How do you measure cognitive ability in Schizophrenia?

Posted on February 28, 2024 by molson50 / 0 Comment

What is Schizophrenia?

Schizophrenia is a psychiatric disorder that is more common than most think. It is characterized by psychotic or positive symptoms that may include delusions, hallucinations, disorganized speech, and cognitive impairment. Typically, this disorder is diagnosed in late adolescence. However, little is known regarding the biological etiology of it. An article by Singh describes the possible underlying genetic risk factors, specifically within the Wnt and glycogen synthase kinase 3 (GSK3) pathway. The issue that they present is overactive GSK3, which ultimately leads to less β-Catenin.

Many factors may contribute to hyperactive GSK3 such as inhibitory phosphorylation of AKT due to increased dopamine receptor activation or increased activation of metabotropic glutamate receptors. Moreover, there are specific genes that have been associated with Schizophrenia like DISC1, which has been found to be deleted in this disorder. This was the first risk gene studied followed by Akt and copy number variations.

All of this goes to show the complexity of Schizophrenia, which raises the question of how we might be able to better treat these individuals. However, treatment must start with assessment, which is more difficult with people who may not know the symptoms or severity of the disorder that they are dealing with. One type of assessment that professionals might begin with includes measures for cognitive function and insight.

Measures of cognitive ability

Studies displayed in an article by Haddad et al. have shown that many patients with Schizophrenia that display severe cognitive impairments do not report those deficits nor have awareness of their cognitive function. Therefore, a number of clinicians utilize neuropsychological assessments instead of self-report measures in these cases. Overall cognitive function typically assesses at least five different categories of abilities which are shown in figure 1. Some others specify what they are looking for such as overall symptoms or insight.

Figure 1. Level of importance in cognitive ability categories [1]

While each assessment for cognitive ability covers similar subscales, each one is specialized for specific questions and situations, which are categorized in figure 2. Shown below are some examples of this.

Assessments primarily for cognition

The brief assessment of cognition in schizophrenia (BACS): 30 minute, pen and paper, neuropsychological battery used to assess cognitive abilities in schizophrenia. This battery contains 6 subscales: verbal memory, digit sequencing (working memory), token motor task (psychomotor function), semantic fluency (verbal fluency), symbol coding (attention and processing), and Tower of London (executive function). Originally, it was developed for clinical trials with key features of portability, repeatability, and multiple forms [2].

The Self-assessment scale of cognitive complaints (SASCCS): Self-report instrument that investigates how patients perceive their cognitive impairment through 21-items on memory, attention, executive functions, language, and praxia. This instrument utilizes a 5-point likert type scale to evaluate symptoms (0=never, 4=very often) [3].

Figure 2. Subcategories of cognitive and diagnostic assessments [4]

Assessments for other specified questions

The Positive and Negative Syndrome Scale (PANSS): 30-item questionnaire to evaluate clinical symptoms based on 3 subscales, positive and negative symptoms and overall psychopathology [5].

Insight Scale for Psychosis (IS): self-report survey that measures the patient’s insight levels with 8 questions divided into 3 subscales: awareness of illness, re-labeling of symptoms, need for treatment. The higher the score, the greater insight the patient has. Individuals with Schizophrenia may be able to estimate cognitive impairment independent of their level of insight [5].

Conclusion

With the changing and advancing scientific background behind psychiatric disorders such as Schizophrenia, it is important to continue to change evaluations and treatments to match our knowledge. One way to do this in schizophrenia specifically is through cognitive assessment. This is vital in this disorder because having an understanding of the patients cognitive impairment as well as their insight into their symptoms will help professionals find a treatment that works best for them.

References

[1] Gebreegziabhere, Y., Habatmu, K., Mihretu, A., Cella, M., & Alem, A. (2022). Cognitive impairment in people with schizophrenia: An umbrella review. European Archives of Psychiatry and Clinical Neuroscience, 272(7), 1139–1155. https://doi.org/10.1007/s00406-022-01416-6

[2] Keefe, R. S. E., Goldberg, T. E., Harvey, P. D., Gold, J. M., Poe, M. P., & Coughenour, L. (2004). The Brief Assessment of Cognition in Schizophrenia: Reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophrenia Research, 68(2), 283–297. https://doi.org/10.1016/j.schres.2003.09.011

[3] Haddad, C., Sacre, H., Abboche, E., Salameh, P., & Calvet, B. (2023). The self-assessment scale of cognitive complaints in Schizophrenia: Validation of the Arabic version among a sample of lebanese patients. BMC Psychiatry, 23(1), 415. https://doi.org/10.1186/s12888-023-04925-3

[4] Sandy. (2013, May 15). Cognition in schizophrenia and bipolar disorder. NeuRA Library. https://library.neura.edu.au/schizophrenia/signs-and-symptoms/cognition/schizophrenia-vs-bipolar/

[5] Birchwood, M., Smith, J., Drury, V., Healy, J., Macmillan, F., & Slade, M. (1994). A self-report Insight Scale for psychosis: Reliability, validity and sensitivity to change. Acta Psychiatrica Scandinavica, 89(1), 62–67. https://doi.org/10.1111/j.1600-0447.1994.tb01487.x

Health

Possible Pathology, and Treatment for Schizophrenia

Posted on February 27, 2024 by speders4 / 0 Comment

Picture 1: Possible pathology, and treatment for schizophrenia[1].

Schizophrenia is a chronic brain disorder, which affects about 1 % of the U.S. population[2]. The symptoms that characterize the disorder can be fall into the categorizes of positive and negative symptoms. Positive symptoms are abnormally present, and can be hallucinations, paranoia and exaggerated or distorted perception, beliefs, and behaviors[3]. While negative symptoms concern what is abnormally absent such as the loss or decrease in ability to speak, express emotion, initiate plans and find pleasure[4].

There is no cure for the disorder, and there has yet to be found a cause or the pathology or the biological bases for how schizophrenia develops. A possible pathway that plays a role and can be correlated with schizophrenia is the wnt signaling pathway. The wnt signaling pathway play a role in neural development in addition to neural circuit function[5]. In relation to schizophrenia there can be understood to be overactivation of GSK-3β, which causes a decrease in β-catenin levels[6]. In the wnt pathway, if there is proper signaling GSK-3β levels are down, while β-catenin levels are increased[7], seen in Figure 1, is the explanation of this process. β -catenin is required for TCF/LEF transcription.[8] Transcription is the process of making RNA from a gene’s DNA sequence[9]. Together β-catenin and TCF/LEF transcription is important for schizophrenia and can be a factor in the development of schizophrenia.

Figure 1: GSK-3β is a part of a destruction complex that keeps β -catenin phosphorylated, which causes the deceased levels of β -catenin. However, when Wnt binds to the receptor which facilitates disengagement of the destruction complex, it decreases the phosphorylation that results in β -catenin being able to transfer into the nucleus[11].

Treatment

Picture 2: The different components in treating schizophrenia[12].

There is no treatment found that treats all the symptoms present in schizophrenia patients, which makes the treatment of the disorder a bigger process, of multiple components. As seen in figure 2, a combination of medications, and nonpharmacological treatment, like psychotherapy, and patient compliance can have an effect in treating the disorder[13].

Medication is the first process in treatment of schizophrenia, and the most typical used is antipsychotics. These drugs bind dopamine receptors, which can relate to the possible hyperactivity in dopamine levels in patient with schizophrenia. In dopamine hyperactivity there are higher levels of GSK-3β, and a deceased amount of β-catenin, which can correlate to the function of the wnt signaling pathway[14]. The antipsychotics predominantly target the positive symptoms related to schizophrenia, while having limited effect on the negative symptoms.

Patient compliance is another important factor in the treatment of the disorder, this concerns ensuring patient are taking their medications. Nonpharmacological therapies therapies can help to ensure that patients remain adherent to their medications[15].

There are various other treatment such as cognitive behavioral therapy[16], transcranial magnetic stimulation[17], and yoga therapy[18]. Nonpharmacological treatments should be used as an addition to medications, not as a substitute for them[19]. Treatment programs in which encourage family support have shown to decrease rehospitalization and to improve social functioning for patient with schizophrenia[20].

There needs to be further research to improve the quality of treatment, and understanding the pathology of the disorder in more detail. In combination, a conversation talking about the ethics of treatment, and how it affects schizophrenia patients should be encouraged.

Bibliography

Aleman, A., Enriquez-Geppert, S., Knegtering, H., & Dlabac-de Lange, J. J. (2018). Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials. Neuroscience & Biobehavioral

Ganguly, P., Soliman, A., & Moustafa, A. A. (2018). Holistic Management of Schizophrenia Symptoms Using Pharmacological and Non-pharmacological Treatment. Frontiers in public health, 6, 166. https://doi.org/10.3389/fpubh.2018.00166

Lodha, P., & De Sousa, A. (2020). Cognitive behavioural therapy and its role in the outcome and recovery from schizophrenia. In A. Shrivastava & A. De Sousa (Eds.), Schizophrenia treatment outcomes: An evidence-based approach to recovery (pp. 299–312). Springer Nature Switzerland AG. https://doi.org/10.1007/978-3-030-19847-3_26

Lpc/Mhsp, J. C. M. (2023, May 29). How schizophrenia is treated. Verywell Mind. https://www.verywellmind.com/schizophrenia-treatments-2330662

Ocampo, T. (2023, January 30). Understanding schizophrenia – Medical Channel Asia. Medical Channel Asia. https://medicalchannelasia.com/understanding-schizophrenia/

Patel, K. R., Cherian, J., Gohil, K., & Atkinson, D. (2014). Schizophrenia: overview and treatment options. P & T : a peer-reviewed journal for formulary management, 39(9), 638–645.

Singh K. K. (2013). An emerging role for Wnt and GSK3 signaling pathways in schizophrenia. Clinical genetics, 83(6), 511–517. https://doi.org/10.1111/cge.12111

Transcription. (n.d.). Genome.gov. https://www.genome.gov/geneticsglossary/Transcription#:~:text=Transcription%2C%20as%20related%20to%20genomics,protein%20information%20encoded%20in%20DNA.

What is Schizophrenia? (n.d.). https://www.psychiatry.org/patients-families/schizophrenia/what-is-schizophrenia

Uncategorized

What’s Behind Autism Spectrum Disorder?

Posted on February 20, 2024 by Kelly / 0 Comment

What is autism spectrum disorder?

Autism spectrum disorder (ASD) is defined as a developmental disorder characterized by difficulties in communication with other people, repetitive behaviors and interests, and that these symptoms negatively impact their ability to function in everyday activities, including work and school. It is defined as a spectrum disorder because types and severity of symptoms can vary. ASD social-related symptoms can look like minimal eye contact, lack of sharing emotion, slow or minimal response, inappropriate facial expressions for the situation, and others. Behavior-related symptoms of ASD include being overly focused on tasks, being upset about changes in routine and transitions, sensitivity to stimuli, and repeating behaviors or phrases. These are symptoms that clinicians look for to diagnose children with ASD. [1]

Figure 1. Autism spectrum disorder (ASD) infographic presentation template with icons has 5 steps such as Rett syndrome, Asperger’s syndrome, PDD-NOS, Autistic disorder and childhood disorder. Diagram vector. [2]

What causes ASD?

The exact cause of ASD is unknown, but there are genetic and environmental risk factors that are known for ASD. Some genetic risk factors are having a sibling with autism, older parents at birth, low birth weight, and genetic factors like fragile X, Rett, and down syndromes. Environmental risk factors are extensive and include exposure to air pollution and toxic materials, maternal disorders like obesity, diabetes, or immune system disorders, and birth difficulties in which there is a period of oxygen deprivation. [3]

Figure 2. Environmental and genetic causes of autism. [4]

What is happening in the brain?

There are three main theories that scientists have about what is going on in the brain of an individual with ASD. The first theory is that there is E/I imbalance in the brain. This means that there is an imbalance of glutamate and GABA levels. It has been found through studies that the problem in individuals with ASD is that there are lower levels of GABA interneurons and GABA activity. The fact that one comorbidity of ASD is seizures, it makes sense that there is a lack of inhibitory neurotransmission in the brain. Another theory is that there is altered network connectivity in the brain. This means that there is decreased connectivity between brain regions which can explain the behavioral abnormalities in ASD. The third theory is the predictive coding hypothesis which looks at how children with ASD have difficulties adjusting to situations that are different from their expectations. This could explain why children with ASD have more sensitivity to stimuli and why changes in routine and transitions can be difficult. One commonality between these three theories is that they all have a connection with the dopaminergic system, so dopamine dysfunction is thought to be a neurological cause of ASD. [5]

Figure 3. Visualization of predictive coding hypothesis. [6]

Treatments and therapies for ASD

The most common treatment for ASD is applied behavior analysis (ABA) in which skills are taught to the child through discrete-trial testing and behaviors are shaped through a reward system. There are other treatments that can be used other than ABA like naturalistic developmental behavioral intervention (NDBI) which utilizes the child’s everyday routine and environment for behavioral interventions. Children with ASD often also go to speech therapy, occupational therapy, and physical therapy as needed. There are no common medications that are used to treat ASD due to how much is unknown about what is going on in the brain. [7]

Figure 4. Visualization of what ABA therapy focuses on and works on with children who have autism. [8]

References

[1] (2023, February). Autism Spectrum Disorder. National Institute of Mental Health. https://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd.

[2] Autism Screening and Diagnosis. Dr. Chantal. https://lifecounselor.net/evaluations/autism-screening-and-diagnosis/.

[3] (2023, April 19). Autism. National Institute of Environmental Health Sciences. https://www.niehs.nih.gov/health/topics/conditions/autism.

[4] (2022). Autism. Dr. Chhabra Healthcare. https://drchhabrahealthcare.com/disease/autism-homeopathy-treatment/.

[5] DiCarlo, G. E. & Wallace, M. T. (2022). Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates. Neuroscience and Behavioral Reviews, 133, 1-29. https://doi.org/10.1016/j.neubiorev.2021.12.017.

[6] Stefanics, G., Kremláček, J., & Czigler, I. (2014). Visual mismatch negativity: A predictive coding view. Frontiers in human neuroscience. 8. https://www.researchgate.net/figure/Simplified-scheme-of-the-hierarchical-predictive-coding-framework-Friston-2005-2008_fig1_266401430.

[7] CDC. (2022, March 9). Treatment and Intervention Services for Autism Spectrum Disorder. Centers for Disease Control and Protection. https://www.cdc.gov/ncbddd/autism/treatment.html.

[8] What is ABA Therapy? OCASG. https://www.otagokidsautism.org/therapy.

Disease

Can We Pinpoint What’s Going Wrong in Autism Spectrum Disorder?

Posted on February 20, 2024 by kloidolt / 0 Comment

Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with different levels of severity, characterized by its core symptoms involving deficits in social communication and interaction, restrictive and repetitive patterns of behavior and interests, and sensory abnormalities.[4] In more severe cases, symptoms can greatly impact an individual’s ability to perform everyday tasks including interpreting social rules, forming relationships, and managing stress. While there is no cure for ASD, early interventions in children with autism, such as behavioral therapy, can enhance their ability to function independently and support their development by teaching them important social and communication skills.

Prevalence:

It was estimated in 2023 by the CDC’s Autism and Developmental Disabilities Monitoring Network that 1 in 36 children had been diagnosed with ASD.[1] ASD affects males nearly four times more than females, and this gender difference has a major gap in ASD research. Symptoms generally appear in early childhood around the age of 2. However, there are individual variations and challenges with diagnoses and treatment. Individuals with higher socioeconomic status and better access to healthcare are found to be diagnosed earlier. Cultural knowledge should be researched further to assess healthcare access and how the process of getting help is impacted by stigmas and cultural values.

Etiology:

There is no single cause of ASD, and the spectrum of severity often comes from combinations of genetic changes and environmental factors. There are a lot of theories, however, about the etiology and pathogenesis of ASD: imbalances in excitatory-inhibitory neural activity; altered network connectivity (because of abnormal synapse formation, neuroinflammation, or oxidative stress), and altered social predictive coding that leads to sensory abnormalities. There are also many genetic mutations (SNPs and CNVs) that have been associated with ASD and examined in their impact on certain signaling pathways. With behavioral symptoms being the key descriptor and diagnostic criteria, various pathway dysfunctions are being looked at to create subgroups within ASD to improve individual treatment, the article we read this week focused on the dopaminergic system.

Figure 1. ASD etiology simplified to highlight the many connections and potential for comorbidities in future research looking at underlying causes.[2]

Comorbidities:

ASD has several comorbidities that are separated into 3 clusters: psychiatric (ADHD, OCD, anxiety, etc.), multisystem (gastrointestinal disorders), and seizures. The diagnosis of these comorbidities can be so closely related to ASD that their known underlying mechanisms are being researched as potential explanations of ASD as well. In the paper we read, they talked about ADHD in relation to dopamine signaling. In ADHD, there are disruptions caused by reduced dopamine transporters and D2 receptors in the nucleus accumbens and midbrain (brain regions that may be vulnerable in ASD).

Dopamine System:

Dopamine is a monoamine neurotransmitter produced in the substantia nigra and ventral tegmental area brain regions. It has a major role in learning and motivated behavior, which is why it could contribute to the underlying neurobiological mechanisms of ASD. However, there is no single cause of dopamine dysfunction that we can pinpoint either in ASD cases.

Figure 2. Dopamine signaling and its downstream functions that may be the connection to ASD – synaptic plasticity and development.[4]

Pharmacological Treatments?

Although there are currently two FDA-approved drugs used to treat irritable and aggressive behaviors associated with ASD, there are no pharmacological interventions approved to treat the core symptoms of ASD. Antipsychotics and SSRIs are the most prescribed to individuals with autism to treat the comorbid symptoms like anxiety. Further research is needed to test new drugs that could potentially target the core symptoms of ASD.

Figure 3. Common intervention strategies for individuals with ASD.[3]

Questions to leave with:

How can we improve school systems to best help teach individuals with autism?
How can we increase inclusion in jobs for individuals with autism?
Should we consider comorbidities when creating subtypes?
How do the various genetic risk factors cause the behavioral symptoms?
How does diagnostic criteria play into the sex-based gap (what are the differences in symptom manifestations)?

References:

[1] “Autism Speaks Pledges to Make World of Difference as Autism Prevalence Rises to 2.7% of Children in U.S.,” Autism Speaks. Accessed: Feb. 19, 2024. [Online]. Available: https://www.autismspeaks.org/press-release/autism-speaks-pledges-make-world-difference-autism-prevalence-rises-27-children-us

[2] V. Khachadourian et al., “Comorbidities in autism spectrum disorder and their etiologies,” Transl Psychiatry, vol. 13, no. 1, Art. no. 1, Feb. 2023, doi: 10.1038/s41398-023-02374-w.

[3] “Treatment Practices for Autism,” Otsimo. Accessed: Feb. 19, 2024. [Online]. Available: https://otsimo.com/en/treatment-practices-autism/

[4] G. E. DiCarlo and M. T. Wallace, “Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates,” Neuroscience & Biobehavioral Reviews, vol. 133, p. 104494, Feb. 2022, doi: 10.1016/j.neubiorev.2021.12.017.

Uncategorized

3 Theories for Autism Spectrum Disorder

Posted on February 20, 2024 by molson50 / 0 Comment

What is autism spectrum disorder?

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder where individuals may display deficits in social communication, restricted interests, and/or repetitive behaviors. In the future, subtypes may be formed due to the symptomology and comorbidities that the individual has which may be defined as psychiatric, multisystem, or seizures [1]. Psychiatric comorbidities are typically ADHD or anxiety and epilepsy falls into the seizures category. Multisystem comorbidities in ASD have shown to be between the gut and brain interaction, particularly through functional gastrointestinal disorders (fGID). This may be shown through exacerbated experience of constipation or diarrhea which, in turn, may increase behavioral symptoms [1].

An article by Dicarlo and Wallace explains different genetic and environmental risks that are also associated with ASD. Specific variants have been found to be important, such as syndromic forms which form by chromosomal abnormalities or single gene mutations. Variants known as copy number variants (CNVs) and single-nucleotide variants (SNVs), which differ in how many base differences they create, also contribute to ASD. Lastly, internal and external environmental factors contribute to the development of ASD, specifically toxins and toxic exposures, perinatal conditions, and an overall male-biased prevalence.

What is the science behind this disorder?

Figure 1 below displays some, but not all of the major areas of the brain associated with ASD. Some of these include the striatum, involved in movement and the reward system, amygdala, which regulates fear and emotion, and the hippocampus, the main memory center of the brain. A lot of these regions receive signals from different parts of the cortex [2]. Each of these then work together in different networks and pathways (figure 2) to produce specific responses and actions such as social motivation and behavior, movements, etc. Dopamine (DA), an important neurotransmitter for social aspects of humans is largely involved in these processes. In an article by Mandic-Maravic et al., the DA pathway is shown to be altered in individuals with ASD, resulting mainly in reward dysfunction. The nigrostriatal circuit (NS), which projects toward the striatum, also involves DA. This means that if DA is dysfunctional, the ability to act suitably toward goal-directed behavior is changed [3]. Further, DA is found to have a connection to gastrointestinal symptoms because of its placement in the enteric nervous system, which is a part of the peripheral nervous system [1]. Overall, connection between different sections of the brain is often weaker in ASD, which is especially evident in the DA system. All of these factors have been taken into account to create theories for the development of ASD.

Fig 1. Regions of the brain

Edit image, resize image, crop pictures and appply effect to your images. (n.d.). Artpictures.Club. Retrieved February 12, 2024, from http://artpictures.club/

Fig 2. Networks and pathways

DiCarlo, G. E., & Wallace, M. T. (2022).

Theories

Excitatory-inhibitory balance disruption theory: This theory claims that there are alterations in the ratio of excitatory and inhibitory (E/I) neurotransmission. Different processes such as altered cellular metabolism, receptor function, or neurotransmission uptake may cause the disruption in the ratio. DA plays a role in the disruption as their inputs onto other neurons might change E/I levels. An example of the outcome of this would be if the disrupted balance took place in the striatum, which would alter the function of reward-mediated behaviors [1].
Altered network connectivity theory: Distortions in communication in and from the cerebral cortex may also drive different behaviors in ASD. This theory uses fMRI to view increases, decreases, and resting states of connectivity in ASD. Overall, it has been found that there are greater distortions and variability in connectivity maps in people with ASD, meaning their brains are unable to communicate as they should [1].
Predictive coding hypothesis: Assumes our brain creates internal models of our external sensory environment that serve as our predictions and perceptions of the world. Individuals with ASD are said to improperly form and fail to update internal models of the environment. This could be the cause to altered social cues and communication as well as an increased reliance on incoming sensory information, leading to their hypersensitivities [1].

While these are all different theories, they are not separate from one another. In fact, they go together very well as each one might lead to the other. For example, E/I balance disruption could lead to altered brain networks [1].

[1] DiCarlo, G. E., & Wallace, M. T. (2022). Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates. Neuroscience and biobehavioral reviews, 133, 104494. https://doi.org/10.1016/j.neubiorev.2021.12.017

[2] Autism in the brain, region by region. (2017, February 27). Spectrum | Autism Research News. https://www.spectrumnews.org/features/legacy-special-reports/autism-brain-region-by-region/

[3] Mandic-Maravic, V., Grujicic, R., Milutinovic, L., Munjiza-Jovanovic, A., & Pejovic-Milovancevic, M. (2022). Dopamine in Autism Spectrum Disorders-Focus on D2/D3 Partial Agonists and Their Possible Use in Treatment. Frontiers in psychiatry, 12, 787097. https://doi.org/10.3389/fpsyt.2021.787097

Community/Disease/Health

What should you know about Autism Spectrum Disorder?

Posted on February 16, 2024 by ephiri / 0 Comment

What is Autism Spectrum Disorder?

Autism Spectrum Disorder (ASD) is a highly heritable neurodevelopmental disorder that is estimated to affect 1 in 59 children [1]. There are several factors that are said to cause Autism. There is not “one gene” responsible for all causes of autism and sex differences may also contribute to ASD risk, but there is evidence to suggest that environmental factors may also play a role in ASD risk, therefore more research is being conducted in this area. Dopamine, the neurotransmitter involved in the brain motivation and reward system, has also been shown to play a role in motor behavior and there is a great deal of evidence linking dopamine with a key clinical domain in autism – social function [2]. Animal models also provide a particularly useful system for gaining insight into the impact of de novo mutations and rare inherited variants on the neurobiological mechanisms that may contribute to the constellation of symptoms associated with ASD.

Autism and the individual

Not all individuals with ASD are equally affected and not all individuals exhibit the same display of symptoms, but early diagnosis helps to significantly improve the lives of children with autism, therefore it is best to get a reliable diagnosis early in childhood. Experts can detect autism spectrum disorder as early as eighteen months and can make a reliable diagnosis between 18-24 months of age [4]. However, some individuals are not diagnosed with autism until their adulthood years. People with ASD often have problems with social communication and interaction, and restricted or repetitive behaviors or interests. People diagnosed with ASD may also have different ways of learning, moving, or paying attention. These characteristics can make life difficult and challenging, but Autism is not a degenerative disorder, therefore individuals can continuously improve with specialized support and services [5]. Children with autism may also tend to be creative and passionate about music, dance, art, theater, etc. Researchers hypothesize that autism symptom presentation in males and females may differ, leading to the latter not getting diagnosed promptly. This may be the result of females hiding their difficulties due to social norm expectations. Females with autism have also been an understudied group in ASD and this could explain the gender gap in research [6].

Why should you learn about Autism?

It is important for each one of us to learn more about ASD as public awareness can be helpful in clearing up stereotypes and misunderstandings. ASD affects all nationalities, all races and both sexes. It doesn’t differentiate or affect only one group, therefore education and raising awareness can help people understand the larger class of neurodevelopmental disorders. Other neurodevelopmental disorders similar to ASD are Williams Syndrome, Obsessive-compulsive disorder (OCD) and Attention Deficit Hyperactivity Disorder (ADHD) [8]. Williams Syndrome is a condition that affects about 1 in 10,000 people. People with Williams Syndrome may exhibit autistic behaviors, such as developmental and language delays, problems with gross motor skills and hypersensitivity to sounds. Obsessive-compulsive disorder (OCD) is a condition that can mimic autism symptoms, such as compulsive hand washing, cleaning, or touching items like doorknobs. ADHD and anxiety disorders can also mimic autism symptoms [9].

[1]Healis Autism Centre. (2021, March 30). Importance of public awareness for autism. https://www.healisautism.com/post/importance-of-public-awareness-for-autism#:~:text=With%20greater%20public%20awareness%20on%20autism%2C%20it,make%20lives%20easier%20for%20families%20and%20caregivers.

[2].Centers for Disease Control and Prevention. (2022, March 28). Signs and symptoms of autism spectrum disorders. Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/autism/signs.html#:~:text=Autism%20spectrum%20disorder%20(ASD)%20is,%2C%20moving%2C%20or%20paying%20attention.

[3].What is autism spectrum disorder?. Psychiatry.org – What Is Autism Spectrum Disorder? (n.d.). https://www.psychiatry.org/patients-families/autism/what-is-autism-spectrum-disorder

[4].U.S. Department of Health and Human Services. (n.d.). Autism spectrum disorder. National Institute of Mental Health. https://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd

[5].Schiller, J. (2022, December 6). Autism statistics & facts: How many people have autism?. The Treetop ABA Therapy. https://www.thetreetop.com/statistics/autism-prevalence

[6].dev. (2021, April 19). Understanding Autism Acceptance and Why It’s So Important. Nuheara. https://www.nuheara.com/news/understanding-autism-acceptance/

[7].firespringInt. (n.d.). Seven Disorders Closely Related to Autism. Autism Research Institute. https://autism.org/related-disorders/

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Uncategorized

Insulin levels in Blood and Cerebrospinal Fluid

Posted on February 14, 2024 by zariye / 0 Comment

Research from as early as 1983 has documented changes in blood insulin levels in Alzheimer’s disease. Fasting blood insulin and insulin response to a glucose challenge are elevated in individuals with Alzheimer’s. This process in which insulin is transported from the blood to the brain is a receptor-mediated process and the receptor of insulin CSF serum shows a subtle decrease with age. The research also found lower levels of CSF/serum in AD and higher blood and lower CSF insulin to be more prominent with disease progression. Although findings on cerebrospinal fluid (CSF) insulin vary, recent data indicates that individuals with Alzheimer’s disease are likely to have increased blood insulin levels.

http://Gabbouj S, Ryhänen S, Marttinen M, Wittrahm R, Takalo M, Kemppainen S, Martiskainen H, Tanila H, Haapasalo A, Hiltunen M and Natunen T (2019) Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway. Front. Neurosci. 13:629. doi: 10.3389/fnins.2019.00629

http://Ray, Lori & Heys, Jeffrey. (2019). Fluid Flow and Mass Transport in Brain Tissue. Fluids. 4. 196. 10.3390/fluids4040196.

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Insulin Signaling in the Brain

Posted on February 14, 2024 by zariye / 0 Comment

Insulin enters the brain through one of three routes: blood-brain barrier, median eminence, or the vascular endothelium by transport proteins. Insulin levels vary throughout the brain, the olfactory bulb is thought to have the highest level, this is mainly due to the high concentration of IRs. When insulin and IR bind this, two branches of insulin signaling are activated, MAPK and PI3-Akt Pathways. IGF1R also activates PI3K. IR and IGF1R both belong to the RTK family. When insulin binds this causes the IR to change this change initiates autophosphorylation and attracts IRS proteins, while the IRS is being activated there are phosphorylation sites inactivating the IRS by making them separate from the insulin receptor and reducing the addition of phosphate groups to tyrosine. Tyrosine-phosphorylated IRS activates PI3Ks, PI3K is a heterometric protein, and its SH2 domain; P85 binds to phosphoserines, P110 changes phosphatidylinositol (3,4)-bisphosphate (PIP2) into phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which results in the activation of many downstream kinases. Akt is from the family of serine/threonine kinases and consists of three isoforms, Akt1, Akt2, and Akt3. These forms showed varied expression in the brain and cells based on their location, an example is how Akt1 and Akt3 are distributed through somatic layers of the hippocampus, however, Akt2 is expressed in astrocytes instead and not neurons. Upon activation, Akt is activated with the PH domain of PIP3 and this then allows PIP3 to phosphorylate threonine. There was a study conducted that measured insulin in low levels of the brain; in humans and rodents, the research revealed that reductions in brain insulin were consistent in both Alzheimer’s patients and age-matched individuals without Alzheimer’s, suggesting that the decline in brain insulin is more likely associated with aging rather than specifically with Alzheimer’s disease. One study couldn’t find insulin mRNA in the cortex, while another study did, making it challenging to interpret the mRNA data. To fully understand insulin’s role in healthy and diseased brains, more research needs to be done to explore its relationship with the severity of Alzheimer’s disease and age-matched controls. However Ongoing studies consistently show that administering insulin, either through intravenous infusion or intranasal delivery, can slightly improve performance on memory tasks for both healthy adults and individuals with Alzheimer’s disease or mild cognitive impairment (MCI) at dosage levels.

http://How does brain insulin resistance develop in Alzheimer’s disease? – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Impaired-neuronal-insulin-signaling-in-Alzheimers-disease-AD-Schematic-outline-of_fig1_260215925 [accessed 14 Feb, 2024]

http://Stanley, M., Macauley, S. L., & Holtzman, D. M. (2016). Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?. The Journal of experimental medicine, 213(8), 1375–1385. https://doi.org/10.1084/jem.20160493

Disease

Alzheimer’s Disease and Precursors; the Impact of Nutrition

Posted on February 13, 2024 by speders4 / 0 Comment

Figure 1: Alzheimer’s disease[1]

Alzheimer’s disease (AD) is one of the most common diseases related to decline in cognitive abilities, but at the same time its causes and hallmarks might be unknown to most people. AD is a gradual and progressive neurodegenerative disorder, which tends to affect the older population. Deficits related to this disorder is such of memory, language, attention, reasoning, comprehension, and judgement[2]. Generally, the decline in cognitive abilities can be defined by the term dementia, however, AD is the most common type of dementia. Pathological AD hallmarks can be categorized as amyloid-β-plaques (clumps of beta amyloid protein) and neurofibrillary tangles (bundles of tangles made up by tau protein) that develops in the brain[3]. A neuromodulator in the brain that has been revealed to be one of the factors of cognitive impairment and the AD pathology is dysregulated brain insulin signaling[4].

Figure 2: The comparison of a normal brain versus the AD brain, with the formations of neurofibrillary tangles and amyloid plaques. [5]

The progression of AD can be seen as a process with many implication factors, as understood with the implications with insulin signaling, but the process of AD is related to some precursors that can start already at the level of healthy eating patterns. Studies have found that a healthy diet is associated with a lower risk of AD[6]. A list of nutrients has been found to have a beneficial effect on the course of AD, such as vitamins B6, B12, folic acid, polyphenols, while on the other hand for example fatty acids promotes the progression of the disease[7]. Additionally, a study found that plant-based diets such as the Mediterranean diet, were associated with lower levels of oxidative stress and inflammation in comparison to a fast-food diet[8]. Healthy diets can be believed to affect underlies mechanisms such as oxidative stress and neuroinflammation[9], which further play a role in influencing pathways, the formation of plaques, and neural death[10]. The formation of plaques (tau accumulation) and neural death contribute to the formation of tangles inside the neurons which is a part of the progression of AD.

Figure 3: The impact of nutrition on the brain. [11]

In relation to both healthy lifestyle and impaired insulin signaling is diabetes type 2, which is a result of both of these. It has been found that people who suffer from diabetes type 2 have a higher likeliness for the progression of AD, because of the strong correlation[12]. So, the process starting at the food one consumes, can play are role in the progression of AD, and the different precursors and factors that play a role in the progression of AD. As can be seen with the interconnecting pathological features of neuroinflammation and insulin resistance that are two of the major factors of synaptic disruption and neurogenerative processes[13]. Diabetes connects with the insulin resistance, and nutrition play are role in the development of diabetes type 2 and neuroinflammation, which can all be tied to the progression of AD.

A big factor with Alzheimer’s disease is time, since there is no cure or treatment that will heal the disease, we are looking for options to give Alzheimer’s patients a longer time to live, maybe even a better quality of life. One of these options can be understood to be nutrition, and your lifestyle. Therefore, interventions should or could be implied as early as possible to minimize the development of the disease. By looking at small bits of the progression of this disease, hopefully we are slowly understanding more on how to deal with Alzheimer`s disease.

[1] What is Alzheimer’s Disease? (n.d.). YouTube. https://www.google.com/url?sa=i&url=https%3A%2F%2Fwww.youtube.com%2Fwatch%3Fv%3D7F-t9yvPP_0&psig=AOvVaw01G76eZhQmR8VmBscxeREB&ust=1707882712431000&source=images&cd=vfe&opi=89978449&ved=0CBMQjRxqFwoTCMDYuYa1p4QDFQAAAAAdAAAAABBV
[2] Kumar, A., Sidhu, J., Goyal, A., et al. Kumar, A. (2022, June 5). Alzheimer Disease. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK499922/
[3] What happens to the brain in Alzheimer’s disease? (n.d.). National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-alzheimers-disease
[4] Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry International, 135, 104707. https://doi.org/10.1016/j.neuint.2020.104707
[5] Amyloid Plaques and Neurofibrillary tangles | BrightFocus Foundation. (2015, July 1). https://www.brightfocus.org/news/amyloid-plaques-and-neurofibrillary-tangles
[6] Hu, N., Yu, J. T., Tan, L., Wang, Y. L., Sun, L., & Tan, L. (2013). Nutrition and the risk of Alzheimer’s disease. BioMed research international, 2013, 524820. https://doi.org/10.1155/2013/524820
[7] Śliwińska, S., & Jeziorek, M. (2021). The role of nutrition in Alzheimer’s disease. Roczniki Panstwowego Zakladu Higieny, 72, 29–39. https://doi.org/10.32394/rpzh.2021.0154
[8] Aleksandrova, K., Koelman, L., & Rodrigues, C. E. (2021). Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies. Redox Biology, 42, 101869. https://doi.org/10.1016/j.redox.2021.101869
[9] Aleksandrova, K., Koelman, L., & Rodrigues, C. E. (2021). Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies. Redox Biology, 42, 101869. https://doi.org/10.1016/j.redox.2021.101869
[10] Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry International, 135,104707. https://doi.org/10.1016/j.neuint.2020.104707
[11] What we know about Alzheimer’s disease and nutrition. (n.d.). Nutri-facts. https://www.nutri-facts.org/en_US/news/articles/what-we-know-about-alzheimers-disease-and-nutrition.html
[12] Akhtar, A., & Sah, S. P. (2020). Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease. Neurochemistry International, 135,104707. https://doi.org/10.1016/j.neuint.2020.104707
[13] Ibid.

Disease

Alzheimer’s Disease and Insulin Resistance

Posted on February 13, 2024 by Olivia / 0 Comment

Figure 1. Photo: The George-Anne Media Group

What Is Alzheimer’s Disease?

Alzheimer’s disease (AD) is a neurological condition that causes millions of people to suffer from cognitive deficits. There is not a set answer for treating and preventing the disease as the pathology is still not completely understood, however, there are a few different theories pertaining to the development of the disease. One of the theories is that dysfunction within the insulin signaling pathway is responsible for the pathogenesis of Alzheimer’s disease. [1]

The two main biomarkers of Alzheimer’s disease are β-amyloid plaques and neurofibrillary tangles (NFT). NFTs are the result of tau proteins becoming hyperphosphorylated, causing them to clump together and disrupt the function of the microtubules. When the microtubules are not working properly, the neuron cannot work properly. β-amyloid plaques are formed by amyloid precursor proteins (APP) and can compete with insulin in binding to insulin receptors, causing dysfunction. Both NFTs and β-amyloid plaques have a role in insulin resistance. [1]

Figure 2. Neurofibrillary tangles and β-amyloid plaques compared to a healthy neuron. Photo: Wikimedia Commons. **Insulin and the Brain**

While insulin was once thought to not have any prevalence in the brain, we now know that there are concentrations of insulin and insulin receptors in some brain regions. Insulin can be synthesized in the brain and can also cross the blood brain barrier. It has a regulatory role in neuroprotection. Insulin also plays a role in memory and learning and has been shown to regulate the accumulation of amyloid β. Some studies have found that dysregulation of glucose metabolism can lead to memory loss and dementia symptoms of AD. [1]

AD and the Insulin Signaling Pathway

There are multiple components throughout the insulin signaling pathway that could be possible sites for AD pathogenesis. Irregularities and dysfunctions regarding these components can lead to the development of AD symptoms including dementia and deficits with working memory and learning. For example, mTOR is a protein involved in the PI3K pathway triggered by growth factors to regulate metabolic activity. Another example is that when GSK-3β is phosphorylated, it facilitates the formation and accumulation of β-amyloid plaques as well as the accumulation of phosphorylated tau proteins leading to NFTs. Amyloid β has also been found to activate GSK-3β which can lead to even more phosphorylated tau proteins. [1]

Figure 3. The insulin signaling pathway is composed of a variety of molecules. Here we can see some of those molecules like PI3K and GSK3 that may have a contribution to the development of Alzheimer’s disease. Photo: Wikimedia Commons.

The article Insulin signaling and AD described an AD mouse model that showed evidence of irregularities in mTOR signaling and that phosphorylated mTOR was elevated in AD subjects. Several of the dysregulated molecules lead to the production and accumulation of β-amyloid plaques and neurofibrillary tangles which are key factors of Alzheimer’s disease. [1]

Is Insulin Resistance Responsible for AD?

While there is substantial evidence for insulin resistance being a probable cause to Alzheimer’s disease, there are still some things researchers need to evaluate. Insulin resistance has been shown to increase other things that have been hypothesized to contribute to the development of Alzheimer’s. These things include oxidative stress, the production of cytokines, and process leading to cell death. Insulin resistance may be a great theory as to why neurological diseases like Alzheimer’s occur but may also just influence other forces that contribute to the disease. [1]

Lifestyle as Prevention

Alzheimer’s disease is not the result of one sole issue. Insulin resistance can begin in the body through a variety of circumstances. Diabetes mellitus is a more commonly known form of insulin resistance, but can also develop from an excessive caloric intake and/or a high-fat diet. Insulin resistance can also develop due to physical inactivity. Making a conscious effort to maintain a healthy lifestyle has a lot of benefits regarding the prevention of neurodegenerative diseases like Alzheimer’s. [2]

[1] A. Akhtar and S. P. Sah, “Insulin signaling pathway and related molecules: Role in neurodegeneration and Alzheimer’s disease,” Feb. 21, 2020. [Online]. Available: https://doi.org/10.1016/j.neuint.2020.104707

[2] U. Pagotto, “Where Does Insulin Resistance Start?: The brain,” Diabetes Care, vol. 32, no. suppl_2, pp. S174–S177, Nov. 2009, doi: 10.2337/dc09-S305.