Psychoses Ebooks Catalog

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


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Author: Ronen David
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Approaches Primarily Targeting Psychosis 41 Dopamine D3 receptor antagonist

Schizophrenia is recognized as a multifactorial disease, but the dopamine hypothesis remains a prevailing theory to describe the disorder 98 . Most of the available evidence suggests that dopamine D3 receptor antagonists may be effective anti-psychotic agents, although some studies have suggested potential efficacy against the negative and cognitive symptoms of schizophrenia as well 99 . It is also believed that a selective compound for D3 vs. D2 should afford an agent with lower EPS potential 100,101 . The D3 receptor is primarily located in the limbic brain areas (islands of Calleja, ventral striatum nucleus accumbens, dentate gyrus and striate cortex), regions implicated in schizophrenia. The medicinal chemistry of selective D3 antagonists continues to evolve 102 , with several recent reports of selective agents. Additional research around the tetrahydroisoquinoline series (SB-277011) of selective D3 antagonists continues to appear in the literature. The tetra-hydrobenzazepine,...

Neurochemistry Of Schizophrenia And Mechanisms Of Action Of Antipsychotics

To a focus on dopaminergic mechanisms of action for antipsychotics. In 1963 Carlsson and Lindqvist1 reported that antipsychotics increased turnover of brain dopamine, and suggested that this was in response to a functional 'blockade' of the dopaminergic system. Creese and colleagues2 demonstrated that the affinity of a wide range of antipsychotics to dopamine D2 receptors was proportionate to their clinical potency (Figure 4.1). Further evidence for the dopamine hypothesis is that amphetamines, which increase dopamine release, can induce a paranoid psychosis and exacerbate schizophrenia and that disulfiram inhibits dopamine hydroxylase and exacerbates schizophrenia3,4. Initial positron emission tomography (PET) studies of D2 receptor densities in drug-naive and drug-free patients with schizophrenia, using different tracers, were equivocal, with one group showing a marked increase in receptor density and

Pharmacotherapy As Maintenance Treatment In Schizophrenia

Although it is widely accepted that antipsychotic medication is the mainstay of treatment in acute schizophrenia, its role in long-term maintenance has been more contentious. Nevertheless, the importance of maintenance drug therapy in the treatment of chronic schizophrenia has been evident since the early 1960s. Initial studies indicated that between one-half and two-thirds of patients with schizophrenia who were stable on medication relapsed following cessation of maintenance pharmacological therapy, compared with between 5 and 30 of the patients maintained on medication28-30.

The Risk Factor Model Of Schizophrenia

It is often said that schizophrenia is a disease of unknown etiology. This is no longer true. Schizophrenia is like other complex disorders such as ischemic heart disease, which have no single cause but are subject to a number of factors that increase the risk of the disorder. Some of the risk factors for schizophrenia are summarized in Figure 2.4. Schizophrenia, however, differs from disorders such as ischemic heart disease in that we do not understand the pathogenic mechanisms linking the risk factors to the illness, i.e. we do not understand how the causes 'cause' schizophrenia.

Course And Outcome Of Schizophrenia

The in-patient psychiatric population has fallen dramatically since the 1950s in Western countries, when effective antipsychotic drug treatments first became available (Figure 1.17). However, the outcome of schizophrenia, even with treatment, remains variable (Figure 1.18 and Table 1.1)11-17. Longitudinally, the typical course of chronic schizophrenia is described in Figure 1.1918. Schizophrenia also carries a high mortality. Rates of suicide in follow-up studies vary from about 2

Functional Imaging Of Formal Thought Disorder In Schizophrenia

Figure 3.15 PET data have been mapped onto a normal magnetic resonance image of a brain in standard stereotactic space, sectioned to provide transverse, coronal and sagittal views. The left side of the brain is shown on the left side of the image. The images show positive correlations between the severity of positive thought disorder and regional cerebral blood flow at the junction of the left parahippocampal and fusiform gyri (marked by cross hairs), and in the anterior part of the right fusiform gyrus. Figure reproduced with permission from McGuire PK, Quested DJ, Spence SA, et al. Pathophysiology of 'positive' thought disorder in schizophrenia. Br J Psychiatry 1998 173 231-5 Figure 3.15 PET data have been mapped onto a normal magnetic resonance image of a brain in standard stereotactic space, sectioned to provide transverse, coronal and sagittal views. The left side of the brain is shown on the left side of the image. The images show positive correlations between the severity of...

Pet Schizophrenia D2 Occupancy

Pet Scan Antipsychotic

Clozapine treated patient with schizophrenia Typical antipsychotic-treated patient with schizophrenia Figure 4.2 Three single photon emission tomography (SPET), scans of striatal D2 and D2-like receptor availability at the level of the basal ganglia. In the scan on the left from a healthy volunteer there is no receptor occupancy and therefore 100 receptor availability for the binding of the D2 receptor tracer 123I IBZM. The scan on the right is from a patient with schizophrenia receiving a typical antipsychotic. The bright areas from the left hand scan indicating high receptor density are not evident on the right-hand scan as the antipsychotic is occupying the majority of the receptors and preventing the tracer from binding. Unfortunately despite this high level of occupancy this patient has failed to respond to treatment. The central scan is from a patient receiving clozapine, although the striatum are not as 'bright' as in the healthy volunteer they are visible. This scan indicates...

Cannabis Consumption At Age 18 And Later Risk Of Schizophrenia

Cannabis Schizophrenia Age Risk

The morphological abnormalities that have been reported in schizophrenia are consistent with a neurodevelopmental event occurring in fetal or early development. Some believe that the onset of frank psychotic symptoms reflects the delayed sequelae of an earlier developmental aberration, which is then expressed as the brain continues to develop in adolescence and adult life - sometimes termed the 'doomed from the womb' view. Delayed emergence of abnormal behavior following lesions sustained during early development is a well recognized phenomenon, and is seen, for example, in animal models where ventral hippocampal lesions, initially 'silent', are followed by hyperactivity and increased responsiveness to stressful stimuli and to dopamine blockade as the animal matures. The inherited neurodevelop-mental disease metachromatic leukodystrophy is more likely to be associated with schizophreni-form symptoms if the clinical onset is in adolescence. In this case, as in schizophrenia, late...

Distinguishing Schizophrenia from Dementia

While the onset of schizophrenia typically occurs in adolescence or young adulthood, schizophrenia may also occur in late life. Schizophrenia with a late life onset is often called paraphrenia, and may occur in individuals who have a history of eccentricity and are socially isolated. However, dementia can also produce hallucinations and delusions, and thus, like depression, it is important to distinguish between the two conditions. Given that late-life onset of schizophrenia is relatively rare, very few systematic studies have been conducted. However, neuropsychological assessment studies have been done, and, in many cases, it is possible to rule out dementing processes.

Schizophrenia Brain X-ray

Lateral Ventricles Schizophrenia

Figure 3.2 Mean ventricle brain ratio (VBR) in controls and patients with schizophrenia from a total of 39 separate studies. The diagonal line indicates the line of equality. Thus, this figure demonstrates that no matter which diagnostic system or method of measuring brain volume is used, patients with schizophrenia do have larger ventricles than controls. Figure reproduced with permission from Van Horn JD, McManus IC. Ventricular enlargement in schizophrenia. A meta-analysis of studies of the ventricle brain ration (VBR). Br J Psychiatry 1992 160 687-97 Figure 3.3 Ventricular size in monozygotic twins discordant for schizophrenia. Coronal magnetic resonance images of twins discordant for schizophrenia show lateral ventricular enlargement in the affected twin. Figure reproduced with permission from Suddath RL, Christison GW, Torrey EF, et al. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med 1990 322 789-4 Figure 3.3 Ventricular...


Psychotic disorders are characterized by delusions, hallucinations, disorganized speech, or disorganized or catatonic behavior. The major psychotic disorders include schizophrenia, schizophreniform disorder, schizoaffective disorder, or delusional disorder. The most widely prescribed antipsychotic drugs are referred to as neuroleptics. The major antipsychot-ics are tricyclic phenothiazines, thioxanthenes, di-benzepines, butyrophenones, benzamides, clozapines, and risperidone. Most drugs of these types block D2 dopaminergic receptors and inactivate dopamine neu-rotransmitters in the forebrain. Some of these medications also affect D1 dopaminergic, 5-HT 2 sero-tonergic, and a-adrenergic receptors. Unfortunately, none of these medications cures psychoses, each one helps only some patients, and there are deleterious side effects, including akathisia, rigidity, tremors, and other neuromuscular effects. In addition to these ma


Schizophrenia is not split personality. The 'split' suggested by 'schizo' is between the person and what is normally considered reality, rather than something within the person. It can take many forms, with each instance being unique, but always involves some or other disorganisation of personality, distortion of reality (through hallucinations, delusions and blunted emotion), and usually means an inability to function in daily life. It seems to occur in most cultures that have been studied and affects about 1 per cent of people, equally divided between the sexes. Both thought process and content may be disturbed in schizophrenia. Words may be said in a very loosely associated way that makes very little sense to anyone else and the thought sequence might be influenced by the sound of the words rather than by their meaning, gleaning, leaning, weaning, dreaming, beaming, scheming, and so on. This seems to be largely due to an inability to focus attention and in so doing cut out whatever...

Signs And Symptoms Of Hyponatremia

In evaluating hyponatremic patients, it is important to assess whether or not the patient is symptomatic, because symptoms are a better determinant of therapy than the absolute value itself. Most patients with serum sodium values above 125 mEq L are asymptomatic. The rapidity with which hyponatremia develops is critical in the initial evaluation of such patients. In the range of 125 to 130 mEq L, the predominant symptoms are gastrointestinal ones, including nausea and vomiting. Neuropsychiatric symptoms dominate the picture once the serum sodium level drops below 125 mEq L, mostly because of cerebral edema secondary to hypotonicity. These include headache, lethargy, reversible ataxia, psychosis, seizures, and coma. Severe manifestations of cerebral edema include increased intracerebral pressure, tentorial herniation, respiratory depression and death. Hyponatremia-induced cerebral edema occurs principally with rapid development of hyponatremia,...

History And Classification

Schizophrenia is arguably the most severe of the psychiatric disorders. It carries a lifetime risk of around 0.5-1 , and its early onset and tendency to chronicity mean that its prevalence is relatively high. Disability results particularly from negative symptoms and cognitive deficits, features that can have a greater impact on long-term functioning than the more dramatic delusions and hallucinations which often characterize relapses. The social and economic impact of the illness is enormous, and its impact on sufferers and their families can be devastating. Although descriptions of people who may have had schizophrenia-like illnesses can be found throughout history (Figure 1.1) the first comprehensive descriptions date from the beginning of the 18 th century (Figures 1.2 and 1.3)1. The modern concept of schizophrenia was first formalized by the German psychiatrist Emil Kraepelin (Figure 1.4)2,3 at the turn of the 20th century. Kraepelin, who drew on contemporary accounts of...

Metabotropic glutamate receptors

The metabotropic glutamate receptors are members of the G-protein coupled receptor family. There are eight metabotropic receptors grouped into three families. Group I receptors (mGluR1 and 5) are linked to Gaq and increase phosphotidylinositol turnover to elevate intracellular Ca2+. Both groups II (mGluR2 and 3) and III (mGluR4, 6, 7 and 8) are negatively linked to adenylyl cyclase via Gai. Group II mGluRs are located presynaptically on glutamate terminals where they may act as autoreceptors regulating glutamate release in vivo. Unlike the group II and III receptors, group I (mGluR1 and mGluR5) are primarily postsynaptic and their effect on intracellular Ca2+ allows them to modulate the activity of other signaling pathways. Each of these receptor subtypes has potential utility for the treatment of schizophrenia. Merck has described three series of mGluR5 potentiators. The benzaldazine series, exemplified by DFB (10), has been reported to exhibit the full spectrum of negative, neutral...

Emerging Mechanisms And Conclusions

Schizophrenia is the focus of intense preclinical and clinical research and is an area in which discoveries in the basic sciences are rapidly reviewed in the context of their potential therapeutic implications. Although it is not feasible to cover either the depth or breadth of the available subject matter in a review of this size, we will conclude with a brief mention of potential targets awaiting the development of the necessary biology and chemistry to establish their importance in this disease. Phosphodiesterases are a small gene family now under active evaluation for their potential as CNS drug targets. PDE4 inhibitors such as rolipram are known to enhance LTP and to improve performance in animal models of cognitive function 117 . Bayer has recently reported that a selective PDE2 inhibitor, Bay 60-7550, increases cGMP in hippocampal and cortical cultures, enhances LTP and improves performance in a novel object recognition task 118 . PDE10A is a dual substrate phosphodiesterase...

Dopamine D1D5 receptor agonists

Many of the cognitive abnormalities in schizophrenia are similar to those resulting from damage to the prefrontal cortex (PFC) including attentional abnormalities, problems in reasoning and judgment and working memory deficits 69 . Together with evidence of reduced prefrontal dopaminergic function in schizophrenia, these observations have lead to the view that positive symptoms are due to subcortical hyperdopaminergia, while cognitive deficits are the results of hypodopaminergia in the PFC 70 . There are in fact data indicating that reduced dopaminergic activity in the PFC may cause over activation of the subcortical dopamine system 71,72 . Clinical reports that PFC D1 receptors are upregulated in schizophrenia due to a localized decrease in dopaminergic activity and that D1 receptor antagonists aggravate psychotic symptoms, are consistent with this hypothesis 73,74 . Loss of efficacy with repeated drug administration has hampered the development of D1 agonists for the treatment of PD...

Alpha7 Nicotine acetylcholine receptor agonists and positive allosteric modulators

Alpha7 Nicotinic Acetylcholine Receptor

It is believed that neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a variety of attention and cognitive processes 47 . These Ca2+ permeable, ligand-gated ion channels modulate synaptic transmission in key regions of the CNS involved in learning and memory, including the hippocampus, thalamus and cerebral cortex 48-50 . Among the nAChRs, physiological, pharmacological and human genetic data suggest a link between the loss of a 7 nAChR and sensory gating deficits in schizophrenia 51 . Conversely, improvements in sensory processing are thought to correlate with enhanced cognitive performance in animal models and in patients with schizophrenia 52 , suggesting a role for selective a7 nAChR agonists in treatment of cognitive dysfunction in schizophrenia. currents in hippocampal interneurons. The compound also demonstrates robust in vivo activity in an amphetamine-induced P50 gating deficit model (0.1-3 mg kg, i.v.). This compound represents a new class of ligands that...

Geographical Variations In Incidence

Although diagnosis still depends on the presence of combinations of symptoms and the course of illness, and diagnostic practice may vary to some extent from country to country, there is a core group of patients who fulfill all definitions and would be diagnosed as suffering from schizophrenia anywhere in the world (Figure 1.8). Both ICD-10 and DSM-IV identify a number of subtypes of schizophrenia. In clinical practice, a distinction is also often made between acute and chronic schizophrenia. A third way of thinking about the varied clinical picture seen in schizophrenia is in terms of syndromes (Figure 1.9). Unlike subtypes, syndromes do not

Clinical Presentation And Symptomatology

The family and personal history may offer important etiological clues. There may be a family history of schizophrenia, complications in pregnancy or birth, or a personal history of childhood problems. Recent studies, including the follow-up of the British 1946 birth cohort10, have suggested that children who later develop schizophrenia are more likely to have a history of developmental delay, as well as slightly lower IQ and educational achievements than other children (Figure 1.10). They are also more likely to have interpersonal and behavioral difficulties. Mothers may describe their pre-morbid personality as having shown emotional detachment 'preschizophrenic' children may appear cold and aloof, avoiding play and engaging in solitary occupations. Some may be prone to temper tantrums, tend to avoid competition, have odd ideas and seek refuge in fantasy. These characteristics are also over-represented in the families of schizophrenics, although they do not reliably...

Efficacy Of Antipsychotics In The Acute Phase Of Treatment

Johnstone and co-workers25, showed that pimozide was antipsychotic (i.e. reducing the positive symptoms of psychosis) in patients with 'functional' psychosis, regardless of whether the patients had prominent manic or depressive symptoms or were euthymic. This proved that 'neuroleptics', as they were then popularly called, were truly antipsychotic rather than simply antischizo-phrenic (Figure 4.12). Figure 4.13 The upper line represents the percentage of patients with schizophrenia who remained stable after gradual reduction of antipsychotic medication. The lower line represents patients whose medication was abruptly stopped. These results indicate that abrupt cessation of antipsychotic medication produces a much higher risk of relapse in schizophrenia than a gradual reduction. Figure reproduced with permission from Viguera AC, Baldessarini RJ, Hegarty JD, et al. Clinical risk following abrupt and gradual withdrawal of maintenance neuroleptic treatment. Arch Gen Psychiatry 1997 54 49-55

Behavioral Dysfunction

Classical antipsychotic drugs that potently block dopaminergic receptors can ameliorate psychotic symptoms but worsen parkinsonism, at times seriously enough to require levodopa (84). Better results in treating psychosis have been obtained with the atypical neuroleptics, possibly owing to their predominant antiserotoninergic rather than antidopaminergic activity. An extensive chart review revealed that 90 of DLB patients had partial to complete resolution of psychosis using long-term quetiapine, although in 27 motor worsening was noted at some point during treatment (85). A large, randomized blinded trial found that olanzapine (5 or 10 mg) reduces psychosis without exacerbating parkinsonism (86). Relatively small doses of clozapine have also been used successfully for the relief of paranoid delusions, psychosis, and agitation, albeit at the risk of agranulocytosis (84). Indeed, caution is generally warranted in using neuroleptics, since sedation, confusion, immobility, postural...

Differential diagnosis

The main differential diagnosis of delirium is from a functional psychosis (such as schizophrenia and manic depression) and from dementia. Functional psychoses are not associated with obvious cognitive impairment, and visual hallucinations are more common in delirium. Dementia lacks the acute onset and markedly fluctuating course of delirium. Fleeting hallucinations and delusions are less common in dementia. It is important to note that delirium is commonly superimposed on a pre-existing dementia.

Frequency Of Life Events

Figure 2.13 The rate of life events is increased in schizophrenia, although the effect is not as great as in depression. Figure reproduced with permission from Bebbington P, Wilkins S, Jones P, et al. Life events and psychosis. Initial results from the Camberwell Collaborative Psychosis Study. Br J Psychiatry 1993 162 72-9 It is estimated that 20-50 of the population with schizophrenia in Western countries may qualify as substance abusers or 'dual-diagnosis' patients. Such patients have a higher use of services and worse outcome than patients who are not abusers they are more likely to be hospitalized and more likely to relapse. Patients with schizophrenia seem to be more vulnerable to significant harm at relatively lower levels of substance use. As substance misuse is so prevalent in the West, this is an area where secondary prevention of relapse could be focused. Psychosocial factors appear to contribute to both the onset and the relapse of schizophrenia. The best documented are...

Generalized Psychiatric Samples

Apart from Gruzelier and Hammond's (1976) investigation, most Wechsler studies of previously defined psychiatric populations seem to produce V P profiles. Todd, et al. (1977), identified a 4J4 point V P profile for their control group of psychiatric patients (N 78, including 17 with depression and 15 with some form of psychosis). Page and Steffy (1984) likewise found high Verbal-low Performance patterns to characterize their sample of 429 adult inpatients with psychiatric disorders, which earned a mean V-IQ 94.3 and a mean P-IQ 88.9 (+5.4 discrepancy). The 6- point Verbal superiority for Page and Steffy's group of patients with schizophrenia was reported previously, but these investigators also observed a 7 J4-point V P profile for 46 patients described as neurotics, although they found a V-P difference of less than 1 point for 108 inpatients with personality disorders. In contrast to these V P profiles, Hawkins, Sullivan, and Choi (1997) found a P V profile for a mixed psychiatric...

Why do I go crazy with steroids

In most patients, there is an initial feeling of well-being induced by steroids, particularly at lower doses. However, mood elevation often is replaced by irritability with continued administration, particularly at higher doses. Psychotic behavior may follow simple mood elevation. Frank manic psychosis occurs in a small proportion of patients treated with steroids by any route of administration. Mood elevation can be managed using lithium carbonate and diazepam. Although it is the more common response, other patients may become depressed. ACTH may also occasionally be associated with these mood changes.

Management Of Neuropsychiatric Symptoms

In light of the high prevalence and clinical importance of neuropsychiatric symptoms in patients with parkinsonian disorders, relatively few adequately designed clinical trials have been reported. In a recent evidence-based review of management of PD, including psychosocial treatments, produced by The Movement Disorder Society (112), the only neuropsychiatric treatment that was concluded to be efficacious was the atypical antipsychotic agent clozapine for hallucinations psychosis. In addition, the tricyclic antidepressant nortriptyline was considered to be likely efficacious. Too few or methodologically inadequate studies precluded positive conclusions for other treatments. To our knowledge, only nine randomized, placebo-controlled studies of neuropsychiatric symptoms in parkinsonian disorders have been reported four trials with cholinergic agents in DLB (rivastigmine) (113), PD (donepezil) (114), and PSP (donepezil and RS-86, a cholinergic agonist) (115,116), two trials with...

Diffuse Lewy Body Disease

Similar results were obtained by Simard, Rikum, and Myran (175). These authors compared the performance on the Benton Judgement Line Orientation Test of patients with DLB and predominant parkinsonism, with DLB and predominant psychosis, and with AD. For this purpose they analyzed errors as resulting from visual attention and visuospatial perception failures. The study did not find significant differences on the total score of the Benton Judgement Line Orientation Test. However, error analysis demonstrated that subjects with DLB and psychosis have more severe visual-perception (VH errors) impairments than subjects with DLB and predominant parkinsonian features, and AD subjects.

Depression as a Syndrome

Major depressive episode is the most common depressive syndrome. A syndrome is a configuration of symptoms that often occur together and constitute a recognizable condition. Although the presence of a major depressive syndrome is a necessary characteristic of major depressive disorder, it is not sufficient. The syndrome can occur for other reasons. For example, medications or drugs of abuse, as well as general medical conditions, can have direct physiological effects which can trigger the symptoms of a major depressive episode. Similarly, the loss of a loved one can result in this configuration of symptoms. In the latter case, unless the symptoms persist for longer than 2 months, or produce marked functional impairment, suicidality, or psychosis, they are considered to be part of the normal course of bereavement.

Pharmacological Treatment Of

Several open-label studies suggest that atypical antipsychotic agents can improve psychotic symptoms in DLB (125,126). However, DLB sufferers seem to be particularly vulnerable to a specific type of adverse reaction to neuroleptic agents. Patients develop severe parkinsonism, impairment of consciousness, autonomic instability, and frequently experience falls and a marked drop in their level of cognitive performance and functioning (127,128). Furthermore, even in DLB patients who do not experience severe neuroleptic sensitivity, there is some evidence that neuronal loss in the caudate and putamen may be exacerbated by neuroleptic treatment (129). Given the major concerns regarding severe neuroleptic sensitivity reactions, neuroleptic agents cannot be considered to be the first-choice management approach for neuropsychiatric symptoms, but may possibly still have a role in severe and intractable cases with psychosis.

Epidemiology And Implications Of Neuropsychiatric Features In Parkinsonian Disorders

Second, caring for a patient with a parkinsonian disorder is associated with considerable emotional, social, and physical distress (33-35). Neuropsychiatric symptoms of PD patients, such as depression, cognitive impairment, delusions, and hallucinations, have been found to be significant and independent contributors to the perceived burden in spouses of these patients (33). Third, a substantial proportion of patients with parkinsonian disorders are admitted to nursing homes (36). In addition to motor symptoms and functional impairment, neuropsychiatric symptoms such as cognitive impairment and psychosis have been found to be independent predictors of nursing home admission in parkinsonsian patients (37,38). Both higher need for care and increased caregiver burden may contribute to the relationship between nursing home admission and neuropsychiatric symptoms. Fourth, neuropsychiatric symptoms may increase the economic costs in patients with parkinsonism. In a recent study of patients...

Therapy of Extensive Disease

Daily monitoring of the patient should include examination of the abdomen and plain films of the abdomen daily or on alternate days. If symptoms do not improve with 5 days of IV steroids, such as Solu-Medrol at doses of 60 mg over 24 hours up to 40 to 60 mg each 8 hours, then proctocolectomy or IV cyclosporine should be considered. Although surgery may be the best alternative, some patients are unwilling to proceed with surgery, and IV cyclosporine (2 to 4 mg d) is a reasonable alternative for 7 to 10 days. Initial combined therapy with steroid and cyclosporine does not appear to be more advantageous than starting with steroids and later adding the cyclosporine, if needed. After the patient improves from the severe flare, AZA (2 to 2.5 mg kg) or 6-MP (1 to 1.5 mg kg) should be overlapped with oral cyclosporine (5 mg kg d) with intended blood levels of cyclosporine of 150 to 300 ng mL for 3 to 6 months. While the patient is on cyclosporine, antibiotic...

Concepts of Health and Disease

Yet where the structural tier of health and disease is concerned, it is worth remembering that even a completely normal diagnostic test does not definitively rule out the possibility of disease. The bone radiograph may be initially normal, and it is only a week later, after demineralization has taken place and some periosteal reaction has formed adjacent to the fracture that we are able to recognize a nondisplaced hairline fracture. Even our most sophisticated imaging studies may not show us the pathology. For example, a patient with severe psychosis may have a normal magnetic resonance imaging (MRI) exam of the brain. Conversely, there is no guarantee that every patient with an abnormality of diagnostic testing actually has the disease. A solitary pulmonary nodule may represent a granuloma, and not a lung cancer at all.

Multimodal neurosurgical strategies for the management of dystonias

In Japan, DYT-1 dystonia is not common because of genetic and racial factors, and the majority of our cases are adult onset idiopathic dystonia without family history. Some of them had a history of psychiatric problems treated with antipsychotic medication, and the symptoms may be classified as tardive dyskinesia, but response to pallidal DBS is generally the same as those without such a psychiatric history. We also experienced some cases of dystonias due to hereditary metabolic disorders such as Lesch-Nyhan syndrome and Hallervorden-Spatz syndrome with favorable results 9 . schizophrenia

Exposure To Obstetric Complications

Figure 2.9 Obstetric complications are more common in people with schizophrenia compared with controls. Patients with schizophrenia are especially likely to have suffered multiple complications Figure 2.9 Obstetric complications are more common in people with schizophrenia compared with controls. Patients with schizophrenia are especially likely to have suffered multiple complications Figure 2.10 Obstetric complications are a risk factor for schizophrenia in patients with a younger age of onset they do not seem to be involved in the etiology of late-onset schizophrenia. Those patients who suffered obstetric complications showed an earlier onset than patients who did not

Score On Wisconsin Card Sort Test

Figure 3.20 Wisconsin card sort test (WCST) in monozygotic twins discordant for schizophrenia. The WCST is a measure of executive function. In twins discordant for schizophrenia, performance on the WCST is uniformly impaired in the affected twin. Data from Goldberg TE, Torrey EF, Bigelow LB, et al. Genetic risk of neuropsychological impairment in schizophrenia a study of monozygotic twins discordant and concordant for the Figure 3.20 Wisconsin card sort test (WCST) in monozygotic twins discordant for schizophrenia. The WCST is a measure of executive function. In twins discordant for schizophrenia, performance on the WCST is uniformly impaired in the affected twin. Data from Goldberg TE, Torrey EF, Bigelow LB, et al. Genetic risk of neuropsychological impairment in schizophrenia a study of monozygotic twins discordant and concordant for the

Relevance Of The Chroniclowdose Mptp Monkey Model To Other Disorders

While the deficits in chronic-low-dose MPTP-treated monkeys described earlier in this chapter are strikingly similar in nature to those described in early Parkinson's disease patients, the frontal attentional executive function deficits observed in these animals have significant overlap with, and clinical relevance for, other disorders such as attention deficit hyperactivity disorder (ADHD) and schizophrenia in which frontostriatal dysfunction has been implicated. Schizophrenia is characterized by dysregulation of attention 49 . Four important domains of cognitive functioning have been described as impaired in schizophrenia attention, verbal fluency, working memory, and executive functioning 50 . Sustained attention appears to be a particular problem in schizophrenia that contributes to problems in other aspects of higher cognitive functioning 51 . Because of the apparent specificity of sustained attention to schizophrenia and its relationship to other important cognitive abilities,...

Environmental Influences

There is no doubt that there is a heritable component to the etiology of schizophrenia. It is equally clear that genetic predisposition is not the whole story. Concordance in MZ twins is only about 50 the rest of the variance must depend on the person's environment. These are often split into early and late environmental factors (Figure 2.4). 2.9). Meta-analyses show that exposure to obstetric complications roughly doubles the risk of later schizophrenia however, this effect only operates for schizophrenic patients who present before the age of 25 years obstetric complications are not involved in the etiology of late-onset schizophrenia (Figure 2.10)13-17. There has been a search to identify which particular obstetric complications are responsible. However, the evidence is that a range of prenatal and perinatal factors may be involved. Hypoxic ischemia has been particularly implicated in the pre- or perinatal period this can lead to intraventricular or periventricular bleeds,...

Classic Syndromes Primary Psychiatric Illness

First, dramatic, unlikely or even impossible physical complaints may of course be symptomatic of primary psychiatric illness. somatic preoccupations are common in both schizophrenia and major depression, and may range from a chronic sense of unwellness to the fixed conviction of a dread disease (acquired immunodeficiency syndrome, cancer), to bizarre ideas of infestation, or to deliberate implantation of foreign bodies or devices. The true anorexia of depression, as well as the odd and rigid eating patterns seen in schizophrenia, obsessive compulsive disorder and eating disorders, may lead to weight loss and delayed transit times suggestive of primary medical illness. indeed, some

Functional Brain Imaging

Functional brain imaging studies have used positron emission tomography (PET), single photon emission tomography (SPET) and, more recently, functional magnetic resonance imaging techniques (fMRI) to investigate regional cerebral blood flow (rCBF) and brain metabolism in schizophrenia (Figure 3.9)5. It was previously thought that a decrease in frontal blood flow and metabolism ('hypofronta-lity') was a constant feature of schizophrenia. However, this now appears to be a function of the cognitive load involved in the test that patients are carrying out at the time. For example, activation studies using 'frontal' tasks such as the Wisconsin

Adverse Events Of Atypical Antipsychotics

It is claimed that clozapine has an almost unique action against the negative symptoms of schizophrenia, out of proportion to its effect on positive symptoms86, but the evidence for this is by no means clear. Tandon and associates87 found that the improvement in negative symptoms covaried with the improvement in positive symptoms, and Hagger and co-workers88 found no improvement in negative symptoms. A more recent finding is that in comparison with haloperidol, clozapine had a significant effect on negative symptoms in patients with non-deficit schizophrenia, but not in those with deficit schizophrenia, i.e. those with enduring negative symptoms89,90. It has therefore been suggested that clozapine's apparently beneficial effect on negative symptoms may simply be a reflection of its reduced tendency to cause EPS91. The weight of current evidence suggests that

Transmetatarsal amputation

A 56-year-old man with type 1 diabetes and schizophrenia, was referred to the diabetic foot clinic for dry gangrene of his hallux, 2nd and 3rd toes (Fig. 8.28). The patient was new to our clinic, having been transferred from another hospital. The patient's medical history was quite remarkable he had recently been very ill, in ketoacidosis, with a blood sugar level 1200 mg dL (66.7 mmol L). The gangrenous changes in his toes developed during this episode, and appear to be related to a shower of emboli to his toes. Pedal pulses were present and Doppler studies were otherwise normal. He underwent a successful transmetatarsal amputation with an unremarkable postoperative course (Fig. 8.29a). A custom-made orthosis with a stump filler was provided for the patient for use in extra-depth therapeutic shoes (Fig. 8.29b). The patient is very satisfied with the results of his amputation and ambulates normally without a limp. This transmetatarsal amputation has been durable with no further...

C LDopa and Other Tracers

PET can also be used with other radiolabels so that receptor binding sites can be imaged. For example, F18 can be attached to L-dopa, a drug that binds to dopamine receptors. This fluorinated L-dopa can then be used to make images of dopamine system function. Such images have been used to study Parkinson's Disease, a disease of dopamine deficiency, and schizophrenia, a brain disorder treated with dopamine acting drugs. This kind of neuroimaging research has potential for predicting drug response of individual patients. For example, Buchsbaum and colleagues reported that schizophrenics with low GMR in some dopamine-rich brain areas (i.e., the basal ganglia) may show a good clinical response to a dopamine acting drug whereas a similar patient without low basal ganglia GMR will not respond to the same drug. In other studies, fluorinated cocaine has been used to image drug abusers to help understand the mechanism of addiction and, possibly, vulnerability to addiction. Many other...

Questions and possibilities

Which of the various explanations suggested to account for schizophrenia do you consider to be the most likely Have you ever experienced any of the splits with reality that characterise schizophrenia, even in minor form If you have, what do you think might have brought them about

Personality disorders

Personality disorders have a large classification to themselves. This is, perhaps, surprising since one might well ask what can possibly be wrong about a personality A personality simply is a personality. Sometimes, however, personality traits become highly maladaptive and inflexible, so much so that they seriously impair the person's ability to function in the normal world. Although they can be extraordinarily disruptive to the individual and to other people, personality disorders are, nevertheless, seen as not as extreme as disorders of mood or as those in the schizophrenic range. It is as if mood disorders, schizophrenia and DID are regarded as being outside of the person's control, whereas there seems to be some doubt about personality disorders.

Neuroimaging Findings And Normal Brain Function

Xenon blood flow, EEG, and CAT scan images have been used to characterize normal and abnormal brains for more than 30 years. PET research on normal brain function began about 1980 when controls were studied for comparisons to various brain disorders like schizophrenia and Alzheimer's Disease. For the last 10 years, many PET studies have studied only normal subjects performing a variety of tasks for the purpose of understanding normal cognition. Functional MRI has been used for this purpose only in the last few years but the use of fMRI is growing dramatically as more and more psychologists and neuroscientists gain access to study language processing, attention, reasoning, personality, emotion, learning and memory. Currently, many cognitive researchers and neuropsychologists favor fMRI or PET over topographic EEG, mostly because the latter is more limited to cortex assessment rather than whole brain, despite the temporal resolu-

Abnormal Illness Behavior

Consider four views of patients and their symptoms that may guide responses (McHugh and Slavney, 1998 Edwin, 2001). The viewpoint of disease assumes that the patient's complaints are caused by a broken body part or system this may imply either a disease of peripheral organs (inflammatory bowel disease or pancreatitis), a disease of brain (delusional depression, schizophrenia, dementing illnesses) or their interaction (metabolic encephalopathy). This is the arena in which physicians are most comfortable and effective, and in which referral or disposition becomes straightforward. The trait method focuses on temperamental attributes (like intelligence or dependency) that render individuals vulnerable to exaggerating, enhancing or otherwise distorting the problems and symptoms of illness. The viewpoint of behavior focuses attention on voluntary choices to sustain hunger or to eat, to remain sober or to drink and the intended and unintended consequences of these decisions. It becomes...

Human Diseases Associated with Aberrant Splice Site Selection Without Obvious Mutations

A number of diseases have been described that are associated with a change in alternative splicing patterns in the absence of mutations or alterations in trans-acting factors. For example, in schizophrenia, the alternative splicing patterns of the gamma2 subunit of gamma amino butyrate type A receptor (Huntsman et al. 1998), the N-methyl-D-aspartate (NMDA) R1 receptor, and the neuronal cell adhesion molecule (Vawter et al. 2000) were altered. Recent results show that the alternative splicing of tau exon 10 is significantly altered in sporadic Alzheimer's disease (Umeda et al. 2004 Glatz et al. 2006). Changes of alternative splicing patterns have been frequently reported to be associated with cancer development, e.g., Wilms' tumor, breast cancer, melanoma, and prostate cancer (Table 2). Furthermore, EST analysis demonstrates widespread changes of alternative splicing patterns in cancer cells (Xu and Lee 2003) when compared with normal cells. However, these changes have to be...

Sideeffects Of Conventional Antipsychotics

The rationale underlying the use of low-dose strategies is that significantly lower doses of medication are required for the maintenance, as opposed to the acute treatment, of schizophrenia. This assumes that all major treatment goals have been met for the patients by the time of dose reduction. The two major aims are to ensure that the stability of symptomatic improvement is at least maintained and to minimize the risk of neurological side-effects and secondary negative symptoms caused by higher doses of anti-psychotics, particularly typical antipsychotics.

Thomas A Widiger And Stephanie Mullinssweatt

The question of whether mental disorders are discrete clinical conditions or arbitrary distinctions along dimensions of functioning is a long-standing issue (Kendell, 1975), but its significance is escalating with the growing recognition of the limitations of the categorical model (Widiger & Clark, 2000 Widiger & Samuel, 2005). Indeed, in the last 20 years, the categorical approach has been increasingly questioned as evidence has accumulated that the so-called categorical disorders like major depressive disorder and anxiety disorders, and schizophrenia and bipolar disorder seem to merge imperceptibly both into one another and into normality . . . with no demonstrable natural boundaries (First, 2003, p. 661). In 1999, a DSM-V Research Planning Conference was held under joint sponsorship of the APA and the National Institute of Mental Health (NIMH), the purpose of which was to set research priorities that would optimally inform future classifications. One impetus for this effort was the...

Preliminary Phenotypic Screening

Behavioral assessment in mice has come a long way in the past century with increasing refinement of paradigms 24-27 . The behavioral phenotype of mice is complex consequently, these animals should first be evaluated on numerous behavioral domains that include the animal's general health and well-being, reflexive and motor capabilities, emotionality, anxiety, affective and social behaviors, consumma-tory responses, and learning and memory. Partially due to the use of mutant mice, the past decade has witnessed numerous advances in identification of molecular mechanisms that underlie a wide variety of behaviors in animals. Over the years, learning and memory processes have received the greatest emphasis for study. Investigators have produced many strains of mutants to examine the roles of different genes in cognitive behavior. However, the focus on this domain of behavior neglects the other possible responses for these animals, some of which may influence performance on cognitive tasks....

Borderline personality

The second of the more extreme personality disorders and one that has received considerable attention recently is the borderline personality. It is not very aptly named because it suggests that someone has a personality that is only acceptable in a borderline way. However, the borderline is between neurotic traits (extreme anxiety, emotional instability) and psychotic tendencies (as in schizophrenia).

Sinister Applications

In the 1930s and 1940s, a wide range of topics were analysed in half a dozen German institutes with the help of the Abwehrfermente 9 . There were tests for various forms of cancer the final objective was cancer therapy. Tests for psychiatric diseases such as schizophrenia were developed the Abwehrfermente were also used for effective shock treatment of psychotic patients. Tests were worked out to diagnose the various psychological types proposed by the psychiatrist E. Kretschmer 10 . (To test how patients dealt with fear, guns were fired behind their heads and pictures were taken one schizophrenic patient is quoted as saying over and over again We want poison gas why do they not give us poison gas ''). The Abwehrfermente were used by Abderhalden's son Rudolf 9 to diagnose various infectious diseases. They were even used to distinguish races of

Characteristic Profiles in Unique Populations

Clinicians have long searched for characteristic subtest profiles associated with brain dysfunction and psychopathology with the same zeal that medical researchers apply to the search for biochemical patterns of cancer or AIDS patients, or that psychiatrists apply to the behavioral patterns of mass murderers. Mostly, these quests have not been fruitful, not unlike the quests of other scientists. Unforeseen and often unknown complexities frustrated Wechsler's search for a subtest profile associated with organic brain syndrome or the search of others for patterns that are pathognomonic of schizophrenia, psychotic depression, and countless other disorders. However, the fact that the search for characteristic profiles for groups has usually been unsuccessful does not alter the value of a diversity of theoretical and clinical approaches for gaining true in

Clinical Psychopharmacology

Psychopharmacologically active agents (e.g., alcohol, opium) have been used for millennia to alter psychological state. Over the past 200 years, specific gases and chemicals have been identified (e.g., nitrous oxide, barbituric acid) that also alter consciousness and psychological state. It was not until the 1950s, however, that use of drugs to treat mental disorders and conditions became formalized and a focus of research and clinical attention. The dramatic reports in the early 1950s of chlorpromazine (Thorazine) to treat psychoses was a breakthrough that allowed previously uncontrollable patients to be cared for in a humane manner. This important development proved to be the genesis of clinical psychopharmacology as a central element in modern psychiatry and as a valuable adjunct to psychotherapy. No single pharmacological class is the panacea for the treatment of mental disorders. In fact, the identification and distinction among mental health disorders continues to be accompanied...

Research And Evaluation

Henry Bachrach, Robert Galatzer-Levy, Alan Skolni-koff, and Sherwood Waldron report the following in their review of psychoanalytic efficacy studies Robert Knight reviewed analytic case outcome research before the late 1930s. The results indicate much improvement or better in 63 of neurotic cases, 57 of character disorder, 78 of psychosomatic conditions, and 25 of psychoses. In a study led by Weber of persons who applied for psychoanalysis and then received either analysis or time-unlimited analytic psychotherapy, the patients in different modalities had a 90 or greater report of being satisfied, and 75 to 90 were rated as improved. In a separate study Jerome Sashin, Stanley Eldred, and Suzanne van Amerowgen reported a 69 agreed-upon completion

Definition And Identification Of Key Neuropsychiatry Symptoms

The definition of psychotic symptoms (i.e., delusions, delusional misidentification, and hallucinations) requires particular consideration as these symptoms are very frequent in some parkinsonian disorders, particularly in patients with dementia. In addition, as they are phenomenologically different from psychotic symptoms occurring in patients with functional psychoses and cannot be reliably observed or inferred from behavior, a specific method is required to identify these symptoms in patients with cognitive impairments. According to Burns, delusions are defined as false, unshakable ideas or beliefs that are held with extraordinary conviction and subjective certainty (3). To minimize overlap with confabulation and delirium, they should be reiterated on at least two occasions more than 1 wk apart. Hallucinations are described as percepts in the absence of a stimulus, reported directly by either the patient or indirectly via an informant, and may occur in any modality. Typically,...

Managing Age Related Disorders

DEMENTIA Nearly half of all elderly patients suffer from various degrees of dementia. Two-thirds are caused by Alzheimer's disease (AD), which is currently irreversible. Reversible dementias are caused by strokes, neoplasms, or toxins such as alcohol, or those produced by infections. Although a complete cure for most dementias is not possible, optimal management can improve the ability of these patients to cope with basic tasks. In many cases, dementia is the result of one or more small strokes caused by hypertension. Thus the first step in managing dementia is aggressive treatment for high blood pressure. This is followed with pharmacological agents that enhance cognition and function, and treat associated problems such as depression, paranoia, delusions, agitation, and even psychoses.

Inner Speech And Auditory Hallucinations

Schizophrenia Inner Speech 2011

Figure 3.13 This study investigated the hypothesis that a predisposition to verbal hallucinations is associated with a failure to activate areas concerned with the monitoring of inner speech. Subjects, who included patients with schizophrenia both with and without a significant history of hallucinations, as well as normal controls, were asked to imagine sentences being spoken in another person's voice. The figure illustrates positron emission tomography data superimposed on a normal magnetic resonance imaging scan, and shows reduced activation in the left middle temporal gyrus and the rostral part of the supplementary motor area in hallucinators compared to non-hallucinators. Similar findings were found in the comparison between schizophrenic patients and controls. Figure reproduced with permission from McGuire PK, Silbersweig DA, Wright I. Speech a physiological basis for auditory hallucinations. Lancet 1995 346 596-600

The Dopaminergic Pathways

Dopaminergic Pathways And Antipsychotics

Dopaminergic innervation supplies fibers to the medial surface of the frontal lobes and to the parahippocampus and cingulate cortex, the latter two being part of the limbic system. Because of this anatomic representation it is thought that this tract is where antipsychotic medication exerts its beneficial effect. The third major pathway is termed the tuberoinfundibular tract. The cell

Axis III General Medical Conditions

Finally, an Axis III medical condition, while not related to the appearance of the symptoms of a mental disorder, might be relevant in the treatment of a disorder. For example, certain antidepressant medications might be ill-advised in the presence of certain cardiovascular conditions. Alternatively, someone with a severe psychosis (Axis I) might have a medical condition (Axis III) that needs careful monitoring or

Antibodies to Nucleosomes Chromatin

Anti-nucleosome antibodies are clinically important for several reasons. The nucleosome is emerging as one of the major nuclear autoantigen targets, and 70-80 of SLE patients are anti-nucleosome antibody positive 36-41 . Independent studies have shown that the contribution of anti-dsDNA and anti-histone antibodies to serum reactivity against nucleosomes in SLE patients is only 2530 at most 36, 37 . One-third of SLE sera studied have high anti-nucleosome activity and little if any anti-dsDNA or anti-histone reactivity 36, 37, 41 . The level of the anti-nucleosome antibody titer correlates with the level of disease activity 39, 42-46 . This finding was also observed in SLE patients negative for anti-dsDNA antibodies 43, 44 . Anti-nucleosome antibodies are also associated with lupus nephritis 36, 39, 42-45 , which is not surprising considering the bulk of evidence suggesting that they contribute to the pathogenesis of lupus nephritis 47-50 . An increase in IgG3 anti-nucleosome titers was...

Psychological Therapies

Psychoanalytic psychotherapies have largely been discredited in the management of schizophrenia, and indeed cast something of a shadow over the development of more effective approaches to treatment. However, a number of very promising new approaches are now emerging. Figure 5.1 Professor Elizabeth Kuipers, one of the pioneers of cognitive behavioral therapy (CBT) for psychosis, treating a 'patient' played here by a colleague Figure 5.1 Professor Elizabeth Kuipers, one of the pioneers of cognitive behavioral therapy (CBT) for psychosis, treating a 'patient' played here by a colleague Figure 5.2 Sixty patients with chronic schizophrenia were randomized to nine months of cognitive behavioral therapy (CBT) and standard care, or standard care alone. At 18 months, patients with delusions who had received CBT were found to hold these with a reduced level of conviction, and were less preoccupied and distressed by their delusional beliefs. Figure reproduced with permission from Kuipers E,...

Serotonin 5HT2C receptor agonists

Baby Entwicklung

The serotonin (5-HT) receptor family are among the most studied of the neurotransmitters. The 5-HT2C receptor subclass has seen a great deal of research during the past 10 years, and evidence has established the potential as a target for treating anxiety, depression 107 , schizophrenia 108,109 and most notably obesity 110,111 . Until recently, attaining selectivity in the 5-HT2C receptor subclass over the closely related 5-HT2A and 5-HT2B receptors had been elusive, but selective agents are now emerging 112 . The rational for the use of selective 5-HT2C agonists in the treatment of schizophrenia is based upon the ability of 5-HT2C receptor activation to reduce dopamine neurotransmission in the mesolimbic system, and the potential to reduce side effects mediated by current antipsychotics such as weight gain 113 . Several noteworthy reports in the area of schizophrenia research have recently appeared. The tetracyclic indole derivative WAY-163909 (45) has been established in

The Frankfurt Institution of the Mentally Ill and Epileptics

Based on this understanding, to develop criteria for their classification. He was convinced that only if the different mental diseases could be clearly defined would it be possible to understand and possibly treat them (Nissl 1916). The combination of being a compassionate psychiatrist and an astute scientist allowed Alzheimer to make important contributions in various areas, including, for example, the various forms of dementia, cerebral atherosclerosis, progressive paralysis, damage caused by acute syphilis infections or chronic alcohol abuse, epilepsy, psychoses and forensic psychiatry (Graeber 2006). But his fame today rests mainly on his case study of a woman in her early fifties who had been admitted to the Frankfurt psychiatric institution on November 25,1901 Auguste D.

Auditory Eventrelated Potentials

Auditory Oddball

Figure 3.16 Abnormalities in evoked potentials have consistently shown abnormalities in schizophrenia. The P300 auditory event-related potential (ERP), seen here as one of several components of the auditory ERP, is seen as a response to 'oddball' or unexpected stimuli, and shows robust changes in both amplitude and latency in schizophrenic patients and their relatives. Figure 3.16 Abnormalities in evoked potentials have consistently shown abnormalities in schizophrenia. The P300 auditory event-related potential (ERP), seen here as one of several components of the auditory ERP, is seen as a response to 'oddball' or unexpected stimuli, and shows robust changes in both amplitude and latency in schizophrenic patients and their relatives.

Unmodified Antisense and the BBB Are Modifications Necessary 41 Antisense Therapy in Pathophysiology Involving

Although many studies have investigated various modification strategies designed to enhance penetration of antisense across the BBB, few studies have considered if unmodified antisense can cross the BBB. It is possible that enzy-matically resistant analogs of unmodified AS-ODNs enter the CNS by binding to transporters receptors present in the BBB for the import of endogenous substances. By analogy, viruses often use this method to enter cells. For example, human immunodeficiency virus-1 binds to the CD4 receptor to promote fusion and entry of the virus into T-cells, dendritic cells, and macrophages (44). Currently, studies examining the ability of unmodified antisense to cross the BBB have shown that two AS-ODN analogs are capable of permeation into the CNS PNAs and phosphorothioate analogs (1,2). To illustrate the points above, we now consider studies that have focused on treatment of pathophysiology through the use of unmodified AS-ODN analogs to target the proteins or receptors...

Neuropsychiatric Symptoms In Multiple System Atrophy

Psychotic symptoms have been described in MSA (97-100), also as part of affective disturbances (101). Of special interest for diagnostic thinking is the observation that paranoid-hallucinatory psychosis with organic character can be initial manifestation of MSA (97,99). The patients described by Ehrt et al. also exhibited visual hallucinations, a symptom typically seen in other synucleinopathies such as DLB and PD. However, in a relatively large clinico-pathologic comparative study, neuropsychiatric toxicity was reported to be less common in MSA (n 38) than PD patients (102). However, this term included confusion or hallucinations or the combination of both, the proportion of dementia was higher in PD than MSA, the number and dosage of dopaminergic drugs in the two groups were not comparable, and the assessments were retrospective and unstructured. Thus, it is not yet proven that visual hallucinations are less common in MSA than PD.

Realistic and Unrealistic Hope

Is not a disorder, but simply a different cognitive style, an approach to life that may in fact be preferable because it is not constrained much by routines and timetables. This is reminiscent of an argument made decades ago by a British psychiatrist, R. D. Laing (1997), who claimed that schizophrenia is not an illness, but simply a more creative way to experience the world. Such views ignore the reality of chronic suffering experienced by many impaired by ADD syndrome and illustrated in many examples in this book.

Frances Widiger And Sabshin 1991

Schizophrenia spectrum disorders. In I. Weiner, G. Stricker, & T. A. Widiger (Eds.), Handbook of psychology Vol. 8. Clinical psychology (pp. 65-92). New York Wiley. Kendler, K. S., Neale, M. C., & Walsh, D. (1995). Evaluating the spectrum concept of schizophrenia in the Roscommon family study. American Journal of Psychiatry, 152, 749-754. McGlashan, T. H., & Fenton, W. S. (1994). Classical subtypes for schizophrenia. In T. A. Widiger, A. J. Frances, H. A. Pincus, M. B. First, R. Ross, & W. W. Davis (Eds.), DSM-IV sourcebook (Vol. 1, pp. 419-440). Washington, DC American Psychiatric Association. Portin, P., & Alanen, Y. O. (1997). A critical review of genetic studies of schizophrenia. II. Molecular genetic studies. Acta Psychiatrica Scandinavica, 95, 73-80. Serreti, A., Macciardi, F., & Smeraldi, E. (1996). Identification of symptomatologic patterns concern in major psychoses Proposal for a phenotypic definition. American Journal of Medical Genetics, 67, 393-400....

Factors Affecting Prognosis

Certain clinical features are associated with a poor prognosis early or insidious onset, male sex, negative symptoms19,20 (Figure 1.8), lack of a prominent affective component or clear precipitants, family history of schizophrenia, poor premorbid personality, low IQ, low social class, social isolation, and significant past psychiatric history. Several studies have demonstrated an association between longer duration of untreated illness and poorer outcome. For example, Loebel and colleagues21 found that a longer duration of both psychotic and prodromal symptoms prior to treatment was associated with a lesser likelihood of remission. The longer the duration of pretreatment psychotic symptoms, the longer the time to remission. These data suggest that early detection and intervention in schizophrenia may be important in minimizing subsequent disability. Figure 1.19 Breier and colleagues18 among others have suggested that, despite the heterogeneity of schizophrenia, a model of a common...

Axis I Clinical Disorders and Other Conditions That May Be a Focus of Clinical Attention

Condition Substance-Related Disorders Schizophrenia and Other Psychotic Disorders Mood Disorders Schizophrenia, Delusional Disorder, Schizoaffective Disorder Also found for each disorder (other than NOS disorders) listed on Axis I are other sections providing more detailed information that may be of use to clinicians. The Diagnostic Features section provides an overview of the essential features of the disorder, along with examples and definitions of criteria and terms that are part of the criterion set for that disorder. The Subtypes and or Specifiers section delineates subtypes of the disorder (e.g., Catatonic Subtype of Schizophrenia) or specifiers of the disorder (e.g., Post-partum Onset for Major Depressive Disorder), where applicable. The Recording Procedures section includes information to assist in reporting the correct name of the disorder and the associated five-digit code that corresponds to the disorder. These five-digit codes correspond to the codes listed in the...

Calculation of Inter Rater Reliability

A second form of the base-rate problem stems from the fact that the base rate of disorders may vary dramatically by setting. For example, while schizophrenia is quite rare in the general population, it is considerably more prevalent among patients in a psychiatric hospital. Because the value of Kappa is influenced by the baserate of the diagnosis, Kappa can vary by setting even when raters apply criteria consistently across these settings.

Appendices to the DSMIV

Dence to include or exclude these entries from future editions of the DSM. The appendix encourages researchers to study refinements in these sets of criteria. Examples of entries in this appendix include Caffeine Withdrawal, alternative descriptions of Schizophrenia and other disorders related to Schizophrenia, other variants of depressive disorders, Premenstrual Dys-phoric Disorder, Mixed Anxiety-Depressive Disorder, a series of Medication-Induced Movement Disorders, and Passive Aggressive Personality Disorder (which appeared as an Axis II disorder in the previous edition of the DSM). The proposed Axes include a scale to measure strategies for coping with emotional states, termed the Defensive Functioning Scale, and two scales modeled after Axis V to measure functioning in specific areas (relationships, and social occupational).

Structural Imaging And Anatomical Studies

The core brain structural finding in schizophrenia, of lateral ventricular enlargement (Figure 3.1) is now well established, but the degree of enlargement is relatively small (Figure 3.2) about 25 on average1. Monozygotic twins discordant for schizophrenia can be distinguished from their co-twins on the basis of ventriculomegaly and decreased temporal cortical volume (Figure 3.3)2. Numerous other morphological abnormalities have been reported (Figures 3.43 and 3.5). People with schizophrenia appear to have very slightly smaller brains with sulcal widening and reduced cortical volume, particularly in the temporal lobes. Figure 3.1 Three-dimensional reconstruction of the ventricular system in schizophrenia. Structural changes appear in the shrunken hippocampus (yellow) and enlarged fluid-filled ventricles (gray) of the brain of a patient with schizophrenia (a) compared with that of a healthy volunteer (b). Figure reproduced with kind permission of Professor Nancy C. Andreasen,...

The Relaxation Response In Psychotherapy

While meditation and other techniques used to elicit the relaxation response can play an important role in the treatment of some psychological problems, such interventions might not be recommended for patients with certain personality disorders, dissociative disorders, or schizophrenia.

The Limits of Neuropsychological Tests of Executive Functions

Some neuropsychological tests traditionally have been labeled as tests of executive function (EF tests). These include the Wisconsin Card Sorting Test, the Stroop Color-Word Test, the Tower of London, the Rey-Osterrieth Complex Figure Test, the California Verbal Learning Test, and various computerized continuous-performance tests. Most of these tests were originally developed to assess patients with schizophrenia or those who had suffered damage to the frontal lobes of the brain. At first glance, such tests might appear to be appropriate measures to assess ADHD. In fact, they are not.

Schizoaffective Disorder

Schizoaffective disorder might be the prototypic boundary condition. It had the unique distinction in DSM-III (APA, 1980) of being the only disorder that lacked the specific and explicit criterion set that was the major innovation of the diagnostic manual (Spitzer et al., 1980). A consensus could not be reached on its defining features in large part because it represented the grey area between schizophrenia and mood disorders. It was to be used in DSM-III for those instances in which the clinician is unable to make a differential diagnosis with any degree of certainty (APA, 1980, p. 202). It is perhaps paradoxical to create a distinct clinical entity that demarcates the overlapping and nebulous area between two other disorders. Schizoaffective disorder might be best understood as an inherently ambiguous condition that occupies the overlapping boundary between the categories of schizophrenia and mood disorder (Blacker & Tsuang, 1992). It could be a phenotypic variation of either...

Disease And Impairment Models In Drug Discovery

Albeit to different degrees given the ceiling effects encountered with normals. An analogy with cardiovascular disease is obvious here. Many blood pressure medications have been identified by tests in normal animals. Hypotensive effects of these compounds can be regarded as toxic in this context, but in someone suffering from hypertension, the effect is therapeutic. The limitation, of course, is that the underlying pathology is not necessarily addressed. At first glance, it would appear that a key difference between blood pressure and cognition is that both high and low blood pressure can be regarded as pathological, whereas pathological changes in cognitive function are always unidirectional. However, for at least some aspects of cognitive function, both increases and decreases in function could be pathological. For example, Sarter 15 has proposed that increased (but indiscriminate) attention can contribute to the distractibility characteristic of schizophrenia, whereas changes in...

Differentiating Between Mental And Physical Health Problems

Perhaps the issue which has received the most attention in the literature concerns the differentiation between mental and physical health. Many mental health scales include physical symptoms, which may be relatively uncommon in younger populations and indicative of psychological distress. However, in older populations, with their greater incidence of chronic health problems, such instruments may yield very high rates of false positives. Further, mental health problems often have physiological concomitants, and physical health problems can affect psychological states. Obviously, identifying the primary source of the symptoms is crucial in determining treatment options, although sometimes the only way in which to determine the precise etiology for a particular illness is to test different treatments. However, there are critical issues in differentiating anxiety, depression, and psychoses from a variety of physical health problems.

Antiribosomal P Antibodies

The reported prevalence of anti-ribosomal P antibodies in SLE ranges from 10-40 prevalence is higher in Asian patients than in black and Caucasian patients 136 . A correlation between anti-ribosomal P and lupus psychosis was reported soon after the discovery of this antibody 127 . Several subsequent studies confirmed this association and also reported an association with depression 137, 138 , although other researchers disagree 139 . Anti-ribosomal P antibody correlates with the activity of lupus 140 , particularly lupus nephritis 141, 142 . Furthermore, the coexistence of anti-dsDNA and anti-ribosomal P antibodies is more closely associated with lupus nephritis than is the presence of either of them alone 143 . Anti-ribosomal P antibody is also associated with lupus hepatitis 144 . Indeed, the association between anti-ribosomal P and lupus hepatitis does not apply to patients with autoimmune hepatitis except when lupus is present this again emphasizes the high specificity of...

Variables Believed to Be Correlates of High Verbal IQ

In Chapter 8, right-hemisphere damage was shown, based on extensive data, to be associated with high Verbal IQ, relative to Performance IQ, a finding that also generally applied to patients with diffuse brain damage (including some samples tested on the WAIS-III). The following variables are also believed to be associated with V P profiles for samples tested on Wechsler's adult scales attendance at college, psychiatric disorders (e.g., schizophrenia, depression), alcohol abuse, motor coordination problems, Alzheimer's-type dementia, and having a Full Scale IQ of 110 or above.

Clinical Manifestations

Psychiatric and mood dysfunctions precede motor dysfunctions and can be destructive to the lives of the patients and their family members.58-60 Paranoid ideations, delusions, and other features of schizophrenia have been noted in 3-11 of HD patients. A significant bihemispheric decrease in metabolism is noted in PET scans of HD patients, a pattern very much similar to that seen in schizophrenics. Varieties of mood disorders are noted in 38 of HD patients, and the most common and fatal consequences are depression and suicidal tendencies. Suicide was the cause of death in 7.8 of HD patients in one study. Suicide risks are of higher frequency in HD patients,61-63 patients at risk for HD,64 and even in normal patients with a family history of HD.65 The suicide rate in HD is four to six times higher than in the general population and the rate is even higher in patients over the age of fifty. Investigators have observed obsessive-compulsive disorder,66,67 para-philia and other sexual...

The Purpose Of Diagnosis

Assigning a diagnostic label may have profound implications for the person receiving the diagnosis. On the one hand, diagnostic labels may allow individuals to receive the treatment they are seeking. On the other hand, such labels may have a stigmatizing effect for the person diagnosed. Consider, for example, how you might think about yourself, and how others might begin to think about you and to treat you, if they learned you had received a diagnosis of a severe psychosis schizophrenia. Diagnostic labels convey a wealth of information, some of it intended, some of it not. Because assigning a diagnostic label may have profound effects on how people may view the person who receives the label, the diagnosis of mental disorders should be taken seriously, and should have the potential for some clear benefits for those diagnosed. would regard as false, such as the belief that one can read verbatim another's thoughts. Yet despite similarity in this particular symptom, individuals with...

Dissociative Identity Disorder DID

DID is the disorder that is mixed up with schizophrenia in everyday language. It involves multiple (that is, split) personalities. Each personality that develops has its own identity (age, name, characteristics, memories, etc.) and takes control of the person while it is present. Then another takes over. Frequently, the alternative identities have characteristics quite different from the original personality. For example, they might be hostile and aggressive rather than gentle and unassuming.

Treatment Of Huntington Disease

Currently, only symptomatic therapy is available for HD.96 The major goals of symptomatic therapy are to control psychosis, treat depression and suicidal tendencies, and possibly control the severity of chorea and other motor manifestations. Dopaminergic and serotonergic receptor blockade with typical and atypical antipsychotics have been the major source symptomatic therapy for HD patients. Among the drugs that are commonly used are haloperidol, risperidol, quetiapine, olanzapine, and clozaril.97-100 Anti-dopaminergic agents appear to be ineffective in the treatment of chorea. However, long-term use of typical antipsychotics may also complicate the course of the disease by inducing either drug-induced Parkinson's disease and or tardive dyskinesias and tardive dystonia. Severe depression is treated with SSRIs and other antidepressants. 98. Erdemoglu, A.K., and C. Boratav. 2002. Risperidone in chorea and psychosis of Huntington's disease. Eur J Neurol 9 182-183.

AMPA potentiators

Direct activation of AMPA receptors carries the risk of producing seizures, ex-citotoxicity and a loss of efficacy due to desensitization. However, the discovery of positive allosteric modulators (PAMs) offers a mechanism for enhancing receptor activity while avoiding these issues 11 . As indicated by their name, AMPA PAMs do not interact with the agonist glutamate site on the receptor but rather at an allosteric site where they affect the kinetics of receptor desensitization and or deactivation. Crystallographic studies of the AMPA receptor have confirmed the location of an allosteric site on the extracellular domain of the receptor. Binding of a PAM at this site stabilizes the receptor in its' active, agonist-bound conformation 12 . The presence of multiple allosteric sites is suggested by experiments demonstrating that some potentiators affect receptor deactivation to prolong signal duration, while others slow desensitization and enhance signal amplitude 13 . Regardless of the...

GlyTl inhibitors

Preclinical evidence confirms that NMDA receptor function can be augmented via GlyT1 inhibition indicating that this transporter may be targeted for the treatment of schizophrenia much in the same way the serotonin transporter is targeted for depression. Early in vitro studies of the GlyT1 transporter used inhibitors such as the glycine ester, glycyldodecylamide and the competitive inhibitor, sarcosine (N-methylglycine) 22 . A breakthrough was achieved with the discovery of ALX-5407 (NFPS) (7), a sarcosine derivative of fluoxetine. NFPS is a single digit nanomolar inhibitor of glycine transport by GlyT1 with no activity at GlyT2. A number of related compounds have been described, although the majority resemble 7 in suffering from behavioral toxicity, apparent irreversibility at the transporter 23 and the need for high systemic exposures to gain access to the CNS 24 . One such analog, NPTS (8), is completely inactive following peripheral administration, but has proven to be a useful...

Jerry J Buccafusco

Pharmacological models are the most commonly used models of cognitive dysfunction. They are key for determining how selected neurotransmitter-receptor systems are involved in various aspects of cognitive function such as learning, memory, and attention. Pharmacological models are also key for testing the possible use of cognition-enhancing drugs for potential treatment of cognitive impairments such as those seen in Alzheimer's disease and other aging-related syndromes, attention deficit hyperactivity disorder (ADHD), Parkinson's disease, and schizophrenia. Acetylcholine is the best-characterized transmitter system in the basis of cognitive function. Both muscarinic and nicotinic cholinergic receptors have been found to be critically involved. Glutamate systems, particularly those using NMDA (N-methyl-D-aspartate) receptors, have also extensively been shown to be involved in cognition. Drugs of abuse can also produce syndromes of cognitive impairment. The best example is ethanol, which...

Behavioral Medicine

Ration between physicians, biomedical scientists, and behavioral scientists. Efforts of psychologists without medical collaborators, or by physicians without behavioral collaborators, have less potential. Second, the definition stresses the application of behavioral knowledge to problems in physical health. Physical health has not traditionally been within the domain of psychology. Third, the definition excludes the more traditional topics of clinical-abnormal psychology, such as psychosis and neurosis. Although some behavioral medicine specialists study substance abuse, they tend to study traditional psychological problems only insofar as they contribute to physical health. Reflecting the view that mental and physical functioning are closely related, the biopsychosocial model of health and illness is endorsed by many practitioners of behavioral medicine. According to this model, health status is determined by multiple factors. The traditional medical model generally views specific...

Olfactory nerve

The term parosmia describes a qualitative change in smell while total loss of smell is known as anosmia. Disorders of smell usually develop slowly and insidiously (except in traumatic brain injury) and are commonly associated with impaired taste. Olfactory hallucinations may accompany seizures or psychosis.

Negative Symptoms

Figure 1.16 Broach shizophrene, by Bryan Charnley. Bryan Charnley illustrated the experience of psychosis in many striking artworks, including a series of self-portraits painted as he came off medication (see Figure 1.20). Reproduced with kind permission of the Bethlem Royal Hospital Archives and Museum, Beckenham, Kent, UK Figure 1.16 Broach shizophrene, by Bryan Charnley. Bryan Charnley illustrated the experience of psychosis in many striking artworks, including a series of self-portraits painted as he came off medication (see Figure 1.20). Reproduced with kind permission of the Bethlem Royal Hospital Archives and Museum, Beckenham, Kent, UK psychotic symptomatology, while others may represent side-effects of antipsychotic drugs. It is often difficult to differentiate between the negative symptoms of schizophrenia and the symptoms of a depressive illness. Depression is common in schizophrenia, and often becomes evident as the acute episode resolves. True primary negative symptoms...


Recent efforts have been directed towards finding an alternative neurochemical target in schizophrenia. The first of these that should be considered is gamma aminobutyric acid (GABA). GABA appears to have a regulatory role on dopa-minergic function. The balance of evidence tends to suggest that GABA decreases dopaminergic firing. This links with human postmortem data indicating that GABAergic reductions correlate with increased dopamine concentrations19,20. Thus, it is possible that in schizophrenia there is a reduction in GABAergic function which leads to a dysregulation of dopamine and the production of psychotic symptoms. A more likely candidate, however, appears to be the glutamatergic system. Glutamatergic dysfunction, particularly at the level of the N-methyl-D-aspartate (NMDA) receptor, has also been implicated in the patho-physiology of schizophrenia. Drugs which are antagonistic at the NMDA receptor, such as ketamine and phencyclidine, produce in healthy volunteers, both the...

Psychiatric Disease

Psychiatric symptoms due to Wilson's disease range from behavioral changes and anxiety disorders to depression and psychosis. In very young patients, the initial manifestations of psychiatric symptoms may be behavioral problems, withdrawal, and difficulty concentrating or performing higher cognitive tasks. In some patients, the psychiatric symptoms may precede any other symptoms of the disease. In adults, depression is the most commonly recognized symptom, occurring even in treated patients. There may be components of reactive depression in some newly diagnosed individuals to the realization that they are afflicted with a chronic illness or disability, or there may be no apparent trigger for the depression. The failure to recognize psychiatric symptoms in patients can lead at times to serious consequences. Depression can deepen and patients can become suicidal. In some, psychosis may be severe and require inpatient psychiatric attention. Treatment of psychiatric signs and symptoms in...


The most recent Report on Confidential Enquiries into Maternal Deaths Maternal and Child Health has highlighted the risk of postnatal depression and its potential to lead to postnatal psychosis and suicide. There are numerous case reports offering conflicting advice about the use of psychotropic drugs in lactating women. The tricyclic antidepressants amitriptyline, nortriptyline and desipramine are all excreted into breast milk, with the baby being exposed to approximately 1 of the maternal dose. This poses a theoretical risk for the infant, but there are no case reports of adverse effects, and the balance of risks is generally believed to favour continuing treatment of the mother and allowing breastfeeding. Information about the selective serotonin reuptake inhibitors (SSRIs) in lactation is limited. The drugs are excreted into breast milk, but there are no controlled

Figure 735

Steroids usually have been ineffective on proteinuria or progression of renal disease in adults and children. Recently, 20 adult patients with HIV-associated glomerulosclerosis or mesangial hyperplasia with proteinuria over 2 g 24 h and serum creatinine over 2 mg dL were studied. These patients showed impressive decreases in pro-teinuria and serum creatinine when given 60 mgd of prednisone for 2 to 6 weeks 181 . Complications of steroid therapy, however, were common. These include development of new opportunistic infections, steroid psychosis, and gastrointestinal bleeding. The short-term improvement in renal function may correlate with an improvement in tubulointerstitial mononuclear cell infiltration 182 . In a single report of three children with perinatal AIDS, HIV-associated glomerulosclerosis, and normal creatinine clearance, cyclosporine induced a remission of the nephrotic syndrome 183 . This report has not been confirmed, and the use of cyclosporine in adults with...

Cobalamin neuropathy

Loss of vibratory and position sense are common sensory signs. Neuropathy is difficult to separate from myelopathy, which involves spasticity, posterior column dysfunction and ataxia. There is also memory loss and confusion. Loss of ankle reflexes may be the most diagnostic sign of neuropathy. Psychosis has also been described.


CNS disturbances can precede neuropathy, including agitation, psychosis, seizures, and eventually coma. Weakness can involve the face and respiratory muscles. Autonomic dysfunction is common. In some forms of porphyria, skin blisters can accompany an acute attack. Attacks can be precipitated by drugs that stress liver function, fasting, stress, and alcohol.


The most important risk factor for schizophrenia is having an affected relative (Figure 2.5 and Table 2.1)3-5. Twin and adoption studies have been used to show that this is consequent upon genetic transmission. The consistently greater concordance in monozygotic (MZ) than dizygotic (DZ) twins4-10 (Figure 2.6) has been taken to indicate a genetic effect but does not prove this beyond doubt, since MZ twins may be treated more similarly by their parents (Figure 2.7). However, adoption studies have demonstrated conclusively that liability to schizophrenia is transmitted through genes and not through some intrafamilial environmental effect (Figure 2.8)11,12. Various models of genetic transmission of schizophrenia have been considered but found not to fit the data. There is no evidence to support the single major locus model, which implies that a gene of major effect causes schizophrenia but has incomplete penetrance or variable expression. The polygenic model implies that there are many...

The Chronic Illness

Eventually, even without treatment, the acute symptoms of schizophrenia usually resolve. Unfortunately this does not always mean that the patient will fully recover. Over 50 of patients diagnosed as suffering from schizophrenia will show evidence of a significant degree of negative symptomatology. Furthermore, in chronic schizophrenia, positive symptoms also frequently remain, although they tend not to predominate.

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