http://www.slideshare.net/adonissfera/brain-art

In Scottsdale, Arizona there is a strange warehouse, called Alcore Life Extension Foundation. This warehouse contains metallic containers called “dewars”. They look like gigant thermos bottles filled with liquid nitrogen. They contain either four human corpses or six human heads. One can join Alcor by guaranteeing a 200,000 payment to be handed over when he or she are pronounced legally dead. For this fee Alcor will preserve their body indefinitely at 196 degrees below zero. Alcor offers discounts if clients chose to preserve their head only_ it cost only 80,000 dollars. This company came into public awareness in 2002 when the baseball star, Ted Williams died and his family sent his body for preservation.
Alcor members are optimists who believe that many years from now science will be able to revive them from their deep cryogenic sleep. In other words they hope in immortality. Let’s open a discussion on wether their belief has any scientific grounds.
From the book “Connectome” by Sebastian Seung

SYNAPTIC COMMUNICATION: Synaptic communication is mostly unidirectional goes from the dendrite, to cell body, to axon, to next neuron’s dendrite( since most synapses are axo-dendritic).
Axons and dendrites not only look differently, but they have different functions.
Axons look like spaghetti, and they fire the action potential (signals).
Dendrites look like capelini and produce an electrical field that resembles static electricity.

Since dendrites contain numerous synapses some of the information dendrites bring to the cell body might be contradictory with the information the next dendrite brings. Moreover there are inhibitory and excitatory synapses.

The cell body has to make sense of this informational input and decide quickly to fire an action potential or not. It works like voting – if the “yes” votes are more prevalent and uninhibited, they reach a threshold and an action potential is being produced.
Synaptic transmission works by binary logic: an action potential is either produced or not.

EXTRASYNAPTIC COMMUNICATION: includes neuron to neuron communication by oher means than the synapse ( neuromodulation, electromagnetic transmission, neurocrine/paracrine transmission, etc)

Extrasynaptic transmission behaves according to non-binary logic also called fuzzy logic.

In the 60s Lofti Zadeh applied mathematical principles to the study of biological systems. He used an algoritm known as centroid averaging. It is appropriate to suggest that the neuron too is a centroid avenger, processing input from synapses and extrasynaptic receptors.

In fact Waldayer and Cajal came up with the “neuron theory” more than 100 years ago. This theory considers the neuron a discrete cellular entity.
About the same time Golgi proposed a reticular or network of nerve cells as an anatomical or functional syncitium.
Today we associate synaptic transmission with Cajal and extrasynaptic transmission with Golgi and we know that they are both true.

For instance precise movements like playing piano would use quick synaptic transmission, but sustained phenomena like wakefulness would use extrasynaptic transmission.
Adonis Sfera, MD

The difference in thinking pattern between people from the East and the West was intuited for a long time. The British writer Rudyard Kipling thought that the Eastern and Western mind could not be reconciled. According to Jung, the Asian mind is more introverted, collectivist and mystical. The West believes “in doing” while the East in “impassive being” (Jung, 1958, p. 560). The West has consequently developed a materialist science that is focused on the outer world–which it endeavors to control and exploit. In Asia, where most religions have arisen, consciousness has been directed inwardly to understand the essential nature of life.

Recently a new branch of science, cultural neuroscience, took shape. In his book “The Geography of Thought”, Richard Nisbett, a social psychologist from the University of Michigan, conducted an experiment. The test subjects of the experiment were 25 American and 27 Chinese students. Each of them was shown 36 photos, and they were allowed to see each photo for 3 seconds. Each photo depicted a single subject against a realistic and complex background. For example, one photo showed a tiger (the single subject) in a forest (the complex background).

Nisbett’s experiment shows that it takes a shorter amount of time for the American test subjects to focus their attention on the foreground image of each photo, and they also spent a longer time looking at the foreground image than the Chinese test subjects did. On the other hand, the Chinese test subjects spent more time looking at the background images and less time on the foreground images. When the test subjects were given memory tests afterwards, the Chinese test subjects could remember the background images more clearly and the American test subjects could remember the foreground images more clearly.

Another similar experiment was completed at the University of British Columbia by Steven Heine. He and three colleagues recruited two groups of students—one Euro-Canadian and the second Japanese—and he gave them a bogus “creativity” task. The test was graded, and the students were told they had done well on some parts and poorly on others. Heine was interested in what would come next. The students were given a second, similar test, and the psychologist and his colleagues secretly watched how the subjects tackled it. Turned out there was a glaring difference. The Westerners worked longer on the stuff they were told they had aced the first time. The Easterners concentrated on the areas they thought they had botched. Students from the West—where the cult of self-esteem reigns supreme—wanted a tummy rub. Students from the East were more concerned with fixing their blind spots, becoming well-rounded. The Westerners polished up their strengths while the Easterners addressed their weaknesses. If you show an “Easterner” (someone of East Asian extraction) and a “Westerner” (of European lineage) a photograph, says Heine, and you track their eye movements, you notice something curious. Both subjects fix on some focal point in the picture for about a second. After that, things change. The Westerner continues to gaze at that spot, on that central tree in the forest of possible places to look. The Eastern eye, however, is all over the place, scanning hither-thither, trying to take in the whole forest. Even if the subjects are instructed to focus on a dot in the middle of a screen, University of Alberta psychologist Taka Masuda found, East Asians continually scan the void around that dot, pumping for context, for linkages.
Trey Hedden, PhD, from Stanford and his colleagues used fMRI to look at these findings. Participants see a square with a line drawn partway down the middle. They then see a larger box and either have to draw a line the same absolute length as the first line or a line the same relative length compared with the bigger size of the new box. Americans did better on the absolute test and Japanese did better on the relative test. It turns out that both Americans and Japanese use the same brain areas for both tests, but when they’re doing the test that is more difficult for them, they also engage an area of the brain associated with increased attention.
“This finding shows that the brain compensates for tasks that we’re not typically exposed to through our culture by turning on an attention circuit to help us,” says Hedden. In contrast, tasks that are commonplace become automatic and don’t require extra concentration.
While cultural neuroscience has mostly shown how culture shapes biology, researchers are also beginning to examine how biology shapes culture.
Northwestern University’s Joan Chiao, PhD, for example, has found that people who live in collectivist cultures are more likely than those in individualistic cultures to have a form of the serotonin transporter gene — the S-allele — that correlates with higher rates of negative affect, anxiety and depression.
In contrast to what you might expect from the genes alone, she also found that people from collectivist societies are less likely to be depressed. This suggests that collectivism, which tends to produce lower levels of negative affect, may have co-evolved with the S-allele, says Chiao, who published her findings in the Proceedings of the Royal Society of Biological Science (Vol. 277, No. 1,681).
In the end, cultural neuroscience could usher in an era of greater understanding between people from different cultures.

ADONIS SFERA, MD

This term was coined by Thomas Insel, director of NIMH in a 2007 article in the journal

Early Intervention in Psychiatry, published by Patrick McGorry who pioneered early

intervention (EI) in mental illness.

Dr. Insel argues that most patients get better with current interventions, but they are not

recovered. Many patients are not responding to available treatments, and many

treatments are not accessible to those who need them.
Indeed even with the new and improved antipsychotics and supportive psychotherapy sustained recovery occurs in less than 14% within the first five years following a psychotic episode. Nearly 20% of people with schizophrenia are homeless. Lack of curative or preventative approaches reflect the lack of basic understanding of the pathophysiology of schizophrenia and what Dr. Insel calls ‘the soft bigotry of low expectations’.
The view of schizophrenia in our society is the one imprinted by Kraepelin who thought that it was irreversible and that it inevitably led to dementia. This led to palliative approaches and discouraged prevention. The same view is being perpetuated by the DSM system which describes schizophrenia in terms of chronicity (the six months duration criterion).
In reality a large recent meta-analysis study examining the outcome of first episode schizophrenia (and other psychosis) looking at data from 1966-2003, found good outcome in 42%, intermediate outcome in 35% and poor outcome in 27% of patients (Menezes, Arenovich, Zipursky, 2006).
Dr. Patrick McGorry from the University of Melbourne, Australia studied early recognition and early intervention (EI) in schizophrenia and concluded that the shorter the duration of untreated psychosis (DUP) the better the prognosis. This led to attempts of identifying people at ultra high risk (UHR) of schizophrenia and treating them preemtively with neuroprotective agents such as omega-3 fatty acids and individual psychotherapy (small doses of antipsychotic medications, lithium and antidepressants were also considered). Eventually an “oncology model” gradually emerged according to which prodromal cases are being treated very differently than those of early onset psychosis or “burn out phase” psychosis.
Australia has been leading the world in early intervention (EI) psychiatry. Ninety
enhanced primary care platforms or ‘headspace’ centers will be spread across the
country by 2015. The US has been lagging behind Australia, Ireland, UK and Canada in
regards to early intervention in mental illness, but we are catching up with
the help of Dr. Kane and Dixon from NIMH and their teams which developed two
programs as part of the Recovery After an Initial Schizophrenia Episode (RAISE)
project. They are:
RAISE Early Treatment Program: http://www.connectionprogram.org/?page_id=17
RAISE Connection Program.: http://www.connectionprogram.org/.
RAISE Project can be found at: http://www.nimh.nih.gov/health/topics/schizophrenia/raise/index.shtml
The journal Early Intervention in Psychiatry is being published for the past five years
with emphasis is on early detection and early intervention in mental illness.
Here is an interview with dr. McGorry: http://www.youtube.com/watch?v=G0ctdsIHHq

FOR DAILY NEWS ON SCHIZOPHRENIA AND NEURODEGENERATIVE DISORDERS PLEASE VISIT DR. SFERA’S LINKEDIN GROUP NEURODEGENERATIVE DISORDERS

Human Endogenous Retroviruses (HERV) are enveloped viruses that contain two stranded ribonucleic acid (RNA) genomes. The virus possesses a reverse transcriptase enzyme that can insert it into the chromosomal DNA.
HERVs exist in two forms: as a viral RNA particle or as a provirus integrated into the DNA. HERVs in their provirus form make about 8% of human genome.

Most of the time HERVs infect somatic cells and cannot be transmitted to offspring. On rare occasions they infect germ cells and get integrated into their genome thus being transmitted to the next generation.

The process of HERVs integration into the host genome is called endogenization. Endogenization depends on three factors: host immunity, innate antiretroviral protein activity, the presence of an adequate viral receptor. After endogenization HERVs are not infectious as they are being inactivated by the host, however in certain circumstances they reactivate. HERVs contain four known antigens: pol, gag, env and LTRs.( long terminal repeats). The gag antigen encodes the capsid proteins, the pol antigen encodes the protease, polymerase and reverse transcriptase and the env antigen is required for viral budding and infection.

Most human tissues contain HERVs and their symbiotic relationship with our genomes has been beneficial, however their aberrant activity could lead to pathology. For instance, HERVs could undergo retrotransposition, (insertion in any part of the genome) and modification of proteins transcription.

HERV-W and HERV-K have been implicated in schizophrenia.
1. An element on chromosome 7q21 has been described containing an intact env gene.
2. Abnormal expression of HERV genes have been described in schizophrenia.
3. Particles containing HERV-W RNA have been identified in the plasma of patients with recent onset schizophrenia.
4. Elevated levels of gag transcripts have been described in the peripheral blood mononuclear cells after the first episode of schizophrenia.
5. Elevated levels of transcripts from the HERV-W gag were found in chromosome 11q13.5 in people transitioning from susceptibility to manifest schizophrenia.
6. Positive antigens for env and gag have been described in the serum of schizophrenic patients.

References:
Raul Alelu-Paz, Ignacio Iturrieta-Zuazo; Human Endogenous Retroviruses: Their possible role in the molecular etiology of schizophrenia; Open Journal of Genetics, 2012,2,70-76; doi 10.4236/ojgen.2012.21009

Flockerzi A, Ruggieri A. Frank O, et al.; Expression patterns of transcribed human endogenous retrovirus hery-k(hml-2) loci in human tissues and the need for a hery transcriptome project. BMC Genomics, 9,354; doi: 10.1186/1471-2164-9-354

Psychiatry continues its slow transition from the neurochemical to the molecular paradigm that started in 2002 with the completion of the Human Genome Project.
In the past quarter we continue to notice a push for biological markers in neurodegenerative disorders, schizophrenia and autism spectrum disorders (ASD) whose prevalence increased to 1 in 88 children according to CDC data published on March 29, 2012.
Here are the areas that have been heavily researched in the past quarter:
1. Connectomics (white matter tractography) remains the buzzword at most neuroscience meetings as well as at the 3rd Biennial Schizophrenia International Research Society Conference held in Florence, Italy April 5-9, 2012. Similar to the Human Genome Project, which charted every one of the three billion chemical base pairs that comprise in human DNA, connectomics aims to physically map the complete set of neural circuits that collect, process, and archive information in the brain. This growing field has the potential for testing a long-standing hypothesis on the pathophysiology of schizophrenia —the “disconnection” hypothesis. The most important paper on schizophrenia connectomics this quarter was: Schizophrenia, neuroimaging and connectomics completed at the University of Melbourne, Australia by Fornito A. et al.
More info: http://www.ncbi.nlm.nih.gov/pubmed/22387165

2. Genomics continues to take a high interest in Copy Number Variation (CNV) as exemplified by a large 5 years study published in Schizophrenia Bulletin in March entitled – De Novo Mutations in Schizophrenia Schizophr Bull (2012); doi: 10.1093/schbul/sbs047; First published online: March 26, 2012

Along with Single Nucleotide Polimorphisms (SNP), Copy Number Variations (CNV) account for approximately 60% of genetic variability. De novo copy number variation (CNV) provides the strongest evidence to date for the association with SZ. De novo mutations could account for replenishing the genetic variants removed by natural selection and could, in part, explain why SZ prevalence has remained stable in the general population despite low birth rate among patients.

3. Epigenetics continue to study microRNAs and their role in achizophrenia. MicroRNAs represent about 50% of small non-coding RNAs that control gene expression. Another small non-coding RNAs that we heard of in the past is interference RNA or iRNA (Nobel Prize was given for its discovery in 06).
A study from February 2012 was able to identify microRNA 132 as being incriminated in the etiology of schizophrenia.
MicroRNA-132 dysregulation in schizophrenia has implications for neurodevelopment and adult brain function Published online before print on February 6, 2012, doi: 10.1073/pnas1113793109.
More info:http://www.pnas.org/content/early/2012/02/03/1113793109.
4. Early detection of schizophrenia is still in the research stage but there are some very positive signs that the risk of developing the disease can be controlled and lowered. A study done at Stavanger University Hospital, in Norway by Wenche ten Velden Hegelstad and her team showed a double remission rate in the early detection group . Ten years after detection of symptoms 30.7% of patients from the early-detection group met criteria for recovery compared with 15.1% of those from the usual-detection group. These findings are in line with NIMH project Recovery After an Initial Schizophrenia Episode (RAISE) that seeks to fundamentally change the trajectory and prognosis of the disease through diagnosing and aggressively treating in the earliest stages of illness.
More info: http://www.medwire-news.md/47/98377/Psychiatry/Early_psychosis_detection_linked_to_improved_long-term_outcomes.html
An area that is growing silently without much noise in the news (probably because of being seen as a scientific alternative to the outdated DSM system) is the NIMH Research Domain Criteria (RDoC) project. The intent of this project is to translate rapid progress in basic neurobiological and behavioral research into an alternative way of classifying mental disorders.
More info: http://www.nimh.nih.gov/about/director/2012/research-domain-criteria-rdoc.shtml
Another area gaining popularity is that of the “jumping genes” or retrotransposones. They are mobile genetic elements that can copy and insert themselves within a genome causing mutations in dividing cells. “Jumping genes” are known to be active in various parts of our brain, but their involvement in schizophrenia and autism is novel. This new discovery suggests that DNA variation occurring in the developing brain could contribute to mental illness, just as mutations in mature tissues contribute to cancer. These surprising findings open a whole new vista in the biology of schizophrenia.
Along those lines a study from Germany by Olivia Diem published in January 2012 is very interesting because it raises the possibility that some psychotropic medications are able to activate human endogenous retroviruses (HERVs) that are natural components of the human genome. Elevated expression levels of various HERV groups have been repeatedly described in patients with schizophrenia and were thought to be associated with the disease. Now for the first time, the research team at Helmholtz Zentrum München has shown that this stimulation may be caused at least partially by the patients’ medication. The researchers conclude that the medication may influence the epigenetic state of some but not all HERV types (Olivia Diem et al. (2012): Influence of Antipsychotic Drugs on Human Endogenous Retrovirus (HERV) Transcription in Brain Cells. PLoS ONE, in press)
More info: http://www.research-in-germany.de/92502/2012-01-24-antipsychotic-drugs-increase-the-activity-of-endogenous-retroviruses-in-humans,print=true,slc=dachportal_2Fen.html
ADONIS SFERA, MD

Antidepressants do “really work” and do not “cause suicide,” said Anthony Rothschild, M.D., at APA’s 2012 annual meeting today during a discussion of his second book in the American Psychiatric Publishing’s Evidence-Based Guides series, the evidence-based guide to antidepressant medications.

Rothschild said that although clinicians have successfully used antidepressants to treat millions of patients suffering from depression for 50 years, Kirsch et al. published a paper in 2008 claiming that although antidepressants are statistically superior to placebo, the magnitude of the drug-placebo difference is small, and that these differences were clinically relevant only in patients with severe depression. The paper received considerable attention in the popular press, including radio, front-page newspaper coverage, and a recent story on “60 Minutes.”

Rothschild said that the focus on questions about whether antidepressants really worked needlessly upset patients and their families. He pointed out that many experts in the field have argued that the analysis by Kirsch and colleagues was seriously flawed because it relied upon unusual statistical techniques biased against antidepressants. Rothschild also noted the fact that some have questioned whether treatment with the SSRIs and other antidepressants can induce suicidal ideation and whether they worsen existing suicidal ideation. Although the totality of the reliable scientific evidence indicates that SSRIs and other antidepressants do not cause suicide, the FDA has required that all antidepressants contain a black-box warning that they are associated with “suicidality” risk in children, adolescents, and young adults up to age 24 years.

Rothschild said that clinicians should be aware of two important points: (1) the FDA’s black-box warning does not indicate that antidepressants increase the risk of suicide in anyone, or that they increase the risk of suicidal thinking or behavior in patients aged 25 and older and (2) although the FDA used the concept of “suicidality” as a proxy for completed suicide, they are not the same thing. The term suicidality has been criticized as grossly overestimating the risk of suicide and as not being as clinically useful as more specific terminology such as ideation, behavior, attempts, and suicide.

The workshop included discussions regarding the fact that antidepressants are prescribed for many patients in addition to those who have major depressive disorder, including patients with bipolar disorder, posttraumatic stress disorder, schizophrenia, and personality disorders, as well as those with other medical illnesses. The workshop reviewed the use of antidepressants for so-called off-label use—to treat illnesses for which the medications do not have FDA approval—and that practicing clinicians need to understand the use of antidepressants among several special populations, including children and adolescents, geriatric patients, and pregnant and lactating women.

“If a woman smokes during pregnancy, it may increase her child’s risk of high-functioning autism,” but a study published online at Environmental Health Perspectives, found that “the raised risk was slight…and researchers found no association between maternal smoking and more severe forms of autism.” The study was based on “data on maternal smoking from birth certificates of nearly 634,000 US children born in 11 states in 1992, 1994, 1996 and 1998,” which was “compared with information on 3,315 children aged 8 and under diagnosed with an autism spectrum disorder from the US Centers for Disease Control and Prevention’s Autism and Developmental Disabilities Monitoring Network.”http://ehp03.niehs.nih.gov/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1289%2Fehp.1104556