First Rank Symptoms: Their Significance in Identifying Schizophrenia

First rank symptoms were introduced by Kurt Schneider in 1938 as a practical tool for non-psychiatrists to identify schizophrenia. While they are highly suggestive of schizophrenia, they are not pathognomonic and can also be seen in affective and personality disorders. Additionally, there is no evidence to support their prognostic significance.

A systematic review in 2015 found that first rank symptoms differentiated schizophrenia from nonpsychotic mental health disorders with a sensitivity of 61.8% and a specificity of 94.1%. They also differentiated schizophrenia from other types of psychosis with a sensitivity of 58% and a specificity of 74.7%.

The first rank symptoms include running commentary, thought echo, voices heard arguing, thought insertion, thought withdrawal, thought broadcast, delusional perception, somatic passivity, made affect, and made volition. While they can be helpful in identifying schizophrenia, they should not be relied upon as the sole diagnostic criteria.

The term ‘schizophrenogenic mother’ was proposed by Fromm-Reichmann, a contemporary of Freud, who believed that defective parenting caused the disorder. However, this concept has since been proven to be unfounded. Lidz later examined the impact of parents’ socialization on a child’s psychological health, further exploring this concept. Bleuler is credited with coining the term ‘schizophrenia’, while Kraepelin had previously described ‘dementia praecox’.

Neurotransmitters are substances used by neurons to communicate with each other and with target tissues. They are synthesized and released from nerve endings into the synaptic cleft, where they bind to receptor proteins in the cellular membrane of the target tissue. Neurotransmitters can be classified into different types, including small molecules (such as acetylcholine, dopamine, norepinephrine, serotonin, and GABA) and large molecules (such as neuropeptides). They can also be classified as excitatory or inhibitory. Receptors can be ionotropic or metabotropic, and the effects of neurotransmitters can be fast of slow. Some important neurotransmitters include acetylcholine, dopamine, GABA, norepinephrine, and serotonin. Each neurotransmitter has a specific synthesis, breakdown, and receptor type. Understanding neurotransmitters is important for understanding the function of the nervous system and for developing treatments for neurological and psychiatric disorders.

While there is some conflicting evidence, it is generally believed that tobacco smoking does not have a significant impact on the effectiveness of lithium.

Tobacco products predominantly smoked tobacco that burns the organic matter produces hydrocarbons. And these hydrocarbons lead to the induction of certain cytochrome p450 enzymes notably CYP1A2 predominantly but also CYP1A1 and also CYP2E1 or other major enzymes that are induced by tobacco. This will lead to the increased clearance of a variety of pharmacologic agents that are used especially in psychiatric populations. The most important ones to remember are antipsychotics and one of the antidepressants specifically fluvoxamine. When it comes to antipsychotics, clozapine and olanzapine are probably the most important ones to remember but also haloperidol and chlorpromazine could be affected as well. But for antidepressants, it’s really fluvoxamine that’s going to be mostly affected. And what this means is that while the person is actively smoking cigarettes, the clearance of these medications is increased probably anywhere from 20% to 50% or sometimes even more. And so what this means is those individuals may require higher doses than usual.

Lithium – Pharmacology

Pharmacokinetics:
Lithium salts are rapidly absorbed following oral administration and are almost exclusively excreted by the kidneys unchanged. Blood samples for lithium should be taken 12 hours post-dose.

Ebstein’s:
Ebstein’s anomaly is a congenital malformation consisting of a prolapse of the tricuspid valve into the right ventricle. It occurs in 1:20,000 of the general population. Initial data suggested it was more common in those using lithium but this had not held to be true.

Contraindications:
Addison’s disease, Brugada syndrome, cardiac disease associated with rhythm disorders, clinically significant renal impairment, untreated of untreatable hypothyroidism, low sodium levels.

Side-effects:
Common side effects include nausea, tremor, polyuria/polydipsia, rash/dermatitis, blurred vision, dizziness, decreased appetite, drowsiness, metallic taste, and diarrhea. Side-effects are often dose-related.

Long-term use is associated with hypothyroidism, hyperthyroidism, hypercalcemia/hyperparathyroidism, irreversible nephrogenic diabetes insipidus, and reduced GFR.

Lithium-induced diabetes insipidus:
Treatment options include stopping lithium (if feasible), keeping levels within 0.4-0.8 mmol/L, once-daily dose of the drug taken at bedtime, amiloride, thiazide diuretics, indomethacin, and desmopressin.

Toxicity:
Lithium salts have a narrow therapeutic/toxic ratio. Risk factors for lithium toxicity include drugs altering renal function, decreased circulating volume, infections, fever, decreased oral intake of water, renal insufficiency, and nephrogenic diabetes insipidus. Features of lithium toxicity include GI symptoms and neuro symptoms.

Pre-prescribing:
Before prescribing lithium, renal function, cardiac function, thyroid function, FBC, and BMI should be checked. Women of childbearing age should be advised regarding contraception, and information about toxicity should be provided.

Monitoring:
Lithium blood levels should be checked weekly until stable, and then every 3-6 months once stable. Thyroid and renal function should be checked every 6 months. Patients should be issued with an information booklet, alert card, and record book.

Intermediate Mechanism: Rationalisation

Rationalisation is a defense mechanism commonly used by individuals to create false but credible justifications for their behavior of actions. It involves the use of logical reasoning to explain away of justify unacceptable behavior of feelings. The individual may not be aware that they are using this mechanism, and it can be difficult to identify in oneself.

Rationalisation is considered an intermediate mechanism, as it is common in healthy individuals from ages three to ninety, as well as in neurotic disorders and in mastering acute adult stress. It can be dramatically changed by conventional psychotherapeutic interpretation.

Examples of rationalisation include a student who fails an exam and blames the teacher for not teaching the material well enough, of a person who cheats on their partner and justifies it by saying their partner was neglectful of unaffectionate. It allows the individual to avoid taking responsibility for their actions and to maintain a positive self-image.

Overall, rationalisation can be a useful defense mechanism in certain situations, but it can also be harmful if it leads to a lack of accountability and an inability to learn from mistakes.

Lithium – Pharmacology

Pharmacokinetics:
Lithium salts are rapidly absorbed following oral administration and are almost exclusively excreted by the kidneys unchanged. Blood samples for lithium should be taken 12 hours post-dose.

Ebstein’s:
Ebstein’s anomaly is a congenital malformation consisting of a prolapse of the tricuspid valve into the right ventricle. It occurs in 1:20,000 of the general population. Initial data suggested it was more common in those using lithium but this had not held to be true.

Contraindications:
Addison’s disease, Brugada syndrome, cardiac disease associated with rhythm disorders, clinically significant renal impairment, untreated of untreatable hypothyroidism, low sodium levels.

Side-effects:
Common side effects include nausea, tremor, polyuria/polydipsia, rash/dermatitis, blurred vision, dizziness, decreased appetite, drowsiness, metallic taste, and diarrhea. Side-effects are often dose-related.

Long-term use is associated with hypothyroidism, hyperthyroidism, hypercalcemia/hyperparathyroidism, irreversible nephrogenic diabetes insipidus, and reduced GFR.

Lithium-induced diabetes insipidus:
Treatment options include stopping lithium (if feasible), keeping levels within 0.4-0.8 mmol/L, once-daily dose of the drug taken at bedtime, amiloride, thiazide diuretics, indomethacin, and desmopressin.

Toxicity:
Lithium salts have a narrow therapeutic/toxic ratio. Risk factors for lithium toxicity include drugs altering renal function, decreased circulating volume, infections, fever, decreased oral intake of water, renal insufficiency, and nephrogenic diabetes insipidus. Features of lithium toxicity include GI symptoms and neuro symptoms.

Pre-prescribing:
Before prescribing lithium, renal function, cardiac function, thyroid function, FBC, and BMI should be checked. Women of childbearing age should be advised regarding contraception, and information about toxicity should be provided.

Monitoring:
Lithium blood levels should be checked weekly until stable, and then every 3-6 months once stable. Thyroid and renal function should be checked every 6 months. Patients should be issued with an information booklet, alert card, and record book.

Freud’s The Psychopathology of Everyday Life was written in 1901, while The Interpretation of Dreams was written in 1899, Mourning and Melancholia in 1917, and The Ego and the Id in 1923. Man and Superman was a play written by George Bernard Shaw in 1903 and is unrelated to Freud’s works.

Mitosis is a process that occurs in somatic cells during the cell cycle and involves four stages: prophase, metaphase, anaphase, and telophase. Prior to mitosis, during the interphase, DNA replication occurs in a separate stage called synthesis of S phase. Mitosis results in the division of a cell that has already replicated its chromosomes into two daughter cells that are genetically identical to the original cell.

On the other hand, meiosis is a process that occurs in the testes and ovaries and results in the formation of haploid cells, which contain 22 single autosomes and 1 sex chromosome, and are used to form gametes. During meiosis, recombination of cross-over occurs, where matching portions of chromosomes are exchanged to ensure genetic variation in the production of gametes.

Priapism: A Painful and Persistent Erection

Priapism is a condition characterized by a prolonged and painful erection, which can occur in males and even in the clitoris. Although rare, certain medications such as antipsychotics and antidepressants have been known to cause priapism. The primary mechanism behind this condition is alpha blockade, although other mechanisms such as serotonin-mediated pathways have also been suggested. Some of the drugs most commonly associated with priapism include Trazodone, Chlorpromazine, and Thioridazine. Treatment involves the use of alpha-adrenergic agonists, which can be administered orally of injected directly into the penis. Priapism is a serious condition that can lead to complications such as penile amputation, although such cases are extremely rare.

Broca’s and Wernicke’s are two types of expressive dysphasia, which is characterized by difficulty producing speech despite intact comprehension. Dysarthria is a type of expressive dysphasia caused by damage to the speech production apparatus, while Broca’s aphasia is caused by damage to the area of the brain responsible for speech production, specifically Broca’s area located in Brodmann areas 44 and 45. On the other hand, Wernicke’s aphasia is a type of receptive of fluent aphasia caused by damage to the comprehension of speech, while the actual production of speech remains normal. Wernicke’s area is located in the posterior part of the superior temporal gyrus in the dominant hemisphere, within Brodmann area 22.

The mental state exam assesses various areas of cognition, including orientation, attention/concentration, short term memory, long term memory, and executive function. Standard tests for each area include asking about time, place, and person for orientation, serial 7’s for attention/concentration, digit span for short term memory, delayed recall of name and address for long term memory, and various tasks such as proverbs, similarities, differences, verbal fluency, and cognitive estimates for executive function.

Beauchamp and Childress have identified four fundamental moral principles that form the basis of clinical ethics: respect for autonomy, non-maleficence, beneficence, and justice. Respecting a patient’s autonomy involves acknowledging their right to make decisions, even if those decisions may not seem wise. To obtain informed consent, patients must be fully informed about the treatment and its potential outcomes, and they must have the capacity to understand and weigh the information before making a decision. Non-maleficence requires healthcare providers to avoid causing harm, while beneficence involves balancing the potential benefits of a treatment against its risks. Finally, justice requires that healthcare providers act fairly and equitably. When a patient lacks the capacity to make decisions about their care, healthcare providers must act in the patient’s best interests, taking into account their previous views and consulting with relevant parties.

Karl Jaspers, a German psychiatrist and philosopher, first described tangentiality as a formal thought disorder where the patient deviates from the topic at hand and introduces new but related words. Although the examiner can usually follow the patient’s train of thought, the patient often loses track of the interviewer’s question. While tangentiality is not specific to any particular mental disorder, it can be present in conditions such as mania, hypomania, and schizophrenia. Other examples of formal thought disorder include loosening of associations, circumstantiality, thought block, perseveration, and flight of ideas.

Neuroimaging studies have shown that Alzheimer’s dementia is linked to a gradual increase in ventricular size, while schizophrenia is associated with non-progressive enlargement of the lateral and third ventricles. Although some studies have reported increased ventricular size in individuals with affective disorders, the findings are not consistent. Additionally, individuals with antisocial personality disorder may have reduced prefrontal gray matter volume.

The Willowbrook School Study was conducted in a state-supported institution for children with learning difficulties in New York during the 1960s. The study involved inoculating healthy children with hepatitis and administering gamma globulin to assess its potential to treat the disorder.

The Tuskegee syphilis experiment was a controversial follow-up study of people with syphilis. Many participants were not informed of their illness and did not receive available treatment, even though it became available halfway through the study. The Belmont report introduced changes to US law on research ethics as a result of this study.

The Stanford prison experiment involved creating a simulated prison environment at Stanford University. Participants were assigned as either a prison of a guard and were given no guidelines for how to behave. Within two days, the participants began to act out their assigned roles, with guards becoming harsh and sometimes cruel to the prisoners. The study was terminated after only six days due to extreme emotional reactions from some of the prisoners.

The Tearooms Study involved Humphreys hanging around public toilets where men meet to have sex in order to study the population and learn more about the types of men that did it. The method was controversial as he never disclosed his motives when he interviewed the men and instead pretended to be a ‘watch queen’, raising issues of informed consent in research.

Milgram’s Study investigated authority and obedience. Participants were assigned the role of teacher and administered fake shocks to a confederate playing the learner. Despite expressing concern, 30% of participants continued to administer shocks until 450 volts was reached. The study raised concerns for the wellbeing of participants, but Milgram decided not to terminate it as prior participants seemed to recover relatively well.

Beecher’s Study

Beecher’s study revealed more than 20 instances where individuals were subjected to experimentation without being fully informed of their participation in research and the potential risks involved. One of the cases cited was the Willowbrook State School study, where children with mental disabilities were intentionally infected with hepatitis under the guise of a vaccination program.

Neurotransmitters are substances used by neurons to communicate with each other and with target tissues. They are synthesized and released from nerve endings into the synaptic cleft, where they bind to receptor proteins in the cellular membrane of the target tissue. Neurotransmitters can be classified into different types, including small molecules (such as acetylcholine, dopamine, norepinephrine, serotonin, and GABA) and large molecules (such as neuropeptides). They can also be classified as excitatory or inhibitory. Receptors can be ionotropic or metabotropic, and the effects of neurotransmitters can be fast of slow. Some important neurotransmitters include acetylcholine, dopamine, GABA, norepinephrine, and serotonin. Each neurotransmitter has a specific synthesis, breakdown, and receptor type. Understanding neurotransmitters is important for understanding the function of the nervous system and for developing treatments for neurological and psychiatric disorders.

Post-traumatic stress disorder (PTSD) is a condition that develops in response to an exceptionally threatening of catastrophic event of situation, such as the one described above. It is only diagnosed if symptoms arise within six months of the traumatic event. The symptoms of PTSD can be categorized into three groups: re-experiencing the traumatic event (such as through nightmares of vivid thoughts), persistent avoidance of stimuli associated with the trauma, and persistent symptoms of increased arousal (such as difficulty sleeping of concentrating).

Agoraphobia is a fear of being in situations of places from which escape is difficult, leading to avoidance of many situations and confinement to the home. This fear is typically triggered by situations such as crowds, public places, of traveling alone of away from home.

Generalized anxiety disorder is characterized by persistent anxiety that is not limited to any specific environmental circumstance. To receive this diagnosis, a patient must experience symptoms of anxiety on most days for several weeks of months, with evidence of impairment in important areas of functioning. However, this diagnosis is not appropriate for the scenario described above, as the anxiety is related to a specific event of trigger.

Panic disorder involves sudden onset of severe anxiety, with at least three panic attacks experienced over a three-week period. Symptoms may include sweating, palpitations, shortness of breath, nausea, trembling, chest pain of discomfort, dizziness of lightheadedness, chills of hot flushes, fear of losing control of dying, paraesthesia, feeling of choking, and derealization or depersonalization.

Social phobia is characterized by a marked fear of social situations in which embarrassment may occur, leading to avoidance of these situations.

Pleiotropy refers to a genetic phenomenon where a single gene has an impact on multiple observable traits. This occurs because the gene produces a product that is utilized by various cells. An instance of pleiotropy is the human condition known as PKU (phenylketonuria).

Understanding Heterogeneity in Genetic Diseases

Heterogeneity is a term used to describe the presence of different genetic defects that can cause the same disease. This phenomenon is commonly observed in genetic disorders, where multiple mutations can lead to the same clinical presentation. For instance, the ABO blood group system is an example of heterogeneity, where different combinations of alleles can result in the same blood type.

Understanding heterogeneity is crucial for accurate diagnosis and treatment of genetic diseases. Identifying the specific genetic defect responsible for a particular disease can help tailor therapies and predict disease progression. However, the presence of heterogeneity can also complicate diagnosis and treatment, as different mutations may require different approaches.

Overall, heterogeneity highlights the complexity of genetic diseases and underscores the need for personalized medicine approaches that take into account individual genetic variations.

The preferred initial treatment for alcohol withdrawal syndrome is benzodiazepines.

– Catatonia is a psychiatric syndrome characterized by disturbed motor functions, mood, and thought.
– Key behaviors associated with catatonia include stupor, posturing, waxy flexibility, negativism, automatic obedience, mitmachen, mitgehen, ambitendency, psychological pillow, forced grasping, obstruction, echopraxia, aversion, mannerisms, stereotypies, motor perseveration, echolalia, and logorrhoea.
– These behaviors are often tested in exam questions.
– Karl Ludwig Kahlbaum is credited with the original clinical description of catatonia.

Projection is a coping mechanism in which one assigns their own unacceptable emotions and desires onto another person, thereby alleviating the discomfort of having conflicting feelings that do not align with their self-perception.

The Four Dopamine Pathways in the Brain

The brain has four main dopamine pathways that play crucial roles in regulating various functions. The nigrostriatal pathway is responsible for motor movement and runs from the substantia nigra to the basal ganglia. However, blocking D2 receptors in this pathway can lead to extrapyramidal side effects (EPSEs).

The tuberoinfundibular pathway, on the other hand, runs from the hypothalamus to the anterior pituitary and is responsible for regulating prolactin secretion. Dopamine inhibits prolactin secretion, which is why D2 selective antipsychotics can cause hyperprolactinemia.

The mesocortical pathway originates from the ventral tegmental area (VTA) and runs to the prefrontal cortex. This pathway plays a crucial role in regulating cognition, executive functioning, and affect.

Finally, the mesolimbic pathway also originates from the VTA and runs to the nucleus accumbens. This pathway is responsible for mediating positive psychotic symptoms, and dopamine hyperactivity in this pathway can lead to the development of these symptoms.

Overall, understanding the different dopamine pathways in the brain is crucial for developing effective treatments for various psychiatric disorders.

Mahler’s Separation-Individuation theory of child development proposes that personality development occurs in distinct stages. The first stage, the Autistic phase, occurs during the first few weeks of life, where the child is mostly sleeping and cut off from the world. The second stage, the Symbiotic phase, lasts until around six months of age, where the child sees themselves and their mother as a single unit. The third stage, Separation-Individuation, has four subphases. The first subphase, Differentiation, occurs between six to ten months, where the child begins to see themselves as an individual and experiences separation anxiety. The second subphase, Practicing, occurs between ten to sixteen months, where the child explores connections with the external world and people other than the mother. The third subphase, Rapprochement, occurs between sixteen to twenty-four months, where the child struggles to balance their desire for independence and proximity to the mother, often resulting in tantrums and the use of transitional objects. The fourth subphase, Object constancy, occurs between twenty-four to thirty-six months, where the child accepts the idea of object constancy and is more comfortable with the mother being separate for periods of time.

The Positive and Negative Syndrome Scale (PANSS) is a tool used to measure the severity of symptoms in patients with schizophrenia. The scale is divided into three categories: positive symptoms, negative symptoms, and general psychopathology symptoms. Each category has several items that are scored on a seven-point severity scale. The positive symptoms include delusions, hallucinations, and hyperactivity, while the negative symptoms include blunted affect and lack of spontaneity. The general psychopathology symptoms include anxiety, depression, and poor impulse control. The PANSS is a valuable tool for clinicians to assess the severity of symptoms in patients with schizophrenia and to monitor their progress over time.

To assess recall failure, the clinician typically asks the client to remember and then recall three objects after a delay. In the scenario described, the client’s difficulty cannot be attributed to a failure to maintain attention on the task, as their performance over the previous minute does not support this interpretation. However, the client’s perseveration in providing examples of words beginning with F suggests a possible issue with set-shifting, while expressive dysphasia may be identified through failure in speech of naming of objects during cognitive assessment. Disorientation, on the other hand, is typically evaluated through ten questions at the beginning of a mini-mental state examination of through screening questions during clinical assessment, and refers to a lack of recognition of place, time, of person.

Paraschemazia is a type of body image distortion that involves a feeling that certain body parts are twisted, distorted, of separated from the rest of the body. This can be caused by various factors, including hallucinogenic drug use, epileptic aura, and migraine. Body image distortions can be caused by both organic and psychiatric conditions. Organic causes may include Brown-Séquard paralysis, epileptic aura, and migraine, while psychiatric causes may include anorexia nervosa, hypochondriasis, depersonalization, and conversion disorders. Hemiasomatognosia is a specific type of body image distortion where the person feels that one half of their body is missing, and it can occur in epileptic aura and migraine. Other types of body image distortions include hyperschemazia, where parts of the body feel magnified in size, and hyposchemazia, where parts of the body feel diminished in size.

The ancient Greeks believed that the body’s health of illness was determined by the balance of four humours: black bile, yellow bile, blood, and phlegm. Each humour was linked to a specific mental state, with an excess of black bile being associated with a melancholic mood, which is where we get the word melancholy from.

The Significance of Active Metabolites in Drug Discovery and Development

Certain drugs are classified as prodrugs, which means that they are inactive when administered and require metabolism to become active. These drugs are converted into an active form, which is referred to as an active metabolite. Some drugs have important active metabolites, such as diazepam, dothiepin, fluoxetine, imipramine, risperidone, amitriptyline, and codeine, which are desmethyldiazepam, dothiepin sulfoxide, norfluoxetine, desipramine, 9-hydroxyrisperidone, nortriptyline, and morphine, respectively.

The role of pharmacologically active metabolites in drug discovery and development is significant. Understanding the active metabolites of a drug can help in the development of more effective and safer drugs. Active metabolites can also provide insights into the pharmacokinetics and pharmacodynamics of a drug, which can aid in the optimization of dosing regimens. Additionally, active metabolites can have different pharmacological properties than the parent drug, which can lead to the discovery of new therapeutic uses for a drug. Therefore, the study of active metabolites is an important aspect of drug discovery and development.

Schizophrenia and Duration of Treatment

The NICE guidelines do not provide a specific recommendation on the duration of treatment for schizophrenia. However, they do caution patients about the risks of stopping medication.

According to the guidelines, patients should be informed that there is a high risk of relapse if they stop taking their medication within the next 1-2 years. This suggests that long-term treatment may be necessary to manage symptoms and prevent relapse. It is important for patients to understand the potential consequences of stopping medication and to work closely with their healthcare provider to develop a treatment plan that meets their individual needs.