Grup de suport pentru TOC-CAP 15

Camrynna Greu de spus, sunt multe posibilitati de evolutie naturala. Dar anxietatea poate aduce mai multe anxietate, poate aduce depresie.

Daniela, neerlandezul. La intrebarea cu "de ce? e cam greu de raspuns. Cel mai simplu raspuns ar fi ca deoarece e o boala cu o etiologie relativ neclara deocamdata, cu factori de risc biologici, sociali, psihologici si ca... viata e nedreapta si ati avut ghinionul sa aveti aceasta afectiune. Insa asa cum stim, noi trebuie sa ne adaptam vietii, iar nu viata noua.
Iar un raspuns mai lung (dar nu comprehensiv) este acesta:
DOI: 10.1176/appi.books.9781585623402.294126

Obsessive-Compulsive Disorder
Definition

The essential features of OCD are obsessions or compulsions. DSM-IV-TR criteria for OCD are presented in Table 12-23.

The terminology of "obsessions" or "compulsions" is sometimes used more broadly to characterize conditions that are not true OCD. Although some activities, such as eating, sexual behavior, gambling, or drinking, when engaged in excessively may be referred to as "compulsive, " these activities are distinguished from true compulsions in that they are experienced as pleasurable and ego-syntonic, although their consequences may become increasingly unpleasant and ego-dystonic over time. Obsessive brooding, ruminations, or preoccupations, typically characteristic of depression, may be unpleasant but are distinguished from true obsessions because they are not as senseless or intrusive and the individual regards them as meaningful, although possibly excessive and painful.

There are several presentations of OCD based on symptom clusters. One group includes patients with obsessions about dirt and contamination, whose rituals center around compulsive washing and avoidance of contaminated objects. A second group includes patients with pathological counting and compulsive checking. A third group includes purely obsessional patients with no compulsions. Primary obsessional slowness is evident in another group, in whom slowness is the predominant symptom. Patients may spend many hours every day washing, getting dressed, and eating breakfast, and life goes on at an extremely slow speed. Some OCD patients, called "hoarders, " are unable to throw anything out for fear they might someday need something they discarded.

In DSM-IV-TR, OCD is classified among the anxiety disorders because 1) anxiety is often associated with obsessions and resistance to compulsions, 2) anxiety or tension is often immediately relieved by yielding to compulsions, and 3) OCD often occurs in association with other anxiety disorders. However, compulsions decrease anxiety only transiently, and the nature of the fears in OCD is distinct from those of other anxiety disorders.

Certain diagnostic disputes regarding OCD were investigated in the DSM-IV field trial and led to some changes in criteria and clarifications in DSM-IV. Even though obsessions are typically experienced as ego-dystonic, there is a wide range of insight in patients with OCD. Although most patients have some degree of insight, about 5% are convinced that their obsessions and compulsions are reasonable. Based on this, the DSM-IV specified a poor insight type if, for most of the time during the current episode, the person does not recognize that the obsessions and compulsions are excessive or unreasonable. DSM-IV also made explicit that compulsions can be either behavioral or mental. Mental rituals are encountered in the great majority of OCD patients and, like behavioral compulsions, are intended to reduce anxiety or prevent harm. Although over 90% of patients have features of both obsessions and compulsions, 28% are bothered mainly by obsessions, 20% by compulsions, and 50% by both (Foa et al. 1995).

More recently, it has been disputed whether OCD belongs with the rest of the anxiety disorders, which are subsumed by the stress and fear circuitry, or in a separate grouping of compulsive spectrum disorders; various sources of evidence support this view, which will be grappled with in DSM-V (Bartz and Hollander 2006).
Clinical Description

Onset

OCD usually begins in adolescence or early adulthood but can begin prior to that time; 31% of first episodes occur between ages 10 and 15 years, with 75% developing OCD by age 30. In most cases, no particular stress or event precipitates the onset of OCD symptoms, and after an insidious onset there is a chronic and often progressive course. However, some patients describe a sudden onset of symptoms. This is particularly true of patients with a neurological basis for their illness. There is evidence of OCD associated with the 1920s encephalitis epidemic, abnormal birth events, and onset following head injury or seizures. Of interest are reports of new onset of OCD during pregnancy (Neziroglu et al. 1992).
Symptoms

Obsessions

Obsessive and compulsive symptoms have been recognized for centuries and were first described in the psychiatric literature by Esquirol in 1838 (Rachman and Hodgson 1980). Obsessional thoughts were defined by Karl Westphal in 1878 as ideas that in an otherwise intact intelligence, without being caused by an emotional or affect-like state, and against the will of the person come into the foreground of the consciousness (Westphal 1878).

An obsession is an intrusive, unwanted mental event usually evoking anxiety or discomfort. Obsessions may be thoughts, ideas, images, ruminations, convictions, fears, or impulses and are often of an aggressive, sexual, religious, disgusting, or nonsensical content. Obsessional ideas are repetitive thoughts that interrupt the normal train of thinking, whereas obsessional images are often vivid visual experiences. Much obsessive thinking involves horrific ideas. The person may think of doing the worst possible thing (e.g., blasphemy, rape, murder, child molestation). Obsessional convictions are often characterized by an element of magical thinking, such as "step on the crack, break your mothers back." Obsessional ruminations may involve prolonged, excessive, and inconclusive thinking about metaphysical questions. Obsessional fears often involve dirt or contamination and differ from phobias because they are present in the absence of the phobic stimulus. Other common obsessional fears involve harm coming to oneself or to others as a consequence of the patients misdoings, such as ones home catching on fire because the stove was not checked or running over a pedestrian because of careless driving. Obsessional impulses may be aggressive or sexual, such as intrusive impulses of stabbing ones spouse or raping ones child.

Attributing these obsessions to an internal source, the patient resists or controls them to a variable degree, and significant impairment in functioning can result. Resistance is the struggle against an impulse or intrusive thought, and control is the patients actual success in diverting his or her thinking. Obsessions are usually accompanied by compulsions but may also occur as the main or only symptom. Approximately 10%-25% of OCD patients are purely obsessional or predominantly experience obsessions (Akhtar et al. 1975; Rachman and Hodgson 1980).

Another hallmark of obsessive thinking involves lack of certainty or persistent doubting. In contrast to manic or psychotic patients, who manifest premature certainty, OCD patients are unable to achieve a sense of certainty between incoming sensory information and internal beliefs. Are my hands clean? Is the door locked? Is the fertilizer poisoning the water supply? Compulsive rituals such as excessive washing or checking appear to arise from this lack of certainty and consist of a misguided attempt to increase certainty.
Compulsions

A compulsive ritual is a behavior that usually reduces discomfort but is carried out in a pressured or rigid fashion. Such behavior may include rituals involving washing, checking, repeating, avoiding, striving for completeness, and being meticulous. Washers represent about 25%-50% of most OCD samples (Akhtar et al. 1975; Rachman and Hodgson 1980). These individuals are concerned with dirt, contaminants, or germs and may spend many hours a day washing their hands or showering. They may also attempt to avoid contaminating themselves with feces, urine, or vaginal secretions.

"Checkers" have pathological doubt and thus compulsively check to see if they have, for example, run over someone with their car or left the door unlocked. Checking often fails to resolve the doubt and, in some cases, may actually exacerbate it. In the DSM-IV field trial, washing and checking were the two most common groups of compulsions.

Although slowness results from most rituals, it is the major feature of the rare and disabling syndrome of primary obsessional slowness. It may take several hours for the obsessionally slow individual to get dressed or get out of the house. This slowness may be a response to a lack of certainty as well. These patients may have little anxiety despite their obsessions and rituals.

Mental compulsions are also quite common and should be inquired about directly, because they could go undetected if the clinician only asks about behavioral rituals. Such patients, for example, may replay over and over in their minds past conversations with others to make sure they did not somehow incriminate themselves. In the DSM-IV OCD field trials, 80% of patients had both behavioral and mental compulsions, and mental compulsions were the third most common type after checking and washing.

Although distinct symptom clusters exist (washers, checkers, those who are purely obsessional, hoarders, and those with primary slowness), these symptoms may overlap or develop sequentially. One study examined the distribution and grouping of obsessive-compulsive symptoms in about 300 OCD patients and found that a total of four symptom dimensions accounted for more than 60% of variance: obsessions and checking, symmetry and ordering, cleanliness and washing, and hoarding (Leckman et al. 1997). Similarly, a more recent meta-analysis of several factor-analytic studies involving more than 2, 000 patients identified the same four consistent "syndromes": symmetry/ordering, hoarding, contamination/cleaning, and obsessions/checking (Mataix-Cols et al. 2005). These four syndromes can coexist in any one patient and be continuous with more normative obsessive-compulsive phenomena. Therefore, these subtypes may prove useful in the future when examining possible genetic, neurobiological, or treatment-response heterogeneity in OCD.
Character Traits

Psychoanalytic theorists have suggested that there is a continuum between compulsive personality and OCD. Janet (1908) stated that all obsessional patients have a premorbid personality that is causally related to the disorder. Freud (1913/1958) noted an association between obsessional neurosis (i.e., OCD) symptoms and personality traits such as obstinacy, parsimony, punctuality, and orderliness.

However, phenomenological and epidemiological evidence suggests that OCD is frequently distinct from obsessive-compulsive personality disorder. OCD symptoms are ego-dystonic, whereas obsessive-compulsive personality traits are ego-syntonic and do not involve a sense of compulsion that must be resisted against. Epidemiological studies show that obsessive-compulsive character pathology is neither necessary nor sufficient for the development of OCD symptoms. When patients with obsessional traits decompensate, they often develop depression, paranoia, or somatization rather than OCD. Although the older literature suggested the presence of definite obsessional traits in as many as two-thirds of OCD patients, structured personality assessments were not used. In more recent standardized evaluations, only a minority of OCD patients had DSM-III-R obsessive-compulsive personality disorder, whereas other personality disorders such as avoidant or dependent were more common (Thomsen and Mikkelsen 1993). In addition, personality disorders may be more common in the presence of a longer duration of OCD, suggesting they could be secondary to the Axis I disorder, and criteria for personality disorders may no longer be met after successful treatment of the OCD (Baer and Jenike 1992). Another recent study supports that there may exist a familial spectrum of OCD and obsessive-compulsive personality disorder (Samuels et al. 2006).
Epidemiology

The ECA study (described earlier in this chapter) suggested that OCD is quite common, with a 1-month prevalence of 1.3%, a 6-month prevalence of 1.5%, and a lifetime rate of 2.5% (Regier et al. 1988). In clinical samples of adult OCD, there is a roughly equal ratio of men to women (A. Black 1974). However, in childhood-onset OCD, about 70% of patients are male (Swedo et al. 1989b). This difference seems to be accounted for by the earlier age at onset in males, and it may suggest partly differing etiologies or vulnerabilities in the two sexes.

Twin and family studies have found a greater degree of concordance for OCD (defined broadly to include obsessional features) among monozygotic twins compared with dizygotic twins (G. Carey and Gottesman 1981), suggesting that some predisposition to obsessional behavior is inherited. There have been no studies of OCD in adopted children or monozygotic twins raised apart. Studies of first-degree relatives of OCD patients show a higher-than-expected incidence of a variety of psychiatric disorders, including obsessive-compulsive symptoms, anxiety disorders, and depression (D. W. Black et al. 1992; G. Carey and Gottesman 1981). Family studies suggest a genetic link between OCD and Tourettes syndrome (Nee et al. 1982). A recent large family study found that OCD was about fourfold more common in relatives of OCD probands than in control relatives, and the finding was more robust for obsessions. Interestingly, age at onset of OCD in probands was very strongly related to familiality; no OCD was detected in relatives of probands with onset after age 18 (Nestadt et al. 2000b). This study suggests, as does a similar one in panic disorder, that there may exist a more strongly familial subtype of OCD with an earlier onset. Family studies have also shown that OCD spectrum disorders, such as body dysmorphic disorder, hypochondriasis, eating disorder, and grooming conditions, occur more frequently than expected in the relatives of those with OCD (Bienvenu et al. 2000).

There are reports demonstrating comorbidity of OCD with schizophrenia, depression, other anxiety disorders such as panic disorder and simple and social phobia, eating disorders, autism, and Tourettes syndrome. Epidemiologically, the OCD comorbidity risk for other major psychiatric disorders was found to be fairly high but nondistinctive (Karno et al. 1988). In a clinical sample of schizophrenic and schizoaffective patients, about 8% met criteria for OCD, highlighting the importance of screening for obsessive-compulsive symptoms in such populations where detection may be more difficult (Eisen et al. 1997).
Etiology

Psychodynamic Theory

Psychodynamic theory views OCD as residing on a continuum with obsessive-compulsive character pathology and suggests that OCD develops when defense mechanisms fail to contain the obsessional characters anxiety. In this model, obsessive-compulsive pathology involves fixation and subsequent regression from the oedipal to the earlier anal developmental phase. The fixation is presumably due to excessive investment in anal eroticism resulting from excessive frustrations or gratifications in the anal phase.

Obsessive-compulsive patients are thought to utilize the defense mechanisms of isolation, undoing, reaction formation, and regression, and ambivalence to control unacceptable sexual and aggressive impulses. These defense mechanisms are unconscious and thus not readily apparent to the patient.
Isolation

Isolation is an attempt to separate the feelings or affects from the thoughts, fantasies, or impulses associated with them. An example is a patient who describes a particularly gruesome thought or fantasy but denies any feelings of anxiety or disgust associated with it.
Undoing

Undoing is an attempt to magically reverse a psychological event, such as a word, thought, or gesture. A real or imagined act can be undone by evoking its opposite, such as turning on and then turning off a light switch. A patient who feels he has spent too much money on an item for his own pleasure may attempt to undo this by returning the object or punishing himself through some other deprivation.
Reaction formation

The defense of reaction formation substitutes an unacceptable unconscious impulse with its opposite. Thus, a patient who has sadistic impulses to hurt people might behave in a passive or masochistic manner or excessively pronounce his love at moments of heightened anger.
Regression

In OCD, regression is theorized to take place from the genital oedipal phase to the earlier pregenital anal-sadistic phase, which has not been fully relinquished. This regression helps the patient avoid genital conflicts and the anxiety associated with them. Themes characteristic of the anal phase typically reflect conflicts surrounding ambivalence, control, dirt, order, and parsimony.
Ambivalence

In normal development, aggressive impulses are neutralized, and loving feelings predominate toward significant objects. In OCD, strong aggressive impulses are thought to reemerge toward love objects, resulting in displaced ambivalence and paralyzing doubts. In addition, the characteristic thought omnipotence results in magical ideation and lack of certainty, such that thoughts of harming someone become confused with action and may lead to a sense of uncertainty over actually having harmed someone.
Cognitive and Behavioral Theories

A prominent behavioral model of the acquisition and maintenance of obsessive-compulsive symptoms derives from the two-stage learning theory of Mowrer (1939). In Stage 1, anxiety is classically conditioned to a specific environmental event (i.e., classical conditioning). The person then engages in compulsive rituals (escape/avoidance responses) in order to decrease anxiety. If the individual is successful in reducing anxiety, the compulsive behavior is more likely to occur in the future (Stage 2: operant conditioning). Higher-order conditioning occurs when other neutral stimuli such as words, images, or thoughts are associated with the initial stimulus and the associated anxiety is diffused. Ritualized behavior preserves the fear response, because the person avoids the eliciting stimulus and thus avoids extinction. Likewise, anxiety reduction after the ritual preserves the compulsive behavior.

Certain types of cognitions and cognitive processes are highly characteristic of OCD and presumably contribute, if not to the genesis, then at least to the maintenance of the disorder. In particular, negative beliefs about responsibility, especially responsibility surrounding intrusive cognitions, may be a key factor influencing obsessive behavior (Salkovskis et al. 2000). Three main types of dysfunctional beliefs have been identified in OCD: responsibility and overestimation of threat, perfectionism and intolerance of uncertainty, and importance and control of thoughts (S. Taylor et al. 2005). Subjects with OCD also appear to have memory biases toward disturbing themes, for example, better memory for contaminated objects than control subjects with comparable memory (Radomsky and Rachman 1999). Individuals with OCD who "check" have been found not to have memory impairments that presumably could account for the increased checking, but rather, they have decreased confidence in their memory (MacDonald et al. 1997). People with OCD have been found to have deficits in selective attention, and it has been proposed that such deficits may relate to their diminished ability to selectively ignore intrusive cognitive stimuli (Clayton et al. 1999).
Biological Theories

Although OCD used to be viewed as having a psychological etiology, a wealth of biological findings that have emerged over the past few decades have rendered OCD one of the most elegantly elaborated psychiatric disorders from a biological standpoint (Table 12-24).

The association of OCD with a variety of neurological conditions or more subtle neurological findings has been known for some time. Such findings include the onset of OCD following head trauma or von Economos disease; a high incidence of neurological premorbid illnesses in OCD; an association of OCD with birth trauma; abnormalities on the electroencephalogram, auditory evoked potentials, and ventricular brain ratio on computed tomography scan; an association with diabetes insipidus; and the presence of significantly more neurological soft signs in OCD patients compared with healthy control subjects. Basal ganglia abnormalities were particularly suspected in the pathogenesis of OCD, given that OCD is closely associated with Tourettes syndrome (Pauls et al. 1986), in which basal ganglia dysfunction results in abnormal involuntary movements, as well as with Sydenhams chorea, another disorder of the basal ganglia (Swedo et al. 1989a). Neuropsychological findings in OCD are also of some interest, although not always consistent, and have suggested abnormalities in memory, memory confidence, trial-and-error learning, and processing speed.

A certain form of OCD with childhood onset is believed to be related to an autoimmune process secondary to streptococcal infection. In such children, enlarged basal ganglia have been found on magnetic resonance imaging scans, which is consistent with an autoimmune hypothesis (Giedd et al. 2000). A particular B lymphocyte antigen, which can be identified by the monoclonal antibody D8/17, is expressed in nearly all patients with rheumatic fever and is thought to be a trait marker for susceptibility to group A streptococcal infection complications. Children with OCD and without a history of rheumatic fever or Sydenhams chorea have now been found to have significantly greater B cell D8/17 expression than control children, suggesting that D8/17 may serve as a marker for susceptibility to childhood-onset OCD (Murphy et al. 1997). More recently, such children have also been found to have elevated anti-basal ganglia antibodies compared with pediatric autoimmune, neurological, or streptococcal control subjects (Dale et al. 2005). Children with multiple streptococcal infections within the past year are threefold more likely to be newly diagnosed with OCD or tic disorder (Mell et al. 2005).
Neuroanatomy and Functional Neurocircuitry

A neuroethological model of OCD has been proposed by Rapoport, Swedo, and their group (Swedo 1989; Wise and Rapoport 1989), based on the hypothesized orbitofrontal-limbic-basal ganglia dysfunction. The basal ganglia act as a gating station that filters input from the orbitofrontal and the cingulate cortex and mediates the execution of motor patterns. Obsessions and compulsions are conceptualized as species-specific fixed action patterns that are normally adaptive but in OCD become inappropriately released, repetitive, and excessive. This could be due to a heightened internal drive state or an increased responsivity to external releasers. For example, OCD behaviors such as excessive washing or saving may be dysregulated manifestations of normal grooming or hoarding behaviors. Studies documenting significant volumetric abnormalities in treatment-naive children with OCD suggest that a developmentally mediated dysplasia of the ventral prefrontal-striatal circuitry may underlie OCD (Rosenberg and Keshavan 1998).

Along the lines of this model, a plethora of neuroimaging studies have yielded a sophisticated neuroanatomical underpinning for OCD, specifically implicating orbitofrontal-limbic-basal ganglia circuits. Volumetric imaging studies have consistently revealed abnormal volumes in the implicated circuit, including reduced orbitofrontal and amygdala volumes (Szeszko et al. 1999); smaller basal ganglia (Rosenberg et al. 1997); enlarged thalamus (Gilbert et al. 2000); increased volume of the orbitofrontal cortex and thalamus (J. J. Kim et al. 2001); smaller globus pallidus and increased anterior cingulate cortex (Szeszko et al. 2004); reduced orbitofrontal cortex gray matter, increased putamen, and reduced amygdala (Pujol et al. 2004); and increased orbitofrontal and decreased anterior cingulate gray matter (Valente et al. 2005). Baxter et al. 1987) compared OCD patients and normal control subjects using PET and found higher metabolic rates in the orbitofrontal gyri and caudate nuclei in OCD. Similarly, Swedo et al. (1989c) showed higher metabolic activity in the orbitofrontal and cingulate regions in OCD. Flor-Henry (1983) hypothesized that the fundamental symptomatology of obsessions was due to a defect in neural inhibition of dominant frontal systems, leading to the inability to inhibit unwanted verbal-ideational mental representations and their corresponding motor sequences. It has been suggested that the severity of obsessive urges correlates with orbitofrontal and basal ganglia activity, whereas the accompanying anxiety is reflected by activity in the hippocampus and cingulate cortex (McGuire et al. 1994). With fMRI, it has been possible to demonstrate that during the behavioral provocation of symptoms in OCD patients, significant increases in relative blood flow occur in "real" time in the caudate, cingulate cortex, and orbitofrontal cortex relative to the resting state (Adler et al. 2000; Breiter et al. 1996; Rauch et al. 1994). Using emotional Stroop tasks, OCD patients displayed specific neural responses to OCD-related words, with increased activation of frontostriatal and temporal regions (van den Heuvel et al. 2005b). White matter abnormalities in the anterior cingulate have also been implicated in OCD, suggesting defects in connectivity of the cingulate with other regions involved in the OCD circuitry (Szeszko et al. 2005). Deficient sensorimotor gating, as measured via the prepulse inhibition paradigm, supports the model of deficient frontostriatal circuits in OCD (Hoenig et al. 2005). Deficits in executive function planning, associated with frontostriatal dysfunction, have also been found in OCD, irrespective of state symptomatology (van den Heuvel et al. 2005a). OCD patients show greater activation of the anterior cingulate in tasks involving error processing (Fitzgerald et al. 2005). There is also some evidence that different OCD symptom dimensions (washing, checking, and hoarding) are mediated by relatively distinct components of the frontostriatothalamic circuits (Mataix-Cols et al. 2004).

Of great interest are a number of studies that have now been conducted that demonstrate not only functional but also structural brain changes after a variety of treatments for OCD. After treatment of OCD with serotonin reuptake inhibitors or behavior therapy, hyperactivity decreases in the caudate, orbitofrontal lobes, and cingulate cortex in those patients who have good treatment responses (Baxter et al. 1992; Perani et al. 1995; Swedo et al. 1992b). Also, after successful behavioral treatment the correlations in brain activity between the orbital gyri and the caudate nucleus decrease significantly, suggesting a decoupling of malfunctioning brain circuits (J. M. Schwartz et al. 1996). In children with OCD, a decrease in initially abnormally large thalamic size has been imaged after successful response to paroxetine treatment (Gilbert et al. 2000). Magnetic resonance spectroscopy has also revealed a decrease in initially elevated caudate glutamate concentration in children with OCD after successful paroxetine treatment (Rosenberg et al. 2000). In another study, after improvement of OCD with SSRI or behavioral therapy, there was decreased activation of the prefrontal and cingulate cortex under symptom provocation (Nakao et al. 2005). A PET study showed that better SSRI treatment response was associated with lower activity in the orbitofrontal cortex and greater activity in the posterior cingulate cortex (Rauch et al. 2002). Interestingly, successful SSRI treatment of OCD or major depression resulted in cerebral activity changes that were disorder specific rather than treatment specific; only OCD treatment was associated with significant metabolic decreases in the caudate, orbitofrontal cortex, and thalamus (Saxena et al. 2002).
Neurochemistry

Parallel to the functional neuroanatomy, the neurochemistry of OCD has become extensively elaborated. Serotonin has been implicated in mediating impulsivity, suicidality, aggression, anxiety, social dominance, and learning. Dysregulation of this behaviorally inhibitory neurotransmitter possibly contributes to the repetitive obsessions and ritualistic behaviors seen in OCD patients. Despite some conflicting and nonreplicated data, extensive research has now clearly implicated the serotonergic system in the pathogenesis of OCD. Considerable indirect evidence supporting the role of serotonin in OCD stems from the well-documented antiobsessional effects of potent serotonin reuptake inhibitors, such as clomipramine, and of the SSRIs in contrast to the ineffectiveness of noradrenergic antidepressants such as desipramine. Furthermore, reduction of OCD symptoms during clomipramine treatment was shown to correlate with a decrease in platelet serotonin level (Flament et al. 1987) and in CSF 5-hydroxyindoleacetic acid (Swedo et al. 1992a).

The use of pharmacological challenge agents to stimulate or block serotonin receptors has also proved a fruitful technique in elucidating the neurochemistry of OCD. Oral m-CPP, a partial serotonin agonist, has been found to transiently exacerbate obsessive-compulsive symptoms in a subgroup of OCD patients (Hollander et al. 1992). After treatment of OCD with serotonin reuptake blockers such as clomipramine or fluoxetine, m-CPP challenge no longer induced symptom exacerbation (Hollander et al. 1991a; Zohar et al. 1988). A blunted prolactin response to m-CPP challenge has also been found in OCD patients by some investigators (Charney et al. 1988; Hollander et al. 1992) but not others (Zohar et al. 1988). Other serotonin agonists, such as tryptophan, fenfluramine, and ipsapirone, or antagonists, such as metergoline, have not been shown to induce consistent behavioral or neuroendocrine response abnormalities in patients with OCD.

More recently, an acute tryptophan-depletion study in SSRI-treated and remitted OCD patients failed to provoke OCD symptom exacerbation, in contrast to its mood-worsening effect, suggesting that obsessive-compulsive symptoms are not dependent on short-term presynaptic serotonin availability (Berney et al. 2006). Increased 5-HT2A receptor binding has been reported in the caudate nuclei of OCD patients, suggestive of diminished serotonin transmission in the corticostriatal loop (Adams et al. 2005). In summary, all studies taken together suggest that serotonergic dysregulation in OCD is complex and probably involves variations in receptor function according to brain region and receptor subtypes.

It also does not appear that serotonergic dysregulation alone can fully explain the neurochemistry of OCD. It is possible that the serotonergic system may, in part, be modulating or compensating for other dysfunctional neurotransmitter systems or neuromodulators. Various neuropeptide abnormalities have started to be elucidated in the past few years. Abnormalities in CSF vasopressin (Swedo et al. 1992a), CSF somatostatin (Altemus et al. 1993), and CSF oxytocin (Leckman et al. 1994) have been implicated in OCD. With clomipramine treatment, CSF levels of vasopressin and somatostatin tend to decrease while oxytocin increases (Altemus et al. 1994). All these neuropeptides may be implicated in arousal, memory, and the acquisition and maintenance of conditioned perseverative behaviors. The noradrenergic 2 agonist clonidine has been reported to induce a transient improvement in OCD symptoms when administered to patients intravenously (Hollander et al. 1991b) or orally (Knesevich 1982), although other noradrenergic challenge findings have been negative (Lucey et al. 1992).

Dopaminergic dysregulation has been variously implicated in OCD (Goodman et al. 1990) through the association between OCD and Tourettes syndrome; reports of exacerbation of obsessive-compulsive symptoms with chronic stimulants; an association between higher pretreatment CSF homovanillic acid and good treatment outcome (Swedo et al. 1992a); blunted growth hormone response to the dopamine agonist apomorphine (Brambilla et al. 1997); use of dopamine blockers to augment partial treatment response with serotonin reuptake blockers (McDougle et al. 1990); and decreased dopamine D2 receptor binding in the caudate nucleus of OCD patients (Denys et al. 2004b). In a putative rat model of OCD, the dopamine D2/D3 receptor agonist quinpirole has been shown to induce compulsive checking in specific locations of an open field (Dvorkin et al. 2006).

Of late, there has been increased interest in possible glutamatergic dysregulation in OCD, and magnetic resonance spectroscopy studies have shown elevated glutamate levels in several regions involved in the hyperactive cortico-striato-limbic-thalamic circuitry (Pittenger et al. 2006). Similarly, CSF glutamate was found to be significantly elevated in medication-naive adult OCD subjects compared with control subjects (Chakrabarty et al. 2005).
Genetics

Segregation analyses have provided support for a single major gene involvement in OCD (Alsobrook et al. 1999; Nestadt et al. 2000a), and genomewide linkage studies have provided evidence for linkage on chromosome 9p (Hanna et al. 2002; Willour et al. 2004). Candidate genes that have been implicated to date include the GABA type B receptor 1 gene (Zai et al. 2005a), the 5-HT1D receptor gene (Mundo et al. 2000), the 5-HT2A receptor gene (Enoch et al. 2001; Meira-Lima et al. 2004), the catechol-O-methyltransferase (COMT) gene (Karayiorgou et al. 1997, 1999; Lochner et al. 2005), the dopamine D4 receptor gene (Millet et al. 2003), the glutamate kainate receptor GRIK2 gene (Delorme et al. 2004), and the glutamate NMDA receptor gene (Arnold et al. 2004). Findings regarding the serotonin transporter gene have been both positive (Bengel et al. 1999) and negative (Billet et al. 1997; Chabane et al. 2004; Frisch et al. 2000); more recently, homozygosity for the long allele L(A) of the serotonin transporter gene was found to exert a moderate effect on risk for OCD (odds ratio = 1.8; Hu et al. 2006). No associations were shown with mutations of the 5-HT2B receptor gene (S. J. Kim et al. 2000), the tryptophan hydroxylase gene (Han et al. 1999), the 5-HT2C receptor gene (Cavallini et al. 1998; Frisch et al. 2000), the dopamine transporter and dopamine D4 receptor genes (Frisch et al. 2000), or the brain-derived neurotrophic factor gene (Zai et al. 2005b). In summary, then, genes predisposing to OCD have not been consistently identified to date. The OCD Collaborative Genetics Study (OCGS) is a six-site linkage study with a National Institute of Mental Health-based cell repository awaiting findings (Samuels et al. 2006).
Course and Prognosis

Studies of the natural course of the illness suggest that 24%-33% of patients have a fluctuating course, 11%-14% have a phasic course with periods of complete remission, and 54%-61% have a constant or progressive course (A. Black 1974; Table 12-25). Although prognosis of OCD has traditionally been considered to be poor, with new developments in behavioral and pharmacological treatments this prognosis is now considerably improved. The disorder usually has a major impact on daily functioning, with some patients spending many waking hours consumed with their obsessions and rituals. Patients are often socially isolated, marry at an older age, and have high celibacy rates (particularly in males) and a low fertility rate. Compounding the situation, depression and anxiety are common complications of OCD.

A major follow-up study was reported that examined the course of patients over a 40-year period in Sweden, from approximately the 1950s to the 1990s (Skoog and Skoog 1999). Findings were more optimistic than expected, with improvement noted in 83% of individuals. Of those, about half were fully or almost fully recovered. Importantly, predictors of worse outcome were earlier onset, a more chronic course at baseline, poorer social functioning at baseline, having both obsessions and compulsions, and having magical symptoms.

In terms of acute treatment, the presence of hoarding obsessions and compulsions is associated with poorer response to both medication treatment (Mataix-Cols et al. 1999) and CBT (Rufer et al. 2006).

Va rog sa nu ma injurati pentru postul infinit de mai sus! Sunt in prima zi de concediu si am zis sa postez niste material cu adevarat util si dintr-o sursa sigura. Voi fi indisponibil pe perioada cocediului (sfarsitul saptamanii viitoare) si pana atunci va urez toate bune si sa fiti sanatoase/sanatosi!