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Hi everyone ^_^
I was wondring if there is a specific technique to study the chemical change responsible for DID and I want to know if I could follow a specific procedure to the neurochemicals behinde this disorder and how the alteration vary between a normal person and a DID patient? also, the most important thing is finding a specific drug to cure this disorder. I know that there are drugs that help the patients endure anixty and depression come with this disorder but there is no direct and specific cure for DID.
I read that contextual treatment helped the patient somehow to know themselves and some of them return the control and can change from one personlaity to the other when they want but it didn't work for most of them although it benfits them somehow but not cure them. So; I read a lot of artiles and reviews from the litreture but most of them focused in the contextual treatment not chemical based treatment!!
I don't know if this is right or not but I think this return to neuropsychopharmacology and I'm a chemistry master student so I want to know if there is a possibility to study this in my thesis project and if I need a high tech equipments to do that?
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If you want to specifically measure chemicals in the brain, then you cannot do it when the subject was alive. Psychiatry is still clouded in mystery, as we cannot objectively measure many things we theorize. It was likely easier to measure brain wave or structural abnormalities from X-ray or MRI. However, even those do not provide reliable outcome, as the changes vary depending on the individuals and specific cut off to determine which is normal and which is not is still debatable. I'd like to brief you about the difficulty faced when measuring chemicals, hoping that one day any one can overcome it.
When we measure chemicals in the brain, we cannot use chemicals in the blood. The problem is because there is a tight clutter of cells preventing large chemicals to pass through, which is termed blood brain barrier. As neurotransmitter (neurochemicals in the brain) cannot pass through this junction, even if we measure it's concentration in the blood, it's hard to make connection with it's level in the brain. It might even be possible that the level in the blood increases while the level in the brain decreases. There are already methods to measure neurotransmitter in urine as representative of it's concentration in the blood, but it's very much debatable as there is no reliable argument of how it reflects anything in the brain.
The second problem is that the neurotransmitter in the brain mainly exists inside neurons (neural cells). When a neuron is active, it would then release neurotransmitter to the next neuron to pass electrical signals. It was a very quick release through junction between neurons, which is called synapse. Once the neuron goes inactive, the excess neurotransmitter in the synapse get recollected (reuptake). Even if we measure the neurotransmitter inside the neuron, it might not be a good clue about how much the chemical is used during neuron activation. And measuring it when it was in synapse for a very brief time is quite an obstacle. Instead, we may be able to measure the amount of neurotransmitter receptors the neuron has. As receptor is necessary during release of neurotransmitter, the increasing amount of receptors reflect the increasing activitty of neurotransmitter. However, receptor is not soluble and remain attached to the neuron. One of the way to visualize it is by sending "dummy neurotransmitter" attached with radioluscent materials visible in X-ray or MRI (so that they attach to the receptors and we can see how much receptor is there). but even then, the result is variable as we mostly use animal study, which may or may not have psychiatric disorder (animal model is yet another obstacle as we cannot diagnose animal with interview).
The third problem is that many neurons use the same neurotransmitter, while they may convey completely unrelated information. Let's assume that we see three neuron and name it neuron A, neuron B, and neuron C. Increase of total amount of neurotransmitter in a single place does not necessarily mean all individual pathways got more active. Even if certain neurotransmitter increases by two-fold the concentration, it doesn't mean the activity of neuron A is increased as well. And each of these three neurons may govern completely different pathways and completely different inputs, even when the target area is close by.
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Zipurshy RB, Reilly TJ, Murray RM. The myth of schizophrenia as a progressive brain disease. Schizophr Bull 2013;39:1363-72
Andreasen NC, Liu D, Ziebell S, et al. Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am J Psychiatry 2013; 170:609-15
Dorph-Petersen KA, Pierri JN, Perel JM, et al. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 2005;30:1649-61
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Dear Giacinto
Antipsychotics are not addictive as are drugs like cocaine, narcotics, benzodiazepine, alcohol. People with schizophrenia usually don't want to take them and stop taking them without withdrawal side effects or developing a craving for them.
Antipsychotics do have a street value in some places. A lot of people abuse painkillers such as paracetamol, not because they are in pain or that they are trying to harm themselves, but that it makes them feel good. Paracetamol is hardly described as addictive. A lot of people love and eat too much chocolate, is that an addiction?. I myself love and eat a lot of fish, am I addicted to fish?
Antipsychotics are probabely as "addictive" as paracetamol, chocolate and fish, but are hardly in the same category of addiction as cocaine, narcotics, benzodiazepine, alcohol.
As to whether schizophrenia exists or not:
What should we call that state where a group of people usually from an early age start to think strange things ( by the standards of an average person) and which have come to be defined "delusions" or that the order of their thoughts gets disrupted (come to be defined as "thought disorder"), start to hear voices (come to be defined as "auditory hallucinations").
And what should society do with these unfortunate people if anything?
When Loren Mosher started his career was Loren not aware that he will have to be dealing with antipsychotic drugs or what his job role would be? What alternatives did he have to offer?
There is still a lot of uncertainties in mental health but this is so in many other fields.
Software is released with the full knowledge that it still contains "bugs" which will need to be fixed later.
The aeroplanes of the 1960's were not as safe as they are now. Even the aeroplanes of today are not 100% safe, they still crash. It is by a process of iteration that improvements are made . We do not need a complete understanding of a problem, before we try to do anything about it. We still fly incompletely safe planes and release software with "bugs" in.
One solution to schizophrenia is antipsychotics and psycho-education (according to the current paradigm).
What is the alternative solution suggested by those who doubt this (and what is the evidence for these alternatives) especially for those who are not happy with their delusions and hallucinations and are suffering massively being driven to suicide for instance?
You state about antipsychotics that:
"It is certain that they involve deep changes in brain function, they are addictive and, above all, difficult to suspend, at the cost of coming back of an increased form of symptoms, often mistaken with a relapse of the disease."
You state about schizophrenia (about which you are not sure whether it exists) that:
"It is a useless operation if we think that schizophrenia is a biological disorder and its symptoms are only something to be attacked and eliminated."
This means that when drugs that act on the brain, about which you do agree, are stopped the "symptoms" come back. How is that possible if schizophrenia has nothing to do with the brain and is not a biological disorder and these drugs do act on the brain and work biologically.  Is it a side effect of these drugs that they get rid of the symptoms, by acting on some other organ and what organ is this? But if they do that they are still acting biologically. How can these agents that affect biology affect a non biological condition? On the other hand, applying Occams Razor the conclusion is that schizophrenia is a neurobiological condition affected by agents that act on the neurobiology.
How do you explain that the symptoms of a non biological condition get worse when these biology altering agents are stopped?
That it is unwise to accept that schizophrenia is a condition that does exist, that it is unwise to accept that it is a brain disorder, that it is unwise to accept that it can be treated by antipsychotics will require a lot of proof that obeys the rules of logic in order to bring about a paradigm shift away from the current. Paradigm shifts have happened before when insulin comma therapy was abolished, thalidomide was withdrawn, sertindole was withdrawn, use of leeches were withdrawn etc.
Doubters of the current schizophrenia paradigm need to bring about a paradigm shift with evidence  that follows the rules of logic in order to get their paradigm accepted by all.
Please see
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I have 2 group of mice, one of them should have seizure like behaviors, however, I didn't notice that phenotype, so I want to induce seizure in mice, and check if there are some difference between the 2 groups, anyone can give me some suggestions? thanks a lot!  Hailong Hou
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I agree with the answers already given, but I would like to add: ECS can be used to measure seizure threshold.  If you are for example, testing antiepileptic drugs, it might be useful to find out if the threshold rises when the mouse has been given the drug.  Good luck!
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Can anyone recommend a drug that either a) increases tonic dopamine in the striatum and has a short half-life, or b) decreases tonic DA but does not affect phasic DA?
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Recently I learned of the potent CYP1A2 induction effects of proton-pump inhibitors (ie. omeprazole etc). These medications can significantly reduce olanzapine and clozapine concentrations. Which medications are we overlooking when it comes to CYP1A2 induction?
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Here are some drugs that induce CYP450 1A2: and that can reduce the AUC of olanzapine. The ratio of the AUC olanzapine alone and in the presence of these inductors(AUC*) is as follows :
1-Ritonavir (200-400mg/d) : AUC*/AUC = 0.89
2-Ritonavir (600-800 mg/d) : AUC*/AUC = 0.56
3-Darunavir: AUC*/AUC = 0.89
4-Lopinavir:AUC*/AUC = 0.84
5-Rifampicine (450-600 mg/d): AUC*/AUC = 0.66
6-and also Tobacco (10-20/d ) is an inducer of CYP 450 1A : AUC*/AUC = 0.78
NB: in the absence of an inducer the ratio is equal to 1.
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Papakostas et al showed adjunctive LMF to be effective in treatment of mdd in 2012 with a NNT of 6 patients. The 2014 follow up article in J Clin Psych by Papakostas et al assessed biomarkers of LMF responders showing no statistically significant difference in HDRS-28 scores between MTHFR 677 CC (wild type) and MTHFR 677 TT (varient, reduced activity) patients.
Reduced or inactive MTHFR activity is not specific to depressive disorders.
Where does this leave us when depressed patients present with reduced or inactive MTHFR? I am thinking it should not lead towards LMF supplementation.
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Agree with Ian Mcgrane. This is a new market, with Deplin claiming to be superior to Enlyte and visa versa: the representatives are doing their job well, as are the new companies that tout the benefits of MTHR genotyping.  BUT THE SCIENCE IS NOT THERE TO JUSTIFY MAKING THIS STANDARD CLINICAL PRACTICE. And we should not be wasting patient's $ on this without basic and translational research making risks vs benefits clear.
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I have been thinking about using Clarity to compare the expression of specific protein before and after addictive drug treatment, to kind of visualizing aberrant plasticity at molecular level. But wondering if the resolution of Clarity would be good enough for this purpose, since the abnormal circuits are the primary reports from the Clarity methodology.
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"Conscious activity" here means Primary Consciousness (G. Edelman), or Sentience in the sense of the capacity of Feeling. There is no doubt that higher cognitive functions are carried by neurons.
Several lines of evidence have related astroglial function with conscious processes. I make a brief summary of the most interesting studies, many of them discussed in my previous publications (Pereira Jr. and Furlan, 2009; 2010; Pereira Jr, 2013; 2014). These results come from several independent respected laboratories. Schummers et al (2009), in a work carried on the M. Sur Lab in MIT, found that astrocytes in the visual cortex are more sensitive to external stimuli than neurons. Thrane et al. (2012) from the M.Nedergaard Lab in Rochester-USA found that astrocytes are more sensitive to three commonly used general anesthetics than neurons. Sfera et al. (2015) argue that conscious delirium derives from a combination of cholinergic inflammatory processes and astroglialfunction failure. A conference summary of empirical results indicating the involvement of glial cells in mental activities appeared in Douglas Fields et al. (2014).
By means of the feedback on neurons, astrocyte information processing can have an effect on learning, memory and behavior (for a recent review, see Robertson, 2013).Takata et al. (2011) found that astrocytes mediate cholinergic neuromodulation into cortical plasticity.  Han et al. (2013) inserted human astrocytes in the mouse forebrain and found an improvement of cognitive performance. In this regard, Lee et al.(2014), from the T.Sejnowski Lab in the Salk Institute found that toxic deactivation of astroglial functions impairs recognition memory, a task that involves conscious recall and processing of novelty.
Astrocytes also seem to be involved in the instantiation of emotional feelings and psychosomatic responses, as in the case of chronic pain (see Chen et al., 2012; 2014; Ji et al., 2013). As the mediation between neurons and blood is made by astrocytes through the blood-brain barrier, astrocytes constitute the effector part of the hypothalamus (Panatier et al., 2006; Gordon et al., 2009) and nucleus accumbens (Bull et al, 2014), controlling the release of neuropeptides and their effects on conscious mood and feelings(e.g. hunger.; see Yang et al., 2015; Wang et al., 2015)and their related somatic responses, as the up-regulation of stress-related proteins (Zhao et al., 2008). More recently,Orstroff et al. (2014) from the J. LeDoux Lab in New York University discovered that astroglial processes retract from synapses with neurons that mediate fear signaling in the amygdala, and Will et al. (2015) related the number of astrocytes in the hypothalamus with the experience-learned ability to reach male orgasm.
References:
Bull C, Freitas K, Zou S, Poland RS, Syed WA et al. (2014 Rat Nucleus Accumbens Core Astrocytes Modulate Reward and the Motivation to Self-Administer Ethanol after Abstinence. Neuropsychopharmacology (2014) 39: 2835–2845.
Chen MJ, Kress B, Han X, Moll K, Peng W, Ji RR,Nedergaard M. Astrocytic CX43  hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury. Glia60(11):1660-70.
Chen G, Park CK, Xie RG, Berta T, Nedergaard M, Ji RR. (2014) Connexin-43 induces chemokine release from spinal cord astrocytes to maintain late-phase neuropathic  pain in mice. Brain137(Pt 8):2193-209.
Douglas Fields R, Araque A, Johansen-Berg H, Lim S, Lynch G, Nave K,Nedergaard M, Perez R, Sejnowski T, Wake H. (2014) Glial Biology in Learning and Cognition. Neuroscientist. 20(5): 426–431.
Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG and Carmignoto G.
(2004) Neuronal Synchrony Mediated by Astrocytic Glutamate Through
Activation of Extrasynaptic NMDA Receptors. Neuron 43(5): 729-43.
Gordon, G.R., Iremonger, K.J., Kantevari, S., Ellis-Davies, G.C., MacVicar, B.A., Bains, J.S. (2009) Astrocyte-mediated distributed plasticity at hypothalamic glutamate synapses. Neuron 64: 391–403.
Han X, Chen M, Wang F, Windrem M, Wang S, Shanz S. et al. (2013) Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12:342–53.
Ji RR, Berta T, Nedergaard M. (2013) Glia and pain: is chronic pain a gliopathy? Pain 154 Suppl 1:S10-28.
Lee HS, Ghetti A, Pinto-Duarte A, Wang X, Dziewczapolski G, Galimi F, Huitron-Resendiz S, Piña-Crespo JC, Roberts AJ, Verma IM, Sejnowski TJ, HeinemannSF (2014) Astrocytes contribute to gamma oscillations and recognition memory. ProcNatlAcadSci U S A111(32):E3343-52.
Ostroff LE, Manzur MK, Cain CK, Ledoux JE. (2014) Synapses lacking astrocyte appear in the amygdala during consolidation of Pavlovian threat conditioning. J Comp Neurol. 522(9):2152-63.
Panatier, A. (2009) Glial cells:indispensable partners of hypothalamic magnocellularneurones.J.Neuroendocrinol. 21:665–672.
Pereira Jr. A (2013) Triple-Aspect Monism: A Conceptual Framework for the Science of Human Consciousness. In A. Pereira Jr. & D. Lehmann (Eds.)The Unity of Mind, Brain and World: Current Perspectives on a Science of Consciousness (pp. 299-337). Cambridge, UK: Cambridge University Press.
Pereira Jr. A (2014) Triple-Aspect Monism: Physiological, mental unconscious and conscious aspects of brain activity. Jnl. Integr.Neurosci., 13(2), 201-227.
Pereira, A. Jr., &Furlan, F.A. (2009) On the role of synchrony for neuron-astrocyte interactionsand perceptual conscious processing. J. Biol. Phys.35 , 465– 481.
Pereira, A. Jr., &Furlan, F.A. (2010) Astrocytes and human cognition: Modeling informationintegration and modulation of neuronal activity. Prog.Neurobiol. , 92 , 405– 420.
Pereira, A. Jr., Barros, R.F. & Santos, R.P. (2013) The calcium wave model of the perception-action cycle: Evidence from semantic relevance in memory experiments. Front. Psychol. 4: 1–-4.
Robertson JM. (2013) Astrocyte domains and the three-dimensional and seamless expression of consciousness and explicit memories. Med Hypotheses 81(6):1017-24.
Schummers,J,Yu, H and Sur, M (2008) Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320: 1638–1643.
Sfera, A, Osorio, C, Price, AI, Gradini, R and Cummings, M (2015) Delirium from the gliocentric perspective. Frontiers in Cellular Neuroscience 9: 171.
Takata, N., Mishima, T., Hisatsune, C., Nagai, T., Ebisui, E., Mikoshiba, K., Hirase, H. (2011) Astrocyte calcium signaling transforms cholinergic modulation to cortical plasticity in vivo.J. Neurosci. 31(49), 18155–18165.
Thrane, AS, Thrane VR, Zeppenfeld D, Lou N, Xu Q, Nagelhus EA & Nedergaard, M. (2012) General anesthesia selectively disrupts astrocyte calcium signaling in the awakemouse cortex. Proc. Natl. Acad. Sci. USA, 109, 18974–18979.
Wang, F. Smith, N.A., Xu, Q., Fujita, T., Baba, A., Matsuda, T., Takano, T., Bekar, L. &Nedergaard, M. (2012) Astrocytes modulate neural network activity by Ca2+-dependent uptake of extracellular K+. Sci Signal., 5, 26.
Wang Y, Hsuchou H, He Y, Kastin AJ, Pan W (2015) Role of Astrocytes in Leptin Signaling.J MolNeurosci. [Epub ahead of print]
Will RG, Nutsch VL, Turner JM, Hattori T, Tobiansky DJ, DominguezJM(2015).Astrocytes in the medial preoptic area modulate ejaculation latency in an experience-dependent fashion.BehavNeurosci. 129(1):68-73.
Yang L, Qi Y and Yang Y (2015).Astrocytes Control Food Intake by Inhibiting AGRP Neuron Activity via Adenosine A1 Receptors.Cell Rep. 11(5):798-807.
Zhao Y, Xiao J, Ueda M, Wang Y, Hines M, Nowak TS Jr, LeDoux MS. (2008) Glial elements contribute to stress-induced torsinA expression in the CNS and peripheral nervous system. Neuroscience 155(2):439-53.
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Dear Alfredo, as a hands-on clinician I always seek to understand what is happening underneath my hands when I work with people and underneath my own skin as I continuously glean information from my inner and outer environments. I very much appreciate the increase in understanding of the astroglial functions you are doing so much to help to bring about. Personally I consider the coherent order of water hydrating the astroglial network of particular importance in view of the protonic and electronic flow of information it makes possible as well as the high degree of sensitivity and responsiveness to resonance itbrings about. 
Recently in an article by James Oschman, which I am trying to find and will post as soon as I do, I read about research that revealed the structure of certain "connective tissue" fibrils in the eye that are right-turning on both sides... the only structures in the head that  are not symmetrical as in a mirror. I have to go, but will try to find this research and post it here.
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Adler et al., (1999) found that formal thought disorder can be induced by administering ketamine to healthy volunteers. Is anyone aware of any literature that shows the long term effects of ketamine administration? Does ketamine only induce formal thought disorder directly after use? Or can ketamine produce an episode of formal thought disorder, even when it has not been used for a while?
I cannot find any studies that illustrate this, but I do not want to assume that there is no research in this area.
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The 2002 World Health Organisation (WHO) Critical Review of Ketamine offers some guidance on the chronic effects of Ketamine use (see p.18), and suggests that long-term, heavy use may result in cognitive deficits similar to those you describe.
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Selective norepinephrine and serotonin reuptake inhibitors (SNRI's) are commonly used in the treatment of cataplexy because cataplexy is the result of down dysregulated norepinephrine, itself the result of missing or greatly diminished orexinergic signaling.  
However, cataplexy is also occasionally treated with Phentermine, which is a norepinephrine releasing agent.
What happens when a person takes both a releasing agent and a reuptake inhibitor (not necessarily specific to this example, but generally)?  Is the result a greater concentration/availability of the protein you're after than you'd get with either individually?
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That's the kind of thing I was hoping for!  The abstract is very clearly written and already has given me some insight, so I'm expecting to enjoy the full text article.  Thanks!
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Does anyone have figures for receptor affinities for older antipsychotics? I would be very grateful as I cannot find any data for drugs like zuclopenthixol, droperidol> I expect that they have significant histamine blockade but cannot see any on various published diagrams.
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Search Bryan Roth's Ki database:  http://pdsp.med.unc.edu/pdsp.php
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If i have left over solution of CNO + DMSO that has been diluted in saline... Can i store this in -20 and reuse it in the future?
Or is making it fresh every time my only option?
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I make a big batch and freeze it in aliquots. I thaw one aliquot and dilute it to working concentration and use that for about 2 weeks (storing at 4C in between uses). It has worked fine for me. I can't remember if I ever refroze it and used it again. I probably did, but my experiments worked, so I didn't think twice about it.
Also I make up CNO in saline, not DMSO.
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Cross addiction refers to the presence of two or more addictions - a common trait among addicts. Many cross addicted patients develop secondary dependencies in an effort to deal with their Cross addiction refers to the presence of two or more addictions - a common trait among addicts. Many cross addicted patients develop secondary dependencies in an effort to deal with their primary addiction..
What are the somatic and psychological factors that cause a cross addiction after primary addiction?
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A different take on addiction is delivered by Bruce Alexander in his 2008 book "The Globalization of Addiction". While he does not directly address cross-addiction in his book, it's easy to see how it would fit within his theory.
Here is the link to a speech Alexander gave that contains salient points of the book. Maybe you find it interesting.http://www.brucekalexander.com/articles-speeches/277-rise-and-fall-of-the-official-view-of-addiction-6
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We use many agents "off label" (eg carbamazepine for bipolar) yet given history of abuse and psychotic reactions to both ketamine and phencyclidine we need to be cautious. In what situations should clinicians cross the line and administer ketamine?
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Great article thanks Devin (I cant work out how to attach articles as I just get an error message!) - I think it is fairly obviously a secondary cascade following ketamines acute effect on the nmda subset of glutamate.  I found this article discussing the meta plasticity changes particularly in the structure and function of the hippocampus to be illuminating as that would have implications on recovery from trauma ie inducing resilience (NMDA Receptors and Metaplasticity: Mechanisms and Possible Roles in Neuropsychiatric Disorders. Neurosci Biobehav Rev. 2012 March ; 36(3): 989–1000)
.  We are about to publish a case report postulating that ketmine could be an adjunct to psychological interventions to deal with depression associated with trauma.
Incidentally all this concern over psychosis being caused by Ketamine - I am concerned that people are confusing the acute dissociation effects for psychosis and they are very different - Oxford have seen zero zilch psychotic effects as have we ie none!! But dissociation certainly!!
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The patient has responded to several APs regarding positive features but the negative features are quite treatment resistant to risperidone, olanzapine, amisulpride, ziprasidone, and aripiprazole.  Thanks.
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Consider to add mirtazapine as a coadjuvant therapy for antipsychotic treatment (e.g., aripiprazole). There is several clinical trials supporting the usefulness of mirtazapine for treating negative symptomatology when a given antipsychotic alone is unable to do it. See for instance: 
- Caforio et al. Mirtazapine add-on improves olanzapine effect on negative symptoms of schizophrenia. J Clin Psychopharmacol. 2013 Dec;33(6):810-2.
- Terevnikov et al. Add-on mirtazapine improves depressive symptoms in schizophrenia: a double-blind randomized placebo-controlled study with an open-label extension phase. Hum Psychopharmacol. 2011 Apr;26(3):188-93.
- Stenberg et al. More evidence on proneurocognitive effects of add-on mirtazapine in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jun 1;35(4):1080-6.
- Cho et al. Mirtazapine augmentation enhances cognitive and reduces negative symptoms in schizophrenia patients treated with risperidone: a randomized controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jan 15;35(1):208-11.
- Terevnikov et al. More evidence on additive antipsychotic effect of adjunctive mirtazapine in schizophrenia: an extension phase of a randomized controlled trial. Hum Psychopharmacol. 2010 Aug;25(6):431-8.
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G'day,
The synthetic cannabinoids (SC) currently being marketed as alternatives to plant cannabis have a higher risk of adverse outcomes than phyto (plant) cannabinoids.
The SC products on the market are much stronger agonists at the CB1 receptor than THC, and none contain a synthetic equivalent to the phyto-cannabinoid CBD, but is part of the increased risk also due to SC substances acting at other receptor sites?
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It is an important question but, unfortunatelly, but there is no published data on effects on non-cannabinoid targets. None. Anything that has been mentioned here in the comments is mere speculation. In vitro studies, such as receptor profiling or enyzme screeing, are urgently needed. At a meeting organized by the European drug agency EMCDDA last year I gave a talk on new and some anticipated SCs as well as some similar structures but with different mode of action. Selected slides relevant to this topic can be found in the downloadable pdf file. Note that the list of structurally related substances such as etonitazene or indibuline, is incomplete. Furthermore, it would be interesting to test these latter 'non-cannnabinoid' compounds for CB receptor effect.
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Thanks in advance!
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Hi Felipe,
Impairment of PPI is thought to be a measure of sensorimotor gating deficits, which appears to be also impaired in several neurological and psychiatric diseases (e.g. schizophrenia, Alzheimer, etc.). However, there is no robust evidence suggesting consistent relationships between lower levels of PPI and higher levels of specific symptoms of schizophrenia such as positive or negative symptoms scores. Similarly, no relationships between acoustic PPI and working memory as well as other formal indices of neurocognitive function, have been detected among schizophrenia patients (e.p., Swerdlow wt al. Psychopharmacology 2009, 199(3):331). It is my suspect that, by now, PPI models would rather be useful to evaluate mechanism involved (or thought involved) in antipsychotic effects (p.e., D2 antagonism, serotonergic, cholinergic, NMDA, etc.) than to evaluate specific effects of schizophrenia simptomatology of antipsychotic drugs.
Regards,
Jordi S
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I was wondering if there was any association between phenylketonuria (PKU) and stuttering. I have tried searching the literature, but unfortunately couldn't find much at all (other a paragraph on p58 of Multilingual Aspects of Fluency Disorders by Howell et al). In your opinion, is it possible for PKU (or its various subtypes) to cause a person to stutter? Why or why not? I am mostly interested in the genetic and pharmacological side of things but would really appreciate any input on the topic.
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Perhaps one of these publications related to BH4 can answer your question:
Shintaku H. Disorders of tetrahydrobiopterin metabolism and their treatment. Curr Drug Metab. Apr 2002;3(2):123-31. [Medline].
Li H, Förstermann U. Pharmacological Prevention of eNOS Uncoupling. Curr Pharm Des. Oct 29 2013;[Medline].
Dubois M, Delannoy E, Duluc L, et al. Biopterin metabolism and eNOS expression during hypoxic pulmonary hypertension in mice. PLoS One. 2013;8(11):e82594. [Medline]. [Full Text].
Kim HK, Ha SH, Han J. Potential therapeutic applications of tetrahydrobiopterin: from inherited hyperphenylalaninemia to mitochondrial diseases. Ann N Y Acad Sci. Jul 2010;1201:177-82. [Medline].
Crabtree MJ, Hale AB, Channon KM. Dihydrofolate reductase protects endothelial nitric oxide synthase from uncoupling intetrahydrobiopterin deficiency. Free Radic Biol Med. Jun 1 2011;11:1639-46. [Medline].
Adlam D, Herring N, Douglas G, et al. Regulation of ß-adrenergic control of heart rate by GTP-cyclohydrolase 1 (GCH1) and tetrahydrobiopterin. Cardiovasc Res. Mar 15 2012;93(4):694-701. [Medline]. [Full Text].
Thony B, Blau N. Mutations in the BH4-metabolizing genes GTP cyclohydrolase I, 6-pyruvoyl-tetrahydropterin synthase, sepiapterin reductase, carbinolamine-4a-dehydratase, and dihydropteridine reductase. Hum Mutat. Sep 2006;27(9):870-8. [Medline].
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It is well established that depressed individuals tend to focus their attention on unhappy and unflattering information, to interpret information negatively, and to harbour pervasively pessimistic belief.
Should we consider negative processing biases when rodent models are used to determine antidepressant-like effects of drugs/extracts? If so, how?
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