Serotonin transporter linked promoter (polymorphism) in the serotonin transporter gene may be associated with antidepressant-induced mania in bipolar disorder

Masoliver, E.; Menoyo, A.; Pérez, Ví­ctor; Volpini, Vı́ctor; Rio, Elisabet Del; Perez, Josefina; Álvarez, Enric; Baiget, M.

doi:10.1097/01.ypg.0000180684.26288.d7

Cited by 51 publications

(37 citation statements)

References 19 publications

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“…We found a marginally significant difference in genotype (see Table 2) and allele (P = 0.04, data not shown) distribution according to diagnosis; a recent meta-analysis showed a small but significant effect of SERPR genotype on the diagnosis of bipolar disorder Mansour et al, 2005;Meira-Lima et al, 2005;Masoliver et al, 2006); furthermore, there is wide knowledge of a bigger genetic influence on the occurrence of bipolar disorder when compared with major depression (Smeraldi et al, 1977;Tsuang and Faraone, 1990;Merikangas and Swendsen, 1997;Moldin, 1997;Reus and Freimer, 1997;Sullivan et al, 2000). Post-hoc analyses made according to diagnosis, however, did not detect any difference nor did adding diagnosis as a covariate in analyses.…”

Section: Discussionmentioning

confidence: 81%

Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants

Smeraldi

Serretti

Artioli

et al. 2006

Psychiatric Genetics

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A functional insertion/deletion (*l/*s) repeat polymorphism within the promoter region of the serotonin transporter (5-HTTLPR) has been described. An association between *l variant and a better and faster response to serotonin selective reuptake inhibitors in depressed patients was reported in Caucasians. The value of the explained variance due to the 5-HTTLPR, however, was 7% only, and different *l and *s variants were reported according to the nucleotide sequence of repeats. In this study, we investigated the antidepressant response to fluvoxamine in individuals carrying different *l and *s variants according to the Nakamura findings. Two hundred and twenty-eight patients affected by bipolar disorder and major depression were administered a daily dose of fluvoxamine up to 300 mg and evaluated at baseline and weekly thereafter until week 7, using the 21-item Hamilton Rating Scale for Depression. We found a marginally significant difference in genotype and allele (P=0.04, data not shown) distribution (*l and *s traditional variants) according to diagnosis (bipolar disorder vs. major depression). We confirmed a better and faster response in our depressed patients bearing the *l variant, but we also found significant differences in response among *l carriers according to the type of *l allele. In fact, 16F *l carriers showed only a partial response, while 16D *l carriers showed a marginally significantly better response than 16A *l allele carriers. These results, although very preliminary, can represent a further step toward a better understanding of the molecular genetics of antidepressant response.

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Section: Discussionmentioning

confidence: 81%

Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants

Smeraldi

Serretti

Artioli

et al. 2006

Psychiatric Genetics

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“…Adolescents who have not manifested the manic component of a bipolar disorder may be particularly vulnerable to SSRI antidepressant-induced mania or hypomania (Frye et al, 2009). Although preliminary studies showed conflicting results regarding the association between 5-HTTLPR polymorphism and antidepressant-induced mania (Mundo et al, 2001; Rousseva et al, 2003; Serretti et al, 2004; Baumer et al, 2006; Masoliver et al, 2006; Ferreira Ade et al, 2009), a recent meta-analysis indicated a higher incidence of antidepressant-induced mania in patients with the “s” variant of 5-HTTLPR (Daray et al, 2010). Likelihood of SSRI monotherapy response is deemed low once failure of the “SSRI challenge” test has been observed in this category.…”

Section: Untoward Effects Of “Ssri Challenge”mentioning

confidence: 99%

A Neurobiological Hypothesis of Treatment-Resistant Depression â€“ Mechanisms for Selective Serotonin Reuptake Inhibitor Non-Efficacy

Coplan

Gopinath

Abdallah

et al. 2014

Front. Behav. Neurosci.

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First-line treatment of major depression includes administration of a selective serotonin reuptake inhibitor (SSRI), yet studies suggest that remission rates following two trials of an SSRI are <50%. The authors examine the putative biological substrates underlying “treatment resistant depression (TRD)” with the goal of elucidating novel rationales to treat TRD. We look at relevant articles from the preclinical and clinical literature combined with clinical exposure to TRD patients. A major focus was to outline pathophysiological mechanisms whereby the serotonin system becomes impervious to the desired enhancement of serotonin neurotransmission by SSRIs. A complementary focus was to dissect neurotransmitter systems, which serve to inhibit the dorsal raphe. We propose, based on a body of translational studies, TRD may not represent a simple serotonin deficit state but rather an excess of midbrain peri-raphe serotonin and subsequent deficit at key fronto-limbic projection sites, with ultimate compromise in serotonin-mediated neuroplasticity. Glutamate, serotonin, noradrenaline, and histamine are activated by stress and exert an inhibitory effect on serotonin outflow, in part by “flooding” 5-HT1A autoreceptors by serotonin itself. Certain factors putatively exacerbate this scenario – presence of the short arm of the serotonin transporter gene, early-life adversity and comorbid bipolar disorder – each of which has been associated with SSRI-treatment resistance. By utilizing an incremental approach, we provide a system for treating the TRD patient based on a strategy of rescuing serotonin neurotransmission from a state of SSRI-induced dorsal raphe stasis. This calls for “stacked” interventions, with an SSRI base, targeting, if necessary, the glutamatergic, serotonergic, noradrenergic, and histaminergic systems, thereby successively eliminating the inhibitory effects each are capable of exerting on serotonin neurons. Future studies are recommended to test this biologically based approach for treatment of TRD.

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“…166,167 After testing candidate drugs at the preclinical level, PET with 11 C-labeled AA and DHA could be used to study the metabolism of these polyunsaturated fatty acids in bipolar disorder patients and to proxy the effectiveness of candidate drugs in healthy humans. [72][73][74] Furthermore, drugs or conditions known to induce mania in susceptible individuals 171 could be studied using 11 C-labeled AA and PET. Because antidepressants can induce switching to mania when given to a depressed bipolar disorder patient, 146,[172][173][174] we examined the selective serotonin reuptake inhibitor fluoxetine in our models.…”

Section: Observations Related To Aa In Bipolar Disorder Patientsmentioning

confidence: 99%

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

et al. 2008

Mol Psychiatry

109

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Bipolar disorder is a major medical, social and economic burden worldwide. However, the mechanisms of action of effective antibipolar disorder drugs remain elusive. In this paper, we review studies using a neuropharmacological approach in unanesthetized rats, combined with kinetic, biochemical and molecular biology techniques, showing that chronic administration of three Food and Drug Administration-approved mood stabilizers (lithium, valproate and carbamazepine) at therapeutically relevant doses, selectively target the brain arachidonic acid (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding activity of activator protein-2 and in turn the transcription, translation and activity of its AA-selective calcium-dependent phospholipase A 2 gene product, valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA synthetase. The net overlapping effects of the three drugs are decreased turnover of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased brain cyclooxygenase-2 and prostaglandin E 2 . Although these observations support the hypothesis proposed by Rapoport and colleagues that the AA cascade is a common target of mood stabilizers, this hypothesis is not necessarily exclusive of other targets. Targeting the AA cascade with drugs or diet may be a useful therapeutic approach in bipolar disorder, and examining the AA cascade in patients might help in better understanding the disease.

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Serotonin transporter linked promoter (polymorphism) in the serotonin transporter gene may be associated with antidepressant-induced mania in bipolar disorder

Cited by 51 publications

References 19 publications

Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants

Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants

A Neurobiological Hypothesis of Treatment-Resistant Depression â€“ Mechanisms for Selective Serotonin Reuptake Inhibitor Non-Efficacy

Mode of action of mood stabilizers: is the arachidonic acid cascade a common target?

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