Schizophrenia is a complex disorder that is associated with multiple candidate genes. No single gene has been identified as the sole cause of schizophrenia, and it is believed that the more genes involved, the greater the risk. Some of the important candidate genes for schizophrenia include DTNBP1, COMT, NRG1, G72, RGS4, DAOA, DISC1, and DRD2. Among these, neuregulin, dysbindin, and DISC1 are the most replicated and plausible genes, with COMT being the strongest candidate gene due to its role in dopamine metabolism. Low activity of the COMT gene has been associated with obsessive-compulsive disorder and schizophrenia. Neuregulin 1 is a growth factor that stimulates neuron development and differentiation, and increased neuregulin signaling in schizophrenia may suppress the NMDA receptor, leading to lowered glutamate levels. Dysbindin is involved in the biogenesis of lysosome-related organelles, and its expression is decreased in schizophrenia. DISC1 encodes a multifunctional protein that influences neuronal development and adult brain function, and it is disrupted in schizophrenia. It is located at the breakpoint of a balanced translocation identified in a large Scottish family with schizophrenia, schizoaffective disorder, and other major mental illnesses.

Antidepressants can cause discontinuation symptoms when patients stop taking them, regardless of the type of antidepressant. These symptoms usually occur within 5 days of stopping the medication and can last up to 3 weeks. Symptoms include flu-like symptoms, dizziness, insomnia, vivid dreams, irritability, crying spells, and sensory symptoms. SSRIs and related drugs with short half-lives, such as paroxetine and venlafaxine, are particularly associated with discontinuation symptoms. Tapering antidepressants at the end of treatment is recommended to prevent these symptoms. TCAs and MAOIs are also associated with discontinuation symptoms, with amitriptyline and imipramine being the most common TCAs and all MAOIs being associated with prominent discontinuation symptoms. Patients at highest risk for discontinuation symptoms include those on antidepressants with shorter half-lives, those who have been taking antidepressants for 8 weeks of longer, those using higher doses, younger people, and those who have experienced discontinuation symptoms before. Agomelatine is not associated with any discontinuation syndrome. If a discontinuation reaction occurs, restarting the antidepressant of switching to an alternative with a longer half-life and tapering more slowly may be necessary. Explanation and reassurance are often sufficient for mild symptoms. These guidelines are based on the Maudsley Guidelines 14th Edition and a study by Tint (2008).

Electroencephalography

Electroencephalography (EEG) is a clinical test that records the brain’s spontaneous electrical activity over a short period of time using multiple electrodes placed on the scalp. It is mainly used to rule out organic conditions and can help differentiate dementia from other disorders such as metabolic encephalopathies, CJD, herpes encephalitis, and non-convulsive status epilepticus. EEG can also distinguish possible psychotic episodes and acute confusional states from non-convulsive status epilepticus.

Not all abnormal EEGs represent an underlying condition, and psychotropic medications can affect EEG findings. EEG abnormalities can also be triggered purposely by activation procedures such as hyperventilation, photic stimulation, certain drugs, and sleep deprivation.

Specific waveforms are seen in an EEG, including delta, theta, alpha, sigma, beta, and gamma waves. Delta waves are found frontally in adults and posteriorly in children during slow wave sleep, and excessive amounts when awake may indicate pathology. Theta waves are generally seen in young children, drowsy and sleeping adults, and during meditation. Alpha waves are seen posteriorly when relaxed and when the eyes are closed, and are also seen in meditation. Sigma waves are bursts of oscillatory activity that occur in stage 2 sleep. Beta waves are seen frontally when busy of concentrating, and gamma waves are seen in advanced/very experienced meditators.

Certain conditions are associated with specific EEG changes, such as nonspecific slowing in early CJD, low voltage EEG in Huntington’s, diffuse slowing in encephalopathy, and reduced alpha and beta with increased delta and theta in Alzheimer’s.

Common epileptiform patterns include spikes, spike/sharp waves, and spike-waves. Medications can have important effects on EEG findings, with clozapine decreasing alpha and increasing delta and theta, lithium increasing all waveforms, lamotrigine decreasing all waveforms, and valproate having inconclusive effects on delta and theta and increasing beta.

Overall, EEG is a useful tool in clinical contexts for ruling out organic conditions and differentiating between various disorders.

The Glasgow Coma Scale is used to assess the depth of coma and impaired consciousness. Scores range from 3 to 15, with impaired consciousness rated as mild, moderate, of severe. The scale assesses eye opening response, verbal response, and motor response, with specific criteria for scoring each behavior. The final score is a combination of these three scores.
Scoring Guide;
Eye opening response
4 Spontaneous opening
3 Opens to verbal stimuli
2 Opens to pain
1 No response
Verbal response
5 Orientated
4 Confused conversation
3 Inappropriate words
2 Incoherent
1 No response
Motor response
6 Obeys commands
5 Purposeful movement to painful stimuli
4 Withdraws in response to pain
3 Flexion in response to pain (decorticate posturing)
2 Extension in response to pain (decerebrate posturing)
1 No response

The working memory is overseen by the central executive, which manages all its functions. Although the exact location of the central executive is not fully comprehended, it is believed to involve various regions of the brain.

Memory Forms

Memory is the ability to store, retain, and retrieve information. There are different forms of memory, including sensory memory, short-term/working memory, and long-term memory.

Sensory memory is the capacity for briefly retaining the large amounts of information that people encounter daily. It includes echoic memory (gathered through auditory stimuli), iconic memory (gathered through sight), and haptic memory (acquired through touch).

Short-term memory is the ability to keep a small amount of information available for a short period of time. Atkinson and Shiffrin’s multistore model (1968) suggests the existence of a short-term storehouse with limited capacity. Baddeley and Hitch (1974) further developed the concept of short-term memory, which eventually became known as Baddeley’s multi-storehouse model (2000). This model includes the central executive, visuospatial sketchpad, phonological buffer/loop, and episodic buffer.

Long-term memory includes declarative (of explicit) memories, which can be consciously retrieved, and nondeclarative (of implicit) memories, which cannot. Declarative memory includes episodic memory (stores personal experiences) and semantic memory (stores information about facts and concepts). Non-declarative memory includes procedural memory (recalls motor and executive skills), associative memory (storage and retrieval of information through association with other information), and non-associative memory (refers to newly learned behavior through repeated exposure to an isolated stimulus).

Overall, memory is a complex and essential cognitive function that plays a crucial role in learning, reasoning, and understanding.

Mental State Exam: Appearance

The appearance of a patient can provide valuable clues to an underlying disorder. It is important to note that the following examples are not always present, but they can be helpful for educational purposes.

Individuals experiencing hypomania or mania may tend to wear bright and colorful clothing and may apply unusual of garish makeup. On the other hand, unfashionable and mismatched clothing may indicate schizoid personality traits of autistic spectrum disorders.

An excessively tidy appearance may suggest an obsessional personality. It is important to consider these cues in conjunction with other aspects of the mental state exam to arrive at an accurate diagnosis. Proper observation and interpretation of a patient’s appearance can aid in the development of an effective treatment plan.

Gait disorders can be caused by a variety of conditions, including neurological, muscular, and structural abnormalities. One common gait disorder is hemiplegic gait, which is characterized by unilateral weakness on the affected side, with the arm flexed, adducted, and internally rotated, and the leg on the same side in extension with plantar flexion of the foot and toes. When walking, the patient may hold their arm to one side and drag their affected leg in a semicircle (circumduction) due to weakness of leg flexors and extended foot. Hemiplegic gait is often seen in patients who have suffered a stroke.

Other gait disorders include ataxic gait, spastic gait, and steppage gait, each with their own unique characteristics and associated conditions. Accurate diagnosis and treatment of gait disorders is important for improving mobility and quality of life for affected individuals.

The doctor’s decision is grounded in the moral righteousness of the act, rather than its consequences, and is therefore based on the principles of deontology, specifically the ‘categorical imperative’.

Ethical theory and principles are important in medical ethics. There are three key ethical theories that have dominated medical ethics: utilitarianism, deontological, and virtue-based. Utilitarianism is based on the greatest good for the greatest number and is a consequentialist theory. Deontological ethics emphasize moral duties and rules, rather than consequences. Virtue ethics is based on the ethical characteristics of a person and is associated with the concept of a good, happy, flourishing life.

More recent frameworks have attempted to reconcile different theories and values. The ‘four principles’ of ‘principlism’ approach, developed in the United States, is based on four common, basic prima facie moral commitments: autonomy, beneficence, non-maleficence, and justice. Autonomy refers to a patient’s right to make their own decisions, beneficence refers to the expectation that a doctor will act in a way that will be helpful to the patient, non-maleficence refers to the fact that doctors should avoid harming their patients, and justice refers to the expectation that all people should be treated fairly and equally.

A woman is experiencing an obsessive thought that manifests as persistent imagery, which she cannot control. She tries to suppress the thought, indicating the development of compulsive behavior. She may also experience autoscopic hallucinations, where she sees a hallucinatory double of herself. Compulsions are repetitive behaviors that she uses to alleviate anxiety caused by obsessive experiences, which can be either motor of cognitive. Additionally, she may experience ruminative cognitions, which are repetitive thoughts that do not lead to any conclusion. In some cases, she may also experience thought insertion, where she attributes the source of the image to an external force.

Inheritance Patterns and Examples

Autosomal Dominant:
Neurofibromatosis type 1 and 2, tuberous sclerosis, achondroplasia, Huntington disease, and Noonan’s syndrome are all examples of conditions that follow an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene is needed to cause the condition.

Autosomal Recessive:
Phenylketonuria, homocystinuria, Hurler’s syndrome, galactosaemia, Tay-Sach’s disease, Friedreich’s ataxia, Wilson’s disease, and cystic fibrosis are all examples of conditions that follow an autosomal recessive inheritance pattern. This means that two copies of the mutated gene are needed to cause the condition.

X-Linked Dominant:
Vitamin D resistant rickets and Rett syndrome are examples of conditions that follow an X-linked dominant inheritance pattern. This means that the mutated gene is located on the X chromosome and only one copy of the gene is needed to cause the condition.

X-Linked Recessive:
Cerebellar ataxia, Hunter’s syndrome, and Lesch-Nyhan are examples of conditions that follow an X-linked recessive inheritance pattern. This means that the mutated gene is located on the X chromosome and two copies of the gene are needed to cause the condition.

Mitochondrial:
Leber’s hereditary optic neuropathy and Kearns-Sayre syndrome are examples of conditions that follow a mitochondrial inheritance pattern. This means that the mutated gene is located in the mitochondria and is passed down from the mother to her offspring.