Tag: Psychopharmacology

What is Neuropsychopharmacology?

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Introduction

Neuropsychopharmacology, an interdisciplinary science related to psychopharmacology (study of effects of drugs on the mind) and fundamental neuroscience, is the study of the neural mechanisms that drugs act upon to influence behaviour.

It entails research of mechanisms of neuropathology, pharmacodynamics (drug action), psychiatric illness, and states of consciousness. These studies are instigated at the detailed level involving neurotransmission/receptor activity, bio-chemical processes, and neural circuitry. Neuropsychopharmacology supersedes psychopharmacology in the areas of “how” and “why”, and additionally addresses other issues of brain function. Accordingly, the clinical aspect of the field includes psychiatric (psychoactive) as well as neurologic (non-psychoactive) pharmacology-based treatments. Developments in neuropsychopharmacology may directly impact the studies of anxiety disorders, affective disorders, psychotic disorders, degenerative disorders, eating behaviour, and sleep behaviour.

Brief History

Drugs such as opium, alcohol, and certain plants have been used for millennia by humans to ease suffering or change awareness, but until the modern scientific era knowledge of how the substances actually worked was quite limited, most pharmacological knowledge being more a series of observation than a coherent model. The first half of the 20th century saw psychology and psychiatry as largely phenomenological, in that behaviours or themes which were observed in patients could often be correlated to a limited variety of factors such as childhood experience, inherited tendencies, or injury to specific brain areas. Models of mental function and dysfunction were based on such observations. Indeed, the behavioural branch of psychology dispensed altogether with what actually happened inside the brain, regarding most mental dysfunction as what could be dubbed as “software” errors. In the same era, the nervous system was progressively being studied at the microscopic and chemical level, but there was virtually no mutual benefit with clinical fields – until several developments after World War II began to bring them together. Neuropsychopharmacology may be regarded to have begun in the earlier 1950s with the discovery of drugs such as MAO inhibitors, tricyclic antidepressants, thorazine and lithium which showed some clinical specificity for mental illnesses such as depression and schizophrenia. Until that time, treatments that actually targeted these complex illnesses were practically non-existent. The prominent methods which could directly affect brain circuitry and neurotransmitter levels were the prefrontal lobotomy, and electroconvulsive therapy, the latter of which was conducted without muscle relaxants and both of which often caused the patient great physical and psychological injury.

The field now known as neuropsychopharmacology has resulted from the growth and extension of many previously isolated fields which have met at the core of psychiatric medicine, and engages a broad range of professionals from psychiatrists to researchers in genetics and chemistry. The use of the term has gained popularity since 1990 with the founding of several journals and institutions such as the Hungarian College of Neuropsychopharmacology. This rapidly maturing field shows some degree of flux, as research hypotheses are often restructured based on new information.

Overview

An implicit premise in neuropsychopharmacology with regard to the psychological aspects is that all states of mind, including both normal and drug-induced altered states, and diseases involving mental or cognitive dysfunction, have a neurochemical basis at the fundamental level, and certain circuit pathways in the central nervous system at a higher level. Thus the understanding of nerve cells or neurons in the brain is central to understanding the mind. It is reasoned that the mechanisms involved can be elucidated through modern clinical and research methods such as genetic manipulation in animal subjects, imaging techniques such as functional magnetic resonance imaging (fMRI), and in vitro studies using selective binding agents on live tissue cultures. These allow neural activity to be monitored and measured in response to a variety of test conditions. Other important observational tools include radiological imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). These imaging techniques are extremely sensitive and can image tiny molecular concentrations on the order of 10-10 M such as found with extrastriatal D1 receptor for dopamine.

One of the ultimate goals is to devise and develop prescriptions of treatment for a variety of neuropathological conditions and psychiatric disorders. More profoundly, though, the knowledge gained may provide insight into the very nature of human thought, mental abilities like learning and memory, and perhaps consciousness itself. A direct product of neuropsychopharmacological research is the knowledge base required to develop drugs which act on very specific receptors within a neurotransmitter system. These “hyperselective-action” drugs would allow the direct targeting of specific sites of relevant neural activity, thereby maximising the efficacy (or technically the potency) of the drug within the clinical target and minimising adverse effects. However, there are some cases when some degree of pharmacological promiscuity is tolerable and even desirable, producing more desirable results than a more selective agent would. An example of this is Vortioxetine, a drug which is not particularly selective as a serotonin reuptake inhibitor, having a significant degree of serotonin modulatory activity, but which has demonstrated reduced discontinuation symptoms (and reduced likelihood of relapse) and greatly reduced incidence of sexual dysfunction, without loss in antidepressant efficacy.

The groundwork is currently being paved for the next generation of pharmacological treatments, which will improve quality of life with increasing efficiency. For example, contrary to previous thought, it is now known that the adult brain does to some extent grow new neurons – the study of which, in addition to neurotrophic factors, may hold hope for neurodegenerative diseases like Alzheimer’s, Parkinson’s, ALS, and types of chorea. All of the proteins involved in neurotransmission are a small fraction of the more than 100,000 proteins in the brain. Thus there are many proteins which are not even in the direct path of signal transduction, any of which may still be a target for specific therapy. At present, novel pharmacological approaches to diseases or conditions are reported at a rate of almost one per week.

Neurotransmission

So far as we know, everything we perceive, feel, think, know, and do are a result of neurons firing and resetting. When a cell in the brain fires, small chemical and electrical swings called the action potential may affect the firing of as many as a thousand other neurons in a process called neurotransmission. In this way signals are generated and carried through networks of neurons, the bulk electrical effect of which can be measured directly on the scalp by an EEG device.

By the last decade of the 20th century, the essential knowledge of all the central features of neurotransmission had been gained. These features are:

  • The synthesis and storage of neurotransmitter substances;
  • The transport of synaptic vesicles and subsequent release into the synapse;
  • Receptor activation and cascade function; and
  • Transport mechanisms (reuptake) and/or enzyme degradation.

The more recent advances involve understanding at the organic molecular level; biochemical action of the endogenous ligands, enzymes, receptor proteins, etc. The critical changes affecting cell firing occur when the signalling neurotransmitters from one neuron, acting as ligands, bind to receptors of another neuron. Many neurotransmitter systems and receptors are well known, and research continues toward the identification and characterisation of a large number of very specific subtypes of receptors. For the six more important neurotransmitters Glu, GABA, Ach, NE, DA, and 5HT (listed at neurotransmitter) there are at least 29 major subtypes of receptor. Further “sub-subtypes” exist together with variants, totalling in the hundreds for just these 6 transmitters (refer to serotonin receptor, for example). It is often found that receptor subtypes have differentiated function, which in principle opens up the possibility of refined intentional control over brain function.

It has previously been known that ultimate control over the membrane voltage or potential of a nerve cell, and thus the firing of the cell, resides with the transmembrane ion channels which control the membrane currents via the ions K+, Na+, and Ca++, and of lesser importance Mg++ and Cl−. The concentration differences between the inside and outside of the cell determine the membrane voltage.

Precisely how these currents are controlled has become much clearer with the advances in receptor structure and G-protein coupled processes. Many receptors are found to be pentameric clusters of five transmembrane proteins (not necessarily the same) or receptor subunits, each a chain of many amino acids. Transmitters typically bind at the junction between two of these proteins, on the parts that protrude from the cell membrane. If the receptor is of the ionotropic type, a central pore or channel in the middle of the proteins will be mechanically moved to allow certain ions to flow through, thus altering the ion concentration difference. If the receptor is of the metabotropic type, G-proteins will cause metabolism inside the cell that may eventually change other ion channels. Researchers are better understanding precisely how these changes occur based on the protein structure shapes and chemical properties.

The scope of this activity has been stretched even further to the very blueprint of life since the clarification of the mechanism underlying gene transcription. The synthesis of cellular proteins from nuclear DNA has the same fundamental machinery for all cells; the exploration of which now has a firm basis thanks to the Human Genome Project which has enumerated the entire human DNA sequence, although many of the estimated 35,000 genes remain to be identified. The complete neurotransmission process extends to the genetic level. Gene expression determines protein structures through type II RNA polymerase. So enzymes which synthesize or breakdown neurotransmitters, receptors, and ion channels are each made from mRNA via the DNA transcription of their respective gene or genes. But neurotransmission, in addition to controlling ion channels either directly or otherwise through metabotropic processes, also actually modulates gene expression. This is most prominently achieved through modification of the transcription initiation process by a variety of transcription factors produced from receptor activity.

Aside from the important pharmacological possibilities of gene expression pathways, the correspondence of a gene with its protein allows the important analytical tool of gene knockout. Living specimens can be created using homolog recombination in which a specific gene cannot be expressed. The organism will then be deficient in the associated protein which may be a specific receptor. This method avoids chemical blockade which can produce confusing or ambiguous secondary effects so that the effects of a lack of receptor can be studied in a purer sense.

Drugs

The inception of many classes of drugs is in principle straightforward: any chemical that can enhance or diminish the action of a target protein could be investigated further for such use. The trick is to find such a chemical that is receptor-specific (cf. “dirty drug”) and safe to consume. The 2005 Physicians’ Desk Reference lists twice the number of prescription drugs as the 1990 version. Many people by now are familiar with “selective serotonin reuptake inhibitors“, or SSRIs which exemplify modern pharmaceuticals. These SSRI antidepressant drugs, such as Paxil and Prozac, selectively and therefore primarily inhibit the transport of serotonin which prolongs the activity in the synapse. There are numerous categories of selective drugs, and transport blockage is only one mode of action. The FDA has approved drugs which selectively act on each of the major neurotransmitters such as NE reuptake inhibitor antidepressants, DA blocker anti-psychotics, and GABA agonist tranquilisers (benzodiazepines).

New endogenous chemicals are continually identified. Specific receptors have been found for the drugs THC (cannabis) and GHB, with endogenous transmitters anandamide and GHB. Another recent major discovery occurred in 1999 when orexin, or hypocretin, was found to have a role in arousal, since the lack of orexin receptors mirrors the condition of narcolepsy. Orexin agonism may explain the antinarcoleptic action of the drug modafinil which was already being used only a year prior.

The next step, which major pharmaceutical companies are currently working hard to develop, are receptor subtype-specific drugs and other specific agents. An example is the push for better anti-anxiety agents (anxiolytics) based on GABAA(α2) agonists, CRF1 antagonists, and 5HT2c antagonists. Another is the proposal of new routes of exploration for antipsychotics such as glycine reuptake inhibitors. Although the capabilities exist for receptor-specific drugs, a shortcoming of drug therapy is the lack of ability to provide anatomical specificity. By altering receptor function in one part of the brain, abnormal activity can be induced in other parts of the brain due to the same type of receptor changes. A common example is the effect of D2 altering drugs (neuroleptics) which can help schizophrenia, but cause a variety of dyskinesias by their action on motor cortex.

Modern studies are revealing details of mechanisms of damage to the nervous system such as apoptosis (programmed cell death) and free-radical disruption. Phencyclidine has been found to cause cell death in striatopallidal cells and abnormal vacuolisation in hippocampal and other neurons. The hallucinogen persisting perception disorder (HPPD), also known as post-psychedelic perception disorder, has been observed in patients as long as 26 years after LSD use. The plausible cause of HPPD is damage to the inhibitory GABA circuit in the visual pathway (GABA agonists such as midazolam can decrease some effects of LSD intoxication). The damage may be the result of an excitotoxic response of 5HT2 interneurons (Note: the vast majority of LSD users do not experience HPPD. Its manifestation may be equally dependent on individual brain chemistry as on the drug use itself). As for MDMA, aside from persistent losses of 5HT and SERT, long-lasting reduction of serotonergic axons and terminals is found from short-term use, and regrowth may be of compromised function.

Neural Circuits

It is a not-so-recent discovery that many functions of the brain are somewhat localized to associated areas like motor and speech ability. Functional associations of brain anatomy are now being complemented with clinical, behavioural, and genetic correlates of receptor action, completing the knowledge of neural signalling (refer to Human Cognome Project). The signal paths of neurons are hyperorganised beyond the cellular scale into often complex neural circuit pathways. Knowledge of these pathways is perhaps the easiest to interpret, being most recognizable from a systems analysis point of view, as may be seen in the following abstracts.

Almost all drugs with a known potential for abuse have been found to modulate activity (directly or indirectly) in the mesolimbic dopamine system, which includes and connects the ventral tegmental area in the midbrain to the hippocampus, medial prefrontal cortex, and amygdala in the forebrain; as well as the nucleus accumbens in the ventral striatum of the basal ganglia. In particular, the nucleus accumbens (NAc) plays an important role in integrating experiential memory from the hippocampus, emotion from the amygdala, and contextual information from the PFC to help associate particular stimuli or behaviours with feelings of pleasure and reward; continuous activation of this reward indicator system by an addictive drug can also cause previously neutral stimuli to be encoded as cues that the brain is about to receive a reward. This happens via the selective release of dopamine, a neurotransmitter responsible for feelings of euphoria and pleasure. The use of dopaminergic drugs alters the amount of dopamine released throughout the mesolimbic system, and regular or excessive use of the drug can result in a long-term downregulation of dopamine signalling, even after an individual stops ingesting the drug. This can lead the individual to engage in mild to extreme drug-seeking behaviours as the brain begins to regularly expect the increased presence of dopamine and the accompanying feelings of euphoria, but how problematic this is depends highly on the drug and the situation.

Significant progress has been made on central mechanisms of certain hallucinogenic drugs. It is at this point known with relative certainty that the primary shared effects of a broad pharmacological group of hallucinogens, sometimes called the “classical psychedelics”, can be attributed largely to agonism of serotonin receptors. The 5HT2A receptor, which seems to be the most critical receptor for psychedelic activity, and the 5HT2C receptor, which is a significant target of most psychedelics but which has no clear role in hallucinogenesis, are involved by releasing glutamate in the frontal cortex, while simultaneously in the locus coeruleus sensory information is promoted and spontaneous activity decreases. 5HT2A activity has a net pro-dopaminergic effect, whereas 5HT2C receptor agonism has an inhibitory effect on dopaminergic activity, particularly in the prefrontal cortex. One hypothesis suggests that in the frontal cortex, 5HT2A promotes late asynchronous excitatory postsynaptic potentials, a process antagonised by serotonin itself through 5HT1 receptors, which may explain why SSRIs and other serotonin-affecting drugs do not normally cause a patient to hallucinate. However, the fact that many classical psychedelics do in fact have significant affinity for 5HT1 receptors throws this claim into question. The head twitch response, a test used for assessing classical psychedelic activity in rodents, is produced by serotonin itself only in the presence of beta-Arrestins, but is triggered by classical psychedelics independent of beta-Arrestin recruitment. This may better explain the difference between the pharmacology of serotonergic neurotransmission (even if promoted by drugs such as SSRIs) and that of classical psychedelics. Newer findings, however, indicate that binding to the 5HT2A-mGlu2 heterodimer is also necessary for classical psychedelic activity. This, too, may be relevant to the pharmacological differences between the two. While early in the history of psychedelic drug research it was assumed that these hallucinations were comparable to those produced by psychosis and thus that classical psychedelics could serve as a model of psychosis, it is important to note that modern neuropsychopharmacological knowledge of psychosis has progressed significantly since then, and we now know that psychosis shows little similarity to the effects of classical psychedelics in mechanism, reported experience or most other respects aside from the surface similarity of “hallucination”.

Circadian rhythm, or sleep/wake cycling, is centred in the suprachiasmatic nucleus (SCN) within the hypothalamus, and is marked by melatonin levels 2000-4,000% higher during sleep than in the day. A circuit is known to start with melanopsin cells in the eye which stimulate the SCN through glutamate neurons of the hypothalamic tract. GABAergic neurons from the SCN inhibit the paraventricular nucleus, which signals the superior cervical ganglion (SCG) through sympathetic fibres. The output of the SCG, stimulates NE receptors (β) in the pineal gland which produces N-acetyltransferase, causing production of melatonin from serotonin. Inhibitory melatonin receptors in the SCN then provide a positive feedback pathway. Therefore, light inhibits the production of melatonin which “entrains” the 24-hour cycle of SCN activity. The SCN also receives signals from other parts of the brain, and its (approximately) 24-hour cycle does not only depend on light patterns. In fact, sectioned tissue from the SCN will exhibit daily cycle in vitro for many days. Additionally, (not shown in diagram), the basal nucleus provides GABA-ergic inhibitory input to the pre-optic anterior hypothalamus (PAH). When adenosine builds up from the metabolism of ATP throughout the day, it binds to adenosine receptors, inhibiting the basal nucleus. The PAH is then activated, generating slow-wave sleep activity. Caffeine is known to block adenosine receptors, thereby inhibiting sleep among other things.

Research

Research in the field of neuropsychopharmacology encompasses a wide range of objectives. These might include the study of a new chemical compound for potentially beneficial cognitive or behavioural effects, or the study of an old chemical compound in order to better understand its mechanism of action at the cell and neural circuit levels. For example, the addictive stimulant drug cocaine has long been known to act upon the reward system in the brain, increasing dopamine and norepinephrine levels and inducing euphoria for a short time. More recently published studies however have gone deeper than the circuit level and found that a particular G-protein coupled receptor complex called A2AR-D2R-Sigma1R is formed in the NAc following cocaine usage; this complex reduces D2R signalling in the mesolimbic pathway and may be a contributing factor to cocaine addiction. Other cutting-edge studies have focused on genetics to identify specific biomarkers that may predict an individual’s specific reactions or degree of response to a drug or their tendency to develop addictions in the future. These findings are important because they provide detailed insight into the neural circuitry involved in drug use and help refine old as well as develop new treatment methods for disorders or addictions. Different treatment-related studies are investigating the potential role of peptide nucleic acids in treating Parkinson’s disease and schizophrenia while still others are attempting to establish previously unknown neural correlates underlying certain phenomena.

Research in neuropsychopharmacology comes from a wide range of activities in neuroscience and clinical research. This has motivated organizations such as the American College of Neuropsychopharmacology (ACNP), the European College of Neuropsychopharmacology (ECNP), and the Collegium Internationale Neuro-psychopharmacologicum (CINP) to be established as a measure of focus. The ECNP publishes European Neuropsychopharmacology, and as part of the Reed Elsevier Group, the ACNP publishes the journal Neuropsychopharmacology, and the CINP publishes the journal International Journal of Neuropsychopharmacology with Cambridge University Press. In 2002, a recent comprehensive collected work of the ACNP, “Neuropsychopharmacology: The Fifth Generation of Progress” was compiled. It is one measure of the state of knowledge in 2002, and might be said to represent a landmark in the century-long goal to establish the basic neurobiological principles which govern the actions of the brain.

Many other journals exist which contain relevant information such as Neuroscience. Some of them are listed at Brown University Library.

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Who was Heather Ashton?

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Introduction

Heather Ashton FRCP (11 July 1929 to 15 September 2019) was a British psychopharmacologist and physician. She is best known for her clinical and research work on benzodiazepene dependence.

Biography

Chrystal Heather Champion was born in Dehradun, northern India, to Harry Champion, a British silviculturalist, and Chrystal (Parsons) Champion, a secretary. From the age of six, she attended a boarding school in Swanage, Dorset, England. When WWII began, she was evacuated to West Chester, Pennsylvania; during the crossing, her ship was attacked by a U-boat.

Ashton went on to study Medicine at Somerville College, Oxford, graduating with a First Class Honours Degree (BA) in Physiology in 1951. She earned her medical degree (DM) in 1956. She completed professional training at Middlesex Hospital. She was elected as a Fellow of the Royal College of Physicians, London, in 1975.

In 1965, Ashton joined the faculty at Newcastle University, first in the Department of Pharmacology and later in the Department of Psychiatry. From 1982 to 1994, she ran a benzodiazepine withdrawal clinic at the Royal Victoria Infirmary in Newcastle. She was on the executive committee of the North East Council on Addictions. Ashton also helped set up the British organisation Victims of Tranquillisers (VOT). She also gave evidence to British government committees on tobacco smoking, cannabis and benzodiazepines.

Ashton died on 15 September 2019 at her home in Newcastle upon Tyne, at age 90.

Research

Ashton’s developed her expertise in the effects of psychoactive drugs and the effects of substances such as nicotine and cannabis on the brain.

During the 1960s, benzodiazepines, like diazepam and temazepam, had become popular and were seen as safe and effective treatments for anxiety or insomnia. One study found that the overdose death rate among patients taking both benzodiazepines and opioids was 10 times higher than among those who only took opioids.

Ashton’s research on these drugs found that they could be used in the short term, but could lead to physical dependence over the long-term. She also recognised that this benzodiazepine withdrawal syndrome was very different from those addicted to illegal drugs. This led to her writing an important manual to help those who were trying to stop their prescribed benzodiazepine. This manual is now used all over the world. This book, Benzodiazepines: How They Work and How to Withdraw, was first published in 1999; it has become known as the Ashton Manual and has been translated into 11 languages. Ashton’s research was influential, leading to changes in prescribing practices and guidelines recommended for benzodiazepines in 2013. Her research on psychotropic drugs led to over 200 journal articles, chapters and books, including over 50 papers concerning benzodiazepines alone.

What is Clinical Neuropsychology?

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Introduction

Clinical neuropsychology is a sub-field of psychology concerned with the applied science of brain-behaviour relationships.

Clinical neuropsychologists use this knowledge in the assessment, diagnosis, treatment, and or rehabilitation of patients across the lifespan with neurological, medical, neurodevelopmental and psychiatric conditions, as well as other cognitive and learning disorders. The branch of neuropsychology associated with children and young people is paediatric neuropsychology.

Clinical neuropsychology is a specialised form of clinical psychology. Strict rules are in place to maintain evidence as a focal point of treatment and research within clinical neuropsychology. The assessment and rehabilitation of neuropsychopathologies is the focus for a clinical neuropsychologist. A clinical neuropsychologist must be able to determine whether a symptom(s) may be caused by an injury to the head through interviewing a patient in order to determine what actions should be taken to best help the patient. Another duty of a clinical neuropsychologist is to find cerebral abnormalities and possible correlations. Evidence based practice in both research and treatment is paramount to appropriate clinical neuropsychological practice.

Assessment is primarily by way of neuropsychological tests, but also includes patient history, qualitative observation and may draw on findings from neuroimaging and other diagnostic medical procedures. Clinical neuropsychology requires an in-depth knowledge of: neuroanatomy, neurobiology, psychopharmacology and neuropathology.

Brief History

During the late 1800s, brain-behaviour relationships were interpreted by European physicians who observed and identified behavioural syndromes that were related with focal brain dysfunction.

Clinical neuropsychology is a fairly new practice in comparison to other specialty fields in psychology with history going back to the 1960s. The specialty focus of clinical neuropsychology evolved slowly into a more defined whole as interest grew. Threads from neurology, clinical psychology, psychiatry, cognitive psychology, and psychometrics all have been woven together to create the intricate tapestry of clinical neuropsychology, a practice which is very much so still evolving. The history of clinical neuropsychology is long and complicated due to its ties to so many older practices. Researchers like Thomas Willis (1621-1675) who has been credited with creating neurology, John Hughlings Jackson (1835-1911) who theorised that cognitive processes occurred in specific parts of the brain, Paul Broca (1824-1880) and Karl Wernicke (1848-1905) who studied the human brain in relation to psychopathology, Jean Martin Charcot (1825-1893) who apprenticed Sigmund Freud (1856-1939) who created the psychoanalytic theory all contributed to clinical medicine which later contributed to clinical neuropsychology. The field of psychometrics contributed to clinical neuropsychology through individuals such as Francis Galton (1822-1911) who collected quantitative data on physical and sensory characteristics, Karl Pearson (1857-1936) who established the statistics which psychology now relies on, Wilhelm Wundt (1832-1920) who created the first psychology lab, his student Charles Spearman (1863-1945) who furthered statistics through discoveries like factor analysis, Alfred Binet (1857-1911) and his apprentice Theodore Simon (1872-1961) who together made the Binet-Simon scale of intellectual development, and Jean Piaget (1896-1980) who studied child development. Studies in intelligence testing made by Lewis Terman (1877-1956) who updated the Binet-Simon scale to the Stanford-Binet intelligence scale, Henry Goddard (1866-1957) who developed different classification scales, and Robert Yerkes (1876-1956) who was in charge of the Army Alpha and Beta tests also all contributed to where clinical neuropsychology is today.

Clinical neuropsychology focuses on the brain and goes back to the beginning of the 20th century. As a clinician a clinical neuropsychologist offers their services by addressing three steps: assessment, diagnosis, and treatment. The term clinical neuropsychologist was first made by Sir William Osler on 16 April 1913. While clinical neuropsychology was not a focus until the 20th century evidence of brain and behaviour treatment and studies are seen as far back as the neolithic area when trephination, a crude surgery in which a piece of the skull is removed, has been observed in skulls. As a profession, clinical neuropsychology is a subspecialty beneath clinical psychology. During World War I (1914-1918) the early term shell shock was first observed in soldiers who survived the war. This was the beginning of efforts to understand traumatic events and how they affected people. During the Great Depression (1929-1941) further stressors caused shell shock like symptoms to emerge. In World War II (1939-1945) the term shell shock was changed to battle fatigue and clinical neuropsychology became even more involved with attempting to solve the puzzle of peoples’ continued signs of trauma and distress. The Veterans Administration or VA was created in 1930 which increased the call for clinical neuropsychologists and by extension the need for training. The Korean War (1950-1953) and Vietnam War (1960-1973) further solidified the need for treatment by trained clinical neuropsychologists. In 1985 the term post-traumatic stress disorder or PTSD was coined and the understanding that traumatic events of all kinds could cause PTSD started to evolve.

The relationship between human behaviour and the brain is the focus of clinical neuropsychology as defined by Meir in 1974. There are two subdivisions of clinical neuropsychology which draw much focus; organic and environmental natures. Ralph M. Reitan, Arthur L. Benton, and A.R. Luria are all past neuropsychologists whom believed and studied the organic nature of clinical neuropsychology. Alexander Luria is the Russian neuropsychologist responsible for the origination of clinical psychoneurological assessment after WWII. Building upon his original contribution connecting the voluntary and involuntary functions influencing behaviour, Luria further conjoins the methodical structures and associations of neurological processes in the brain. Luria developed the ‘combined motor method’ to measure thought processes based on the reaction times when three simultaneous tasks are appointed that require a verbal response. On the other side, environmental nature of clinical neuropsychology did not appear until more recently and is characterised by treatments such as behaviour therapy. The relationship between physical brain abnormalities and the presentation of psychopathology is not completely understood, but this is one of the questions which clinical neuropsychologists hope to answer in time. In 1861 the debate over human potentiality versus localisation began. The two sides argued over how human behaviour presented in the brain. Paul Broca postulated that cognitive problems could be caused by physical damage to specific parts of the brain based on a case study of his in which he found a lesion on the brain of a deceased patient who had presented the symptom of being unable to speak, that portion of the brain is now known as Broca’s Area. In 1874 Carl Wernicke also made a similar observation in a case study involving a patient with a brain lesion whom was unable to comprehend speech, the part of the brain with the lesion is now deemed Wernicke’s Area. Both Broca and Wernicke believed and studied the theory of localisation. On the other hand, equal potentiality theorists believed that brain function was not based on a single piece of the brain but rather on the brain as a whole. Marie J.P Flourens conducted animal studies in which he found that the amount of brain tissue damaged directly affected the amount that behaviour ability was altered or damaged. Kurt Goldstein observed the same idea as Flourens except in veterans who had fought in World War I. In the end, despite all of the disagreement, neither theory completely explains the human brains complexity. Thomas Hughlings Jackson created a theory which was thought to be a possible solution. Jackson believed that both potentiality and localisation were in part correct and that behaviour was made by multiple parts of the brain working collectively to cause behaviours, and Luria (1966-1973) furthered Jackson’s theory.

The Role

When considering where a clinical neuropsychologist works, hospitals are a common place for practitioners to end up. There are three main variations in which a clinical neuropsychologist may work at a hospital; as an employee, consultant, or independent practitioner. As a clinical neuropsychologist working as an employee of a hospital the individual may receive a salary, benefits, and sign a contract for employment. In the case of an employee of a hospital the hospital is in charge of legal and financial responsibilities. The second option of working as a consultant implies that the clinical neuropsychologist is part of a private practice or is a member of a physicians group. In this scenario, the clinical neuropsychologist may work in the hospital like the employee of the hospital but all financial and legal responsibilities go through the group which the clinical neuropsychologist is a part of. The third option is an independent practitioner whom works alone and may even have their office outside of the hospital or rent a room in the hospital. In the third case, the clinical neuropsychologist is completely on their own and in charge of their own financial and legal responsibilities.

Assessment

Assessments are used in clinical neuropsychology to find brain psychopathologies of the cognitive, behavioural, and emotional variety. Physical evidence is not always readily visible so clinical neuropsychologists must rely on assessments to tell them the extent of the damage. The cognitive strengths and weaknesses of the patient are assessed to help narrow down the possible causes of the brain pathology. A clinical neuropsychologist is expected to help educate the patient on what is happening to them so that the patient can understand how to work with their own cognitive deficits and strengths. An assessment should accomplish many goals such as; gage consequences of impairments to quality of life, compile symptoms and the change in symptoms over time, and assess cognitive strengths and weaknesses. Accumulation of the knowledge earned from the assessment is then dedicated to developing a treatment plan based on the patient’s individual needs. An assessment can also help the clinical neuropsychologist gauge the impact of medications and neurosurgery on a patient. Behavioural neurology and neuropsychology tools can be standardised or psychometric tests and observational data collected on the patient to help build an understanding of the patient and what is happening with them. There are essential prerequisites which must be present in a patient in order for the assessment to be effective; concentration, comprehension, and motivation and effort.

Lezak lists six primary reasons neuropsychological assessments are carried out: diagnosis, patient care and its planning, treatment planning, treatment evaluation, research and forensic neuropsychology. To conduct a comprehensive assessment will typically take several hours and may need to be conducted over more than a single visit. Even the use of a screening battery covering several cognitive domains may take 1.5-2 hours. At the commencement of the assessment it is important to establish a good rapport with the patient and ensure they understand the nature and aims of the assessment.

Neuropsychological assessment can be carried out from two basic perspectives, depending on the purpose of assessment. These methods are normative or individual. Normative assessment, involves the comparison of the patient’s performance against a representative population. This method may be appropriate in investigation of an adult onset brain insult such as traumatic brain injury or stroke. Individual assessment may involve serial assessment, to establish whether declines beyond those which are expected to occur with normal aging, as with dementia or another neurodegenerative condition.

Assessment can be further subdivided into sub-sections:

History Taking

Neuropsychological assessments usually commence with a clinical interview as a means of collecting a history, which is relevant to the interpretation of any later neuropsychological tests. In addition, this interview provides qualitative information about the patient’s ability to act in a socially apt manner, organise and communicate information effectively and provide an indication as to the patient’s mood, insight and motivation. It is only within the context of a patient’s history that an accurate interpretation of their test data and thus a diagnosis can be made. The clinical interview should take place in a quiet area free from distractions. Important elements of a history include demographic information, description of presenting problem, medical history (including any childhood or developmental problems, psychiatric and psychological history), educational and occupational history (and if any legal history and military history).

Selection of Neuropsychological Tests

It is not uncommon for patients to be anxious about being tested; explaining that tests are designed so that they will challenge everyone and that no one is expected to answer all questions correctly may be helpful. An important consideration of any neuropsychological assessment is a basic coverage of all major cognitive functions. The most efficient way to achieve this is the administration of a battery of tests covering: attention, visual perception and reasoning, learning and memory, verbal function, construction, concept formation, executive function, motor abilities and emotional status. Beyond this basic battery, choices of neuropsychological tests to be administered are mainly made on the basis of which cognitive functions need to be evaluated in order to fulfil the assessment objectives.

Report Writing

Following a neuropsychological assessment it is important to complete a comprehensive report based on the assessment conducted. The report is for other clinicians, as well as the patient and their family so it is important to avoid jargon or the use of language which has different clinical and lay meanings (e.g. intellectually disabled as the correct clinical term for an IQ below 70, but offensive in lay language). The report should cover background to the referral, relevant history, reasons for assessment, neuropsychologists observations of patient’s behaviour, test administered and results for cognitive domains tested, any additional findings (e.g. questionnaires for mood) and finish the report with a summary and recommendations. In the summary it is important to comment on what the profile of results indicates regarding the referral question. The recommendations section contains practical information to assist the patient and family, or improve the management of the patient’s condition.

Educational Requirements of Different Countries

The educational requirements for becoming a clinical neuropsychologist differ between countries. In some countries it may be necessary to complete a clinical psychology degree, before specialising with further studies in clinical neuropsychology. While some countries offer clinical neuropsychology courses to students who have completed 4 years of psychology studies. All clinical neuropsychologists require a postgraduate qualification, whether it be a Masters or Doctorate (Ph.D, Psy.D. or D.Psych).

Australia

To become a clinical neuropsychologist in Australia requires the completion of a 3-year Australian Psychology Accreditation Council (APAC) approved undergraduate degree in psychology, a 1-year psychology honours, followed by a 2-year Masters or 3-year Doctorate of Psychology (D.Psych) in clinical neuropsychology. These courses involve coursework (lectures, tutorials, practicals etc.), supervised practice placements and the completion of a research thesis. Masters and D.Psych courses involve the same amount of coursework units, but differ in the amount of supervised placements undertaken and length of research thesis. Masters courses require a minimum of 1,000 hours (125 days) and D.Psych courses require a minimum of 1,500 hours (200 days), it is mandatory that these placements expose students to acute neurology/neurosurgery, rehabilitation, psychiatric, geriatric and paediatric populations.

Canada

To become a clinical neuropsychologist in Canada requires the completion of a 4-year honours degree in psychology and a 4-year doctoral degree in clinical neuropsychology. Often a 2-year master’s degree is required before commencing the doctoral degree. The doctoral degree involves coursework and practical experience (practicum and internship). Practicum is between 600 and 1,000 hours of practical application of skills acquired in the programme. At least 300 hours must be supervised, face-to-face client contact. The practicum is intended to prepare students for the internship/residency. Internships/residencies are a year long experience in which the student functions as a neuropsychologist, under supervision. Currently, there are 3 CPA-accredited Clinical Neuropsychology internships/residencies in Canada, although other unaccredited ones exist. Prior to commencing the internship students must have completed all doctoral coursework, received approval for their thesis proposal (if not completed the thesis) and the 600 hours of practicum.

United Kingdom

To become a clinical neuropsychologist in the UK, requires prior qualification as a clinical or educational psychologist as recognised by the Health Professions Council, followed by further postgraduate study in clinical neuropsychology. In its entirety, education to become a clinical neuropsychologist in the UK consists of the completion of a 3-year British Psychological Society accredited undergraduate degree in psychology, 3-year Doctorate in clinical (usually D.Clin.Psy.) or educational psychology (D.Ed.Psy.), followed by a 1-year Masters (MSc) or 9-month Postgraduate Diploma (PgDip) in Clinical Neuropsychology. The British Psychological Division of Counselling Psychology are also currently offering training to its members in order to ensure that they can apply to be registered Neuropsychologists also.

United States

In order to become a clinical neuropsychologist in the US and be compliant with Houston Conference Guidelines, the completion of a 4-year undergraduate degree in psychology and a 4 to 5-year doctoral degree (Psy.D. or Ph.D.) must be completed. After the completion of the doctoral coursework, training and dissertation, students must complete a 1-year internship, followed by an additional 2 years of supervised residency. The doctoral degree, internship and residency must all be undertaken at American Psychological Association approved institutions. After the completion of all training, students must apply to become licensed in their state to practice psychology. The American Board of Clinical Neuropsychology, The American Board of Professional Neuropsychology, and The American Board of Paediatric Neuropsychology all award board certification to neuropsychologists that demonstrate competency in specific areas of neuropsychology, by reviewing the neuropsychologist’s training, experience, submitted case samples, and successfully completing both written and oral examinations. Although these requirements are standard according to Houston Conference Guidelines, even these guidelines have stated that the completion of all of these requirements is still aspirational, and other ways of achieving clinical neuropsychologist status are possible.

On This Day … 07 April

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People (Deaths)

  • 1999 – Heinz Lehmann, German-Canadian psychiatrist and academic (b. 1911).

Heinz Lehmann

Heinz Edgar Lehmann, OC FRSC (17 July 17 1911 to 07 April 1999) was a German-born Canadian psychiatrist best known for his use of chlorpromazine for the treatment of schizophrenia in 1950s and “truly the father of modern psychopharmacology.”

Early Life

Born in Berlin, Germany, he was educated at the University of Freiburg, the University of Marburg, the University of Vienna, and the University of Berlin. He emigrated to Canada in 1937.

Hospital Work in Canada

In 1947, he was appointed the clinical director of Montreal’s Douglas Hospital. From 1971 to 1975, he was the chair of the McGill University Department of Psychiatry. He was also a humane lecturer in psychiatry in 1952, and was able to give empathetic lectures on the plight of people suffering from anxiety, depression obsessions, paranoia etc. No one to that time had been able to understand or help schizophrenic patients, who filled mental hospitals around the world, so when chlorpromazine showed some promise he helped to promote it in North America and start the drug revolution. He was ahead of his time in that he supported research in the use of the active ingredient psilocybin to alleviate anxiety.

Le Dain Commission

From 1969 to 1972, he was one of the five members of the Le Dain Commission, a royal commission appointed in Canada to study the non-medical use of drugs. He was an advocate for decriminalisation of marijuana.

DSM Work

In 1973, he was a member of the Nomenclature Committee of the American Psychiatric Association that decided to drop homosexuality from the Diagnostic and Statistical Manual of Mental Disorders, i.e. to depathologise it.

Honours and Awards

In 1970 he was made a Fellow of the Royal Society of Canada and, in 1976, he was made an Officer of the Order of Canada. He was inducted into the Canadian Medical Hall of Fame in 1998.

Heinz Lehmann Award

In 1999, the Canadian College of Neuropsychopharmacology established the Heinz Lehmann Award in his honour, given in recognition of outstanding contributions to research in neuropsychopharmacology in Canada.

Principles for Improving Investment in Translational Neuroscience Aimed at Psychiatric Drug Discovery

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Research Paper Title

Time to re-engage psychiatric drug discovery by strengthening confidence in preclinical psychopharmacology.

Background

There is urgent need for new medications for psychiatric disorders. Mental illness is expected to become the leading cause of disability worldwide by 2030. Yet, the last two decades have seen the pharmaceutical industry withdraw from psychiatric drug discovery after costly late-stage trial failures in which clinical efficacy predicted pre-clinically has not materialised, leading to a crisis in confidence in preclinical psychopharmacology.

Methods

Based on a review of the relevant literature, the researchers formulated some principles for improving investment in translational neuroscience aimed at psychiatric drug discovery.

Results

The researchers propose the following 8 principles that could be used, in various combinations, to enhance CNS drug discovery:

  1. Consider incorporating the NIMH Research Domain Criteria (RDoC) approach;
  2. Engage the power of translational and systems neuroscience approaches;
  3. Use disease-relevant experimental perturbations;
  4. Identify molecular targets via genomic analysis and patient-derived pluripotent stem cells;
  5. Embrace holistic neuroscience: a partnership with psychoneuroimmunology;
  6. Use translational measures of neuronal activation;
  7. Validate the reproducibility of findings by independent collaboration; and
  8. Learn and reflect.

They provide recent examples of promising animal-to-human translation of drug discovery projects and highlight some that present re-purposing opportunities.

Conclusions: We hope that this review will re-awaken the pharma industry and mental health advocates to the opportunities for improving psychiatric pharmacotherapy and so restore confidence and justify re-investment in the field.

Reference

Tricklebank, M.D., Robbins, T.W., Simmons, C. & Wong, E.H.F. (2021) Time to re-engage psychiatric drug discovery by strengthening confidence in preclinical psychopharmacology. Psychopharmacology (Berl). doi: 10.1007/s00213-021-05787-x. Online ahead of print.

Book: Case Studies: Stahl’s Essential Psychopharmacology, Volume 02

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Book Title:

Case Studies: Stahl’s Essential Psychopharmacology, Volume 02.

Author(s): Stephen M. Stahl.

Year: 2016.

Edition: First (1ed).

Publisher: Cambridge University Press.

Type(s): Paperback.

Synopsis:

Following the success of the first collection of Stahl’s Case Studies, published in 2011, we are pleased to present this completely new selection of clinical stories.

Designed with the distinctive user-friendly presentation readers have become accustomed to and making use of icons, questions/answers and tips, these cases address complex issues in an understandable way and with direct relevance to the everyday experience of clinicians.

Covering a wide-ranging and representative selection of clinical scenarios, each case is followed through the complete clinical encounter, from start to resolution, acknowledging all the complications, issues, decisions, twists and turns along the way.

The book is about living through the treatments that work, the treatments that fail, and the mistakes made along the journey. This is psychiatry in real life – these are the patients from your waiting room – this book will reassure, inform and guide better clinical decision making.

Book: Case Studies: Stahl’s Essential Psychopharmacology

Published on by Andrew Marshall1 Comment

Book Title:

Case Studies: Stahl’s Essential Psychopharmacology

Author(s): Stephen M. Stahl (Author), Debbi A. Morrisette (Editor), and Nancy Muntner (Illustrator).

Year: 2011.

Edition: First (1ed).

Publisher: Cambridge University Press.

Type(s): Paperback.

Synopsis:

Designed with the distinctive, user-friendly presentation Dr Stahl’s audience know and love, this new stream of Stahl books capitalise on Dr Stahl’s greatest strength – the ability to address complex issues in an understandable way and with direct relevance to the everyday experience of clinicians.

The book describes a wide-ranging and representative selection of clinical scenarios, making use of icons, questions/answers and tips. It follows these cases through the complete clinical encounter, from start to resolution, acknowledging all the complications, issues, decisions, twists and turns along the way.

The book is about living through the treatments that work, the treatments that fail, and the mistakes made along the journey. This is psychiatry in real life – these are the patients from your waiting room – this book will reassure, inform and guide better clinical decision making.

Find Volume 02 here.

On This Day … 15 February

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People (Births)

  • 1856 – Emil Kraepelin, German psychiatrist and academic (d. 1926).
  • 1940 – Vaino Vahing, Estonian psychiatrist, author, and playwright (d. 2008).

Emil Kraepelin

Emil Wilhelm Georg Magnus Kraepelin (15 February 1856 to 7 October 1926) was a German psychiatrist. H. J. Eysenck’s Encyclopaedia of Psychology identifies him as the founder of modern scientific psychiatry, psychopharmacology and psychiatric genetics.

Kraepelin believed the chief origin of psychiatric disease to be biological and genetic malfunction. His theories dominated psychiatry at the start of the 20th century and, despite the later psychodynamic influence of Sigmund Freud and his disciples, enjoyed a revival at century’s end. While he proclaimed his own high clinical standards of gathering information “by means of expert analysis of individual cases”, he also drew on reported observations of officials not trained in psychiatry.

His textbooks do not contain detailed case histories of individuals but mosaic-like compilations of typical statements and behaviours from patients with a specific diagnosis. He has been described as “a scientific manager” and “a political operator”, who developed “a large-scale, clinically oriented, epidemiological research programme”.

Vaino Bahing

Vaino Vahing (15 February 1940 to 23 March 2008), was an Estonian writer, prosaist, psychiatrist and playwright. Starting from 1973, he was a member of Estonian Writers Union.

Vaino Vahing has written many articles about psychiatry, but also literature – novels, books and plays with psychiatric and autobiographical influence. He has played in several Estonian films.

Book: Psychiatric and Mental Health Nursing: The craft of caring

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Book Title:

Psychiatric and Mental Health Nursing: The Craft of Caring.

Author(s): Mary Chambers.

Year: 2017.

Edition: Third (3rd).

Publisher: Routledge.

Type(s): Hardcover, Paperback and Kindle.

Synopsis:

This new edition of a bestselling, evidence-based textbook provides a comprehensive overview of psychiatric and mental health nursing. Keeping service users and their recovery at the centre of care, the holistic approach will help nurses to gain the tools and understanding required to work in this complex area.

Extensively updated for this new edition, the text looks at:

  • Aspects of mental health nursing: covering topics such as ethics, developing therapeutic relationships and supervision.
  • The foundations of mental health nursing: discussing diagnosis, assessment and risk.
  • Caring for those experiencing mental health distress: looking at wide range of troubles including anxiety, bipolar disorder, eating disorders and issues around sexuality and gender.
  • Care planning and approaches to therapeutic practice: exploring ideas, pathways and treatments such as recovery, CBT, psychodynamic therapies and psychopharmacology.
  • Services and support for those with mental health distress: covering topics such as collaborative work, involvement of service users and their families and carers, and a range of different mental healthcare settings.
  • Mental health nursing in the twenty-first century: highlighting emerging and future trends including the political landscape, physical health and health promotion, and technological advances.

This accessible and comprehensive textbook integrates service user perspectives throughout and includes student-friendly features such as learning outcomes, key points summaries, reflection points and further reading sections. It is an essential resource for all mental health nursing students, as well as an invaluable reference for practising nurses.

Book: Psychopharmacology: A mental health professional’s guide to commonly used medications (Nursing)

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Book Title:

Psychopharmacology: A mental health professional’s guide to commonly used medications (Nursing).

Author(s): Herbert Mwebe.

Year: 2018.

Edition: First (1st).

Publisher: Critical Publishing Ltd.

Type(s): Paperback and Kindle.

Synopsis:

This jargon-free guide is suitable for all trainee and registered health professionals who require knowledge and understanding of drugs used in the treatment of mental health conditions for prescribing or administering purposes. A life-saving pocketbook that you can easily carry anywhere you go!

Introductory material provides a background on psychotropic drugs, the aetiology of mental illness, some of the commonly used drugs in practice and brief notes on common non-pharmacological interventional options. It also examines biochemical and neurodevelopmental theories and the link to the pathophysiology of mental illness as well as clinical decision making.

The central chapters of the book provide comprehensive coverage of all the major medications used in mental health. Each focuses on a specific class of drug, detailing the most commonly used medicines, including side effects, average doses, contra-indications and clinical management interventions that may be required. At the end of each chapter a series of review questions enable readers to review their learning, and theory is clearly related to practice throughout.