Melatonin as a treatment for mood disorders: a systematic review.

OBJECTIVE: Melatonin has been widely studied in the treatment of sleep disorders and evidence is accumulating on a possible role for melatonin influencing mood. Our aim was to determine the efficacy and acceptability of melatonin for mood disorders. METHOD: We conducted a comprehensive systematic review of randomized clinical trials on patients with mood disorders, comparing melatonin to placebo. RESULTS: Eight clinical trials were included; one study in bipolar, three in unipolar depression and four in seasonal affective disorder. We have only a small study on patients with bipolar disorder, while we have more studies testing melatonin as an augmentation strategy for depressive episodes in major depressive disorder and seasonal affective disorder. The acceptability and tolerability were good. We analyzed data from three trials on depressive episodes and found that the evidence for an effect of melatonin in improving mood symptoms is not significant (SMD = 0.37; 95% CI [-0.05, 0.37]; P = 0.09). The small sample size and the differences in methodology of the trials suggest that our results are based on data deriving from investigations occurring early in this field of study. CONCLUSION: There is no evidence for an effect of melatonin on mood disorders, but the results are not conclusive and justify further research.

SSRI treatment decreases prolactin and hyperthermic responses to mCPP.

We studied the effect of 3 weeks treatment with the selective serotonin re-uptake inhibitor (SSRI), paroxetine (30 mg daily), on the neuroendocrine and hyperthermic responses to the 5-HT2C receptor agonist, m-chlorophenylpiperazine (mCPP) (0.05 mg/kg i.v.), in seven healthy volunteers. Following paroxetine treatment, both the prolactin and hyperthermic responses to mCPP were significantly attenuated. These data are consistent with experimental animal studies indicating that repeated SSRI treatment leads to a functional desensitisation of 5-HT2C receptors. This effect may be linked to the anxiolytic properties of SSRIs.

Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors.

We measured the cortisol response to the 5-HT precursor, 5-hydroxytryptophan, (5-HTP) in seven patients with major depression before and after 8 weeks treatment with the tricyclic antidepressant, clomipramine. The cortisol response to 5-HTP was significantly increased following clomipramine treatment, suggesting that clomipramine, like selective serotonin re-uptake inhibitors (SSRIs), enhances this 5-HT2 receptor mediated response. Because other tricyclic antidepressants do not increase 5-HTP-mediated cortisol release, it seems unlikely that enhancement of 5-HT2 receptor function is a critical mechanism for antidepressant action. However, facilitation of neurotransmission at 5-HT2 receptors could account for the efficacy of clomipramine and SSRIs in the treatment of obsessive compulsive disorder and also for their liability to cause orgasmic dysfunction.

Serotonin transporter (5-HTT) promoter genotype may influence the prolactin response to clomipramine.

RATIONALE: A 44-base-pair insertion/deletion polymorphism in the promoter region of the human serotonin (5-HT) transporter (5-HTT) gene gives rise to a bi-allelic polymorphism designated long (l) and short (s). The s variant is associated with a lower expression of 5-HTT sites and a reduced efficiency of 5-HT reuptake. OBJECTIVE: The aim of the present study was to determine whether the increase in brain 5-HT function produced by acute 5-HT reuptake blockade is influenced by the 5-HTT promoter l/s polymorphism. METHODS: We measured the increase in plasma prolactin that follows acute administration of the tricyclic antidepressant clomipramine as an index of 5-HT neurotransmission in 14 healthy female subjects (7 with ss genotype and 7 with ll genotype) using a placebo-controlled crossover design. RESULTS: Clomipramine-induced prolactin release was significantly greater in subjects with the ll genotype. CONCLUSION: Our findings suggest that acute 5-HT reuptake blockade produces a greater increase in 5-HT neurotransmission in subjects with the ll genotype than in those with an ss genotype. These results are consistent with clinical data indicating that subjects with an ss genotype may have a poorer therapeutic response to selective serotonin reuptake inhibitor (SSRI) monotherapy.

If Schizophrenia is enantiomorphism, is light the morphogen?

Schizophrenia remains an enigmatic condition. It would appear that both genetic and environmental influences are relevant to the aetiopathogenesis of the disorder. Although a great amount of research has been carried out concerning the condition, the results have often lead to further questions and attempts to more closely delineate the object of study have lead to the originally observed findings becoming tenuous. One way to objectively view some aspects of this large body of work is to consider the condition as a cerebral situs inversus, as data from various lines of reasoning have suggested an inversion of the situation seen in normal controls. The hypothesis presented here draws on existing biological evidence to argue the likely role of light as a relevant, stimulatory variable which may interact with asymmetrical cerebral maturation in the establishment of functional laterality.

Pathophysiology of 'positive' thought disorder in schizophrenia.

BACKGROUND: Formal thought disorder is a characteristic feature of psychosis, but little is known of its pathophysiology. We have investigated this in schizophrenia using positron emission tomography (PET). METHOD: Regional cerebral blood flow was measured using H2(15)O and PET while six people with schizophrenia were describing a series of 12 ambiguous pictures which elicited different degrees of thought-disordered speech. In a within-subject design, the severity of 'positive' thought disorder was correlated with cerebral blood flow across the 12 scans in each subject. RESULTS: Verbal disorganisation (positive thought disorder) was inversely correlated with activity in the inferior frontal, cingulate and left superior temporal cortex, and positively correlated with activity in the parahippocampal/anterior fusiform region bilaterally, and in the body of the right caudate (P < 0.001). The total amount of speech produced (independent of thought disorder) was positively correlated with activity in the left inferior frontal and left superior temporal cortex. CONCLUSIONS: The severity of positive thought disorder was inversely correlated with activity in areas implicated in the regulation and monitoring of speech production. Reduced activity in these regions may contribute to the articulation of the linguistic anomalies that characterise positive thought disorder. The positive correlations between positive thought disorder and parahippocampal/anterior fusiform activity may reflect this region's role in the processing of linguistic anomalies.