Psychosis 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


4.6 stars out of 11 votes

Contents: EBook
Author: Ronen David
Price: $12.00

My The Schizophreniafree Package Review

Highly Recommended

The author has done a thorough research even about the obscure and minor details related to the subject area. And also facts weren’t just dumped, but presented in an interesting manner.

This ebook does what it says, and you can read all the claims at his official website. I highly recommend getting this book.

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What Causes Schizophrenia

When a young person develops a mental illness, the knee-jerk response is often what did the parents do wrong Schizophrenia is not a disease that parents cause. Nor is it a disease that parents can prevent or arrest, much to the despair of people like Phil and Sue. Despite parental love and care, the disease strikes, injures, and leaves its suffering victims and their families in pained submission. Schizophrenia is a brain mind disease. In Studies showing that genetic factors may contribute to the development of schizophrenia provided the earliest evidence that schizophrenia has a biological basis. As described in chapter 5, our methods for studying genes and their contribution to disease has grown steadily more sophisticated. The earliest genetic work on schizophrenia was based on the simple observation that mental illnesses sometimes run in families an observation that suggests a role for genes but does not prove this, since familial aggregation could be due to learned behavior and...

Psychiatric Disorders 601411 Schizophrenia

Schizophrenia (see 6.02 Schizophrenia) is a complex and debilitating neurodevelopmental psychiatric disorder that affects approximately 1 of the population. It is characterized by diminished drive and emotion during childhood followed by a deviation from reality with hallucinations, and appears to have both genetic and epigenetic causality. Schizophrenia presents with a spectrum of positive, negative, and cognitive symptoms. Positive symptoms include auditory and visual hallucinations, delusions, disorganized thought, and antisocial or violent behavior. Negative symptoms include dissociation, apathy, difficulty or absence of speech, and social withdrawal. Cognitive symptoms Schizophrenia and other psychotic disorders Mood disorders include disorganized thought, difficulty in attention or concentration, and poor memory. Symptoms usually begin in adolescence or early adulthood, but can occur at any stage of life including childhood. Current diagnostic criteria rely on the DSM-IV-TR...

Disruptedin Schizophrenia 1 DISC1

Disrupted-in-schizophrenia 1 (DISC1) at chr1q is a component of the microtubule-associated dynein motor complex that is key to maintaining the centrosome complex and maintaining microtubular function. Depletion of endogenous DISC1 or mutated DISC1 causes neurite dysfunction in vitro and impairs cerebral cortex function in vivo, suggesting a neurodevelopmental role in schizophrenia.38 More recently, DISC1 has been found to interact with the UCR2 domain of the phosphodiesterase PDE4B, suggesting a possible role in cAMP signaling processes that may involve CREB (cAMP response element binding protein) elements.

Schizophrenia And Other Psychotic Disorders

The title of this diagnostic class is potentially misleading for two reasons (1) there are other disorders that have psychotic features that are not included in this diagnostic class (e.g., mood disorders with psychotic features, delirium) and (2) it may incorrectly imply that the other psychotic disorders included in this section are related in some way to schizophrenia (which is only true for schizophreniform disorder and possibly schizoaffective disorder). Instead, what ties together all of the disorders in this diagnostic class is the presence of prominent psychotic symptoms. Included here are schizophrenia, schizophreniform disorder, schizoaf-fective disorder, delusional disorder, shared psychotic disorder, and brief psychotic disorder, each of which is discussed in varying detail in Chapter 25. It should be noted that the definition of the term psychosis has been used in different ways historically and is not even used consistently across the various categories in the DSM-IV-TR....


Other than nicotine, alcohol is the most commonly abused drug in patients with schizophrenia. Schizophrenia occurs in about 1 of the population, but ECA data revealed that 33.7 of people with schizophreniform disorder (same symptoms as schizophrenia but lasting less than 6 months) or schizophrenia have a diagnosis of alcohol abuse or alcohol dependence at some time in their lives. The high rate of alcohol use disorders in patients with schizophrenia may be related to biological factors, such as self-medication to alleviate symptoms of schizophrenia, or side effects of antipsychotic medications underlying abnormalities of dopamine regulation may provide a common basis for the high rate of co-occurrence or patients with schizophrenia may be particularly vulnerable to the negative effects of substance use due to the impaired thinking and impaired social judgment that are part of the schizophrenic syndrome, thus increasing their vulnerability for a substance use disorder. It is critical...

Social Cost and Market

The pervasiveness of psychiatric disorders, e.g., depression, substance abuse, anxiety, schizophrenia, etc., and the comorbidity of depression and anxiety with neurological disease has enormous costs for society, estimated in the trillions of dollars. Additionally, it has been estimated that over 60 of individuals with diagnosable mental disorders do not seek treatment.

Central Nervous System Disorders Psychiatric and Neurodegenerative

Disorders of the CNS are broadly categorized as either psychiatric or neurodegenerative with a major degree of overlap in symptoms. Thus neurodegenerative disorders also have a high incidence of psychiatric comorbities including anxiety and depression. Psychiatric disease includes a variety of disorders such as schizophrenia, depression, obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and others. The underlying pathology is usually considered to be the result of synaptic dysfunction driven by (1) a dysregulation of neurotransmitter availability or (2) signaling, the latter at the receptor and or signal transduction levels. The net result is an alteration in neuronal circuitry involving multiple neurotransmitter neuromodulator systems.

Disease State Diagnosis

The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) category for the schizophrenic disease spectrum is designated as 295.xx, 'schizophrenia and other psychotic disorders'4 with the main subclasses being paranoid type (295.30) disorganized type (295.10) catatonic type (295.10) undifferentiated type (295.90) and residual type (295.6) as well as schizophreniform disorder (295.40) schizoaffective disorder (295.70 including bipolar and depressive types) delusional disorder (297.1) brief psychotic disorder (298.8) and shared psychotic disorder (297.3). The three main symptoms of schizophrenia are 'positive', 'negative' symptoms, and 'cognitive dysfunction.' Positive symptoms (although by no means positive to the patients) are defined as an excess or distortion of normal function and include bizarre behavior, auditory, and, more rarely, visual hallucinations, paranoid and other types of delusions, and disorganized thought. Negative symptoms include a diminution or loss of...

The Dopamine DA Hypothesis

Until recently, the modal hypothesis on the pathophysiology of schizophrenia was that excessive dopaminergic transmission in the forebrain is a key causative factor. This DA hyperfunction hypothesis was primarily based on the observation that all clinically effective antipsychotic drugs have potent antagonist or inverse agonist activity at DA D2 receptors, and that the therapeutic efficacy of these compounds was highly correlated with their affinity for striatal D2 receptors. In addition, the psychotomimetic properties of indirect DA agonists like amphetamine and cocaine, and observed alterations in striatal DA release in schizophrenic patients, further supported the involvement of DA in the pathophysiology of schizophrenia. The DA hypothesis has been useful in stimulating research on the neurochemical alterations underlying schizophrenia, placing the DA D2 receptor at the center of antipsychotic drug development, in essence recapitulating existing antipsychotic agents in a circular...

The yAmino Butyric Acid GABA Hypothesis

G-Amino-butyric acid (GABA) is the major inhibitory transmitter in the CNS, and has many effects that are opposite to those of glutamate, some of which involve GABAergic inhibition of glutamate function. The GABA uptake inhibitor, CI-966 9, has been associated with psychotic episodes in humans,17 a similar phenotype to that seen with the psychotomimetics that block the effects of glutamate at the NMDA receptor. A role of GABA in the etiology of schizophrenia was first proposed in the early 1970s based on GABAergic regulation of DA neuronal function with a special focus on the role of GABA in working memory. GABA uptake sites are decreased in hippocampus, amygdala, and left temporal cortex in schizophrenics with some evidence of GABAa receptor upregulation18 and reductions in GABA interneurons.19 An extensive review of the use of benzodiazepines, the classical GABAA agonists, the GABAg agonist

Social Isolation Model

The post-weaning social isolation of rats produces a model that exhibits behavioral abnormalities with some potential relevance to schizophrenia, including hyperactivity in response to novelty and amphetamine, disruption in PPI, and decreased social interactions. These abnormal behaviors are at least partially responsive to atypical antipsychotics.50 While social isolation produces an interesting behavioral model with some face validity, there are clear issues regarding construct validity. Since many of the systems disrupted by social isolation appear to be similar to changes observed in schizophrenic patients, this model may provide a fruitful path for basic research into potential developmental mechanisms of schizophrenia. However the incomplete response to atypical antipsychotics suggests that results from this model should be interpreted with caution.

Preface and Acknowledgments

In their discussion of the molecular genetic basis of behavioral traits, Stephanie Sherman and Irwin Waldman describe current methods for finding genes for complex traits. They use schizophrenia, dyslexia, and anxiety as examples of successful investigations of the molecular basis of human behavior. The authors point to major advances in isolating the biological from the environmental components of complex behavioral traits.

Dopamine transporter polymorphisms

DAT terminates dopaminergic neurotransmission by reuptake of dopamine (DA) in presynaptic neurons and plays a key role in DA recycling. DAT can also provide reverse transport of DA under certain circumstances. Psychostimulants such as cocaine and amphetamines and drugs used for attention deficit hyperactivity disorder (ADHD) such as methylphenidate exert their actions via DAT. Altered DAT function or density has been implicated in various types of psychopathology, including depression, BPAD, suicide, anxiety, aggression, and schizophrenia. Altered transport properties associated with some of the coding variants of DAT suggest that individuals with these DAT variants could display an altered DA system.17'20 Multiple human dopamine transporter (hDAT, SLC6A3) coding variants have been described, though to date they have been incompletely characterized. The antidepressant, bupropion (6) dose-dependently increases vesicular DA uptake an effect also associated with VMAT-2 protein...

Neuropsychiatric Manifestations Of Hiv Infection

HIV is a neurotropic virus that enters the central nervous system at the time of initial infection and persists there. Subtle neuropsychological impairment may be found in 22 to 30 of otherwise asymptomatic patients with HIV infection (Wilkie et al., 1990 White et al., 1995) these findings may or may not have functional significance. Neuropsychiatric complications of the direct effects of HIV in the brain become more frequent as illness advances (Bartlett and Ferrando, 2004). Common problems include decreased attention and concentration, psychomotor slowing, reduced speed of information processing, executive dysfunction, and, in more advanced cases, verbal memory impairment (Bartlett and Ferrando, 2004). Neuropsy-chiatric manifestations occur with a range of severity varying from subclinical to specific disorders that include, most commonly, minor cognitive-motor disorder (MCMD) and HIV-associated dementia (HAD). Psychiatric illnesses associated with HAD, where symptoms range from...

Rates Of Hiv Infection Among People With Substance Use Disorders

Psychosis An overview of the literature suggests that the pathophysiology of psychosis in HIV infection is complex, and a multifactorial etiology of psychotic symptoms is likely in many cases. There are many reports of psychotic symptoms in HIV-infected persons in the absence of concurrent substance abuse, iatrogenic causes, evidence of opportunistic infection or neoplasm, or detectable cognitive impairment. A common clinical feature of new-onset psychosis in HIV-infected patients is the acute onset of symptoms. Estimates of the prevalence of new-onset psychosis in HIV-infected patients vary widely, from less than 0.5 to 15 , (Navia et al., 1986 Halstead et al., 1988

Use in Prevention and Therapy

Deficiency in the central nervous system (even with normal blood levels of vitamin B12 and without anemia6) may cause psychosis, depression, and or mania. Dementia with confusion and memory loss, particularly in the elderly, may benefit from vitamin B12.7,8

Nonarteriosclerotic Diseases of Cerebral Arteries

The diagnosis of these diseases often presents difficulties early diagnosis, however, is important because appropriate therapy may halt or even reverse the disease process. The clinical presentation varies across a broad spectrum. The disease may begin acutely as a TIA or a full blown stroke, or it may progress gradually with headaches, multifocal neurologic signs, seizures, behavioral changes, psychosis, and cognitive decline often progressing to dementia. Several diseases also affect the systemic blood vessels and produce visceral and cutaneous changes. Segmental constriction (beading) of the arterial wall, as seen on angiogram, is characteristic for some for others, the definite diagnosis may require tissue biopsy. The cerebral pathology also ranges widely Some angiopathies have a predilection for the large, and some for the small vessels infarctions and hemorrhages may be solitary or multiple, small or large.

How Psychiatrists Can Contribute To Containment Of The Most Challenging Public Health Problem The World Has Faced On A

The range of mental health issues encountered by HIV AIDS care providers is broad (e.g., abuse of alcohol, cocaine, crystal methamphetamine personality disorders agitation psychosis) and population-specific (e.g., adolescents, Latinas, people who are homeless or incarcerated). Because service delivery systems (medical care, mental health care, substance abuse treatment) are structured to work separately (historically due to different funding streams), efforts to navigate multiple systems often fail. Integrated HIV mental health care remains rare (Satriano et al., 2007), and comprehensive listings of regional HIV mental health service agencies do not exist. Patients may not themselves recognize the role that mental health problems are playing in their health (Messeri et al., 2002). As a result, HIV AIDS medical service providers may be unable to integrate adequately HIV AIDS, mental health, and substance abuse treatment services, even through existing referral networks, let alone to...

Identifying the Molecular Genetic Basis of Behavioral Traits

For a variety of reasons, the promise of interesting new findings has been actualized to a much greater extent for the genetics of medical diseases than for the genetics of psychiatric disorders or behavioral traits, although the recent advances mentioned above are just as pertinent for both fields. While the major genes underlying diseases such as Huntington disease, cystic fibrosis, Duchenne muscular dystrophy, and breast cancer have been located and cloned, a succession of initial positive findings and subsequent failures to replicate those findings have been reported for psychiatric disorders, including schizophrenia, bipolar disorder, and Tourette syndrome. likely that genetic influences of psychiatric disorders act at the level of component traits rather than at the level of the disorders per se. For example, specific genes that influence schizophrenia are more likely to affect its component symptoms or symptom dimensions such as thought disorder, flat affect and anhedonia,...

Mary Ann Cohen and David Chao

Have comorbid psychiatric disorders that are co-occurring and may be unrelated to HIV (such as schizophrenia or bipolar disorder). The complexity of AIDS psychiatric consultation is illustrated in an article (Freedman et al., 1994) with the title Depression, HIV Dementia, Delirium, Posttraumatic Stress Disorder (or All of the Above).''

Diseases with Akinetic Rigidity Idiopathic Parkinsons Disease

Combinations of extrapyramidal disorders and auto-nomic dysfunctions, frequently accompanied by neuro-psychiatric symptoms, define the disease. The cardinal motor symptoms are cogwheel rigidity of muscle tone, bradykinesia akinesia, postural instability, and pill-rolling tremor at rest. A stooped posture, shuffling and festinating gait, lack of facial expression, micrographia, weak monotonous speech, and dysphagia are additional characteristic features. In some patients, akinetic-rigidity predominates in others, resting tremor. Characteristic autonomic dysfunctions include orthostatic hypotension, seborrhea, sialorrhea, hyperhydrosis, constipation, bladder disorder, sleep disorder, and, rarely, sexual dysfunction. Anxiety, depression, psychosis, hallucination, and cognitive decline may emerge at any time during the course of the disease, which ranges from 10 to 20 years. No specific diagnostic tests are available. PET and SPECT show diminished striatal dopamine uptake.

Early Childhood Developmental Social and Family History

And other family members as well as discussions about parental drug and alcohol use can follow. Family history also includes information about illness patterns, particularly psychiatric illnesses such as bipolar disorder or schizophrenia. History and chronology of early childhood losses are highly significant and deserve careful interest and documentation. Educational history includes the following questions and is relevant in determination of current level of intellectual and occupational function (1) How far did you go in school '' (2) How did you do in school '' (3) What was school like for you '' (4) Were there any problems with learning '' may have a multiplicity of serious and often incapacitating psychiatric illnesses. Persons with HIV and AIDS are at especially high risk for cognitive disorders, affective disorders, substance use disorders, and post-traumatic stress disorder. There is also an association between serious mental illness and HIV-related illness, documented in a...

Alcohol Induced Persisting Amnestic Disorder

Alcohol-induced persisting amnestic disorder constitutes a continuum involving Wernicke's acute encephalopathy, the amnestic disorder per se (commonly known as Korsakoff's psychosis), and cerebellar degeneration. Alcohol-induced persisting amnestic disorder typically follows an acute episode of Wernicke's encephalopathy. The latter consists of ataxia, sixth cranial nerve (abducens) paralysis, nystagmus, and confusion. Wernicke's often clears with vigorous thia-

Differential Diagnosis

Smokers with psychiatric illness such as schizophrenia, alcoholism, and depression also have an extremely difficult time quitting smoking (Glassman, 1993 American Psychiatric Association, 1996), and for smokers who succeed in quitting, negative affect and stress play a major role in smoking relapse (Shiffman, 1986).

A Therapeutic Alliance

A 38-year-old patient suffering from chronic paranoid schizophrenia was referred to consultation liaison psychiatry after his refusal to continue palliative treatment of a testicular cancer, known to respond to chemotherapy. Upon evaluation, the patient appeared competent with regard to medical treatment decisions he understood the situation, knew the treatment options and their outcomes and explained his refusal to continue treatment by the fact that each treatment and contact with the medical staff was associated with unbearable anxiety, despite an adequate psychopharmacological treatment. He had informed his son, a teenager, that he would not accept any further treatment, that he knew that he would die of the disease in the near future and told him how much he loved him and how sad he was of not having been able to

Literary Analysis

Chief Bromden's observations as narrator make him the most important character in the novel. The deaf and dumb American Indian, who has seen his lands taken away to build a hydroelectric dam and his family destroyed, tells the story, at first in a flashback sequence and then in hallucinatory visions. It is possible to trace throughout the novel his self-evolving passage out of the fog of schizophrenia. The action centers on the free-spirited Randle P. McMurphy (Mack), who of course personifies the counterculture Beat Generation. He was a giant come out of the sky to save us from the Combine, the Big Chief believes. Mack faces off against Nurse Ratched, who personifies governmental authority and repression and in whom the Combine (evil government forces seeking conformity) culminates. The Combine includes Ratched's network of handpicked and personally trained nurses, doctors, and aides. Mack, crazy like a fox, has capitalist intent in feigning mental illness to leave a prison work...

Voluntary False Confessions

By contrast, some people making this type of confession do so because they are unable to distinguish between fact and fantasy. Such individuals are unable to differentiate between real events and events that originate in their thinking, imagination, or planning. Such a breakdown in reality monitoring is normally associated with major psychiatric illness, such as schizophrenia.

Synopsis Of The Novel

Through the fog of his schizophrenia the Big Chief keenly watches the new admission, McMurphy, in the group psychotherapy meeting. Ratched begins the discussion from a topic logged in the ward book having to do with Dale Harding's promiscuous, well-endowed young wife, his feelings of inferiority, and resultant sexual dysfunction. He is a probable case of situational madness resulting from his wife's emasculating nature. Mack had initially challenged Harding, the effeminate, college-educated president of the Patients' Council, for the role of the Bull Goose Loony or the alpha male, but they soon become friendly when Harding proves a valuable source of information. Mack garners the most interest in the meeting, however, when Ratched introduces him as a recipient of the Distinguished Service Cross in Korea for leading a Communist prison camp escape. Subsequently, he was dishonorably discharged for insubordination and later arrested for drunkenness, gambling, assault and battery, and...

The Impact of Psychiatric Illnesses

There has been a considerable amount of research on the manner in which certain functional psychiatric illnesses can affect the reliability of testimony (78,79). Thus, anxiety increases a suspect's suggestibility and depression can lead to feelings of guilt and poor self-esteem that render a suspect vulnerable to providing a false confession (52). Psychiatric illness may also render a person unfit for interview by virtue of its effect on cognitive processes or because of associated thought disorder (80,81). However, careful questioning that avoids the use of leading questions and coercive pressures can often elicit reliable testimony. That a suspect suffers from an illness, such as schizophrenia, does not necessarily mean that he or she is unfit for interview (82) such an opinion would depend on the likely demand characteristics of the interview and the functional assessment by the doctor.

And Diagnostic Criteria

Neuropsychological deficits in HIV-associated neuro-cognitive disorders reflect underlying subcortical-frontal pathology (see Chapter 19 for a full discussion of neuropsychological deficits in HIV infection). Briefly, impairments are seen in the areas of attention, concentration, psychomotor processing speed, speed of information processing, executive function (abstraction, divided attention, shifting cognitive sets, response inhibition), and verbal memory (particularly retrieval of stored information) (Heaton etal., 1995). Disorders of language, visuospatial abilities, and praxis generally occur in later-stage dementia. Associated neuropsy-chiatric symptoms include apathy, depression, mania, and psychosis.

Clinical Presentation

The clinical presentation of late-onset psychosis depends in large part on the underlying diagnosis. Mood disorder with psychosis is described in Chapter 3 ( Mood Disorders Diagnosis ), and dementia with psychosis is discussed in Chapter 5 ( Dementia and Alzheimer's Disease ) the typical picture of VLOSLP follows DSM-IV-TR diagnostic criteria for schizophrenia there are Table 7-9. Summary of DSM-IV-TR diagnostic criteria for schizophrenia F. If there is a history of autistic disorder or another pervasive developmental disorder, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated). B. Criterion A for schizophrenia has never been met. delusions that may be bizarre, hallucinations (which are more likely to be visual than in early- or late-onset cases), and a relative absence of formal thought disorder and affective blunting. The presentation of delusional disorder similarly...

Neuropsychological Tests

Most patients with schizophrenia spectrum disorders have neuropsychological deficits, with severity ranging from mild frontal executive deficits to clinical dementia. In a study of community-residing outpatients with schizophrenia (Heaton et al. 2001), the average global neuropsychological score was 1.62 stan dard deviations (SDs) lower for patients compared with control subjects, and about 30 of the patients had very impaired cognitive scores ( 3 SDs below the level of nonschizophrenic control subjects). Deficits of this magnitude contribute in significant ways to the functional and social limitations associated with schizophrenia-like conditions. However, in contrast to neurodegenerative disorders such as Alzheimer's disease and dementia with Lewy bodies, most studies have found schizophrenia-related cognitive deficits to be stable over time. In the Heaton et al. study, for example, mean changes over time and test-retest reliabilities were the same for schizophrenic patients and...

Treatment Of Psychiatric Disorders In The Context Of

Specific considerations should be given to patients with HIV and severe, chronic mental illness. Approximately 2.6 of persons in the United States meet the criteria (based on duration, disability, and diagnosis) for severe mental illness (SMI) in a given year (Kessler et al., 1996). Most individuals with SMI have schizophrenia, bipolar disorder, and major depressive disorder (MDD), requiring extended or frequent hospitaliza-tions (Regier et al., 1990). Schizophrenia and bipolar disorder impair a person's ability to perceive HIV risk, modify behavior, and participate in treatment. Adequate consideration and treatment of the specific symptoms in individual patients will maximize their adherence to a comprehensive treatment plan.

Severe Mental Illness And Hiv Risk

Chronically mental ill patients have an increased risk of acquiring HIV through practicing risky sexual behaviors, abusing substances, and taking part in social networks that have a higher prevalence of HIV. Individuals with mental illness have variable knowledge of HIV risks and safer sex practices, with a diagnosis of schizophrenia being a specific predictor of having poor knowledge of such risks and practices. More importantly, increased knowledge of HIV risk behaviors does not translate to less risk behaviors on the part of individuals with mental illness. In fact, some studies have found that mentally ill individuals who practice risky behaviors had greater knowledge of HIV risks than those who did not (Chuang and Atkinson, 1996, McKinnon etal., 1996). Risk behaviors more common among psychiatric patients include multiple partners, partners with known HIV-positive status, substance use during sex, trading sex for money, drugs, or housing, and lack ofcondom use (Treisman and...

Guidelines For Selection

Any individual who has experienced CSA and additional assaults in childhood or adulthood may be considered for this treatment. Assessment of role functioning, dissociation, alexithymia, interpersonal schemas, and posttraumatic stress symptomatology will help determine where the emphases in treatment should be placed. There are certain problems for which this treatment is not ideally suited and which require referral to alternative programs. These include substance dependence, moderate to severe self-mutilation, high risk for suicide, and presence of a dissociative disorder. We have been successful in treating individuals with substance abuse, mild self-mutilation, and chronic suicidal ideation. The judgment remains with the clinician to determine the degree of coping skills available to the patient to manage states of high distress as well as the degree of his or her motivation to learn new skills. Individuals in domestic violence situations or battering relationships also need direct...

Other Magnetic Resonance Methods

Changes in relaxation times may reflect anomalous cerebral development, as recently demonstrated in schizophrenia (Andreasen et al., 1991 Williamson et al., 1992 Yurgelun-Todd et al., 1995). Alternatively, alterations in cerebral perfusion may lead to small changes in T2 which can be detected using echo planar imaging (Teicher et al., 2000). In the area of substance abuse, relaxation time measurements have also been used to assess brain hydration. In general, as brain water content decreases, relaxation times become shorter.

The Downside of Diagnostic Criteria

Validity in order to achieve reliability. The evolution of the criteria for schizophrenia illustrates this problem very nicely. Historically, and probably correcdy, schizophrenia was defined by Kraepelin and Bleuler as a multisystem disorder affecting multiple mental functions. In particular, it produced changes in emotional responsiveness and the ability to think clearly.These concepts were well reflected in DSM I and DSM II. When DSM III was written, however, concerns about overdiagnosis of schizophrenia and poor reliability led to an emphasis on symptoms that were easily defined because they were more objective than subjective. Specifically, the definition emphasized hallucinations (hearing voices) and delusions (a variety of false beliefs, such as being controlled by outside forces or persecuted). The definition of schizophrenia became more reliable with the new DSM III criteria, but the essence of its concept may have been lost in the process. Psychiatrists who trained after...

And Amnestic Disorders

This chapter reviews delirium, dementia, and amnestic disorders. Traditionally, these conditions have been classified as organic brain disorders to distinguish them from such diseases as schizophrenia, mania, and major depressive disorder, the so-called functional disorders. With the publication of the DSM-IV, the distinction between functional and organic disorders was eliminated. Significant research into the neurobiological aspects of mental disorders and the utilization of sophisticated neurodiagnostic tests such as positron emission tomo-graphic scanning in individuals with schizophrenia led to the inescapable conclusion that every psychiatric condition has a biological component. Thus, the term functional became obsolete and even misleading.

Complications of Alcohol Withdrawal

Wernicke's encephalopathy is an acute, potentially reversible neurologic disorder that is believed to result from a deficiency of thiamine and is often secondary to chronic alcohol abuse. Features include disturbance of consciousness (ranging from mild confusion to coma), ophthalmoplegia, nystagmus, and ataxia. The disorder has a high mortality and can lead to death within 24 hours. If untreated, it can progress to Korsakoff's psychosis. This is a chronic condition that usually presents as impairment of short-term memory with inability to learn new information and compensatory confabulation. Korsakoff's psychosis probably represents irreversible brain damage secondary to the combined toxic-ity of alcohol and metabolic derangement resulting from thiamine deficiency.

Psychotic Disorder Due to a General Medical Condition

That do not necessarily cause dementia ( multi-infarct disease ) are associated with late-life onset of schizophrenia. Whether this syndrome should be thought of as a psychotic disorder secondary to a general medical condition or as late-onset schizophrenia cannot be determined from the available data. Some specific delusion-like false beliefs also have been observed in patients with damage to the occipital lobe (denial of blindness) and parietal lobe (denial of hemipare-sis). Blindness and deafness have been associated with visual and auditory hallucinations, and complex partial seizures have been associated with olfactory hallucinations and delusions. Psychosis has been reported as a consequence of vitamin B12 deficiency, meningioma, and antiretroviral therapy. Alcoholic hallucinosis is a specific syndrome that occurs within 2-3 days after termination of drinking. In this syndrome, frightening auditory or visual, sometimes tactile, hallucinations occur in an otherwise clear...

Implementing The Mind

Specific outstanding problems in this context concern autobiographical episodic memory, metacognition (higher-order thoughts), representation of others' minds ( theory of mind ), selected neurological disorders, including schizophrenia, multiple personality, autism, and the forbidden topic3 consciousness. Remarkably, all these topics have one element in common they all involve the concept of an agent (27). There is no doubt that much human brain information processing deals with abstract representations of agents, such as instances of the self and others (as opposed to representations of physical bodies of these agents and other things). This sort of representation and information processing could be the key building block missing at all levels of the structure of cognitive neuropsychology. This could be the answer to the question regarding the principal difference between brains and computers as we know them today. If so, then implementing the right sense of agency (based on a...

TABLE 91 Classification of Mood Disorders

Mood disorders usually occur in episodes that come and go. Some of the more debilitating mental illnesses, such as schizophrenia and dementia, tend to be chronic. People with mood disorders, however, spend much of their lives hovering around the neutral point on the emotional temperature scale. When at that point, or even when in the mildly elevated range, they function very normally. Jim, described in chapter 2, had only a single

The Relationship Between Substance Abuse And Psychopathology

Psychopathology may be a risk factor for SUDs. As described previously, studies of patient and community samples have shown that the risk of having a co-occurring SUD is elevated in persons with psychiatric disorders. For example, dopaminergic dysfunction in patients with schizophrenia has been hypothesized to increase their risk of SUDs particularly cocaine use disorders (Green et al., 1999 Smelson, Losonczy, Kilker, et al., 2002). Another theory, widely known as the self-medication hypothesis (Khantzian, 1989, 1997), suggests that psychopathology leads patients to use substances in an attempt to decrease unwanted psychiatric symptoms. For example, a patient with insomnia due to PTSD nightmares may use alcohol or marijuana to induce sleep. Although research has not found direct connections between particular psychopathologi-cal symptoms and specific substances (rather, patients tend to misuse a wide variety of substances to treat a range of symptoms), the general principle is an...

Dsmivtr Diagnostic Criteria

The disturbance is not better accounted for by another Axis I disorder (e.g., major depressive disorder, schizophrenia). Anxiety and psychosis, particularly paranoid delusions, are common in AD. Benzodiazepines can be disinhibiting in such individuals and may exacerbate confusion and should be avoided if possible. If minor tranquilizers are required, agents with a shorter duration of action (e.g., lorazepam, oxazepam) are preferred. Antipsychotic medications with high anticholinergic potential (e.g., thioridazine, chlorpromazine) may also affect memory adversely. While these agents have been favored in the past because of their tendency to produce sedation, newer agents such as olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel) ziprasi-done (Geodon) and aripipevazole (Abilify) have been reported to have lower incidences of neuroleptic-related side effects. However, a reported increase in cerebrovascular events (e.g., stroke, TIA) in elderly patients taking these...

The History Of Biological Psychiatry

14 The process of self-reconstitution can only be understood if the history of terms, concepts and behaviours is considered independently. For example, the fact that the word melancholia has lasted for more than 2000 years has led some to believe that the current condition called melancholia is, in fact, the same as that known by the same word 2000 years ago. This is an anachronism based on the ontological view of disease. The same error has led some to express surprise about the fact that schizophrenia was not reported before the eighteenth century. The explanation regarding melancholia is that all that survived was the word as an empty shell. In the case of schizophrenia, the condition was not reported simply because it did not exist it was only constructed during the late nineteenth century (see Berrios, 2000b). 18 Why Jackson has had so little influence on British (and later) AngloSaxon psychiatry (compared with neurology) is an interesting and understudied question (Berrios, 1977...

Severely and Persistently Mentally III Populations

Several investigators have examined integrated treatments for SPMI adults. Effectiveness trials by Drake and colleagues have obtained more success in decreasing substance use (Drake et al., 1998 McHugo, Drake, Teague, & Xie, 1999) and hospitalization (McHugo et al., 1999) than in diminishing psychiatric symptoms (Drake, Yovetich, Bebout, Harris, & McHugo, 1998 Drake et al., 1998) or improving functional status or quality of life (Drake et al., 1997). However, these interventions did not compare patients randomized to different treatments. Rather, treatment clinics were assigned to administer one intervention versus another. A recent review of the prospective, controlled trials of integrated treatment programs for SPMI dually diagnosed individuals (Jeffery, Ley, McLaren, & Siegfried, 2003) concluded that methodological flaws precluded determining whether one particular integrated treatment model is more effective than another, or whether integrated treatment in general is superior to...

Dementia Due to Parkinsons Disease

An expressionless facial countenance. The tremor in Parkinson's disease has a regular rate and is most prominent when the individual is sitting with arms supported and has been described as an intention tremor. Paranoid delusions and visual hallucinations may occur, but auditory hallucinations are rare. Antipsychotics with low incidence of extrapyramidal symptoms such as quetiap-ine, olanzapine, and ziprasidone are recommended. The pharmacological treatment of Parkinson's disease involves the use of a number of types of medication. These include selegiline (Eldepryl), a selective monoamine oxidase inhibitor, levodopa, other dopamine agonists (pramipexole Mirapex , bromocriptine, pergolide mesylate Permax , amantadine), and various anticholinergic agents (e.g., benztropine). Selegiline should not be given to individuals on antidepressant medication as there is a risk that dopaminergic agents may activate psychosis or mania. When discontinuing levodopa after a long course of treatment,...

Attention and consciousness

The CODAM model allows Taylor and his colleagues to arrive at several important conclusions. For example, they explain the meditational processes aimed at achieving a state of 'pure consciousness' found in several Eastern religions. They argue that advanced forms of meditation force the attentional corollary discharge to block sensory input and turn to attending only to itself. Another application is the explanation of the at-tentional blink which occurs when someone is asked to attend to several objects presented in succession to one another. Schizophrenia, inattention blindness and blindsight are also approached through the CODAM model.

Shortcomings of current therapy

By the ASDA) had higher frequency of psychosis, paranoia or disordered thinking, alcohol or poly-drug abuse, and psychiatric hospitalizations compared to patients using standard doses 112 . The presence of rebound hypersomnia is more frequent with higher dosages of amphetamines.

Pharmacotherapy Targeting Substance Dependence in Dually Diagnosed Populations

Although pharmacotherapies aimed specifically at decreasing alcohol or drug use (e.g., naltrexone, disulfiram) can be efficacious in improving SUD outcomes in non-dually-diagnosed populations, the literature on the use of these medications in dually diagnosed populations is quite thin. Concerns that disulfiram may cause or exacerbate psychosis (Mueser, Noordsy, Fox, & Wolfe, 2003) have contributed to a reluctance to prescribe it in patients with SPMI (Kingsbury & Salzman, 1990). While there have been no controlled studies of disulfiram in populations with alcohol dependence and SPMI, there have been a few published case reports (Brenner, Karper, & Krystal, 1994) and case series (Kofoed, Kania, Walsh, & Atkinson, 1986 Mueser et al., 2003) describing its tolerability and potential benefit for improving alcohol outcomes and hospital-ization rates for those who remain in treatment. Additionally, there is preliminary evidence that naltrexone may improve drinking outcomes in patients with...

Postmortem Brain Studies

The reciprocal changes in the levels and activity of Gaq 11 in BD occipital cortex also appear to uniquely distinguish this disorder from Alzheimer's disease (79a), schizophrenia (44), alcoholism (44), and major depression (80), in which the activity of Gaq 11 is either increased or decreased in the absence of changes in Gaq 11 and PLC-P1levels. It is also noteworthy that the largest differences in Gas levels and forskolin-stimulated adenylyl cyclase activity were observed in the occipital cortex of BD subjects (10,11). Given the substantial evidence of crossregulation between cAMP and PPI signaling pathways, the possibility that the observed differences in Gaq 11 and PLC-p1 levels may reflect the consequences of relatively greater disturbances in cAMP signaling in this brain region in BD cannot be excluded.

Integration Of Psychotherapy And Pharmacotherapy For Dually Diagnosed Patients

Barrowclough, C., Haddock, G., Tarrier, N., Lewis, S. W., Moring, J., O'Brien, R., et al. (2001). Randomized controlled trial of motivational interviewing, cognitive behavior therapy, and family intervention for patients with comorbid schizophrenia and substance use disorders. Am J Psychiatry, 158(10), 1706-1713. Batki, S. L., Dimmock, J., Cornell, M., Wade, M., Carey, K. B., & Maisto, S. A. (2002). Directly observed naltrexone treatment of alcohol dependence in schizophrenia Preliminary analysis. San Francisco Research Society on Alcoholism. Bellack, A. S., & DiClemente, C. (1999). Treating substance abuse among patients with schizophrenia. Psychiatr Serv, 50(1), 75-80. Brunette, M. F., Mueser, K. T., Xie, H., & Drake, R. E. (1997). Relationships between symptoms of schizophrenia and substance abuse. J Nerv Ment Dis, 185(1), 13-20. Buckley, P., Thompson, P., Way, L., & Meltzer, H. Y. (1994). Substance abuse among patients with treatment-resistant schizophrenia Characteristics and...

Two Recent Discoveries in Psychiatric Mental Genetics

Two recent discoveries in the genetics of mental phenomena, one from the genetics of schizophrenia and the other from a genetic discovery involving a personality trait known as novelty seeking, illustrate the problems of a purely genetic approach to mental illnesses. The following sections discuss some of the methodological problems with the research in these areas and argue that the genetics of mental health are best understood through a study of behavioral genetics. A review of recent advances in this area suggests potential problems as well as possible future successes in explaining and treating mental disorders. Schizophrenia Schizophrenia is a major mental disorder that occurs in approximately one out of every hundred individuals, a startlingly high prevalence for such a serious illness. It has been known for many years that the disorder runs in families, and a number of family, twin, and adoption studies have indicated that genetic factors are an important component. The 1980s...

The Scientific Evidence

The final area of scientific inquiry, behavioral traits, is the most contentious. There are several scientific obstacles to correlating genotype and behavior. One problem is in defining the end point, whether it be schizophrenia or intelligence. Another problem is in excluding other possible causes of the condition, thereby permitting a determination of the significance of any supposed correlation. Much of the research today on genes and behavior engenders very strong feelings, because of the social and political consequences of these supposed truths. Thus, more than any other aspect of genetics, discoveries in behavioral genetics should not be expressed as irrefutable until there has been substantial scientific corroboration.

Psychiatric Disturbance

Structured diagnostic interviews have been increasingly utilized in the objective formulation of substance use disorder diagnoses, as well as other psychiatric diagnoses. Several instruments, all with good psychometric properties, are currently available. The Structured Clinical Interview for DSM-III-R (SCID Spitzer, Williams, & Gibbon, 1987) is presently the most frequently used instrument. Other structured interviews are the Diagnostic Interview Schedule (DIS Robins, Helzer, Croughan, &Ratcliff, 1981) and the Schedule for Affective Disorders and Schizophrenia (SADS Spitzer, Endicott, & Robins, 1975). There are some important differences among the SCID, DIS, and SADS. In contrast to the SCID and SADS, which are semistructured interviews requiring a high level of clinical skill to administer and interpret, the DIS is fully structured, so that it can be administered by paraprofessionals. Three diagnostic interviews are available for adolescents. These include the Diagnostic Interview...

Delirium Dementia Amnestic Disorder And Other Cognitive Disorders

In DSM-III-R, delirium, dementia, amnestic disorder, and other cognitive disorders were included in a section called organic mental disorders, which contained disorders that were due to either a general medical condition or substance use. In DSM-IV, the term organic was eliminated because of the implication that disorders not included in that section (e.g., schizophrenia, bipolar disorder) did not have an organic component. In fact, virtually all mental disorders have both psychological and biological components, and to designate some disorders as organic and the remaining disorders as nonorganic reflected a reductionistic mind-body dualism that is at odds with our understanding of the multifactorial nature of the etiological underpinnings of disorders.

Lysosomal Disorders

In the adult form of metachromatic leukodystrophy, initial symptoms are often psychiatric, leading to a misdiagnosis of schizophrenia, or behavioral, leading to a diagnosis of dementia (25,26). Neurologic symptoms, such as chorea or dystonia, appear late and may be missed (27,28). Adult patients with MLD may also present with recurrent neuropathies (29,30) or new seizure disorders (31). The diagnosis of adult MLD often is suspected only because of white matter abnormalities detected by CT and or MRI.

Functional Visual Loss and Malingering

Demonstrable Organic Disease Examples

Malingering is an intentionally deceptive mimicry of a nonexistent disorder, and augmentation is an intentionally exaggerated account of an existing disorder. Functional visual loss is a subjectively described visual disorder without an objectively observed abnormality. It is an unconscious, often subconscious, simulation of a nonexistent disease. (Synonyms include psychogenic visual loss, conversion, and hysterical visual loss). The related group of psychogenic ocular disorders includes functional disease, psychosomatic disease, and artificial eye diseases. Psychosomatic eye disease is initiated by a psychically triggered (or heavily influenced) organic disease with demonstrable pathological findings, as for example, in some reported cases of glaucoma, uveitis, or central serous retinopathy. Artificial eye diseases arise by self-inflicted trauma (autoaggression) and have demonstrable pathological findings during the eye examination. This type is usually associated with psychoses or...

Comparison Of Dsmivtr And Icd10 Diagnostic Criteria

The DSM-IV-TR and ICD-10 item sets and diagnostic algorithms for autistic disorder are almost identical. However, the ICD-10 exclusion criterion is considerably more broad, requiring that a number of other disorders should be considered instead (e.g., early onset schizophrenia, mental retardation with an associated

Rates Of Psychiatric Disorders Among People Living With Hiv Infection

The landmark HIV Cost and Services Utilization Study (HCSUS) found that a large, nationally representative probability sample of adults receiving medical care for HIV in the United States in early 1996 (N 2,864 2,017 men, 847 women) reported major depression (36 ), anxiety disorder (16 ), and drug dependence (12 ) (Bing et al., 2001 Galvan et al., 2002), as well as heavy drinking at a rate (8 ) almost twice that found in the general population and high rates of drug use (50 ). The HCSUS study remains the most comprehensive view we have of the prevalence of psychiatric disorders among people living with HIV AIDS, though the study was not designed as a diagnostic assessment of psychiatric disorders among people with HIV AIDS and so rates of psychosis, bipolar disorder, alcohol abuse or dependence, and substance abuse, among others, were not obtained. Disorders of alcohol and other drug (AOD) abuse are differentiated from dependence in the Diagnostic and Statistical Manual of Mental...

Dextromethorphan Robitussin

An OTC synthetic opioid agonist and analog of codeine with no analgesic activity that is used as a cough suppressant, like codeine. In overdose, causes miosis and CNS depression, with choreoathetosis and dystonia from increased presynaptic serotonin release. Also acts as a sigma agonist and can cause a PCP-like psychosis.

Variations in Clinical Presentation

(N 18,980), subjects who reported feelings of worthlessness or guilt were the most likely to have psychotic features (Ohayon and Schatzberg 2002). Most studies find that depressive symptoms are more severe in patients with psychotic features than in those without psychosis, but suicide attempts are probably not more frequent (Lykouras et al. 2002). Identification of psychotic depression as a mood disorder is relatively straightforward when symptoms occur in the classic sequence that is, when mood and neurovegetative changes occur before the development of hallucinations, delusions, and bizarre behavior. The clinician's task is rendered easier still when typical depressive delusions (i.e., mood-congruent delusions) are present or when the patient has a history of mood disorder. More challenging are patients in whom the presenting complaint, often registered by family members, is of a persecutory delusion accompanied by prominent behavior disturbance. The following cases are...

Psychopharmacotherapy for Geriatric Depression

With this limited evidence base in mind, in the following section, we review the advantages and disadvantages of currently available antidepressants in the treatment of nonpsychotic depression, including major depression, dys-thymia, and minor depression. Because the presence of psychosis (hallucinations, delusions, severe thought disorder, or behavioral regression) appears to significantly reduce the rate of response to antidepressant therapy, even when concomitant antipsychotic medications are prescribed, psychotic depression is discussed under a separate heading later in this chapter ( Psychopharmaco-therapy for Psychotic Depression ).

In Search and Discovery of Potential New Therapeutic Indications

Beyond this application, research focused on diseases in which symptoms could be related to cognition deficits. In the five-choice serial reaction time task of attentional function in rats, modafinil had attention-enhancing effects that may be relevant to the treatment of cognitive deficits in schizophrenia.85 Likewise, in patients with schizophrenia, modafinil produced a significant improvement in attentional set shifting (despite no effect of modafinil on this task being seen in healthy volunteers), that led to the assumption that the compound may have potential as an important therapy for cognitive impairment.86 The results of a preliminary open study suggested that modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition in patients with schizophrenia or schizoaffective disorder.87 Other applications resulted from case observations such as spastic cerebral palsy.88

The Clozapine Hypothesis

Clozapine 12 is the prototypic atypical antipsychotic, which has broad spectrum efficacy in schizophrenia, being efficacious in the treatment of refractory schizophrenics, with potential efficacy in treating cognitive deficits and having a lower extrapyramidal side effects (EPSs) liability.20'21 These positive attributes are however limited by a high incidence of potentially fatal agranulocytosis that requires continuous monitoring in the clinical situation.

Obsessive Compulsive Disorder

OCD is a chronic and often disabling disorder that affects 2-3 of the US population. OCD has been labeled a 'hidden epidemic' and is ranked 20th in the Global Burden of Disease studies among all diseases as a cause of disability-adjusted life years lost in developed countries. OCD is often associated with substantial quality of life impairment especially in individuals with more severe symptoms. The disease usually begins in adolescence or early adulthood with 31 of first episodes occurring at 10-15 years of age and 75 by the age of 30. The essential features of OCD are recurrent obsessions or compulsions that are severe enough to be time consuming (i.e., take more than 1 h per day) and or cause significant levels of distress or interference with normal daily activities. OCD can have comorbidity with major depression and social phobia, as well as other mental disorders such as eating disorders and schizophrenia.9

First Generation Typical Antipsychotic Drugs

The serendipitous finding in 1951 that the major tranquilizer, chlorpromazine 1, was effective in treating delusions and hallucinations associated with schizophrenia and other psychotic disorders marks the beginning of modern therapy for schizophrenia.3 Unfortunately, treatment with chlorpromazine was accompanied by the development of EPS, some appearing even after the first dose (e.g., dystonias, akathisia). Other adverse effects were delayed for days or weeks such as parkinsonism, and the sometimes fatal neuroleptic malignant syndrome. Tardive dyskinesia, characterized by abnormal involuntary movements of the tongue, facial muscles, or limb muscles, develops in about 20 of patients and may be irreversible. Chlorpromazine also increased prolactin secretion leading to gynecomastia, galactorrhea, menstrual irregularities, sexual dysfunction, and possibly bone loss over the long term. Sedation, hypotension, and weight gain were also common with chlorpromazine. Despite these concerns,...

Neuronal Nicotinic Receptor Agonists

The incidence of smoking is high in patients with schizophrenia, a rate at least three times higher than the general population. In fact, nicotine appears to produce a modest transient improvement in cognitive and sensory deficits in these patients. It has been suggested that smoking in schizophrenia represents an attempt to self-medicate.39 However, these views must be interpreted with caution. Overall, schizophrenic patients have a high degree of comorbid abuse of a variety of substances including nicotine, alcohol, cannabis, cocaine, and amphetamine. Importantly, the rate of substance abuse is higher than in the general population for all of these substances in spite of the fact that such abuse is associated with poorer outcomes, exacerbation of positive symptoms, increased hospitalization, and increased frequency of homelessness. This increased propensity to abuse a variety of substances regardless of consequences suggests that there may be a disregulation of reward systems in...

Experimental Disease Models

Schizophrenia is clearly a disorder with a primary impact on higher cognitive function. Therefore, the modeling of this disorder in less cognitively developed species than human represents a significant challenge. The validity of an animal model for any disorder can be rated on three scales predictive, construct, and face validity. 'Predictive validity' focuses on how well results produced in the animal model are borne out in the clinic. More often, and particularly in the case of schizophrenia, animal models are back-validated using clinical benchmarks to provide a basis for arguing for future predictive validity. While this reasoning seems to hold for recent atypical antipsychotics in that they produce preclinical effects similar to that observed for older atypicals, the fact that these newer compounds are largely subtle variations on the clozapine theme discussed above raises questions regarding the usefulness of this back-validation. This is a significant caveat in that there is...

Dopamine Receptor Modulators Dopamine Partial Agonists

To the extent that DA overactivity and excessive stimulation of the D2 family of DA receptors are responsible for at least the positive symptom component of schizophrenia, therapeutic avenues other than direct antagonists may be available to modulate these DA neurochemical abnormalities. By exploiting the differential receptor reserve of various tissues and brain regions, it may be possible to use partial agonists of differing intrinsic activity to modulate DA activity. The full spectrum of pharmacology is available for the DA system from full inverse agonists to neutral antagonists to partial agonists to full agonists. Most existing antipsychotic agents are inverse agonists at the D2 receptor family. Regardless of the tissue receptor reserve, inverse agonists will act as antagonists. However, partial agonists have, by definition, lower intrinsic activity. Partial agonists, therefore, can behave as antagonists or agonists depending upon the tissue receptor reserve and their level of...

Neurokinin3 Antagonists

Two neurokinin3 (NK3) antagonists, osanetant 76 and talnetant 77, which have selective interactions with the NK3 receptor in the range of 1 nM, have been reported to have clinical efficacy in schizophrenia.74 Osanetant had similar efficacy to haloperidol on positive symptoms with reduced EPS and weight gain liabilities. NK3 receptors present on DA neurons in the A9 and A10 groups are thought to modulate DA release, agonists increasing DA release.

Acquired immune deficiency syndrome dementia

Dementia in AIDS is an exclusionary diagnosis characterized by cognitive and motor disturbances and behavioral changes including impaired short- and long-term memory, decreased concentration, and slowed thought processing. The pathophysiology involves neurovirulent strains of HIV, excitotoxicity, and inflammation. AIDS dementia is treated with the antiviral zidovidine, together with drugs for the treatment of the associated psychosis and depression. A number of autoimmune neuroinflammatory disorders (see 6.09 Neuromuscular Autoimmune Disorders) affect either the central or peripheral nervous system. Many of these disorders are exceptionally rare such as Moersch-Woltman syndrome (stiff-man), Lambert-Eaton myasthenic syndrome, and myasthenia gravis (MG). While uncommon, these disorders tend to be highly debilitating as they directly alter neuromuscular transmission. The most common of these disorders is MG which affects an estimated 60 000 people in the USA. The primary pathology...

Impulse Control Disorders Not Elsewhere Classified

As is suggested by the title of this diagnostic grouping, no one diagnostic class in DSM-IV-TR comprehensively includes all of the impulse control disorders. A number of disorders characterized by impulse control problems are classified elsewhere (e.g., conduct disorder, attention-deficit hyperactivity disorder, oppositional-defiant disorder, delirium, dementia, substance-related disorders, schizophrenia and other psychotic disorders, mood disorders, antisocial and borderline personality disorders). What ties together the disorders in this class is that they present with clinically significant impulsive behavior and that they are not better accounted for

Pharmacotherapeutic Considerations

May be associated with the exacerbation of psychotic symptoms in persons with preexisting psychotic illness or with a vulnerability to developing psychosis, and may further be associated with the relapse into psychosis in persons with schizophrenia. The use of cannabinoids should be conducted with great caution in individuals with a history of mental illness.

Clinical Trial Issues

Trials for novel antipsychotic drugs usually employ the randomized double blind placebo-controlled design and focus on a reduction in acute psychotic symptoms and the prevention of relapse as primary outcomes.52 Trials usually average 50-60 participants, but large studies have been reported with sample sizes ranging from 200 up to 2000 subjects. Typical trial length is 6 weeks or less, but trials lasting for more than 6 months have provided valuable information on long-term treatment. Several issues are apparent in generalizing the results obtained from clinical trials to the general population of schizophrenics, and to clinical practice. Most large clinical trials for novel antipsychotic medications are carried out in a population of acute exacerbated schizophrenic patients, or in patients that are resistant to available treatments. The trials typically exclude individuals with comorbid psychiatric disorders or those that require continued use of antidepressants or mood stabilizers....

Norepinephrine transporter polymorphisms

At least 13 polymorphisms of NET have been identified,20 the functional significance of which is unknown. Alterations in the concentration of NE in the CNS have been hypothesized to cause, or contribute to, the development of psychiatric illnesses such as major depression and BPAD. Many studies have reported altered levels of NE and its metabolites NMN and dihydroxyphenylglycol (DHPG) in the CSF, plasma, and urine of depressed patients as compared with normal controls. These variances could reflect different underlying phenotypes of depressive disorders with varying effects on NE activity. The melancholic subtype of depression (with positive vegetative features, agitation, and increased hypothalamic-pituitary-adrenal (HPA) axis activity) is most often associated with increased NE. Alternatively, so-called atypical depression is associated with decreased NE and HPA axis hypoactivation. In one study, urinary NE and its metabolites were found to be significantly higher in unipolar and...

Caveats in Interpreting Electrophysiologic Data in Substance Abuse Research

Similarly, even though the reductions in P300 amplitude observed during withdrawal from either heroin, cocaine or ethanol (Poijesz et al., 1987 Kouri et al., 1996 Bauer, 1997 Noldy and Carlen, 1997) are very similar to those observed in a number of psychiatric disorders including dementia (Pfefferbaum et al., 1984) schizophrenia (Roth et al., 1980), depression (Diner et al., 1985) and borderline personality disorder (Kutcher et al., 1987), this lack of diagnostic specificity of the P300 has provided important information on the similarities between acute withdrawal from drugs of abuse and these other psychiatric disorders.

Complexity and Research Strategies in Behavioral Genetics

Rather, its themes point toward complexity, multilevel interactionism, and the critical role of environment and learning in explanations of and interventions in mental disorders. Part of what motivates an interest in genetics, particularly psychiatric genetics, is the hope that identification of the gene, or more likely genes, contributing to serious mental disorders may give us information that we can use to diagnose and treat these disorders. This is based on the premise that an understanding of the molecular origin of a disorder such as schizophrenia or manic-depressive illness can simplify and clarify our approaches to existing illnesses. I have some doubts that such simplifications and clarifications will occur, but offer some suggestions for where we might look to achieve these hoped-for advances.

Physiological Effects

Mon in first-time users or in older experimenters who have not used marijuana for a long time. Hypervigilance, sometimes resembling frank paranoia, is seen with higher doses. Cannabis-induced psychosis is rare but does occur, especially in countries where heavy smoking is more common and the THC concentration of the plant is higher (Chopra & Smith, 1974). The term hemp insanity refers to this type of psychosis. The question of whether the drug causes long-term psychotic disorders is more difficult to answer. Clearly, first-break psychotic episodes are commonly associated with marijuana ingestion, but again, whether they are causal is a matter of debate. More probably, individuals who are prone to psychosis are attracted to the drug. In a population that is prone to psychosis, such as individuals with schizophrenia, marijuana is a risk factor for relapse and psychosis (Arseneault, Cannon, Witton, & Murray, 2004 Verdoux, Gindre, Sorbara, Tournier, & Swendsen, 2003).

Patterns of Psychoactive Substance

Socially sanctioned, episodic psychoactive substance use may involve heavy use, with marked intoxication or drunkenness (Bunzel, 1940). In a low-technology environment, this pattern may cause few problems, although psychotomimetic drugs such as cannabis can cause toxic psychosis (Chopra & Smith, 1974). In a high-technology environment, with modern methods of transportation and industrial machinery, intoxication even at mild traditional levels may be life threatening (Stull, 1972). Binge-type alcohol problems include delirium tremens, fights, sexually transmitted disease, and falls.

Electroconvulsive Therapy

ECT remains the single most effective treatment for major depression with or without psychosis in elderly patients. Remission rates in the range of 75 90 or greater can be obtained in nai've patients (i.e., those who have not tried and failed other treatments), but in the more typical elderly patient who has had an inadequate response to other treatments, response rates (defined as a decline of 50 or more in pretreatment depression ratings) are in the 80 -90 range, even in the old-old (i.e., older than 75), and side effects are usually limited to transient memory impairment (Tew et al. 1999). ECT is about equally effective in psychotic and nonpsychotic depression however, because psychopharmacological therapy has relatively limited effectiveness in psychotic depression, this condition is the strongest indication for ECT as a first-line therapy. Other indications for ECT as the treatment of first choice include One effective approach is to use brief-pulse, bilateral electrode placement...

The Glutamate Hypofunction Hypothesis

Glutamate is the major excitatory neurotransmitter in the CNS, and antagonists of the NMDA (N-methyl-D-aspartate) subtype of glutamate receptor, the psychotomimetics, phencyclidine 2 (PCP) and ketamine 3, mimic the positive, negative, and cognitive symptoms of schizophrenia.13 In the clinic, NMDA receptor antagonists faithfully mimic the symptoms of schizophrenia to the extent that it is difficult to differentiate the two. Controlled human studies of psychosis induced by the NMDA receptor modulators, PCP or ketamine, as well as observations in recreational PCP abusers, have resulted in a convincing list of similarities between the psychosis induced by NMDA receptor antagonism and schizophrenia. In addition, NMDA receptor antagonists can exacerbate the symptoms in schizophrenics, and can trigger the re-emergence of symptoms in stable patients. Finally, the finding that NMDA receptor coagonists such as glycine 4, D-cycloserine 5, D-serine 6, and milacemide 7, produce modest benefits in...

Neurogenesis creation of new neurons critical to antidepressant action

The seminal studies by Duman and co-workers14 on neurogenesis may help to explain why antidepressants typically take a few weeks to have an effect and may indicate why a rapid-acting antidepressant may not be a viable propositition.14 These workers created a strain of 5HT1A'knockout' mice that as adults show anxiety-related traits, such as a reluctance to begin eating in a novel environment. While unaffected by chronic treatment with the SSRI fluoxetine, the mice became less anxious after chronic treatment with TCAs that act via another neurotransmitter, NE, suggesting an independent molecular pathway. While chronic fluoxetine treatment doubled the number of new hippocampal neurons in normal mice, it had no effect in the knockout mice. The tricyclic imipramine boosted neurogenesis in both types of mice, indicating that the 5HT1A receptor is required for neurogenesis induced by fluoxetine but not imipramine. Chronic treatment with a 5HT1A-selective drug confirmed that activating the...

NAcetyl LaspartylLglutamate

As discussed above, activators of the group II mGluRs hold promise as novel antipsychotics. Therefore, it has been suggested that inhibitors of NAAG peptidase could increase the levels of NAAG and provide antipsychotic efficacy through the activation of group II mGluRs.71 A number of potent and selective NAAG peptidase inhibitors have been discovered, including 2-PMPA 70, the more potent analog GPI-5693 71, and the structurally distinct ZJ38 72. The ability to selectively target these enzymes provides an opportunity to explore potential efficacy in animal models of schizophrenia.

Methods for Locating Genes

Linkage studies require collecting DNA from multiplex families (i.e., multiply affected families or families where two or more members have a particular disease). Locating multiply affected families, collecting samples to extract DNA, and making careful diagnoses is obviously quite labor-intensive. To extract the maximum power from linkage studies, scientists need families running through several generations with many ill members, and with the illness arising from only one side of the family. Because of the labor-intensiveness of this work, investigators usually band together in collaborative groups and pool their data. Much of the early work that reported locating genes for various mental illnesses has depended on these methods. At least until the late 1990s, when you read that the gene for schizophrenia has been found on Chromosome 6, the data usually came from a linkage analysis. An alternate method is known as the the affected sib pair study. In this variant, DNA is obtained from...

Psychiatric Comorbidity And Sequelae

Studies conducted with both inpatients and outpatients with schizophrenia show prevalence of cocaine use falling between 20 and 93 (Regier et al., 1990 Rosenthal, Hellerstein, Miner, & Christian, 1994 Schwartz, Swanson, & Hannon 2003 Ziedonis & Fischer, 1996). Cocaine-abusing persons with schizophrenia have fewer negative signs (Lysaker, Bell, Beam-Goulet, & Milstein, 1994), but more depression and anxiety at the time of hospital admission (Serper, Alpert, Richardson, & Dickson, 1995) at posttreatment, no differences in negative signs or mood are observed, suggesting that differences result from the effects of cocaine. Persons with schizophrenia who abuse cocaine have increased morbidity, evidenced by higher rates of hospitalization, greater suicidality, and the need for higher doses of neuroleptics than both users of other drugs and nonusers (Seibyl, Satel, Anthoy, & Southwick, 1993). Cocaine use may itself induce noxious psychiatric effects, some of them psychotic in nature....

Conditioned avoidance

The ability of a compound to inhibit the conditioned avoidance response (CAR) to an aversive stimulus is one of the oldest predictors of antipsychotic efficacy. In this test, rats are trained to move from one side of shuttle box to the other on presentation of an audible cue (the conditioned stimulus) in order to avoid a footshock (the unconditioned stimulus). Once the animals have been trained, both typical and atypical antipsychotics are effective in decreasing the CAR to the conditioned stimulus without altering the escape response elicited by the unconditioned stimulus. This inhibition of the CAR is thought to be mediated by a reduction in dopaminergic function in the striatum and nucleus accumbens.41 Therefore, inhibition of CAR is not an actual preclinical model of schizophrenia, but rather a facile in vivo method of detecting DA receptor blockade. The comparison between doses of antipsychotics that inhibit CAR and doses that induce catalepsy provides a convenient method to...

Cocaine and Methamphetamine

Ecstasy (3,4-methylenedioxymethamphetamine) showed that basic vehicle control is only moderately affected but risk taking is increased. It seems likely that abrupt discontinuation of either drug in a chronic user could result in driving impairment, but that situation has never been tested (70). Large doses can result in toxic psychosis with symptoms indistinguishable from paranoid schizophrenia, a condition that is extremely unlikely to improve driving performance.

The Serotonin 5HT Hypothesis

The serotonin (5HT) hypothesis of schizophrenia actually pre-dates that of DA. The ability of the hallucinogen lysergic acid diethylamide (LSD) to antagonize the effects of 5HT on smooth muscle led to the hypothesis that schizophrenia was caused by a decrease in central serotonergic function.11 This theory, largely predicated on the similarities between schizophrenic psychosis and LSD-induced hallucination, was modified with the discovery that LSD could act as a 5HT agonist in some systems. These findings led to the search for endogenous psychotogens, an effort that never bore convincing fruit. With the discovery of chlorpromazine 1, interest in DA D2 receptors rapidly supplanted interest in the 5HT system. The observation that 5HT2A antagonism is a defining characteristic of the newer 'atypical' antipsychotics, together with recent evidence that all effective antipsychotics are 5HT2A inverse agonists,12 has reawakened interest in the role of 5HT in schizophrenia. To date there has...

Reduced Side Effect Liability

Current pharmacological approaches to the treatment of schizophrenia suffer from two major issues side effects and limited efficacy. The first major unmet medical need is improved side effect liability. Even the best of the modern atypical antipsychotics produce significant side effects with a low therapeutic index. Individuals with schizophrenia have an increased risk of death and, in general a 20 shorter life span84'85 that, in part, may be attributable to the use of current antipsychotic medications. As discussed above, atypical antipsychotics have a clear lower risk of inducing EPS and hyperprolactinemia (with the exception of risperidone) when compared to typical antipsychotics, but the risk still exists. Furthermore, several atypicals, particularly clozapine and olanzapine, increase the risk of sedation, obesity, high blood sugar and diabetes, and dyslipidemia. Very rare cases of neuroleptic malignant syndrome, a rare but potentially fatal reaction characterized by fever,...

Normal Grief Bereavement

Studies generally concur that uncomplicated grief or bereavement may include any or all of the features of major depression except suicidality, psychosis, severe loss of self-esteem and or functionality, and psychomotor retardation. Appetite and sleep disturbance, multiple somatic complaints, anhedonia, anxiety, mild feelings of self-deprecation, the passive wish to join the loved one, sadness,

History Of Substance Abuse Treatment

Beginning with Galenic medicine, a key strategy has been to identify certain syndromes as having their etiology in alcohol and drug abuse. Once the etiology is determined, the specific treatment (i.e., cessation of substance abuse) can be prescribed. Examples of such substance-associated disorders include delirium tremens (i.e., alcohol and sedative withdrawal), withdrawal seizures, morphinism (i.e., opioid withdrawal), cannabis-induced acute psychosis, stimulant psychosis, and various fetal effects, such as fetal alcohol syndrome. Thus, description of pathophysiological and psychopathological processes, together with diagnostic labeling, has been a crucial historical step in the development of modern assessment and treatment for substance use disorders (Rodin, 1981).

Miscellaneous associations

Additional schizophrenia associations include GABBR1 (GABAb receptor) on chr6p21.3, a Ser9Gly polymorphism in the DA D3 receptor,40 the 5HT2A receptor, and CAPON (carboxy-terminal PDZ ligand of neuronal nitric oxide synthase). The reproducibility and uniqueness of these associations to schizophrenia is still under debate. The large number of studies focused on elucidating the genetic basis of schizophrenia and the multiple genetic foci thus far identified appear to be inversely proportional to the knowledge gained in understanding disease causality and treatment.27 Thus it is likely that another decade will be needed for the many interesting gene targets and their contribution to the hypotheses of disease causality will be put in an appropriate context. Schizophrenia is a complex genetic disorder with multiple risk genes of small effect that are made more complex by possible allelic heterogenicity and epistatic influences.7 In several instances (G72, GRM-3, and GRIN1) the genetic...

Historical Context

Besides sterilization procedures performed for the greater good, in the 1930s Washington, D.C., neuropsychiatrist Dr. Walter Freeman pioneered his drastic ice-pick psychosurgery. Also known as lobotomy, it initially involved partially destroying one of the brain's frontal lobes, thus causing great disfiguration. Freeman explains in Glimpses of Postlobotomy Personalities how, when all else fails, the desired change in the patient's anxious and fearful personality is effected Without the long, painful process of developing insight in the patients, psycho-surgery somehow relieves them of their sufferings and makes it possible for them to go back to their homes and to survive in the very environment in which their disorders developed (Robinson and Freeman, 15). In his case studies, however, the postoperative realities sound grim. Patients often were described as slothful, irritable, and angry. Nonetheless, in A History of Psychiatry Edward Shorter points out, The idea of operating on the...

Catechol Omethyltransferase

COMT is localized to chr22q11 where a microdeletion results in velocardiofacial syndrome (22qDS DiGeorge or Shprintzen syndrome), a genetic subtype of schizophrenia. The COMT gene exists in two versions Met158 and Val158, the former coding for a form of COMT that is less thermostable and thus has lower activity than the Val158. COMT is important for regulating DA but not norepinephrine (NE) levels in the prefrontal cortex.28 Val158Met heterozygotic mice which have high COMT activity and, correspondingly, low prefrontal cortex DA levels show greater tyrosine hydroxylase expression in the midbrain, indicative of increased DA synthetic capability. In human Val158 carriers, neuroimaging studies showed greater midbrain F-DOPA uptake than Met158 carriers, consistent with increased DA biosynthesis. DA levels in prefrontal cortex play a key role in cognitive function and high-activity Val158 is associated with poorer performance and 'inefficient' prefrontal cortex function in some but not all...

Screening Instruments and Rating Scales

Most brief mental status examinations do not assess frontal executive functions, and as a result, individuals with frontotemporal dementia may score in the normal range on brief examinations in the early to middle stages of disease. Several short batteries have been developed to help clinicians test for frontal lobe changes, including the Executive Interview (Royall et al. 1992) and the Frontal Assessment Battery (FAB Dubois et al. 2000). Both measures take about 10 minutes to administer and cover several different aspects of behavior, cognition, or motor function affected by frontal lobe syndromes. The FAB differentiates better between frontotemporal dementia and Alzheimer's disease than does the Mini-Mental State Examination (MMSE) (Slachevsky et al. 2004), and it is now used frequently in clinical research (e.g., Mendez et al. 2005). The Executive Interview correlates well with neuropsychological measures of executive function and is sensitive to differences in everyday functional...

Table of Contents

Chapter 25 Schizophrenia and Other Psychotic Disorders 219 Schizophrenia 219 Diagnosis 219 Treatment 228 Schizoaffective Disorder 242 Diagnosis 242 Treatment 243 Brief Psychotic Disorder 244 Diagnosis 244 Treatment 245 Schizophreniform Disorder 246 Diagnosis 246 Treatment 246 Delusional Disorder 247 Diagnosis 247 Treatment 249 Shared Psychotic Disorder 249 Diagnosis 249 Treatment 250

Disease Basis

Like the majority of central nervous system (CNS) disorders, the initial understanding of the factors causing schizophrenia was based on serendipity, in this instance, the finding that chlorpromazine, the first drug used for the treatment of the disease, was a dopamine (DA) receptor antagonist.3 Since then it has been well established that schizophrenia is a multifactorial disease involving both genetic and epigenetic factors7 that may also exist in several distinct subtypes. Identified risk factors for schizophrenia include winter birth low socioeconomic status cannabis use obstetric complications and intrauterine infection related to birth immigration living in a city (urbanicity) and the neighborhood cognitive social capital8 low intelligence quotient and a family history of the disorder. There is increasing data81 that schizophrenia can be associated with autoimmune diseases, e.g., celiac disease, acquired hemolytic anemia, thyrotoxicosis, interstitial cystitis, and Sjogren's...


Neuregulin (NRG1) on chr8p13 contains a core epidermal growth factor (EGF) domain and activates Erb-3 or -4 receptor tyrosine kinase.30 It is involved in migration of GABAergic interneurons, signaling between axons and Schwann cells and the interactions between NMDA receptors and PSD-95. NRG-1 knockout mice show symptoms of schizophrenia. While 17 of 21 genetic association studies showed polymorphisms in NRG-1 associated with schizophrenia, the majority lie in noncoding regions of the genome. The NRG-1 genotype has been associated with the therapeutic response to clozapine in a Finnish population. The evidence for the involvement of NRG-1 in schizophrenia is typified as 'substantial but not incontrovertible'30 and there have been studies with failure to replicate.31

Prepulse inhibition

A disruption in sensory and cognitive gating is hypothesized to be at the core of many of the symptoms of schizophrenia. Prepulse inhibition (PPI) refers to the ability of a low-intensity stimulus, or prepulse, to diminish the startle response elicited by a higher-intensity stimulus. This model has gained significant favor in recent years largely due to the findings that schizophrenic patients exhibit deficits in sensory and cognitive gating. This is particularly evident in studies of event-related potentials (ERPs) in the electroencephalogram of schizophrenic patients. The most common ERP paradigm has examined the latency and amplitude of P300 in response to an unpredictable change in a stimulus series (the 'oddball' paradigm). Reduced P300 amplitude in response to novelty in schizophrenic patients has been observed in a large number of studies.43 The P50 ERP exhibits interesting behavior in response to pairs of brief auditory stimuli presented in rapid succession. In normal...