Friday, March 6, 2020

Schizophrenia—Evolution of Humanness

brain diagram showing distortions in language and perception
Is schizophrenia bound to human evolution? Schizophrenia is a neuro-developmental disorder characterised by delusions, hallucinations, and bizarre behaviours. No other animal displays these symptoms. Depression, addiction, anxiety are all found in other animal species, but not schizophrenia. Schizophrenia is not even found in chimpanzees our most recent evolutionary ancestors. It is inheritable, and highly disadvantageous to survival of the affected person. Given this, schizophrenia should be almost non-existent. Yet it continues to affect a massive 1% of the global population. Something is pushing for the persistence of this disorder and its spontaneous manifestation in humans.

Human evolution separated from the chimpanzees 5.5 million years ago when we walked upright and then acquired language abilities. Language ability developed after 'lateralisation', the separation of brain functions into the left (sequential) and right (parallel processing) hemispheres. The peculiar delusions and hallucinations of schizophrenia can be understood as failure of the complex brain mechanism that enables the speaker to distinguish his thoughts from his speech or that of others. This brain mechanism evolved with lateralisation of brain functions. Loss of brain laterality in schizophrenia has been demonstrated.

Comparison of the gene sequences of early humans and their close evolutionary relatives, the Neanderthals have shown that regions of the human genome that underwent positive selection are enriched by association with schizophrenia. This suggests that schizophrenia susceptibility factors may be a "side effect" of human achievements like language and creative thinking. 

Recent evolutionary modifications in brain wiring and connections may have played a role in the development of schizophrenia in humans. Compared to our closest living relative the chimpanzee, brain connections present only in humans show a higher involvement in schizophrenia. Evolutionary changes in the human brain related to supporting more complex brain functions are paralleled with a higher risk for brain dysfunctions that can manifest as schizophrenia.

However, this genetic susceptibility is actually reducing. A study comparing modern-human-specific gene sites with archaic ones has shown that schizophrenia-risk related genes in modern humans are much less than those in Neanderthals and Denisovans (archaic humans). So negative selection of schizophrenia risk-related genes are probably being gradually removed from the modern human genome.

References

  1. https://en.wikipedia.org/wiki/Human_evolution
  2. Crow TJ. Is schizophrenia the price that Homo sapiens pays for language? Schizophr Res. 1997;28(2-3):127–141. doi:10.1016/s0920-9964(97)00110-2
  3. Crow TJ. Schizophrenia as the price that homo sapiens pays for language: a resolution of the central paradox in the origin of the species. Brain Res Brain Res Rev. 2000;31(2-3):118–129. doi:10.1016/s0165-0173(99)00029-6
  4. Srinivasan S, Bettella F, Mattingsdal M, et al. Genetic Markers of Human Evolution Are Enriched in Schizophrenia. Biol Psychiatry. 2016;80(4):284–292. doi:10.1016/j.biopsych.2015.10.009
  5. van den Heuvel MP, Scholtens LH, de Lange SC, et al. Evolutionary modifications in human brain connectivity associated with schizophrenia. Brain. 2019;142(12):3991–4002. doi:10.1093/brain/awz330
  6. Liu C, Everall I, Pantelis C, Bousman C. Interrogating the Evolutionary Paradox of Schizophrenia: A Novel Framework and Evidence Supporting Recent Negative Selection of Schizophrenia Risk Alleles. Front Genet. 2019;10:389. Published 2019 Apr 30. doi:10.3389/fgene.2019.00389

Friday, March 27, 2015

Treat schizophrenia even if your teenager refuses

schizophrenia treatment in teenagers
Treat schizophrenia as you would any other serious medical illness in your teenager

"My 18yr son is aggressive, hearing voices, and not sleeping."
"Since the last two months he is not attending college. He talks to himself in his room and is not going out with his friends."
"He feels he is being tracked through the TV and yesterday assaulted his mother when she put it on."
"We tried taking him to our doctor but he refuses saying there is nothing wrong with him."
This is a common introduction to the more severely ill teenagers presenting at Pathfinder Clinic.

Why teenagers with schizophrenia refuse to see a psychiatrist 

Teenagers refuse to see a psychiatrist for illness related and personal reasons

Illness related factors

Schizophrenia is a brain disease. Your teenager has difficulties recognising his own symptoms. In schizophrenia there are changes in brain structure, chemistry and functioning. The individual is unable to recognise the problems in thinking, and perception. They hear voices threatening harm to themselves and their families. The  same voices command them not to see the doctor. Reality is distorted and they are unable to correct it through feedback from others. Your teenager perceives this distorted internal image of the world as the real one. They attribute their problems to the external environment. Technically this is termed as a lack of insight. The disease process prevents them from seeing these distortions as an illness. Because of the illness they refuse to see the doctor or take medications.

Personal reasons

Many adolescents refuse or drop out of treatment due to stigma of mental illness. They have high levels of self-stigma. They believe that schizophrenia is a result of a laziness, weakness or incompetence. This belief is reinforced by parents, society and friends who give advice like
"You really need to get your act together"
or
"You better snap out of it or people will think you’re crazy."
So in their mind your adolescent rationalises the problems as being outside themselves
 – "You won’t let me do what I want and now you are trying to label me as crazy, you need therapy, you go to the doctor."
Taking medication is seen as an acknowledgement of their own failure. To the teenager denial of illness and rejection of medical care appears more acceptable.

Parents

Parents of an adolescent with schizophrenia are working through their own public stigma. They may see schizophrenia as occurring due to faulty parenting and lack of control. They struggle against the stereotype of their son or daughter as incompetent and requiring supervision. They mistakenly fear they will need to protect the teenager from being labelled and shunned socially. In their mind going to the doctor will accelerate the stigmatising process. So the symptoms are ignored or controlled to the greatest extent possible. This may include keeping the teenager out of school or college for months until the exams are due. When the illness makes life unbearable at home they seek medical help. This is often in an atmosphere of shame and a sense of failure. Many families are unable to overcome these prejudices. They delay treatment for decades until they realise there may be no one to care for their son or daughter when they are gone.

The advisers and 'well wishers' of teenagers and their families are a third set of influencers whose lack of specific knowledge can reinforce self-stigma. Statements like
"Send him to us for a few weeks and he’ll be OK"
and
"Avoid ‘psychiatric’ medications because they are addictive"
or
"Medicines will cause permanent damage"
add further obstacles to the path to standard and adequate treatment.

When the adolescent is functioning well on the medication these misinformed 'well wishers' are the ones who advise
"What do you need the medicine for? I can see nothing wrong with you"
and set the stage for relapse and refusal to meet with the doctor when the illness relapses
 – "Chacha said there is nothing wrong with me, why are you trying to label me?"

What to do?

Refusing help for schizophrenia is not an option.
  • We have already seen what can be done to get a reluctant patient to see the psychiatrist
  • However, for schizophrenia, more urgent measures may be required.  Involuntary admission to a mental health facility for initiation of treatment may be needed. This is especially so when the adolescent is violent, suicidal, using addictive substances, or repeatedly missing from home. Involuntary admission helps in the same way that it helps get your adolescent admitted to hospital if they had dengue fever even if they did not want it. There are provisions in the Mental Health Act to ensure this is done in safety with respect for your adolescent’s rights. After they receive treatment and brain function returns to normal they will thank you. For they will be relieved from the terrors of reality distortions and desperation of suicide thoughts. 
  • Once treatment is initiated ensure they take medications every day as prescribed. Don’t take on any other responsibility regarding the medication. Leave that as a dialogue between your teenager and their psychiatrist. Just make sure it continues to happen.

Why teenagers with schizophrenia must get treatment even if  they don't want it

Brain cell death

Schizophrenia is associated with death of brain cells and shrinking of brain volume. The longer the duration of untreated symptoms the greater the toxic “dose” of delusions and hallucinations delivered to the developing adolescent brain. Delusions and hallucinations are merely the tip of the iceberg – underlying brain changes have already set in. When treatments are delayed for more than a week the illness becomes even more severe and impairing. The person is less likely to recover, and is at greater risk for addiction to cannabis and other substances. These negative changes related to delay persist even after a year when treatment is finally started.

Academic impact

Schizophrenia symptoms make it difficult for the teenager to attend school or college. There is difficulty focusing. In the earliest stages there is an accelerated deterioration in academic performance. This usually takes place in late adolescence. Research suggests this may be a marker for schizophrenia onset. Deteriorating academic performance is seen even before social or other symptoms to appear. Unfortunately this is the very stage of life at which academic performance is critical and shapes career choices for adult employment. Many formerly brilliant students are anguished when they are suddenly struggling to even pass their exams. In fact studies have shown schizophrenia is more likely to affect those who excel at academics, making it all the more devastating. Missing or failing in board exams has an adverse impact that timely treatment can obviate.

References

  1. Compton MT, Gordon TL, Weiss PS, Walker EF. The "doses" of initial, untreated hallucinations and delusions: a proof-of-concept study of enhanced predictors of first-episode symptomatology and functioning relative to duration of untreated psychosis. J Clin Psychiatry. 2011 Nov;72(11):1487-93. doi: 10.4088/JCP.09m05841yel. Epub 2011 Jan 11.
  2. Fung KM, Tsang HW, Corrigan PW. Self-stigma of people with schizophrenia as predictor of their adherence to psychosocial treatment. Psychiatr Rehabil J. 2008 Fall;32(2):95-104. doi: 10.2975/32.2.2008.95.104.
  3. Guo X, Li J, Wei Q, Fan X, Kennedy DN, Shen Y, Chen H, Zhao J. Duration of untreated psychosis is associated with temporal and occipitotemporal gray matter volume decrease in treatment naïve schizophrenia. PLoS One. 2013 Dec 31;8(12):e83679. doi: 10.1371/journal.pone.0083679. eCollection 2013.
  4. Harrigan SM, McGorry PD, Krstev H. Does treatment delay in first-episode psychosis really matter? Psychol Med. 2003 Jan;33(1):97-110.
  5. Karlsson JL. Psychosis and academic performance. Br J Psychiatry. 2004 Apr;184:327-9.
  6. Strauss GP1, Allen DN, Miski P, Buchanan RW, Kirkpatrick B, Carpenter WT Jr. Differential patterns of premorbid social and academic deterioration in deficit and nondeficit schizophrenia. Schizophr Res. 2012 Mar;135(1-3):134-8. doi: 10.1016/j.schres.2011.11.007. Epub 2011 Nov 29.
  7. Penttilä M, Jääskeläinen E, Haapea M, Tanskanen P, Veijola J, Ridler K, Murray GK, Barnes A, Jones PB, Isohanni M, Koponen H, Miettunen J. Association between duration of untreated psychosis and brain morphology in schizophrenia within the Northern Finland 1966 Birth Cohort.Schizophr Res. 2010 Nov;123(2-3):145-52. doi: 10.1016/j.schres.2010.08.016. Epub 2010 Sep 15.
Want more references? View my collection, "Teenagers with schizophrenia need treatment even if they don't want it" from PubMed

Thursday, May 31, 2012

Cannabis, teenagers and schizophrenia

cannabis-stash

Cannabis or marijuana use by teenagers and adolescents is highly associated with the onset of psychosis and schizophrenia. Cannabis goes by many names including hash, pot, grass, weed, or ganja. This gateway drug is falsely thought to be innocuous and as having no lasting effects. Cannabis use by teenagers is often not recognised as a problem. Cannabis is cheap and easily accessible in most student populations. Pune is a major hub for the cannabis drug trade. This week a quarter tonnne of ganja was found dumped in a well. Cannabis use is rampant in Pune colleges and hostels, where students assiduosly guard and maintain their 'stash'. During the 57th National School Games the highest number of students testing positive for marijuana came from Maharashtra.

Regular cannabis use increases the risk for schizophrenia and psychosis by upto 4 times. There is increasing evidence that cannabis use can precipitate schizophrenia in vulnerable individuals. This is especially so with early onset use of cannabis. Cannabis also exacerbates symptoms of schizophrenia in those who have already developed the disorder. Psychotic disorders like schizophrenia involve disturbances in the dopamine neurotransmitter systems of the brain. Δ9-tetrahydrocannabinol (THC) - the key neurochemical in cannabis - interacts with dopamine to adversely affect its functioning by multiple mechanisms.

Teenagers are especially vulnnerable to the schizophrenia-inducing effects of cannabis. Cannabis like substances (anandamide) called endocannabinoids, produced by the body, play an important role in several processes of brain maturation. Regular marijuana use affects this process of brain maturation in teenagers. Schizophrenia is also a disorder of brain maturation. Disruption of the endocannabinoid system in the adolescent brain by exposure to cannabis interferes with brain maturation. This provides a mechanism to increase the risk for development of schizophrenia in adolescence.

How to cut down and stop cannabis use

  1. Write down a list of reasons for wanting to stop - you will need to review this at times when you are feeling low or experiencing craving.
  2. Tell someone you trust that you are quitting
  3. Get rid of the paraphernelia for smoking cannabis - the stash, wrappers, lighters, matches. You may be surprised at the number of places where small amounts are hidden. Get rid of it all.
  4. Take measures to prevent fresh procurements - avoid places and people associated with replenishments
  5. Make a list of things to do to occupy the time freed-up from procuring and using cannabis.
  6. Review your list of reasons and things to do when you feel low and when craving is intense.
References
  1. Paola Casadioa, Cathy Fernandesb, Robin M. Murray, Marta Di Forti. Cannabis use in young people: The risk for schizophrenia.  Neuroscience & Biobehavioral Reviews. Volume 35, Issue 8, August 2011, Pages 1779–1787. doi:10.1016/j.neubiorev.2011.04.007
  2. Degenhardt L, Hall W. Is cannabis use a contributory cause of psychosis? Can J Psychiatry. Aug 2006;51(9):556-65.
  3. Deepak Cyril D’Souza,Richard Andrew Sewell,and Mohini Ranganathan. Cannabis and psychosis/schizophrenia: human studies. Eur Arch Psychiatry Clin Neurosci. 2009 October; 259(7): 413–431. Published online 2009 July 16. doi: 10.1007/s00406-009-0024-2