondary to sensory impairment or organic brain syndrome. Paranoid schizophrenia, with delusions of grandeur, is rare in later life. The authors classified 273 institutionalized geriatric patients by means of staff ratings into categories such as lucid and alert, confused, hypochondriacal, paranoid, etc. Among confused patients there was a correlation of .45 (p less than .001) between hypochondriasis and paranoia. Even among nonconfused patients, there was a slight positive correlation. The authors concluded that geriatric paranoia and hypochrondriasis have similar structure (delusion) and functions (safeguarding self-esteem and manipulating others). An interpersonal perspective can also provide guidelines for when to treat these conditions.

California↗

[The concept of madness in Talmudic literature and its commentaries].

In spite of their spatial and temporal dispersion, the talmudic literature and its commentaries proceed from a fundamental unity. On one hand, the definition of madness are, a priori, extremely rigid; originally, they were exemplaries, quoted to resolve practical problems. On the other hand, the handling of these definitions requires a very important suppleness in the jurisprudence of legal implications of madness. Obviously, the dialectics of the rabbis show the care to respect the personal life of the individual and the spiritual life of the community. And if these conceptions have still an application nowadays, that is because the Talmud speaks of the mad and not of the mental ill without any cross-checking between the socio-legal model of madness and the medical model.

Deafness↗

On early and mid-adolescent schizophrenia.--Part II: prognosis, course and defect.

Twenty-three adolescent schizophrenics were studied in regard to the problems of the course of illness, prognosis and defect. Illustrations of cases (follow-up for three to 15 years) were presented. 1) The course was considered chiefly from the viewpoint of positive symptoms, namely paranoid-hallucinatory experiences. It was divided into the following four categories; remittent, persistent, scanty and fading types. At the same time, general characteristics of each type were discussed. 2) As to the changes in clinical forms, hebephrenia was gradually manifested in more than half of the cases. There were some cases in which the expansion of paranoid activities were observed. These two prominent tendencies might be explained in terms of personality disintegration and maturation. We were impressed, in this regard, that autistic tendencies and behavior disturbances were more manifest in the initial stages in patients who later turned more hebephrenic. 3) A mild defect was observed in fourteen cases, while a medium or severe defect was recognized in eight cases. Generally, the degree of defect seemed to be more manifest in female patients than in males. Moreover, the defect was generally more severe in early adolescent cases and in patients with insidious onsets as well as in those with a longer duration of illness than in mid-adolescent patients and those with acute onsets and a shorter duration of illness. 4) As the result of this investigation, it was substantiated that the prognosis in adolescent schizophrenia, especially in early adolescence, was unfavorable. 5) Finally, we were impressed by the fact that there were many patients who were treated mainly in ambulatory clinics or who stayed at home in spite of the above-mentioned unfavorable prognosis.

Adolescent↗

Differences between paranoid and nonparanoid schizophrenic patients on the somatosensory P300 event-related potential.

Event-related potentials were recorded from schizophrenic patients (n = 30) and healthy controls (n = 30) using a somatosensory-reaction-time version of the oddball paradigm, by stimulating the right and the left median nerve. Latency, amplitude, duration and area of the P300 were measured. The patient group was subdivided into a paranoid (n = 16) and a nonparanoid (n = 14) subgroup and each was compared to controls. After stimulation of the right median nerve the nonparanoid group had a significantly prolonged P300 latency and a normal amplitude. The paranoid subgroup had a trend toward reduction of the P300 amplitude; its P300 latency was normal. After stimulation of the left median nerve, a prolongation of the P300 latency was observed in the paranoid subgroup. This subgroup had also a reduced P300 amplitude, while the nonparanoid patients had both values comparable to those of the controls. Duration and area were not significantly different between the two subgroups of patients and controls. Paranoid and nonparanoid patients showed a different behavior on reaction time parameters. No relationship was observed between P300 parameters and clinical ratings, neuroleptic dose and demographic data. The P300 parameters did not correlate with the reaction time measures. These results are discussed in terms of a disturbance of CNS inhibitory mechanisms in cognitive processes of paranoid schizophrenic patients and could be a further indication that different subtypes of schizophrenia may have different biological substrates.

Adult↗

The use of selegiline in Alzheimer's patients with behavior problems.

BACKGROUND: Currently there is no regimen for managing the inappropriate behavior seen in Alzheimer's disease that does not cause significant patient sedation. Preliminary evidence suggests selegiline may be effective in behavioral modification without the adverse effects observed with other regimens. The purpose of this study was to document the efficacy of selegiline in Alzheimer's patients with behavior problems. METHOD: Eight Alzheimer's patients (6 women and 2 men) ranging in age from 50 to 82 years (mean +/- SD = 74.0 +/- 10.5) were enrolled in this single-blind study. Patients received selegiline 10 mg each day for 8 weeks. Prior to drug administration and at the end of Weeks 1, 2, 4, 6, and 8, patients were evaluated for behavior (BEHAVEAD), cognitive function (Mini-Mental State Examination), and caregiver stress (Caregiver Burden Scale). RESULTS: Of eight enrolled patients, five were available for analysis. No statistically significant differences were found between mean baseline and mean 8-week scores for any of the three tests. However, clinical significance was noted by improvement in cognition (orientation and recall), caregiver stress, and behavior. Behavior was noted to improve in the areas of paranoid and delusional ideation, hallucinations, activity disturbances, anxiety, and phobias. CONCLUSION: These data suggest that some Alzheimer's patients with behavior problems may benefit from selegiline therapy.

Aged↗