Neuropeptide Therapies in Chronic Schizophrenia: TRH and Vasopressin Administration

Abstract

Twenty-three chronic undifferentiated schizophrenics, 13 women and 10 men, aged 37-64 years with 15-to 40-year histories of the disease were given either thyrotropin-releasing hormone (TRH) (10 subjects) or DDAVP (13 subjects) with the aim to improve the negative symptoms of the disease and memory. TRH (600 µg i.v.) and DDAVP (4 µg i.m.) were administered every other day for 30 days. Negative symptoms were monitored by the Andreasen rating scale and by the Honingfeld NOSIE rating scale, memory by the Folstein ‘Mini mental State’ rating scale and by the Luria-Nebraska rating scale before therapy and then at days 15, 16, 30 and 31 of treatment. Both therapies significantly improved negative symptoms. Memory was significantly improved in all the patients treated with TRH and in 9 of the 13 patients treated with DDAVP, who presented less severe cognitive impairments. A peripheral mechanism of action of DDAVP was excluded by the observation that plasma electrolytes and osmolality, blood pressure, ECG patterns, 24-hour urine volume and specific gravity, basal plasma cortisol and growth hormone levels and weight of the patients were unchanged during therapy. TRH treatment induced a transient borderline hyperthyroidism at day 15 and a progressive decrease of the thyrotropin response to TRH stimulation. A common mechanism of action of the two peptides on the central noradrenergic system is suggested.

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

“…These data confirm those obtained in a previous open study [Brambilla et al, 1986] and thus exclude that the improvement of negative symptoms and memory after DDAVP therapy is due to a placebo effect.…”

“…Repeatedly administered in combi nation with neuroleptics, DDAVP induced improve ment of negative symptoms and memory, with no mod ifications of thought disorders [Brambilla et al, 1986]. Since the improvement occurred in the absence of cardiocirculatory effects and of electrolyte-fluid balance al terations, we suggested that the peptide was acting cen trally and not through activation of peripheral mecha nisms, as had been proposed previously [Koob et al" 1981;Le Moal et al, 1984;Lebrun et al, 1985], The possible mechanism of action of DDAVP of inducing a general psychological arousal, however, was not evi denced in our study.…”

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].…”

“…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.…”