Temporal patterns of self-injurious behavior correlate with stress hormone levels in the developmentally disabled.

While the origins and developmental course of self-injurious behavior (SIB) remain relatively unknown, recent studies suggest a biological imbalance may potentiate or provoke the contagious recurrence of SIB patterns in individuals with severe developmental disabilities (DD). Evidence from several laboratories indicates that functioning, relations, and processing of a stress-related molecule, proopiomelanocortin (POMC) may be perturbed among certain subgroups of individuals exhibiting SIB. The current investigation employed a unique time-pattern analysis program (THEME) to examine whether recurrent temporal patterns (T-patterns) of SIB were related to morning levels of two POMC-derived hormones: beta-endorphin (betaE) and adrenocorticotropic hormone (ACTH). THEME was used to quantify highly significant (non-random) T-patterns that included SIB within a dataset of in situ observational recordings spanning 8 days ( approximately 40 h) in 25 subjects with DD. Pearson's product-moment analyses revealed highly significant correlations between the percentage of T-patterns containing SIB and basal levels of both betaE and ACTH, which were not found with any other "control" T-patterns. These findings support the hypothesis that the recurrent temporal patterning of SIB represents a unique behavioral phenotype directly related to perturbed levels of POMC-derived stress hormones in certain individuals with severe DD.

Pharmacokinetics of lithium in rat brain regions by spectroscopic imaging.

Lithium (Li) and its salts have been demonstrated to be the most effective drug in both acute and prophylactic treatment of bipolar disorder. The exact molecular mechanisms and particular target regions accounting for its mood-stabilizing effect remain unknown. Knowledge of Li distribution and its regional pharmacokinetic properties in the living brain is of value in localizing its action in the brain. Pharmacokinetic measurements in different anatomical regions of the human brain are not yet available. Limited pharmacokinetic measurements in rat brain subvolumes have been performed using atomic absorption technique. However, a noninvasive way of estimating the pharmacokinetics in different regions of the brain where the drug exerts its beneficial effects would allow such methods to be used in the study of patients undergoing Li therapy. Earlier (7)Li MR studies on rat brain regions have provided preliminary pharmacokinetic information from the whole brain. Using (7)Li MR spectroscopic imaging (SI) technology, Li distribution in brain regions of the rat at therapeutic dosages has been recently demonstrated by us. Here we report feasibility of local pharmacokinetic measurements on brain regions obtained by magnetic resonance SI technology. Our results suggest that Li is most active in a region stretching from the anterior cingulate cortex and striatum to the caudal midbrain, with greatest activity including the preoptic area and hypothalamic region. Some activity was seen in prefrontal cortex, but only minimal amounts in the region of the cerebellum and metencephalic brainstem.

Localized 7Li MR spectroscopy: in vivo brain and serum concentrations in the rat.

The brain concentration of lithium (Li) in treated rats was measured using a recently developed method based on in vivo 7Li PRESS localized MRS. Comparison was made to the corresponding serum concentration at two treatment durations. The brain and serum Li concentrations were highly correlated with each other, more so than found previously for humans. The brain and serum Li concentrations also correlated with dose. Both the brain Li concentration and the serum concentration at 16.1 days of treatment correlated with the corresponding measure at 6.6 days. After correction of the brain Li concentrations for reduced 7Li MRS visibility, the mean brain/serum Li ratio for rats was close to unity, unlike most previous values found for humans. However, in some individual cases the ratio deviated substantially from the mean, suggesting that serum Li is not always a reliable indicator of brain Li.

Very mild stress of pregnant rats reduces volume and cell number in nucleus accumbens of adult offspring: some parallels to schizophrenia.

Pregnant rats subjected to very mild stress give birth to pups who, when examined as adults, exhibited behavioral and anatomical anomalies that resemble some aspects of schizophrenia. The nucleus accumbens (NAcc) is reduced in volume by 20.7 +/- 3.4% (p = 0.003) in pups born to mothers who were stressed during pregnancy by injections of either saline or amphetamine in saline. The total number of cells is decreased in proportion to the reduction in volume, so the volume cell density of the NAcc is not changed with treatment. The affected volume is localized in the ventral rostral area of the NAcc. Both males and females are affected, but males are slightly more sensitive to the challenge to the mother. Rats born to mothers stressed in mid-pregnancy appear to provide useful parallels to the fetal developmental hypothesis of schizophrenia and to the brain abnormalities seen in this disease.

Increased temporal patterns in choice responding and altered cognitive processes in schizophrenia and mania.

RATIONALE: The THEME method for measuring time-determined patterns (T-patterns) in behavior has been suggested as a new, more objective method for assessing cognitive disturbances in schizophrenia. OBJECTIVES: THEME was used to compare responses of schizophrenic patients with those having mood, schizoaffective, or severe anxiety disorders, and with healthy control subjects. METHODS: A two-choice, button-pressing task was used to elicit T-patterns among responses, with knowledge-of-results (K) rewards and coin reinforcements (RF) as reinforcers. Subjects were compared by diagnosis, drug treatment, and gender. RESULTS: Schizophrenic and manic patients showed excessive numbers of, and more complex T-patterns than controls. Schizophrenic and manic patients frequently demonstrated repetitive (stereotyped) responding, an effect never seen in healthy controls. Although clozapine (CLZ) reduced both excessive T-pattern structure and stereotyped responding, it also reduced growth of responding to the coin RF. CONCLUSIONS: Significant T-pattern increases may represent a common, time-related symptom of schizophrenia and mania. CLZ's effect on T-pattern production suggests that receptor effects other than the DAD(2) antagonism of "typical" neuroleptics' may be relevant to these findings.