When the first edition of our book was published in 1975, biochemistry was emerging as a new discipline that had the potential to unify the previously divergent -ologies that constituted the biological sciences. It placed emphasis on the understanding of the structure, function and expression of individual proteins and their related genes, and relied on the application of analytical techniques such as electrophoresis, chromatography and various forms of spectrometry. In the ensuing 40 years the completion of the Human Genome Project has confirmed the central role of DNA in all of the activities of individual cells and the emergence of molecular biology as the means of understanding complex biological processes. This in turn has led to the new disciplines of bioinformatics, chemoinformatics, proteomics and metabolomics. The succeeding six editions of our book have attempted to reflect this evolution of biochemistry as a unifying discipline. All editions have placed emphasis on the experimental techniques that undergraduates can expect to encounter during the course of their university studies and to this end we have been grateful for the excellent feedback we have received from the users of the book.

The point has now been reached where we believed that it was appropriate for us to hand over the direction and academic balance of future editions to a new editorial team and to this end we are delighted that Andreas Hofmann and Samuel Clokie have agreed to take on the role. We wish them well and look forward to the continuing success of the book.

INTRODUCTION

Biological centrifugation is a process that uses centrifugal force to separate and purify mixtures of biological particles in a liquid medium. The smaller the particles, the higher the g-forces (see next section) required for the separation. It is a key technique for isolating and analysing cells, subcellular fractions, supramolecular complexes and, with higher g-force instruments or ‘ultra’-centrifuges (up to 60 000 revolutions per minute corresponding to ~ 200 000×g) isolated macromolecules such as proteins or nucleic acids. Such high-speed devices require a vacuum to avoid overheating of samples. The development of the first analytical ultracentrifuge – with a specially designed optical system for monitoring and recording the sedimentation process – by Svedberg in the late 1920s and the technical refinement of the preparative centrifugation technique by Claude and colleagues in the 1940s positioned centrifugation technology at the centre of biological and biomedical research for many decades. Today, centrifugation techniques represent a critical tool for modern biochemistry and are employed in almost all invasive subcellular studies. While analytical ultracentrifugation is mainly concerned with the study of purified macromolecules or isolated supramolecular assemblies, preparative centrifugation methodology is devoted to the actual separation of tissues, cells, subcellular structures, membrane vesicles and other particles of biochemical interest.

Most undergraduate students will be exposed to preparative centrifugation protocols during practical classes and might also experience a demonstration of analytical centrifugation techniques. This chapter is accordingly divided into a short introduction into the theoretical background of sedimentation, an overview of practical aspects of using centrifuges in the biochemical laboratory, an outline of preparative centrifugation and a description of the usefulness of ultracentrifugation techniques in the biochemical characterisation of macromolecules. To aid in the understanding of the basic principles of centrifugation, the general designs of various rotors and separation processes are diagrammatically represented. Often, the learning process of undergraduate students is hampered by the lack of a proper linkage between theoretical knowledge and practical applications. To overcome this problem, the description of preparative centrifugation techniques is accompanied by an explanatory flow chart and the detailed discussion of the subcellular fractionation protocol for a specific tissue preparation.

WHY USE A RADIOISOTOPE?

When researchers contemplate using a radioactive compound there are several things they have to consider. First and foremost, they must ask the question: is a radioisotope necessary or is there another way to achieve the objectives? The reason for this is that use of radioisotopes is governed by very strict legislation. The rules are based on the premise that radioactivity is potentially unsafe (if handled incorrectly) and should therefore only be used if there are no alternatives. Then, once it is decided that there is no alternative, the safest way of carrying out the work needs to be planned. Essentially this means using the safest isotope and the smallest amount possible. But why do we use radioisotopes in the first place? First, it is possible to detect radioactivity with exquisite sensitivity. This means that, for example, the progress of an element through a metabolic pathway or in the body of a plant or animal can be followed relatively easily. Very small amounts of a radioactive molecule are needed, and detection methods are well established. Second, it is possible to follow what happens in time. Imagine a metabolic pathway such as carbon dioxide fixation (the Calvin cycle). All the metabolites in the cycle are present simultaneously; so a good way to establish the order of the metabolism is to add a radioactive molecule (in this example, 14 C-labelled carbon dioxide in the form of sodium bicarbonate) and see what happens to it by extracting the metabolites from the plant and identifying the radioactive ones. Third, it is possible to trace what happens to individual atoms in a pathway. This is done, for example, by creating compounds with a particular isotope in specific locations in the molecule. Fourth, we can identify a part or end of a molecule, and follow reactions very precisely. This has been very useful in molecular biology, where it is often necessary to label one end of a DNA molecule (e.g. for techniques such as gel mobility shift assay or DNA footprinting, methods for investigating sequence-specific DNA protein binding), or immunochemical diagnostics; see Section 7.2.9).

Psychosocial perspectives focus on the interplay between our inner and outer worlds, specifically the complex interactions between features of our social environment and personal attributes such as self-esteem and coping. Considerable importance is therefore attached to a person's biography (i.e. his/her previous and current experiences) and context. The latter tends to be neglected in the theory, research and practice of both psychiatry and clinical psychology (Boyle, 2011).

We begin this chapter by asking whether distress caused by adverse social circumstances and negative life experiences should be considered a clinical disorder. Next, we introduce the vulnerability–stress hypothesis, which is often used as a framework for conceptualising how inner and outer worlds connect in the development of mental distress. We then provide an overview of a major area of research within social psychiatry, which has furthered our understanding of the impact of stressful life events on psychological well-being. Following this, we outline two further psychosocial perspectives on the development of distress. The first, a social cognitive perspective, is drawn from abnormal psychology and focuses predominantly on people's inner worlds. By contrast, the second, a social materialist perspective, resoundingly rejects the emphasis in mainstream psychology on explaining distress in terms of people's interior worlds and psychological dysfunctions. This perspective is more closely aligned to critical and community psychology.

Distress: A Normal Response or a Clinical Disorder?

Most of the studies cited in this chapter examine the contribution made by psychosocial factors to the development of so-called common mental health problems, specifically depression and anxiety. Anxiety and depression are highly comorbid conditions with much in common (Goldberg, et al., 2009). As noted in the previous chapter, factor analysis of patterns of co-morbidity among mental health problems suggests that depression and anxiety share a common underlying core factor, a so-called anxiety–misery factor, which Krueger (1999) considers to be one of the two sub-factors of internalising disorders. This shared ‘heritage’ is unsurprising as both categories of distress were hewn by the authors of DSM-III from the broad range of neuroses that had been articulated by psychoanalysis and the more general system of psychodynamically oriented psychiatry (Horwitz, 2002). Although the focus of this chapter is largely on common mental health problems, distress is certainly not co-terminous with these. For instance, distress can also manifest as demoralisation (see Box 6.1).

We have reached something of an impasse in the treatment and care of those of us who experience mental health problems. Despite the huge budget and resources allocated to research and treatment of mental health problems, the lifetime risk of being diagnosed with a major depressive episode is nearly 15% in wealthy developed countries (Bromet, et al., 2011). The World Health Organization (WHO) believe that the day-to-day burden of depression is increasing and will take second place in the global rating of disease burden by 2020. Approximately one in 100 people experience a psychotic episode; a statistic that has remained unchanged since Emil Kraepelin (1899) started to classify types of mental distress. Clearly, we are not making much acceptable progress in the prevertion of such conditions.

For over a hundred years, psychiatrists and other mental health workers, as well as pharmaceutical companies and medical researchers, have been trying to find the evidence to support the paradigm of ‘mental illness’. So far, no unequivocal evidence to show that mental distress problems are caused by neurological and neurochemical changes has been found. We continue to search for this evidence, in part because the advocates of this paradigm are loud and strong, but also because we must find more effective ways to help people in mental distress. Mental health problems can be complex, life-changing and sometimes life threatening. We have to stop and take stock, as we are not making discernible progress in identifying a biological cause for mental distress. We can identify the effects of distress in the brain, but have failed to show clear genetic and biological markers that signal the inevitable onset of a mental health problem.

The progress we have made in the treatment of such problems is not trivial. We have come a long way from dropping cold water on the heads of the mad, but not far enough to ensure that everyone experiencing mental distress can live productively. We talk about ending the stigma of mental health problems but, in fact, only seem to be making such stigma worse (Read and Harré, 2001). The surge to proclaim mental distress as illness seems defeated by the inability to cure these problems permanently.

The previous chapter looked at the representation of emotions in the normal brain and the way that they are regulated in terms of motivation for action. This chapter continues the story of normal processes by looking at stress, coping and control. Stress is the perception and appraisal of dangerous or challenging external events. Humans seem to have a unique response to stress in that we can use it for the good to motivate performance. However, uncontrolled or uncontrollable stress can also augur mental distress. Stress can become troublesome when we run out of options for action. Sometimes, for some people, the closer a deadline gets, the more motivated they are to work. However, if your workload unexpectedly increases or you suddenly do not have the right tools for the job, for example, stress will probably increase. Too much prolonged stress can affect the immune system and you can become ill. However, if there are other predispositions in place, stress can affect the way you think and behave. Stress can be a cornerstone for mental health problems.

This chapter will discuss stress and the way we deal with it in normal situations. To do so, it is important first to consider the way that humans normally deal with the conflicting demands of stimuli. This involves continuing the story of prefronal cortex started in the previous chapter.

The Further Actions of Prefrontal Cortex

It takes time for the PFC to develop. In fact, as the PFC is needed for processing fast reactions to novel experiences (among other things), you could argue that the area must remain plastic to some extent throughout the lifespan. We handle novel experiences by comparing them with prior experiences. This enables contextual information to be added to our experiences. For example, a first day at a new job is compared to other first day experiences. We would then go over the expectations and possible emotions of this day in our minds to establish how we will probably feel during the new experience. We have this ability because it is a form of cognitive shorthand, something that affords quicker responses to contingencies.

Introduction

Definitions of recovery tend to fall into one of two categories: clinical or personal (Slade, 2009). Clinical definitions usually construe recovery as an outcome-based phenomenon, in which criteria in particular domains (such as symptom reduction) are met. By contrast, personal or person-centred definitions are based on individuals’ lived experiences of mental distress and imply a process of identity change that includes the broadening of self-concept and the rebuilding of a meaningful life (Silverstein and Bellack, 2008). In personal narratives of recovery, recovery is often likened to a journey with the emphasis placed on the centrality of hope, meaning, identity and personal responsibility (Slade, 2010; Leamy, et al., 2011). Although this chapter starts with a brief review of various models of mental distress, personcentred perspectives on recovery are its primary focus.

The personal perspectives on recovery discussed in this chapter are predominantly based on studies of the lived experiences of people with severe mental health problems who have first-hand (and often extensive) experience of using mental health services. As David Pilgrim (2009b) notes, the criteria by which recovery is judged are likely to vary from one mental health problem to another. The multiplicity of personal perspectives on recovery among people who have received the same diagnosis indicates that there is no ‘right way’ for a person to recover and that no one approach to recovery is going to ‘fit’ everyone (Slade, 2010). This needs to be borne in mind when reading the section on ‘what helps’ a person's recovery, where a number of facilitative factors are outlined, including adaptation and coping strategies, taking back power and control, supportive relationships, employment, and de-stigmatisation. Taken together, these factors indicate the importance of a social model of mental health. In such models, mental health problems are seen as manifestations of extreme emotional distress in the face of overwhelming stressors, and great importance is attached to activities that make the greatest difference in terms of people's aspirations, quality of life and social inclusion (Tew, 2005). Given this, this chapter ends by considering, from a person-centred perspective, what contribution mental health professionals can make to a person's recovery.

Bringing together neuropsychological and psychosocial perspectives on mental distress, we outline in this book a way of thinking about mental health problems that emphasises the importance of context, relationships and neuroplasticity. In doing so, we seek to present alternative ways of understanding mental distress to that provided by the biomedical model.

Despite its many limitations, the biomedical model (also referred to as the psychiatric model) of mental distress not only informs clinical practice and research, but is also perpetuated by such activities. It is, therefore, unsurprising that, with certain exceptions, the biomedical model tends to dominate the discussion of mental distress in psychology textbooks.

Unlike many ‘abnormal psychology’ textbooks, which use traditional psychiatric diagnostic categories as a framework for talking about mental distress, this book addresses two broad categories of mental suffering: distress, which includes emotional problems such as depression and anxiety (often referred to as ‘common mental health problems’), and psychosis, a term used to denote various forms of mental distress, where, at times, contact with reality is assumed to be lacking or impaired. We decided to take this approach partly because of concerns about the validity and reliability of many traditional diagnostic categories, but also because it enabled us to consider in more depth how the alternative approaches we outline might explain mental distress. Despite this, as we wrote this book, we were constantly reminded of how deeply the biomedical model has insinuated itself into our thinking; it is difficult to escape the psychiatric perspective fully and this is apparent sometimes in our writing. Indeed, it is apparent in the very title of this book. The term ‘psychopathology’ is a medical concept that equates mental distress with disease and sickness. Yet the psychosocial and neuropsychological perspectives we outline in this book challenge this medical conceptualisation of mental distress in different ways, suggesting that far from being manifestations of pathology, the experiences and behaviours that constitute mental distress are often understandable when a person's context and the meaning s/he attaches to his/her experiences are taken into account.

The perspectives on mental distress discussed in this book reflect our own professional interests: AL is a neuropsychologist and RI is a social psychologist with a particular interest in therapeutic psychology.

Introduction

With over 400 different types of psychological therapy, it is unsurprising that no definition exists that adequately captures this diverse field of practice. Although modern psychological therapies have relatively short histories, the elements from which most are constituted are similar and date back many centuries (Jackson, 1999). For the purposes of this chapter, we use the term psychological therapy to refer to psychotherapy, counselling or any form of ‘talking treatment’ that aims to promote subjective well-being and mental health.

This chapter aims to help you to think more critically about the claims made about psychological therapies. Firstly, we consider whether the practice of psychological therapy should be guided by diagnosis or formulation. This debate is, in part, about the extent to which the practice of psychological therapy can or should be decoupled from the medical model (Sanders, 2007; Deacon, 2013). In the next section, the focus shifts to how we can establish whether a psychological therapy works. Here we introduce and critique the concept of empirically supported therapies. Opinion within the field of psychological therapy is generally divided as to which elements of therapy help to bring about change; some claim that it is therapeutic techniques and the theories that underpin them (the differential effectiveness position), while others argue that it is the quality of the therapeutic relationship and nonspecific factors (the common factors position). In the final part of the chapter, we consider some of the potential detrimental effects psychological therapy may have at an individual and societal level.

Diagnosis or Formulation?

Whether practice should be guided by diagnosis or formulation is a moot point in the field of psychological therapy. In the therapeutic process, it is usually a diagnosis or formulation that links assessment to therapeutic intervention or ‘treatment’. Psychiatric classification systems divide mental distress into categories (clinically significant syndromes) based on certain configurations of diagnostic criteria (commonly referred to as symptoms). Two of the most commonly used classification systems are the American Psychiatric Association's DSM-5 (APA, 2013) and the World Health Organisation's ICD-10 (WHO, 1992).

Although psychiatry is a specialist branch of medicine, important differences exist between the diagnostic process in general medical practice and psychiatric diagnoses made using the guidance given in manuals such as the DSM.

The previous chapter detailed the relatively short-term problems caused by stress.

As discussed in Chapter 3, the hippocampus is involved in the brain's reward system and its role in motivation. It appears that the hippocampus could be very important in the context of the development of mental health problems. The present chapter will outline some of the newer research of the PFC and especially the links between this area and the other emotional areas of the brain. This will be used as a backdrop to explain the behaviour seen in disorders such as depression and the anxiety disorders. To set this research in context, first it is necessary to learn more about the different iterations of mental distress by considering such disorders in some depth. Thus, we will consider ways of classifying the mood and anxiety disorders before trying to establish the neural mechanism of these conditions.

Depression and Anxiety

The Basics

Traditionally, diagnostic manuals have classified anxiety and depression as two separate states. This is because the manifestations of these two conditions seem qualitatively different. When pathologically anxious, the person will tend to avoid confrontation with the source of his/her anxiety specifically, or more generally (and seriously), anything that threatens his/her comfort zone. Apart from the perception of terror or apprehension, anxiety is primarily a somatic disorder producing symptoms of agitation, such as a racing heart, sweaty palms and difficulty breathing.

Depression, on the other hand, is perceived more as a mood problem, manifesting as a general sadness or a disinterest. It could be characterised as a failure to maintain engagement with the world. Depression is represented by a series of behavioural symptoms, such as not maintaining an adequate sleep pattern and under- or overeating. It is common for depressives to wake in the early hours and then fail to return to sleep or to have difficulty initiating sleep in the first place. Insomnia or simply poor sleep hygiene brings its own problems, such as blunted appetite and difficulty maintaining concentration.

Thus, the representation of the distress caused by anxiety and depression seems different. However, both conditions are driven undeniably by emotion. You must also consider that the gross behavioural outcome is the same: the person withdraws from his/her life or from some aspect of his/her life.

Introduction

It was Kurt Lewin, considered by many to be the father of social psychology, who first proposed the equation: B = f (P, E); that is, behaviour is a function of the person, the environment and the interaction between the two (Lewin, 1951). Yet a general bias undoubtedly persists in psychology towards the P component of Lewin's equation. Nowhere is this more apparent than in relation to psychosis. This chapter seeks to redress this imbalance by attending to environmental factors associated with the onset and recurrence of psychotic experiences.

For the purpose of this chapter, psychosis is used as an ‘umbrella term’ for unusual perceptions or unusual beliefs that may suggest to others that a person's contact with reality is sometimes impaired (BPS, 2000). As indicated in Chapter 7, the division of functional psychosis into depressive psychosis, manic psychosis and non-affective psychosis (or schizophrenia) is, at best, somewhat vague (Allardyce, et al., 2007). Given that people with ‘non-affective’ psychosis often experience emotional problems such as depression, social anxiety and the symptoms of trauma (Birchwood, 2003; Freeman and Garety, 2003), we simply use the term psychosis in this chapter without employing ‘non-affective’ as a qualifying adjective.

The comparative lack of attention given to possible environmental factors in the aetiology of psychosis is, in part, a consequence of the distinction that is often made between psychosis and emotional problems (neurosis). It is generally assumed that neurosis has a psychological aetiology, whereas the aetiology of psychosis is primarily organic, underpinning the idea that psychosis is the result of some (as yet unidentified) progressive brain disorder. Over the last couple of decades, this assumption has been challenged by increasingly sophisticated endeavours to understand and explain the symptoms of psychosis in psychological terms. However, one regrettable consequence of the continued tendency to ascribe a predominantly organic aetiology to functional psychosis has been the relative neglect of the subjective experience of individuals who are living with psychosis.

This chapter starts with a brief outline of some of the possible causal factors for psychosis suggested by people who have first-hand experience of it.