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. Read more here...

The Schizophreniafree Package Overview

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Schizophrenia Animal studies

Musty et al. (2000) tested the effects of the of the CB 1 receptor antagonist SR141716 in two animal models of schizophrenia. In the first model, ibotenic acid lesions of the hippocampus were made in neonatal rats, which results in a brain degeneration pattern similar to that observed in schizophrenics, as well as abnormal play behavior in an anxiety-provoking environment. In the second model, ketamine-induced enhancement of pre-pulse inhibition was tested. In both of these tests, SR141716 reversed the abnormal behavior. These findings in animal models are consistent with the hypothesis that CBX receptor antagonists have antipsychotic activity.

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...

Schizophrenia

Some of the negative symptoms seen in schizophrenia are also seen in depression. Children with clinical presentation of bipolar disorder and psychotic mood disorders are often misdiagnosed as having schizophrenia (Ferro et al. 1994) however, their symptoms may be distinguishable by the associated mood-incongruent hallucinations and paranoia seen in patients with schizophrenia. Furthermore, patients with schizophrenia have an insidious onset and are less likely to have episodic pattern of mood changes and lack family history of bipolar disorder.

Psychosis

It does not appear that psychosis raises the risk of suicide in bipolar illness. Angst and Preisig (1995) found in their Zurich cohort that the presence of schizophrenic symptoms did not have a differential impact on suicide rates. Grunebaum et al. (2001) reported that the presence of delusions in 429 subjects with schizophrenia, unipolar depression, and bipolar disorder did not correlate with whether they had suicidal ideation or had made a suicide attempt. Tsai et al. (2002) reported that in a cohort of Chinese patients, mood-congruent psychotic symptoms at the onset of illness were in fact associated with reduced risk of having made a suicide attempt.

Cannabis And North America

In 1860, a committee of the Ohio State Medical Society published a report on the medical uses of cannabis. Information was provided on its use to treat puerperal psychosis, various pains (inflammatory, neuralgic, abdominal), gonorrhoea, cough and so forth. One of the contributors, Dr Fronmueller, compared cannabis favourably to opium as an analgesic. He suggested that although cannabis was a less reliable and less potent analgesic, the side effect profile was better. Unlike opium, cannabis did not reduce appetite, produce constipation, cause nausea or vomiting, affect lung function and the nervous system is also not so much affected (McMeens, 1860).

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.

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

Depressive Phenomenology

Psychotic depression also appears to be more common in bipolar depression than in unipolar depression (Mitchell et al. 1992, 2001 Parker et al. 2000). Often the presence of psychotic symptoms can be difficult to establish. This may be because psychotic depressed patients seem to have more insight into their symptoms than do manic or schizophrenic patients and thus are more likely to hide these symptoms (Dell'Osso et al. 2002). Depressive symptoms that may be more prominent in such psychotic depressed patients, compared with nonpsychotic depressed patients, include markedly increased guilt and psychomotor agitation or retardation (Schatzberg and Rothschild 1992). Thus, in the guarded, very agitated, guilty bipolar depressed patient, one should have a high index of suspicion for concomitant psychosis. Clinical experience also suggests that psychotic depression in a young person is a common initial presentation of a bipolar illness. In such a person, especially if he or she has a family...

The Validators Of Diagnosis

The classic validators of psychiatric diagnoses were first discussed by Eli Robins and Samuel Guze in 1970 in reference to schizophrenia. They identified five validators signs and symptoms, delimitation from other disorders, the follow-up study (outcome), family history, and laboratory tests. The basic rationale for having multiple validators for a psychiatric diagnosis is the absence of a gold standard. Whereas in medicine clinicians often argue over a potential diagnosis only to have the pathologist declare the right answer, in psychiatry there is no such definitive and instantaneous resolution psychiatry has no pathologist. (In fact, since many pathologists spent entire careers searching in vain for simple brain abnormalities in patients with schizophrenia, it had become something of a rueful joke to say that schizophrenia is the graveyard of pathologists.) In the absence of a specimen from an organ, psychiatric nosologists like Robins and Guze returned to the classic work of Emil...

Psychiatric Comorbidity

Smokers more often suffer from psychiatric diseases, namely depression, anxiety disorder and schizophrenia, than do non-smokers. At least 70-90 of all schizophrenia patients smoke.15 There is a clear connection between smoking and depression and anxiety disorders. On the one hand, depression makes smoking lead to nicotine addiction more easily and, on the other hand, smoking promotes the development of depression. The same holds for anxiety and panic disorders. Smoking cessation can cause a temporary aggravation of the depression or anxiety.15

Drug Therapy In Relation To Psychologicaltreatment

As a general rule, psychotic illnesses (e.g. schizophrenia, mania and depressive psychosis) require drugs as first-line treatment, with psychotherapeutic approaches limited to an adjunctive role, for instance in promoting drug compliance, improving family relationships and helping individuals cope with distressing symptoms. By contrast, for non-psychotic depression and anxiety disorders such as panic disorder and obsessive-compulsive disorder, forms of psychotherapy are available which provide alternative first-line treatment to medication. The choice between drugs and psychotherapy depends on treatment availability, previous history of response, patient preference and the ability of the patient to work appropriately with the chosen therapy In many cases there is scope to use drugs and psychotherapy in combination.

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.

Classical Versus Atypical Antipsychotics

As atypical antipsychotics have become established as alternatives to classical agents, clinicians are presented with the dilemma as to which should be their first choice in patients with schizophrenia and psychotic illnesses, and indeed whether there is sufficient justification to transfer a patient stabilised on a classical agent over to an atypical. 2 Whilst the advantages of atypicals over classical antipsychotics may seem clear cut, one analysis using only trials where doses of classical antipsychotics were at or below a dose of haloperidol 12 mg day or equivalent (now regarded as the upper limit for optimised use of these agents) produced rather different results. Although the atypicals retained their advantage in causing extrapyramidal side effects less frequently, overall tolerability and efficacy appeared to be similar. Geddes J et al 2000 Atypical antipsychotics in the treatment of schizophrenia systematic overview and meta-regression analysis. British Medical Journal 321...

Behavior or Psychomotor Activity

Excessive body movements may be associated with anxiety, drug reactions, or the manic phase of bipolar disorder. Reduced movements may represent organic brain dysfunction, catatonic schizophrenia, or drug-induced stupor. Depression can manifest either via agitation or psychomotor retardation. Sometimes, paranoid clients constantly scan their visual field in an effort to be on guard against external threat. Repeated motor movements (such as dusting off shoes) may signal the presence of obsessive-compulsive disorder. Similarly, repeated picking of imagined lint or dirt off clothing or skin is sometimes associated with delirium or toxic reactions to drugs medications.

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.

Polymorphic structure of cannabinoid receptor genes

Improved information about Cnr and its allelic variants in humans and mice can add to our understanding of vulnerabilities to addictions and other neuropsychi-atric disorders. However, little information is available at the molecular level about Cnr gene structure, regulation and polymorphisms. Different human Cnr gene polymorphisms have been reported. A silent mutation of a substitution from G to A, at nucleotide position 1359 in codon 453 (Thr) that turned out to be a common polymorphism in the German population (Gadzicki et al., 1999). In this study, allelic frequencies of 1359(G A) in genomic DNA samples from German Gilles de la Tourette sydrome (GTS) patients and controls were determined by screening the coding exon of the CBX Cnr gene using PCR single-stranded conformation polymorphism (PCR-SSCP) analysis (Gadzicki et al., 1999). This was accomplished by the use of a PCR based assay by artificial creation of a MSP1 restriction site in amplified wild-type DNA (G-allele), which is...

Mental Disorders and Psychiatric Treatment

Most suicides are associated with a relatively small number of mental disorders or conditions. Patients with affective disorders (depression and bipolar disorder) and schizophrenia are at higher risk for suicide (Rossau & Mortensen, 1997 Roy, 1989). Thought disorders such as a paranoid delusional system or auditory hallucinations that tell a person to kill himself or herself or a loved one, especially when combined with depressed mood, put the sufferer at high risk (Resnik, 1980). Individuals with psychotic depressive reactions are at especially high risk for suicide.

Diseases with Akinetic Rigidity Idiopathic Parkinsons Disease

Lewy Body Pathology

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.

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.

Assessment and Diagnosis Problems

Differential diagnosis Although some clients report symptoms consistent with more than one diagnostic entity and are appropriately assigned two or more diagnostic labels, other clients report confusing symptom clusters requiring extensive questioning for diagnostic clarity. For example, it is notoriously difficult, albeit important, to discriminate some diagnoses from others (e.g., mood disorder with psychotic features versus schizoaffective disorder versus schizophrenia versus delusional disorder American Psychiatric Association, 2000 Sheitman, Lee, Strauss, & Lieberman, 1997 Weiner, 1966 1997). Despite the difficulty of sorting out these various disorders, diagnostic specificity is very important because of treatment implications (i.e., medication type, treatment approach, hospitalization, prognosis).

Diagnostic Interviewing

Many diagnostic interviews require considerable time for administration. For example, the Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kiddie-SADS or K-SADS Puig-Antich, Chambers, & Tabrizi, 1983) may take one to four hours to administer, depending on whether both parent and child are interviewed. Most diagnostic interviews require training for therapists who use them, which makes them even more time-consuming.

Hyperviscosity Syndrome

The circulatory disturbances resulting from hyper-viscosity lead to various clinical manifestations. Headache, blurred vision, reduced visual acuity, and drowsiness are common. Occasionally, patients may present with dementia or psychosis.104 Progressive, severe CNS dysfunction results in obtundation, vertigo, seizure, gait ataxia, and coma. Dyspnea may precede overt congestive heart failure. Bleeding occurs most commonly as epistaxis, ecchymosis, and sometimes GI

Functional Visual Loss and Malingering

Ophthalmic Differential Diagnosis Tables

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...

Perceptual Disturbances

Hallucinations may occur in any of the five major sensory modalities visual, auditory, olfactory, gustatory, and tactile. Auditory hallucinations are most commonly reported. Clients who report hearing things (usually voices) that others do not hear usually suffer from either an affective disorder or schizophrenia. However, on occasion, such experiences may be produced by states of chemical intoxication or because of acute traumatic stress. In other instances, clients may report having especially good hearing or they may report listening to their own inner voice. Although such reports are worth exploring, they are not in and of themselves signs of perceptual disturbance. In addition, people often report odd perceptual experiences, similar to hallucinations, that occur as they fall off to sleep or when they are just waking up. Such perceptual disturbances are normal and occur during the hypnogogic or hypnopompic sleep states and are a consistent part of many people's sleep patterns...

Drug Induced Ventricular Arrhythmias

Astemizole, and cisapride) because their risk for triggering lethal arrhythmias was believed to outweigh therapeutic benefits (Walker et al. 1999). A number of histamine receptor-blocking drugs, including astemizole and terfenadine and more recently loratadine, have been shown to block IKr as an adverse side effect and prolong the Q-T interval of the electrocardiogram (Crumb 2000). Cisapride (Propulsid), a widely used gastrointestinal prokinetic agent in the treatment of gastroesophageal reflux disease and gastroparesis, also blocks KCNH2 K+ channels and is associated with acquired LQTS and ventricular arrhythmias (Wysowski and Bacsanyi 1996). Cisapride produces a preferential prolongation of the APD of M cells, leading to the development of a large dispersion of APD between the M cell and epi endocardium (Di Diego et al. 2003 Fig. 4). Changes in the morphology of the T wave were observed in more than 85 of patients treated for psychosis when the plasma concentration of the...

Clinical Approach

For patients with Alzheimer disease, the average life expectancy after diagnosis is 7-10 years. The clinical course is characterized by progressive decline of cognitive functions (memory, orientation, attention, and concentration) and the development of psychological and behavioral symptoms (wandering, aggression, anxiety, depression, and psychosis Table 49-3). The goals of treatment in Alzheimer disease are to (a) improve cognitive function, (b) reduce behavioral and psychological symptoms, and (c) improve the quality of life. Donepezil (Aricept) and rivastigmine (Exelon) are cholinesterase inhibitors that are effective in improving cognitive function and global clinical state. Antagonists to N-methyl-n-aspartate (NMDA) receptors, such as memantine. also seem to reduce the rate of decline in patients with Alzheimer dementia. Risperidone reduces psychotic symptoms and aggression in patients with dementia. Other issues include wakefulness, nightwalking and wandering, aggression,...

Side Effects Of Cannabis And Nabilone

Clinical trials with nabilone showed that nearly all patients experienced at least one side effect. The most common being drowsiness followed by dizziness, euphoria, dry mouth, ataxia, visual disturbances, concentration difficulties, sleep disturbance, dysphoria, hypotension, headache and nausea (in decreasing order of incidence). Other reported side effects include confusion, disorientation, hallucinations, psychosis, depression, decreased co-ordination, tremors, tachycardia, decreased appetite and abdominal pain. Tolerance to drowsiness and euphoria develops rapidly without any noticeable drop in analgesic capability.

Target Validation And Functional Genomics

A second example, more directly related to the human genome, is the search for genes that are associated, and by inference may be causative, in producing the psychiatric disorder schizophrenia. This disease affects nearly 1 of the population and has a strong genetic association. From studies comparing schizophrenic patients with individuals lacking symptoms of the disorder, l.o.d. scores of 2.46.5 on markers between or close to markers D1S1653 and D1S1679 on chromosome lq have been reported (113,114). A l.o.d. score of above a numerical value of 3 is considered by experts in genetics to be indicative of a relevant association akin to a significant P value (P< 0.05) in statistics. With this information, a search for the gene on chromosome lq and the delineation of its function in humans would be a logical approach to finding novel genomic targets that could lead to new drugs that would more effectively and safely treat schizophrenia. However, a subsequent study (115) using eight...

Imaging dopamine metabolism with PET

Dopamine is a chemical messenger produced within the nerve cells that is essential for the transmission of the nerve impulse and hence involved in a wide range of important functions, including movement, cognition and behaviour. Dysfunctions in the central nervous dopamine system can lead to diseases such as Parkinson's and schizophrenia. Alterations in the levels of this neurotransmitter have also been implicated in a variety of behavioural problems such as attention deficit and hyperactivity.

Molecular imaging in drug discovery and development

Tomographic images of the site of interest. In vivo competition studies can then be carried out by adding the unlabelled drug candidate and analysing the PET images of the site of interest this can then provide a direct measure of the occupancy of the specific receptor in the presence of the drug candidate. A specific example of this approach has been used to show that drugs currently used for the treatment of schizophrenia block certain post-synaptic dopamine receptors (see Section 13.3.2) with occupancies higher than 70 per cent at therapeutic doses. The radiotracers that have been used for these studies have been either N- 11C -methylspiperone or 11C raclopride (Figure 13.6).

Approach To Illicit Drug Effects

PCP. also called angel dust, is a veterinary anesthetic that can be smoked or taken orally or intravenously. In a dose-dependent manner, people will develop agitation, excitability, acute psychosis, and convulsions when intoxicated with this drug.

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.

Scientific Evaluation and Clinical Applications

The prominence of the Bupleurum species cannot be overstated. Across China and Japan, it serves as a main or supplementary ingredient in over two thirds of traditional medications. For over 2000 years, it has been used to treat fevers, intestinal maladies, malaria, and countless other afflictions. Modern research indicates that it may possess anti-tumor qualities, and researchers continue to report its impact on a wide range of ailments, from hepatitis and epilepsy, to irregularity and menopause, as well as psychosis and schizophrenia.

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...

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...

TABLE 164 Psychotic Disorders

Schizophrenia Schizophrenia impairs major functioning, as at work or school or in interpersonal relations or self care. For this diagnosis, performance of one or more of these functions must have decreased for a significant time to a level markedly below prior achievement. In addition, the person must manifest at least two of the following for a significant part of 1 month (1) delusions, (2) hallucinations, (3) disorganized speech, (4) grossly disorganized or catatonic behavior,* and (5) negative symptoms such as a flat affect, alogia (lack of content in speech), or avolition (lack of interest, drive, and ability to set and pursue goals). Continuous signs of the disturbance must persist for at least 6 months. Subtypes of this disorder include paranoid, disorganized, and catatonic schizophrenia. A schizophreniform disorder has symptoms similar to those of schizophrenia but they last less than 6 months, and the functional impairment seen in schizophrenia need not be present. A...

Nicotinic acetylcholine receptor Figure 2134 shows the nicotinic acetylcholine receptor

Adrenergic Receptor - Another kind of synapse uses catecholamines instead of acetylcholine and is called adrenergic. Catecholamines include dopamine, norepinephrine, and epinephrine. In patients with Parkinsonism, dopamine levels are abnormally low in a particular area of the brain. Dopamine does not cross the blood-brain barrier, however, so patients do not respond to treatment with dopamine. Dopa, on the other hand, a precursor of dopamine, does cross the barrier, giving relief to many individuals with Parkinsonism. Dopaminergic neurons (neurons secreting dopamine) may be involved in schizophrenia. In this case, the neurons secrete too much dopamine.

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...

Atypical Neuroleptics

Preliminary studies suggest that atypical neuroleptics may exhibit some beneficial effects in bipolar depression. Most studies were uncontrolled or studied the effects of atypical neuroleptics on depressive symptoms in mixed bipolar patients. However, given the clear efficacy of typical antipsychotics in depression (whose clinical use was prevented mostly by extrapyramidal symptoms and tardive dyskinesia) it is likely that atypical antipsychotics will be increasingly useful in depression. If so, this may blur the traditional diagnostic boundaries between schizophrenia and affective disorder. It might also make the continuum between mania, mixed states, and depression less relevant to treatment.

Psychobiological Functioning Of Girls At Risk For Depression

Participants in this ongoing study are 11- to 14-year-old daughters and their biological mothers. All of the daughters are being interviewed with the Washington University Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS Geller et al., 2001) their mothers complete the K-SADS with reference to their daughters. Regardless of the diagnostic status of the mothers, all daughters in this study must have never had a diagnosable Axis I disorder. Mothers are interviewed with the Structured Clinical Interview for DSM (SCID-I First, Spitzer, Gibbon, & Williams, 1996), to establish whether they meet diagnostic criteria for having had two discrete episodes of MDD within their daughters' lifetime (recurrent depressed mothers) or for never having had an Axis I disorder (never-disordered mothers). At the time of testing, recurrent depressed mothers must not be experiencing an episode. Thus no mother or daughter meets criteria for a current diagnosis of MDD at the time of her first...

CSF Proteomic Applications in Central Nervous System Diseases

Several CSF proteins, discovered by 2-DE, have been proposed as diagnostic markers for neurodegenerative disorders for example, the 14-3-3y protein (originally p130 and p131) as a surrogate marker for Creutzfeldt-Jakob disease (CJD) 27, 60 , and the middle isoform of a2-haptoglobulin for Alzheimer's disease (AD) and schizophrenia 30 . In AD, many studies have found various assays for CSF tau and CSF -amyloid to be very informative 61-63 . Only a few comparative proteomic analyses of CSF proteins have been employed for studies of pathophysiological mechanisms in neurodegenerative diseases. Using 2-DE gel and the silver staining technique, large differences in protein patterns in CSF between patients with brain disorders such as AD, schizophrenia, Parkinson's disease, and multiple sclerosis were shown 24, 25, 28, 73 , however many of these proteins have not yet been identified. Fonteh and Harrington reported at the 2002 meeting in Siena an increase of specific isoforms of...

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

From Clinical Phenomenology To Diagnostic Validity

Validity studies also can be used to sharpen the reliability of diagnostic criteria for mood disorders. Such sharpening would have an impact on the current estimates of the prevalence of mood disorders, which are based substantially on the Epidemiological Catchment Area (ECA) study using the Diagnostic Interview Schedule (DIS) as its instrument (based on DSM-III) administered by lay persons. It is interesting to note, however, that clinician-administered research interviews correlated poorly with DIS-based diagnoses in one of the ECA sites (Anthony et al. 1985). Later, ECA-like diagnostic methods were used in the National Comor-bidity Survey even with similar methods, the prevalence of mania was twice as high as in the ECA study (1.6 compared with 0.8 ) and the prevalence of unipolar depression was also much higher (17 vs. 8 ) (Kessler et al. 1994). Rediagnosis of a subsample in that study by clinician researchers reported lower rates of nonaffective psychosis diagnoses than those...

Progress In Neurobiology

Advances in neuroimaging are another exciting area of progress in neurobiological research. Mood disorders still lag behind schizophrenia in being a focus of such work, and future neuroimaging research should focus more on mood disorders. The relative paucity of work in mood disorders raises the likelihood of type II error (false negatives) in the interpretation of available small data sets due to lack of statistical power to find existent differences. Functional neuroimaging, like positron emission tomography (PET), is beginning to demonstrate subtle patho-physiological differences that have eluded structural brain imaging, such as computed tomography (CT) or magnetic resonance imaging (MRI) (Mayberg 2003). Recent data suggest neuroanatomical mechanisms of antidepressant response in unipolar depression (Mayberg et al. 2005) similar work needs to be done in bipolar depression.

Extensive Reading Definition

What Causes Aphasia

When taking a history, the physician may find that the problem is not limited to reading and writing. There can be other sources of trouble poor aptitude, inadequate schooling, up to and including illiteracy, auditory deficits, neurological diseases (aphasia, alexia, cerebral palsy), and or primary psychiatric disorders (psychoses and severe neurotic disorders).

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.

Human Correlational Studies

Low MAO levels are also found in various forms of psychopathology, including attention-deficit hyperactivity disorder, antisocial and borderline personality disorders, alcoholism and drug abuse, pathological gambling disorder, and paranoid schizophrenia (see Table 3.2). With the possible excep- Schizophrenia with paranoid delusions and hallucinations (high MAO in schizophrenia with withdrawal and behavioral retardation) tion of paranoid schizophrenia (sensation seeking is actually low in more withdrawn individuals with schizophrenia), these are disorders characterized by impulsive and sensation-seeking behaviors in their active stages. Mania is a caricature of sensation seeking in its active stage, but even when patients with bipolar disorder are not having a manic episode, they score high on the SSS. Relatives of persons with alcoholism and sons of individuals with bipolar disorder also have low levels of MAO, even though they do not yet have the disorders this suggests that MAO is a...

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...

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...

Neurodegenerative Pathology within the Hippocampus

Performed single-cell RNA amplification combined with custom-designed cDNA array analysis to evaluate the effects of aging on DRD1-DRD5 DA receptor mRNA expression levels in hippocampal CA1 pyramidal neurons and entorhinal cortex layer II stellate cells from a cohort of normal control postmortem human brains aged 19 to 95 years 58 . Results indicate a significant age-related decline for all five DA receptor mRNAs in CA1 pyramidal neurons 26, 58 . Downregulation of DA receptor subtypes appears to be relatively selective, as no age-related decrement in other mRNAs is observed in CA1 pyramidal neurons, including the cytoskeletal elements beta-actin, three-repeat tau (3Rtau), and four-repeat tau (4Rtau) 58 . In contrast, no significant changes in DA receptor subtype expression are observed in entorhinal cortex stellate cells across the same cohort 26, 58 . Alterations in hippocampal DA function impact cognitive and mnemonic functions, and disruption in the functional integrity of...

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.

Intravenous anaesthetics

Contraindications include moderate to severe hypertension, congestive cardiac failure or a history of stroke acute or chronic alcohol intoxication, cerebral trauma, intracerebral mass or haemorrhage or other causes of raised intracranial pressure eye injury and increased intraocular pressure psychiatric disorders such as a schizophrenia and acute psychoses.

The Linkage Approach

Mendelian disease genes has spawned large-scale efforts to track down genes involved in the more common complex disease phenotypes. This approach is not restricted to academic research groups many pharmaceutical and biotechnology companies have joined what many would perceive to be a 'genetic gold-rush', in an attempt to identify new drug targets for common diseases such as asthma, diabetes and schizophrenia, in a manner reminiscent of the rush to mine drug targets from expressed sequence tags (ESTs) in the late 1990s (Debouck and Metcalf, 2000). The application of a linkage approach to complex disease typically involves combining data from a large number of affected sib-pairs. Publicly available software for linkage analysis of sib-pairs is described in detail in Chapter 11.

Pub Med

Many of the same guiding principles applied to searching the web also apply to PubMed, but there are some differences between this tool and other more general web search engines. Firstly the boolean operators are limited to the three main operators AND, OR and NOT. One major improvement over most web search engines is the availability of a wildcard function (*) to designate any character or combination of characters. The creative use of wildcards and boolean terms is important to widen the search without retrieving excessive and irrelevant results. For example, to find publications which present evidence of schizophrenia association on chromosome 8q21, an appropriate PubMed query might be schizo* AND 8q* searching the text word field. Using a wildcard search with 'schizo*' instead of 'schizophrenia' retrieves articles which mention schizoaffective, schizophrenia or schizophrenic, all of which may be relevant. By using a wildcard with

Maturation

Another source of invalidity is called maturation, which refers to biological or psychological processes that change over time. Again, if these maturational changes occurred at the same time as the manipulation of the independent variable, they could explain the findings. Suppose that this woman had a sudden spontaneous remission of her psychosis. Presumably, this would account for why she no longer wanted to hoard towels. Although her 9 years of hospitalization argue against this possibility, the researcher should have gathered evidence about her psychiatric condition before and after the experiment.

Cannabis

The effects can be unpleasant, especially in inexperienced subjects, particularly timelessness and the feeling of loss of control of mental processes. Feelings of unease, sometimes amounting to anguish and acute panic occur as well as 'flashbacks' of previously experienced hallucinations, e.g. on LSD. There is also, especially in the habitual user, a tendency to paranoid thinking. High or habitual use can be followed by a psychotic state this is usually reversible, quickly with brief periods of cannabis use, but more slowly after sustained exposures. Evidence suggests that chronic use may precipitate schizophrenia in vulnerable individuals.

Summary

Despite substantial progress using brain imaging and genetic techniques, our ability to study the biology of bipolar depression is limited by our imperfect ability to describe the phenotype of bipolar disorder. The presence of past mania or hypomania is not sensitive enough, since depression usually precedes mania. This problem can potentially be addressed by the study of endophenotypes, or characteristics like P300 amplitude or response to stimulants that may represent expression of underlying susceptibility genes (Lenox et al. 2002). Bipolar disorder may share characteristics with schizophrenia or with unipolar disorder, while other features may distinguish it from either illness. This would explain the genetic and clinical overlap between bipolar disorder and both schizophrenia and unipolar disorder, as well as the spectrum-like presentation of affective disorders and schizophrenia.

Diagnostic Issues

Older classifications of psychiatric disorder divided diseases into 'psychoses' and 'neuroses'. The term 'psychosis' is still widely used to describe a severe mental illness with the presence of hallucinations, delusions or extreme abnormalities of behaviour including marked overactivity, retardation and catatonia, usually accompanied by a lack of insight. Psychotic disorders therefore include schizophrenia, severe forms of depression and mania. Psychosis may also be due to illicit substances or organic conditions. Clinical features of schizophrenia may be subdivided into 'positive symptoms', which include hallucinations, delusions and thought disorder and 'negative symptoms' such as apathy, flattening of affect and poverty of speech.

Interactions

Some combinations may have an unexpected adverse outcome unless anticipatory dose adjustment is made, e.g. paroxetine + thioridazine (CYP 2D6), fluoxetine + sertindole (CYP 3A4) and fluvoxamine + olanzapine (CYP 1A2) but others, e.g. fluoxetine + quetiapine (CYP 3A4) appear to be of less significance. An interaction of particular importance involves zuclopenthixol acetate used rapidly to tranquillise psychotic patients who are also receiving fluoxetine or paroxetine and an oral antipsychotic (see p. 363). Inhibition of zuclopenthixol metabolism (CYP 2D6) by fluoxetine or paroxetine, and exacerbated by competition from another antipsychotic CYP 2D6 substrate, can provoke serious over-sedation and respiratory depression.

Classification

The continuing search for greater efficacy and better tolerability led researchers and clinicians to reinvestigate clozapine, a drug which was originally licenced in the 1960s but subsequently withdrawn because of serious haematological effects. Clozapine appeared to offer greater effectiveness in treatment-resistant schizophrenia, to have efficacy against negative in addition to positive psychiatric symptoms (see Table 19.4), and to be less likely to cause extrapyramidal motor symptoms. It regained its licence in the early 1990s with strict requirements on dose titration and haematological monitoring. The renewed interest in clozapine and its unusual efficacy and tolerability stimulated researchers to examine similar 'atypical' antipsychotic drugs.

Indications

Antipsychotic drugs are used for the prophylaxis and acute treatment of psychotic illnesses including schizophrenia and psychoses associated with depression and mania. They also have an important role as an alternative or adjunct to benzodiazepines in the management of the acutely disturbed patient, both for tranquillisation and sedation. Antipsychotics have been used short-term in severe anxiety but are now given only as a last resort. Certain antipsychotics have an antidepressant effect which is distinct from their ability to treat the psychosis associated with depression but use as antidepressants is difficult to justify given the many pharmacological options now available for treating depression. Antipsychotics have also proved useful in the tic disorder Tourette's syndrome and for recurrent self-harming behaviour.

Mechanism Of Action

Historically the beneficial effects of classical antipsychotic agents were explained by their action on brain pathways in which dopamine is the neurotransmitter. Dopaminergic pathways include the tuberoinfunibular pathway (moderating prolactin release from the hypothalamus), the nigrostriatal pathway (involved in motor control and deficient in Parkinson's Disease) and the mesolimbic pathway, which runs from the ventrotegmental area via the nucleus accumbens to the prefrontal cortex (Fig. 19.3) (and is overactive in psychotic illness according to the dopamine hypothesis of schizophrenia). Five dopamine receptor types are identified. Dj- and D5-receptor activation increases intracellular cyclic AMP concentrations whereas activation of D D3 and D4 subtypes has the opposite effect. Since all classical antipsychotic agents shared an ability substantially to block D2-receptors, their effects in ameliorating psychosis were ascribed to preventing activation of these receptors. Thus it was...

Efficacy

Symptoms in schizophrenia are defined as positive and negative (Table 19.4). Whilst a classical antipsychotic drug should provide adequate treatment of positive symptoms including hallucinations and delusions in at least 60 of cases, patients are often left with unresolved negative symptoms such as apathy, flattening of affect and alogia. Evidence suggests that clozapine and the newer atypicals have a significant advantage over classical drugs against negative symptoms. Clozapine has a Schizophrenia often runs a chronic relapsing and remitting course. Less than one-quarter of patients who experience a psychotic episode and are diagnosed as having schizophrenia succeed in avoiding further episodes. Nevertheless, taking antipsychotics as prophylaxis significantly reduces the likelihood of relapse.

Things To Come

Pharmaceutical company research on sedative-hypnotics rose and peaked within the several decades after the introduction of the ben-zodiazepines and has waned since then because CNS-related drug discovery efforts have focused instead on improved therapy for such disorders as depression and schizophrenia and the unmet medical need of stroke, Alzheimer's disease, and other neurodegen-erative maladies. However, given the imperfections of available drugs and the high incidence of sleep disorders among the evergrowing elderly population, more efficacious and safer agents are certainly needed. The current stable of drugs typically act as CNS depressants that do not promote physiological sleep and that may cause cognitive and memory impairment, motor skills impairment (especially when ingested along with alcohol), and have potential abuse liability. Where then, should we look for better agents, agents that may be better classified as sleep normal-izers rather than sedative-hypnotics Use of...

Suicide Statistics

Though completed suicides are rare and difficult to predict, efforts to assess suicide risk during clinical interviews are justifiable on many grounds. First, suicide occurs much more frequently in a clinical population than in the general population (e.g., clients with clinical depression, panic disorder, alcoholism, and schizophrenia are at greater risk Moscicki, 1997 Rossau & Mortensen, 1997). Second, suicide attempts occur about 20 times more frequently than completed suicides (about 1,900 adults attempt suicide in the United States each day R. Anderson, Kochanek, & Murphy, 1997). The clinical interviewer's task is to try to reduce the incidence not only of completed suicides, but also of suicide attempts (especially severe suicide attempts, which seem to be associated with many of the same factors as completed suicides Beautrais, 2001). Finally, clinically, ethically, and legally speaking, it is better to err in assuming a client may be suicidal and proceed with a thorough...

Clonazepam

Unwanted effects from drugs sometimes become apparant only following prolonged use, and vigabatrin is a case in point. Vigabatrin had been licenced for a number of years, before it was found to cause visual field constriction in up to 40 of patients, an effect that is insidious and leads to irreversible tunnel vision.7 Its discovery emphasises the value of postmarketing drug surveillance programmes.8 Vigabatrin is now indicated only for patients with the specific seizure disorders responsive to the drug (above), and no other. Patients should undergo visual field monitoring at six-monthly intervals whilst taking the drug. Other adverse effects on the CNS are similar to those of antiepilepsy drugs in general but include confusion and psychosis. Increase in weight also occurs in up to 40 of patients during the first 6 months of treatment.

Chromosome

Several groups have reported suggestive to significant linkage to chromosome 22 in bipolar samples, including the NIMH Genetics Initiative samples, the NIMH neurogenetics pedigrees, and Kelsoe et al. (2001). In Badner and Gershon's (2002) meta-analysis of published whole-genome scans of bipolar disorder and schizophrenia, there was strong evidence for 22q harboring a common susceptibility locus for both disorders. Potash et al. (2003) also reported evidence of linkage in families with psychotic mood disorders to 22q12, reporting a nonpara-metric LOD score of 3.06 including families without psychotic mood disorders resulted in little evidence for linkage to this region. Badenhop et al. (2002) detected a two-point LOD of 2.0 on chromosome 22q11 at marker D22S420 under a recessive, broad model, but only within a single pedigree.

Speech and Thought

Sometimes clients from nondominant cultural backgrounds have difficulty responding quickly and smoothly to mental status examination questions. For example, as noted by Paniagua (2001), Clients who are not fluent in English would show thought blocking (p. 34). This particular phenomenon, characterized by a sudden cessation of thought or speech, may signal symptoms of anxiety, schizophrenia, or depression. However, African American clients who use Black English in most conversational contexts would . . . spend a great deal of time looking for the construction of phrases or sentences in Standard American English when they feel that Standard American English is expected (p. 34). Loose Associations A lack of logical relationship between thoughts and ideas. Sometimes, interviewers can perceive the connections but must strain to do so for example I love you. Bread is the staff of life. Haven't I seen you in church I think incest is horrible. In this example, the client thinks of attraction...

Amfetamines

As well as oral use, i.v. administration (with the pleasurable 'flash' as with opioids) is employed. Severe dependence induces behaviour disorders, hallucinations and even florid psychosis, which can be controlled by haloperidol. Withdrawal is accompanied by lethargy, sleep, desire for food and sometimes severe depression, which leads to an urge to resume the drug. Acute poisoning is manifested by excitement and peripheral sympathomimetic effects convulsions may occur also, in acute or chronic overuse, a state resembling hyperactive paranoid schizophrenia with hallucinations develops. Hyperthermia occurs with cardiac arrhythmias, vascular collapse and death. Treatment is chlorpromazine with added antihypertensive, e.g. labetalol, if necessary these provide sedation and a- and (3-adrenoceptor blockade (not a P-blocker alone), rendering unnecessary the enhancement of elimination by urinary acidification. Chronic overdose can cause a psychotic state mimicking schizophrenia. A vasculitis...

Future Directions

Expanding genetic studies of bipolar disorder to include endophe-notypes (i.e., traits associated with the disease that are heritable, precede disease onset, and are present in unaffected relatives) may also prove to be a fruitful approach, because such traits may reflect the underlying genetic phenomena more closely than diagnostic criteria. In schizophrenia research, endophenotypes have received a great deal of attention but are less widely used in research on bipolar disorder. It is somewhat unclear at present which endophenotypes for bipolar disorder would prove most useful, but candidates include circadian rhythm disruption, response to sleep disruption and psychostimulants, tryp-tophan depletion, and white matter hyperintensities (Lenox et al. 2002 Gould and Manji 2003), as well as electroencephalographs asymmetries (Hayden et al. 2003), temperament (Johnson et al. 2000 Kwapil et al. 2000 Lozano and Johnson 2001), cortisol (Ellenbogen et al. 2004), and melatonin levels...

Naloxone

Sudden cessation of benzodiazepines can lead to a recognized withdrawal syndrome (34) with anxiety symptoms, disordered perceptions, and major complications, such as seizures and psychosis (35). A long-acting benzodiazepine, such as diazepam or chlordiazepoxide, is preferable in treating symptoms of withdrawal and preventing the major complications. Both enjoyable and unpleasant effects, a bad trip may occur in a firsttime user or with repeated use (47). Five major categories of psychiatric adverse effects have been described, which include anxiety and panic attacks, self-destructive behavior, hallucinations, acute psychosis, and major depressive reactions (48). Polydrug users may use benzodiazepines to alleviate anxiety and panic attacks. Chronic toxic effects include a prolonged psychosis, major depressive illness, disruption of personality, and post-hallucinogen perceptual disorder (48) characterized by flashbacks even months or years after LSD use. Euphoria, heightened awareness,...

Phencyclidine

Phencyclidine, known as angel dust, is usually smoked, although it can be taken orally, intravenously, or by nasal inhalation. It is commonly used as an additive to other drugs, such as cannabis or LSD, and the symptoms and signs may vary greatly (49). At low doses, euphoria, relaxation, and an altered body image may occur, but at higher doses, there may be agitation, bizarre behavior, and a paranoid psychosis (50). Analgesia occurs, which may lead to self-injury. Physical effects include nystagmus (lateral and vertical), and with severe intoxication there is adrenergic stimulation with hypertension, tachycardia, flushing, hyperthermia, and cholinomimetic stimulation with sweating, hypersalivation, miosis, dystonia, ataxia, and myoclonus eventually resulting in coma, respiratory arrest, and circulatory collapse (51). Death may also result from intoxication or from violent behavior. Chronic effects of phen-cyclidine abuse include memory impairment, personality changes, and depression...

Ecstasy

Regular users may habitually use chewing gum to overcome the effects on the jaw muscles. The clenching of teeth in the acidic environment caused by carbonated (fizzy) drinks will result in an increased likelihood of tooth wear on the back teeth (56). Other adverse effects have been described, including jaundice and hepatotoxicity (57) flashbacks and psychosis (58) pneumomediastinum (59) urinary retention (60) hyperthermia coagulopathy (61) rhabdo-myolysis and cardiovascular complications resulting in death (62-64). Development of chronic paranoid psychosis has been described after heavy misuse of the drug (65), and the serotonin syndrome (66) (altered mental state, hyper-thermia, and autonomic dysfunction) has also been reported following MDMA ingestion (67). Evidence is emerging of possible long-term damage to the brain in the form of serotonin neural injury, which may result in depression, anxiety, and memory disorders (68). However, there are other factors, such as other...

Amphetamine

Speed runs describe repeated use over a period of days, with several grams of amphetamine used daily. At the end of the run, the user may sleep for several days. Alcohol, sedative-hypnotic drugs, and heroin may be used to reduce the anxiety caused by amphetamine or, alternatively, amphetamine may be used to reduce the sedative effects of such drugs. Psychological dependence occurs, and psychosis may occur, which resolves when the drug is stopped. However, it is possible that amphetamine use may trigger latent schizophrenia.

Current Situation

Adults can also be unaware of their family histories or details about their own development. Patients with psychosis or personality disorder may not have enough perspective to judge accurately many of their own symptoms. In any of these situations, the history you obtain from people who know your patient well may strongly influence your diagnosis. (p. 203)

Abstract

Cannabis has been used for medical purposes for centuries. With the discovery of cannabinoid receptors, there has been an explosion of research on both natural and synthetic cannabinoids. This chapter reviews both animal and human research demonstrating the potential role of cannabinoids in motivational processes and their associated disorders (hunger, appetite, pain), psychological disorders (anxiety, depression, bipolar disorder, schizophrenia, alcohol dependence) and central nervous system disorders (vomiting and nausea, spasticity, dystonia, brain damage, epilepsy). The most likely applications for can-nabinoid agonists are for the treatment of loss of appetite, pain, anxiety, vomiting, nausea and epilepsy. The most likely applications for cannabinoid antagonists may be for anxiety, schizophrenia, spasticity, and dystonia. It is difficult to formulate an hypothesis concerning the potential treatment of depression, bipolar disorder and alcohol dependence since very little work has...

Clinical Picture

The diagnostic criteria and symptom profile of pediatric bipolar depression are the same as those for adults however, the way the symptoms are expressed varies with the developmental stage of the child (Table 4-1). For example, instead of communicating the sad feelings, children may act out and be irritable towards others, or express multiple somatic complaints, like headaches and stomachaches. Presence of specific symptoms such as psychosis, psychomotor retardation, medication-induced disinhibition hypomania, or a family history of bipolar disorder may indicate that the depressed patient is at risk to develop bipolar disorder (Geller et al. 1994 Strober and Carlson 1982 Strober et al. 1993). Somatic complaints and thoughts of death are common. Adolescent patients may be more likely to present with rapid cycling or mixed episodes. These patients are difficult to treat and are at an increased risk for suicide (Brent

Adolescents

Strober et al. (1993) studied 60 hospitalized, depressed adolescents (ages 13-16 years) and found that at the 3- to 4-year follow-up, 20 of these patients had developed bipolar disorder. This was predicted by the rapid onset of depressive symptoms, psychomotor retardation, family history of bipolar disorder, medication-induced mania hypomania, and mood-congruent psychosis. Geller et al. (1994, 2001b) also noted similar presentation in two studies.

S100b

S100B protein is not essential for survival since S100B- -mice present only mild phenotypes (Table 3). They show an enhanced spatial and fear memory associated with strengthened neuronal plasticity (Nishiyama et al., 2002). In addition, enhanced epileptogenesis has been reported (Dyck et al., 2002), probably because of abnormalities in calcium-handling in astrocytes, as evidenced by increased Ca2+ transients upon KCl and caffeine treatment in S100B-deficient neonatal cerebellar glia cells (Xiong et al., 2000). Transgenic mice overexpressing S100B exhibit enhanced explorative activity, reduced anxiety and impaired learning and memory capabilities (Bell et al., 2003 Gerlai et al., 1995 Gerlai and Roder, 1996 Winocur et al., 2001). Interestingly, in humans, higher S100B concentration has been detected after brain trauma and ischemia, making S100B a potential diagnostic protein in traumatic brain damage (Rothermundt et al., 2003). An increased concentration of S100B has also been found in...

Physical Findings

Grooming or hygiene along with significant weight changes. Speech may be normal, slow, monotonic, or lacking in content. Pressured speech is suggestive of mania, whereas disorganized speech suggests the need to evaluate for psychosis. The thought content of patients with depression includes feelings of inadequacy, helplessness, or hopelessness. Sometimes patients complain of being overwhelmed. Psychomotor retardation can manifest as slowing of movements or reactions, especially in the elderly. Inpatient management is indicated when the patient presents a significant risk to self (suicide, inability to care for self) or others (risk of violence), or the symptoms are sufficiently severe to initiate treatment in controlled settings. Involvement of a psychiatrist is warranted in the care of patients in whom more severe symptoms require more intensive care (suicidal ideations, psychosis, mania, and severe decline in physical health). Bereavement is defined as symptoms of a major depressive...

Linkage

Accuracy of genotyping and exclusion of Mendel errors are important for success, but so is the careful definition of affection status. This may not always be easy for diseases like asthma, schizophrenia or systematic lupus erythematosus (SLE). Even with diabetes, the definition is based upon artificial cut-offs of plasma glucose. Dichotomising variables may result in loss of power. One alternative is therefore to search for linkage to a qualitative trait, e.g. blood glucose, blood pressure or body mass index, instead of diabetes, hypertension and obesity. Heritability (h2) is often used as a measure of the genetic component of a quantitative trait. The higher the heritability, the more likely it is a genetic cause of a trait will be found. Several statistical programmes have been developed to support genome-wide scans of quantitative trait loci (QTL), such as the variance component models SOLAR and Merlin Linkage will only identify relatively large chromosomal regions (often > 20...

Epidemiology

The Guze and Robins finding has been criticized as not being gener-alizable to the general population on several grounds, most commonly because subjects were not actually followed over their entire lifespan, and since suicide accounts for a larger percentage of overall mortality in younger populations, the prevalence of suicide was markedly overestimated. Blair-West et al. (1997) accounted for this in major depression by adding the lifetime risk for suicide in each age group, and concluded that the rate is 2.5 . After adjustment for an estimated rate of 40 for underreporting of suicide, the lifetime risk climbs to 3.5 . Similarly, Inskip et al. (1998) recalculated the lifetime risk of death from affective disorders using computer modeling techniques to take into account the fact that subjects are not followed until the entire cohort has died and that suicide is a disproportionately high cause of death in younger patients. They thereby estimated that the lifetime risk of death from...

Psychiatric Effects

Typically users presenting with psychotic symptoms have taken large doses. The reaction can present in a variety of ways, but it is often characterised by paranoid delusions, agitation, disordered thinking and hypomania. Hallucinations can also occur. Sometimes these episodes are described as schizophreniform reactions, and they can occur in those already suffering from psychosis (or latent psychosis), as well as those with no apparent tendency to mental illness. Usually the sufferer exhibits marked or complete improvement within a week of abstinence from cannabis, often with minimal treatment. There has been a reluctance to label this reaction officially as acute cannabis psychosis, perhaps because the presentation is very variable, but this is in the nature of the action of psychoactive substances. The effects of acute intoxication vary widely between individuals, and for the same individual, depending on the factors already discussed. Several studies have shown that there is...

Heavy Metal Toxicity

Heavy metal exposure, such as from mercury and lead, can be acute or chronic. Heavy metals can cause serious toxicological consequences that may be initially confused with drug-of-abuse or alcohol exposure due to behavioral and neurological manifestations. For example, high doses of lead can cause systolic hypertension and encephalopathy, while high or chronic exposure to mercury can cause psychotic behavior. Encephalopathy is a general term for disease of the brain, while neuropathy means disease of the nerves or neurons that may impair voluntary nerve function or functions of the brain. Psychosis, or confusion, complete disorientation, and loss of reasoning power, can be a result of heavy metal neurotoxicity. In addition, chronic low-dose exposure to heavy metals is a concern for proper neurological and other organ development in the young. Therefore, physical examination and history can be helpful in determining if heavy metal toxicity is suspected. Specific laboratory tests are...

Neurologic Syndromes

With PCD,125 which occurs in about 0.5 of patients with HD.126 It has been reported in all phases of the disease and is characterized by the symptom complex of dysarthria, nystagmus, ataxia, and intention tremor. The pathogenesis involves Purkinje cell destruction in the cerebellum by antineuronal antibodies such as anti-Tr antibodies127 128 and anti-mGluR1 antibodies129 in HD. PLE is more infrequent than PCD, and HD accounts for 4-7 of this rare disorder.130 While anti-Hu and anti-Ta antibodies have been described in patients with PLE in the context of other solid tumors, no specific antibodies have been identified in patients with PLE in the setting of HD. Personality changes, depression, memory loss, cognitive impairment, and occasionally psychosis are the predominant clinical manifestations. Prognosis is poor, and neurological improvement is rare.

Separation Anxiety

In accordance with psychiatric criteria, the duration of disturbance must be at least 4 weeks, and the onset must before age 18 (15). There must also be some functional impairment, including clinically significant distress or impairment in social, academic, or other important areas of functioning. In addition, separation anxiety disorder does not occur exclusively during the course of a pervasive developmental disorder, schizophrenia, or other psychotic disorder and, in adolescents and adults, is not better accounted for by panic disorder with agoraphobia.

Conclusion

This review has suggested that cannabinoids may be useful in the treatment of many disorders. The most likely applications for cannabinoid agonists are for the treatment of loss of appetite, pain, anxiety, vomiting, nausea and epilepsy. The most likely applications for cannabinoid antagonists may be for anxiety, schizophrenia, spasticity, and dystonia. It is difficult to formulate an hypothesis concerning the potential treatment of depression, bipolar disorder and alcohol dependence since very little work has been done with these disorders at this point of time.

Oxcarbazepine

Despite being poorly studied with respect to bipolar illness, oxcarba-zepine has made it into the American Psychiatric Association practice guideline for bipolar treatment (2002). Its utility in bipolar depression is even more poorly studied than in mania and hypomania. The observation that oxcarbazepine reverses abnormal behavior in two rat models of depression (Beijamini et al. 1998) suggests that it may indeed have antidepressant properties. In a group of 56 bipolar patients presenting with depression (n 23), mania (n 19), or psychosis (n 14), there were

Cerebrospinal Fluid

Besides these global approaches of CSF protein content, some authors have started to focus on groups of CSF proteins related to particular neural structures or functions. For example, Borghini et al. 78 specifically analyzed and characterized the apolipoprotein content of lipoprotein particles in CSF and showed a considerable structural and size heterogeneity of these compounds, possibly mirroring the complexity of lipid transport processes going on in the CNS. Even more relevant for the purpose of identifying biomarkers for neurodegenerative diseases, Davidsson et al. 79 have studied the synaptic proteins SNAP-25, GAP-43, synap-totagmin, rab3a, and neurogranin in CSF using a specific procedure including TCA precipitation, liquid-phase IEF and western blotting. These authors were able to confirm that these compounds were indeed present in the CSF in trace amounts, opening the door to a quantitative CSF testing which may reflect altered synaptic function and integrity as it is known to...

Miscellaneous

Besides the quite common neurological diseases reviewed above, various protein abnormalities have also been found in brain trauma, amyotrophic lateral sclerosis, Down's syndrome, mental retardation, progressive supranuclear palsy (PSP), corti-cobasal degeneration (CBD), and in rare conditions, including Machado-Joseph disease, aceruloplasminemia, Norrie disease, and Hashimoto encephalopathy. Furthermore, proteomics approaches have been applied to a variety of psychiatric conditions, in particular schizophrenia, and promising findings have already been reported by some groups in CSF, brain tissue, and peripheral samples. Finally, neuropharmacology has also been the target of some preliminary proteomic studies, showing protein alterations after exposure to the antiepileptic vigabatrin or to the neuroleptic haloperidol.

Svlv

1997), analysis of subcortical structure volumes in schizophrenia (Iosifescu et al., 1997), estimation of structural variation in normal and diseased populations (Collins et al., 1994b Thompson et al., 1997), and segmentation and classification of multiple sclerosis lesions (Warfield et al., 1995). Projection of digital anatomic models into PET data can also serve to define regions of interest for quantitative calculations of regional cerebral blood flow (Ingvar et al., 1994). These template-driven segmentations require extensive validation relative to more labor-intensive manual delineation of structures but show considerable promise in medical imaging applications. typically driven by the need to catalogue functional activation studies or to describe pathways of connectivity. However, with the advent of deformable maps that can incorporate variability, individual structures such as specific nuclei or other distinguishable anatomic features are more frequently the subject of...

Treatment of AAION

Elderly patients with arteritic disease have a high level of sensitivity to the side effects of these drugs. Particularly important in the initiation of treatment with high-dose corticosteroids is the unpredictable complication of acute psychosis, which can be potentially life threatening. It is a good practice to admit patients to hospital for at least the first 24 h of therapy, so that a complication of this sort will be noticed. Routine testing of the blood levels of glucose and electrolytes is always indicated. Prophylaxis for the prevention of osteoporosis and or gastric ulcer is always indicated as well. It is difficult to say for how long these precautions should be maintained. Recurrent disease more than 6 months after the initial diagnosis is rare, though possible. There have not been many reports of patients losing vision at these later stages of treatment. Any recurrence of ischemic neuropathy would be difficult to differentiate from the nonarteritic form. There is always a...

Mode Of

Conservative starting doses are also recommended in the elderly and for patients with learning disabilities who may require antipsychotics for psychosis or severe behavioural disturbance. The dose can be titrated up at intervals, until the desired effect in treating psychotic symptoms, calming disturbed behaviour or effecting sedation is achieved. The interval depends on the context, with the urgency of the situation and previous use of antipsychotics being factors which would accelerate the upward titration. An important issue is that the longer a psychosis is left untreated the less favourable is the outcome thus drug treatment should be instigated as soon as an adequate period of assessment has allowed a provisional diagnosis to be established. TABLE 19.4 Symptoms of schizophrenia Prescription of atypical antipsychotics follows similar rules to those for classical drugs, starting at low doses in neuroleptic naive patients. Whereas there is a wide range of effective doses...

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