Some Major Causes Of The Syndrome Of Dementia Introduction

As already noted, there are many brain diseases that can cause dementia. In this chapter we are primarily interested in the dementing diseases associated with aging and will focus on the four most common dementing diseases Alzheimer's disease, frontotem-poral dementia, vascular dementia, and dementia with Lewy bodies. TABLE 15.2. The Dementia Work-up TABLE 15.2. The Dementia Work-up Studies that should be done routinely in all Studies commonly done in clinical practice, but costs benefits not...

Etiology of MCI

Given the preliminary and general nature of the concept of MCI, a clear and concise list of possible etiologies is unlikely although systemic diseases likely account for some cases. Clearly, a significant percentage of the cases represent early stages of dementia, most commonly AD. Petersen et al. (2001) reviewed six longitudinal studies of patients who fit the general description of MCI and found that the annual rate of conversion to a diagnosis of dementia ranged from 6 to 25 percent, with...

Side Effects of Antidepressants

The pharmacological properties that underlie the side effects of antidepressants have been better characterized than the properties responsible for the therapeutic effects. While newer antidepressants have provided little additional therapeutic efficacy compared to older drugs, they are unequivocally safer and much better tolerated. In general, side effects can be divided into those that occur early in the course of treatment and those that emerge gradually over continuous use. Frequently...

Adjunctive Medication

Judicious use of additional medications may be appropriate in selected schizophrenic patients and is very frequently utilized. The basis for the use of adjunctive medication may be treatment of side effects, refractory psychotic symptoms, comorbid conditions, or specific nonpsychotic symptoms such as agitation, anxiety, depression, or mood elevation. Careful consideration of potential side effects, additive effects, and drug interactions is essential. Anticholinergics. Anticholinergic agents...

Psychopharmacological Treatments

Several antidepressant medications and benzodiazepines have been found to be efficacious for panic treatment. Currently, selective serotonin reuptake inhibitors (SSRI's) are considered first-line treatment with regard to issues of safety and tolerability (APA, 1998). Paroxitene (Lydiard et al., 1998), fluvoxamine (Hoehn-Saric et al., 1993), fluox-itene (Michelson et al., 1998), sertraline (Rappaport et al., 1998), and citalopram (Wade et al., 1997) have all been found to be effective in...

From Pathophysiology To Pathogenesis

A clear description of pathophysiological processes is essential for the generation of insights into underlying pathogenic processes. At one time, there was the hope that psychiatric disorders would turn out to be as simple as gout, where elevated uric acid levels lead to buildup at susceptible joints causing inflamed tissues and excruciating pain. Elimination of uric acid buildup (whether by blockade of synthesis with allopuri-nol or reduced ingestion of purine precursors) eliminates the...

Neuroendocrine Responses to Stress

The hypothalamic-pituitary-adrenal (HPA) axis is one of the most widely studied of the stress responsive systems. This cascade begins with the release of CRH from the parvocellular neurons of the paraventricular nucleus of the hypothalamus into the external zone of the median eminence. From here CRH is carried through the portal blood system to the anterior lobe of the pituitary gland, where it acts as a secretagogue for adrenocorticotrophic hormone (ACTH). ACTH is then released into the...

Circadian Dysregulation

Abnormal sleep is a core symptom of major depressive disorder, with sleep disruption seen at all stages in the sleep cycle (Benca, 1994). Symptoms include difficulty falling asleep, or staying asleep, as well as early-morning awakening. Hypersomnia is also described. Electroencephalography (EEG) abnormalities in depressed patients include prolonged sleep latency, decreased slow-wave sleep, and reduced rapid eye movement (REM) latency with disturbances in the relative time...

Intergenerational Transmission

In a study of risk factors for the development of PTSD, Yehuda and her colleagues examined the association between cortisol and PTSD in children of holocaust survivors. Low cortisol levels were significantly associated with both PTSD in parents and lifetime PTSD in subjects, whereas having a current psychiatric diagnosis other than PTSD was relatively, but nonsignificantly, associated with higher cortisol levels. Offspring with both parental PTSD and lifetime PTSD had the lowest cortisol levels...

PET and fMRI Procedures

During the 1990s PET was the gold-standard of neuroimaging. In PET a small amount of a radiotracer is injected intravenously into the subject, and the concentration of tracer in brain tissue is measured by the scanner (see Fig. 2.2, top). While decaying, the radionucleotides emit positrons that, after traveling a short distance (3 to 5 mm) encounter electrons. The two types of particles annihilate each other, resulting in the emission of two gamma rays in opposite directions. The image...

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation is a technology that has been developed to nonin-vasively activate nerve cells through the scalp (Barker et al., 1985). For example, if a single TMS pulse is applied over the thumb area of the motor cortex, it will induce a movement in the contralateral thumb. A unique aspect of TMS is its relative safety, ease of application, and the awake and interactive state of the subject being stimulated (Nahas et al., 2000a). The major side effect is unwarranted...

Structural Abnormalities

Lesion deficit correlation studies demonstrate that certain disorders are more likely to be associated with a major depression than others (a) discrete brain lesions, as seen with trauma, surgery, stroke, tumors, and certain types of epilepsy (b) neurodegenerative diseases with regionally confined pathologies such as Parkinson's, Huntington's, and Alzheimer's diseases (c) disorders affecting diffuse or multiple random locations such as multiple sclerosis and (d) system...

General Treatment Principles

With the growth in knowledge and the availability of newer drugs has come an increase in the number of factors that should be taken into account in appropriately selecting antidepressant medications. This section will provide an overview of the decision-making process involved in using available medications for depression, including known benefits, potential side effects, and proper usage. It is important to note the limitations in our current concepts of antidepressant, mood stabilizer, and...

Diagnosis Of Dementia

Once a patient is found to have the syndrome of dementia, it is necessary to identify the etiology. Numerous illnesses can cause dementia as broadly defined (see Table 15.1). Differentiation of these illnesses is important because some of them are reversible and some can be arrested. It is also important to identify the diseases that are neither reversible nor arrestable (e.g., neurodegenerative diseases) because some disease-specific symptomatic and neuroprotective treatments are now available...

Magnetic Seizure Therapy

If the axiom that a seizure is necessary to obtain antidepressant effects holds true, the current mode of seizure induction needs to improve. The retrograde anterograde amnesia due to nonintended passage of electricity through the hippocampus limits the widespread use of ECT. ECT research has gone through many refinements including electrode placements, intensity of stimulation, and waveforms applied. Current research in brief and ultrabrief pulses is an effort to increase the efficacy and...

Disintegration of Experience Accompanying PTSD

In a series of studies we demonstrated that memories of trauma initially tend to have few autobiographical elements When PTSD patients have their flashbacks, the trauma is relived as isolated sensory, emotional, and motoric imprints, without much of a storyline. We have shown this in victims of childhood abuse (van der Kolk and Fisler, 1995), assaults, and accidents in adulthood (van der Kolk et al., 1997) and in patients who gained awareness during surgical procedures (van der Kolk et al.,...

Basic Models Of The Etiology Of Panic Disorder Neurophysiological Models

Several lines of evidence suggest a neurophysiological basis for panic disorder, including genetic studies. The illness's medication responsiveness (discussed in the treatment section below) has been interpreted to imply a neurophysiological etiology. Evidence for a genetic basis for panic disorder has also been derived from studies of twins that demonstrate a higher rate of concordance for panic in monozygotic than dizygotic twins (Torgersen, 1983, Kendler et al., 1993 Skre et al., 1993)....

Fragile X

Fragile X, a relatively common form of mental retardation caused by a single mutation in the long arm of the X chromosome, occurs once in every 2000 to 4000 live births. Approximately 20 percent of such children exhibit autistic symptoms. Conversely, 8 percent of males and 6 percent of females diagnosed with autism carry the fragile X abnormality. The mutation alters brain development and produces a distinctive physical, cognitive, and neuropsychiatric phenotype. Clinical symptoms are...

Etiological Risk Factors

Pathogenesis Depression

Family history, female gender, neurotic temperament, gene polymorphisms as well as developmental and early life insults, environmental stress, biochemical abnormalities Figure 7.2. Depression pathogenesis. Schematic representation of the ongoing interactions between biological risk factors, exogenous environmental stressors and critical limbic-cortical circuits responsible for maintaining normal responses to ongoing emotionally salient stimuli. Decompensation of this system precipitated by...

Hemispheric Lateralization in PTSD

Both Rauch et al. (1996) and Teicher and his group (2002) found marked hemispheric lateralization in PTSD subjects who were exposed either to a negative memory or to a personalized trauma script. This suggests that there is differential hemispheric involvement in the processing of traumatic memories. The right hemisphere, which developmentally comes on-line' earlier than the left hemisphere (Schore, 1994), is involved in the expression and comprehension of global nonverbal emotional...

Newer Anticonvulsants

Several drugs that have been approved by the FDA as anticonvulsants have been studied as possible mood stabilizers or antimanic drugs (lamotrigine, gabapentin, and topiramate). In spite of extremely limited data on short- or long-term efficacy, their use for the treatment of bipolar disorder and refractory depression in the United States has become widespread. Lamotrigine is the best studied of the newer anticonvulsants. While showing efficacy for treatment of depression and for maintenance...

Prognostic Markers

In light of the described differences between responders and nonresponders with treatment, an obvious related question is whether baseline findings predict eventual treatment outcomes. Several studies have found that pretreatment metabolic activity in the rostral (pregenual) cingulate uniquely distinguishes medication responders from nonresponders (Mayberg et al., 1997), a pattern replicated in Parkinson's disease and other unipolar depressed cohorts (Kennedy et al., 2001...

Dilemma Of Psychiatric Diagnostics Dsms And Beyond

Some mental disorders arise through stressful life circumstances. Others emerge more from constitutional infirmities. Nature-nurture arguments do not help us much in unraveling such intertwined complexities, unless discrete genetic differences can be discovered, as in fragile X and Williams syndrome (Chapter 14). Ultimately psychiatric thought must continue to be guided by a careful appreciation of the evolving stories of selves in action on the stage of life. Neither the brainless psychiatry...

Clinical Presentations

Some patients want only symptom relief and have no intrinsic interest in self-understanding. They are best treated with a straightforward psychopharmacologic approach that includes education to improve adherence. Others, aware that painful affects have important psychic determinants, can be engaged in psychotherapy but develop resistance to deepening the process, especially once symptoms are under control. Some enter psychotherapy or analysis already on medication for severe symptoms, and...

Playfulness and ADHD

No peptide facilitator of playfulness has yet been discovered except for the capacity of low doses of opioids to promote rough-and-tumble play and social dominance in rats (Panksepp et al., 1985). Considering that this social process of the mammalian brain may be a fundamental source of joy, the search for other brain transmitters and neuromodulators that promote play, perhaps through modern molecular biological techniques, may lead to molecules that promote such positive affective states in...

Definition Of Psychoanalytic Concepts

Psychoanalysis is a theory of human psychology and a treatment method based on several basic principles, including The dynamic unconscious, that is, the existence of mental contents that we are not aware of due to the process of repression, or the keeping of certain mental contents out of awareness. Freud emphasized the conflict between id (instinctual wishes pressing for gratification) and superego (the result of the oedipal conflict in which the young child accepts the superior strength and...

Roughand Tumble PLAYJoy System

Among the genetically ingrained emotive systems of the mammalian brain, perhaps the most ignored has been the one that mediates playfulness. We can now be certain that certain mammals possess PLAY systems, largely subcortically situated, that encourage them to indulge in vigorous social engagements that probably promote socialization and the relevant forms of brain development (Panksepp, 1998a). It would be perplexing if the human brain did not contain psychobiological processes homologous to...

World War Ii Through The 1970s The Psychoanalytic Era

Although psychoanalytic ideas have been percolating in American psychology since Freud and Jung's visit to Clark University in 1909, the full impact of depth psychology on psychiatry had to await the massive exodus of psychoanalysts to England and America with the onslaught of World War II. As these energetic immigrants captivated American psychiatry with remarkable speed, there was a dramatic shift toward the psy-chodynamics of the mental apparatus, as well as the controversy that still...

Hormonal Response in Posttraumatic Stress Disorder

In a well-functioning person, stress produces rapid and pronounced hormonal responses. However, chronic and persistent stress inhibits the effectiveness of the stress response and induces desensitization. PTSD develops following exposure to events that overwhelm the individual's capacity to reestablish homeostasis. Instead of returning to baseline, there is a progressive kindling of the individual's stress response. Initially only intense stress is accompanied by the release of endogenous,...

PANICSeparation Distress Grief and Social Bonding

Among the most common and powerful human feelings are those related to pain of loss, especially the grief of social loss. This emotional process has been modeled by the study of the neurochemistries that are able to specifically reduce separation distress in young animals isolated from their social support systems (Panksepp, 2003b). The resistance of this emotional system to most psychotropic drugs has been a surprise, with only antidepressants such as imipramine and in some species...

Factors that Promote and Impair Sleep

It is well known that satisfying basic bodily needs, from hunger to sexual urgency, promote sleepiness. Conversely, all kinds of emotional distress tend to reduce sleep onset and quality. This effect is very prominent in the difficulty that depressed individuals commonly experience in falling asleep and sustaining sleep, and also in the disrupted sleep patterns found in various anxiety disorders, mania, and schizophrenia (Kryger et al., 2000). It is well known that physical exertion during the...

References

Abell F, Krams M, Ashburner J, Passingham R, Friston K, Frackowiak R, Happe F, Frith C, Frith U (1999). The neuroanatomy of autism A voxel based whole brain analysis of structural scans. Neuroreport 10 1647-1651. Abitbol M, Menini C, Delezoide AL, Rhyner T, Vekemans M, Mallet J (1993). Nucleus basalis magnocellularis and hippocampus are the major sites of FMR-1 expression in the human fetal brain. Nat Genet 4 147-153. Alaghband-Rad J, McKenna K, Gordon CT, Albus KE, Hamburger SD, Rumsey JM,...

What Are Personality Disorders

The Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) describes several overarching aspects of personality disorders (Axis II) that theoretically distinguish them from other psychiatric disorders (Axis I). The personality disorders were originally placed on Axis II along with mental retardation because, in theory, they begin early in development and last a lifetime. However, recent research suggests that some personality disorder symptoms may respond to both...

Electroconvulsive Therapy

Between 1917 and 1937, four methods for producing physiological shock were discovered, tested, and used in psychiatric practice for treating psychosis fever, insulin-induced coma, medication-induced convulsions, and electrically induced convulsions (electroconvulsive therapy). In the Western world, only electroconvulsive therapy remains as a standard and effective treatment for psychiatric conditions (APA, 1998). First, malaria-induced fever was used to treat neurosyphillitic paresis. Later,...

Extrahypothalamic CRH Systems

To reiterate a point made earlier, it is not simply exposure to aversive events that ultimately propagates stress in an individual, but also the anticipation of aversive events. The anticipation of aversive events may include learned associations that are formed across the life span as well as species-specific innate responses to biologically hard-wired threats. For instance, learned associations between fearful stimuli and the context where those stimuli are encountered are readily formed....

Neurochemistry of Fear

Future anxiolytic drug development is dependent on further clarification of the neu-rochemical systems that control fearfulness in the brain (Davis, 1999 LeDoux, 2000 Panksepp, 1998a, 2000). The abundant BZ receptors that exist along the main artery of the FEAR circuit that courses between the amygdala and PAG (Fig. 16.1) provide a substrate whereby traditional minor tranquilizers (as well as alcohol and barbiturates) may inhibit anxiety (Haefely, 1990). The distinct GABA and BZ binding sites...

Psychiatric Neurosurgery

Of all the somatic therapies in psychiatric practice today, psychiatric neurosurgery requires the most knowledge about functional neuroanatomy since it is the most radical and irreversible of all interventions. It was only in the last years of the 19th century that rational approaches to psychosurgery were first tried, pursuant to well-publicized clinical cases like Phineas Gage whose frontal lobe lesion in a mining accident showed that frontal lesions could alter a person's personality. In...

Psychophysiological Effects Of Trauma

Posttraumatic stress disorder is not an inevitable outcome of stress Only about 25 percent of individuals who have been exposed to a potential traumatic stressor develop PTSD (Yehuda and McFarlane, 1995). Hence, the central question regarding the biology of PTSD is how to account for the failure of the organism to reestablish its homeostasis and return to its pretraumatic state. Yehuda (2002) has pointed out that understanding the biological response that occurred during the traumatic event...

Vagus Nerve Stimulation

The vagus nerve is classically described as the wandering nerve. It sends signals from the central nervous system to control the peripheral cardiovascular, respiratory, and gastrointestinal systems. However 80 percent of its fibers are afferent, carrying information from the viscera back to the brain (Foley et al., 1937). The fibers first enter the midbrain at the nucleus tractus solitarius (NTS) level. From the midbrain, they either loop back out to the periphery in a reflex arc, connect to...

Neuropeptides In Psychiatric Disorders

Similarly to the classic neurotransmitters, mounting evidence is available about changes in neuropeptide expression and processing in several psychiatric disorders. Neuropep-tides are present in brain tissue as well as in cerebrospinal fluid (CSF). Although the neurotransmitter function of neuropeptides is associated with their synthesis in situ in brain and anatomical distribution via neuropeptidergic fiber systems, their abundant presence in the CSF may be primarily due to simple drainage...