Prognostic significance of depression occurrence in infantile autism.

Autistic children undergoing therapeutic programs, which adopt in our service (USL 3 CT) different theoretical approaches, sometimes show a marked reduction in motor activities, a lowering of tone of voice, physical expression of sadness. We observe that animation is absent in the scene they may draw and colours are no longer used in their drawings. Sleep disturbance may appear or reappearance of enuresis. Many authors consider these symptoms as signs of depression. These changes, even though they create new problems in therapeutic management, are, in our opinion, a very important index of the unblocking of autistic withdrawal and beginning of development of those emotional, relational and cognitive components which seem to be frozen in autistic children and inhibit the birth of the mind, according to the U. Frith Theory. We report in this paper the psychoanalytic, cognitive, systemic, biological viewpoint on the occurrence of depression in infantile autism. We submit three cases of patients being treated in our service with the cognitive-behavioural oriented educational program and pharmacological therapy and discuss the multidimensional approach. The temporary occurrence of depression symptoms may be an index of a change within the resisting autistic balance, which may have a biological basis, but indicates the disorganization of the autistic child's mind in view of further development.

Opioid-immune interactions in autism: behavioural and immunological assessment during a double-blind treatment with naltrexone.

The emerging concept of opioid peptides as a new class of chemical messengers of the neuroimmune axis and the presence of a number of immunological abnormalities in infantile autism prompted us to correlate biological (hormonal and immunological) determinations and behavioural performances during treatment with the potent opiate antagonist, naltrexone (NAL). Twelve autistic patients ranging from 7 to 15 years, diagnosed according to DSM-III-R, entered a double-blind crossover study with NAL at the doses of 0.5, 1.0 and 1.5 mg/kg every 48 hours. The behavioural evaluation was conducted using the specific BSE and CARS rating scales NAL treatment produced a significant reduction of the autistic symptomatology in seven ("responders") out of 12 children. The behavioural improvement was accompanied by alterations in the distribution of the major lymphocyte subsets, with a significant increase of the T-helper-inducers (CD4+CD8-) and a significant reduction of the T-cytotoxic-suppressor (CD4-CD8+) resulting in a normalization of the CD4/CD8 ratio. Changes in natural killer cells and activity were inversely related to plasma beta-endorphin levels. It is suggested that the mechanisms underlying opioid-immune interactions are altered in this population of autistic children and that an immunological screening may have prognostic value for the pharmacological therapy with opiate antagonists.

Nerve growth factor inhibits some acute experimental inflammations.

Nerve growth factor (NGF) displays an inhibitory effect on peritoneal dye leakage in mice and on some types of acute inflammation in rats, i.e. acetic acid peritonitis and paw oedema induced by carrageenin, serotonin and dextran. Activity was only present in a restricted dose range, either after subcutaneous (1-8 micrograms/kg) or subplantar (0.5-5 micrograms) injection, and was characterized by a rapid onset of response. In the carrageenin test, NGF administered s.c. was more potent than indomethacin (INDO) and betamethasone (BTM); in addition, while the activity of INDO and BTM was observed only 2-3 hr after carrageenin challenge, the response of NGF developed within 1 hr, suggesting that NGF inhibits the early phase of the oedema. NGF exhibited a different action than BTM and INDO also in serotonin and dextran paw oedema. NGF (0.008 mg/kg s.c.) inhibited the serotonin oedema as early as 15 min and reached its maximum at 1 hr, whereas BTM (0.8 mg/kg) required at least 3 hr to attain the same effect. Serotonin oedema was not inhibited by INDO (even at 16 mg/kg) up to 0.25-6 hr, proving that this model of inflammation is insensitive to the inhibitors of prostaglandin synthesis. When given subplantary, NGF reduced dextran oedema, whereas BTM and INDO were ineffective. Pretreatment with specific anti-NGF antibodies abolished all the above effects of NGF, but did not modify the anti-inflammatory activity of BTM and INDO. NGF was less effective in reducing the exudate volume on carrageenin pleurisy and did not prevent cell migration. Tested in vitro, NGF showed no direct scavenging effect on superoxide radicals. These findings suggest that NGF may be involved in some types of acute inflammation by reducing vascular permeability.

Characterization of the antinociceptive effects of a ganglioside derivative in rodents.

The results of a broad pharmacological screening on a natural mixture of gangliosides (GA) and an inner ester (AGF1) are reported. Up to relatively high doses, GA and AGF1 did not affect general behavior and neurologic functions and were devoided of diuretic, antipyretic, ulcerogenic, antireserpine, antiapomorphine, anticholinergic and anticonvulsivant actions. Both compounds interfere specifically with some induced conditions of inflammation and pain, but AGF1 shows a stronger action in reducing phenylquinone writhing than GA which appears to possess a more pronounced anti-inflammatory activity. In the rat paw oedema the anti-inflammatory effect of GA and AGF1 developed 1 hr after carrageenin and reached its maximum at 2 hr, suggesting that an inhibition of the serotonin and kinin phases might be partly responsible. Therefore, it would seem that the anti-inflammatory action of gangliosides is not exerted by an inhibition of the prostaglandin (PG) system. This assumption is supported by the finding that GA and AGF1 did not influence yeast-induced hyperthermia nor produced ulcerogenic effects in fasted rats. Subcutaneous administration of AGF1 is less potent than indomethacin (2 times) in reducing phenylquinone writhings, but more effective than GA (6 times), codeine (9 times) and acetylsalicylic acid (187 times). After i.c.v. administration the anti-writhing activity of AGF1 was far more potent than that of all the other compounds. The neuronal substrate involved in the AGF1 antinociception is unknown at this time. The comparative study with GA suggests a dissociation between the anti-inflammatory activity and the antinociceptive response. The lack of analgesia in the hot plate test and the naloxone insensitive anti-writhing effect of AGF1 in mice indicate that a central opioid mechanism is not involved in the antinociceptive action. Furthermore, the negativity of the neurogenic plasma extravasation test seems to exclude also an interaction with peripheral opiate receptors. It is suggested that the antinociceptive action of AGF1 has both a peripheral and a central component via an interference with peripheral exsudative phenomena and the central serotonergic tonus.

Gangliosides antinociceptive effects in rodents.

The present paper shows that a mixture of gangliosides (GA = GM1 + GD1a + GD1b + GT1b) is provided with a specific and powerful antinociceptive activity. The GA is active in reducing acetic acid and phenylquinone writhings, the acetic acid capillary-induced permeability and some acute inflammatory reactions. These actions seem to be mostly due to an anti-exudative property of the compounds which shows up right after the administration. The mixture of four gangliosides given in the proportion naturally occurring in the nervous system is more active than each single component in increasing the pain threshold, presenting therefore a synergistic effect. It is suggested that gangliosides can reduce the exudative phenomena interfering with the membrane permeability of the nerve-endings breaking interfering with the membrane permeability of the nerve-endings breaking the vicious circle of the neurogenic mechanisms of plasma extravasation.