jbn22

1.) Postsynaptic dopamin receptors fluctuate in density. This can be influenced by pharmaceuticals, but other environmental or endogenous factors aswell. This feature is not specific for dopamine receptors, but can occur in other neurotransmitter systems as well. This is relevant in clinical settings because it requires constant vigilance for EPS in order to determine the correct dosage. A patient that may be on a neuroleptic for years may still develop early-onset EPS without a change in serum concentration. Similarly, a patient may exhibit psychosis without a change in serum concentration. Both observations show (clinically) that pharmacodynamic effects can vary with time. 2.) Aripiprazole rarely causes MNS, but some cases have been reported. ---- I am unsure as to what cases of "antipsychotics causing psychosis" you're referring to. I haven't seen such a case yet (which doesn't mean they don't exist, I'm just curious as to where you picked that up). I would expect antipsychotics to cause or aggravate negative symptoms, but not productive psychosis.

Well, first off, Aripiprazole defines a structural class distinct from FGAs (Butyrophenones, Thioxanthenes, Benzamides, Phenothiazines, etc.) and SGAs (Dibenzepines, Benzisoxalderivatives). Unlike FGAs and SGAs, Aripiprazole is a partial agonist instead of a full antagonist. This means its effect is inherently limited (ceiling) and it has a very good profile of unwanted sideeffects (no net weight gain, good function in terms of negative symptoms, etc.). The partial agonism also leads to aripiprazole being able to (when added to the regimen) actually reduce EPS in patients receiving high-dosed FGAs because it competitively inhibits FGA function. The term "third generation" antipsychotic is something I haven't heard of yet. But Aripiprazole is so much unlike the other antipsychotics due to its partial agonism that I guess you could call it that.

All the studies I know that have been conducted on the subject show that during acute phases, talking therapies have no effect on delusions or other productive symptoms. Nonetheless, I would say that - after a partial remission has been induced by neuroleptics - guiding a patient and encouraging them to reevaluate their psychotic beliefs may benefit them in terms of discerning symptoms from reality (in addition to a continuous use of neuroleptics). But that's just my opinion, I don't have studies to back that up. As for talking therapies in the intervals between active exacerbations, psychoeducation is the way to go. It's important for patients to recognize warning signs, to be informed about medication benefits and side effects and about measures to cope with stress. This has been shown to have a beneficial effect. Also I find it important for patients and caregivers to build a trusted relationship since many symptoms (and side effects of medication, e.g. sexual dysfunction) may be embarassing to speak about. I'm not sure as to how negative symptoms (apathy, alogy, lack of incentive, anhedonia, etc.) may be influenced by talking therapies.

Formal thought disorders are disorganized thinking. Since we can't "see" or "hear" thoughts, formal thought disorders are characterized by disorganized speech. Somewhat simplified, thought disorders can be an abberation in speed, initiation and coherency - or a combination of any three. A less severe thought disorder may be, for example, associative derailment (the professional term may be different, English is not my mother tongue). This would be characterized by the patient jumping from topic to topic without a sense of coherency. An example: I was brought here by the police. Police wear green uniforms. I always loved the color green. The Green Party really steps up for the environment. The environment is in big danger, due to global warming. I myself feel warm today. My coffee was very hot. I nearly burnt my tongue. => In other words, the formal thinking is constantly derailed by topics that have some relation to the sentence beforehand but the patient is not able to coherently explain why he was brought here by the police. A more severe thought disorder may be absentmindedness (again, I don't know if this is the professional English term). In this, sentences are correct in syntax but are completely incoherent. Example: I was brought here by police. Oh Jesus, oh Jesus! Trump is a great president. I have four fingers and two toes. The most severe thought disorder (in terms of coherency) is schizophasia, in which the entire language structure including is completely lost. Questions may elecit a response that seem to fit the topic, but are absolutely not understandable. For example: answering to the question "who brought you here": Trump fingers toes Jesus walking green green evil man Abu Dhabi come here you tabletop chair. Thought disorders can also be a matter of speed, where accelerated thinking/speech is witnessed in manic episodes. Patients may speak very quickly (but coherently), to the point where the examiner may be unable to follow their train of thought because they are simply "too fast". Conversely, organic dysfunctions (intoxications, for example with benzodiazepines or alcohol) may cause decelerated thinking, in which the coherency remains but the time necessary to report is significantly slower. And, last but not least, formal thought disorders can also be a matter of initiation/termination. Schizophrenics often suddenly stop during the middle of the sentence and don't realize that they had a thought that was suddenly terminated. Some even report that they are under the impression that someone else is "stealing" their thoughts from the outside as a way to explain why their train of thought is suddenly disrupted. Conversely, in major depressive disorder, patients may need a long pause before being able to answer a question. Upon asking the patients why they responded to the question only with such a delay, they often say that it's as if they "try to think but there's a blockade they need to overcome", or that they lack the drive to think. Additionally, aside from formal thought disorders, schizophrenics oftentimes also exhibit disorders in higher cognitive functions. This means, for example, they have troubles in abstraction. When asked for the meaning of a common proverb, for example, they may have troubles explaining. Or, when asked for (for example) the difference between a child and a dwarf, they may also have troubles explaining. Understanding sarcasm or irony may also be periodically disturbed during phases of increased disease activity. Also, mentalization may be disrupted. This refers to the ability to switch one's perspective into the mind of one else. That is, understanding that someone may have a different opinion or viewpoint, or that someone else may have different information. For example, someone with an acute psychosis may refer to family members and friends by their names, assuming the examiner already knows all of them.

The exact mechanisms are still not understood. Fact is that psychopharmaceuticals that counteract this imbalance lead to a significant recovery in patients suffering from schizophrenia. This is well documented (and the basis for every FDA approval of antipsychotic medication). As for studies, you will find plenty of reviews that summarize the evidence for aberrations in neurotransmitters between control groups and schizophrenia groups. As for neuroimaging data - I believe it's a matter of economics and evidence based medicine. As a practicitioner in a country with a socialized medical welfare system, it is impossible for me to justify gathering neuroimaging data of every single of my patients before perscribing them antipsychotic medications. I really wish it were easier - not so much in the area of schizophrenia (in my opinion, clinical diagnosis of schizophrenia is, in the vast majority of cases, very simple) but especially in the area of diagnosis of depression. After all, it's not rare for me to have the impression that a patient may be aggravating his symptoms in order to be diagnosed with a major depressive disorder in order to gain some welfare benefits when in fact the problem lies elsewhere. Psychiatric diagnostics is mostly clinical. The only way that I can justify further diagnostics (every first manifestation of a schizophrenic episode or major depression gets an cMRI for example) is by saying I need further diagnostics to ensure that no organic component (inflammation, tumor) is causing the symptoms. That is limited to a cMRI and, in some cases, the collection and analysis of spinal fluid. Have you ever been in a psychiatric ward that treats acutely mentally ill patients? I think there might be a misconception as to how ill someone with an acute psychotic episode actually is. It's not a matter of "believing" delusions or not - I'm no investigator. It is, much rather, a question of formal thought disorders that provide the basis for all accessory symptoms (hearing voices, delusions, ego-disorders).

RBCs do not have the necessary receptors to mediate transendothelial migration (unlike, for example, Leukocytes). Bear in mind that leukocytes also do not migrate through the cells but much rather find a gap between the cells. See the schematic below:

"No evidence" is misleading. The model of a neurotransmitter dysfunction in the genesis of depression and psychosis is something that has significant clinical relevance. In terms of psychosis, the productive symptoms quickly (i.e. within days) respond to antipsychotic medication. Of course, this isn't to say that there's an underlying cause (especially considering newer genetic findings, brain atrophy caused by neuropil degeneration, etc.). But in the end, the symptoms do also seem to be caused by dopaminergic hyperactivity in the mesolimbic system. And seeing as we have yet to find a potent pharmaceutical to stop synaptic pruning in schizophrenia, we're stuck with resorting to antidopaminergic substances. In terms of major depressive disorder, the mechanism of action of antidepressants seems to be more complex and related to gene expression. In clincal practice, I find that antidepressant therapy is mainly successful in major melancholic depression. Sadly, many general practitioners seem to perscribe antidepressants whenever a patient says they're sad. Melancholic depression is, in my opinion, not characterized by sadness, but much rather in a lack of emotional response. A

Thanks a lot! While you're right about the MHC locus, the plot in question highlights an association of schizophrenia to the MHC-III locus - a follow-up study that was published in February showed that, to be specific, the complement-4 receptor gene (which is part of the MHCIII locus) expression seems to correlate directly with schizophrenia risk. As far as I understood it, SNPs are just single areas on a gene that are used as markers in genome wide association studies. If my understanding is correct - and please, someone correct or confirm this - a haplotype is defined as a set of genes that correlate with a given SNP (that is, that have a very high linkage disequilibrium with said SNP). But, as I said, I may be wrong. Can someone help? Your line of thought got me thinking, though. In GWAS, are both sets of alleles (parental and maternal) analyzed? As such, would you have a data set of two Y-values per SNP? As in, one chromosome as an SNP of "AAAC" at position XYZ, that correlates with a risk of x for a given disease, whereas the other chromosome might have an SNP of "AGAC" that correlates with given risk? This seems sound. Thanks! Thanks anyway. I never understood those HLA-genes anyway. Do you happen to know the difference between HLA-A, HLA-DQ, HLA-DR? Do they all present to CD8/CD4 cells? Or does each subtype have a different function?

Hey guys, I need some help wrapping my head around a study on the genetics of Schizophrenia. Perhaps you guys could lend me a hand? 1.) How does a Manhattan plot work? I understand the Y-Axis shows significance and the X-Axis shows the location on the genome/chromosome, but how does the individual data add up? I would have expected one value per point on the X-Axis (that is, the value of significance that a given SNP is associated with an increased risk in the disease group). Alternatively, I could explain up to four values on the X-Axis (that is, the respective significance of an SNP (G,A,C or T) being associated with an increased risk in the disease group). And yet, when I look at the plot, I see far more Y-values for a point on the X-axis. I am afraid that I may have completely misunderstood GWAS.