Coping With Schizophrenia and Psychosis

The Schizophrenia-free Package

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

The Schizophreniafree Package Overview

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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...

Therapy of Schizophrenia

Schizophrenia is an endogenous psychosis of episodic character. Its chief symptoms reflect a thought disorder (i.e., distracted, incoherent, illogical thinking impoverished intellectual content blockage of ideation abrupt breaking of a train of thought claims of being subject to outside agencies that control the patient's thoughts), and a disturbance of affect (mood inappropriate to the situation) and of psychomotor drive. In addition, patients exhibit delusional paranoia (persecution mania) or hallucinations (fearfulness hearing of voices). Contrasting these positive symptoms, the so-called negative symptoms, viz., poverty of thought, social withdrawal, and anhedonia, assume added importance in determining the severity of the disease. The disruption and incoherence of ideation is symbolically represented at the top left (A) and the normal psychic state is illustrated as on p. 237 (bottom left).

Disruptedin Schizophrenia 1 DISC1

Disrupted-in-schizophrenia 1 (DISC1) at chrlq 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 Spectrum Disorders

As reviewed before, strong evidence exists that schizophrenia is a familial disorder and that genetic influences are involved in the clustering of schizophrenia in families. The liability to schizophrenia seems to be manifested in families not only through the occurrence of the classical disorder, but through other related phenotypes as well. That is, the predisposition to schizophrenia may be expressed in a number of different ways, including schizophrenia-like personality traits and cognitive dysfunctions, personality disorders, and possibly some other nonschizophrenic psychoses. Disorders that occur more frequently in the bio logical relatives of schizophrenic individuals than in the biological relatives of nonschizophrenic individuals are called schizophrenia spectrum disorders. Disagreement exists as to the exact composition of this spectrum, however. An accurate description of its boundaries is necessary so that researchers can determine which phenotypes reflect susceptibility...

Schizophrenia

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.

Autoimmuneneuromuscular disorders

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 underlying MG appears to be the production of autoantibodies directed against the alpha subunit of the neuromuscular nicotinic acetylcholine receptor. Through direct interference and complement-mediated lysis of the postsynaptic muscle membrane, the autoantibodies cause disruption in the motor endplate that leads to a weakness in skeletal muscle throughout the body. The autoimmune disorder systemic lupus erythematosus (SLE) and the neuroinflammatory...

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

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...

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...

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...

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...

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.

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....

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,...

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...

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,...

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.

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...

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.

Target Discovery and Validation

Probably the foremost expectation that accompanied the advent of large-scale expression-profiling methods was that completely novel biological insights would be generated at a much higher speed, including a better understanding of disease mechanisms, especially in complex diseases, where current therapies are often unspecific or only symptomatic. A good example of such a disease is schizophrenia.105 Schizophrenia has a notable genetic disease component and hence a significant number of chromosomal 'hot spots' have been identified in families with a distinct prevalence of the disease. However, because of the complexity and heterogeneity of the disease, none of these hot spots has yielded a clear connection to a disease mechanism. A plausible reason for these inconsistencies is that those linkage studies are limited to the genetic predisposition for the disease, not taking the important environmental aspect into account. And of course schizophrenia is just one, albeit highly complex,...

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...

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...

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.

Specificity of Cognitive Vulnerability Factors

There is an important distinction for cognitive models between specific and nonspecific causal factors in emotional disorders. Specific causal factors are relatively unique or focal factors in that they influence and predict the development of a particular disorder, but they do not apply equally to all psychopathology in general. For example, some cognitive vulnerability factors may apply to just a single form of anxiety disorder (e.g., just to OCD). In contrast, others may extend to the whole spectrum of anxiety disorders, but not apply to depression or other psychopathology (e.g., chap. 7, this vol. N. L. Williams, Shahar, Riskind, & Joiner, 2004). Alternatively, nonspecific (or common) causal factors potentially cut across a range of different disorders (e.g., depression, anxiety, bipolar disorders, even schizophrenia) and, in this way, have relatively low discriminatory power (Ingram, 1990 see also D. A. Clark, 1997). Two examples appear to include the experience of...

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

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...

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...

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...

Rates Of Hiv Infection Among People With Substance Use Disorders

Psychosis An overview of the literature suggests that the patho-physiology 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

Olfactory Disturbances Dysosmia

Cirrhosis And Cerebral Edema

Genital olfactory disturbances manifest themselves as partial anosmia (olfactory blindness). The perceived intensity of a persistent odor decreases or disappears with time (olfactory adaptation). External factors such as an arid environment, cold, or cigarette smoke impair the ability to smell diseases affecting the na-sopharyngeal cavity impair both smell and taste. Odors and emotions are closely linked and can influence each other. The perception of smell may be qualitatively changed (parosmia) because of autonomic (hunger, stress) and hormonal changes (pregnancy) or disturbances such as ozena, depression, traumatic lesions, or nasopharyngeal empyema. Olfactory hallucinations can be caused by mediobasal and temporal tumors (focal epilepsy), drug or alcohol withdrawal, and psychiatric illnesses such as schizophrenia or depression.

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...

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...

Cvd Project Design Participant Selection

In the second phase of the screening process, a randomly selected subsample of HR and LR participants, who were under age 30, were administered an expanded version of the Schedule for Affective Disorders and Schizophrenia-Lifetime (SADS-L) diagnostic interview (Endicott & Spitzer, 1978). The SADS-L was expanded to allow for the Diagnostic and Statistical Manual (DSM-III-R American Psychiatric Association, 1987), as well as Research Diagnostic Criteria (RDC Spitzer, Endicott, & Robins, 1978) diagnoses, and the data were also recoded according to DSM-IV (American Psychiatric Association, 1994). Individuals were excluded from participation in the study if they exhibited any current Axis I disorder, current psychotic symptoms, past history of any bipolar-spectrum disorder, or any serious medical illness that would preclude participation in a longitudinal study. Participants who had a past unipolar mood disorder but had remitted for a minimum of 2 months were retained so as not to...

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...

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).''

Clinical Diagnosis Some Possible Meanings

Psychiatry, the branch of medicine concerned with psychopathology, has modeled itself after the practices of the parent field. Various neurologists and psychiatrists during the latter part of the nineteenth century and thereafter identified specific mental illnesses which they discovered or described, for example, general paresis, Korsakoff's syndrome, and Alzheimer's disease. This process has been relatively more successful in organic or neurological disorders where both the symptomatology and the course of the disorder can be more successfully described and the etiology more clearly ascertained. This, however, has not kept psychiatrists from describing and designating forms of mental illness which do not always fit the disease entity model successfully. Since the time that catatonia and hebephrenia were identified as separate types of mental illness more than 100 years ago, numerous designations and classifications have been devised by psychiatrists, individually or in organized...

Reliability and Validity of Clinical Diagnosis

As indicated, clinical diagnosis usually results in a specific categorization or label. After the patient has been appraised, the clinician offers a diagnosis (e.g., schizophrenia, paranoid type). If the diagnosis reflects a specific disease process that is known and understood, there is a reasonable probability that most diagnosticians might agree on the correct diagnosis. However, if the diagnostic category lacks preciseness and covers a moderate variety of behaviors, the reliability of the diagnosis may be impaired. This is of some importance for both practice and research. For example, if a specific treatment is indicated for a given disorder, a misdiagnosis may lead to improper treatment. In research investigations, unreliable diagnoses for the subjects studied may lead to unreliable or invalid results. Thus, the reliability of the diagnosis is of some consequence most of the research in the past has not secured high agreement among psychiatrists who provided diagnoses on the...

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 ''

Research Issues and Problems

As indicated, investigators usually can study only small samples of the population they are interested in evaluating. An immediate critical issue is how well the sample selected for study actually represents the population or group it supposedly represents. How typical, for example, is a sample of thirty or fifty patients diagnosed as cases of schizophrenia in a state hospital in New Jersey, of all schizophrenics or of those in other types of settings How far can one generalize from the findings obtained with this specific sample Ostensibly, at least, findings obtained from a particular sample representative of a given category of disorder presumably have relevance for other comparable samples. The problem, therefore, is how does one define both the sample studied and the other samples of the population or diagnostic group to which the results are supposedly applicable The problems mentioned are particularly apparent when samples of modest size are drawn from institutional settings...

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-

Clinical Diagnosis Some Concluding Comments

It is readily apparent that any research on diagnostic groups (e.g., schizophrenia or bipolar disorder) can be no better than the validity or mean-ingfulness of the diagnoses obtained and used. This problem has plagued research in this area for many years. On the one hand, systematic and reliable classification of subjects facilitates research and the accumulation of potentially meaningful data about types of psychopathology. On the other hand, if the classification scheme used for such research is beset with problems of clarity, reliability, and validity, the results based on such classification are bound to be limited in their usefulness. An unreliable and loose scheme is bound to produce unreliable and variable results. The most highly quantified data and the most exacting statistical analyses cannot provide worthwhile conclusions if the assumptions or foundation upon which they are based are weak. In line with suggestions discussed earlier, investigators need to specify and...

Psychotomimetics Psychedelics Hallucinogens

Psychotomimetics are able to elicit psychic changes like those manifested in the course of a psychosis, such as illu-sionary distortion of perception and hallucinations. This experience may be of dreamlike character its emotional or intellectual transposition appears inadequate to the outsider.

Chlorpromazine hydrochloride

Uses Acute and chronic psychoses, including schizophrenia manic phase of manic-depressive illness. Acute intermittent porphyria. Preanes-thetic, adjunct to treat tetanus, intractable hiccoughs, severe behavioral problems in children, neuroses, and N& V. Treatment of choreiform movements in Huntington's disease. Special Concerns Use during pregnancy only if benefits outweigh risks. PO dosage for psychoses and N& V has not been established in children less than 6 months of age. Severe psychoses. Adults 25-50 mg (of the base) repeated in 1 hr if needed then, repeat the dose q 3-4 hr as needed and tolerated (the dose may be increased gradually over several days). Pediat-ric, over 6 months 0.55 mg kg (15 mg m2) q 6-8 hr as needed. N& V.

Gender Differences in Psychopathology

Eysenck (1995) suggested that the dispositional trait underlying schizophrenia is an important ingredient of creativity and noted that the incidence of schizophrenia is higher in men than women. The Diagnostic and Statistical Manual of Mental Disorders (4th ed.) (DSM-IV) (American Psychiatric Association, 1994) stated, however, that although men tend to be institutionalized at a greater rate, community-based studies have suggested an equal gender ratio between the men and women who have schizophrenia. As I mention in the chapter on neurotransmitters (chapter 8), enhanced creativity appears to be associated with affective disorders. According to the dSm-IV, bipolar disorders are also equally distributed between men and women. Major depressive disorders, however, are reported more frequently with women. Although the higher incidence of depression in women might be related to an ascertainment-reporting bias (e.g., men are less likely to go for professional help), the incidence of mood...

[KLOHnihdeen Pregnancy Category C

Epidural use causes analgesia at presynaptic and postjunctional al-pha-2-adrenergic receptors in the spinal cord due to prevention of pain signal transmission to the brain. tv2, distribution, epidural 19 min elimination 22 hr. Uses Oral, Transdermal Mild to moderate hypertension. A diuretic or other antihypertensive drugs, or both, are often used concomitantly. Non-FDA Approved Uses Alcohol withdrawal, atrial fibrillation, attention deficit hyperactivity disorder, constitutional growth delay in children, cyclosporine-associated nephro-toxicity, diabetic diarrhea, Gilles de la Tourette's syndrome, hyperhidrosis, hypertensive emergencies, mania, menopausal flushing, opiate detoxification, diagnosis of pheochromocy-toma, postherpetic neuralgia, psychosis in schizophrenia, reduce allergen-induced inflammatory reactions in extrinsic asthma, restless leg syndrome, facilitate smoking cessation, ulcerative colitis.

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

Genetic Considerations

Increased calcium in the cerebrinospinal fluid may result in behavior changes. The symptoms can range from slight personality changes to the manifestations of psychosis. They may include mental confusion, impaired memory, slurred speech, or hallucinations. Assess the patient's mental status and the family's response to alterations in it.

Gender Ethnicracial And Life Span Considerations

The hypercalcemic patient or the significant others may note memory changes, confusion, irritability, and symptoms of depression or paranoia (or both). The psychological clinical manifestations may range from mild to acute psychosis, or possibly paranoid hallucinations. The patient and significant others may be understandably upset or anxious about the changes in the patient's behavior.

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

Molecular Genetic Studies of Psychopathology

Consider the case of the genetics of schizophrenia as a specific example. Recent results suggest that linkage analyses based on more specific phenotypic indicators than the schizophrenia diagnosis alone may be more successful than a search for linkage among individuals diagnosed with schizophrenia but with disparate syndromes and symptoms. For example, Brzustowicz et al. (1997) hypothesized that different aspects of the schizophrenic phenotype may be influenced by different genes. Their evaluation of genetic markers on the short arm of chromosome 6 revealed no evidence for linkage by using categorical schizophrenia diagnostic definitions (i.e., narrow, broad, and very broad). Examining linkage for positive symptom, negative symptom, and general psychopathology symptom scales, however, yielded significant evidence for linkage for the positive symptom scale only (empirical p < .05). The specificity of these results suggests that the positive and negative dimensions of schizophrenia...

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).

Secondary Sleep Disorders

Secondary Sleep Disorders

Depression (of various types) can impair sleep, though paradoxically sleep deprivation can ameliorate depression. Depressed persons typically complain of early morning awakening, nocturnal restlessness, and difficulty in starting the day. Sleep disturbances are also common in patients suffering from psychosis, mania, anxiety disorders, alcoholism, and drug abuse.

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.

[hahlowPAIRihdohl Pregnancy Category C

Uses Psychotic disorders including manic states, drug-induced psychoses, and schizophrenia. Aggressive and agitated clients, including chronic brain syndrome or mental retardation. Severe behavior problems in children (those with combative, explosive hyperexcitability not accounted for by immediate provocation). Short-term treatment of hyperactive children. Control of tics and vocal utterances associated with Gilles de la Tourette's syndrome in adults and children. The decanoate is used for prolonged therapy in chronic schizophrenia. Non-FDA Approved Uses Anti-emetic for cancer chemotherapy, phencyclidine (PCP) psychosis, infantile autism. IV for acute psychiatric conditions.

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.

Alcohol related disorders

Thiamine deficiency is responsible for the clinical manifestations (gaze paralysis, ataxia, nystagmus, and mental confusion) of Wernicke's encephalopathy and Korsakoff psychosis (retrograde amnesia, impaired short-term memory) seen in alcoholics.3 The morphologic features (seen in 1.7 to 2.7 of consecutive autopsies)11 include petechiae and pink discoloration of the mammillary bodies (Figure 2.4.2), hypothalamus, periventricular region of the thalamus, periaqueductal grey matter, and beneath the floor of the fourth ventricle.1 The lesions are bilateral and symmetric when present. These gross features are seen in only 50 of acute cases,12 therefore microscopic examination is essential. The lesions vary with the stage and severity of the deficiency. Acute lesions consist of dilated, congested capillaries with perivascular ball and ring hemorrhages and ischemic neuronal changes (Figure 2.4.3). Chronic lesions

Commonly abused drugs 2421 Excited Delirium

Excited delirium is a drug-induced delirium or psychosis accompanied by agitation and hyperthermia, and often ending with respiratory arrest and sudden death. Cocaine is the drug most often implicated in this syndrome,13 but amphetamines have also been implicated in some cases. The syndrome is not due to any contaminants that may accompany the cocaine sample.

Mental Health Findings Population Studies

More recently, other Eastern European studies have investigated the mental health impact of the disaster. Rahu et al. 16 reported that suicide was the leading cause of death among Estonian clean-up workers. However, methods of registration of causes of death among the heavily monitored clean-up workers group differed substantially from those used in the general population, thereby making comparison with the general population risky. Another report suggested that there was an increase in the rates of schizophrenia and dementia in clean-up workers 17 , but this finding has not been verified. More likely, selection bias, non-blind evaluations, confounding variables (especially alcoholism), and other methodological factors explain these implausible findings.

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...

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...

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 posttrau-matic 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...

Diffuse Lewy Body Disease

Diffuse Lewy body disease (DLBD) is considered to be a variant or overlapping condition lying between Alzheimer's disease and Parkinson's disease. Clinical differentiation may therefore be difficult. In most patients with DLBD, however, psychosis and dementia are often found to precede parkinsonism (gait disturbance, rigidity, and resting tremor). The differentiation between DLBD and other parkinsonian syndromes, especially progressive supranuclear palsy, is particularly difficult when a patient with parkinsonism and dementia is also found to have oculomotor deficit.

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.

Genetic Contributions

The massive literature on the genetics of schizophrenia can be assimilated into a multifactorial polygenic model but cannot be made to fit a single-major-locus model with high penetrance (Faraone & Tsuang 1985 Gottesman, 1991 Moldin & Got-tesman, 1997 Risch, 1990). There is no clear evidence against a simple multifactorial polygenic model, but Gottesman (e.g., 1991) notes the possibility of a mixed model. This model includes a small number of mostly genetic cases (a few single rare genes with high penetrance), a small number of cases due primarily to environmental factors, and a large number of cases falling within one of two polygenic models (one simply polygenic, the other a specific major gene of small effect embedded in a polygenic etiology). Thus, the vast majority of cases involve a polygenic etiology. Heterogeneity in schizophrenia in the form of a chronic versus an episodic course is, at least as a first approximation, easy to conceptualize in a polygenic model. In the...

Retrospective Studies

In a sample of remitted depressed bipolar and unipolar patients retrospectively assessed over a long 1-year interval, Perris (1984) found that bipolar patients reported an average of 2.5 independent events and unipolar patients reported an average of 1.9 independent events in the year prior to episode onset. Using both a retrospective and prospective design, Sclare and Creed (1990) reported that manic patients experienced more independent events prior to onset than after recovery. In a study of manic, psy-chotically depressed, and schizophrenic patients and nonpsychiatric controls, Bebbington et al. (1993) reported that the psychotically depressed patients experienced more severe, independent life events in the 6 months prior to onset of psychosis than did both manic and schizophrenic patients. However, the manic patients also reported more severe, independent events prior to relapse than did the nonpsychiatric controls. In contrast, Chung, Langeluddecke, and Tennant (1986) found that...

The Dopamine Hypothesis

The second major development in biological approaches to schizophrenia was the demonstration of at least some therapeutic benefit from neu- roleptics or antipsychotic drugs in treating schizophrenia and the determination that it is positive rather than negative symptoms (see later for this distinction) that respond to these drugs (e.g., Buckley & Meltzer, 1995 Crow, 1980 Weinberger & Lipska, 1995 Wirshing, Marder, Van Putten, & Ames, 1995). The therapeutic efficacy of antipsy-chotic drugs can be attributed to their ability to block DA receptors (e.g., Grace & Moore, 1998 Haracz, 1982 Losonczy, Davidson, & Davis, 1987 Snyder, 1978 Weinberger & Lipska, 1995). This suggests that DA pathways are important in schizophrenia and leads to the dopamine hypothesis of schizophrenia (Snyder, 1978). Much debate has centered on whether an increased sensitivity to dopamine might be a primary etiological factor in schizophrenia. At present, it appears more likely that dopamine makes...

Positive and Negative Symptoms

Symptoms, promoting awareness of an important aspect of heterogeneity in schizophrenia. Carpenter (1992 Liddle, Carpenter, & Crow, 1993) emphasized the challenge of this distinction to the conceptualization of schizophrenia. Positive symptoms are the presence of abnormal functioning, such as hallucinations and delusions, whereas negative symptoms reflect an inadequacy of normal functioning, such as affective flattening, poverty of speech, and social withdrawal (Sommers, 1985). Crow (1980, 1985) proposed a Type I dimension of schizophrenia characterized by prominent positive symptoms, responsiveness to anti-psychotics, an acute onset, an episodic course, and good premorbid adjustment. Because of the role of DA in positive symptoms, Crow suggested that the Type I dimension is due to a neurochemical imbalance that involves dopamine. In contrast, Crow's Type II dimension involves prominent negative symptoms, a chronic course, an insidious onset, poor premorbid adjustment, intellectual...

The Schizoaffective Continuum

Although our diagnostic system treats schizophrenia and the affective disorders as unrelated diseases, there is a continuum from schizophrenia to affective disorders, patients with schizoaffec-tive symptoms outnumber those with purely schizophrenic or purely affective symptoms (Kendell, 1982). Crow (1998, p. 502) concludes that ''no objective genetic boundaries can be drawn'' between predominantly affective and predominantly schizophrenic patients. The theoretical challenge of the schizoaffective disorders is well recognized (e.g., Baron & Gruen, 1991 Crow, 1986, 1991 Kendell, 1982 Meltzer, 1984 Taylor, 1992 Taylor, Berenbaum, Jampala, & Cloninger, 1993). In schizoaffective disorder with manic symptoms, the DA theory of schizophrenia combined with Depue's DA theory of mania points to the obvious possibility that some vulnerability to schizophrenia (a primary schizophrenia deficit) combines with the high level of BAS-based DA activity in mania to produce schizophrenic symptoms....

Clinical and Medical Uses of Chronometry

Cognitive effects of normal aging, mild cognitive impairment, senile dementia, traumatic brain and closed head injuries, mortality, under-nutrition and malnutrition in children, eating disorders, parasitic infections, neurological effects of HIV and AIDS, drug effects and addictions, multiple sclerosis, sleep disorders, diabetes, attention deficit and hyperactivity disorder (ADHD), stroke, vascular dementia, degenerative brain diseases associated with aging (Huntington, Alzheimer, Parkinson), epilepsy, chronic fatigue syndrome, hypoxia, post-traumatic stress disorder (PTSD), psychiatric disorders (anxiety, schizophrenia, depression, bipolar), yoga and meditation, chemical, pharmaceutical, and nutriceutical (e.g., Gingko biloba) agents.

Medical Alcohol Drug Abuse or Dependence Detoxification or Other Symptom Treatment with CC

Tolerance to the drug results in the need for increasing amounts, and the physiological and psychological dependence on the drug leads to maladaptive behaviors. Attempts to discontinue or control use of the drug lead to withdrawal symptoms, which, if left untreated, can range from feeling flulike symptoms to coma and possibly death. The withdrawal from a drug produces feelings and sensations opposite of the effects produced by using the drug. Withdrawal can be treated to avoid withdrawal symptoms. Chronic abuse of psychoactive substances may lead to complications, including pulmonary emboli, respiratory infections, trauma, musculoskeletal dysfunctions, psychosis, malnutrition disturbances, gastrointestinal disturbances, hepatitis, thrombophlebitis, bacterial endocarditis, gangrene, and coma.

Psychological Involvement

Psychiatric disorders such as depression, irritability, psychosis, attempted suicide, and actual suicide have been reported in individuals during and after isotretinoin therapy. However, there is no evidence that the use of isotretinoin is associated with an increased risk for depression or suicide. Psychiatric evaluation and treatment may still be needed (Brecher and Orlow 2003, Ellis and Krach 2001).

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...

Endogenous Mental Disease Acute Psychotic Episodes

Excited delirium may also occur in the absence of stimulant drugs such as cocaine, methamphetamine or alcohol in individuals with endogenous mental disease. Clinically, these are usually referred to as acute psychotic episodes, and tend to occur in individuals with schizophrenia, schizoaffective disorders or delusional disorders. Acute psychotic episodes happen both in and out of mental facilities. They may occur because of the patient's discontinuance of medications or development of tolerance to the medications. If the episode occurs outside a mental health facility, the police are usually called on to deal with the individual if inside the facility, it is nursing or support personnel. Sudden death can be caused by either the physiological effects of catechola-mine and hypokalemia following the struggle or a combination of these effects and the effects of the medications the patient is or was on. Many patients, nowadays, are on medications, some of which have a cardiotoxic...

Lysergic acid diethylamide

LSD may be self administered orally, nasally, or by parenteral ingestion however, the oral route is the most common. Doses of 50 to 300 ug are ingested, with a minimum effective dose of 20 to 25 ug. Absorption is rapid and complete regardless of the route of administration. However, food in the stomach slows absorption when ingested. Effects are observed within 5 to 10 min, with psychosis evident after 15 to 20 min. Peak effects have been reported 30 to 90 min after dosing effects decline after 4 to 6 h.4 The duration of effects may be 8 to 12 h.

Certification of Death

In the aforementioned cases, the authors suggest two ways of certifying the cause of death. First is to sign out the cause of death as excited delirium and then list struggle, cocaine intoxication, etc., as contributory causes. The other way is to sign out the cause of death in a descriptive manner, e.g. Cardiopulmonary arrest during violent struggle in individual under influence of cocaine, alcohol, etc. In individuals with psychoses, this is listed either as a contributory cause or incorporated in the descriptive diagnosis.

Severely and Persistently Mentally Ill 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...

Variation Across Different Types of Mental Disorders

Marsella (1987) offers a slightly different perspective that accounts for variation among mental disorders. He proposes that the least cultural variation occurs in mental disorders that are the most biologically based, such as severe neurological disease, and the most cultural variation occurs in mental disorders that most closely resemble normal behavior (and therefore, are presumably the least biologically based). Thus, he classifies disorders in the following way (from the least to the most culturally variable) severe neurological disease, minor neurological disease, functional psychotic disorders, neurotic disorders, and minor transient states. According to Marsella (1987), disorders such as schizophrenia would vary less across cultures than unipolar depression or general anxiety disorder. Although this perspective appears to explain much of the current empirical findings, it is limited by our incomplete knowledge of the biological aspects of various mental disorders. Thus, it is...

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.

Summary And Conclusions

Regardless of the source, endogenously generated H202 reverses conventional glutamatergic excitation by opening KAtp channels to inhibit striatal DA release. These findings help clarify normal DA-glutamate interactions in striatum. Moreover, because DA-glutamate dysfunction has been implicated as a causal factor in Parkinson's disease (Olanow and Tatton, 1999 Chase and Oh, 2000 Greenamyre, 2001), schizophrenia (Deutsch et al., 2001 Sawa and Snyder, 2002), and addiction (Koob, 2000 Hyman and Malenka, 2001), exploration of this process may also suggest novel pathways through which dysfunction could occur. One final point is that neuromodulation by H202 is a double-edged sword an imbalance between H202 generation and regulation could result in oxidative stress, which has been implicated in nigrostriatal degeneration in Parkinson's disease (Cohen, 1994 Sonsalla et al., 1997 Olanow and Tatton, 1999 Xu et al., 2002) and, more recently, as a causal factor in schizophrenia (Do et al., 2000...

[thighohRIDahzeen Pregnancy Category C

To the strong anticholinergic effects. tV2 10 hr. Metabolized in the liver to both active and inactive metabolites. Uses Acute and chronic schizophrenia moderate to marked depression with anxiety sleep disturbances. In children Treatment of hyperactiv-ity in clients and those with retarded and behavior problems. Geriatric clients with organic brain syndrome. Alcohol withdrawal. Intractable pain.

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...

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...

Type of Headache Symptoms and Signs Syndromes

Posttraumatic, drug-induced, vascular (p. 182), intracranial mass, hydrocephalus, sinusitis, parkinsonism, cervical dystonia, myoarthropathy of the masticatory apparatus,1 mental illness (depression, schizophrenia, hypochondria), cervical spine lesions (degenerative lesions, fractures, Klippel Feil syndrome), Down syndrome, basilar impression, osteoporosis, skull metastasis, spondylitis, rheumatoid arthritis, lesions of cervical spinal cord meningismus (tumor, hemorrhage, syringomyelia, cervical myelopathy, von Hippel-Lindau syndrome, meningitis, carcinomatous meningitis, intracranial hypotension)

Chilblain Lupus Erythematosus

Chilblain Lupus Erythematosus

Hyperviscosity from immunologic abnormalities may play a role (Mascaro et al. 1997, Yell et al. 1996). In most reported cases, patients with CHLE present a polyclonal hypergammaglobulinemia, increased serum immunoglobulin levels, and a positive rheumatoid factor. In addition, anti-double-stranded DNA or anti-Ro SSA antibodies have often been detected, but laboratory examinations usually fail to reveal evidence of cryoglobulins, cryofibrinogens, or cold agglutinins (Su et al. 1994). In a few patients, CHLE has been described in association with antiphospholipid syndrome (Allegue et al. 1988, De Argila Fernandez-Auran et al. 1996). The evolution of lesions in patients with CHLE is usually chronic, and sometimes these lesions precede other manifestations of SLE (Doutre et al. 1992). The risk of developing SLE is estimated to be approximately 20 , but in this rare form of CCLE, only a few studies have been reported nevertheless, long-term follow-up of these patients is warranted (Viguier...

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...

Methamphetamine and Amphetamine

Blocking its re-absorption, causing hyperstimulation of receptor neurons. Methamphetamine is also a cardiovascular stimulant. It blocks re-uptake of norepinephrine and causes an increase in catecholamine release. The euphoric effect is similar to cocaine but may last as long as ten times that of cocaine. Methamphetamine is metabolized to amphetamine, its major active metabolite. Amphetamine itself is rarely encountered. In overdoses, meth-amphetamine causes restlessness, confusion, hallucinations, coma, convulsions, and cardiac arrhythmias. With chronic abuse, just like cocaine, it can produce a chemical paranoid psychosis. Methamphetamine may be sold as cocaine. It is usually taken orally or intravenously though it may be snorted or smoked. Methamphetamine may be transformed into amphetamine hydrochloride (ice) which is smoked like crack cocaine. Methamphetamine has a half-life of 11-12 hours, with 45 excreted in urine unchanged over a number of days. Long-term use may be associated...

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).

Basic Tenets Of Cognitive Models Of Emotional Disorder

Most individuals in stressful situations do not develop clinically significant disorders. Moreover, the specific disorder that emerges for different individuals is not determined just by the precipitating stress alone (i.e., precipitating stresses do not just occur in conjunction with any one clinical disorder). For example, stressful events are elevated in depression (Brown & Harris, 1978 Paykel, 1982), bipolar disorder and mania (see chap. 4, this vol. Johnson & Roberts, 1995), anxiety disorders (Last, Barlow, & O'Brien, 1984 Roy-Byrne, Geraci, & Uhde, 1986), and even schizophrenia (Zucker-man, 1999). In light of these findings, cognitive vulnerability-stress models are offered to help account for not only who is vulnerable to developing emotional disorder (e.g., individuals with a particular cognitive style), and when (e.g., after a stress), but to which disorders they are vulnerable (e.g., depression, eating disorder, etc.).

Diagnosis

The current system for the diagnosis of CNS disorders in the USA is DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision).3 This text, which has a long and chequered history,4 'facilitates the identification and management of mental disorders' to help provide a consensus view of these disorders and their treatment, and a better understanding of their etiology. The general classification of mental disorders that comprise DSM-IV-TR is shown in Table 1 where the major headings are shown with illustrative data, where appropriate, on the syndromes within each heading. These diagnostic criteria lack a specific etiological conceptualization3 and are thus organized principally around syndromes - a group or pattern of symptoms that appear in individuals in a temporal manner - reflecting, to a major extent, comorbidities. However DSM-IV-TR is confounded by ethnic, societal, and gender differences both in terms of diagnosis (physician) and disease...

Anxiety

While defined as an anxiety disorder, obsessive compulsive disorder (OCD) has several distinct features that set it apart. It is characterized by an overwhelming sense that negative consequences will arise from the failure to perform a specific ritual. The rituals are repetitive, taking a variety of forms including hand washing, checking to see if the stove is turned off, or the recitation of particular words or phrases. DSM-IV-TR criteria require that the symptoms include obsessions or compulsions that cause marked distress and occupy at least 1 h per day. OCD interferes with normal routine and produces a social impairment equivalent to schizophrenia. In addition to the disabling effect OCD has on the patient, it also produces a significant strain on family relations as relatives become caregivers and are drawn into a routine of providing reassurance and ritual maintenance. OCD becomes apparent at between 22 and 36 years, affecting males and females equally. OCD is highly prevalent,...

Sleep disorders

From a disease causality perspective, more than 90 of narcoleptic individuals carry the human leukocyte antigen (HLA) gene haplotype, HLA-DR2 DQ1, a reliable genetic marker for narcolepsy with a 100 association of the disease, but this is neither a necessary nor a sufficient causative factor for the disorder. A COMT polymorphism has been associated with the severity of narcolepsy although it may be noted that COMT polymorphisms have also been associated with gender differences in sensitivity to pain, breast cancer, and schizophrenia. Mutations in the

Future Prospects

CNS drug discovery has a long history of serendipity.11 For example, the first antidepressant, the MAO-1 iproniazid, was originally developed for the treatment of tuberculosis while the anticonvulsant actions of a variety of NCEs were found to be due to the vehicle in which they were dissolved, valproic acid. The complexity of CNS diseases and the empirical nature of the animal models designed to show efficacy have led to many NCEs entering the clinic for one indication and being found useful in another. A key example in this regard is the antipsychotic clozapine.9'18 Discovered in the prebiotech era of the 1970s based on empirical similarities to the dopamine antagonist haloperidol, clozapine was introduced in the early 1970s as a novel antipsychotic with a superior human efficacy profile, the mechanism for which was unknown. The superior attributes of clozapine were limited by the incidence of sometimes fatal agranulocytosis leading to a search for clozapine-like agents lacking this...

Physical Examination

Acid-base imbalances frequently affect patients with both acute and chronic illnesses. Their response to yet another problem is at best unpredictable. Neurological changes such as confusion, agitation, or psychosis are upsetting if they occur, as are electrolyte disturbances. Anticipate the patient's feeling powerless, and plan care to support all psychological needs.

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...

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