Coping With Schizophrenia and Psychosis

The Schizophrenia-free Package

What are you going to find in the Schizophrenia-FreeYour New Life Begins Today e-book: Relationships and Friends: In this chapter, I share with you my way of thinking about friends and relationships. I provide my point of view about how I see this interesting issue. I also give you some tips about how to get friends, deal with friends, and treat relationships. About Schizophrenia and Getting Well: In this chapter, I describe my way of thinking about schizophrenia and other similar mental illnesses. Living on Your Own and Being Independent: In this chapter, I share my perspective about our independence as sufferers and how to live on our own and be independent. Other Sufferers' Recovery Examples: I decided to share other sufferers' stories so you won't feel alone in your illness. Finding Your Mate and Getting Married: Having a mate is one of the most important pillars in your life as a sufferer. In this chapter, you learn some of the most important basics in this matter. Preventing Future Seizures and Getting Help: This chapter shows how to reduce the chance of having future psychotic disorder seizures and, even if you experience one, how to make it as minimal as possible. Dieting and Exercising: This chapter demonstrates how to acquire easy life habits in order to survive your years to come in the healthiest manner possible. Living by Yourself and Earning Your Own Money: This chapter shows how to earn your own money and live by yourself as a result. Ways of Getting Support: There is nothing like a good support system in order to rehabilitate in the best matter possible. This chapter discusses the most basic and powerful ways of getting support. Quitting Smoking: In this chapter, you learn the basic principles of why and how to quit smoking. Learning a Profession and Finding a Job: In this chapter, you learn the most important factors for learning a profession and finding a job.

The Schizophreniafree Package Summary


4.6 stars out of 11 votes

Contents: EBook
Author: Ronen David
Price: $12.00

My The Schizophreniafree Package Review

Highly Recommended

Of all books related to the topic, I love reading this e-book because of its well-planned flow of content. Even a beginner like me can easily gain huge amount of knowledge in a short period.

Overall my first impression of this ebook is good. I think it was sincerely written and looks to be very helpful.

Download Now

The contribution of psychiatric epidemiology Cultural influences on the psychoses

Epidemiologists have been keen to discover whether psychiatric conditions are universal and appear with the same incidence across human populations. Universality would minimize the role of culture in shaping the form of a condition, while a uniform incidence would indicate that biological factors played a major role in aetiology. Schizophrenia has been the focus of many epidemiological surveys, especially the cross-national studies conducted by the World Health Organization ( WHO). The International Pilot Study of Schizophrenia(4) showed that it was possible to conduct a psychiatric epidemiological study across a wide variety of cultures and languages.(5) The use of standardized assessment and diagnostic techniques revealed that the core symptoms of schizophrenia were subject to few cultural variations. The most striking difference in the form of the illness was that catatonic symptoms were relatively frequent in patients from developing countries, but rare in the other centres. The...

Schedule for Affective Disorders and Schizophrenia and the Structured Clinical Interview for DSM

The series of instruments developed by Spitzer and his colleagues at Biometrics of the New York State Psychiatric Institute have been of several different kinds and, in the early years at least, had a much more rigid structure than the PSE. Users of the Mental Status Schedule and the longer Psychiatric Status Schedule were instructed to follow the order of the questions as printed in the schedule, the only deviation from this being a repetition of the same questions if thought necessary by the interviewer. However, later instruments such as the Schedule for Affective Disorders and Schizophrenia (56) and, more recently, the Structured Clinical Interview for DSM-III and DSM-IV(61 allow more flexibility for the interviewer in both interview style and the choice of a little or a lot of training (despite its length, the Structured Clinical Interview for DSM is recommended for clinical use as well as for research). There has also been an increasing tendency for instruments from the New York...

Neuropathological findings in schizophrenia since 1975

Advances in the last 40 years have produced more reliable psychiatric diagnostic criteria, improved structural and functional neuroimaging techniques, a large array of highly sensitive and specific molecular probes and labelling procedures, suitable for use in neuropathological studies, and computer-assisted image analysis methodologies. For these and other reasons, there has been a resurgence of interest in the neurobiological substrates of schizophrenia, and contemporary neuropathological studies have enumerated many findings in the brains of patients with schizophrenia (for reviews see Bogerts and Lieberman, Falkai and Bogerts,(22) Arnold and Trojanowski,(29 Roberts et al.,(23) and Harrison(2f ). In addition during this period there has been extensive neurochemical and neuroreceptor research and this aspect of postmortem schizophrenia research has been the subject of several recent reviews.(2,25,26) In another prospectively accrued series, Bruton et al.(28) found that five of 56...

Schizophrenialike psychosis

A psychotic illness may develop long after the acute confusional state has resolved, which is difficult to distinguish from psychotic illness occurring in the absence of manifest organic brain disease. The patient may develop a typical schizophrenia indistinguishable from idiopathic schizophrenia. Would he or she have developed schizophrenia regardless of having had a head injury The best estimate of the increased risk of developing a schizophrenia-like psychosis as a result of a head injury comes from Davison and Bagley's study of 30 years ago 44) They estimated a two- to threefold increased risk compared with the general population. There were large variations in the different studies they examined, and most were cohorts of war veterans. It is not clear whether the same relative risk will be found in civilian cohorts with mainly closed head injuries. Those who develop schizophrenia after head injury may be at high risk anyway, for example due to a family history of schizophrenia or...

Cannabis and schizophrenia

There is good clinical and epidemiological evidence of an association between schizophrenia and cannabis use, which suggests that cannabis use can precipitate schizophrenia or exacerbate its symptoms. But this is not the only explanation of the association. Persons with schizophrenia may use cannabis as a form of self-medication, or there may be other variables that explain both for example, cannabis use is a marker of other psychotogenic drug use, or of vulnerability to schizophrenia 2) There is clinical and epidemiological evidence that cannabis use exacerbates the symptoms of schizophrenia in affected individuals. This includes the findings of a number of prospective studies that have controlled for confounding variables. (12) It is also a biologically plausible relationship. Psychotic disorders involve disturbances in the dopamine neurotransmitter systems, since drugs that increase dopamine release produce psychotic symptoms when given in large doses, and neuroleptic drugs that...

Schizophrenia a conceptual history

According to some, the history of schizophrenia consists of a progression of definitions culminating in the present. (1) However, instead of the 'continuity' implicit in this view, historical research indicates that (a) the history of 'schizophrenia' is a series of unconnected and contradicting research programmes, and (b) the current definition of schizophrenia is a patchwork of features. The 'continuity' version also includes only alienists making modern-sounding points. This would matter little were it not that it denies researchers access to important aspects of the history of schizophrenia.(2) For example, it is a moot point whether the Kraepelinian view would be as popular as it is had it not been for the untimely death of Wernicke, who by 1905 was developing an exciting neuropsychological classification for the psychoses. Hence, rather than asking who were the alienists who 'foresaw' the wonders of the present, this chapter will ask what historical factors made some views...

Dimensions of psychopathology in schizophrenia

Schizophrenia is heterogeneous in its clinical presentation, suggesting that several different pathophysiological processes might contribute to the illness. Positive and negative symptom dimensions Positive symptoms are those that reflect the presence of an abnormal mental process, and include delusions, hallucinations, and formal thought disorder. Negative symptoms reflect the diminution or absence of a mental function that is normally present. They include poverty of speech and blunted affect. In schizophrenia, positive symptoms tend to be transient, while negative symptoms tend to be chronic. In an influential hypothesis, Crow (1,9) proposed that positive symptoms arise from dopaminergic overactivity, while negative symptoms reflect structural brain abnormality. While a substantial body of evidence supports this hypothesis, it does not account adequately for the complexity of the heterogeneity of the clinical features in schizophrenia.

The diagnosis of schizophrenia

Until the early 1970s, the diagnosis of schizophrenia was one of the most contentious and fraught issues in the whole of psychiatry. Since then a massive international effort has been put in motion out of which explicit diagnostic criteria emerged. Some achieved widespread and even multinational agreement, allowing the painstaking process of calculating diagnostic specificity, sensitivity, reliability, and (perhaps) validity to begin. Although criticism of the diagnosis of schizophrenia continues, mostly from outside psychiatry, the vast majority of psychiatrists look upon the major sets of diagnostic criteria with weary acceptance, seeing them as flawed but useful and possibly 'as good as it gets' given our current state of knowledge ignorance.

Differential diagnosis Other psychiatric disorders Other psychoses

It could be argued that distinguishing schizophrenia from schizoaffective disorder, schizophreniform disorder, delusional disorder, etc. is a largely academic exercise. Until recently, treatment in psychiatry was entirely symptom or syndrome based. Thus manic symptoms respond to antimanic agents including lithium, psychotic symptoms respond to neuroleptics, and depressive symptoms respond to antidepressants.(1. ,. 8) Other 'mood-stabilizing' agents are also of value especially when combined with neuroleptics. However, it is possible that with increasing clinical experience and research using the new generation of 'atypical' antipsychotic agents such as clozapine, risperidone, and olanzapine, more specific indications will emerge. A recent report of efficacy of olanzapine in schizoaffective disorder in comparison to haloperidol is a case in point. (19 However, a tendency to reduce all psychotic disorders to 'serious mental illness' is unfortunate. It encourages a sloppy approach to...

The disease and disability burden of schizophrenia

According to World Bank and WHO estimates, (75 no less than 25 per cent of the total 'burden of disease' in the established market economies is at present attributable to neuropsychiatric conditions. Measured as proportion of the disability-adjusted life-years ( DALYs) lost, schizophrenia, bipolar affective disorder, and major depression together account for 10.8 per cent of the total, i.e. they inflict on most communities losses that are comparable to those due to cancer (15 per cent) and higher than the losses due to ischaemic heart disease (9 per cent).

Can schizophrenia be prevented

The increasing interest in the early diagnosis and treatment of first episodes of schizophrenic and affective psychoses has raised the questions of whether people likely to develop schizophrenia can be reliably recognized prior to the onset of symptoms, and whether early pharmacological, cognitive, or social intervention can prevent the development of the disorder. While early diagnosis and treatment of symptomatic cases are feasible and may have the potential of improving the short- or medium-term outcome, the pre-onset detection of likely cases with a view to preventative intervention is problematic. It has been proposed that screening young age groups in the population by using predictors of high risk (such as a family history of psychosis, obstetric complications, or abnormal eye tracking) could identify potential patients long before onset. (H8) However, the poor specificity of such putative risk factors is likely to result in low positive predictive values. Other candidate risk...

The neurobiology of schizophrenia

FunctionaLneurobiologyof schizophrenia The neurobiology of schizophrenia may be divided into functional and structural aspects. Significant progress has been made in both areas as a result of the development of imaging modalities and the emergence of molecular techniques to study the underlying cellular processes.

Schizophrenia and Alzheimers disease

The belief that Alzheimer's disease is commoner in schizophrenia (independent of any cognitive impairment) originated in the 1930s. It received some recent support from three uncontrolled, retrospective studies, and tangentially from data suggesting that antipsychotic drugs promote neurofibrillary tangles. However, a meta-analysis shows that Alzheimer's disease is not more common, and may even be rarer, in schizophrenia. (29 This applies even in elderly schizophrenic patients with prospectively assessed severe dementia, who show no evidence of any other neurodegenerative disorder.(30) Nor is there good evidence that antipsychotic drugs cause Alzheimer-type changes. How, therefore, is the cognitive impairment of schizophrenia explained One possibility is that it is a more severe manifestation of whatever substrate underlies schizophrenia. Or, it may be that the brain in schizophrenia is more vulnerable to cognitive impairment in response to a normal age-related amount of...

Firstepisode psychosis

The recent resurgence of interest in the early detection and treatment of first episodes of psychosis, driven by theoretical considerations and clinical concerns, is supported by empirical evidence suggesting that the course and outcome of the earliest stages of a schizophrenic illness may have a pathoplastic effect on its subsequent course. Specifically, the period between the first onset of psychotic symptoms and the initiation of treatment (duration of untreated psychosis) has been shown to correlate with increased time to remission and poor response to treatment.(43) Plausible clinical considerations have been proposed in support of the view that the first episode of psychosis represents a critical developmental transition that may impact the subsequent course of schizophrenia, possibly by inducing irreversible changes in the connectivity between neural networks and thus preparing the ground for chronic illness. (44 An extension of this mode of thinking is the suggestion that a...

Depression in schizophrenia

In the WHO International Pilot Study of Schizophrenia, (33) the proportion of patients with initial schizophrenic symptomatology who developed non-schizophrenic (mostly affective) episodes in the course of time increased from 3 per cent in the first 2 years to 17 per cent at the end of the 5-year follow-up. In contrast, subsequent episodes with schizophrenic features occurred in fewer than 10 per cent of the patients with an initial diagnosis of major depression. Depression is the most common non-schizophrenic syndrome intercurrent with schizophrenia also in those patients who retain the essentially schizophrenic character of their illnesses. The proportion who develop clear-cut episodes of major depression ranges from 15 per cent during a 5-year follow-up (50) to 24 per cent during a 12-year follow-up.(20) This is a much higher period prevalence rate than in the general population, which suggests that depression is part of the clinical spectrum of schizophrenia. Based on such data, a...

Delusional disorderparaphreniaparanoid schizophrenia

Somewhat anecdotally, the literature suggests that approximately 10 per cent of individuals with delusional disorder or paraphrenia will 'shift to the right' at some stage and deteriorate to schizophrenia. (The proportion may seem higher if the original diagnoses are less than rigorous and if cases of early schizophrenia are included). Otherwise, it seems that the majority of cases of delusional disorder and paraphrenia remain diagnostically stable over a prolonged period. Several reports have indicated that, as one moves to the left on the spectrum, a family history of schizophrenia becomes progressively less common. The risk for schizophrenia in the close family of a case of delusional disorder appears to be much the same as in the general public. Although paranoid schizophrenia is invariably grouped with other schizophrenia subtypes, there is still justification for Kraepelin's original concept of its belonging with the delusional disorders. A family history of schizophrenia is...

F231 Acute polymorphic disorder with symptoms of schizophrenia bouffe dlirante or cycloid psychosis with symptoms of

This diagnostic category combines the symptoms of acute polymorphic psychotic disorder with some typical symptoms of schizophrenia (F20) present for most of the time. However, the schizophrenic symptoms are not precisely listed. F23.1 can be a provisional diagnosis, which is changed to schizophrenia if the criteria of F20 persist more than a month. Acute polymorphic disorder with symptoms of schizophrenia satisfies the general criteria for acute and transient psychotic disorders Leonhard(9) described cycloid psychosis as an episode with clouding of consciousness and a marked alteration of thinking. Many authors have reported follow-up studies of cycloid psychoses,(2 2 and 23 which confirm the better prognosis of cycloid psychoses than of schizophrenias and schizoaffective disorders.

OCD and schizophrenia

About 25 per cent of patients with chronic schizophrenia may also present with OCD symptoms (range 5 to 45 per cent) (16) 15 per cent of patients with schizophrenia may qualify for the diagnosis of OCD. As in OCD, the OCD symptoms in these patients will not necessarily surface unless specific questions are asked. Many patients with schizophrenia can distinguish the egodystonic, obsessive-compulsive symptoms, perceived as coming from within, from the egosyntonic delusions perceived as introduced from the outside. Follow-up studies demonstrate a diagnostic stability over the years, and it seems that the presence of OCD in schizophrenia predicts a poor prognosis 6* Several studies among patients with schizophrenia and OCD reported an improvement in OCD symptomatology after the addition of a specific anti-obsessive medication 16' The poor prognosis of patients with schizophrenia and OCD, preliminary data regarding their response to the unique combination of antipsychotic and...

Management of acute psychoses

When the psychosis is believed to be triggered by the perceived stress of the treatment environment, it is advisable to transfer the patient as soon as possible to a less intimidating environment, for example from an intensive care unit to a general ward or from a general ward to the patient's home, if adequate care is available there. Rapid tranquillisation may be needed if there is aggressive or disruptive behaviour. Chlorpromazine or haloperidol may be given in doses similar to those used in acute mania. If very rapid control of symptoms is required, diazepam can be given intravenously in a dose of 5-10 mg as Diazemuls. Intravenous therapy ensures near immediate delivery of the drug to its site of action and effectively avoids the danger of inadvertent accumulation of

F232 Acute schizophrenialike psychotic disorder schizophreniform psychosis

The duration criterion is the most important. This category is a provisional diagnosis and appears to include such disparate descriptions as oneirophrenia (oneiroid states or Erlebnisform(8J), schizophrenic reaction (DSM.IV 298.8, Brief reactive psychoses), and schizophreniform psychosis. (11) In ICD-10, if the first episode lasts for more than a month, it has to be considered as an acute onset of schizophrenia. The Scandinavian psychiatric school (2i justify the retention of this category because of the very good and rapid recovery, and have tried to determine factors in the personal and family history predicting the onset of schizophrenia. Schizophreniform disorder remains in DSM-IV (295.40) because the evidence linking it to typical schizophrenia remains unclear, but the duration criterion is less restrictive (up to 6 months). Features suggesting a good prognosis are onset within 4 weeks, confusion at the height of the psychotic episode, previously good social and occupational...

The Disease Of Schizophrenia

Schizophrenia is a group of heterogeneous, chronic psychotic disorders. Key symptoms include hallucinations, delusions, and abnormal experiences, such as the perception of loss of control of one's thoughts, perhaps to some outside entity. Patients lose empathy with others, become withdrawn, and demonstrate inappropriate or blunted mood. Discrimination of several subtypes of the disease represents only different patterns of symptoms with little value in relating behavior to neu-ropathology. The disorder has a strong genetic component, as demonstrated by a concordance of 40 to 50 between monozygotic twins, but no objective physiological or biochemical diagnostic tests exist. Schizophrenic patients appear to have small brains with large ventricular volumes, indicating a relative deficit of neurons. Structural and functional brain imaging studies have strongly suggested that regions of the medial temporal lobe (e.g., hippocampus) have diminished numbers of neurons and also have...

Motor Functions and Schizophrenia

Based on the above, it is not surprising that investigations are conducted into the possibility of using cannabinoid-based medicines for the treatment of impaired motor functions, many of which are thought to involve the dopamine system. Such conditions include Parkinson (128) and Huntington's diseases (129), Tourette syndrome (130), multiple sclerosis (131), and schizophrenia (132). However, especially in the case of schizophrenia, the complexity and chronicity of the condition and its treatments (133,134) warrant further experimental work until widespread clinical applications may be endorsed (135).

Defined disorders Schizophrenia

During the first two decades after its introduction, convulsive therapy became the primary treatment for dementia praecox and remained so until the introduction of chlorpromazine and other new medications in the 1950s. Medications also replaced insulin coma and leucotomy, two other treatments for schizophrenia developed in 1933 and 1935. These treatments were highly risky with limited efficacy. Because they were introduced at the same time as ECT, with the same target population, and produced similar electrophysiological and neuropsychological effects, many clinicians and many in the public confused the three treatments and still do so today. In the succeeding two decades, however, numerous cases proved resistant to pharmacotherapy, despite megadosages of antipsychotic drugs, complex and experimental combinations, and adjunctive measures. Faced with these failures, clinicians once again tried ECT and found it effective. In a noteworthy study, May(4) randomly assigned 228 'middle...

Psychosocial treatments for schizophrenia

The direct health and social care costs for schizophrenia in England in 1992-1993 amounted to 810 million, and the overall cost of illness was approximately 2.6 billion, even without including carer costs.(23) These high costs are recurrent schizophrenia is an early-onset chronic incurable illness which can severely damage the quality of life of sufferers and families. It also raises societal concerns, for example about public safety. Not surprisingly, therefore, much policy and practice attention has been devoted to ways of changing the nature or quality of support and treatment for people with schizophrenia so as to improve cost-effectiveness. Among the principal concerns today are the heavy demands on inpatient services (one NHS bed in 20 was occupied by a schizophrenia patient in England in 1992-1993), about the inappropriateness of currently available care regimes for some patient groups (particularly black and ethnic minority groups), and about the higher prices of the atypical...

Schizophrenia and paranoid disorders

When viewed across the lifespan, the incidence of schizophrenia shows strong age-group differences. (33) In males, the incidence rises steeply in adolescence, reaching a peak in the early twenties and then steadily declines to old age. Females show a similar rise in young adulthood with a subsequent drop, but there is also a second peak around the time of menopause. This second peak may occur because oestrogen delays the onset of schizophrenia in some vulnerable women. In younger adults, males have a higher incidence of schizophrenia, whereas in later life females have the higher incidence. The prevalence, as well as the incidence, of schizophrenia appears to be low in the elderly. However, while almost all younger adults with schizophrenia or paranoid disorders come to treatment, it is believed that a considerable proportion of the elderly refuse treatment because of suspiciousness, they are not recognized to have a treatable disorder, or their behaviour is attributed to senility....

Why Focus On Smoking In Patients With Schizophrenia

Patients with schizophrenia smoke at much higher prevalence rates (70-80 ) than the general population (25 to 30 ).1-5 This is true even when patients are identified in their first psychotic episodes, before they have been institutionalized or treated with antipsychotic medications.6 Smokers with schizophrenia also smoke more heavily than smokers in the general population, or smokers with other psychiatric illnesses.78 The increased prevalence of smoking, and the heavy smoking, suggest that nicotinic mechanisms are involved in the pathophysiology of schizophrenia. Smoking takes its cost in this population. Mortality rates for patients with schizophrenia are two to four times that of the general population, and patients with schizophrenia die, on average, ten years earlier than would otherwise be expected. The prevalence rates for respiratory and cardiovascular disease are significantly elevated among patients with schizophrenia in some studies twice as high as seen in age-matched...

Nicotineresponsive Elementary Phenotypes In Schizophrenia

Schizophrenia is a complex genetic disorder i.e., the illness does not have a pattern of inheritance resulting from a single genetic abnormality.10 Two nicotine-responsive neurophysiological abnormalities, one in auditory sensory gating and the other in smooth pursuit eye movements, are currently under investigation as potential elementary phenotypes representing gene effects that, in combination with other specific gene effects, may result in the development of schizophrenic illness.1112 These neurophysiological abnormalities appear to be transmitted as autosomal dominant characteristics in some families with high occurrence rates for schizophrenia, and they are both normalized by nicotine administration. The subjective experience of this normalization may contribute to the drive to smoke among patients with schizophrenia. In nearly all neuronal systems, when stimuli are repeated, the electroencephalo-graphic response to the second stimulus is less than that to the first. The first...

Psychosis certainty and action

Is it possible to take further the account of the formation of psychotic symptoms, especially those of the acute phase, delusions and hallucinations The simplest dopamine hypothesis would predict that the symptoms are the consequence of over stimulation of neurones a non-intentional explanation. However it may be that the origin and nature of these abnormal beliefs and experiences is not qualitatively different from those of individuals who are not psychotic. The diagnostic classifications and research instruments create a sharp distinction but in practice it is not clear-cut (Strauss 1992). If we put this together with the neuropsychological theories of schizophrenia we may emerge with a different formulation. The theory provides an explanation of disordered, chaotic, overwhelmed, and unpredictable thoughts and behaviours. Delusions and hallucinations are by contrast, clear, unambiguous, and relatively or absolutely uninfluenced by evidence. Consider further contrasts. The experience...

Specific psychiatric disorders and criminal acts Schizophrenia

Both acute and chronic phases of schizophrenia may be associated with offending and the latter may be of any type. Attempts to identify the significance of particular phenomena are fraught with problems. Case-note studies may be based on poor data, phenomena (e.g. grandiose delusions and command hallucinations) are difficult to define with high inter-rater reliability and accuracy, and appropriate control groups may be lacking. Typical research cohorts are inpatients, patients evaluated for admission, or offenders the extent of psychotic phenomena in community-based samples is poorly understood. It is therefore difficult to be confident that research findings in this area are generalizable.

Snap25 And Schizophrenia

Antipsychotic drugs on levels of SNAP-25 in different brain regions in rodents. One study reported that there was no effect of chronic treatment with haloperidol on levels of SNAP-25 in multiple brain regions that are strongly innervated by dopamine neurons, including the prefrontal cortex, nucleus accumbens, striatum, substantia nigra, and ventral tegmental area64. Recently, we have assessed the effects of treatment for 21 days with the typical antipsychotic drugs haloperidol, chlorpromazine, and trifluoperazine on levels of SNAP-25 in the trisynaptic pathway of the hippocampus65. Levels of SNAP-25 were measured by quantitative immunohistochemistry. Our findings revealed that both haloperidol and chlorpromazine increased SNAP-25 throughout the hippocampus, with greatest effects for haloperidol-treated rats in the mossy fiber region, while chlorpromazine-treated rats exhibited largest increases of SNAP-25 in the mossy fiber and Schaffer collateral regions. However, these effects only...

Prognosis of schizophrenia subtypes

The evidence that each of the 'classic' subtypes of schizophrenia is associated with a characteristic patterns of course is generally weak but surprisingly good for some of the subtypes. Thus, consistent differences have been reported between paranoid, hebephrenic, and undifferentiated schizophrenia (diagnosed according to DSM-III) on a long-term follow-up of 19 years.(52) Paranoid schizophrenia tended to have a remittent course, and to be associated with less disability, in contrast to hebephrenia which had an insidious onset and poor long-term prognosis. Undifferentiated schizophrenia occupied an intermediate position. In the WHO International Pilot Study of Schizophrenia,(33) four alternative groupings of the ICD-9 subtypes were tested by a discriminant function for differences with regard to six course and outcome measures. Clear discrimination was achieved between simple and hebephrenic schizophrenia grouped together on the one hand and the schizoaffective subtype on the other....

Effects of head injury on schizophrenia

The cognitive and behavioural problems of schizophrenia overlap considerably with those produced by traumatic brain injury. Antisocial behaviours, apathy and lack of spontaneity, and erratic mood swings are common to both. Both will show cognitive problems including disorders of communication, memory, and planning. Will a head injury therefore aggravate these more negative symptoms of schizophrenia Given that a significant proportion of head trauma is found in people with schizophrenia who have jumped from a height, the question arises from time to time. As yet there are no studies of the outcome.

Theory Of Mind In Schizophrenia

Jokes About Perspective

Schizophrenic individuals demonstrate (1) a poor understanding of false belief and deception in stories, despite being matched to healthy controls on IQ (2) a lack of appreciation of visual jokes when understanding the humor depends upon inferred mental states, despite being able to explain control jokes as well as healthy participants3 (3) a difficulty with sequencing picture-card stories that require inferences of false beliefs in order to determine the logical order of events, despite controlling for any difficulties with logical cause-and-effect reasoning in patients versus controls and (4) an impaired capacity to go beyond the strict literal meanings of words in order to infer speakers' thoughts when speakers use either indirect hints or verbal irony, despite controlling for any limitations of verbal IQ and verbal memory in patients versus controls (for reviews, see Harrington, Siegert, & McClure, in press Langdon, 2003). These findings present several challenges to current...

Changes In Other Molecular Markers In Schizophrenia

Synaptic Plasticity

While the focus of the present review is on the relationship between presynaptic proteins and neuropsychiatric disorders, this represents an analysis at just one level of these complex diseases. In the case of schizophrenia, there is also substantial interest at the neural circuit level. In particular, there has been recent interest in the nature of inhibitory circuits within the dorsolateral prefrontal cortex (DLPFC), and how alterations in these circuits may lead to cognitive deficits (reviewed in detail by Lewis and colleagues in ref. 79). Primate studies demonstrate that GABAergic interneurons in the DLPFC appear to play an essential role in working memory processes, by regulating both the spatial and temporal electrophysiological activity of surrounding pyramidal neurons. Multiple postmortem human studies have revealed that levels of glutamic acid decarboxylase (GAD67), an enzyme that synthesizes GABA and is specific to interneurons in the frontal cortex, is significantly...

Imaging pathophysiology examples from schizophrenia research Imaging dopamine receptors

Much research effort has focused on in vivo PET SPET measurement of striatal dopamine D2-receptor number in schizophrenia following the initial post-mortem reports of increased striatal dopamine receptor number. Initially, using (11)C N-methylspiperone as a radiotracer, a two- to threefold raised striatal D 2-receptor number in drug-naive schizophrenics was reported.(7) However, subsequently other investigators using Cjraclopride, (11)C N-methylspiperone, (123)I iodobenzamide, (76)Br bromolisuride failed to detect such elevations of striatal dopamine D 2-receptor number 89) The different radiotracer methodologies used, the selectivity of radiotracers for dopamine D2, D3, and D4 receptor subtypes, and the clinical characteristics of the patients studied have been advanced as possible explanations for the failure to replicate raised striatal dopamine D 2-receptor number. However, given these conflicting but essentially negative results, attention has shifted in recent years to reports...

Secular trends a decreasing incidence of schizophrenia

A number of studies have suggested that a decrease of 40 per cent or more may have occurred in the first admission rates for schizophrenia over the last 30 years in some of the developed countries.(76) The data are not entirely consistent the drop in rates is more marked in females or in late-onset cases according to some reports, is more pronounced in young males according to others, or is of the same magnitude in both sexes and in all age groups. Downward trends have been identified mainly by using national or regional admission and discharge statistics. Attempts to replicate such trends on a local level using case register data have not produced consistent results, while studies in which research diagnoses were made after a case review show no decline in incidence rates. Other concurrent changes, such as a reduction in the number of psychiatric beds and in the total number of first admissions, have also been noted in many of these studies. However, increases have been reported in...

Patterns and stages of the course of schizophrenia

The great heterogeneity of the course of schizophrenia can be reduced to a limited number of patterns into which cases tend to cluster over time. In the long-term follow-up studies referred to above, eight different categories of course were described by Bleuler (12) and Ciompi,(28 and 12 by Huber et al.'(lf. These classifications were derived from empirical observation, rather than statistical modelling, and conflated into single categories the mode of onset, longitudinal aspects such as psychotic episodes and remissions, and end states. Treating the various aspects of the longitudinal profile of the illness as independent axes in a multidimensional construct has been recommended 3 ,.32 However, the complexity of statistical modelling of the course of schizophrenia is such that the development of a classification of course that would be both useful in clinical practice and rigorous in a mathematical sense may not be feasible. Therefore, an heuristic compromise between these two...

Factors maintaining the incidence of schizophrenia in populations

Since schizophrenic patients have a reduced rate of reproduction, compared with the general population, the maintenance of a relatively stable rate of schizophrenia in the population requires an explanation. A high mutation rate can practically be ruled out since the rate required for a polygenic disorder would exceed by far the theoretically possible mutation rate. Selective advantages of individuals with schizophrenia (balanced polymorphism) (1J) that could offset their low fertility have been suggested, such as resistance to physiological stress or certain diseases, and an increased fertility in their biological relatives has been postulated. None of these hypotheses is at present supported by empirical data, although some evidence of normal or increased fertility among relatives of schizophrenic patients has been reported. However, the whole argument that, in the absence of a reproductive compensation for the low fertility of schizophrenic individuals, the disorder will gradually...

Neuroses Psychoses and Personality Disorders

Freud's conception of psychosis also plays a fundamental role in modern psychoanalytic interpretations of the more severe personality disorders Schizoid, Schizotypal, Borderline, and Paranoid Personality Disorders. Contemporary psychoanalysts (e.g., Kernberg, 1996) view psychoses as a crisis in identity fusion and diffusion in the integration of self and others. There is a prominence of primitive ego defenses such

Can Schizotypal Disorder Disintergrate Into Frankschizophrenia

Schizotypals are often described as odd and eccentric and seemingly engrossed in their own world. Most researchers believe that the schizotypal personality lies on a continuum with schizophrenia called schizotypy. Schizotypals, like schizophrenics, experience both positive and negative symptoms. As one of the three structurally defective personalities (the paranoid and the borderline are the other two), schizotypals are set apart from other personalities in that they rarely find a comfortable niche in society and repeat the same setbacks again and again. However, most schizotypals are able to pull themselves together enough to prevent slipping into more serious decompensated states. The schizotypal personality is a relatively new construct that has its origins in both the writings of Kraepelin and Bleuler, who studied dementia praecox patients and noticed how diverse their symptoms were. Bleuler conceptualized these patients on a continuum with schizophrenics at the most severe end...

The natural history of schizophrenia before the neuroleptic era

Another, long-term perspective on the course of schizophrenia over successive generations is provided by a meta-analysis of 320 outcome studies on schizophrenia or dementia praecox published between 1895 and 1992 and including a total of 51 800 subjects.(6) Overall, about 40 per cent of the patients were reported as improved after an average length of follow-up 5.6 years. There was a significant increase in the rate of improvement during the period 1956 to 1985 compared with 1895 to 1955, clearly related to the introduction of neuroleptic treatment, (7) but a secular trend towards better outcomes with every successive decade had been present for much longer. Coupled with the virtual disappearance of the most malignant or 'catastrophic' forms of schizophrenia resulting in a profound defect state after a first psychotic episode, or death ('lethal catatonia'), these observations suggest that some transition to a less deteriorating course of the disorder had occurred prior to modern...

Does the categorical disease concept of schizophrenia constrain aetiological research

It has been suggested that the categorical disease concept of schizophrenia is no longer tenable and may be an obstacle to further progress in aetiological research.(112ll3) The reasons advanced include the variation in the clinical phenotype, the likely genetic heterogeneity, and the absence, following several complete genome scans in large samples of families, of clear evidence for genetic linkage of the diagnostic entity. Reasons for revising the original formulation of the problem of the psychoses were given by Kraepelin himself, who concluded in 1920 that schizophrenia and manic-depressive illness do not represent particular pathological processes but rather indicate which 'areas of our personality' are affected by them. (H4) Whether schizophrenia is a single disease or a syndrome arising as a 'final common pathway' for a variety of pathological processes, the validity of the concept is supported by the epidemiological evidence. This makes it unlikely that the concept will be...

Schizophrenia as a disorder of brain maturation

There is evidence from clinical research implicating aberrant neurodevelopmental processes in the pathophysiology of schizophrenia, (.33 but there is also a growing literature suggestive of progressive deterioration in the disease for at least some patients. (3i It should be noted that abnormal neurodevelopmental processes are not mutually exclusive of neurodegenerative mechanisms in the pathogenesis of complex neuropsychiatric disorders. Indeed, while some genetic disorders are purely developmental (e.g. fragile X syndrome) and others purely neurodegenerative (e.g. Huntington's disease), some have both developmental and degenerative pathologies (e.g. Down syndrome). Based on the neuropathological literature of the last 30 years some suggestions can be made concerning the pathophysiology of schizophrenia. no evidence for astrogliosis in schizophrenia (Fig 3) 1 Although the question of fibrous gliosis (i.e. increase in glial cell fibres) remains more controversial, the well-controlled...

Antipsychotic Drugs Smoking And Schizophrenia

Antipsychotic drugs ameliorate the psychopathology and course of schizophrenia. Recent research has begun to examine how antipsychotic drugs affect smoking among patients with schizophrenia, how they affect nicotine-responsive phenotypes, and how these effects relate to the drugs' effects on psychopathology and cognitive psychomotor performance. There are substantial advantages to studying smoking among hospitalized inpa-tients with schizophrenia 1) patients with schizophrenia have high rates of noncom-pliance with clinical or investigational procedures without the close supervision that the inpatient setting can provide 2) the inpatient environment is stable, and patients are largely protected from stressful events or concurrent substance abuse that may alter their response to nicotine and, 3) the protective containment of the inpatient environment permits rapid detection of and attention to any adverse reactions developing in relation to novel interventions under study. Two-hour...

Molecular epidemiology of schizophrenia

Notwithstanding the difficulties accompanying the genetic dissection of complex disorders, novel methods of genetic analysis will eventually identify genomic regions and loci predisposing to schizophrenia. The majority are likely to be of small effect, although one cannot exclude the possibility that genes of moderate or even major effects will also be found, especially in relation to the neurophysiological abnormalities associated with schizophrenia. Clarifying the function of such genes will be a complex task. Part of the solution is likely to be found in the domain of epidemiology, since establishing their population frequency and associations with a variety of phenotypic expressions, including personality traits and environmental risk factors, is a prerequisite for understanding their causal role. Thus a molecular epidemiology of schizophrenia is likely to be the next major chapter in the search for causes and cures.

The Dopamine Hypothesis of Schizophrenia

The dopamine hypothesis of schizophrenia is the most fully developed theory of causation for this disorder, and until recently, it has been the foundation for the rationale underlying drug therapy for this disease. The hypothesis is based on multiple lines of evidence suggesting that excessive dopaminergic activity underlies schizophrenia (1) drugs that increase dopaminergic activity, such as levodopa and amphetamines, either aggravate existing schizophrenia or induce a psychosis indistinguishable from the acute paranoid form of the disorder (2) traditional antipsychotic drugs strongly block D2-dopaminergic receptors in the central nervous system (CNS), and clinical efficacy is highly correlated with the potency of individual agents to bind to this receptor (3) some postmortem studies have reported increases in dopamine receptor density in brains of schizophrenics who were not treated with antipsychotic drugs and (4) clinical response to antipsychotic drug treatment is correlated with...

Simulation Theory And Schizophrenia

Svg Blank Tumbler Cup

Langdon and colleagues (2002) were interested to see whether people with schizophrenia, like autistic individuals, show the co-occurrence of theory-of-mind deficits and poor appreciation of indirect speech. Happ (1993) had earlier investigated first-order and second-order theory of mind and comprehension of metaphors and irony in autism. First-order, in this context, refers to a capacity to infer A believes that x, whereas second-order refers to a capacity to infer A believes that B believes that x. The first-order versus second-order distinction purportedly helps to elucidate the distinction between the processes required for understanding of metaphors versus irony. More specifically, appreciation of indirect speech (whether metaphors or irony) requires, first, an understanding that speakers have thoughts that go beyond their words. Next, in order to understand a metaphor, a listener makes a first-order inference (e.g., in order to understand My lawyer is a shark, a listener infers...

Schizophrenia and other psychotic disorders Studies between 1898 and 1975

Subsequently to Alzheimer, Southard reported cortical atrophy in schizophrenia and mentioned that association areas of the cerebral cortex were most affected in this disorder 10,) Buscaino(U described various histopathological changes, mainly in the basal ganglia, which he assumed to be responsible for catatonia-like and stereotyped behaviour. Another approach to the neuropathology of psychiatric diseases had been made by Vogt and Vogt and their coworkers, who reported cellular alterations in the cortex, thalamus, and basal ganglia of schizophrenics. (1. , 3,14, 5.,11 I8 and 9 These considerable efforts on the part of many well-known neuroanatomists and neuropathologists to prove that schizophrenia is a primary brain disorder, ended in inconsistent and unsubstantiated findings. (45) To a large extent these inconsistencies can be attributed to a variety of methodological inadequacies including diagnostic uncertainties, inadequate control samples, flawed tissue-handling procedures,...

Cannabis psychosis

High doses of THC have been reported to produce visual and auditory hallucinations, delusional ideas, and thought disorder in normal volunteers. (2) In traditional cannabis-using cultures, such as India, a 'cannabis psychosis' has been reported in which the symptoms are preceded by heavy cannabis use and remit after abstinence.(1,12) The existence of a 'cannabis psychosis' in Western cultures is still a matter for debate. In its favour are case series of 'cannabis psychoses', and a small number of controlled studies that compare the characteristics of 'cannabis psychoses' with those of psychoses in individuals who were not using cannabis at the time of hospital admission 13) Critics of the hypothesis emphasize the fallibility of clinical judgements about aetiology, the poorly specified criteria used in diagnosing these psychoses, the dearth of controlled studies, and the striking variations in the clinical features of 'cannabis psychoses'. (14)


Some of the earliest psychiatric sleep studies were performed in schizophrenic patients because of the similarities between psychosis and dreaming. Although no evidence for REM sleep 'intrusions' into wakefulness has been documented, it is of interest that frontal brain regions (e.g. dorsolateral prefrontal cortex) which seem to be affected in schizophrenia are also relatively inactivated during REM sleep. (14 Schizophrenics often suffer from disturbed sleep, particularly during acute exacerbations of illness. Behavioural and illness factors such as social withdrawal, paranoid delusions and general behavioural disorganization can lead to increased nocturnal wakefulness and daytime napping. Underlying central nervous system abnormalities in dopaminergic and serotonergic systems may also contribute to sleep abnormalities. Objective studies of sleep in groups of schizophrenic patients have generally shown significant sleep disruption j29.) frankly psychotic patients may have profound...


Psychotic symptoms ('levodopa psychosis') occur at some point in 20 per cent of patients with Parkinson's disease, and the role of antiparkinsonian medication is central in their causation. Psychosis is more common in elderly patients and occurs in clear consciousness, although some degree of confusion is often present. Psychosis in Parkinson's disease tends to have a progressive course. In addition to levodopa, many other drugs (selegiline, bromocriptine, and pergolide) have been implicated. Amantadine and anticholinergic drugs are more likely to cause confusional states. Stimulation of hypersensitive dopaminergic receptors in the nigrostriatal system by levodopa and related drugs may explain psychosis early in the course of treatment, but it is unlikely to explain the psychotic symptoms that appear after years of treatment. The therapeutic efficacy of atypical neuroleptics suggests a role for mesolimbic dopaminergic and serotonergic pathways.


Chronic interictal psychoses Throughout the first half of this century the relationship between epilepsy and schizophrenia was debated at length, usually in terms of whether the presence of one condition encouraged or discouraged the development of the other the affinity and antagonism hypotheses respectively. In recent years, particularly following the publication of Slater's seminal studies,(9) informed opinion has moved firmly behind the first view. Epidemiological studies based on national registers (l0,i1.) find a higher prevalence of chronic psychosis in epileptic subjects than in the general population. A neurology outpatient clinic study (12 reported schizophrenia to be nine times more common in epilepsy than in a migraine control group. The onset, cause, and clinical characteristics are, to a very large extent, indistinguishable from those of more usual forms of schizophrenia, although there is some very limited evidence that the outcome may be more benign. A family history...

Acute schizophrenia

A small number of therapeutic communities have been established in the United Kingdom, the United States, and Switzerland to discover whether young people with first or second admissions suffering from acute schizophrenia or schizophreniform psychosis could be effectively treated in small family-like settings with the minimal use of neuroleptics. Two studies using controls treated in conventional settings demonstrated comparable or better outcome on a number of indices in the therapeutic community samples. Reliance on medication at follow-up was significantly lower, although there were no cost savings.(2 26) A 20-year study of an acute psychiatric ward in Finland found that acute psychotic and borderline patients seemed to benefit from the therapeutic community model with a high level of support, negotiation, order, and organization.(27)

Postpartum psychoses

A variety of different psychoses can begin after childbirth. A group of rare organic disorders occur early, including confusional states similar to those seen during parturition, exhaustion to the point of stupor, delirium tremens, posteclamptic delirium, and infective delirium. Psychogenic (reactive) psychosis is occasionally seen. The best example is morbid jealousy, which can arise as an understandable reaction to changing relationships and the quiescence of sexual life. The psychoses reported in adoptive mothers,(48) and in fathers after childbirth belong to this psychogenic group. The bulk of postpartum psychoses are endogenous functional disorders, with manic, cycloid, or depressive features. The rest of this section will deal with this group ('puerperal psychosis'). Since the first clear description by Osiander(35) in 1797 and the authoritative accounts by Esquirol (49 in 1818 and Marce .9 in 1858, there has been a long-standing controversy about their place in the nosology of...

The pace of scientific advance

Advances in genetics and in the neurosciences have already increased knowledge of the basic mechanisms of the brain and are beginning to uncover the neurobiological mechanisms involved in psychiatric disorder. Striking progress has been achieved in the understanding of Alzheimer's disease, for example, and there are indications that similar progress will follow in uncovering the causes of mood disorder, schizophrenia, and autism. Knowledge of genetics and the neurosciences is so extensive and the pace of change is so rapid that it is difficult to present a complete account within the limited space available in a textbook of clinical psychiatry. We have selected aspects of these sciences that seem, to us and the authors, to have contributed significantly to psychiatry or to be likely to do so before long.

The burden of mental illness

Using the DALY as the basic statistic, the World Development Report(2) concludes that mental health problems make up 8.1 per cent of the total GBD. Of that 8.1 per cent, the largest contributors are depressive disorders, self-inflicted injuries. Alzheimer's disease and other dementia, and alcohol dependence, followed by epilepsy, psychoses, drug dependence, and post-traumatic stress disorder. Depressive and anxiety disorders account for between one-quarter and one-third of all primary-health-care visits worldwide.(3,,4) When appropriately diagnosed and treated, suffering is alleviated, disability prevented, and function restored when ignored, major losses persist.(5) By the year 2025, three-quarters of all elderly persons with dementia (about 80 million) will live in low-income societies. Mental retardation and epilepsy rates are three to five times higher in low-income societies compared with industrialized countries. In some Asian and African countries, up to 90 per cent of patients...

Cultural influences on the neuroses

Whereas neither the form nor the incidence of psychoses vary much across cultures, neuroses show dramatic variations in both respects. So-called culture-bound syndromes are an extreme example of variation in frequency since it is claimed that they are confined to specific cultural groups (see Ch pter 4.16). However, even with common conditions such as depression, the range of prevalence rates from studies across cultures is extremely wide. A review of 19 studies mostly conducted in developing countries found a difference in prevalence of neuroses of more than 300-fold from the highest to the lowest. (19. There are at least three plausible explanations. Unlike psychoses, there is no clear boundary between depressive symptoms severe enough to constitute an illness and subclinical depression. Shifting the threshold for a depressive illness towards the milder end of the spectrum will automatically increase the prevalence rate. Few comparative studies of neuroses across cultures have been...

Year III of residencyspecific goals and objectives

The goal of this year is to enhance the resident's acquired competencies in ambulatory care by supervised experience in more complex arenas of psychiatric service. A whole variety of new competencies are derived from this emphasis on mastering the problems of psychiatric assessment and treatment in unique domains within the health-care system. The resident continues to treat patients in an office-based practice, but, through a comprehensive outpatient service, also has closely supervised experience in the assessment and treatment of chronic schizophrenia and affective disorders, anxiety disorders, drug and alcohol disorders, and sexual disorders. Special treatment experiences psychopharmacology for chronic disorders, couples therapy, family therapy are provided under close supervision along with an extended series of psychodynamically oriented lecture demonstrations. A significant exposure to community-based psychiatry is provided, including rehabilitative and outreach services....

Preface to the First Edition

Throughout the discussion philosophical theories are brought to bear on the particular questions of the explanation of behaviour, the nature of mental causation, and eventually the origins of major disorders including depression, anxiety disorders, schizophrenia, and personality disorder.

Competing Classifications

Unfortunately, much of the pressure for change has continued to originate from clinical and political demands. Revisions have sometimes had the appearance of tinkering in order to capture some imagined essence of the disorders included (Birley, 1990). What looks like fine-tuning can nevertheless make considerable differences to whether individual cases meet criteria or not, and thus disproportionately affects the putative frequency of disorders. We should jettison classifications only on grounds of inadequate scientific utility and as seldom as possible, since too rapid revision defeats the objective of comparison. Like all such classifications, DSM and ICD are created by committees. The natural tendency to horse-trading between experts selected precisely because they are powerful and opinionated leads to an over-elaborate structure, an excess of allowable classes and subclasses, and complicated defining criteria. Thus, in DSM-IV-R (APA, 1994), there are potentially 14 categories to...

The Limits Of Classification

As classification aspires to 'carve nature at the joints', the empirical relationships between psychiatric symptoms create special difficulties of their own. In particular, symptoms are related non-reflexively thus, some symptoms are common and others are rare, and, in general, they are hierarchically related, rather than being associated in a random manner. Rare symptoms often predict the presence of common symptoms, but common symptoms do not predict rare symptoms. Deeply (that is, 'pathologically') depressed mood is commonly associated with more prevalent symptoms, such as tension or worry, while, in most instances, tension and worry are not associated with depressed mood (Sturt, 1981). Likewise, depressive delusions are almost invariably associated with depressed mood, whereas most people with depressed mood do not have delusions of any kind. The consequence is that the presence of the rarer, more 'powerful' symptoms indicates a case with many other symptoms as well, and therefore...

National classifications

In France and Scandinavia, the Kraepelinean concept of psychoses was accepted only partially or rejected. Magnan and Serieux (16) developed a classification(17) which remained restricted to Francophone psychiatry. Some disturbances like acute and chronic delusional states ( bouff es d lirantes and d lires chroniques) were recognized in France but were not really understood beyond the confines of French psychiatry. The French psychiatrists were particularly resistant to the Kraepelinean concept of schizophrenia, although they accepted the concept of manic depressive psychosis, perhaps because several French authors had already used similar concepts. In Scandinavia the concept of psychogenic psychoses was advocated,(19) as were early concepts of multidimensional diagnosis.(20) The special classification of psychoses according to Wernicke, Kleist, and Leonhard adopted in Germany should also be noted. (21) These authors claimed that, according to the phenomenological description of...

Future development in international classification

Aetiology, diagnosis, and therapy should be interrelated. Although most current diagnoses are descriptive, it is possible that nosology may eventually have a stronger basis in aetiology. It is likely that the aetiology of the psychoses will be better understood in the future, especially if an attempt is made to study subgroups of these conditions, relating them as far as possible to somatic abnormalities. This may be achieved with bipolar affective disorders and seasonal depressions, and also with special types of schizophrena such as periodic catatonia with its high genetic load, as described by Kleist and Leonhard. (2 Future work on both psychotic and non-psychotic disorders should focus on developing a new nosology and overcoming the currently popular atheoretical approach to diagnosis.

Are the results relevant for your patient

To determine the relevance of the study to real-life patients, it is important to examine the inclusion and exclusion criteria of the trial. The main inclusion criteria are discussed above. Patients excluded from the trial were women who were pregnant or of child-bearing age but unwilling to use an effective contraceptive method. Exclusion criteria also included major medical conditions, bipolar disorder, psychosis, panic disorder, concurrent major depressive disorders, generalized anxiety disorder, history of alcohol or other drug dependency within the previous 12 months, serious suicidal risk, previous non-response to two or more adequate antidepressant trials, and use of psychotropic drugs within 2 weeks of enrolment. The use of the study results will have to take these inclusion and exclusion criteria into account, and the clinician needs to judge the relevance of the results for the individual patient.

Laura P W Ranum 1 Introduction

Microsatellite repeat expansions have been shown to cause a number of neurodegenerative diseases (1). Most of the disease genes identified to date involve the expansion of a trinucleotide repeat motif, but recently tetra- and pentanucleotide repeat expansions have been shown to cause myotonic dystrophy type 2 (DM2) and spinocerebellar ataxia type 10 (SCA10), respectively (2,3). Most microsatellite diseases are characterized by the presence of anticipation, or a decrease in the age of onset in consecutive generations due to the tendency of the unstable repeat tract to lengthen when passed from one generation to the next (1,4,5). In addition, the involvement of trinucleotide repeat expansions in a number of other diseases including schizophrenia (6) and bipolar affective disorder (7,8) has been suggested both by the presence of anticipation and by Repeat Expansion Detection (RED) analysis (9,10). The involvement of trinucleotide expansions in these diseases, however, can only be...

Modulation of cortical activation and the anatomy of the reticular activating system

Specific information to the cerebral cortex, for example relating to sensory stimuli in the periphery, is relayed via the main thalamic nuclei. The other, diffusely projecting, systems are most likely to be involved in the regulation of cortical responsivity. Such a role has been demonstrated electrophysiologically for the claustrum, and the pharmacology of the antihistamines indicates a role for this transmitter system in the regulation of cortical arousal. The cholinergic input from the basal forebrain is necessary for the proper functioning of the cortex, and its degeneration is associated with cognitive decline and memory impairment. The possible relationship of mesolimbic dopamine pathways to schizophrenia is well known. Similarly, the psychopharmacology of serotonin also implies a major role for this transmitter system in the proper functioning of the cortex. There are two routes by which these 'non-specific' pathways affect the cortex direct projections, and an indirect pathway...

Cell death and trophic factors during development

The co-ordinated expression, in space and time, of many genes underlies neurodevelopment. Mutations in these 'neurodevelopmental genes' are increasingly being recognized as causes of developmental neurological disorders(15) such as cortical dysplasia and epilepsy they may also be relevant to learning disability and schizophrenia. Different gene families are involved in the major component processes of neurodevelopment, such as organogenesis, neurogenesis, neuronal migration, synaptogenesis, and programmed cell death (apoptosis).(1, ,17 The details are beyond the scope of this book, but a few examples are given here.

The hypothalamicgrowth hormone axis

Affective disorders research.(29) The mechanism underlying this phenomenon remains obscure, but it is of particular interest that, at least in some studies, it appears to persist upon recovery from depression, suggesting that it is a trait marker for depression vulnerability. There are reports of similar findings with other growth hormone-provocative stimuli, such as the use of apomorphine, desipramine, or levodopa. In addition, the blunted growth-hormone response to clonidine in depressed patients is particularly robust in those who have recently attempted suicide. Clearly, further work in this area is warranted, especially in the context of several reports of alterations in basal growth-hormone secretion in this disorder. The nature of this alteration is a reduction in the normal nocturnal rise in growth-hormone secretion, though this is not a universally agreed-upon finding. Alterations in growth-hormone secretion in other psychiatric disorders (particularly schizophrenia) have...

Conclusionsimplications for psychiatry

Intracellular effectors activated by binding to dopamine receptors are presumably involved in their actions. It is possible that drugs may attenuate some signal transduction cascades while activating others, depending on the cell type and precise combination of G proteins expressed in particular neurones. Changes in transcription of discrete sets of genes may follow, with the genes being turned on or off to yield a favourable clinical response. Furthermore, disease states such as depression or schizophrenia may themselves result from alterations in activity of distinct signal transduction cascades. Appreciation of these processes will therefore contribute in the long run to increased understanding of both the pathology of mental illness and psychopharmacology.

Microscopic findings Table2

There are a number of studies of neurone number, density, and size in schizophrenia. As summarized in Table .2, the majority of these have focused on the ventromedial temporal, and frontal lobes. In summary, morphometric microscopic studies in schizophrenia frequently find alterations in neurone density, size, shape, and positioning mainly in temporolimbic and frontal regions. Findings in other regions require replication, especially taking the small study samples into account.

Imaging 5hydroxytryptamine receptors

(11)C M-methylspiperone, (18)F altanserin, (18)F ethylspiperone, (18)F setoperone or (18)F altanserin, and the SPET tracer (123)I ketanserin have been used to measure 5-HT2 receptor number a receptor implicated in depressive illness, suicidal behaviour, and psychosis. Many of these 5-hT 2 ligands have been hampered by either the

Imaging bloodflow change in depressive disorder

Similarly to brain-mapping studies of patients with schizophrenia, regional deficits of neural activity (indexed by cerebral blood flow or glucose utilization) can be As demonstrated in schizophrenia, significant associations between cortical activity and cognitive function, symptom clusters, including mood, and response to treatments are apparent.*25' Similarly to schizophrenia, the resting-state functional brain abnormalities may represent the physiological correlates of aspects of the depressed state such as depressed mood, retardation, or cognitive impairment rather than trait markers of the illness itself.

Dopamine and Serotonin Receptors

Clozapine is a potent drug in the treatment of schizophrenia however, not all patients benefit from treatment, and some patients react adversely to therapy while others fail to respond adequately. Several studies have reported an association between clozapine response and polymorphisms in the dopamine receptor 3 (D3) gene (60-62), dopamine receptor 4 (D4) gene (63,64), and in the serotonin receptor 2A (65,66) and 5A genes (67). In a recent study, Arranz et al. (68) screened for the combination of upto 19 polymorphisms that predicted clinical response to clozapine in schizophrenic patients with high accuracy. These 19 single-nucleotide polymorphisms (SNPs) were located in eight receptor genes and one transporter gene, including the a2A-adrenoceptor, dopamine D3 receptor, 5-HT2A, 5-HT2C, 5-HT3A, 5-HT5A, histamine H1 receptor, histamine H2 receptor, and the serotonin transporter gene. A combination of six polymorphisms, including the 5-HT2A 102T C, His452Tyr, 5-HT2C-330GT -244CT,...

Data analysis Clinical analysis

Structural MRI is most often used in clinical practice to exclude non-psychiatric causes for psychopathology. For example, it is routine in many centres to obtain an MRI examination in all first episodes of psychotic illness to exclude tumours, arteriovenous malformations, or other rare (but surgically treatable) causes of psychosis. Clinical examination of these cases may also sometimes reveal abnormalities such as hippocampal sclerosis or callosal agenesis which suggest that psychopathology has been determined by birth injury or abnormal development. In assessment of a patient with dementia, MRI may usefully demonstrate signs of vascular disease (such as infarcts or periventricular white matter changes), or a focal pattern of grey matter atrophy suggestive of Pick's disease (frontal cortex) or Huntington's disease (caudate nucleus and frontal cortex). All of these abnormalities may be detected simply by skilled visual examination of the data. However, clinical diagnosis of the...

Individualize Therapy

The treatment of PD needs to be individualized each patient presents with a unique set of symptoms, signs, response to medications, and a host of social, occupational, and emotional problems that need to be addressed. As mentioned above, a major goal is to keep the patient functioning independently as long as possible. The practical guidelines for how to direct treatment are to consider the patient's symptoms, the degree of functional impairment, and the expected benefits and risks of available therapeutic agents. Ask the patient what specific symptoms trouble him the most. Also, keep in mind that younger patients are more likely to develop motor fluctuations and dyskinesias older patients are more likely to develop confusion, sleep-wake alterations, and psychosis from medications.

Significance of gamma

Gamma rhythms have been linked with sensory processing and with perception and other cognitive functions. Gamma rhythms may play roles in other psychiatric conditions. For instance, a recent study reveals increased beta and decreased gamma band signals in patients with schizophrenia. It is tempting to speculate that rather subtle changes in the networks responsible for gamma and beta rhythms could be at fault.

Clinical and research uses

PET scanning is of particular value in elucidating the relationships between cerebral blood flow, oxygen utilisation and extraction in focal areas of ischaemia or infarction (page 237) and has been used to study patients with dementia, epilepsy and brain tumours. Identification of neurotransmitter and drug receptor sites has aided the understanding and management of psychiatric (schizophrenia) and movement disorders.

Effects of psychosocial factors on the course of disease

Long-term survivors with clinical AIDS and those who remain asymptomatic for prolonged periods of time in the face of very low CD4 counts seem to be those who have good coping skills, lead meaningful lives, find new meanings as a result of illness, are relatively not distressed, and are emotionally expressive and assertive. HIV-associated dementia, which is reversible in its early stages, appears to be closely related to the action of proinflammatory cytokines, particularly tumour necrosis factor, on neurones. Psychiatric symptoms, as well as cognitive defects, probably also cytokine induced, also occur in conjunction with HIV infection (primarily of microglia) of the brain they include apathy, withdrawal, psychosis, and regressive behaviours.

Methods based on relative pairs

The underlying principle of the affected sib-pair approach is simple. For any given locus the probabilities that siblings share 0, 1, or 2 alleles that are identical by descent from their parents is respectively , , . On the other hand, if both members of a sib pair are affected by the same disease and we are studying a locus close to a gene that confers susceptibility to that disease, there will be increased allele sharing. This will occur irrespective of the mode of transmission of the susceptibility gene and hence simple non-parametric statistics can be used to test whether there is any perturbation of the expected identical-by-descent proportions. Affected sib-pair methods are therefore robust and are now generally considered to be the method of choice in detecting linkage in oligogenic or polygenic disorders. In order to be certain that a pair of siblings share alleles identical by descent, one needs to know their parents' genotypes. Otherwise it could be that a shared allele...

Neurobiology of learning and memory

The important observation here is that genetic approaches on their own do not tell us how genes shape behaviour. In fact they often raise more questions than they answer, and this has implications for the hopes placed in positional cloning as a method of unravelling the biology of the mind. Accessing the neural correlates of mood disorders and psychosis or normal behavioural and cognitive traits appears possible by using the positional candidate cloning strategies described above. But, even with the genes in our hand, we may be no wiser about what they do. The detailed functional assays described above for memory have only been possible because so much was already known about its anatomical, cellular, and molecular basis.

The molecular basis of complex disorders

We do not know the molecular basis of any common psychiatric disorder, but it is almost certain that we will before long. Loci that determine susceptibility to psychosis, mood disorders, and personality disorders are being mapped, despite fluctuating levels of agreement between research groups. Once genes are identified, there is every reason to expect that subsequent genetic investigations will be equally daunting, as has been explained in the context of the neurobiology of learning and memory. The complex genetic basis of disorders with simple patterns of inheritance suggests that understanding complex inheritance will be, quite simply, very difficult.

Chapter References

Molecular genetic studies of schizophrenia. Cold Spring Harbor Symposia on Quantitative Biology, 61, 815-22. 3. Karayiorgou, M. and Gogos, J.A. (1997). A turning point in schizophrenia genetics. Neuron, 19, 967-79. 27. Bowen, T., Guy, C.A., Craddock, N., et al. (1998). Further support for an association between a polymorphic CAG repeat in the hKCa3 gene and schizophrenia. Molecular Psychiatry, 3, 266-9. 28. Odonovan, M.C., Guy, C., Craddock, N., et al. (1995). Expanded CAG repeats in schizophrenia and bipolar disorder. Nature Genetics, 10, 380-1. 29. Odonovan, M.C., Guy, C., Craddock, N., et al. (1996). Confirmation of association between expanded CAG CTG repeats and both schizophrenia and bipolar disorder. Psychological Medicine, 26, 1145-53. 62. Karayiorgou, P., Morris, M.A., Morrow, B., et al. (1995). Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. Proceedings of the National Academy of Sciences of the...

Psychophysiological parameters

In general, the search for unique biological markers of psychiatric diagnoses has produced disappointing results. A good diagnostic marker is one that possesses sufficient sensitivity (i.e. high detection rate of a specific disease) and specificity (i.e. strong discrimination between a specific disease and other diseases). Although psychophysiological research has discovered a variety of deviations in psychiatric populations, ranging from an excess of fast EEG activity in alcoholism to abnormal eye-tracking movements in schizophrenia 3,38 none of these deviations satisfy the criteria for being good markers. Apparently, the organizing principle behind these deviations is quite different from that of the Diagnostic and Statistical Manual of Mental Disorders (DSM). This has led some authors to conclude that we should stop looking for biological markers of the nosological categories listed in the DSM. After all, there is no reason to treat the taxonomy provided by the DSM as the gold...

Treatment Of Parkinsons Disease By Severity Of Symptoms

For patients older than 70 years or those with any cognitive decline, employ levodopa therapy. Not only is there less need for a dopa-sparing strategy in these elderly patients, they are more susceptible to confusion, psychosis, or drowsiness from other antiparkinson drugs, including dopamine agonists. Levodopa provides the greatest benefit at the lowest risk of these adverse effects, compared to the others.

Secular changes in incidence

This refers to the rise and fall of diseases in populations, with the possibility of making projections into the future. For example, there is some evidence that schizophrenia has been dropping in incidence and becoming more benign in its clinical course, (8) it is possible that depressive disorder has become more frequent in persons born since the Second World War(9l0) (the suicide rate of young persons has indisputably increased in many industrialized countries), it is likely that eating disorders have increased in frequency in some industrialized countries, and it is certain that the use of heroin and the AIDS epidemic with its neuropsychiatric sequelae are new arrivals and will be a continuing burden.

The search for causes

In this, the focus moves from the population back to the individual. For example, if the annual incidence rate for schizophrenia is known in a population and if this information is age-specific, it is possible to estimate the probability that a person of a given age will develop this disorder within the next year. This is the base rate, before one starts to consider risk factors such as family history. Next, by aggregating data on the course of schizophrenia, it is possible to estimate the chances of recovery for persons who are currently having their first episode. The common principle is that data based on large numbers of persons are used to make probability estimates for individuals.

Nonignorable nonresponse

The other occasion when non-response is a problem is in longitudinal studies, where a sample is followed over several years. If a disorder with an increased mortality is the topic, such as dementia or schizophrenia, it is recognized that some cases will be lost at follow-up. This means that those who are successfully re-examined are a survival lite and are different in important ways from the original cohort. These distortions could lead to mistaken conclusions if the losses are not allowed for. Various techniques have been developed to handle these difficulties, including Bayesian methods which adjust final estimates on the basis of prior knowledge. (19

Specifying the disorders Diagnostic categories

The epidemiology of mental disorders could have made no real progress without methods for specifying the disorders to be investigated, then measuring these, so that research on, say, depression or schizophrenia can be comparable between sites, within and between countries. Whether the study is at the level of the community, primary healthcare or mental health services, it is essential to specify which symptoms or which diagnoses are to be studied. Having consistency in diagnosis has been made much easier through the development of the diagnostic criteria now in wide international use.

Standardized psychiatric interviews

The Schedule for Clinical Assessment in Neuropsychiatry (SCAN) belongs to the first type. It is the successor to the groundbreaking Present State Examination ( PSE) developed by Wing et al.(39) and now revised(40) for the World Health Organization. SCAN is a clinician's instrument because it requires familiarity with the phenomenology of mental disorders. It assumes that the interviewer is comfortable in examining persons with a mental disorder. In complete contrast to interviews for use by laypersons, the clinician asks the main question, but is allowed to probe with further questions if necessary, before deciding if a symptom is present or not. The correct use of SCAN requires formal training in one of the designated centres around the world. SCAN has a number of modules, each dealing with a group of disorders such as anxiety states, affective disorders, substance abuse, or psychoses. It is available from the World Health Organization.

Molecular genetics and epidemiology

It has long been recognized by psychiatric epidemiologists that the addition of biological measures would be theoretically desirable, but these have not been highly practicable for administration to large numbers of persons in field surveys. The situation has recently changed and exciting new opportunities have become available. These lie in the unprecedented advances being made in molecular genetics. What has become available is a new set of predictor variables in the form of genotypes. It is not a matter of psychiatric epidemiology turning its back on psychosocial variables. Instead, genes can be assessed in their interaction with a full range of experiential and social factors. Two complementary strategies are being followed. The first is a continuing search for genes associated with discrete diseases such as bipolar affective disorder or schizophrenia. The second strategy is quite different to search not for genes that may cause or be directly related to disorders, but for genes...

Nineteenth century psychiatry

Kraepelin's important differentiation of manic-depressive illness from dementia praecox (schizophrenia) did not begin to be defined until 1896. Asylums contained patients suffering from many varieties of psychiatric illness who had nothing in common with one another except their inability to comply with the standards of behaviour demanded by society.

From drive theory to object relations

Psychoanalysis started its life as a drive theory. By what means, Freud asked, did the instinctual life of the infant become tamed in the process of development so that the end result was the civilized man and woman of adult society To this he had two sets of answers. The first, roughly, was repression and sublimation. In the Oedipal situation the child experiences sexual desire for the opposite-sex parent. These feelings arouse anxiety ('castration anxiety'), and so are repressed, or diverted into harmless exploratory and creative sublimatory activities. If, however, the process of repression is excessive the consequence in adult life is emotional inhibition. When repression is insufficient, anxiety-based or psychosomatic disorders result, or, ultimately, psychosis. A second answer, coming later, and forged in the face of the horrors of the First World War, was to suggest that 'civilization' was only skin deep. Here Freud invoked the death instinct and regression. Eros, the love...

Applications of psychodynamic thinking to diagnosis and treatment Dynamic pharmacotherapy

Non-compliance is one of the most challenging problems facing psychiatric practitioners. After 12 weeks of antidepressant prescription, only 40 per cent of patients were complying with the medication as prescribed.(33) In patients with bipolar illness, up to 60 per cent of patients may be non-compliant with lithium carbonate. (34) In one study of schizophrenia, Weiden et al.3) found that 74 per cent of schizophrenic outpatients became non-compliant with their neuroleptic regimen within 2 years of discharge from the hospital. Overall, only about one-third of patients comply adequately with medications, one-third comply somewhat, and one-third are non-compliant.(36)

Diagnosis and differential diagnosis

It is unusual for patients with delirium to seek medical attention themselves the main exception being the alcoholic who notices the emergence of visual hallucinations whilst withdrawing. Rather, drowsiness or disturbed behaviour will alert others. Disturbed behaviour may include agitation at the presence of delusions or hallucinations, or the expression of false ideas, for example that a carer or family member is trying to harm them. The presence of a diminished level of consciousness may be obvious in some cases, but can easily be missed if it is mild and not associated with overactive behaviour disturbance. A common presentation to liaison psychiatry is for general hospital ward staff to refer a patient as ' psychotic', on the basis of apparent delusions or hallucinations. The task here includes distinguishing a new episode of functional psychosis (uncommon) from delirium (common in this situation).

Diagnosis of delirium

There are numerous assessment scales, some intended for routine clinical testing by non-specialists. (8) An example of a brief assessment is the Cognitive Test for Delirium.(9) However, only two of the scale's attributes (visual attention span and recognition memory for pictures) were able to distinguish delirium from dementia, schizophrenia, and depression (p 0.0001) and delirium from moderate to severe dementia (p 0.0002). This confirms the importance of testing attention and short-term memory in this group. Special investigations (such as electroencephalography (10)) have little role in the diagnosis of delirium itself. Their main role is in identifying the underlying cause of delirium (see above), especially in making sure that treatable causes have been excluded.

Neuropsychiatry symptoms

Psychosis Psychotic symptoms occur in many patients, although, as with depression, the difficulty in determining the presence of delusions or hallucinatory experiences in the moderately to severely demented gives rise to a very wide range of frequency rates. Few studies have been able to determine the rates of psychosis in community-dwelling, fully representative samples of patients with AD. However, of those known to, largely, psychiatric services, between 10 and 50 per cent suffer from delusions and between 10 and 25 per cent experience hallucinations. (14,1 and .6) Delusions are frequently paranoid and the most common delusion is one of theft. In the context of the confusion and amnesia of dementia, it is easy to appreciate how the experience of mislaying an object becomes translated into conviction of a theft. Other patients become convinced that someone, often a family member, is trying to harm them. Various factors have been associated with psychosis in AD, but few have been...

Advice about management

Until safe and effective medications become available, there is no doubt that the mainstay of clinical management is to educate patients and carers about the nature of their symptoms and to suggest coping strategies. The clinician must ascertain which symptoms are most troublesome for the sufferer and explain the risks and benefits associated with changes in medication. (33) In these circumstances where the clinician is walking a therapeutic tightrope between parkinsonism and psychosis, the best outcome is invariably a compromise between a relatively mobile but psychotic patient and a non-psychotic but immobile individual. The patient and his carers may only be able to decide which is the lesser of these evils after experiencing both states.

Differential diagnosis

Several other diseases classified as movement disorders include all the features of the subcortical triad. They often have an autosomal dominant inheritance pattern, and some are caused by expansion of unstable trimeric repeat sequences. These include Fahr' syndrome (calcification of the striatum), some forms of spinocerebellar degeneration, chorea acanthocytosis, and dentato-rubral-pallido-lusian atrophy ( DRPLA). The latter two disorders, while much rarer than Huntington' disease, can look so similar that they can only be diagnosed confidently by genetic testing (in the case of DRPLA) and by a blood smear for acanthocytes (in the case of chorea acanthocytosis). The most common movement disorder that resembles Huntington' disease is tardive dyskinesia. Patients with Huntington' disease occasionally have several years of a schizophrenia syndrome before the movement disorder begins. If they have been treated with neuroleptics, the involuntary movements of Huntington' disease are often...

Head injury in children

Children often sustain a bilateral prefrontal injury, which may explain the deficits in concentration, controlling impulsivity, and self-monitoring. The commonest psychiatric disorders that follow childhood head injuries are personality changes, attention-deficit hyperactivity disorder, and obsessive-compulsive disorder. (62 Children who develop attention-deficit hyperactivity disorder after head injury tend to demonstrate less hyperactivity than is seen in the idiopathic form of this disorder. In the long term the head-injured child may be at increased risk of developing schizophrenia. Children are more likely to develop post-traumatic epilepsy than adults.

FNeuropsychiatry Disturbances

Disturbances of the mind or psyche may produce neuroses, psychoses, or character and behavior disorders. Such disturbances may or may not be inherited the environment, childhood experiences, and many other factors have a bearing on the production of psychiatric disturbances.