The serotonin-N-acetylserotonin–melatonin pathway as a biomarker for autism spectrum disorders

Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35–46%) of patients), as well as the deficit in melatonin (51% (45–57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41–54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS–melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS–melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD

Antibiomania : penser au syndrome maniaque secondaire à une antibiothérapie

International audienceIntroductionAntibiomania is characterized by the emergence of a manic episode in reaction to antibiotics. Although relatively uncommon, this kind of side effect is observed in a growing number of cases and mostly occurs in patients who do not have a history of bipolar disorder. Several dozen cases have been reported showing the onset of manic symptoms after taking antibiotics. The antibiotic most frequently involved is clarithromycin.Clinical caseWe report the case of a 61-year-old patient who presented a manic episode after taking an antibiotic combination to treat Helicobacter pylori. Five days after the start of highly active antiretroviral therapy (HAART), behavioral problems appeared (aggressiveness, irritability, talkativeness, insomnia). At the time of hospitalization, she had an acute delusional symptomatology, with a theme of persecution, associated with intuitive, interpretive and imaginative mechanisms. Manic symptoms were obvious: psychomotor excitement, aggressiveness and irritability, flight of ideas, verbal disinhibition and a denial of problems. There was no toxic cause. Brain magnetic resonance imaging (MRI) was normal. Her condition improved very quickly and delusions disappeared in four days. Mrs. H. could critic her delirium and recovered a euthymic state. During hospitalization, treatment divalproate sodium was introduced (250 mg, 3 times a day), was maintained following hospital discharge for 2 years for prevention, and then decreased to the stop. There are currently no further behavioral problems or sleep disorders two years after this episode.DiscussionFacing this clinical case, several questions arise: Which drug therapy is the most suitable for this type of mental disorder? Are there predictors of antibiomania? Is there a risk of recurrence of mood episodes following an antibiomania that occurs spontaneously? What are the pathophysiological mechanisms that could explain this reaction? In all cases identified, stopping the antibiotics was decisive. However, the introduction of a psychotropic and the duration of this treatment remain unclear. First, longitudinal follow-up would assess this variable. Second, it is unclear whether the presence of personal psychiatric history is a predictor of antibiomania. Finally, there are several hypotheses to explain antibiomania: the competitive effect of GABAergic inhibitory receptors, seizure-like phenomena that mimic psychiatric symptoms, and disruption of the intestinal microbiota by antibiotics leading to a modification of the functioning of the central nervous system. The explanatory model of antibiomania is not yet known and requires further research.L’antibiomania se définit par l’apparition d’un épisode maniaque en réaction à la prise d’antibiotiques. Ce phénomène, bien qu’assez rare, n’est pas négligeable étant donné le nombre croissant de cas observé. Il se manifeste en général chez des sujets n’ayant pas d’antécédent de trouble bipolaire. Nous décrivons le cas d’une patiente de 61 ans qui a présenté un épisode maniaque suite à la prise d’une trithérapie antibiotique reçue pour l’éradication d’Helicobacter pylori dans le cadre d’un ulcère gastroduodénal. À l’arrêt du traitement antibiotique, les symptômes maniaques ont régressé en quelques jours. Plusieurs questions se posent notamment sur l’attitude thérapeutique à adopter et les causes expliquant l’antibiomania. Celles-ci sont encore floues. Nous abordons par ailleurs plusieurs hypothèses étiologiques : l’effet compétitif inhibiteur au niveau des récepteurs gabaergiques, l’effet épileptogène mimant un tableau psychiatrique, et la perturbation du microbiote intestinal par les antibiotiques, modifiant de façon indirecte le fonctionnement du système nerveux central

Bright light therapy in seasonal bipolar depressions

INTRODUCTION: Bipolar disorders (BD) are frequent mood disorders associated with a poor prognosis mainly due to a high relapse rate. Depressive relapses may follow a seasonal cyclicality, and bright-light therapy (BLT) has been established as the treatment of choice for seasonal affective disorder (SAD). The use of BLT for seasonal unipolar depression is well known, but the scientific literature is much poorer on the management of seasonal depressive episodes in BD. In addition, some specificities related to BD must be taken into account. METHODS: We conducted a comprehensive review using Medline and Google Scholar databases up to August 2014 using the following keywords combination: "bipolar disorder" and "light therapy" or "phototherapy". Papers were included in the review if (a) they were published in an English or French-language peer-reviewed journal; (b) the study enrolled patients with BD and SAD; and (c) the diagnosis was made according to the DSM or ICD criteria. RESULTS: BLT was considered among the first-line treatments for SAD with a size effect similar to antidepressants. Most of the studies did not distinguish between patients with unipolar and bipolar disorders. However, it has been demonstrated that the most significant risk of BLT in patients with BD is the mood shift. Thus, the most important therapeutic adaptation corresponds to the use of an effective mood stabilizer, as with any antidepressant. Another therapeutic adaptation in first intention is that the times of exposure to light should be shifted from morning to midday. This review also includes therapeutic guidelines regarding the management of BLT in seasonal bipolar depressive episodes. DISCUSSION: There are very few specific data on seasonal bipolar depressive episodes. This literature review has highlighted that BLT should be handled as a regular antidepressant treatment in patients suffering from seasonal bipolar depressive episodes