Depression

Why is cognitive assessment important in depression?

Why it is important to do research in depression?

Cognitive deficits are often seen in individuals with mood disorders, potentially reflecting underlying dysfunction of monoamine neurochemical systems3 and emotional processing circuitry4 

The search is on for treatments that can reduce cognitive impairment in mood disorders, in order to maximise long-term outcomes and quality of life. Another key area of ongoing research is the search for objective markers capable of identifying, for a given individual, treatment options that are most likely to be effective and well-tolerated. 

What is depression?

Mood disorders are highly prevalent across the world, affecting 5-10% of the adult population in a given year1, 2. The most common mood disorders are major depressive disorder, dysthymia, and bipolar disorder. 

Major depressive disorder (also known as depression) is characterised by low mood and/or loss of interest in previously pleasurable activities; in addition to a combination of several other symptoms such as impaired attention, changes in body weight, sleep disturbance, fatigue, excessive feelings of guilt, and negative thoughts. 

In bipolar disorder, individuals experience at least one episode of manic symptoms, but depressive episodes are also common. Mania refers to a distinct period of elevated, expansive, or irritable mood coupled with excess energy. 

Collectively, mood disorders cause considerable distress to affected individuals and can have a devastating impact on quality of life and everyday functioning. 

Treatment options for mood disorders can vary, but may include pharmacological treatments such as selective serotonin reuptake inhibitors (SSRIs) for depression and lithium or divalproex for bipolar disorder. Psychotherapy, particularly Cognitive Behavioural Therapy (CBT) may also be recommended, especially for those with depression.  

Why is it important to do research in core cognitive function?

Brain disorders are common, debilitating and economically crippling. Existing treatments often do not reverse underlying cognitive impairment or cannot be tolerated by patients. Our core cognition test battery incorporates the core cognitive domains often impaired in brain disorders, as well as those affected by cognitive enhancing drugs or interventions. 

What is core cognitive function?

Cognitive functions are critical for everyday functioning, including in the workplace and social situations. 

Problems with cognition are central to understanding psychiatric and neurological conditions across the lifespan. Examples include childhood-onset conditions such as Attention Deficit Hyperactivity Disorder (ADHD) or autism, conditions with onset in adolescence or early adulthood such as schizophrenia and depression, and disorders of older age including dementia. 

In a given year, approximately one-third of the adult population will experience a mental disorder, but less than one-third of these individuals receive any form of treatment1,2. 

Collectively, brain disorders represent a leading cause of morbidity across the globe, and this burden of disease is likely to increase over time3. 

Treatments capable of reversing cognitive dysfunction in brain disorders can help maximise quality of life and everyday functioning for affected individuals, in turn minimising suffering and the economic impact of these illnesses. 

Cognitive enhancement is also relevant in our daily lives, even in people without brain disorders. Caffeine consumption is an everyday occurrence in much of the world, and is used to regulate alertness and concentration, including in high-level athletes4. “Brain training” products are being investigated as a means of maintaining ‘brain health’ as we age5 

Certain conditions that cause cognitive dysfunction do have evidence-based treatments available. For example, ADHD can be successfully treated with psychostimulants or selective norepinephrine reuptake inhibitors such as atomoxetine. However, many people cannot take these medications due to intolerance or because of contraindications. Many other conditions, including schizophrenia and multiple sclerosis, do not have treatments that modify the underlying disease at all. This means that there is still a great need for novel interventions that can treat conditions with cognitive dysfunction.  

Why it is important to do research in cognitive safety?

Cognitive impairment is increasingly recognised as an important potential adverse effect of medication. Medications can exert untoward cognitive effects both via direct effects on the brain (by crossing the blood-brain barrier) and via indirect actions (peripheral mechanisms in the body). However, many drug development programmes do not incorporate sensitive cognitive measurements. 

This field is still at an early stage, and precisely what designs should be adopted, what outcome measures should be used, and what statistical approaches are most appropriate will vary depending on the drug in question and the indication. 

Even if a drug is shown to induce some cognitive impairment, it might still be beneficial to prescribe it; but pharmaceutical companies, regulators, clinicians, and patients need to understand the possible cognitive risks and their implications for everyday function. 

What is cognitive function?

Cognitive functions are vital for everyday functioning, including in the workplace and in social situations. They are especially crucial in safety-critical scenarios, such as when driving a car, or operating machinery. 

Detection of negative cognitive effects of pharmaceutical interventions is of vital importance from the perspective of patients, clinicians, and the public. Cognitive Safety signals are also an increasing focus of regulatory agencies including the US Food and Drug Administration (FDA) and European Medicines Agency (EMA)1. 

Assessment of the cognitive effects of medication is crucially important in drug development, licensing, and post-marketing surveillance. During drug development, objective measurement of cognitive effects can inform key decisions such as selection or rejection of compounds, choice of doses, and in support of the target indication(s). 

Safety-relevant cognitive data are extremely valuable in support of regulatory submissions and drug differentiation claims. Testing for cognitive function, motor skills and mood has been highlighted by the FDA as being important when conducting clinical trials for medications suspected to impact brain function2. 

Why is it important to do research in autism?

Individuals with autism spectrum disorder often exhibit cognitive deficits that reflect underlying abnormalities in brain structure and function5,6. Our recommended test battery for research of autism spectrum disorder’s assesses the core domains impaired in ASD, as well as those likely to be affected by novel interventions.  

The search is on for treatments that can ameliorate the core symptoms of ASD, and cognitive impairment, in order to maximise long-term outcomes and quality of life for affected individuals. 

What is autism?

Autism is a neurodevelopmental disorder associated with problems with social communication and/or interaction, and occurrences of restricted or repetitive patterns of behaviour, interests, or activities. 

Autism was previously distinguished from Asperger’s syndrome, but the latest version of the Diagnostic and Statistical Manual (DSM-5) instead uses a broader ‘umbrella’ category of Autism Spectrum Disorder (ASD). 

The condition affects approximately 1 in every 100 children. It is not fully known what causes autism but it is thought to include a mixture of environmental and genetic factors1. 

The UK National Institute for Health and Care Excellence (NICE) has a number of guidelines regarding the recognition, diagnosis, and treatment of autism2-4. Generally speaking, people with autism should be supported via a multidisciplinary approach, by people with expertise in the disorder. This can involve support from clinical psychologists, nurses, occupational therapists, psychiatrists, social workers, speech and language therapists, and other support staff. 

What is ADHD?

Attention-Deficit Hyperactivity Disorder (ADHD), otherwise known as hyperkinetic disorder, is a condition that affects people’s behaviour. ADHD can cause restlessness, trouble concentrating and impulsive behaviour1. For example, children with ADHD may blurt out answers in the classroom, fidget and find it impossible to keep still and struggle to focus on what a person is saying. 

ADHD is the most common psychiatric disorder of childhood, affecting at least 5% of children globally. Symptoms persist into adulthood in up to 60% of childhood cases2. 

For a diagnosis of ADHD to be given, the symptoms must be functionally impairing and occur in at least two distinct settings, for example at home and at school. 

Considerable research has examined the long-term consequences of ADHD, highlighting its global importance for society. In a systematic review of the data, untreated ADHD was associated with poorer long-term outcomes across all categories considered: these included academic performance, job performance and employment status, self-esteem, quality of life, and risk of driving accidents3. 

ADHD is a treatable psychiatric disorder, with medium to large effect sizes in terms of symptomatic improvement, versus control conditions, over the short-medium term4

ADHD is often misdiagnosed, and is frequently comorbid with other mental (and physical health) disorders. First-line treatment options for ADHD can include consideration of psychotherapy and/or medication, but these should always be offered as part of a comprehensive package of care. The most appropriate treatment options and sequencing of treatment options can vary considerably depending on factors such as the age of the individual, severity of disease, and patient/family preference. 

Why it is important to do research in ADHD?

The core symptoms of attention deficit disorders are cognitive in nature (inattention, hyperactivity, and/or impulsivity). These cognitive deficits often reflect underlying brain circuitry dysfunction (including prefrontal regions) and of neurochemical transmission, including the dopamine and noradrenaline/norepinephrine pathways5-9. Our recommended test battery for attention deficit disorders assesses the cognitive domains most likely to be impaired, as well as those likely to be affected by interventions. 

Sample CANTAB test battery for depression

We have developed the cognitive battery listed below as a starting point to aid the discussion between our clinical scientists and the sponsor’s clinical team regarding your specific study protocol, clinical population and the study goals.

Our sample test battery for depression and affective disorders assesses key cognitive domains often impaired in mood disorders, as well as those likely to be affected by interventions. 

Endpoints measured

Feedback sensitivity

Executive function

Sustained attention

Emotion recognition

Episodic memory

Key research for CANTAB® in depression and mood disorders

The tests within this battery have been shown to discriminate the neuropsychological profile of bipolar disorder from unipolar depression5, as well as be sensitive to the effects of different interventions in patients6.

Impaired performance on these tests correlated significantly with abnormal thinning of the cortex in young people with bipolar disorder7, demonstrating their sensitivity to disease-specific neuropathology. Cognitive performance on these tests also correlates with quality of life, even early in the course of bipolar disorder, making the battery not only biologically but also clinically relevant for mood disorders8.

A meta-analysis by Rock et al highlighted that cognitive impairment is still observed in individuals that had previously experienced a depressive episode, despite remission of their mood symptoms9. The CANTAB® tests demonstrated high sensitivity to cognitive dysfunction in depression, with moderate impairments seen in attention, memory and executive function.3 

Abbreviated from Rock et al, 2014. 

Pathology and functional impact of depression and mood disorders

Current biological models for mood disorders emphasise dysregulation of the prefrontal cortex and subgenual cingulate cortex, which play important roles in emotional regulation and executive processes; as well as dysfunction of the hippocampus and amygdala, which are involved in memory formation and detection of threatening stimuli4,10. 
According to the ‘monoamine hypothesis’, depression is linked with dysregulation of the serotonin, dopamine, and norepinephrine systems11. 

Given the centrality of these brain regions and neurochemical systems in cognition, it is not surprising that cognitive deficits are extremely common in people with mood disorders9,12. 

Get in touch

Scroll to Top