Halil Ozcan

A Review of Melatonin, Its Receptors and Drugs.

After a Turkish scientist took Nobel Prize due to his contributions to understand clock genes, melatonin, closely related to these genes, may begin to shine. Melatonin, a hormone secreted from the pineal gland at night, plays roles in regulating sleep-wake cycle, pubertal development and seasonal adaptation. Melatonin has antinociceptive, antidepressant, anxiolytic, antineophobic, locomotor activity-regulating, neuroprotective, anti-inflammatory, pain-modulating, blood pressure-reducing, retinal, vascular, anti-tumor and antioxidant effects. It is related with memory, ovarian physiology, and osteoblast differentiation. Pathologies associated with an increase or decrease in melatonin levels are summarized in the review. Melatonin affects by four mechanisms: 1) Binding to melatonin receptors in plasma membrane, 2) Binding to intracellular proteins such as calmoduline, 3) Binding to Orphan nuclear receptors, and 4) Antioxidant effect. Receptors associated with melatonin are as follows: 1) Melatonin receptor type 1a: MT1 (on cell membrane), 2) Melatonin receptor type 1b: MT2 (on cell membrane), 3) Melatonin receptor type 1c (found in fish, amphibians and birds), 4) Quinone reductase 2 enzyme (MT3 receptor, a detoxification enzyme), 5) RZR/RORα: Retinoid-related Orphan nuclear hormone receptor (with this receptor, melatonin binds to the transcription factors in nucleus), and 6) GPR50: X-linked Melatonin-related Orphan receptor (it is effective in binding of melatonin to MT1). Melatonin agonists such as ramelteon, agomelatine, circadin, TIK-301 and tasimelteon are introduced and side effects will be discussed. In conclusion, melatonin and related drugs is a new and promising era for medicine. Melatonin receptors and melatonin drugs will take attention with greater interest day by day in the future.

Synthetic Cannabis-Induced Mania

Synthetic cannabinoids (SC), cannabinoid 1 and cannabinoid 2 receptors agonists, are the psychoactive substances. SC was originally produced to treat medical conditions. Compared to other narcotics, SC is easier to obtain, cheap, and highly potent and has a long half-life. In addition, routine analysis does not detect SC, which has led to widespread use. A case is presented that manic episode was developed with the use of SC. Hospitalization and admission to psychiatric units depending on SC use have been observed mostly with psychosis. Although SC-induced affective symptoms were mentioned in the literature, mania has not been reported before. We aimed to discuss the psychiatric conditions induced by widespread use of SC via our case.

Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

Female attempted suicide patients with low HDL levels are at higher risk of suicide re-attempt within the subsequent year: A clinical cohort study

Our aims were, to clarify the blood lipid differences [Total serum cholesterol (TC), High-density lipoprotein (HDL), Low density lipoprotein (LDL), Triglyceride (TG)] between female patients who had attempted suicide and controls and to determine whether we could use the patients׳ initial lipid profiles to predict suicide re-attempt within the subsequent year. A total of 284 participants (110 cases and 174 controls) were recruited, with no differences in body mass index, age, blood sampling time and gender. Blood samples were collected from all participants for serum lipid profiles and assayed in an auto-analyzer. We divided the suicide re-attempter group into suicide attempters in the subsequent year (SSY) and suicide attempters after the subsequent year (SASY). The TC, LDL, and TG levels were significantly lower in the suicidal group than in the control group. HDL was significantly higher in the suicidal group than in the control group. Low TG (<70mg/dL) (OR (odds ratio)=12.8; 95% CI (confidence interval)=5.4-30.5; p<0.0001)and low LDL/HDL (<1.8) (OR=4.1; 95% CI=1.8-9.3; p=0.001) were significantly associated with a current suicide attempt. HDL levels in the SSY (41.5±4.5mg/dL) were lower than in the non-suicide attempters group (NSA) (50.9±10.3mg/dL) and SASY (58.7±12.8mg/dL)(d.f.=2, F=5.2, p=0.007). Serum HDL level may be a potential candidate predictor for the future risk of suicidality.

Serum brain-derived neurotrophic factor differences between the luteal and follicular phases in premenstrual dysphoric disorder

OBJECTIVE We hypothesized that comparison of the serum brain-derived neurotrophic factor (BDNF) levels between women with premenstrual dysphoric disorder (PMDD) and women without PMDD in the luteal and follicular phases of their menstrual cycles would reflect the altered neuromodulator responses that compensate the underlying pathogenesis in PMDD. METHOD Twenty-nine participants without PMDD and 20 with PMDD were enrolled in the study. The serum BDNF, estrogen and progesterone levels were assessed at the follicular and luteal phases in their two consecutive menstrual cycles. RESULTS Participants with PMDD had significantly higher luteal serum BDNF levels than the control subjects. The serum BDNF levels were significantly higher in the luteal phase than in the follicular phase in women with PMDD. The difference in the serum BDNF levels between the luteal and follicular phases were significantly higher in the PMDD patients than in the control. CONCLUSIONS The higher serum BDNF levels in the luteal phase in the PMDD patients may reflect compensatory process that results in subsequent improvement of the PMDD-associated depressive symptoms in the follicular phase. The higher difference in the serum BDNF levels between the phases in PMDD patients may reflect an altered neuromodulator response.

Dose-Dependent Paliperidone Associated With Angioedema.

resolution of symptoms suggesting an acute dystonic reaction as the diagnosis. Early recognition of this adverse effect and prompt administration of an anticholinergic in all the cases averted invasive ventilation and more importantly fatal asphyxiation. There is no evidence to suggest that benzodiazepines are necessary for treatment. In fact, these may compromise valuable respiratory reserve. That this reaction develops rarely and with exposure to a disparate variety of dosages of therapy suggest that certain patients may have an underlying predisposition to develop this adverse effect. Other diagnoses that may mimic ALD include anaphylaxis, tardive laryngeal dystonia, neuroleptic malignant syndrome, and respiratory dyskinesia. With particular relevance to our case, we would like to point out that tardive laryngeal dystonia and respiratory dyskinesia are phenomena that develop after prolonged exposure to the drug. They are often seen to coexist with tardive dyskinesia in other parts of the body and do not usually respond to anticholinergics. In our case, the patient had a history of extrapyramidal adverse effects with haloperidol, and unmasking of tardive dystonia from withdrawal of clozapine was also a possibility as this phenomenon has previously been documented in the literature. However, the sudden worsening of dyspnea newly associated with stridor along with rapid improvement after the administration of diphenhydramine all support ALD over tardive dystonia. Furthermore, the absence of fever, hyperthermia, and altered mental status rule out the possibility of neuroleptic malignant syndrome in all the above cases. The most salient diagnosis on the differential for ALD is anaphylaxis. Visualization of adducted vocal cords, absence of edema on laryngoscopy, and prompt response to anticholinergics are all findings suggestive of the former. Nevertheless, it is imperative that physicians maintain a high index of suspicion for ALD in an appropriate clinical scenario, even if administering antihistamines as a first response. Premedication with anticholinergics in the first few weeks of therapy in patients known to experience this reaction has been suggested. Educating physicians about the potential of ALD with SGA use and instructing patients to promptly selfadminister anticholinergic therapy should they notice suggestive symptoms may result in significant reduction of unnecessary invasive ventilation.

Biyolojik ritmi etkileyen psikotrop ilaçlar

Birçok canlı organizmada, omurgalı ve memeli canlıda olduğu gibi insanda da biyolojik işlevler çeşitli aralıklarla salınan ritimlerle yürür. Sirkadyen, ultradien ve infradian ya da daha uzun aralıklarla salınan iç ritimlerimiz kendi iç düzenlerini her şartta devam ettiren, bağımsız biyolojik organizasyonlardır. Biyolojik olarak kendiliğinden işleyen, istikrarlı bir yol varsa da, gerek psikiyatrik hastalıklar ve gerekse de psikotrop ilaçlar bu iç ritimleri değiştirebilir. Psikotrop ilaçlar, etki düzeneklerindeki nörotransmmitter ya da nöromediatörler vasıtasıyla doğrudan veya daha uzun vadede hormonal ya da genetik değişikliklere neden olarak da biyolojik ritimler üzerine etkili olabilir. Biyolojik ritim düzensizliklerinin duygudurum bozuklukları açısından hem neden hem de sonuç olarak önemine dikkat çeken birçok çalışma vardır. Duygudurum bozukluklarının takip ve tedavisinde psikofarmakolojik ajanların biyolojik ritimlere olan muhtemel etkisi de değerlendirilmesi önemlidir.

Unintentional injuries in preschool age children: is there a correlation with parenting style and parental attention deficit and hyperactivity symptoms

AbstractUnintentional injuries are the leading cause of death among children. Previous research has shown that most of the injuries occur in and around the home. Therefore, parents have a key role in the occurrence and prevention of injuries. In this study, we examined the relationship among home injuries to children and parental attention deficit hyperactivity disorder (ADHD) symptoms, parental attitudes, and childrens behavioral problems.Forty children who were admitted to the emergency department because of home injuries constitute the study group. The control group also consisted of 40 children, who were admitted for mild throat infections. The parents filled out questionnaires assessing parental ADHD, child behavioral problems, and parenting attitudes.Scores were significantly higher for both internalizing disorders and externalizing disorders in study groups. We also found that ADHD symptoms were significantly higher among fathers of injured children compared with fathers of control groups. Democratic parenting was also found to correlate with higher numbers of injuries.Parenting style, as well as the psychopathology of both the parents and children, is important factors in childrens injuries. A child psychiatrist visit following an emergency procedure may help to prevent further unintentional injuries to the child.

Diffuse Hair Loss Induced by Sertraline Use.

Hair loss is a rare side effect of psychotropic drugs. The most related drug class with this side effect is the mood stabilizers. Studies reporting the sertraline-induced alopecia are limited in number. Sertraline is a potent antidepressant which inhibits the serotonin reuptake from the presynaptic terminals selectively. The reason for hair loss could not be elucidated completely. Psychotropic drugs are usually considered to lead to hair loss through influencing the telogen phase of hair follicle. This paper reports a 21-year-old male with diffuse hair loss induced by sertraline use and improved by quitting the drug. To the best of our knowledge, there are no other case reports on sertraline-induced alopecia within 2 weeks.

Gadolinium-Based Contrast Agent Extravasation Mimicking Subarachnoid Hemorrhage After Electroconvulsive Therapy

BACKGROUND Electroconvulsive therapy (ECT) is a safe method that has been applied for many years in medical treatment-resistant depression treatment. In this case report, contrast extravasation due to deterioration of the blood-brain barrier after ECT mimicking subarachnoid hemorrhage (SAH) on magnetic resonance imaging (MRI) is discussed. CASE DESCRIPTION A 70-year-old male patient who underwent ECT presented with sulcal hyperintensities suggesting subarachnoid hemorrhage on fluid-attenuated inversion recovery sequence of MRI obtained after ECT. However, there was no evidence to suggest SAH on nonenhanced brain computed tomography. CONCLUSION It should be kept in mind that patients may have contrast extravasation due to deterioration of the blood-brain barrier after ECT, and other alternative methods should be used for the diagnosis of SAH in these patients, not MRI.