Vasopressin (DDAVP) Therapy in Chronic Schizophrenia: Effects on Negative Symptoms and Memory

Abstract

Ten chronic undifferentiated schizophrenics, 6 men and 4 women, aged 28–63, with 6- to 31-year histories of the disease were given DDAVP to observe the effects of this neuropeptide on the prevalent negative symptoms of their illness. Patients were maintained on neuroleptic therapy and first given a 20-day course of placebo followed by 20 days of DDAVP i.m., 4 µg. Andreasen Scale for assessment of negative symptoms, the Brief Psychiatric Rating Scale, the NOSIE Rating Scale and the Luria-Nebraska Rating Scale were administered to monitor negative symptomatology, behavior and memory before the study began, after placebo and after DDAVP administration. Patients were also given a growth hormone-clonidine test and in addition plasma basal concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were measured at the same intervals. DDAVP therapy induced a significant improvement of negative symptomatology and a trend toward improvement of short- to medium-term memory. No changes in homovanillic acid, MHPG, 5-HIAA and DOPAC, nor of growth hormone response to clonidine stimulation were observed.

Influence of Desglycinamide-(Arg⁸) Vasopressin on Memory in Healthy Subjects

“…Semantic recognition was not im proved and there was no effect on nonspecific arousal as assessed by visual reaction time [Millar et al, 1987], In schizophrenic patients. DDAVP improved short to me dium memory with no parallel increase in attention [Brambilla et al, 1988], The significant improvement of memory by DGAVP in the present study without effects on vigilance is con tradictory to a recent observation on arginine vasopres sin, which increased vigilance without effects on mem ory in student volunteers [Fehm-Wolfdorf et al, 1988]. Thus, the analogue DGAVP may have a profile of action that differs from the physiological substance in man.…”

Social Interaction Deficits Caused by Chronic Phencyclidine Administration are Reversed by Oxytocin

“…A post-mortem study of tissue AVP concentrations found decreased AVP amounts in the temporal lobe of schizophrenic brain tissue, but the hypothalamic content was not different from controls (Frederiksen et al, 1991). AVP analogues have been shown to be effective adjunctive treatments of schizophrenic symptoms, particularly negative spectrum symptoms (Brambilla et al, 1986(Brambilla et al, , 1989Iager et al, 1986), and poorly controlled trials reporting psychotic symptom improvement after OT administration also exist (Bujanow, 1974).…”

Differential sensitivity of the Brattleboro rat to glutamatergic and dopaminergic perturbation

“…DDAVP, a synthetic VP agonist, produced improvements in negative symptom profiles in schizophrenia patients [24,[27][28][29][30]. However, DDAVP did not improve cognitive performance in humans with amnesia [31].…”

“…VP is also involved in behavioral outcomes important in the etiology of schizophrenia such as learning and memory, aggression, and sociality [23]. In addition, both glutamate and VP antagonism have been associated with negative symptoms of schizophrenia, suggesting a potential interaction between glutamate and VP signaling in the brain [24][25][26]. Moreover, there is evidence that VP activity in the hypothalamus may be regulated by glutamatergic signaling [22].…”

“…Furthermore, VP is critically important in social recognition, social communication, and aggression in other mammalian species suggesting good translatability to human populations [34]. Although VP and its analogs can improve social performance in humans, it results in peripheral side effects associated with anti-diuretic effects as well as an increased activation of the HPA axis and the resulting stress response [24,30,35]. Therefore, direct activation of VP signaling is limited as a treatment for schizophrenia.…”