Tag Archives: Mental disorder

Anxiety, Depression and the Internalizing Spectrum

Pathological mental health problems in children and young adults have been classified into externalizing (substance abuse, conduct disorder etc) and internalizing disorders (depression , anxiety etc). Today’s post will try to  work out the structure of this internalizing spectrum.

English: An anxious person

English: An anxious person (Photo credit: Wikipedia)

The first major difference, that is made in say DSM, is between Mood disorders (disturbance in mood) and Anxiety disorders (characterized by anxiety and avoidance behaviors) . However, Watson in this article (pdf) emphasizes that this classification is not proper and in many cases these disorder say depression (say MDD) and Anxiety (say Panic disorder) are co-morbid with each other.

To explain this as well as other genotypical and phenotypical findings, Watson has developed a structure of these ‘distress disorders’ – however the road was long, an intermediate stop was tripartite model of depression/anxiety.

According to this tripartite model (developed by Watson and Clark), both depression (MDD, dysthymia etc)  and anxiety disorders (phobia, panic etc) share a common non-specific factor called Negative Affect (NA) which is characterized by things like preponderance of negative emotions like sadness, fear, guilt, anger etc as well as irritability, difficulty concentrating etc.

Depressive disorders meanwhile are specifically characterized by lack of Positive Affect (PA), which means less emotions like happiness, interest etc, but also Anhedonia or inability to derive pleasure from earlier pleasurable experiences.  Anxiety disorders, on the other hand, are characterized by physiological hyper arousal (PH) (shortness of breath, dizzyness etc) .

This model however was also found wanting and replaced with an hierarchical integrative model, which posited that there was a generic non-specific factor of NA common to both anxiety and depressive disorders, and a lower order low PA factor characterizing depression and more specific multiple low order factors (instead of one PH hyperarousal factor) associated with the different types of anxiety disorders like panic/ agoraphobia, Phobia-specif stimuli, phobia social etc .

However , Watson further modified the structure and came up with this model shown below:   One broad factor of distress/NA; two specific factors of anxious-misery and fear and then further unique factor specific to individual diagnosis.

To summarize and also extending it a a bit,

  1. At top there is an internalizing spectrum and associated with it a non-specific NA factor.
  2. In middle there are four spectrum:-  a depressive spectrum , a Fear spectrum and a bipolar spectrum and an Obsessive compulsive spectrum.
  3. each of these can be further divided into discrete diagnosis along two factors/dimensions (I will not eb focusing too much on bipolar or OCD for the purposes of this post) :
    1. Depressive spectrum :
      1. group 1: MDD and dysthemia
      2. group 2: GAD and PTSD
    2. Fear Sepctrum
      1. group 1: Panic and agarophobia
      2. group 2: Phobia (specific stimuli) and Social Phobia
    3. Bipolar spectrum (bipolar I, II and cyclothymia)
    4. OCD

Lets focus more closely on Depressive and Fear Spectrum and try to see alignment with ABCD model. MDD/Dysthemia imho are mainly about mood or Affect;  GAD/PTSD are more Cognitive (reaming stuck in a thought loop) ; Panic/agorophobia more Physiological or Dynamic in nature and Phobia (both specific and Social) more Behavioral in nature (avoiding people, places and animals).

Each of these in turn splits into four factors; for ex PTSD splits into four factors- Dysphoria (A), Intrusions (C), Hyperarousal(D) and Avoidance (B). Similarly, recent research has shown that MDD is itself heterogeneous made up of four neural subtypes- one way to list those would be – marked primarily by Anhedonia (A), Anxiety (C) , Psychomotor retardation (D) and Fatigue (B) . Similar analysis should be possible for other discrete diagnosis.

For now, we will turn to the structure of Bipolar and OCD spectrum by analogy to dep/anxiety spectrum.

  1. Biploar spectrum:
    1. Euphoria (Affective)
    2. Flight of ideas (Cognitive)
  2. OCD spectrum
    1. Obsessions (Dynamic)
    2. Compulsions (Behavioural)

Within this OCD can be seen to be comprising  of four factors: Hoarding (A?) , Order and symmetry (C), Obsessions and Checking (D) and Washing and cleaning (B).

Another way to think about the depressive and anxiety spectrum is to say that Depression rgoup 1 is characterized by Low PA, depression group 2 by high PH; Fear group 1 by High PH and Fear group 2 by low PA. What distinguished Fear spectrum from Depression spectrum is the fact that much more variance is explained by High NA for depressive syndromes and only moderate variance explained by NA for Fear syndromes.

What do you think is missing from the above model? Where might it be wrong? where might it be correct? If correct what are the implications?

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.

The BioPsychoSocioEnvironmental model

Most of us have heard about the BioPsychoSocial model of mental illnesses and have also heard about the stress-diathesis model. Today as I was contemplating the two, taking cue from my ABCD model of psychology, I tried combining the two and find quite some merit in that approach.

Schematic of diathesis–stress model.

Schematic of diathesis–stress model. (Photo credit: Wikipedia)

To recap, BioPsychoSocial model says that any disease is a result of multiple interacting factors- some of them biological in nature while others psychological and social. The mind affects the body and the body affects the mind and together they may lead to health or illness. This model is as opposed to the BioMedical model which considers the disease to be predominantly due to biological factors.

The stress-diathesis model posits that people have underlying biological or psychological vulnerabilities and when exposed to an environmental stressor may develop a mental disease with varying probabilities. The same stressor may be harmless to a person who does not have those many vulnerabilities, but prove detrimental for someone with the right kind of vulnerabilities.

Combining the two models together, one can have biological, psychological or social diathesis or vulnerabilities and when exposed to the right environmental toxin/stressor may lead to the emergence of a mental health issue in the individual.

To  elucidate by way of an example. Consider a person whose serotonin neurotransmitter system is such that he typically has lower levels of baseline serotonin. This would be a biological vulnerability to depression. He also has tendency towards negative automatic thoughts or pessimism.  This would be a psychological vulnerability. Moreover he has limited social support and is unmarried and from a low SES background. This would be the social vulnerability. Strike three. On top of this, lets say he suddenly loses hos job and is laid off. That environmental life event may be enough to drive this person to clinical depression.

The BioPsychSocioEnvironmental model has application not only in psychopathology, but I believe its a powerful framework for normal development too. For e.g., if we replace diathesis-stress model with differential susceptibility thesis  then the diathesis or sensitivity to context can interact with both positive and negative environmental events to lead to positive or negative life outcomes.

To me combining the two models is immensely fruitful; hope you too find it useful.

Depressive symptoms

On the Threshold of Eternity

On the Threshold of Eternity (Photo credit: Wikipedia)

I was reading ‘Depression’ by Aaron T Beck, who was instrumental in pioneering the treatment of depression with the cognitive behavioral approach, and was surprised to find that Beck had classified depressive symptoms in four buckets which correspond to the ABCD system.

For example, like the Affect, Behavior, Cognition and Drive (motivation) ABCD model, he parses depressive symptoms as either emotional manifestations,  cognitive manifestations, motivational manifestations and vegetative and physical manifestations. A complete list of symptoms is given below:

Emotional Manifestations

  • Dejected mood
    Negative feelings toward self
    Reduction in gratification
    Loss of emotional attachments
    Crying spells
    Loss of mirth response

Cognitive Manifestations

  • Low self-evaluation
    Negative expectations
    Self-blame and self-criticism
    Indecisiveness
    Distortion of body image

Motivational Manifestations

  • Paralysis of the will
    Avoidance, escapist, and withdrawal wishes
    Suicidal wishes
    Increased dependency

Vegetative and Physical Manifestations

While the world has moved beyond these models to the DSM V (although DSM IV-TR ) is still widely used) and its good to be up to speed regarding the latest diagnostics criteria for depression, this historical classification of symptoms to me proves once more the power of the ABCD conceptualization.

Book review: A Lethal Inheritance

Rethink Mental Illness

Rethink Mental Illness (Photo credit: Wikipedia)

 

Today, i.e. 15th may 2013 is being celebrated as a mental health blog day by APA and in the spirit of the day I am posting a review of ‘A Lethal Inheritance’ by Victoria Costello. It is a book chronicling how ‘ a mother uncovers the science behind three generations of mental illness‘  and is an apt topic for the day highlighting the importance of public education and discourse about the topic of mental health.  this blog pots and book review is a homage to all the people who silently suffer from mental illness, most of the time undiagnosed, or even after diagnosis kept under warps due to associated stigma, and their family members who face the burden of not just care-giving but the counterproductive and unnecessary guilt that many of them either by themselves feel or are made to feel by indirect societal gestures.

 

Let me also take this opportunity to apologize to Prometheus Books and Victoria :  the book had come out a year ago and I was sent a review copy promptly, but could not review it earlier. Better late than never!

 

The book, as the subtitle reveals, revolves around three generations of Victoria’s family (this book is autobiographical) :  her two sons Alex and Sammy, which have their own mental health challenges  and  the unraveling of one of them: a first time encounter with a psychotic experience which could be quite disconcerting for everyone involved: leads her on on her journey to trace the roots of this malady affecting her family and also on a scientific pilgrimage where she  continues to search for reasons, symptoms and preventive measures for the various mental health conditions afflicting her family’s  three generations.

 

If the third generation is her sons, the second generation comprises of her and her sister Rita. While she struggles with undiagnosed/ untreated depression for most of her life, her sister is found struggling with serious substance dependence and addiction- which in the end cost her her life.

 

The first generation consist of an Irish immigrant grandpa in USA, whose claim to family fame, is that nobody wants to talk about his death: a purported accident where he feel asleep /drunk on the railroads and died. Now Victoria is a journalist and a good investigative journalist at that. Not satisfied with the account her mother has narrated to her, she undertakes an investigation of her own that leads to surprising discoveries like the fact that her grandpa had dies seven months before hew mother was born , rather than afterwards as believed. Also that his official death transcript reads as died from accidental drowning in a lake, thus casting doubts over the real conditions surrounding his death and also raising a question, could we ever really know if someone had committed suicide or died accidentally even if the incident was of yesterday and not many years before. The fact that his grandpa was an alcoholic, an immigrant laborer most probably facing economic stress and suffering from some mental illness, and likely committed suicide, based on the guilt/ disgust and many other emotions it aroused in his relatives (wife , daughter etc) points to the various ways genes (Irish inheritance) and environmental factors come together to wreak havoc.

 

The book is large part sensitive narration of one’s own story, some part thrilling investigative journalism and remaining parts informed scientific documentation of symptoms, risk factors, early signs, preventive measures and genes-environment interplay in the making and unmaking of mental health. While the scientific facts are up-to-date, they wont be path breaking as this is not mostly a scientific book- its value lies more in a first hand account of how a family deals with mental health issues and how there are common genetic risk factors that manifest in various forms- from a teen having conduct problems and eventually psychosis, to an adult in the grips of substance use and addiction, to a mother fighting and feigning at the same time that she does not suffer from depression, to a long dead grandpa who was alcoholic and probably committed suicide, to traces of violence in other relatives.

 

The book is also important as it highlights that mental illness and genetic risk does not respect diagnostic boundaries- from depression to conduct disorders to substance use to psychosis – all manifest in the same family tree and were perhaps myriad manifestations of a same common inheritance.

 

 

 

My recommendations; read it, read it as a piece of fiction , as an autobiographical account; as an educative opportunity to know more about mental illness and risk factors or just to get a first hand experiential account of what it meas to live under the weight of a lethal inheritance- read it whichever way you like, but you are bound to come out with an enhanced and more nuanced perspective that would be richer for having read this .

 

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Am happy, will broaden-and-build; am angry, will narrow-and-save

ResearchBlogging.org

Sympathetic (red) and parasympathetic (blue) n...
Image via Wikipedia

Regular readers of this blog will be aware of my conception of positive emotions  in terms of promotion focus and negative emotions in terms of prevention focus. Today I will try to relate this to the specific action-tendency theory of negative emotions and broaden-and-build theory of positive emotions (as proposed by Barbara Fredrickson).

First its instructive to distinguish between negative and positive emotions. Negative emotions, like Fear, Anger, Disgust, traditionally have been conceptualized as specific action tendencies that get triggered or activated by particular type of threatening situations/stimuli. I view them as sensory driven. A stimuli impinges and is either presumed to be attacking/trespassing (thus arousing anger) or dangerous and threatening survival (thus arousing fear) or intimidating and overbearing (thus arousing sadness and disengagement)  or sickening and to be avoided (thus arousing disgust) ; in all cases a stimuli or situation acts as an immediate trigger for a specific action tendency – that of defending, fighting or fleeing, disengaging and surrendering or vomiting and keeping away.

In contrast consider positive emotions like Joy, Interest, Contentment and Love. They all happen when the environment is safe and bodily needs are met- they are not need driven, but growth oriented. They are not based around survival, but around growth.  they are non -specific thought action repertoire that is a broadened set and is not narrowly focused- rather one of the prime effects of positive emotions is to broaden attention, thought/cognition,  actions and interactions. I consider them as motor driven. they are not a response to a stimulus. Rather they are specific patterns of spontaneous action tendencies and opportunities to practice giving outlet to ones spontaneous action tendencies in a safe environmental. That is why every sort of play- be it physical rough-and-tumble or intellectual play of creativity or social play of flirting – is associated with the positive emotions.

To make my analogy more clear consider the fact that actions can be classically conditioned (and thus response to US/CS stimulus) or operant conditioned (and thus not reactive or reflexive but intrinsically driven and proactive) and while former may be more or less determined by  the external stimulus and internal associations and is deterministic in nature, the latter has spontaneous behavioral variability and initiation as its premise and has room for free will.  What I claim today is that negative emotions are reactive and thus keep you stuck in deterministic rut, while positive emotions are expansive and provide opportunities for exercise of free will in safe and playful environments by encouraging spontaneous behavioral fluctuations and felkxibility.

It has been found time and again that positive emotions are associated with a broadening and resource-building effect. Consider Joy. It encourages one to engage in acts for acts sake or encourages rough and tumble play- it builds physical resources.  Consider Interest . It encourages one to engage in exploration of a domain- be it actual physical domain or conceptual domain – it builds cognitive maps and cognitive or intellectual resources. Consider contentment. It encourages one to engage in reflection and self assessment and self integration – it builds psychological resources. consider Love (care-giving variety not romantic which is pathological and more of a negative emotion). It encourages one to engage in reciprocal interactions and to explore, act on and reflect on the other- it builds social resources.

Thus it is evident that positive emotions do help to broaden and build. That much has been proved by Barbara’s research program .  My additional claim is that negative emotions are sensory oriented and reactive while positive emotions are motor oriented, spontaneous and proactive. By signalling safe environments in which behavioral flexibility can be played around with they push us to relate to life more intrinsically.

Perhaps another analogy will be relevant.  there is a sympathetic nervous system and there is parasympathetic system. the sympathetic system helps us respond to stressful situations and readies the body. the parasympathetic restores the body and helps in regeneration of the body. So do negative emotions help us react to outside threats and make the mental-illness dimension while positive emotions help match intrinsic activity to opportunities in the environment and makes the mental health dimension.

The former (mental illness continuum)  is a zero sum game– if I win someone looses. For eg if a dominance hierarchy is there and I am on top I may feel manic while the person at bottom may feel depressed..but as long as dominance and survival and predation and germs are there the negative emotions would be there …the latter (mental health continuum)  is a win-win game.  There are more opportunities for everyone to fare better if everyone is positioned high on mental health spectrum as then doors to creativity and productivity open right then and there for all concerned. thus, I have become an advocate of the positive psychology movement and would like more efforts devoted to study of positive emotions.

Fredrickson, B. (1998). What good are positive emotions? Review of General Psychology, 2 (3), 300-319 DOI: 10.1037//1089-2680.2.3.300

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Autism, Schizophrenia and CNV in 16p11.2

Schizophrenia album cover
Image via Wikipedia

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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