Mehmet Emin Ceylan

The Gut-Brain Axis: The Missing Link in Depression

The gut microbiota is essential to human health and the immune system and plays a major role in the bidirectional communication between the gut and the brain. Based on evidence, the gut microbiota is associated with metabolic disorders such as obesity, diabetes mellitus and neuropsychiatric disorders such as schizophrenia, autistic disorders, anxiety disorders and major depressive disorders. In the past few years, neuroscientific research has shown the importance of the microbiota in the development of brain systems. Recent studies showed that the microbiota could activate the immune and central nervous systems, including commensal and pathogenic microorganisms in the gastrointestinal tract. Gut microorganisms are capable of producing and delivering neuroactive substances such as serotonin and gamma-aminobutyric acid, which act on the gut-brain axis. Preclinical research in rodents suggested that certain probiotics have antidepressant and anxiolytic activities. Effects may be mediated via the immune system or neuroendocrine systems. Herein, we present the latest literature examining the effects of the gut microbiota on depression.

Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders

Fecal microbiota transplantation has a 1700-year history. This forgotten treatment method has been put into use again during the last 50 years. The interest in microbiota-gut-brain axis and fecal microbiota transplantation is rapidly increasing. New evidence is obtained in the etiopathogenesis of neuropsychiatric disorders. There is a large number of experimental and clinical researches in the field of gut-brain axis. There is limited information on fecal microbiota transplantation. Despite this, initial results are promising. It is commonly used in the treatment of gastrointestinal diseases such as Clostridium difficile infection, Crohn’s disease, ulcerative colitis. It is also experimentally used in the treatment of metabolic and autoimmune diseases. There are case reports that it is effective in the treatment of autism, Parkinson’s disease, multiple sclerosis, chronic fatigue syndrome and irritable bowel syndrome. Its implementation is easy, and it is a cheap and reliable treatment method. However, the long-term risks are unknown. Additionally, standard application protocols have not yet been established. There are a lot of questions to be answered. A university in Turkey has got official permission this year, and started to apply fecal microbiota transplantation. In this review, neuropsychiatric areas of use of fecal microbiota transplantation have been discussed in the light of the current information.

Long-term remission in schizophrenia and schizoaffective disorder: Results from the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE)

Objective: The objective of this study was to report the long-term remission results from the ConstaTRE relapse prevention trial, in which clinically stable adults with schizophrenia or schizoaffective disorder treated with oral risperidone, olanzapine, or oral conventional antipsychotics were randomized to risperidone long-acting injectable (RLAI) or oral quetiapine, dosed according to package-insert recommendations. Methods: In the ConstaTRE trial, efficacy and tolerability were recorded for up to 24 months. This post hoc analysis presents remission data, defined, according to the Schizophrenia Working Group criteria, as achieving and maintaining eight core symptoms of schizophrenia that are mild or less over 6 months. Additional secondary outcome measures are also presented. Results: A total of 710 patients were randomized to RLAI (n = 355) or quetiapine (n = 355). Mean mode ± standard deviation (SD) drug doses were RLAI 33 ± 10 mg every 2 weeks and quetiapine 413 ± 159 mg daily. Full remission was achieved by 51.1% of patients with RLAI and 39.3% with quetiapine (p = 0.003). Mean ± SD of full remission durations were not significantly different with RLAI (540 ± 181 days) and quetiapine (508 ± 188 days). Overall tolerability was similar between treatment groups. Conclusions: Among stable patients with schizophrenia or schizoaffective disorder, remission was more likely after switching to RLAI than quetiapine.

Neural synchronization as a hypothetical explanation of the psychoanalytic unconscious

Cognitive scientists have tried to explain the neural mechanisms of unconscious mental states such as coma, epileptic seizures, and anesthesia-induced unconsciousness. However these types of unconscious states are different from the psychoanalytic unconscious. In this review, we aim to present our hypothesis about the neural correlates underlying psychoanalytic unconscious. To fulfill this aim, we firstly review the previous explanations about the neural correlates of conscious and unconscious mental states, such as brain oscillations, synchronicity of neural networks, and cognitive binding. By doing so, we hope to lay a neuroscientific ground for our hypothesis about neural correlates of psychoanalytic unconscious; parallel but unsynchronized neural networks between different layers of consciousness and unconsciousness. Next, we propose a neuroscientific mechanism about how the repressed mental events reach the conscious awareness; the lock of neural synchronization between two mental layers of conscious and unconscious. At the last section, we will discuss the data about schizophrenia as a clinical example of our proposed hypothesis.

Long-term use of fluoxetine and multiple skeleton fractures

Dear Editor: We report a 33-year-old female patient treated with fluoxetine for 8 years for depression. She had the first depression attack 14 years ago. She was treated with fluoxetine 20 mg/day and used that dose continuously for 5 years. After quitting the medication, her depression returned and fluoxetine was begun at 20 mg/day and increased to 40 mg/day and used at that dose for 3 months, than lowered to the original dose. At the end of 8 years of using fluoxetine 20 mg/day, three fractures occured within a short interval. The first fracture appeared on the right radius and distal third of the ulna. After 8 months, a second fracture at the left distal third of the spinal cruris emerged. One and a half years later, a fragmented fracture was seen at the collum chirurgicum and tuberculum majus in the proximal third of the right humerus. The patient was operated on four times due to those fractures. At the time of the fractures, there were no biochemical abnormalities other than slight elevations in the levels of LH and FSH. The bone densitometry was within normal limits. A poor densitometry rating was found (−1.5) only for the corpus femoris. Based on that finding, the patient was considered to be in the initial stages of osteopenia. All of those fractures however could not be explained by this diagnosis. Lerner [1] documented that there could be osteoporosis due to the administration of selective serotonin reuptake inhibitors (SSRIs) because serotonin might work as a signal molecule in the brain and there are serotonin receptors on osteoblasts and osteoclasts. There would be a decrease in the bone mass when the serotonin gene transporter was left out of the circuit in gene knock-out studies. These findings reveal that osteoporosis may occur secondary to the use of SSRIs and can cause bone fractures. Ziere et al. [2] reported that SSRIs and tricyclic antidepressants (TSAs) can cause fractures, especially in the bones of older patients, and fractures have appeared in the vertebrae of patients using SSRIs for long periods but not with TSAs. In the presented case, the patient was relatively young and had fractures one after another. It is also interesting that the fractures appeared in the eighth year of using an SSRI. This is in keeping with Ziere’s report that the long-term use of SSRIs may provoke formation of fractures. The fractures due to the use of SSRIs occur without any change in the hormonal regulations in the metabolism of bones, and the deficiency in the bone mass cannot be caught with bone densitometry scans because the pathology is related to the loss of the function of serotonin as a signal molecule in the brain. We propose that rather than continuing the use of SSRIs for more than 5 years, the medication might be shifted to different types of drugs such as MAOIs that are relatively benign to bone mass.

Paroxetine may cause increase in carcinoebmryonic antigen (CEA)

IntroductionCarcinoebmryonic antigen (CEA) is mostly used to detectearly recurrences after surgery in patients with colorectalcancer [1]. In this report, we present a case in whichparoxetine use caused increase in CEA. In literature, asimilar case has not been previously presented.CaseA 61-year-old male patient, married, with a child, sufferedtwo depressive episodes, with the first one occurring 15years ago and the second one 7.5 years ago. After thesecond episode, he received paroxetine treatment for ayear, but 6 months after the cessation of treatment, a thirddepressive episode occurred, and paroxetine was startedagain at 20 mg/day. After a response was obtained, hecontinued to use 10 mg/day. Six years after the lastepisode, in routine controls, CEA levels began to increase.CEA level was 20 in April 2008, 27 in June 2008 and 34in September 2008. A whole-body cancer screening wasperformed. However, clinical examination and laboratorytests [computed tomography (CT) and ultrasound (US)]did not reveal cancer. Therefore, in this patient, theincrease in CEA was attributed to paroxetine, and thetreatment was discontinued. A month later, CEA levelbecame 17.DiscussionCEA increase during paroxetine use may be related to theincrease in serotonin, serotonin

The Contribution of the Cerebellum in the Hierarchial Development of the Self.

What distinguishes human beings from other living organisms is that a human perceives himself as a “self”. The self is developed hierarchially in a multi-layered process, which is based on the evolutionary maturation of the nervous system and patterns according to the rules and demands of the external world. Many researchers have attempted to explain the different aspects of the self, as well as the related neural substrates. In this paper, we first review the previously proposed ideas regarding the neurobiology of the self. We then suggest a new hypothesis regarding the hierarchial self, which proposes that the self is developed at three stages: subjective, objective, and reflective selves. In the second part, we attempt to answer the question “Why do we need a self?” We therefore explain that different parts of the self developed in an effort to identify stability in space, stability against constantly changing objects, and stability against changing cognitions. Finally, we discuss the role of the cerebellum as the neural substrate for the self.

Psychiatric Symptoms in Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Syndrome and its Treatment: A Case Report

To the Editor: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disease. It is diagnosed in childhood (usually at 3–4 years of age). It affects endocrine, respiratory, and autonomic nervous systems. It shows different symptoms at different ages. Rapid weight gain, obesity, alveolar hypoventilation, hypernatremia, cardiopulmonary arrest, hyperprolactinemia, diabetes insipidus, excessive sweating, increase pain perception, obstructive sleep apnea, cold hands/feet, and digestive dysmotility can be seen. Alveolar hypoventilation is essential for the diagnosis.[1] Behavioral problems, mental retardation, personality changes, and mood disorders may accompany. There is no any special diagnostic test. Its treatment is symptomatic.[2] This study is intended to inform clinicians about psychiatric symptoms of a girl with ROHHAD syndrome.

The Soul, as an Uninhibited Mental Activity, is Reduced into Consciousness by Rules of Quantum Physics

This paper is an effort to describe, in neuroscientific terms, one of the most ambiguous concepts of the universe—the soul. Previous efforts to understand what the soul is and where it may exist have accepted the soul as a subjective and individual entity. We will make two additions to this view: (1) The soul is a result of uninhibited mental activity and lacks spatial and temporal information; (2) The soul is an undivided whole and, to become divided, the soul has to be reduced into unconscious and conscious mental events. This reduction process parallels the maturation of the frontal cortex and GABA becoming the main inhibitory neurotransmitter. As examples of uninhibited mental activity, we will discuss the perceptual differences of a newborn, individuals undergoing dissociation, and individuals induced by psychedelic drugs. Then, we will explain the similarities between the structure of the universe and the structure of the brain, and we propose that consideration of the rules of quantum physics is necessary to understand how the soul is reduced into consciousness.

Venlafaxine induced akathisia: a case report

Venlafaxine – a serotonin, noradrenaline and dopamine reuptake inhibitor1 – is a new generation antidepressant. The drug has been rarely reported to be associated with the development of akathisia.2 A review of the literature in PubMed revealed only four cases reported to date. Different from previous cases in which patients developed akathisia at a dose of 150 mg/day, we present the case of a 35-year-old male patient who developed akathisia with venlafaxine 75 mg/day. Our patient had been receiving psychiatric treatment for obsessive-compulsive disorder and avoidant personality disorder for the last 10 years. He was started on sertraline 50 mg/day and shifted to venlafaxine 75 mg/day with cross-tapering. He was not on any other psychotropic or non-psychotropic drugs. Akathisia started on the third week of venlafaxine treatment. The patient could not fall asleep at night because of agitation: need to move his feet constantly, inability to sit for a long time, and need to rock his feet during daytime if he had to remain seated. As venlafaxine provided a marked improvement in compulsions, we continued the treatment and added propranolol 40 mg/day for akathisia. Although propranolol relieved the patient’s akathisia, symptoms did not disappear until we added clonazepam 1 mg/day to the treatment as well. The patient complained about the sleepiness caused by clonazepam, so we withdrew this medication from the treatment. Even though he was taking propranolol, akathisia symptoms became more intense than before, leading us to gradually discontinue venlafaxine. Akathisia symptoms continued until 1 week after complete venlafaxine withdrawal. Meanwhile, compulsions significantly increased after venlafaxine discontinuation, and the patient was started on paroxetine 20 mg/day, with no signs of akathisia. The patient’s mother had a diagnosis of bipolar disorder for which she had used tricyclic antidepressants and classical neuroleptic drugs for a long time, without any akathisia symptoms. Four cases of venlafaxine induced akathisia have been reported in the literature. Three of those cases experienced akathisia at the dosage of 150 mg/day, and one at 225 mg/day.2 In our case, the patient developed akathisia at the dosage of 75 mg/day. Also, all the cases previously reported used other drugs and had comorbid diseases,2 whereas our patient did not have any comorbid disease and was not using any other medication that might lead to drug interactions. Finally, the patient’s mother had taken psychotropic drugs for a long time, without any extrapyramidal side effects (EPS), which helped us rule out any genetic inheritance for EPS. Therefore, our conclusion is that even low doses of venlafaxine, such as 75 mg/day, may cause akathisia.