Posts tagged Bipolar disorder

Research Summaries: Childhood IQ and risk of bipolar disorder in adulthood: prospective birth cohort study

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Today’s research summary focuses on an article [pdf] that throws some light on the oft debated question of the association between intelligence, creativity and mental illness.

Age-standardised disability-adjusted life year...

Age-standardised disability-adjusted life year (DALY) rates from Bipolar disorder by country (per 100,000 inhabitants). (Photo credit: Wikipedia)

  1. It has been hypothesized that various mental illnesses like Bipolar disorder, Schizophrenia etc persist in the gene pool because they are associated with some positive mechanisms that also confer survival or mating benefits, either to the patients or their close relatives. One such mechanism is thought to be apophenia (ability to see patterns, sometimes when there are none:-) ) , which is related to divergent thinking, imagination and creativity; another such mechanism is thought to be intelligence or the ability to solve complex adaptive problems flexibly.
  2. One method to settle the debate is correlational in nature. Sweden maintains rich and exhaustive data about its citizens. Mining data form the Swedish population registries, it was found that bipolar patients, as well as their relatives,  were more likely to be in creative professions;  and that bipolar traits may be associated with leadership qualities.
  3. Another method is to look at twins, one of which has the bipolar disorder, while the other hasn’t; and it was found that the other twin had high scores on sociability and verbal fluency; hinting that these may be linked to the bipolar proband.
  4. Yet another method is to look at longitudinal studies like the Dunedin studies, which track a child cohort since birth or early age and track them over time. The Dunedin studies found that low childhood IQ was associated with Schizophrenia spectrum disorder, depression an anxiety in adulthood; but high IQ was associated with mania in adulthood.
  5. The authors of this study used a longitudinal study design, analyzing the results of ALSPAC, a large UK birth cohort. This cohort consist of about 15,500 participation, but after all the dropout etc only about 2000 subjects results were part of the study results.
  6. This study focused on association of childhood IQ (which is an imperfect measure of true intelligence) with propensity for bipolar disorder in young adulthood. This study did not look at creativity and did not look at actual occurrence of bipolar disorder, thus all the results should not be extrapolated wildly.
  7. Childhood IQ at age 8 was measured using WISC-III and separate verbal and performance IQ as well as Full IQ scores were used in analysis. Propensity towards bipolar was measured using HCL-32 (hypo-mania checklist) which consist of 32 yes/no answers to statements like ‘I am more easily distracted’ when in a state of ‘high’ not associated with drug use. Only 28 items from this checklist were used.  This was administered at ages 22-23 years.
  8. Childhood IQ was indeed associated with higher scores on HCL-32. The scores on HCL-32 were converted into percentile scores. Those subjects, who were in the lowest decile of HCL-32, or alternately had the lowest risk for later bipolar, had IQ scores that were 10 points on average lower than those subjects who were in the highest decile of HCL32 (had the highest bipolar risk).
  9. The IQ scores were also made categorical. Looking at data from another way, those who had the lowest verbal IQ scores (were in the ‘extremely low’ of VIQ) had on an average 7.1 points less score on HCL-32 than the ‘average’ VIQ group. The ‘ Very superior’ VIA group had scores  1.83 points higher than ‘average’ IQ group.
  10. As the age at which, HCL-32 was administered, not many people have the first manic/ depressive episode; so it might be capturing risk towards bipolar rather than actual incidence. Verbal fluency seems a more stronger predictor of bipolar risk than intelligence per se.
  11. As per my views, Bipolar pro-band may have more to do with creativity than intelligence and if future studies could operationalise and measure childhood creativity and look at later risk or occurrence of bipolar disorder, than that will settle the debate to an extent. Also important to remember that intelligence and creativity though correlated are different, with one perhaps requiring a threshold of intelligence to be creative.
  12. Lastly, if you are intelligent or creative, don’t fear, the risks seem to be too small and other factors like stress play a much more important role in triggering an illness. And even when triggered, it can be managed well!

If you liked the study and want to dig deeper, the full text  article [pdf] is online.

A tale of two diseases

I have Obstructive Sleep Apnea (OSA). I am also bipolar.

Now which of the above statements shocked/ surprised you more? If I am guessing correctly the latter statement about my being bipolar came across as more of a shock/ surprise/ concern. Now what does that say about your own reactions to mental illness and your own involvement in perpetuating the stigma against mental illness?

Both of the above are chronic diseases to an extent. My OSA (snoring in popular parlance) cannot be treated by surgery, so the only viable option I have is to use a CPAP machine while sleeping to get a good night’s sleep. Bipolar disorder as we all know can only be contained, and I take my medicines regularly to ensure that there are no relapse into either a manic or a depressive episode.

Both, if un-diagnosed and untreated can cause havoc. OSA which was un-diagnosed/ untreated for about a couple of years or so in my case led to excessive daytime drowsiness, less alertness and lowered productively etc; if untreated OSA can cause increased risk of injury to self and others while driving as you may actually get into micro sleeps while driving. Even if not that dramatic, on a daily basis the quality of your sleep and waking life can become very diminished.  The downsides of having a manic or depressive episodes are well known- at least to readers of this blog. However, what may be less well known is that even in the throes of psychotic extremes, the risk to others from violence by bipolar people is very little and if anything they may be subjected to violence than otherwise.

When treated, that is when I use my CPAP machine regularly I have no problems at all due to my OSA either in my work life or in my personal life – I am as refreshed in morning as ever. Rather I believe I might be getting better sleep than the average person. When treated, that is when I regularly use medicine, and take other precautions like having regular sleep cycles etc for my bipolar, I am totally episode free- rather I believe I have an advantage when it comes to managing my energy and mood.

However, given all the above, which disclosure do you think has drastically lowered my chances of employment (if I was seeking employment, which I am thankfully not:-)); which disclosure would have led to discrimination in the workplace or at least got me some amused and funny looks? About which of these are my friends and acquaintances likely to gossip more? Why as a society we are still not that accepting of mental illness and stigmatize those who have it?

Some immediate consequences I can think of:

  1. readers of The Mouse Trap will no longer take my interest in psychology as non-partisan. They will think of me as being interested in psychology only due to my being bipolar (to set the record straight I became interested in psychology in 1996 during my IIT delhi days, while my first episode happened while I worked with Hughes in 2001).  Also when I take a position like association of biploar with creativity, I will be considered biased; however nobody will say that a ‘normal’ person advocating otherwise is biased due to his being ‘normal’.
  2. Some will start to see signs of craziness in my old/ new posts and wonder whether when I was writing them I was in a normal frame of mind or episodic. Its usually my style to try and combine seemingly disparate research ideas and that is especially prone to this analysis.
  3. I will start getting sympathy, but like anyone living with say OSA or diabetes etc I think one should just ignore the fact about my being bipolar and not let it redefine my relationship with you. I am much more than a person with bipolar or OSA, and I prefer it that way.
  4. there will be some embarrassment for my near and dear ones.

Why did I not disclose for so many years?

  1. because I feared discrimination (and funny looks) at the workplace. It might have been imaginary but I was not strong enough to experiment. Now that I am self employed the stakes are much lower and I don’t care.
  2. I myself was grappling with my being bipolar. For initial some years it was hard to accept; later I struggled with accepting medication as necessary ; but now for quite some years I am at peace and thankfully episode free.
  3. As I believe it never affected adversely my performance at work , I did not deemed it necessary to inform my employers etc as I thought ,and still think, its none of their business.

Why did I decide to disclose publicly about this?

  1. I have no delusions (pun intended) that I am Deepika Padukone that my talking about a mental health issue is going to raise awareness drastically; still I want to do my bit to fight stigma and the journey starts with oneself. I had a decent career in software despite my being biploar and being biploar hasn’t stopped me from taking risks and experimenting with a second career; hopefully that can inspire or provide mental support to a person or two.
  2. Some immediate triggers- a mouse trap reader on facebook privately messaged me asking if I only have theoretical knowledge about psychosis etc or if I had some personal experiences too. I think it was a legitimate question that deserves a legitimate answer.
  3. Another immediate trigger- I came across a tweet by https://twitter.com/akhileshlinky about his year end ‘confession’ about being bipolar and I though heck why not ‘come out’ yourself.
  4. but really, it doesn’t matter to me one way or other – the only upside of sharing more publicly is that it can help combat stigma.

 

What I expect from you?

  1. don’t define me exclusively as being biploar.
  2. reflect on your own attitudes about mental illness and try to overcome that implicit bias
  3. resist discrimination and stigma

Lastly, thanks are due to my family and friends who have been prone to this ‘secret’ over the years and who have provided the necessary support and encouragement.

Autism, Psychosis and circadian clock

ResearchBlogging.org

Diagram illustrating the influence of dark-lig...
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I recently came across this post by Michelle Dawson that states the thesis that one of the abnormalities in Autism spectrum disorders is due to abnormal circadian clock functioning. More specifically, the clock is internally driven and has a greeter ‘free running’ period and does not entrain readily to environmental and social clues.

Autistics whose sleep-wake cycles carry on independently from environmental and social cues are said to be “freerunning.”
The usual response to freerunning in autism is to see this as an autism-related sleep disorder. There is very preliminary evidence that freerunning autistics can be successfully treated with melatonin. Bourgeron (2007) refers to a short case study about an autistic whose free-running was remediated by melatonin treatment.

If you feel a bit overwhelmed by all the circadian clock related terminologies, I wholeheartedly recommend BoraZ’s clock tutorial series , especially this one.

Dawson further says:

Glickman (2010) speculates that some autistics’ failure to chain our sleep-wake cycles to environmental cues may arise from our atypical perception. My totally wild guess might be that an extreme freerunning phenotype in autism may be contributed to in part by cognitive versatility in autism, which would result in perceived environmental cues affecting sleep-wake cycles in an optional rather than mandatory way.

I wont speculate about the reasons behind why autistics have a greater free-running period and less entrainment to social and environmental clue, but I woudl say that instead of giving them flexibility, I would presume that this locks them into their internal rhythms, while others are more responsive to environment and better adapted. That brings me to the opposite phenotype of ASD…the psychotic phenotype shown by Schizophrenics, depressives and Bipolars.

As per this PLOS Genetics article:

The contribution of the circadian regulatory system, arising from conflicts between internal biological clocks and environmental (solar) and social clocks, is evident in affective disorders. All major affective disorders (such as unipolar depression, OMIM #608516; bipolar disorder, and schizophrenia, OMIM #181500) include circadian phase disturbances in sleep, activity, temperature, and hormone levels (for reviews see [84]–[86]). Moreover, there is evidence that if rhythms can be altered/stabilised using relevant therapies, improvements in the primary symptoms can occur. For example, in some instances sleep deprivation has an antidepressant effect in patients [87]. Conversely, many disorders with a primary anomaly in the circadian system are associated with depressed mood. Seasonal affective disorder (SAD; OMIM #608516) is a common condition where depressive symptoms occur during shorter winter days [88]–[90]. Two inherited sleep phase disorders, familial advanced sleep phase syndrome (FASPS; OMIM #604348) and delayed sleep phase syndrome (DSPS), are both associated with abnormal affective states [91],[92]. Furthermore, individuals with a behavioural preference for “eveningness” have a greater tendency to develop depression [93].

The above to me seems hypersensitivity to social and environmental cues in affective/psychotic disorders. contrast this with ASD description by the same authors:

Other behavioural disorders with circadian and sleep-related disturbances include autism spectrum disorders (ASD) (OMIM %209850) [81]). Behavioural disturbances in ASD may arise in part from an inability of an individual’s circadian oscillator to entrain to environmental and social cues. One specific correlate of ASD is a low level of melatonin, and one of the enzymes critical in the synthesis of melatonin, acetylserotonin-O-methyltransferase (ASMT, OMIM *300015), is implicated as a susceptibility gene for ASD [82].

The role of melatonin seems to provide a clue. In autism, there seems to be low levels of melatonin and perhaps hypo-sensitivity to melatonin changes. In contrast Bipolar is marked by hypersensitivity of Melatonin receptors:

It has been suggested that a hypersensitivity of the melatonin receptors in the eye could be a reliable indicator of bipolar disorder, in studies called a trait marker, as it is not dependent on state (mood, time, etc.). In small studies, patients diagnosed as bipolar reliably showed a melatonin-receptor hypersensitivity to light during sleep, causing a rapid drop in sleeptime melatonin levels compared to controls.[58] Another study showed that drug-free, recovered, bipolar patients exhibited no hypersensitivity to light.[59] It has also been shown in humans that valproic acid, a mood stabilizer, increases transcription of melatonin receptors[60] and decreases eye melatonin-receptor sensitivity in healthy volunteers[61] while low-dose lithium, another mood stabilizer, in healthy volunteers, decreases sensitivity to light when sleeping, but doesn’t alter melatonin synthesis.[62] The extent to which melatonin alterations may be a cause or effect of bipolar disorder are not fully known.

The above is not the only source implicating Bipolar disorder and circadian clock dysfunction., See more here and here. The big question is not whether ASD and Affective disorders are both circadian rhythm disorders, but the big question is whether they show opposite phenotypes with respect to circadian clocks- one showing too little entrainment while the other too much?
Barnard, A., & Nolan, P. (2008). When Clocks Go Bad: Neurobehavioural Consequences of Disrupted Circadian Timing PLoS Genetics, 4 (5) DOI: 10.1371/journal.pgen.1000040

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Creativity-psychosis linkage via reduced white matter /myelination

ResearchBlogging.org
I have been following, and am passionate about, the positive psychology movement for quite some time, but was surprised to discover that there was something called positive neuroscience also in place. I recently came across this new scientist article about the research paper of Rex Jung et al and was pleased to discover that Jung was working on the frontier of applying latest in neuroscience research to Positive brain states and substrates like that involved in creativity.

The article is in PLOSOne, an open access journal and is lucidly written , so you should go and read it now. I’ll anyway like to summarize their study results. First a bit of background about creativity psychopathology linkage.

Some research reports positive correlations between various definitions of creativity and a diagnosis of psychopathology [1], [2], [3], [4]. Other studies report that psychopathology is rarely, if ever, associated with creative insight, capacity, or productivity [5]. When artists are studied more carefully, certain personality characteristics appear to reside upon a continuum of both normal behavior and psychopathology. For example, creative expression in the visual arts and poetry has been linked with the overlapping personality traits of schizotypy and Openness to Experience (Openness), and particularly to self-reports of “unusual experiences” and “unconventional nonconformity”, but not the “introvertive anhedonia” characteristic of schizophrenia [6].

This is inline with what we have been covering at mouse trap regarding association of creativity with the psychotic spectrum especially the creativity that is artistic or revolutionary in nature rather than scientific and methodical in nature. This is how the authors distinguish between types of creativity inline with my views that one type of creativity is autistic (cognitive) in nature while the other is psychotic (emotional) and these are on a continuum.

First, there does not exist one “creativity”; rather, this construct is hypothesized to reside upon a continuum between cognitive (i.e., scientific) and emotional (i.e., artistic) behavioral domains [41], [42]. Thus, when comparing scientists and artists directly, researchers have found lower lifetime rates of psychopathology for: 1) scientists compared to artists, 2) natural scientists compared to social scientists, 3) nonfiction writers compared to fiction writers and poets, and 4) formal artists compared to “expressive” artists [3], [4], [43]. These findings have led researchers to hypothesize a hierarchical structure of creativity across disciplines [42], which echoes the notions of “paradigmatic” (i.e., a fundamental model of events) versus “revolutionary” (i.e., rejection of doctrines) approaches as applied to the sciences [44]. The benefits of working within the lines of a given field appear to be lower levels of psychopathology; alternately, individuals with lower levels of psychopathology may be attracted to such endeavors. Similarly, there is increasing evidence that the cost of “revolutionary” approaches to creative endeavors, whether it is in the arts or sciences, may be associated with increased levels of psychopathology although, again, causative links are weak at best.

So that fits in with broader creativity/ psychopathology linkage, but to get back to the current study the authors had already established earlier that performance on Divergent Thinking (DT) (a measure of creativity) “exhibited significant inverse relationships with both cortical thickness in frontal lobe regions and metabolite concentration of N-acetyl-aspartate (NAA) in the anterior cingulate cortex in normal young subjects “. Thus, some theoretical relationship between creativity and underlying brain circuitry in the frontal reagion was available a priori. Also, research by other researchers has already established that ” Both schizophrenic and bipolar patients have been shown to have reduced fractional anisotropy (FA) in the anterior thalamic radiation [12], [13] and uncinate fasciculus [14] within frontal brain regions. Similarly, reduced FA was observed within the uncinate fasciculus of a cohort with schizotypal personality disorder, providing strong support for the hypothesis that similar neural phenotypes may not result in full-blown clinical symptoms [15]. Finally, in normal subjects, the Neuroregulin-1 (NRG1) single nucleotide polymorphisms (SNP’s) SNP8NRG243177 and SNP8NRG221533 were found to predict lower FA in the left anterior thalamic radiation [16]. As NRG1 has been found to predict higher risk of schizophrenia [17], [18] and bipolar disorder [19], and is linked with axonal myelination and migration [20], these authors hypothesize a mechanistic link between NRG1 within the anterior thalamic radiation and risk for psychotic disorders [16].”

Thus, from the above it is easy to see that there should be a inverse relationship between Fractional Anisotropy (a construct related to myelination of axons) in the frontal regions and creativity if one assumes that creativity and psychopathology are related and are on one end of a continuum. And this inverse relationship between creativity and FA is exactly what they found:

Our results suggest a convergence between a cognitive measure of divergent thinking, a personality measure of Openness, and a white matter integrity measure within the inferior frontal lobes. We found that normal young subjects with lower levels of FA within predominantly left inferior frontal white matter (i.e., regions overlapping the uncinate fasciculus and anterior thalamic radiation) scored higher on the CCI; similarly subjects with lower levels of FA within the right frontal white matter (i.e., regions overlapping the uncinate fasciculus and anterior thalamic radiation) scored higher on self-reported measures of Openness. These two regions of white matter overlap with those reported by other researchers who found lower FA in both schizophrenia and bipolar disorder [13], [14], [30].

They could also nail the reduced FA to reduced myelination as radial diffusion was affected more than axial diffusion. As reduced myelination has been shown as a diatheisis for psychosis, this fits in with previous research linking risk factors common to psychosis and creativity.

Whereas more neural resources are often associated with higher intellectual capacity in a parieto-frontal network of brain regions [39], studies in DT appear to suggest that less is often better in a different network of brain regions, particularly fronto-cingulate-subcortical networks linked via white matter loops [40].

One can speculate that frontal region, more concerned with executive control , when with reduced activity or functional connectivity , may not inhibit the other brain regions that much, and may thus lead to flowering of inherent creativity and cross-talk amongst different brain regions. On the other hand too much white matter/ gray matter in this region may lead to too much control and leave little room for flexibility and creativity.

However, while lower FA is commonly seen in diseases where both cognition and white matter integrity are impaired (e.g., Traumatic Brain Injury, Schizophrenia, Alzheimer’s disease) [45], [46], [47], evidence is accumulating that higher FA in particular brain regions may also be associated with clinical disorders including post-traumatic stress disorder [48], obsessive-compulsive disorder [49], panic disorder [50], synaesthesia [51], and Williams syndrome [52].

It is interesting to note that enhanced FA is associated with clinical disorder of Williams syndrome, which is associated with Autism; on the other end of continuum, reduced FA in particular brain region is associated with psychosis proneness, thus providing another convergent linkage of autism and psychosis as opposites.

Jung, R., Grazioplene, R., Caprihan, A., Chavez, R., & Haier, R. (2010). White Matter Integrity, Creativity, and Psychopathology: Disentangling Constructs with Diffusion Tensor Imaging PLoS ONE, 5 (3) DOI: 10.1371/journal.pone.0009818

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Autism, Schizophrenia and CNV in 16p11.2

Schizophrenia album cover
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ResearchBlogging.org
There is a letter published in the advance online edition of Nature Genetics, that reports that microduplication of genes in the region 16p11.2 are associated with the risk of schizophrenia in a large cohort. It has been earlier shown that microdeletions in the same region confer the risk of Autism.Thus, it seems that the region codes for genes too much of which causes schizophrenia and too little autism.  Here is the abstract of the study:

Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 times 10-5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 times 10-7), bipolar disorder (P = 0.017) and autism (P = 1.9 times 10-7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 times 10-13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).

Here is what medical news today (via which I found this article) has to say about the findings:

An international team of researchers led by geneticist Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL), has identified a mutation on human chromosome 16 that substantially increases risk for schizophrenia.

The mutation in question is what scientists call a copy number variant (CNV). CNVs are areas of the genome where the number of copies of genes differs between individuals. The CNV is located in a region referred to by scientists as 16p11.2. By studying the genomes of 4,551 patients and 6,391 healthy individuals, Sebat’s team has shown that having one extra copy of this region is associated with schizophrenia. The study appears online today ahead of print in the journal Nature Genetics.
Schizophrenia and autism: two sides of the same coin?

“This is not the first time that the 16p11.2 region has caught our eye,” says Sebat. It was previously spotted in a 2007 study with Professor Michael Wigler at CSHL — a deletion of the identical region was identified in a girl with autism. Studies by several other groups have shown that losing one copy of 16p11.2 confers high risk of autism and other developmental disorders in children.

Taken together these studies suggest that some genes are shared between schizophrenia and autism, according to Sebat and colleagues. “In some ways, we might consider the two disorders to be at opposite ends of the same neurobiological process” says Shane McCarthy, Ph.D., the lead author of the study, “and this process is influenced by the copy number of genes on chromosome 16.” One hypothesis is that the loss of 16p11.2 leads to the deprivation of key genes involved in brain development, while an extra copy of this region might have the opposite effect.

A correlation between 16p11.2 mutations and head size

It is not known what biological processes are affected by the copy number of 16p11.2, Sebat notes. He believes, however, that the team may have stumbled on to an important clue. By studying the clinical records of patients, they discovered that patients with deletions of the region differ significantly in head size from those with duplications of the same region. Sebat reports, “Head circumference of patients with the deletion were larger than average by more than one standard deviation. Head circumference was slightly below average in patients with the duplication.” These findings, he notes, are consistent with some previous studies that have observed a trend towards larger brain size in autism and an opposite trend toward smaller brain size in schizophrenia.

All this nicely fits in with what I have been proclaiming from the rooftops from the early days of this blog: that autism and Schizophrenia are opposites on the same continuum and the genes involved should also be the same. More copy numbers leading to propensity towards psychosis while lesser number or deletions associated with autistic traits. One more puzzle piece fits in and now we know why the brain size differences exist in autistic and schizophrenic persons and what the poetntial function (mentalizing) of region 16p11.2 may be.

McCarthy, S., Makarov, V., Kirov, G., Addington, A., McClellan, J., Yoon, S., Perkins, D., Dickel, D., Kusenda, M., Krastoshevsky, O., Krause, V., Kumar, R., Grozeva, D., Malhotra, D., Walsh, T., Zackai, E., Kaplan, P., Ganesh, J., Krantz, I., Spinner, N., Roccanova, P., Bhandari, A., Pavon, K., Lakshmi, B., Leotta, A., Kendall, J., Lee, Y., Vacic, V., Gary, S., Iakoucheva, L., Crow, T., Christian, S., Lieberman, J., Stroup, T., Lehtimäki, T., Puura, K., Haldeman-Englert, C., Pearl, J., Goodell, M., Willour, V., DeRosse, P., Steele, J., Kassem, L., Wolff, J., Chitkara, N., McMahon, F., Malhotra, A., Potash, J., Schulze, T., Nöthen, M., Cichon, S., Rietschel, M., Leibenluft, E., Kustanovich, V., Lajonchere, C., Sutcliffe, J., Skuse, D., Gill, M., Gallagher, L., Mendell, N., Craddock, N., Owen, M., O’Donovan, M., Shaikh, T., Susser, E., DeLisi, L., Sullivan, P., Deutsch, C., Rapoport, J., Levy, D., King, M., & Sebat, J. (2009). Microduplications of 16p11.2 are associated with schizophrenia Nature Genetics DOI: 10.1038/ng.474

UPDATE: I just revisited my 20th may 2008 post on the matter and realized how prophetic my musings were. Reproducing part of it below the fold for the benefit of newbies to this blog:

CNVs on the other hand present a different model of disease. One can have one or more types of CNVs (deletions, duplications, multiple duplications etc) associated with the same genetic code sequence and this in my view would lead to spectrum like diseases where one may find variations along a continuum on a particular trait- based on how many copies of the genetic sequence one has. One would remember that I adhere to a spectrum based view of schizophrenia/psychosis and also a spectrum based view of Autism. Moreover I believe that Schizophrenia and Autism are the opposite ends of the spectrum, whose middle is normalcy and that the appropriate traits may have to do with social brain, creativity etc.

now as it happen previous research has also found that CNVs are also found to a higher extent in autistics. Moreover, research has indicated that the same chromosomal regions have CNVs in both Autism and Schizophrenia. To me this is exciting news. Probably the chromosomal region (neurexin related is one such region) commonly involved in both schizophrenia and autism is related to cognitive style, creativity and social thinking. Qualitatively (deletions as opposed to duplications) and quantitatively (more duplications) different type of CNVs may lead to differential eruption of either Schizophrenia or Autism as the same underlying neural circuit gets affected due to CNVs, though in a different qualitative and quantitative way.

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