By W. Boss. Colorado Christian University.

The full document is not presented because the second half made accusations against named people buy cheap propranolol 40mg on line. The writer believed the owners of a coffee lounge were persecuting him safe 40 mg propranolol. He was jailed and died in prison order 40mg propranolol mastercard, by suicide, days later. Prominent pathological features were the bizarre and persecutory delusional material, and that while disorder of the form of thought (loss of logical connections) made the delusion difficult to follow, it was systematized and remained relatively unchanged over time. This is a passage from a biography written by a man who subsequently drowned himself. The injections referred to are injections of long-lasting antipsychotic medication. These “depot” medications help prevent relapse in psychotic disorders and can be given once every few weeks. After this man had ceased his injections for six Pridmore S. Last modified: November, 2015 4 months and his body was completely free of antipsychotic medication, he began to misinterpret the environment in a persecutory manner. He believed his friends had been “backbiting” and that a church leader (whose name has been replaced with “Anonymous”) said that he should be in prison. It is reasonable to conclude that the clergyman used the name Peter by mistake and the patient failed to recognize the mistake, and concluded instead, that this misuse was purposeful. Another possibility is that the patient was hallucinating when he heard the name Peter and the comment that he (the patient) should be in prison. The two documents above, along with a CD of other documents, were mailed to many neurosurgeons and psychiatrists at leading hospitals around Australia. The writer provided full contact details and welcomed any response. He believed that an implant was placed in his head by the CIA in 1999 and it had caused him to attempt suicide. He attributed various events over the years (Deaths of Princess Diana, Dr David Kelly, and others) to the same process. These beliefs have the hallmarks of a detailed delusional system which may have been present for some years. The second letter is a response to this individual from the Australian Federal Police. He had written to them regarding his beliefs, and they responded stating they were unable to help with his complaint. Named delusions This section is added for completeness. Mention is made of some delusions which get quite a bit of attention in some books, because they are exotic and interesting. However, they are rare and are managed as are any other delusion. They do provide a fascinating window into psychosis. Capgras syndrome is the delusion that a person (usually a family member or someone close to the patient) has been replaced by an impostor of nearly identical appearance. This most commonly occurs in schizophrenia and organic brain disease. Last modified: November, 2015 6 de Fregoli syndrome is the delusion that a person (usually a suspected tormentor) can change into different people, and many of the people the patient meets are misidentified as transformed version of the suspected person. The issue may be whether the person who is misidentified is known or unknown to the patient. Folie a deux (shared psychotic disorder) is diagnosed when two people share the same delusion (Shimizu et al, 2007). Usually one of these people is psychotic and the second is not psychotic; but the non-psychotic person has come to accept what the psychotic person believes. It is common for the psychotic person to have been intelligent and authoritative, and for the non-psychotic individual to be somewhat dependant. The psychotic person should be managed in the normal manner. When removed from the influence of the psychotic person, the non-psychotic individual rapidly gains “insight”. Cotard syndrome is the nihilistic (denying the existence) syndrome. It is rare in some forms, such as, when a psychotic person believes their head has been removed. The most common form may be when people with psychotic depression believe they are dead (a way of non- existence). The syndrome may lead to phone calls, unwanted letters and other attention. On more than one occasion the patient presented at his offices without an appointment, and disrobed in the waiting-room. Possible difference between the delusions of delusional disorder and the delusions of other disorders The following generalizations has some clinical relevance: Delusional disorder Other disorders not bizarre Bizarre Systematized Not systematized Charlton and McClelland (1999) observed that in delusional disorder there is fundamental mistake about the motives of others, but that thereafter, the thinking processes are logical, while in other disorders with delusions, there is evidence of many breaks in logic. Further, the delusions of Delusional disorder can be understood in an evolutionary context. The delusions of delusional disorder fit into 5 main categories: 1) belief of threat Pridmore S. Last modified: November, 2015 7 from gangs or organizations, 2) belief (particularly by the male) of infidelity of the spouse, 3) belief (particularly by females) that a high status individual is in love with the patient, 4) belief of a life threatening disease, and 5) belief of an unattractive bodily/facial deformity (in DSM5, this last example has been removed from Delusional disorders and placed under Obsessive-Compulsive and Related Disorders). Successful evolution requires the transmission of genes, and this is better achieved if the individual lives a long life and is attractive to members of the opposite sex. Accordingly, the 4 categories of delusional disorder may be linked to the facts that in the ancestral environment, 1) homicide by gangs (other tribes) was a major cause of mortality, 2) infidelity by the female spouse meant the supportive male was contributing to the welfare of the genes of another male, and 3) presence of disease, or 4) deformity may reduce attractiveness to members of the other gender, and thus reduce the chances of passing on genes. This may reflect the presence of disorder of the form of thought, that is, where there is loss of logical connection between ideas. The delusions of both delusional disorder and other disorders often have some grandiose content. It is has been observed that for a delusion of persecution (bizarre or otherwise) to be present, the individual must be “important” enough to warrant the attention of others. Unknown prevalence of delusional disorder The prevalence of Delusional disorder is uncertain. People with this disorder can often function reasonably well in the community. Lacking insight, they usually do not believe they have a mental disorder and do not go to the doctor for help. Feeling persecuted, they often avoid contact with others and try to attract as little attention as possible. In large blocks of flats there are often people who have many locks on their doors, who believe that the neighbours come into their residences and move things around or steal things during the night. Some people with delusional disorder are well known to the police as they make frequent calls about being persecuted.

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A prospective propranolol 80mg for sale, randomized Pulmonary vein isolation using segmental study purchase propranolol 80 mg without prescription. J Interv Card Efficacy of an additional MAZE procedure Electrophysiol order propranolol 40mg online. PMID: using cooled-tip radiofrequency ablation in 18418704. Catheter ablation of atrial fibrillation in 2002;23(7):558-66. J Cardiovasc paroxysmal patients: randomized Electrophysiol. Circ Arrhythm fractionated atrial electrograms versus Electrophysiol. PMID: potential-guided pulmonary vein antrum 22139886. A short-term, randomized, double-blind, Catheter ablation treatment in patients with parallel-group study to evaluate the efficacy drug-refractory atrial fibrillation: a and safety of dronedarone versus prospective, multi-centre, randomized, amiodarone in patients with persistent atrial controlled study (Catheter Ablation For The fibrillation: the DIONYSOS study. Left atrial posterior wall isolation does not Circumferential pulmonary-vein ablation for improve the outcome of circumferential chronic atrial fibrillation. J Am radiofrequency catheter ablation in patients Coll Cardiol. Van Breugel HN, Nieman FH, Accord RE, during atrial fibrillation ablation in patients et al. A prospective randomized multicenter without atrial flutter: a randomised comparison on health-related quality of life: controlled trial. J Comparison of antiarrhythmic drug therapy Cardiovasc Electrophysiol. Substrate and Trigger Ablation for Reduction of Atrial Fibrillation (STAR AF): 229. Mitral valve surgery plus concomitant Amiodarone to prevent recurrence of atrial atrial fibrillation ablation is superior to fibrillation. Canadian Trial of Atrial mitral valve surgery alone with an intensive Fibrillation Investigators. Prospective Efficacy of three different ablative randomized comparison of left atrial and procedures to treat atrial fibrillation in biatrial radiofrequency ablation in the patients with valvular heart disease: a treatment of atrial fibrillation. Substrate modification combined with Impact of systematic isolation of superior pulmonary vein isolation improves outcome vena cava in addition to pulmonary vein of catheter ablation in patients with antrum isolation on the outcome of persistent atrial fibrillation: a prospective paroxysmal, persistent, and permanent atrial randomized comparison. Effectiveness of the maze procedure using cooled-tip radiofrequency ablation in 248. Maintenance of sinus rhythm in patients with atrial fibrillation: an 249. De Simone A, De Pasquale M, De Matteis AFFIRM substudy of the first C, et al. Combined radiofrequency modified maze and mitral valve procedure through a port 250. Isolation: long-term results of a prospective PMID: 12895612. Randomized study of surgical isolation of the pulmonary veins for correction of 251. J Thorac Cardiovasc ablation strategies in patients with Surg. Results from a prospective randomized Pulmonary venous isolation versus study. Long-term efficacy and safety of propafenone and sotalol for the maintenance 253. Jessurun ER, van Hemel NM, Defauw JJ, et Randomized comparison between al. A randomized study of combining maze pulmonary vein antral isolation versus surgery for atrial fibrillation with mitral complex fractionated electrogram ablation valve surgery. Ablation of superior pulmonary of catheter ablation and surgical CryoMaze veins compared to ablation of all four procedure in patients with long-lasting pulmonary veins. J Cardiovasc persistent atrial fibrillation and rheumatic Electrophysiol. Comparison of effectiveness of circumferential pulmonary vein isolation carvedilol versus bisoprolol for maintenance preferable to stepwise segmental pulmonary of sinus rhythm after cardioversion of vein isolation for patients with paroxysmal persistent atrial fibrillation. J isolation for atrial fibrillation: a randomized Cardiovasc Electrophysiol. Kochiadakis GE, Igoumenidis NE, Hamilos Noninducibility of atrial fibrillation as an MI, et al. Long-term maintenance of normal end point of left atrial circumferential sinus rhythm in patients with current ablation for paroxysmal atrial fibrillation: a symptomatic atrial fibrillation: amiodarone randomized study. Kochiadakis GE, Igoumenidis NE, Comparison of surgical cut and sew versus Marketou ME, et al. Low dose amiodarone radiofrequency pulmonary veins isolation and sotalol in the treatment of recurrent, for chronic permanent atrial fibrillation: a symptomatic atrial fibrillation: a randomized study. Amiodarone, sotalol, Maintenance of sinus rhythm after electrical or propafenone in atrial fibrillation: which is cardioversion of persistent atrial fibrillation; preferred to maintain normal sinus rhythm? Surgical treatment of permanent atrial Bhuripanyo K, et al. A randomized clinical fibrillation using microwave energy trial of the efficacy of radiofrequency ablation: a prospective randomized clinical catheter ablation and amiodarone in the trial. Does Pulmonary vein isolation and linear lesions additional linear ablation after in atrial fibrillation ablation. J Interv Card circumferential pulmonary vein isolation Electrophysiol. PMID: improve clinical outcome in patients with 17318445. Randomized study comparing combined pulmonary vein-left atrial junction 279. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment 280. Epicardial microwave ablation of permanent atrial fibrillation during a coronary bypass 281. Pulmonary randomized assessment of the incremental vein isolation combined with superior vena role of ablation of complex fractionated cava isolation for atrial fibrillation ablation: atrial electrograms after antral pulmonary a prospective randomized study. Am ablation after left atrial ablation of complex Heart J. PMID: fractionated atrial electrograms for long- 17383295. Thyroid function abnormalities during PMID: 19808388.

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The first example of this approach was the DNA binding and activation specificity of the tetR order propranolol 40 mg line. The inactivation of the glutamate receptor subunit NMDAR1 desired regulatable gene of interest is placed under tetO plus in CA1 pyramidal neurons of the hippocampus discount 40 mg propranolol amex, with a minimal promoter (Pmin) cheap propranolol 80 mg with amex, that contains the basic promoter expression in other brain areas mostly intact (31). Activa- NMDAR1 is the predominant N-methyl-D-aspartate tion of this system requires the binding of the tTA to the (NMDA) receptor subunit and is widely expressed in most tetO operator sequence (39). The presence of tetracycline, 248 Neuropsychopharmacology: The Fifth Generation of Progress A B C FIGURE 19. Strategy for cell-type–selective mutations using Cre-mediated recombination. A: The loxP DNA sequence indicating the core region and the inverted repeats that constitute Cre binding sites. B: In the presence of Cre, a gene flanked by tandomly oriented loxP sites (floxed gene) will be excised by homologous recombination. The recombination occurs in the core region of the loxP site, leaving a single recombinant loxP site in the genome after Cre excision. C: Use of the Cre-lox system to generate cell-type–specific gene inactivation in mice. The wild-type expression pattern of this gene is shown (black) in the coronal section beneath the floxed mouse. In this example, there is expression of the gene in the cortex (ctx), striatum (str), and hypothalamus (hypothal). This floxed mouse can be crossed to a transgenic mouse expressing Cre in a distribution dictated by the promoter used in the transgene construct. In this example, Cre expression is shown (gray) and is limited to the striatum. A breeding program is pursued to produce animals in which expression of the floxed gene is normal except in the striatum, where the expression of Cre results in the excision of the floxed gene. The tetracycline-controlled transactivator, tTA, is a fusion pro- tein consisting of the tetracycline repressor (tetR) domain and a tran- scriptional activation domain (VP16). Binding of doxycycline (Dox) to the A tTA dimer prevents the binding of tTA to tetO, and transcription of the gene is prevented. Therefore, the tTA system has been called the Tet- off system, because in the presence of doxycycline, transcription is pre- vented. In the Tet- on system, the tetracycline-con- trolled activator has been mutated to reverse the action of doxycycline on the transactivator. By contrast with tTA, doxycycline binding to rtTA enables the complex to bind to tetO and activate gene transcription. In the absence of doxycycline, rtTA is unable to bind to tetO and cannot activatetranscription. Therefore,the rtTA system is also called the Tet-on system, because doxycycline acti- vates transcription of the regulated B gene. This is referred to as the tet-off sys- A line of mice was generated in which expression of a FosB tem—that is, when tetracycline is present, transcription is transgene was suppressed by continuous doxycycline treat- off. A tet-on system has also been developed, in which tetra- ment throughout development. Discontinuation of treat- cycline induces transcription of the gene of interest. It uti- ment in adult animals led to overexpression of the transgene lizes a reverse tetracycline transcriptional activator (rtTA), in the nucleus accumbens and to augmentation of the re- designed so that it would bind to tetO and activate tran- warding and locomotor stimulant properties of cocaine scription only in the presence of tetracycline-related com- (42). The utility of the tet-on system has also been demon- pounds (38). Doxycycline is most frequently used because strated. For example, a line of mice was developed to exam- it is a potent regulator in both the tet-off and tet-on systems ine the role of the Ca2 -activated protein phosphatase cal- (38), and can be easily supplied to mice through their water cineurin in synaptic plasticity. First, a tissue-specific promoter can be used to express Rather than generating regulatable gain of function mu- tTA or rtTA in a region or cell-type specific manner; then tants with the Tet system, regulatable loss of function mu- the gene of interest is inserted behind tetO and a minimal tants can also be generated by combining the Tet system promoter. This can be achieved by creating two separate with the Cre-lox system (43,44). In this arrangement, a cell- transgenic lines of mice and then cross-breeding to produce type–specific promoter drives rtTA expression and Cre is bigenic lines. In these lines, expression of the gene of interest linked to tetO and a minimal promoter. In the presence of may be induced by doxycycline (tet-on) or by the discontin- doxycycline, Cre is expressed in the cell type specified by uation of doxycycline treatment (tet-off). For example, the the promoter used to drive rtTA expression, and somatic 250 Neuropsychopharmacology: The Fifth Generation of Progress cell recombination excises floxed DNA fragments in those REFERENCES cells—achieving an inducible cell-type–specific knockout. Genetic transforma- This inducible knockout approach may be utilized to cir- tion of mouse embryos by microinjection of purified DNA. Proc cumvent concerns discussed above in the interpretation of Natl Acad Sci USA 1980;77:7380–7384. Integration and stable germ line trans- In these inducible knockout mice it must be remembered mission of genes injected into mouse pronuclei. Science 1981; 214:1244–1246 that although the excision of the floxed gene can be induced 3. Impairment of spatial relatively quickly, the appearance of any phenotype result- but not contextual memory in CaMKII mutant mice with a ing from the absence of the gene product will occur gradu- selective loss of hippocampal LTP in the range of the theta fre- ally, depending on the degradation rate of the relevant quency. CaMKII regulates the frequency-response function of hippocampal synapses for the limitation of strategies utilizing the Tet system relates to production of both LTD and LTP. OCD-Like behaviors of unwanted gene expression may occur during periods in caused by a neuropotentiating transgene targeted to cortical and which gene expression is expected to be turned off. Recent findings with tetracycline controlled tran- 7. Directing gene expression to cere- scriptional silencers indicate that it may be possible to mod- bellar granule cells using gamma-aminobutyric acid type A recep- ify the tet system to substantially reduce unwanted gene tor alpha6 subunit transgenes. In addition, workhas begun on alternative 9417–9421. One such system utilizes the insect hormone tein-coding regions of the adjacent beta 4 and alpha 3 acetylcho- line receptor genes direct neuron-specific expression in the central ecdysone as an induction signal. Conversion of normal behavior to shiverer by myelin basic protein antisense cDNA in transgenic mice. Impaired type II glucocorticoid- receptor function in mice bearing antisense RNA transgene. The development of transgenic and gene targeting technolo- 11. Glutamatergic synap- gies is significantly enhancing understanding of cellular and tic responses and long-term potentiation are impaired in the CA1 molecular functions of genes and their contributions to neu- hippocampal area of calbindin D(28k)-deficient mice. Synapse ral processes relevant to clinical disorders. Mutant strains are also providing models for proto-oncogene int-2 in mouse embryo-derived stem cells: a gen- studying the pathophysiology and treatment of particular eral strategy for targeting mutations to non-selectable genes.

The strongest pharmacologic evidence concerns the studies examining candidate genes proposed as the result of serotonergic system and the well-established efficacy of po- several lines of investigation that implicate both the seroto- tent serotonin reuptake inhibitors in the treatment of OCD nergic and dopaminergic neurotransmitter systems are sum- (2 buy 40mg propranolol visa,3); however discount propranolol 80 mg visa, other systems have also been implicated order propranolol 80mg otc. The most widely accepted alternative neurochemical theory Historically, the serotonin (5-HT) hypothesis has its basis for OCD suggests that the dopamine (DA) neurotransmis- in the pharmacology of OCD. In the late 1960s it was sion system also may be important in the pathophysiology observed that clomipramine, the only tricyclic antidepres- of some cases of OCD (3–6). Specifically, the DA hypothe- sant with potent 5-HT reuptake blocking properties, had sis has been proposed for those cases of OCD that appear antiobsessional activity (8,9). Subsequently, several studies to be related to Gilles de la Tourette syndrome (GTS) or have shown that clomipramine and several other selective other tics disorders, and/or those that occur with schizotypal serotonin reuptake inhibitors (SSRIs) are effective antiob- personality disorder and/or poor insight. In fact, results were taken as evidence that etiologic hypothesis for OCD involving an autoimmune serotonin plays a fundamental role in the pathogenesis of mechanism, particularly relevant for early-onset cases. These observations have led to the examina- tion of the serotonin system and its function in OCD pa- tients. Peripheral markers for the 5-HT system and a num- ber of parameters of the 5-HT function have been David L. Pauls: Child Study Center, Yale University School of Medicine, investigated. These include CSF 5-hydroxyindoleacetic acid New Haven, Connecticut. Kennedy: Department of Psychiatry, (the major metabolite of serotonin) (19–22), whole blood University of Toronto, Toronto, Canada. The results of these studies, al- by the well-documented clinical response to haloperidol and though not definitive, suggest that a 5-HT dysfunction is other dopamine antagonists (58), by the exacerbation with present in OCD. More detailed information has come from L-dopa and central nervous system stimulants (such as am- pharmacologic challenge studies in which compounds were phetamines) (59,60), and reports of lower CSF levels of administered that, acting presynaptically or postsynapti- the dopamine metabolite homovanillic acid (HVA) (61). In these studies behav- Moreover, OCD patients with comorbid tic disorder or ioral and neuroendocrine responses in OCD patients were GTS are usually resistant to conventional pharmacotherapy assessed after challenges with meta-chloro-phenyl-pipera- with proserotonergic compounds, and may benefit from zine (mCPP) (20,31–36), intravenous clomipramine (37, adjuvant treatment with dopamine (DA) or DA/5-HT 38), the 5-HT precursor tryptophan (39,40), the 5-HT re- blockers (6,55,56,62,63). This body of evidence suggests leasing agent fenfluramine (41–45), ipsapirone (46), buspir- that there is an involvement of DA in at least some OCD one (47), and sumatriptan (48,49). Overall, about 64), whereas the administration of fenfluramine produced 50% of the OCD patients challenged acutely with prosero- increased inhibition of HVA secretion (33,65). The DA tonergic compounds experienced a transient worsening of involvement has been assessed by measures of growth hor- obsessive symptoms. These results suggest that for some mone response to apomorphine (66,67), and challenge with OCD patients there would be a basal hyperactivity of the d-amphetamine (68) and methylphenidate (69), with con- 5-HT neurotransmission system, owing either to a hyper- flicting results. This could explain both the worsening of OCD been implicated in the pathogenesis of obsessive-compulsive symptoms after acute 5-HT stimulation and the clinical phenomenology by several studies (1,70–72). The involvement of the Other Neurobiological Hypotheses presynaptic desensitization as a key step for the neurobiolog- ical mechanism of the antiobsessional response to prosero- Alternative neurobiological mechanisms have been pro- tonergic compounds is also suggested by both the long la- posed for OCD but they are in need of further confirma- tency of clinical efficacy (6 to 8 weeks, longer than the tion. As already reported, functional neuroimaging studies latency for the antidepressant response induced by the same have demonstrated dysfunction in the orbitofrontal cortex, compounds) and the high doses required (54). Neuroendocrine mechanisms were im- to clomipramine or SSRIs and approximately 40% of them plicated in the pathogenesis of obsessions and compulsions, have no clinical improvement (55,56) may reflect the bio- based on studies employing oxytocin, vasopressin, and so- logical heterogeneity of the OCD phenotype already sug- matostatin (64,80–82). These studies also need further rep- gested by the variability of the response to acute 5-HT chal- lication. Thus, consideration of more homogeneous subgroups of OCD patients defined by response to biologi- The Autoimmune Hypothesis cal challenges or different symptom subtypes could lead to clarification of the pathogenesis of the disease and the role Allen, Leonard, and Swedo first proposed the intriguing of alternative hypotheses to the serotonergic one. An association was drawn between infection with group A -hemolytic Streptococcus (as well The Dopamine Hypothesis as other agents, including viruses), and the onset or the There is now considerable evidence that some forms of exacerbation of OCD in some children. The observation of OCD are etiologic related to GTS (57). When a diagnosis of obsessive coccus-induced autoantibodies reacting with the basal gan- symptoms was used, these investigators found that 87% of glia) and OCD led to the characterization of the 'pediatric the MZ twins were pair wise concordant compared to 47% autoimmune neuropsychiatric disorders associated with of DZ twins, yielding a heritability estimate of approxi- streptococcal infections' (PANDAS) by Swedo and col- mately 80%. Similar links between In a more recent study, Torgersen (94) investigated the group A -hemolytic Streptococcus and GTS have been concordance of anxiety disorders (including obsessive-com- observed (86,87). A monoclonal antibody that identifies B- pulsive disorder) in the co-twins of 32 MZ and 53 DZ same- lymphocyte antigen (D8/17) has been shown to be a marker sex Norwegian twins. The sample consisted of all twins born for susceptibility to rheumatic fever, PANDAS, and early- between 1910 and 1955 who were admitted for treatment onset OCD in general (88,89). Moreover, D8/17 levels have of neurotic or borderline psychotic disorders at any time been found to follow a segregation pattern most consistent before 1977. After ascertainment each twin was interviewed with autosomal recessive inheritance in rheumatic fever using a structured psychiatric interview that recorded life- families (89,90). There is evidence that PANDAS is familial, time occurrence of psychiatric symptoms; this information with dramatically increased rates of clinical and subclinical was then combined with the hospital records to make DSM- OCD observed in parents of children with PANDAS (91). A group of six DSM-III anxiety disor- The importance of this hypothesis cannot yet be deter- ders was examined: panic disorder, agoraphobia with and mined, however, because it is not known how many child- without panic, social phobia, OCD, and generalized anxiety hood-onset cases of OCD are associated with this autoim- disorder (GAD). It is possible that inherited genetic factors for the same anxiety disorder. Thus, the author examined interact with the autoimmune mechanisms, making a sub- concordances in the larger context of an 'anxiety spectrum. Genetic variants in the human leukocyte phobia, social phobia, and OCD was, a statistically signifi- antigen (HLA) system may be interesting candidates to ex- cant difference in concordance rates was seen: 45% in MZ amine in this group of OCD subjects. This differ- ence was not seen when considering GAD alone, nor when a combined proband diagnostic category including GAD THE GENETICS OF OCD was used. Two important aspects of these studies critically limit There has been considerable controversy regarding the in- their usefulness. The first limitation is the lack of standard- heritance of OCD. This is surprising since the familial na- ized diagnostic criteria across studies. It is difficult to inter- ture of OCD has been documented since the 1930s and pret results when different diagnostic criteria are used in twin studies have provided evidence for the importance of the different studies being compared. The second limitation genetic factors in the manifestation of OCD. The investi- gators doing the evaluations of the co-twin, knew the diag- nosis of the index case. The lack of any procedural blind for Twin Studies obtaining diagnostic information or for making the actual In 1986, Rasmussen and Tsuang (92) reviewed the literature diagnoses of a co-twin is a serious source of bias that could on OCD twins and found 32 of 51 (63%) MZ twins were lead to spurious results. Furthermore, when those twins Two studies were completed that used twins ascertained where zygosity was in doubt were eliminated from the sam- through twin registries. Furthermore, the evaluations of the ple, 13 of 20 (65%) were concordant for OCD. Clifford (95) and Clifford and concordance rates are similar to those reported for affective associates (96) analyzed data collected from 419 pairs of and anxiety disorders. However, the results need to be inter- unselected twins who had been given the Eysenck Personal- preted with caution because no data from DZ twins were ity Questionnaire (EPQ) and the 42-item version of the available for comparisons. Multivariate analyses This shortcoming was addressed by Carey and Gottes- provided separate heritability estimates of 44% for obses- man (93) who studied a consecutive series of 15 MZ and sional traits (as defined by the 10-item 'Trait Scale' of the 15 DZ twins ascertained from the Maudsley Twin Register. LOI) and 47% for obsessional symptoms necessary for a The index twin in each pair had received a psychiatric diag- diagnosis of OCD (as defined by the 32-item 'Symptom nosis of obsessional neurosis, obsessional personality, or Scale' of the LOI). In a separate study using twins from phobic neurosis at local hospitals during a 32-year interval the Australian Twin Registry, Andrews and associates (97) (1948 to 1979).

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