Schizophrenia's genetic signalling protein and receptors

A search for genetic information about schizophrenia shows that a genetically expressed protein, NRG1, and two of its receptors, ErbB3 and ErbB4, are central to schizophrenia. Recent studies implicating NRG1 in schizophrenia often implicate it in bipolar disorder with the same evidence. But different studies focus on two different areas, myelin and neurotransmitters, and hence seem contradictory. Myelin implies neural speed, and neurotransmitters bring to mind, as an example, dopamine as a component of stress.

A myelin, or ErbB3, study (McIntosh, 2009), shows that NRG1/ErbB3 signaling failures cause oligodendrocyte activity to be impaired so that less "white matter" is produced resulting in a diminished "anterior internal capsule in subjects with both disorders" (p. 2). This effect is assumed to be developmental, and myelin formation in "frontal lobes, continues into late adolescence and beyond" (p. 3), giving optimism that new drugs based on NRG1 could reinforce myelination (p. 4).

Genetic loading for psychosis and the internal capsule (McIntosh, 2009)

Neurotransmitter, or ErbB4, studies have a brain-wide view with a focus on neuron development and transmitter activities such glutamatergic hypofunction (Li, 2007), failures in the formation of inhibitory synapses (Fazzari, 2010), and the "wiring" of GABA-mediated circuits (Fazzari, 2010), all in the context of schizophrenia. While bipolar disorder can be linked to schizophrenia in the context of ErbB4 (Chong, 2007), the more detailed material on neural activity focuses on schizophrenia.

As dopamine hyperactivity is part of the schizophrenia pharmacological model (Stone, 2007), and methamphetamine is used to simulate it experimentally (Homayoun, 2008), studies concentrating on stimulants may give clues about the neural activity of schizophrenia and bipolar disorder in relation to behavior.

The "white matter" study is optimistic that new drugs may reinforce myelination, and so raises an idea about myelination and plasticity with respect to maturity: could such drugs help the elderly retain plasticity?


References

Chong, V., Thompson, M., Beltaifa, S., Webster, M., Law A., and Weickertad, S. (2007). Elevated Neuregulin-1 and ErbB4 protein in the prefrontal cortex of schizophrenic patients: Schizophr Res. 2008 March ; 100(1-3): 270–280. doi:10.1016/j.schres.2007.12.474.

Fazzari, P., Paternain, A., Valiente, M., Pla, R., Luján, R., Lloyd, K., et al. (2010). Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling. Nature, 464(7293), 1376-1380. doi:10.1038/nature08928.

Homayoun, H., & Moghaddam, B. (2008). Orbitofrontal cortex neurons as a common target for classic and glutamatergic antipsychotic drugs. Proceedings of the National Academy of Sciences of the United States of America, 105(46), 18041-18046. doi:10.1073/pnas0806669105.

Li, B., Woo, R., Mei L., Malinow, R., (2007, May 24). The neuregulin-1 receptor ErbB4 controls glutamatergic synapse maturation and plasticity. Neuron, 54(4), 583-597.

McIntosh, A., Hall, J., Lymer, G., Sussmann, J., and Lawrie, S. (2009). Genetic risk for white matter abnormalities in bipolar disorder. International Review of Psychiatry, 21(4), 387-393. doi:10.1080/09540260902962180.

McIntosh, A., Hall, J., Lymer, G., Sussmann, J., and Lawrie, S. (2009). Genetic loading for psychosis and the internal capsule disorder. International Review of Psychiatry, 21(4), 387-393. doi:10.1080/09540260902962180.

Stone, J., Morrison, P., and Pilowski, L. (2007, January 26). Review: Glutamate and dopamine dysregulation in schizophrenia — a synthesis and selective review. Journal of Psychopharmacology June 2007 vol. 21 no. 4 440-452

Executive function in depression

Conduct disorder, ADHD, and anxiety disorder” (Sigelman & Rider, p. 482) are often comorbid with depression in children, showing an overlap between depression and ADHD in children.  In my writing about ADHD in children (van Vlaanderen, 2010), I describe evidence of an executive function (EF) component to ADHD, and James (2008) supports an EF component for depression because depressive hyper-activity occurs in the executive function regions.  He promotes the idea that EFs for the depressed can be enhanced with CBT in ways that are similar to my speculation that EF functioning can be enhanced for children with ADHD through psychoeducation. 

In depressed adults, James finds "rigid and concrete thinking, attentional problems" and "memory difficulties" (p. 10) associated with executive function deficit (EFD).  In adults with ADHD who had it as children, Barkley (2004) shows socialization problems that are similar to conduct disorder (CD) and oppositional defiant disorder (ODD) such as arrests and other anti-social behaviors, and Clark (2002) confirms that socialization problems are related to EFD in ADHD-affected children--even for children not diagnosed with CD or ODD.

Speculating along these lines, psychoeducational and -therapeutic strategies may be developed to help with depression (and adult ADHD) that will focus directly on EFD and can be evaluated by their efficacy with respect to EF.  With time, EF monitoring and imaging will improve, perhaps to the point where it can be part of individual evaluation.

References
Barkley, R., Fischer, M., Smallish, L., & Fletcher, K. (2004). Young adult follow-up of hyperactive children: antisocial activities and drug use. Journal of Child Psychology & Psychiatry, 45(2), 195-211. doi:10.1111/j.1469-7610.2004.00214.x.

Clark, C., Prior, M., & Kinsella, G. (2002). The Relationship Between Executive Function Abilities, Adaptive Behaviour, and Academic Achievement in Children with Externalising Behaviour Problems. Journal of Child Psychology & Psychiatry & Allied Disciplines, 43(6), 785-796. Retrieved from Academic Search Premier database.

James, I., Reichelt, F., Carlsonn, P., & McAnaney, A. (2008). Cognitive Behavior Therapy and Executive Functioning in Depression. Journal of Cognitive Psychotherapy, 22(3), 210-218. doi:10.1891/0889-8391.22.3.210.

Mckinley, C., (2010). The Treatment of Depression in Children. Retrieved October 19, 2010 from http://campus.yorkvilleu.ca/mod/forum/discuss.php?d=87127&parent=556350
http://campus.yorkvilleu.ca/mod/forum/discuss.php?d=87127&parent=556350

Sigelman, C.K., & Rider, E.A. (2009). Life-Span Human Development, 6th edition . Thomson Wadsworth.

van Vlaanderen, J., (2010). Executive function, working memory control, and ADHD. Retrieved October 19, 2010 from http://campus.yorkvilleu.ca/mod/forum/discuss.php?d=85380&parent=544331

Body work

Wohlrab reports that tattoos and piercing (collectively here as "body work") are mainstream for adolescents (Wohlrab, 2007). Those with body work are largely "Sensation Seekers," with multiple sexual relationships. "Previously" he says, body work was seen as "showing antisocial, aggressive, high-risk or deviant behaviours."

Koch reports that body work is still deviant, as multiple tattoos or piercings are likely to mean "regular marijuana use, occasional use of other illegal drugs, and a history of being arrested" (Koch, 2010).

Tattooing is tribal, having been introduced to modern society by crew of the explorer, James Cook (Utanga, 2006). Native tribes decorate their bodies for the "aesthetic and symbolic" and to show a connection with nature (Jefkin-Elnekave, 2006). The majority of contemporary tattoos are tribal- or nature-based, perhaps showing a desire for a natural connection as part of a rebellious expression rather than behavioral deviance (Wohlrab, 2007).

To show the extremes of body work as rebellious expression, the conceptual artist Orlan had herself physically reconstructed to represent the ideal "in classical works of art" (Mullis, 2006). With eight operations she represented "the body as meat" for audiences around the world via satellite.

Pain
While society has sanctioned piercings and tattoos as "socially normative practices" (Toste, 2010), and separates them from self-injury, pain still links them. Siorat says that tattoos are symbols of the pain of the "many hours under the needles" necessary to create them (Siorat, 2006). Tribal scarring can be different different from tribal body decorations in that it often represents the pain of war (Jefkin-Elnekave, 2006).

If we allow for gray area between body work and self-injury defined by pain, perhaps we can speculate about a biopsychological connection: depression. For this speculation, let's allow for a link through pain. The physical pain of self-injury can be an escape from the pain of depression (Dickstein, 2009) where the most common diagnosis for self-injury is depression followed by PTSD. If we allow for the "old school" view that body work, specifically tattooing, is representative of lower and criminal classes, and we can show depression at these social levels: "increased frequency of child exposure to poverty is a consistent predictor of adolescent and young adult anxiety and depression" (Ying, 2010). More challenges, and hence stresses, exist for the present adolescent generation than did for previous generations (TODAY Health, 2010), so perhaps body work is a way to cope and express the increasing stresses of the adolescent contemporary experience.

JefkiElnekave, D. (2006). Tribal identity through body art: Extraordinary people living in the remnants of itme. PSA Journal, 72(7), 22-25.

Koch, J., Roberts, A., Armstrong, M., & Owen, D. (2010). Body art, deviance, and American college students. Social Science Journal, 47(1), 151-161. doi:10.1016/j.soscij.2009.10.001.

Mullis, E. (2006, May). The violent aesthetic: A reconsideration of transgressive body art. Journal of Speculative Philosophy, pp. 85-92. Retrieved from Academic Search Premier database.

Wohlrab S, Stahl J, Rammsayer T, Kappeler P. Differences in personality characteristics between body-modified and non-modified individuals: associations with individual personality traits and their possible evolutionary implications. European Journal of Personality [serial online]. November 2007;21(7):931-951.

Dickstein, D. (2009). A closer look at non-suicidal self-injury in adolescents. (Cover story). Brown University Child & Adolescent Behavior Letter, 25(12), 1-6.

Siorat, C. (2006). The Art of Pain. Fashion Theory: The Journal of Dress, Body & Culture, 10(3), 367-380. Retrieved from Academic Search Premier database.

TODAY Health (2010). Students report more serious stress. Retrieved September 29, 2010, from http://today.msnbc.msn.com/id/34803404/ns/health-kids_and_parenting/

Ying, S., Fangbiao, T., Jiahu, H., & Yuhui, W. (2010). The Mediating Effects of Stress and Coping on Depression Among Adolescents in China. Journal of Child & Adolescent Psychiatric Nursing, 23(3), 173-180. doi:10.1111/j.1744-6171.2010.00238.x.

fMRI of recognition

Schulte-Rüther (2007) provides graphic evidence of the emotional processes of identifying emotions in others, using fMRI, in terms of empathy.   He pinpoints simpler recognition and related processing to specific parts of the brain.  He connects the empathic reaction to facial expressions with the areas used for theory-of-mind processing that utilize mirror neurons.

"self- (relative to the other-) task differentially activated the" (p. 1):

• medial prefrontal cortices (MPFC)
  
• Posterior cingulate cortex (PCC)/precuneus
• temporo-parietal junction bilaterally

Covariation of mirror neuron activation and empathic ability.

References

Schulte-Rüther, M., Markowitsch, H., Fink, G., & Piefke, M. (2007). Mirror Neuron and Theory of Mind Mechanisms Involved in Face-to-Face Interactions: A Functional Magnetic Resonance Imaging Approach to Empathy. Journal of Cognitive Neuroscience, 19(8), 1354-1372. Retrieved from Academic Search Premier database.

Cognitive agility

Executive function and memory rehabilitation

As dementia effectively means the loss of cognitive and memory abilities, helping the elderly maintain these abilities is a direct approach that forestalls dementia (Barclay, 2009) and should help the elderly maintain other aspects of their lives.  Cognitive rehabilitation, also cognitive remediation, focuses on executive function (EF) and memory in a way that creates common strategies for diverse therapies concerned with the prefrontal cortex--brain injuries, angioma, ADHD, schizophrenia, and dementia--with its cognitive flexibility, working memory, and planning functionalities.

As cognitive rehabilitation is time-costly, it tends to focus only on the immediate needs of lower-functioning cognitive abilities, and higher executive dysfunctions may never get addressed.  A universal antidote for high cost is, of course, computer automation, and this has not gone unnoticed by cognitive rehabilitators.  Virtual reality (VR) is emerging as a supportive strategy (Castelnuovo, 2003) that is being received with enthusiasm by both clinicians (Weiss, 2009) and patients (da Costa, 2004).  Efficacy-testing, which is also in early stages, is showing benefits for schizophrenics so far (Chan, 2010). 

Interestingly, Web surfing has been shown through imaging to stimulate decision-making components of EF in the elderly, though the benefit only comes with Internet experience (Parker-Pope, 2008).


References

Barclay, L. , Hall, C., Lipton, R., Sliwinski, M., Katz, MJ, Derby, C., Verghese, J. (2009). Cognitive activities delay onset of memory decline in persons who develop dementia. Neurology 73, 356-361

Castelnuovo, G., Lo Priore, C., Liccione, D., 3, Cioffi, G. (2003). Virtual Reality based tools for the rehabilitation of cognitive and executive functions: the V-STORE. PsychNology Journal, 1(3), 310-325.

Chan, C., Ngai, E., Leung, P., & Wong, S. (2010). Effect of the adapted virtual reality cognitive training program among Chinese older adults with chronic schizophrenia: a pilot study. International Journal of Geriatric Psychiatry, 25(6), 643-649. Retrieved from Academic Search Premier database.

da Costa, R., & de Carvalho, L. (2004). The acceptance of virtual reality devices for cognitive rehabilitation: a report of positive results with schizophrenia. Computer Methods & Programs in Biomedicine, 73(3), 173. doi:10.1016/S0169-2607(03)00066-X.

Parker-Pope, T. (2008, October 16). Surfing the Internet boosts aging brains. New York Times. Retrieved October 20, 2008, from http://well.blogs.nytimes. com/2008/10/16/does-the-internet-boost-your-brainpower

Weiss, P., Sveistrup, H., Rand, D., & Kizony, R. (2009). Video capture virtual reality: A decade of rehabilitation assessment and intervention. Physical Therapy Reviews, 14(5), 307-321. doi:10.1179/108331909X12488667117339.

ADHD and parenting

A study about ADHD and parenting styles reports that "aspects of the family environment and parental limit setting" appear to correlate with the growth of "executive functions in children" (Schroeder, 2009). But while it is recognized that children with ADHD suffer from executive function impairments such as "inhibition, working memory, set shifting, and planning" (Toplak, 2009), the improved parenting did not help them (Schroeder, 2009). Interventions in schools are effective (Fabiano, 2003), so presumably similar strategies could be used by parents too.

The Incredible Years program uses parent training intervention program to help "children with early onset conduct problems" (Incredible Years, 2010). An efficacy study of it reports that it should be considered as "a first-line intervention" that has "lasting positive effect on ADHD symptoms in pre-school children" (Jones, 2007, p. 9). Children retained a significant portion of the program's benefits "18 months after the end of intervention" (p. 9). But the study notes limitations: the children were pre-school (ADHD is not typically diagnosed until elementary school), and there are limitations to parent self-reporting (their biases will affect their reports). The benefits of the program, he persuasively argues, are significant if it can be used in lieu of, or forestalls, stimulant medication. Criticism of intervention programs that avoid medication should be balanced against the liabilities associated with stimulants: expense, possible negative side-effects, resistance to stimulant medication based on ethical issues. Fabiano echos this (Fabiano, 2003).

The program seeks to improve family communication with affective involvement by using less-harsh and consistent discipline (Incredible Years, 2010):

• using "attention and appreciation" to build "self-esteem"
• playing with children
• "ignoring negative behavior" by not making eye contact
• avoiding criticism and demands
• developing friendship and empathy skills

References

Incredible years (2010). Retrieved September 19, 2010 from http://www.incredibleyears.com/

Incredible years (2010). Agendas and Checklists for ADHD Protocol Retrieved September 19, 2010 from http://www.incredibleyears.com/Library/items/parent-training-program-ADHD-montreal_08.pdf

Jones, K., Daley, D., Hutchings, J., Bywater, T., & Eames, C. (2007). Efficacy of the Incredible Years Basic parent training programme as an early intervention for children with conduct problems and ADHD. Child: Care, Health & Development, 33(6), 749-756. doi:10.1111/j.1365-2214.2007.00747.x.

Schroeder, V., & Kelley, M. (2009). Associations Between Family Environment, Parenting Practices, and Executive Functioning of Children with and Without ADHD. Journal of Child & Family Studies, 18(2), 227-235. doi:10.1007/s10826-008-9223-0.

Toplak, M., Bucciarelli, S., Jain, U., & Tannock, R. (2009). Executive Functions: Performance-Based Measures and the Behavior Rating Inventory of Executive Function (BRIEF) in Adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). Child Neuropsychology, 15(1), 53-72. doi:10.1080/09297040802070929.

Self-esteem in youth

Kutob reports low self-esteem in elementary and middle school girls in California and Arizona manifested as "low academic performance, social isolation, depression, anxiety, fatigue, headaches, and stomachaches"  (Kutob, 2010).   The low self-esteem was largely caused by cruel teasing and bullying associated with appearance: body weight.  Kutob promotes "zero tolerance" for teasing.  He blames society for allowing a "mindless acceptance and promotion of stereotypic definitions of personal value based on 'Hollywood' appearance standards."

Self-esteem issues can be cultural
Self-esteem for White and Hispanic girls declined by age 11, but, for Black girls, self-esteem remained the same "between the ages of 9 and 14."  The Black girls were immune.  As global self-esteem for Black and White children is equal (Jackson, 2009), the difference appears to be cultural.

Chinese children with "absent migrant parents" suffer low self-esteem (Li-Juan, 2010).  Loneliness predicts low self-concept, which is restored when their parents spend quality time with them.  Here, family affection links to self-esteem and -concept rather than appraisal.

Top down (social) and bottom up (biopsychological)
Low self-esteem for White and Hispanic girls in California and Arizona resulted from negative appraisal rather than self-concepts of appearance.  There seem to be distinct internal and external components of low self-esteem and poor self-concept.  Mentoring improves self-concept and reduces anxiety, but may not improve school behavior or relationships, and depression may remain (Schmidt, 2007).  Bonding in group therapy benefits self-esteem (Marmarosh, 2005), but those who attempt bonding to reduce depression often become more depressed (Cambron, 2010).

Top down
Low self-esteem includes normal reactions (Hendel, 2006):

• need to win
• pleasing others
• perfectionism
• self-criticism
• withdrawing

Bottom up
It is also associated with three indicators of psychological distress (Huajian, 2009):

• depression
• anxiety
• "low subjective well-being"

Exercise improves self-concept, and hence self-esteem

Psychomotor programs "correlated with increased global self-esteem and decreased depression and anxiety levels" (Peter PV Van de, 2005).  Increased physical self-concept elevates low self-esteem--whatever its cause.


Reference

Cambron, M., & Citelli, L. (2010). Examining the link between friendship contingent self-esteem and the self-propagating cycle of depression. Journal of Social & Clinical Psychology, 29(6), 701-726. Retrieved from Academic Search Premier database.

Hendel, A. (2006). Restoring Self-Esteem in Adolescent Males. Reclaiming Children & Youth, 15(3), 175-178. Retrieved from Academic Search Premier database.

Huajian, C., Qiuping, W., & Brown, J. (2009). Is self-esteem a universal need? Evidence from The People's Republic of China. Asian Journal of Social Psychology, 12(2), 104-120. doi:10.1111/j.1467-839X.2009.01278.x.

Jackson, L., Yong, Z., Witt, E., Fitzgerald, H., von Eye, A., & Harold, R. (2009). Self-concept, self-esteem, gender, race, and information technology use. CyberPsychology & Behavior, 12(4), 437-440. doi:10.1089/cpb.2008.0286.

Kutob, R., Senf, J., Crago, M., & Shisslak, C. (2010). Concurrent and longitudinal predictors of self-esteem in elementary and middle school girls. Journal of School Health, 80(5), 240-248. doi:10.1111/j.1746-1561.2010.00496.x.

Li-Juan, L., Xun, S., Chun-Li, Z., Yue, W., & Qiang, G. (2010). A survey in rural China of parent-absence through migrant working: The impact on their children's self-concept and loneliness. BMC Public Health, 101-8. doi:10.1186/1471-2458-10-32.

Marmarosh, C., Holtz, A., & Schottenbauer, M. (2005). Group cohesiveness, group-derived collective self-esteem, group-derived hope, and the well-being of group therapy members. Group Dynamics: Theory, Research, and Practice, 9(1), 32-44. doi:10.1037/1089-2699.9.1.32.

 

Peter PV Van de, V., Herman HV Van, C., Ans AD, D., Joseph JP, P., Guido GP, P., & Koen KK, K. (2005). Comparison of changes in physical self-concept, global self-esteem, depression and anxiety following two different psychomotor therapy programs in nonpsychotic psychiatric inpatients. Psychotherapy & Psychosomatics, 74(6), 353-361. Retrieved from Academic Search Premier database.

Schmidt, M., McVaugh, B., & Jacobi, J. (2007). Is mentoring throughout the fourth and fifth grades associated with improved psychosocial functioning in children?. Mentoring & Tutoring: Partnership in Learning, 15(3), 263-276. doi:10.1080/13611260701201943.