Cortisol level predicts executive and memory function in depression, symptom level predicts psychomotor speed.

OBJECTIVE: On a group level depression is related to hypercortisolism and to psychomotor retardation, executive dysfunction and memory impairment. However, intra-group heterogeneity is substantial. Why some are impaired while others remain in the normal range, is not clear. The present study aims at discerning the relative contribution of present symptom severity and hypercortisolism to impairment in the three domains of cognition. METHOD: Morning saliva cortisol was measured in 26 subjects with recurrent major depression prior to a neuropsychological examination with tests known to be sensitive to cognitive impairment in depression. RESULTS: Cortisol level correlated with executive dysfunction and post-encoding memory deficits, but not with processing speed. Depression level correlated with processing speed. These patterns remained significant after controlling for confounders through partial correlations. CONCLUSION: The association between cortisol and cognition is not an artifact of psychiatric symptom load. High level of saliva cortisol is associated with aspects of cognition that can be dissociated from psychomotor retardation, which is dependent on symptom load.

Honig's model of working memory and brain activation: an fMRI study.

The present study investigated changes in neuronal activation with fMRI related to Honig's model of working memory, which is much less studied compared with other working memory models. In contrast to other studies which have applied recognition procedures, the primary aim with the present study was to examine brain activation when subjects had to continuously recall and forget items held in working memory. The results showed that the mid-ventrolateral frontal cortex was particularly activated in the left hemisphere, whereas the mid-dorsolateral frontal cortex was particularly activated in the right hemisphere during execution of the working memory task. The findings are discussed in relation to process- and domain-specific accounts of working memory.

Schizophrenia: a review, with emphasis on the neurodevelopmental hypothesis.

The neurodevelopmental hypothesis of schizophrenia has gained increasing acceptance. This hypothesis assumes a disruption in the normal development of the brain, secondary to genetic factors, environmental factors, or, most likely, a combination of both. After a brief review of the various aetiologic models since the first description of the disease, we review relevant aspects of normal brain development and then focus on the pathologic findings supporting the neurodevelopmental hypothesis. Although this hypothesis of schizophrenia appears to be valid in some cases, it is important to keep in mind that there are many cases of schizophrenia in which one finds no documented brain abnormality. It therefore seems wrong to speak of schizophrenia in general as a neurodevelopmental disorder. It appears that there is a group of patients with schizophrenia who fit into a neurodevelopmental model. There is a need to further investigate whether these patients can be identified clinically and what this may imply with regard to treatment and prognosis.

Different functions of spinal 5-HT1A and 5-HT2 receptor subtypes in modulating behaviour induced by excitatory amino acid receptor agonists in mice.

The modulating effects of 5-HT1A and 5-HT2 receptor agonists on behaviour spinal excitatory amino acid (EAA) agonists were examined. Intrathecal (i.th.) administration of both N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) produce a behavioural syndrome of caudally directed biting and scratching. Serotonin (5-HT) agonists were coadministered with either NMDA or AMPA, and changes in EAA-induced behaviour were scored. All drugs were administered i.th. The 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) (15-60 nmol) reduced both NMDA (0.25 nmol) and AMPA (0.06 nmol) induced behaviour in a dose-dependent manner, and preadministration of the 5-HT1A receptor antagonist, 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide (NAN-190) (20 nmol) reversed this effect. The administration of the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (0.7-28 nmol) produced a dose-dependent behavioural syndrome similar to the EAA agonists. This was reversed by preadministration of ritanserin (10 nmol), a 5-HT2 antagonist. When DOI was coadministered with NMDA (0.25 nmol) or MAPA (0.06 nmol) there was an increase in the behaviour recorded and this effect was antagonised by ritanserin. The results of this study implicate that in the spinal cord subtypes of 5-HT receptors have different effects on modulation of behaviour induced by activation of the NMDA or the AMPA receptors; the activated 5-HT1A receptors have an inhibitory effect whereas activation of the 5-HT2 receptors enhance the induced behaviour.

Chronic, combined treatment with desipramine and mianserin: enhanced 5-HT1A receptor function and altered 5-HT1A/5-HT2 receptor interaction in rats.

A greater percentage of depressed patients respond to combined treatment with a tricyclic antidepressant and the tetracyclic antidepressant mianserin than to treatment with these drugs given alone. The functional sensitivity of the 5-hydroxytryptamine (5-HT)1A receptor, and the functional interaction between the 5-HT1A and the 5-HT2 receptors were investigated after treatment with desipramine and mianserin either alone or combined for 21-28 days. Pretreatment with desipramine and mianserin in combination induced the most intense 5-HT syndrome and the greatest fall in colonic temperature after injection of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT). The rats pretreated with desipramine alone had the largest elevation of the response temperature in the increasing temperature hot-plate test after injection of 8-OH-DPAT. After the combined pretreatment with desipramine and mianserin, no enhanced functional response in these tests was found when the 5-HT1A and the 5-HT2 receptors were stimulated simultaneously using 8-OH-DPAT and the 5-HT2 agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), contrasting the findings for desipramine or mianserin treatments given alone, where an increased functional response was found for the colonic temperature and the response temperature in the increasing temperature hot-plate test. In vitro receptor binding using [3H]-8-OH-DPAT as ligand revealed an increase in Kd and Bmax in the spinal cord after chronic treatment with the combination of desipramine and mianserin. In the hippocampus and the frontal cortex the changes were small.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduction of NMDA-induced behaviour after acute and chronic administration of desipramine in mice.

The mechanisms of the antinociceptive effect of desipramine (DMI) are only partly known. It is generally accepted that excitatory amino acids act as neurotransmitters in primary nociceptive fibres and recent in vitro studies have shown an interaction between tricyclic antidepressants and the N-methyl-D-aspartic acid (NMDA) receptor complex. In this study, the modulatory effect of DMI on the biting and scratching behaviour induced by intrathecal (i.th.) administration of NMDA (0.25 nmol) was investigated. Desipramine was administered acutely, either intrathecally (0.7-35 micrograms) or intraperitoneally (i.p., 10 mg/kg), or chronically in the drinking water (0.15 g/l) for 3 weeks. The NMDA-induced behaviour was significantly reduced both after acute and chronic administration of DMI. Several studies have shown a functional upregulation of the 5-HT1A receptor after chronic treatment with DMI. The activation of this receptor using the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), leads to a reduction in NMDA-induced behaviour. Using the 5-HT1A antagonist NAN-190 (10 micrograms, i.th.), the effect of chronic administration of DMI on the NMDA-induced behaviour was reversed. However, NAN-190 also increased NMDA-induced behaviour in the control group, suggesting that a tonic inhibition of this behaviour, mediated by the 5-HT1A receptor, may exist. These findings indicate that DMI may reduce glutaminergic transmission at the spinal NMDA receptor. As this receptor is central in spinal nociceptive transmission, this could be one mechanism for the antinociceptive effect of DMI.

The role of 5-HT1A and 5-HT1B receptors in spinal nociceptive transmission and in the modulation of NMDA induced behaviour.

The effects on nociception of intrathecal (i.th.) administration of selective 5-HT1A and 5-HT1B agonists were studied in rats. Nociception was evaluated using the tail-flick test with adjustments for tail-skin temperature, the increasing temperature hot-plate test and the scoring of biting and scratching behaviour after i.th. N-methyl-D-aspartate (NMDA). Activation of the spinal 5-HT1A receptor induced an antinociceptive effect in the increasing temperature hot-plate test and produced a dose dependent decrease in NMDA-receptor mediated behaviour. No significant change in nociception measured by either of the nociceptive tests was found after administration of the 5-HT1B agonist. These results support the hypothesis that spinal 5-HT1A receptor activation has an antinociceptive effect, and indicate a possible interaction between the serotonergic and glutaminergic transmitter systems.

[Diabetes mellitus in children under 2 years of age]. / Diabetes mellitus hos barn under to år.

We studied the clinical course in 18 children who were admitted to our department during the time period 1973-87 for onset of diabetes mellitus before two years of age. During these years a total number of 242 diabetics (0-14 years) were admitted from a population of approximately 100,000 children. The 18 cases showed a sex ratio (female/male) of 12/6. In nine cases the duration of symptoms before admittance to hospital was one week or less. The onset of the disease showed no particular seasonal pattern. 13 patients presented with a blood glucose of 25 mmol/l or more. Severe ketoacidosis was observed in nine patients. None of the patients exhibited any well-defined remission period. In the course of the disease, 11 patients had frequent hypoglycemic episodes, nine patients had convulsive attacks, poor metabolic control was evident in five cases, and major psychological problems were frequently encountered. In conclusion, diabetes mellitus in small children can be extremely difficult to manage, both from a medical and a psychosocial point of view. All efforts should be made to support the families of children with this disease.