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Major depressive disorder (MDD) is a highly prevalent psychiatric disorder and is reported as one of the most leading cause of disabilities and markedly contributes to a significant global burden o...

Although recent research in neuroscience and genetics is providing new insights into the etiology of psychiatric disorders, progress in treatment development has been hindered by reliance on diagnostic categories that are based primarily on presenting signs and symptoms. The NIMH Research Domain Criteria (RDoC) framework seeks to provide a neuroscience-based nosological background for future research on psychopathology, categorizing individuals for research purposes using a dimensional approach that benefit from significant progress in modern neuroscience. These scientific advances combined with new approaches to classification can inform the development of novel, circuit-based interventions and the personalization of treatments available. In this editorial, we describe the RDoC framework compared with Diagnostic and Statistical Manual/International Classification of Disease systems and highlight some of the emerging progress in RDoC-based research that is consistent with these developments.

WOS: 000390418700002 Objective: Schizophrenia involves white matter abnormalities that might have a central role in the pathophysiology. Abnormal brain connectivity especially in prefrontal and temporal heteromodal cortex has been suggested as the leading structural impairment in patients with schizophrenia. In this study we examined the relationship between potential white matter changes and clinical response, as well as associations with antipsychotic treatment follow-up. Methods: 18 first-episode schizophrenia (FES) patients were recruited from the outpatient unit of the GATA (Gulhane Military Medical Academy) Haydarpasa Research and Training Hospital, between June 2009-February 2010. Fourteen patients with FES were recruited, and 16 healthy control subjects were recruited from the community. Diffusion tensor MRI (DT-MRI) was obtained from participants at baseline and after 4 weeks of standard antipsychotic treatment. A color-coded fractional anisotropy map for each 11 patient was extracted from the 4-week follow-up and the baseline splenium and genu FA measurements. According to Basser and others major eigenvector linear maps were transformed into the color-coded maps. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Brief Psychiatric Rating Scale (BPRS) scores between baseline and follow up were also evaluated. Results: In this study; in the FES patients, both genu FA (p=0.001) and the splenium FA (p=0.013) values were statistically significantly lower than the healthy control group. There were mild FA increases respectively genu and splenium (p=0.533, p=0.318) in the FES patients after the treatment. But the FA changes did not correlate with the changes in clinical symptoms. A negative, moderate, statistically significant correlation (Pearson's r=-0.569, p=0.034) was found between baseline splenium FA values and BPRS scores. The duration of illness prior to treatment was negatively, weak, statistically non-significantly correlated (r=-0.066; p=0.846) between baseline and follow-up splenium FA changes. Conclusions: The reduced mean Callosal FA (CFA) values might indicate myelination defects and problems in axonal transport. The existence of white matter changes even in first episode drug-naive schizophrenia patients supports the view that these problems occurs in earlier stages of development. Although the callosal FA changes did not correlate with symptom improvement or the dose of antipsychotic medication, there was a mild increase in follow-up FA measurements. These findings show that CC which is the main conduit of interhemispheric connection is affected distinctly in patients with schizophrenia. Further collaborative studies are needed to clarify the potential long-term effects of antipsychotics on white matter microstructure and also its reversibility.

Schizophrenia is a serious mental illness that affects approximately 1% of the population worldwide, with positive, negative and cognitive dysfunctions and a significant deterioration in psychosocial functioning. Interactions between genetic predisposition and environmental stressors at the early stages of life, and subsequently a molecular level neurodegeneration process are important in the development of schizophrenia. Current approaches suggest that cytokines-induced neuroinflammation might have a role in the development of several psychiatric disorders, including schizophrenia. Uncontrolled microglial activation, increase in pro-inflammatory cytokines, and subsequent neurotransmitter dysfunctions can induce schizophrenia. Microglial activation induced by pro-inflammatory cytokines in central nervous system is responsible for the initiation and proceeding of the inflammatory process and consequently developing neurodegeneration. Here in this review, we aimed to provide an overview to the latest findings related to the cytokines-mediated peripheral and central immune responses in the development of schizophrenia.

In this case report, we present two patients who developed serious dermatological adverse reactions following vortioxetine use. Dermatological signs and symptoms disappeared following discontinuation of vortioxetine. These two cases can be useful in routine clinical practice to recall the parameters that need to be systematically addressed in cases of suspected adverse drug reactions with vortioxetine use in depressed patients.

Since ancient times, various forms of the plant cannabis sativa have been used and more recently for therapeutic purposes including (but not limited to) antiemetic, anticonvulsant, anti-inflammator...

Major Depressive Disorder (MDD) is a serious mental health problem that leads to patients' disability and has huge impact on social and economic burden to society. The current available medications for the treatment of depression are mainly targeted on enhancing monoamine neurotransmission. However, antidepressant treatments are still lacking high efficacy in many cases which is associated with low treatment response and remission rates. However, the latest knowledge regarding the pathophysiology of depression indicates that depression is developed by highly complex and integrated mechanisms in which monoaminergic deficiency could only be part of. The paradigm is now shifting from monoaminergic hypothesis to significance of other novel mechanisms that could possibly play substantial role for the development of depression in a highly inter-related manner. In fact, neuroinflammation, amongst other mechanisms does seem to be a key pathological component by having impact on certain pathway pathologies...

(2016). Risk Evaluation and Mitigation Strategy for Clozapine. Klinik Psikofarmakoloji Bulteni-Bulletin of Clinical Psychopharmacology: Vol. 26, No. 1, pp. 1-6.

(2015). A Futuristic Approach to Psychiatric Diagnosis. Klinik Psikofarmakoloji Bulteni-Bulletin of Clinical Psychopharmacology: Vol. 25, No. 4, pp. 321-325.

Sleep is an important part of life and its quality is indispensable to a number of brain functions, including communication of neurons and therefore maintenance of brain health. Several studies have systematically demonstrated adverse effects when sleep behavior is compromised. Inadequate amount of sleep may cause: emotional and cognitive impairment. Sleep is regulated by the circadian system that times daily sleep which is driven by an internal timing system. Clock genes control rhythms in physiology and behavior which are associated with sleep and wakefulness and transcriptional level of them leads the gene networks that are released with a 24-hour cycle (1). It has been accepted that disruption of circadian rhythms is associated with sleep disorders, and some chronic diseases including infectious diseases, autoimmune diseases, metabolic syndrome, neurodegenerative diseases. It is also highlighted that coordination between circadian clock of immune response through innate and adaptive immune cells and a regulatory layer relative to circadian clock. Inflammation based disorders such as infections can disrupt the circadian clock and reduce the amplitude of circadian rhythms significantly. Results obtained from autoimmune disease models neuroinflammation and demyelination may be due to an increase in pathogenic T lymphocytes showing the involvement of inflammation (2). Sleep is known to play an important role in immune function. However, the effects of sleep quality during hospitalization for COVID-19 remain unclear was investigated in a retrospective, single-center cohort study. It was conducted to investigate the effects of sleep quality on recovery from lymphopenia and clinical outcomes in hospitalized patients with laboratory-confirmed COVID-19. It has been found that poor sleep quality during hospitalization in COVID-19 patients with lymphopenia is associated with a slow recovery from lymphopenia and an increased need for ICU care (3). It has been accepted that sleep problems are the most prominent symptom among with psychiatric disorders including major depressive disorder (MDD), bipolar disorder (BD), generalized anxiety disorder, post-traumatic stress disorder (PTSD), schizophrenia etc. In approximately 90% of depressive patients have some types of sleep disorder (sleep apnea syndrome, insomnia, parasomnias, restless legs syndrome etc.). Therefore, psychiatric disorders have an impact on sleep, sleep disorders have an impact on psychiatric conditions, treating sleep disorders. MDD has been associated with the decreased REM sleep latency. Transition into REM sleep is accompanied by a rapid decrease in monoamines such as serotonin [5‐HT], norepinephrine [NE] and dopamine and an increase in cholinergic activity. It is known that bi-directional interaction of cholinergic and monoaminergic neurons regulates the onset of REM sleep and main cause of depression is significant reduction of monoaminergic neurotransmitters (mainly 5‐HT and NE) (4-6). About 80 percent of depressive patients suffer from impaired sleep which show characteristic sleep-EEG changes such as impaired sleep continuity, disinhibition of REM sleep and changes in non-REM sleep. In the hypothalamus, the suprachiasmatic nucleus (SCN) which increases production of the hormone melatonin in order to trigger sleep is important for matching the body’s circadian rhythm to the external cycle of light and darkness through pineal gland. In communication with the brain stem, especially the pons and medulla, thalamus, cerebral cortex, basal forebrain and midbrain regulates sleep and wakefulness whereas the amygdala is involved in sleep more related with the mood (4). Recent accumulating data support a key role of gut microbiota, food intake and pathogen-associated molecular patterns (PAMPs) in triggering production of inflammatory mediators causing sleep changes. Environment, including stress, physical activity, and food intake can increa

Sleeping has a critical function to promote health. Studies over the past ten years has documented that sleeping disorders has a strong influence on the risk of infectious diseases and in particular occurrence and progression associated with several major health issues including depression. Recent studies have focused on elucidating the underlying mechanisms that play a role in this situation. This article has been written to review the dynamics of sleep disturbance, sleep restriction, and insomnia on depression and the immune system. Also aimed to discuss the multi-faceted relationship that connect sleep disorder and immunity in terms of the neurobiology of sleep, inflammation and depression. In this context, what is known about the role of sleep on the immune system and the relationship between sleep disorder and depression and the immune system of depression will be reviewed.

(2016). Comment on FDA's Breakthrough Therapy Designation of Intranasal Esketamine for the Treatment of Major Depressive Disorder with Imminent Risk of Suicide. Klinik Psikofarmakoloji Bulteni-Bulletin of Clinical Psychopharmacology: Vol. 26, No. 4, pp. 329-331.

WOS: 000359611700004 Objectives: Psychopathy is a distinct personality organization and differs from antisocial personality disorders in many aspects. Its diagnosis is challenging but also critical to predict criminality. In this context, Psychopathy Checklist Revised (PCL-R) is a useful tool in the diagnosis of psychopathy. Its reliability and validity was shown in various populations but has not been studied in a Turkish population. Our aim was to demonstrate the reliability and validity of PCL-R in a sample from Turkey. Methods: 425 male subjects with antisocial personality disorder and 125 controls without any psychiatric diagnoses were included in the study. DSM-5 diagnostic criteria were used and PCL-R was administered to all participants. The reliability of the Turkish version of PCL-R was determined by test-retest and internal consistency methods. In the ROC analysis performed with PCL-R, DSM-5 criteria were taken as a gold standard, the sensitivity; specificity and cut-off values of PCL-R were estimated. To evaluate the adequacy of the scale construct validity, Exploratory Factor Analysis and Kaiser-Meyer-Olkin (KMO) and Barlett tests were applied. Reproducibility of the test was evaluated by Pearson correlation coefficient. Re-testing was performed with 171 subjects two weeks after the first test. Results: In reliability analysis, the Cronbach's alpha internal consistency coefficient was calculated to be alpha=0.977. Pearson correlation coefficient of test-retest was r=0.94 (p

ABS TRACT: Relationship between plasma levels of prolactin and the severity of negative symptoms in patients with schizophrenia Objective: The aim of this study was to evaluate the relationship between plasma levels of prolactin and negative symptoms. Methods: One hundred fourteen patients with schizophrenia were included in this crosssectional study. The patients were classified into groups with and without hyperprolactinemia. Plasma levels of prolactin and clinical features were compared between these groups. Results: Negative symptom scores in the group with hyperprolactinemia were significantly higher than in the non-hyperprolactinemic group. There was also a positive correlation between plasma levels of prolactin and negative symptom scores. However, there was no statistically significant difference between schizophrenia subtypes with regard to plasma prolactin levels. Patients treated with conventional neuroleptics or novel antipsychotics such as risperidone, paliperidone and amisulpride had higher prolactin levels than patients treated with aripiprazole, olanzapine, quetiapine, ziprasidone, and clozapine. Conclusion: This study indicated that we should be aware of prolactin levels, especially when negative symptoms are prominent in patients with schizophrenia. Plasma levels of prolactin could be an important biological marker for the severity of negative symptoms in the treatment of patients with schizophrenia. Thus, this finding may change the present pharmacotherapy for negative symptoms in schizophrenia based on prolactin levels.

Clozapine, the progenitor of atypical antipsychotic drugs, was first synthesized at Wander Laboratories in Bern, Switzerland in 1956, only a few years after the discovery of the first antipsychotic, chlorpromazine. However, it is interesting that in the beginning it was debated whether this drug, which did not cause catalepsy in animal models like other antipsychotics, could be a potential antipsychotic. Indeed, evidence suggests that clozapine does not cause extrapyramidal side effects, as also evidenced with the fact that it is well tolerated by patients with Lewy Body Dementia or L-DOPA-induced psychosis in Parkinson’s disease. Clozapine started to be used in Europe after 1971, but in 1975, because of deaths resulting from agranulocytosis, the pharmaceutical manufacturer withdrew clozapine from the market in all countries

1Pleasing serendipities that brings a little smile to our lips, such as the discovery of hydrostatics by Archimedes because of floating in a bath or the discovery of gravity by Sir Isaac Newton when an apple fell on his head when he was sleeping beneath a tree, have occurred several times in the history of science. Similar serendipities have happened in medicine in the discovery of new drugs. That is why the late 19

WOS: 000339983000016 This report evaluation of the psychotropic drug usage in Turkey based on the data provided by Intercontinental Marketing Service (IMSHealth), Ministry of Health, Turkish Statistical Institute, Turkish Mental Health Profile. A total of 14.24 millions units of antidepressants were used in 2003. By increasing 162%, annual antidepressant usage reached 37.35 millions units by the end of 2012. Antipsychotic drug usage increased by 71% during the last 5 years, from 7.20 millions units in 2005 to 12.32 millions as of the end of 2012. The total number of prescriptions including an antidepressant was 18.14 millions in 2007, by increasing 50% in the last 5 years, it reached 26.60 millions in 2012. The total number of prescriptions including any antipsychotic drug increased from 3.92 millions in 2007 to 5.76 millions in 2012, increasing by 46.7%. In the worst case scenario considering concurrent psychiatric disorders, prevalence of disorders requiring antidepressants and antipsychotic drugs could be as high as 20% and 5%, respectively. The calculated frequency (prescription/population) was much higher than the worst case scenario estimates. In 2007, family physicans and practitioners, psychiatrists, neurologists, and specialists of other disciplines prescribed 33, 37, 20, and 11% of all antidepressants, respectively. In 2012, they prescribed 48, 31, 14, and 7% of all antidepressants, respectively. The first time antidepressant prescriptions in 2012 were done at the rate of 37, 34, 19, and 11% by above mentioned specialists, respectively. In 2007, family physicans and practitioners, psychiatrists, neurologists, and specialists of other disciplines prescribed 18, 67, 13, and 3% of all antipsychotics, respectively. In 2012, the same set of specialisations prescribed 21, 63, 14, and 2% of antipsychotics, respectively. The "first time" antipsychotics were prescribed at the rate of 6, 73, 19, and 3% by above mentioned order of specialists, respectively. In conclusion, the data suggest that there was an unnecessary and/or excessive prescribing of psychotropic agents. The increase is not related to increased population and/or prevalance of psychiatric disorders. The numbers of first time prescriptions suggest that non-psychiatrists diagnose and initiate treatment for psychiatric disorders. This requires re-evaluation of authorization to presribe psychotropic agents.

Number Needed to Treat (NNT) is a concept first found in papers published by Laupacis et al. in the New England Journal of Medicine in 1988. NNT is the average number of patients who need to be treated to prevent one additional bad outcome (e.g. the number of patients that need to be treated for one to benefit compared with a control in a clinical trial) 1 . This measure assessing the clinical significance of any kind of intervention has since been applied with increasing frequency. This concept is frequently used in psychiatry, especially when comparing the efficacy and effectiveness of drugs and is seen as an important indicator to demonstrate the advantage of a new drug over a standard or reference drug and/or placebo treatment 2-5 .

Despite huge amount of efforts and resources spent to improve the pharmacotherapeutic tools to treat major psychiatric disorders such as depression and schizophrenia, there still exist unmet needs in the field. Treatment resistance, non-adherence, and severe adverse effects such as diabetes mellitus type II, extrapyramidal side effects, etc. are among the unmet needs commonly faced by clinicians, probably due to the fact that the pathophysiology of both schizopherenia and depression have not been fully elucidated. Today, neither the monoamine hypothesis of depression nor the dopamine hypothesis of schizophrenia explains either disorder in full. In spite of its widespread presence throughout the brain, the glutamatergic system has remained almost unexplored with respect to drug discovery for psychiatric illnesses.Recently, the promising outcomes of intravenous use of ketamine to overcome resistance to antidepressant treatment and the administration of a nitroprusside infusion to address resistance ...

In this review, we aimed to study the pharmacological profile, efficacy, and tolerability and safety data of asenapine, a drug approved in Turkey, in the treatment of schizophrenia and manic and mi...

WOS: 000376663300005 Objective: The number of studies investigating the traumatic events experienced during childhood period in patients with bipolar disorder (BD) are limited and to our knowledge no previous study was conducted about alexithymia and dissociative experiences of these patients as well. Besides investigation of childhood traumas and associated dissociative and alexithymic properties, identification of the differences between BD patients with and without childhood trauma (CT) was aimed in this study. Methods: Among the admissions to the psychiatry outpatient clinic, 70 BD patients and 70 healthy control subjects were included into the study. Structured Clinical Interview for DSM-IV Axis-I Disorders, Dissociative Experiences Scale (DES), Childhood Trauma Questionnaire (CTQ) and Toronto Alexithymia Scale (TAS-20) were administered. Results: Mean subscale and total scores of patients with BD in both CTQ and TAS-20, and mean DES score were found to be significantly higher than healthy control subjects. Psychopathological acts, number of episodes and suicide attempts were higher in the BD patients with childhood trauma history than that of the BD patients without any history of childhood trauma. Additionally, positive correlations were found between 'sexual abuse' and alexithymia total score along with 'difficulty identifying feelings' subscale score. Moreoever, mean DES score was also found to be positively correlated with 'difficulty identifying feelings' subscale score, 'difficulty to describe feelings' subscale score, alexithymia total score, and episode frequency. Conclusion: These results highlight the importance of protective mental health in the treatment of BD and reveal that childhood traumas should be questioned when evaluating patients especially with the diagnosis of BD.

Despite all efforts even in the half of the first quarter of the twenty-first century, psychiatric disorders are still lifelong conditions, which cannot be treated fully and mostly continue to be chronic. Therefore, psychiatric disorders and their treatments require more skills and care than physical disorders. In the area of preclinical research in psychopharmacology, clinical trials, research, meta-analyses, and clinician experiences provide useful information for psychopharmacological applications. Although there is still a long distance to cover andat times opposing views, developments in the field of psychopharmacology are rapid and satisfactory. In this review, current issues in psychopharmacology, such as effectiveness, efficacy, new avenues of enquiry, side effects, adverse effects, and drug interactions of psychotropics, generic and reference drug issues, and pharmacoeconomics will be discussed.

OZET: Norobilimde nanoteknoloji uygulamalari: Gelismeler, firsatlar ve sorunlar Metrenin milyarda birine esit olan "nanometre", 21. yuzyi- lin ikinci yarisinda yasamin her alaninda duyulmaya bas- lamistir. Santral sinir sistemi hastaliklarinin insidansinda gozlenen artis, bu alanda yeni tedavi ve profilaksi yon- temlerine ihtiyaci gundeme getirerek nanoteknoloji ve sinir bilim konseptlerini biraraya getirmistir. Bu durumun temel sebebi, kan-beyin bariyerinin (KBB) yapisinin kon- vansiyonel ilac uygulamalarini etkisiz birakmis olmasidir. Nanoteknolojik urunler, uyuncta ve biyoyararlanimda artma, ilac molekullerinin KBB'ye penetrasyonunu kolay- lastirma ve gorulen yan etkilerde azalma saglamistir. Bu derleme, KBB'den gecisi kolaylastiran bazi tedavi yakla- simlari ile kullanimi fark yaratan onemli nanoteknolojik ve mikro-elektro mekanik sistem orneklerini ozetlemek- tedir. Ayrica, bazi urunlerin uygulanmasindaki invazif prosedurler ile mikrocip ve nano cihazlarin kullanimi hakkinda temel tartisma konularindan da bahsedilmistir.

To the Editor,Early recognition of adverse drug reactions is crucial in the medication management of psychiatric disorders. Several diagnostic assessment tools have been proposed to evaluate and ma...