Wagner H. Bridger

Spontaneous alternation behavior : an animal model for obsessive-compulsive disorder ?

This study entailed the adoption of a well-established behavioral paradigm, spontaneous alternation, as a possible animal model for some of the symptoms observed in obsessive-compulsive disorder (OCD) in humans. Food-deprived rats were run in a T-maze in which both a black and a white goal box were equally baited with a small amount of chocolate milk. Each rat was given 7 trials every other day during which it was placed in the start box and allowed to make a choice. The mean number of choices until an alternation occurred was recorded. After a stable baseline of spontaneous alternation was achieved the effects of manipulating the serotonergic system were tested. Both the nonselective 5-HT agonist 5-MeODMT (1.25 mg/kg) and the more selective 5-HT1A agonist 8-OH-DPAT (2 mg/kg) disrupted spontaneous alternation. A course of chronic treatment (2 x 5 mg/kg for 21 days) with the selective 5-HT uptake blocking agent fluoxetine had a protective effect on the 5-MeODMT-induced disruption of spontaneous alternation behavior. Serotonergic manipulations of spontaneous alternation may be a simple animal model for the perseverative symptoms or indecisiveness seen in people diagnosed with OCD.

Neuroendocrine responses to challenge with dl-fenfluramine and aggression in disruptive behavior disorders of children and adolescents

Prolactin (PRL) and cortisol (CORT) responses to a single oral administration (1.0 mg/kg) of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated prepubertal and adolescent males with disruptive behavior disorders (DBD). Neuroendocrine responses were correlated with scores on aggression rating scales in prepubertal and adolescent DBD patients and compared with those of matched adolescent normal control subjects. Net dl-fenfluramine-induced PRL and CORT release was not correlated with aggression rating scores in prepubertal and adolescent DBD patients and did not differ significantly between adolescent DBD patients and normal control subjects. Although the present study does not demonstrate a serotonergic abnormality in aggression or DBD, this may be more a reflection of limitations of the neuroendocrine challenge test procedures or the methods used than evidence that serotonergic function in the central nervous system is normal in aggression.

Reduction of (3H)-imipramine binding sites on platelets of conduct-disordered children.

Binding characteristics of tritiated imipramine on blood platelets were determined in daytime hospitalized prepubertal children who had mixed diagnoses of conduct disorder (CD) plus attention deficit disorder hyperactivity (ADDH) and in inpatient adolescents who had a history of aggressive behavior. The number of (3H)-imipramine maximal binding sites (Bmax) was significantly lower in the prepubertal patient group of CD plus ADDH; the dissociation constant (Kd) was not significantly different. There were significant negative correlations between Bmax and the Externalizing or Aggressive factors of the Child Behavior Checklist when the CD plus ADDH prepubertal patients were combined with their matched controls and within the adolescent inpatient group. We propose that a decreased platelet imipramine binding Bmax value, as an index of disturbed presynaptic serotonergic activity, is not specific to depression and may be used as a biologic marker for the lack of behavioral constraint in heterogeneous. populations of psychiatric patients.

Platelet imipramine binding and serotonin uptake in obsessive-compulsive patients.

Platelet imipramine binding was measured in 16 drug‐free nondepressed patients (aged 20‐61 years, mean ± SD 35 ± 8) suffering from obsessive‐compulsive disorder (OCD) and in 16 sex‐, race‐ and age‐matched healthy controls. Imipramine binding capacity and affinity were not different in the 2 groups. Platelet serotonin (5‐HT) uptake capacity, Vmax, was also measured in 15 of these patients and their matched controls. Vmax was significantly higher in the patients (309 ± 149 pmol/109 cells/min) than in the controls (181 ± 110). An increase in platelet 5‐HT uptake supports the involvement of 5‐HT in OCD and may suggest that a hyperactive serotonergic system is present in this disorder.

Elevated Platelet MAO is Related to Impulsivity in Disruptive Behavior Disorders

Platelet monoamine oxidase (MAO) activity was measured in 32 drug-free prepubertal boys with externalizing symptoms of disruptive behavior disorders and 47 boys with no DSM-III-R diagnoses, and correlated to questionnaire and laboratory performance measures of impulsivity. A subgroup of boys with high MAO activity exhibited significantly poorer performance (i.e., more impulsivity) than a subgroup of low MAO activity on laboratory tasks requiring response inhibition. High MAO patients were more impulsive than high MAO controls on some performance tasks and elevated platelet MAO was unrelated to personality questionnaire measures of impulsivity or to patient status. These data suggest that biological markers such as MAO activity may correlate better with performance than clinical questionnaire measures. Abnormally high platelet MAO activity may not be sufficient to produce externalizing symptoms in children, perhaps interacting with an underlying behavioral dimension of impulsivity.

Platelet 3H-imipramine binding, serotonin uptake, and plasma α1 acid glycoprotein in disruptive behavior disorders ☆ ☆☆

Tritiated imipramine labels with high affinity a recognition site associated with the serotonergic transporter in blood piatelets (Langer and Galzin 1988). Concomitant measurement of platelet 3Himipramine binding (IB) and 3H-5-hydroxytryptamine (5-HT) uptake in various diseases does not usually reveal parallel changes in these parameters. De~ eased platelet 5-HT uptake without accompanying changes in platelet IB has been observed in depression or schizophrenia (Wood et al 1983), panic disorder (Pecknold and Suranyi-Cadotte 1986), alcoholic cirrhosis (Ahtee et al 198 ! ), hypertension (Kamal et al 1984), Alzheimcrs dis~a~ (Suranyi-Cadotte et al 1985), and Parkinsons disease (Suranyi-Cadotte et al 1985). Decreased platelet IB but no corresponding changes in platelet 5-HT uptake has been found in depressed women (Roy et al 1987) and adolescents with obsessive--compulsive disorder (Weizman et al 1986a), anore,da nervosa

Amino Acid Levels in Elderly Nursing Home Residents

We have compared levels of albumin and serum amino acids in a group of 87 recent admissions to a nursing home, average age 83 years, with a group of healthy moderately old subjects, average age 69 years. We found that the nursing home group was characterized by decreased levels of albumin, by increased total levels of the measured amino acids, and by increased levels of the nonessential amino acids. In contrast, there were no significant group differences in the essential amino acids. Among the nursing home patients, there was a negative correlation between essential amino acids and disability, consistent with nutritional deficits in the more disabled patients, and a positive correlation between essential amino acids and subjective complaints of pain, suggesting that pain is associated with breakdown or mobilization of endogenous protein stores. Though the nursing home patients had decreased serum levels of tryptophan, there was no association between serum tryptophan or other variables that could be related to the availability of tryptophan for transport into brain, with ratings of either depression or pain. Glutamine levels were significantly increased in the nursing home residents, and among these patients they were positively correlated with measures of cognitive impairment. (J Geriatr Psychiatry Neurol 1989;2:215-222).

Undivided publication of research findings: A uniform editorial policy of the consortium of editors of journals relating to human development and psychopathology

Effective research on development and psychopathology requires consideration of a broad range of important variables, and responsible reporting of research results demands a thoughtful presentation and integration of the complete interrelations among critical variables. The division of small amounts of data into numerous publications, submitted to many different journals, defeats the central aims of integrated and thoughtful scholarship. Furthermore, the repetitive reporting of data that accumulate as a sample size enlarge, even when the data are difficult to obtain or slow to collect, leads to fragmentation of the scientific literature. We believe it is important to discourage these practices. A consortium of journal editors, which publishes manuscripts on development and psychopathology organized under the auspices of the National Institute of Mental Health, has adopted the following principles:

The role of serotonin in compulsive behavior: an animal model

Abstract This report presents a possible animal model for compulsive disorders in humans, based on the principles of spontaneous alternation in rats. Challenge with a serotonin agonist disrupted spontaneous alternation, whereas a chronic course of treatment with a selective serotonin reuptake inhibitor prevented such a deficit.