Rita A. Shaughnessy

Relatives of unipolar and bipolar patients have normal pursuit.

Impaired smooth pursuit eye movements are significantly less prevalent among the first-degree relatives of patients who have major affective disorders than among the first-degree relatives of schizophrenics. The distribution of normal and abnormal smooth pursuit among the relatives of unipolar and bipolar patients does not differ from that of normal individuals having no family history of major psychosis. Smooth pursuit impairment is thus specific to relatives of schizophrenic patients and is not characteristic of relatives of patients with major affective disorders.

Genetic control of platelet monoamine oxidase activity: Studies on normal families

Abstract Some groups of psychiatric patients differ from normal individuals with respect to mean platelet monoamine oxidase (MAO) activity. Twin studies indicate that genetic factors contribute to the considerable interindividual variability in the activity of this enzyme. To evaluate the degree of genetic control, we measured platelet MAO activity in 255 normal adult members of 112 families. Between-family variance was significantly greater than within-family variance, as would be expected. Parent-offspring and sibling-sibling correlations indicated that genetic factors control platelet MAO activity to a substantial extent.

Reduced platelet MAO activity and vulnerability to psychiatric disorders

Platelet monoamine oxidase (MAO) is a genetically controlled mitochondrial enzyme that metabolizes amines in the brain by deamination. We investigated the relationship between MAO activity and the presence or absence of psychopathology by determining MAO activity and the psychiatric diagnosis in 61 first-degree relatives of 31 patients with bipolar (manic-depressive) illness. Relatives who themselves were diagnosed as having bipolar I illness or alcoholism had a significantly lower mean MAO activity level than did other relatives or 255 normal individuals. These findings indicate that a relationship exists within pedigrees between MAO activity and psychiatric disorders. Reduced MAO activity may play a role in vulnerability to some types of psychopathology.

Double-Blind, Placebo-Controlled, Multicenter Trial of a Vasopressin V2-Receptor Antagonist in Patients with Schizophrenia and Hyponatremia

OBJECTIVES Hyponatremia (serum sodium [Na+] concentration <136 mmol/L) is a prevalent and potentially life-threatening medical comorbidity for schizophrenic patients. No definitive pharmacological treatments have been established. Tolvaptan (OPC-41061), an oral non-peptide V2-receptor antagonist, was recently shown to correct hyponatremia in a diverse population of 448 hyponatremic patients. Efficacy in a sub-set of 19 schizophrenic patients with idiopathic hyponatremia included in that sample is specifically examined. METHODS Nineteen subjects were randomly assigned to receive placebo (n = 12) or tolvaptan (n = 7) once daily for 30 days. Dosage adjustment was based on serum Na+ changes, initially 15 mg, titratable to 30 or 60 mg. The average daily area under the curve (AUC) changes in serum Na+ from baseline to Day 4 and Day 30 were co-primary end points. RESULTS Increases in serum Na+ concentrations were significantly greater with tolvaptan than placebo at Day 4 (p = .0055) and at Day 30 (p < .0001). Two subjects receiving tolvaptan (28.6%) became dehydrated and experienced hypotension, and five subjects receiving placebo (41.7%) experienced symptoms associated with dilutional hyponatremia. CONCLUSIONS These results suggest that tolvaptan effectively normalizes idiopathic hyponatremia in schizophrenic patients. Clinicians are advised to carefully monitor fluid status especially at the beginning of treatment to prevent dehydration.

Variability among brain regions in the specificity of 6-hydroxydopamine (6-OHDA)-induced lesions

6-Hydroxydopamine (6-OHDA; 200 μg, 150 μg or 110 μg) or vehicle was infused stereotaxically into the lateral ventricles of rats, usually following pretreatment with desmethylimipramine (DMI). Various brain regions were then assayed for dopamine (DA), serotonin (5-HT) and norepinephrine (NE). As expected, 6-OHDA depleted DA in all brain regions examined. Unexpectedly, however, the two highest doses of 6-OHDA significantly decreased 5-HT levels in the hippocampus and increased 5-HT levels in the striatum. In addition, despite pretreatment with doses of DMI commonly considered adequate to block 6-OHDA-induced depletion of NE, all doses of 6-OHDA tested significantly reduced NE levels in the hippocampus, hypothalamus and septum. We interpret our data as suggesting that some brain regions are susceptible to nonspecific toxic effects of 6-OHDA at doses commonly employed. Furthermore, these nonspecific effects may or may not occur, depending on seemingly minor variations in experimental technique.

Effects of caffeine and PD 116,600 on the differential-reinforcement-of-low rate 72-S (DRL 72-S) schedule of reinforcement.

Caffeine and PD 116,600 were found to decrease the reinforcement rate and increase the response rate in rats performing under a differential-reinforcement-of-low rate 72-s (DRL 72-s) schedule of reinforcement. In contrast, antidepressant drugs previously have been found to increase the reinforcement and decrease the response rate. Caffeine has been found to test similar to antidepressant drugs on at least one other behavioral screen, but caffeine does not possess clinical antidepressant properties. These results provide further support for the DRL 72-s schedule as a behavioral screen for antidepressant drugs.

Personality correlates of platelet monoamine oxidase activity and red cell lithium transport

Platelet monoamine oxidase (MAO) activity and the ratio of red cell to plasma lithium concentrations (Li ratio) may be important in the pathophysiology of, and genetic vulnerability to, some psychiatric disorders. By using the Clinical Analysis Questionnaire, we assessed personality correlates of MAO activity and the Li ratio in vitro in a sample of psychiatrically normal adult women. We found that there were correlates of each variable, and a unique constellation of personality traits when the two variables were considered simultaneously.

Tolvaptan: a new tool for the effective treatment of hyponatremia in psychotic disorders

Importance of the field: Hyponatremia (serum sodium concentration < 136 mEq/liter) is a common and potentially life-threatening medical comorbidity seen in patients with psychotic disorders. Tolvaptan, a selective antagonist of the V2-receptor, is FDA-approved for the treatment of clinically significant hypervolemic and euvolemic hyponatremia. This represents a major development in the care of psychotic individuals with hyponatremia. Areas covered in the review: This review provides an overview of the existing literature on prevalence rates and risk factors associated with hyponatremia in psychotic patients (1923 – present). Tolvaptan is discussed as a potential advance in the treatment of hyponatremia in patients with psychotic disorders, and preliminary data are reviewed. What the reader will gain: The reader will gain an appreciation of the prevalence of hyponatremia among psychotic individuals, an understanding of the distinctions between acute and chronic hyponatremia in this population, and awareness that effective treatments are becoming available. Take home message: A modest literature exists regarding prevalence rates and risk factors associated with hyponatremia in psychotic populations. Hyponatremia is common and serious enough to merit clinical concern. Perhaps, now that tolvaptan has been FDA-approved, progress will accelerate and new insights will develop that begin to bring relief from this medical comorbidity among psychotic patients.

Psychomotor Deficits Associated With Hyponatremia: A Retrospective Analysis

Hyponatremia (serum sodium concentration [Na+] < 136 mEq/L) is a potentially life-threatening condition. Recent evidence (Renneboog, Musch, Vandemergel, Manto, & Decaux, 2006) shows that even mild hyponatremia is associated with disorders of balance/gait. This retrospective analysis explored the influence of serum [Na+] on neuropsychological (NP) measurements at baseline from 44 patients with chronic hyponatremia who participated in an efficacy and safety study of an experimental compound over a decade ago. Group mean serum [Na+] was 124.8 ± 4.9 mEq/L. Age-adjusted partial correlations were computed between serum [Na+] and NP measurements, 39% of which were statistically significant—all involving psychomotor functioning. These findings replicate and extend previous observations that psychomotor deficits are, at least in part, associated with hyponatremia in these patients. While chronic hyponatremia is known to have deleterious effects on quality of life, motor and gait disturbances represent manifestations of mild hyponatremia that have until now gone unrecognized. A new class of medication, vasopressin antagonists, has been shown to correct hyponatremia. It will be important to explore the effects of correcting hyponatremia on psychomotor functioning in individuals with hyponatremia.

Early intervention with second-generation antipsychotics in first-episode psychosis: results of an 8-week naturalistic study.

Objective: The objective was to compare short‐term effectiveness of aripiprazole with three other second‐generation antipsychotics (SGAs) in the treatment of first‐episode psychosis.