World Mental Health Day

Today, October 10th, is world mental health day, a day that promotes awareness of mental health conditions and provides support to those who suffer. Truth is we all have a brain, therefore we ALL have mental health. However, the most recent statistics suggest that one in four individuals in the world will be affected by mental health disorders at some point in their lives, and that currently, 450 million people are suffering. The likelihood is, therefore, that you know someone who is dealing with a mental health issue, whether they make that public knowledge. The brilliant thing about studying neuroscience as a degree is that you learn so much more information about these conditions than what your typical google search reveals, and with that, you learn about the constant endeavors of scientists desperately seeking how to treat them. It is sad, but very true that mental health discrimination is still most definitely prevalent in today’s society, and often those that suffer can face shame or stereotyping – the classical ‘it’s all in your head’ springs to mind. Today, we decided to cover the science of some of the most common mental health conditions, and discuss with you why they are very much real. We hope that by understanding some of the known, proven science of why these disorders occur in people, we will raise awareness and also compassion for those that experience them.

Anxiety and OCD – Rosie Porter

Obsessive Compulsive Disorder (OCD) is classified as an anxiety disorder where suffers often experience intrusive thoughts. These thoughts bring about compulsive and repetitive behaviours in an attempt to alleviate their anxiety (Figure 1). It is ranked as one of the world’s top 10 disabling conditions by the World Health Organisation and can affect up to 12 in every 1000 people. While the individual understands the thoughts are irrational, sufferers are unable to control their anxiety and behaviours. Actions such as compulsive cleaning, hoarding and trichotillomania (where a person feels compelled to pull their hair out) are common.


Figure 1 The OCD cycle

The underlying pathology behind OCD is still being discovered. However, with recent advances in technology some developments have been made. In a study conducted using resting-state functional-connectivity MRI, the connections in the brains of OCD patients and their family members were compared. The imaging found that siblings of patients had increased connections within and between areas of the brain responsible for cognitive control (fronto-parietal and cingulo-opercular regions). These pathways that are diminished are hypothesised to give an impaired ability to control their own cognition, and therefore their anxiety and behaviour. Patients were also found to have increased connectivity within the fronto-limbic pathway; an area responsible for our emotions (Froukje et al., 2017).

Other studies have found that the orbitofrontal-basal ganglia pathways are altered in OCD (a pathway related to cognitive control of movement), as well as abnormal volume and function in the amygdala (an area responsible for emotion; Nutt and Malizia, 2006). Alterations in the amygdala are seen in most anxiety related disorders, but OCD is unique in that sufferers help relieve their anxiety by performing impulsive behaviours (Figure 1).

Research conducted into the genetic basis behind OCD has flagged up the hSERT gene; hSERT encodes a serotonin transporter in synpases. Serotonin is a neurotransmitter that is thought to be imbalanced in different anxiety disorders and depression. A mutation that has been detected in the hSERT gene (I425V) leads to significantly less serotonin in the synapses of OCD sufferers. This mutation underlies the theory that people can have a genetic predisposition to OCD, that environmental factors can exacerbate.

These discoveries linking dysfunctional neural connections and proteins with behaviour provide evidence for the underlying pathology of the disorder. With further research, the hope is to better understand the disorder and find more effective ways to manage and treat it.

Schizophrenia – by Rachel Coneys

From being one of the most misunderstood and negatively portrayed mental disorders, there has been a new wave in the attempt to decode Schizophrenia’s complex causes and pathologies, to break the misconceptions and develop more effective treatments. Schizophrenia, meaning to ‘spilt mind’ is a severe and progressive psychiatric illness, emerging in young adults at the prime of their lives, spanning all socio-economic and cultural groups. Symptoms vary for each individual and are grouped as positive or negative depending on the type of impairment. Positive symptoms describe experiences such as hallucinations or delusions. Negative symptoms include lack of motivation and social withdrawal.

For over a decade, neuroscientists have been trying to uncover the pathology behind Schizophrenia. A universal belief is that there is a strong genetic predisposition, which when coupled with certain environmental factors, triggers Schizophrenia.

Neurochemical Pathology
Until recently the dominant theory was that of an up-regulation of the neurotransmitter Dopamine within the brain. This was centered on the action of anti-psychotic drugs, which work by blocking dopamine receptors. However it became clear these drugs were ineffective at treating negative symptoms, indicating that another neurochemical system must be involved, otherwise these drugs would work.

The latest theory attributes the major excitatory neurotransmitter Glutamate and the receptor that it binds to, ‘NMDAr’, as key players. The suggestion of an NMDAr ‘hypo-function’ in Schizophrenia came from studying drugs that block this receptor (e.g. Ketamine) and therefore induce psychotic symptoms. Scientists believe that in schizophrenic patients, reduced NMDAr functioning occurs during post-natal development, resulting in structural and behavioural changes. During this period, NMDAr are needed for neuronal signaling and survival, and since NMDAr are widespread throughout our brain, loss of function can have devastating effects. NMDAr dysfunction in the prefrontal cortex (Figure 1) is thought to have a downstream effect on Dopamine and GABA (inhibitory neurotransmitter) networks, resulting in psychosis later on in life. This theory is effective at explaining both the positive and negative symptoms.


Figure 1: The Prefrontal cortex is located in the frontal lobe and is implicated in complex executive functions and personality development. NMDAr dysfunction in this area implicates Dopamine and GABA networks, consequently impairing the prefrontal cortex’s functioning.

Genetic Predisposition

Additionally, there is a strong genetic element to Schizophrenia, with a 50% concordance rate in identical twins. Until recently the genetic risk factors were elusive, but thanks to a remarkable study they are being identified. This Genome Wide Association Study found the expression of a certain variant of a gene called ‘C4’ was elevated in patients with Schizophrenia. C4 is implicated in synaptic pruning (removing the connections between neurons that communicate with one another in the brain) during development. They hypothesized the elevated C4 variant leads to excessive synaptic pruning, causing a thinner cerebral cortex (a physiological hallmark in Schizophrenic patients), and consequent psychotic symptoms.

The Future
The identification of clear genetic associations and development of more eloquent neurochemical models is a huge step forward. Increased understanding of causes and pathologies can help pave the way for more effective treatments for patients with the hope of allowing them to live a less debilitating lifestyle.

Major depressive disorder – Molly Campbell

Depression is a disorder that is heterogenous in nature, meaning that there are different types of depression that vary in severity, from mild to extreme, in which a sufferer may present with psychotic symptoms. Major depressive disorder (MDD) is one of the most common psychiatric diseases and is an example of one of the types of depression. The diagnostic and statistical manual of mental disorders bases a diagnosis of MDD on the presence of low mood or inability to experience pleasure, or perhaps both, for more than two weeks; in addition to profound cognitive dysfunction and sleep disturbances. However, it should be considered that difficulty arises in the diagnosis and treatment of MDD due to the fact that these diagnostic criteria are somewhat arbitrary.

A universally effective treatment for MDD remains to be found, and this is due to the fact that the associated neurobiology remains ambiguous. The credibility of the infamous monoamine hypothesis, in which alterations in levels of the monoamine neurotransmitters serotonin and nor-adrenaline were deemed responsible, is now heavily questioned. This is due to the fact that unfortunately, various monoaminergic antidepressant drugs that rely on this theory are not clinically effective across all patients. For some individuals they appear to work, however in the majority they do not, and so alternative neurobiological theories have arisen (Aan het Rot et al., 2009)

One proposed theory – genetics

Multiple scientific studies have aimed to identify a genetic cause for MDD, as there is strong evidence of heritability due its presence through families. An interesting study by Hyde et al (2016) looked at data from 75,607 European individuals that had received a clinical diagnosis. They identified five independent variants from four regions of the genome associated with self-report of clinical diagnosis of MDD. Further analysis found a total of 17 single-nucleotide polymorphisms associated with a diagnosis of MDD. Put simply; it was found that a significant number of individuals who had received a diagnosis of MDD had differences in their DNA compared to individuals that did not have MDD. The genetic variant that was most strongly associated with MDD was MEF2C (unfortunately, genes are often given pretty complicated names!), a gene involved in the regulation of synapses. Synapses are essentially the communication points between neurones, and this gene has also been shown to be involved in epilepsy and intellectual disability.

Whilst this is only one example of research that investigates the neurobiology of MDD, I think it is particularly interesting as it highlights the emerging role of pharmacogenomics in the treatment of mental health conditions – essentially tailoring the treatment for individuals who are suffering based on the make-up of their DNA.

Bipolar Disorder – Kate Pearman

Bipolar disorder (BD) is a psychiatric disorder that progresses through an individual’s lifetime.  More than 3 % of people are affected worldwide. Individuals with BD experience recurring episodes of depression and mania which significantly affect an individual’s quality of life and is positively associated with an increase in risk of suicide. Around a third to a half of BD patients attempt suicide on one occasion in their lifetime and an estimated 15-20% of these attempts are successful (Schaffer et al 2015). BD is also primarily diagnosed in young adulthood and thus affects the economically active population and therefore causes high costs to society (Gardner et al 2006). Therefore, highlighting the severity of this disorder and the need for a greater understanding into the pathology of BD for possibility of more efficacious treatment methods.

Knowledge of the pathogenesis and pathophysiology of BD has significantly increased over the last few decades. BD is one of the most heritable psychiatric disorders however, a multifactorial model in which both gene and environment interact, is thought to describe the disorder most appropriately. Mood disorders were thought to be caused by an imbalance in monoaminergic neurotransmitter systems, in regards to BD the dopaminergic. Although evidence has shown these circuits are likely to have a role in BD, no singular dysfunction of these systems have been identified. However, modulation of synaptic and neural plasticity is thought to be important in the circuitry regulating cognitive functions (Martinowich et al 2009). Neurotrophic molecules like the brain-derived neurotrophic factor, have a strong role in signalling pathways such as dendritic sprouting and neural plasticity. Dendritic spine loss has been observed in post-mortem brain tissue of patients with BD (Konopaske et al 2014). Alternative pathways that can affect neuronal interconnectivity are also being investigated such as mitochondrial dysfunction and endoplasmic reticulum stress, neuroinflammation, oxidation, apoptosis and epigenetic changes, particularly histone and DNA methylation (Berk et al 2011). Also due to the main phenotype of BD being a biphasic energy shift the monitoring of phasic dysregulation in mood, sleep and behaviour is also being investigated. The understanding of underlying pathogenesis of BD is crucial in discovering novel drug targets and the development of biomarkers for the prognosis, risk and therapeutic response.


Figure 1- Life chart showing the progression of bipolar disorder, with severity, manic and hypomanic symptoms registered above the phase of euthymia (normal mood state) whereas depressive symptoms depicted below.


Thanks for reading…

We hope you found this article an interesting and insightful snapshot of the research into mental health conditions. Please note this article is for informative purposes and should not be used as a tool for self-diagnosis based on the symptoms we have discussed. If you, or anyone you know are suffering from a mental health condition, this is a great source of information for the various charities that can help:


Mental health is equally as important as physical health, and we at All That Is Neuro wish to help to fight the stigma and encourage awareness.




Snyder, M. A., & Gao, W.-J. (2013). NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia. Frontiers in Cellular Neuroscience7, 31.


Nakazawa, K., Jeevakumar, V., and Nakao, K. (2017). Spatial and temporal boundaries of NMDA receptor hypofunction leading to schizophrenia. Npj Schizophrenia, 3(1), 1. Doi:10.1038/s41537-016-0003-3


Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., McCarroll, S. A. (2016). Schizophrenia risk from complex variation of complement component 4. Nature530(7589), 177–183.


Rompala, G. R., Zsiros, V., Zhang, S., Kolata, S. M., & Nakazawa, K. (2013). Contribution of NMDA Receptor Hypofunction in Prefrontal and Cortical Excitatory Neurons to Schizophrenia-Like Phenotypes. PLoS ONE8(4), e61278.


Schizophrenia (2017). Mind. [Online] Accessed from:





Froukje E. de Vries, Stell J. de Wit, Odile A. van den Heuvel, Dick J. Veltman, Danielle C. Cath, Anton J. L. M. van Balkom and Ysbrand D. van der Werf (2017). Cognitive control networks in OCD: A resting-state connectivity study in unmediated patients with obsessive-compulsive disorder and their unaffected relatives. The World Journal of Biological Psychiatry.

Nutt D, and Malizia A (2006). Anxiety and OCD – the chicken or the egg? Journal of Psychopharmacology, 20(6). 729-731.

Imaged sourced from:



Aan het Rot, M., Mathew, S. J., & Charney, D. S. (2009). Neurobiological mechanisms in major depressive disorder. CMAJ : Canadian Medical Association Journal, 180(3), pp. 305–313.


Hyde, C., Nagle, M.W., Tian, C. et al. (2016). Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature genetics. 48(2016), pp. 1031-1036.


Bipolar disorder


HH Gardner, NL Kleinman, RA Brook, K Rajagopalan, TJ Brizee, JE Smeeding

The economic impact of bipolar disorder in an employed population from an employer perspective. J Clin Psychiatry, 67 (2006), pp. 1209-1218

A Schaffer, ET Isometsä, L Tondo, et al. International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder. Bipolar Disord, 17 (2015), pp. 1-16.


K Martinowich, RJ Schloesser, HK Manji. Bipolar disorder: from genes to behavior pathways

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M Berk, F Kapczinski, AC Andreazza, et al. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neurosci Biobehav Rev, 35 (2011), pp. 804-817.


GT Konopaske, N Lange, JT Coyle, FM Benes. Prefrontal cortical dendritic spine pathology in schizophrenia and bipolar disorder. JAMA Psychiatry, 71 (2014), pp. 1323-1331





Through Your Mind

Through Your Mind

This week we bring the audience of All That is Neuro something that is a little out of the ordinary for our blog. You may be aware that the 8th-14th of May marked Mental Health Awareness week – where people from all over the world took it upon themselves to help spread awareness of mental health and help fight the stigma. Continuing the pledge to ‘spread the word’, here we feature a post about the work of Chloe Thomas, a final year graphic design student at Nottingham Trent University who utilised her artistic talents to portray the anxious mind in its many different states.

What is the topic of your project, how did you approach it and why? 

Anxiety is something that is really close to my heart. I struggle to express how it is making me feel sometimes and don’t believe that people fully understand it. With the “Through Your Mind” project, I aim to raise awareness of what it feels like to be anxious by creating visual representations of the anxious mind. 

I asked friends and family who suffer from anxiety to draw diagrams of what their brain ‘looks like’ when they are feeling anxious. Using this research, I then recreated their ‘brain drawings’ as 3D sculptures.

Discovering mould-making and casting recently has really inspired my work, so I really loved being able to use what I’ve learned in the studio in my final year of university to make something tactile and visually interesting.”

What are the key features of your designs and how do they relate to anxiety? 

“For this project, I built three brains:

  • One in concrete (to represent the heaviness that an anxious brain can feel).

brain 1.jpeg

  • A pink plaster brain covered in silly string (to communicate the confusion and muddled thoughts that can be felt).

brain 2

  • A black and white layered brain (cast in resin to show the lack of enthusiasm and motivation that anxiety can leave you with).”brain 3.jpeg

What do you hope your project will bring to the general public? 

“I’d love to continue with Through Your Mind by creating a larger collection of brain sculptures to represent more individuals. This would show that anyone can suffer from anxiety in their own individual way – which I think is a really important message to communicate.”

I’d like people to feel able to open up about their anxieties by seeing others who have done so. I’d also like to be rid of the stigma attached to anxiety by helping people to gain some understanding of what it feels like and see the sheer number of people who suffer from anxiety. It’s completely normal and nobody should feel that they can’t speak out about it!” 


If you are feeling inspired and want to have a gander at more of Chloe’s work, please take a look at her portfolio:


By Molly Campbell








Brain Disorders: Electroconvulsive Therapy vs Transcranial Magnetic Stimulation.

Shock Therapy: A barbaric treatment no longer in use?
Previous treatments of mental illnesses are often now viewed as extreme. Back in the 1800’s the use of primitive treatment to cut away a section of the patient’s skull to release the ‘evil spirits’ from their body was a common treatment of mental disorders. A tranquilizing chair was also often adopted, where the individual would have to place their head inside a box to reduce blood flow to their brain (Griggs, 2014). Yes, this seems outrageous, terrifying and barbaric in today’s society. In modern day medicine however, the use of biomedical treatments such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS or rTMS) can actually be used to treat mental disorders, and have shown to be particularly successful in treatment-resistant depression. The unusual historical treatments have often led to the common misconception of ECT in that it is invasive and unsafe, however this is no longer viewed as the case.  These two approaches have actually revolutionized the treatment of depression, and now recent research also supports the use of TMS in those with autism and epilepsy, which will be discussed in this essay.

The History of Electroconvulsive Therapy
Italian neurologists Ugo Cerletti and Lucio Bini developed electroconvulsive therapy. Cerletti was an epilepsy specialist who knew that an electric shock across the head would lead to seizures. He thought that induced convulsions could be used to treat schizophrenia, however these convulsions were far too severe. Along with Kalinowski, a German physician, the researchers developed experiments to test brief electric shocks on humans. Around 10 – 20 ECT shocks on alternate days produced improvement in patients with acute-onset schizophrenia. Another side effect, which appeared to be beneficial, was the retrograde amnesia it caused, as it meant that patients did not report bad experiences towards the therapy. In further use, the treatment was found to be highly effective in depression (Sabbatini, 2016). Today ECT is executed under anesthesia, where small electrical currents are passed through the brain to specific areas via electrodes on the patient’s skull. This targeted therapy makes for an improvement on the previously used treatments such as drugs, as the side effects are minimal. The misconceptions associated with ECT were due to its improper use in its early days. It was often used to control psychiatric patients, whilst conscious and mostly without consent. Various media has depicted ECT in this way, such as the movie/novel One Flew Over the Cuckoos Nest – which is not how the treatment is used (Lilienfeld and Arkowitz, 2014).

ECT Success in Depression
ECT is currently one of the most successful therapies for severe depression, and sometimes in bipolar disorder, however less frequently in other mental disorders. In a meta-analysis by Pagnin et al (2004), ECT was shown to be the superior treatment in comparison to placebos, simulated ECT (a procedure were shocks are not given) and antidepressants, including tricyclic antidepressants and monoamine oxidase inhibitors. Tew et al (1999) found that even older patients with more severe depression and cognitive impairment could tolerate the use of ECT as equally as the younger patients with severe major depression, and even showed some improvement in results.

How does ECT work?
This is one thing we are unsure about, there are many theories postulated however the specific mechanisms leading to improvement in depressive disorders are unknown. It is possible that ECT increases the monoamine neurotransmitters, such as dopamine and serotonin, which are thought to be reduced in those with depression. Another theory is that the treatment stimulates the release of hormones from the hypothalamus or pituitary, as the hypothalamic-pituitary-adrenal axis is thought to be disturbed in depression. The treatment is also thought to have an anti-convulsant nature, rising the threshold for seizures and decreasing their duration. The final theory is that the efficacy of the treatment is due to an increase in synaptogenesis and neurogenesis.

Research by Madsen at al (2000) suggests that ECT leads to an increase in neurogenesis. Rats in this study were either given single electroconvulsive seizures, or a series of 10. Bromodeoxyuridine (BrdU) was administered to the rats; this is a marker commonly used to highlight newly born cells – an indicator of neurogenesis. This marker was used in combination with a specific neuronal marker and co-staining could therefore indicate these new cells were specifically neurons. One month following a single electroconvulsive seizure, there was a 3-fold increase in cells stained with BrdU in the dentate gyrus of the rat’s hippocampus (Figure 1), thus supporting the neurogenesis theory of ECT.


Figure 1: A single electroconvulsive seizure (ECS) stimulates cell proliferation. Double immunofluoroscence images showing a rat dentate gyrus from (top) a sham-treated animal and (bottom) an ECS treated-animal. Bromodeoxyuridine (BrdU) was injected six times with 12-hour intervals, starting 72 hours after ECS. Animals survived 1 month after the ECS treatment. Red cells are positive for the mitotic marker BrdU, and green cells are positive for the neuronal marker NeuN. Scale bar, 50 μm (Madsen et al 2000).

Transcranial Magnetic Stimulation: An advancement of ECT
TMS is another brain stimulation technique, which uses magnetic field (similar to that used in an MRI). It is non-invasive and unlike ECT the patients do not have to be under anesthesia. The magnetic currents pass through the brain and skull to induce currents in the brain tissue underlying a coil placed on the scalp of the individual. Similarly to ECT, TMS is a targeted therapy leading to fewer side effects than commonly used medications. This technique does have possible use as a therapeutic method, as it has been shown to be successful in depression. At the American psychiatric association’s annual meeting in 2013 they showed that TMS induced improvement in depression, and these results were maintained throughout the 12-month study, suggesting that the effects of TMS are long lasting. More recently however, TMS has been successfully used as a diagnostic tool for many disorders such as depression, epilepsy and autism (Narayana et al 2015). In epilepsy it has been used to determine the changes in the excitability of neurons in the brains of patients, and how this has altered after treatment with anti-epileptic drugs. TMS can then be applied to these epilepsy patients therapeutically as low-frequency TMS can reduce cortical excitability- it is a very promising treatment approach for people with treatment-resistant refractory epilepsy (Narayana et al 2015). Again, similarly to ECT the biology behind why TMS works is not completely understood. 

Autistic Spectrum Disorder – an upcoming use of TMS
Autistic Spectrum disorder has been considered a possible candidate for the therapeutic use of TMS. Autism affects around 700,000 people in the UK alone. It is a disorder that causes an individual to present with deficits in social interaction and communication across multiple contexts (according to DSM-5).  Advances within Neuroscience have allowed us to determine differences in the brains of those with autistic spectrum disorder, one such variation is that people with autism have larger brain sizes – possibly due to larger numbers of neurons. There is thought to be a lack of communication between various regions in the brain, which could explain why those with autism have difficulties integrating different cognitive functions. Although TMS has been used effectively in the treatment of depression, its use in autism is relatively novel and still being studied.

John Elder Robison, an individual with autistic spectrum disorder, was involved in a six-month study where he received weekly TMS treatments. He revealed that this treatment gave him empathy he had never felt before and the ability to perceive music in a way he had never experienced. To read more about John’s experience, his book ‘switched on’ is available, which details his use of TMS treatment and its effects.

Both of these techniques, ECT and TMS have been very successful in the treatment of depression, and particularly TMS as a diagnostic tool and potential therapeutic tool for many other brain disorders. These brain stimulation techniques hold many advantages over more commonly used treatments such as pharmacotherapy and unquestionably over the tranquilizing chair and primitive treatment. These treatments are not dangerous and could possibly change the way we diagnose and treat specific disorders, including autism, which there is currently few treatments for.

Author: Abbie Byford 

Editor: Molly Campbell



Griggs, R. 2014. Concise introduction to psychology. Worth Pub.

Sabbatini, R. 2016. The History of Shock Therapy in Psychiatry. [Online].

Pagnin, D et al. 2004. Efficacy of ECT in Depression: A Meta-Analytic Review. The Journal of ECT. 20(1),pp.13-20.

Lilienfeld, S. and Arkowitz, H. 2014. The Truth about Shock Therapy. [Online].

Tew, J et al. 1999. Acute Efficacy of ECT in the Treatment of Major Depression in the Old-Old. Am J Psychiatry. 156(12),pp.1865–1870.

Madsen, T el al. 2000. Increased neurogenesis in a model of electroconvulsive therapy. Biological Psychiatry. 47(12),pp.1043-1049.

Narayana, S et al. 2015. Clinical Applications of Transcranial Magnetic Stimulation in Pediatric Neurology. Journal of Child Neurology. 30(9),pp.1111-1124.



A Neuroscience Insight into Anxiety Disorders.

I read an article recently in a magazine aimed at individuals my age titled ‘Generation Anxiety’, and this sparked a series of thoughts and questions. The mental health charity Mind reported that 1 in 4 individuals in the UK will experience a mental health problem each year. 1 in 4. A quarter. That’s a lot. Of the listed mental health issues, 4.6 in 100 people will experience anxiety related problems this year.

What is anxiety?
Anxiety disorders describe pathological worry that actually stems from our cave man impulses, our ‘fight or flight response’ to put it simply. In the case of anxiety however an individual may not necessarily have a scenario to trigger such response, it occurs without stimuli, or with stimuli that wouldn’t necessarily be considered as dangerous. The DSM 5 (the diagnostic and statistical manual of mental health disorders) divides pathological anxiety into 3 categories: Obsessive compulsive related disorders, trauma and stressor related disorders and anxiety disorders (Calhoon et al). The stimuli differ for these diagnoses, but in all cases the cognitive and behavioral symptoms of anxiety adversely affect normal functioning.

Having read the initial statistics, I was shocked at how many people are actually affected by this condition. Having read the criteria for diagnosis, I was less shocked, because I most definitely can appreciate how easily worry can spiral and affect an individual in a pathological sense. At the end of the day, life can be very worrying; we are faced with stress every day be it through studying, through work, through financial stresses, all the things that make being an adult quite a burden. As a neuroscience student, I then began to question: what is happening in the brains of individuals for which this worry is becoming pathological? In addition to, why, despite the high incidence of individuals suffering, are there relatively few therapeutic targets identified for treatment? I wanted to explore these questions and present to you the answers from a neuroscience perspective.

Firstly, I encountered this statement from a source discussing mindfulness that I really quite liked:

The underlying mechanism of any mental illness is adaptive and present throughout the human population. A mental disorder is not a new and aberrant development of the human mind but an under- or over-representation of a native mechanism’ (Matthew, 2014).

The brain is complex, and with its complexity it poses the possibility of developing new ‘alternate’ circuits, new mechanisms of neurotransmission with far too much, or less, of the signalling molecule required.

When considering this, anxiety is a sum of its parts. So what has neuroscience taught us?

The Amygdala:
If you keep up to date with our blog you may have read a previous article discussing the role of the amygdala in fear responses. The amygdala is regarded as the ‘central hub’ for the circuitry that creates the sense of fear in our brains. Upon presentation of a threat, the lateral nucleus of the amygdala is activated, and through connections to the central nucleus of the amygdala initiates defensive behavioural mechanisms, freezing being the best example. Connections from the lateral amygdala to the basal amygdala to the nucleus accumbens enable defensive actions, such as avoidance, to be regulated. Don’t worry if the terminology baffles you, the schematic diagram (Figure 1) is a visual representation of these circuits.


Figure 1: A schematic of the circuits underlying defensive reactions and actions (LeDoux and Pine, 2016).

In accordance, individuals with lesions to the amygdala (i.e. damage) fail to show bodily reactions to threat. Imaging studies illustrate that in healthy individuals, a posing threat activates the amygdala, but in the case of an anxiety suffer there is exaggerated amygdala activation. In healthy individuals, cortical areas down-regulate the amygdala, however this capacity is destabilised in individuals with anxiety disorders (LeDoux and Pine, 2016).

Furthermore, a really interesting piece of research by Qin et al (2014) adopted structural and functional MRI to investigate the brain structure of young children who had been diagnosed with early childhood anxiety. Even in children as young as 7-9, MRI illustrated an enlarged amygdala volume, specifically the basolateral amygdala. Findings also showed increased connectivity between the amygdala and distributed brain systems implicated in attention and emotion perception. Machine algorithms suggest that the levels of childhood anxiety could be reliably predicted via amygdala morphometry and intrinsic functional connectivity.

The Bed Nucleus of the Stria Terminalis (BNST):
In neuroscience, one of the techniques in research that I find the most fascinating is optogenetics. This is where neuroscientists transfect cells with genes and render them responsive to light – you can physically turn on and turn off a gene through the presentation of a light stimulus. Two very elegant studies, Jennings et al (2013) and Kim et al (2013) have adopted optogenetics to examine the role of the BNST in anxiety disorders.

Jennings et al looked at the role of the ventral BNST (vBNST) in regulating motivated behaviour and generating anxiety. Interestingly, the study showed that learned anxiety associated with specific environments led to an increase in the activity of some vBNST neurons, and a decrease in activity of others – in accordance with the vBNST consisting functionally distinct cell populations. The vBNST cell populations were found to synapse with neurons of the ventral tegmental area (VTA) that is involved in motivated behaviour and also addiction. Cells that were found to be excited by anxiety-inducing environments excited the VTA cell to which they were synaptically linked, and this activity increased anxiety and decreased reward seeking behaviour. Consistent results were found in vBNST neurons that were inhibited by anxiety seeking behaviour, and activating these connections encouraged reward-seeking behaviour and a reduction in anxiety levels. It must be considered however in these findings that the neurons were artificially excited to induce a state of anxiety – findings might differ in natural anxiety states. Nonetheless this research illustrates nicely that the BNST neuronal population, particularly the ventral neurons, are involved in anxiety. It might be the interplay of these neuronal populations that creates a specific level of anxiety.

Kim et al (2013) investigated whether the cells of the two subregions of the dorsal BNST, the oval nucleus and the anterodorsal BNST regulate anxiety. Their research showed that oval nucleus neurons promoted anxiety, whereas inputs from the amygdala activated the anterodorsal BNST and reduced anxiety. The inhibition of the anterodorsal BNST regions therefore enhanced anxiety. In mice models, the anterodorsal BNST neurons were more active when the mouse was in a safe, familiar environment when compared to an anxiety enhancing one.

The proposed mechanisms from this study are illustrated in figure 2.


Figure 2: A schematic illustrating the collective findings of Kim and Jennings et al (2013) and the proposed mechanisms underlying anxiety based on their research.

Collectively, these findings suggest evidence that in individuals with anxiety, there are physical structural changes to the brain, producing circuitry alterations that act overall to enhance fear.

For some people, particularly anxiety sufferers themselves, such evidence might be quite daunting; the idea that the brain can actually change its circuitry to produce pathology is quite hard to appreciate. For some, it might be reassuring, as it fights the stigma that unfortunately some associate with mental health conditions as being ‘not real’ – if a structural brain change doesn’t convince you then frankly I’m not sure what will. Regardless of which category you fall into, I would like to point you in the direction of neuroscience research that, using animal models, implies that these alterations can actually be corrected, or silenced, using select methods.

For example, a 2013 study investigated exposure therapy, an element of cognitive behavioural therapy (CBT) and its effects on the structure of the mouse brain. The research showed that exposure therapy silenced and stimulated remodelling of the perisomatic inhibitory synapse. This synapse enables one group of neurons to silence another, and the number of these synapses specifically increased around the fear neurons aforementioned in the amygdala. In the study, mice were placed in a box and exposed to a fear-stimulating situation. A control group did not receive the exposure therapy, whereas a comparison group did. In the exposure therapy group, the mice were placed in the box without the fear inducing situation repeatedly, and this led to a decreased response to the fear stimuli (Trouche et al., 2013). This research nicely demonstrates how the physiological changes in the brain present as behavioural changes. The study also suggested potential new drug targets for improving exposure therapy in humans, which has been found to show a varying success rate thus far.

I hope you will appreciate that the scope of research into anxiety and mental health in neuroscience is extremely large, and thus extends far beyond the content of this article. However, what I do hope to have shown you is how neuroscience research can greatly enhance our understanding of the underlying mechanisms that lead to disorders of the brain such as anxiety, and how these mechanisms produce the behaviour and symptoms that present clinically in sufferers.

Author: Molly Campbell


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Cure for Schizophrenia?

A Cure for Schizophrenia?

I decided to write an article on schizophrenia, seeing as it has been prevalent in the news recently. If you’re unsure why, a scientific breakthrough regarding schizophrenia development has been discovered by Steve McCarroll (Associate Professor and Director of Genetics for Harvard) and his research team. After almost two decades of research and billions of pounds spent, these scientists from Harvard Medical School have may have discovered the biological origin of the illness – the role of the gene complement component 4 (C4).

Before we get into the science, I’ll cover a bit about the illness. So what is schizophrenia? If we split the word up, we have ‘schizo’ or the Greek term ‘skhizein’, meaning ‘to split’, and the ending ‘phren’ meaning ‘mind’. But contrary to popular belief, this mental disorder doesn’t really have anything to do with having a split personality, or drastically changing from a calm and collected mood to a raging, manic episode. It’s an illness affecting over 200,000 individuals in the UK alone and over 200 million people across the globe with onset starting from late adolescence to early adulthood. It involves symptoms that have been split into categories of positive and negative. Positive symptoms represent delusions, auditory and visual hallucinations, and negative symptoms refer to feelings of disconnection from yourself, people around you and a lack of interest in general life. This tends to have a pretty big impact on your day to day activities and maintaining responsibilities including going to work, looking after your family etc.

Schizophrenia is probably one of the most misunderstood mental disorders that is heavily stigmatised and feared by many people in the public. It’s usually due to lack of understanding of the illness or the ability to empathise with people affected by schizophrenia. Portrayal of schizophrenia and mental illnesses in general in the media and on screen is usually associated with violence and sinister behaviour, which is probably the stem of the fear behind this illness. It’s easy enough for you to believe that you suddenly know everything you could possibly know about schizophrenia after watching a 90 minute psychological thriller about it on Netflix one night, but there’s more to the disorder that is usually forgotten about – the direct impact on the patient having to deal with the illness itself, in addition to knowing that your peers are perceiving you as strange or out of the ordinary. One of the main ways we can change the public perception on many psychiatric illnesses is to be able to educate people about areas they are unfamiliar about. This really emphasises how important it is for scientists to continue research and why we’re so excited by the recent breakthrough discovered that could possibly lead to the development of new therapies and treatment.

So now I should probably tell you what the breakthrough actually is. After McCarroll et. al analysed 100,000 human DNA samples from 30 different countries, they were able to locate genetic variants in particular regions of the genomes that are related to the increased risk of schizophrenia. The gene that stood out to them the most was C4, which is involved in the complement cascade and is part of the immune system. The variability in structure of most human genes is not usually much, unlike the gene C4. By genetically analysing more than 65,000 people, it was found that individuals with a particular form or structure of the gene showed higher expression of C4, consequently having a higher risk of developing schizophrenia.


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Figure 1 – Image credit: Psychiatric Genomics Consortiu. Studies by McCarroll et al., 2016.

You can see in Figure 1 how the C4 gene on chromosome 6 is pretty much dominating and is much higher than the other genes, all of which have been linked to schizophrenia. This is indicating that C4 may possibly pose the strongest risk for the disorder. But how is the C4 gene related to this disorder? C4 is a critical component of the classic complement cascade and has a key role in pruning synapses whilst the brain matures. Previous studies and this study in particular have found that animals with a high level of C4 activity had more of their synapses eliminated during a key stage of brain development. Elimination of connections between cells has long been associated with schizophrenic patients.



Figure 2 – C4 protein localisation in human brain tissue (McCarroll et al.)

The group of confocal images in Figure 2 show the localisation of the C4 gene in hippocampal tissue. This increased C4 activity is thought to lead to impairment in cognition, which is a symptom seen in schizophrenia. These findings suggest that therapies in the future may involve reducing C4 activity to prevent synaptic pruning in patients showing early symptoms and help prevent further progression of the disorder.

This study has been described as a crucial turning point in the fight against mental illness by the director of the US National Institute of Mental Health. For over a hundred years, the pathology of complex brain diseases that comprise cognition have been studied using carefully constructed behavioural tasks and it is thought that the regulation of biogenic amine neurotransmitters is abnormal in psychiatric disorders such as schizophrenia. Findings by McCarroll et al. have provided additional knowledge that may be important in dealing with many symptoms associated with the disorder, which are fundamental in scientists’ quest to try and find a cure. Although this breakthrough is unlikely to lead towards immediate treatments, researchers are one step closer towards understanding the key molecular and cellular events of the illness.

If you’d like to read about McCarroll’s study in depth, here’s a link to the journal that was published in Nature:


Whiteman, Honor. “Schizophrenia breakthrough: scientists shed light on biological cause.” Medical News Today. Available from:

Purves D. & Augustine G.J. et al. 2001. Neuroscience. 2nd ed. Sunderland MA: Sinauer Associates.

Author: Aisha Islam 

Editor: Molly Campbell