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A large and comprehensive study recently performed in Korea has produced a surprising and disturbing result. The rate of 

 is reported to be an astounding 1 in 38-almost 3% of the population. Not so very long ago, 

 was one of the rarest of disorders, afflicting only 1 child in every 2000 to 5000. Since the publication of DSM-IV in 1994, rates in the United States have exploded to about 1 per 100. The new Korean study adds fuel to widespread fears that some sort of environmental toxin is causing this raging “epidemic.”

No one can know for sure what is going on-how much each of the following 5 possible contributing factors has actually influenced the huge jump in the 

. I will give you my best educated guesses and the rationales supporting them:

•Possible Factor 1: There has been a change in the definition of autism


We know definitely that this is a partial contribution. Before DSM-IV, autism was among the most narrowly and clearly defined of disorders. The symptoms began very early in life, before age 3 years, and were a striking and devastating combination of severe language deficits, inability to form even the rudiments of social relationships, and a preoccupation with a very narrow set of rigid rituals and stereotyped behaviors.

In preparing DSM-IV, we made the decision to add a new category that described a milder (and therefore much more difficult to define and distinguish) form of autism, Asperger Disorder. This seemed necessary because some (still quite rare) children presented with more or less normal language development, but with grave difficulties in making social contact and in engaging flexibly in the expectable range of behaviors. We knew that Asperger was about 3 times more common than classic autism and expected its inclusion to triple the rate of autistic disorders to about 1 per 500 to 1000. That gets us part way up to higher rates, but not nearly to 1 per 38.

•Possible Factor 2: Previously missed cases are now being picked up


An increased awareness of the symptoms of autism and better training in its diagnosis has undoubtedly resulted in improved case finding-thus identifying people who should have been, but previously had not been, diagnosed. It is impossible to determine just how significant a contribution to skyrocketing rates comes from this improved diagnosis. My guess is that this is a factor-but not one that comes close to bringing us from 1:500 to 1:100, much less 1:38.

•Possible Factor 3: An environmental toxin is causing an outbreak of autism


This has been the most popular and most feared explanation. It is almost certainly a quite small factor, if it is a factor at all. There has been no sudden environmental change that would account for such a sudden explosion in rates. The previously most widely accepted contender, Wakefield’s vaccine theory, was proven to be the result of bad and dishonest science. That there is no plausible alternative environmental vector does not disprove the possibility that there might be one, but it certainly makes it quite remote-especially in the face of far more plausible explanations.

•Possible Factor 4: The jump in rates is due to a change in diagnostic habits as autism became an ever more popular fad diagnosis


As the spectrum of autism widened, it came to include people previously considered to be unusually creative, or normally eccentric, or to have a schizoid or schizotypal personality disorder. Autism is no longer seen as a disabling condition and a wide variety of people have discovered their inner autistic self.

Redefined and reinterpreted, autism now casts a wide net catching much milder, everyday problems on the boundary with normality. Once rare and unmistakable, autism is now used loosely to describe people who do not really satisfy the narrow criteria intended by DSM-IV. Widespread publicity, Internet support and advocacy groups, and the fact that expensive school services are provided only for those who are given a diagnosis of autism have occasioned the dramatic swing from false negative to false positive diagnosis. Of interest, an autism advocacy group that could barely contain its enthusiasm at the high rates that were reported financed the Korean study.

•Possible Factor 5: Epidemiological studies always over-report rates


There is a systematic bias in all large-scale epidemiological studies to report as mental disorder even mild presentations of symptoms that may not have any clinical significance. It is entirely plausible that 3% of the population might have a smidgen of autism- completely implausible that so many would have an autistic mental disorder. Rates in epidemiological studies should be seen as no more than a screening upper limit- not a true reflection of the rate of actual mental disorder in the population being studied.

Human nature and the true rates of neurological illness and psychiatric disorder all change very slowly. Environmental toxins are more labile, but generally don’t just pop out of nowhere to make a condition 100x more common than it was just 15 short years ago. By far the most plausible explanations for the autism “epidemic” are factors 1,4, and 5. DSM-IV gave autism purchase by introducing a milder form close to the populous boundary to normality. Then autism took flight on the wings of definitional diffusion, Internet contagion, financial incentive, and nave interpretation of epidemiological results. The overall rate of autistic symptoms is probably the same as it always has been since time immemorial- only the naming of them has changed.

A large and comprehensive study recently performed in Korea has produced a surprising and disturbing result. The rate of autism is reported to be an astounding 1 in 38...

The Autism “Epidemic” Marches On: What is Driving Rates Even Higher?

Given the often irreversible deconstruction of a life that psychosis can bring to individuals and their families, strategies for early detection and intervention have become a focus of increasing interest. These strategies aim to prevent disorder by identifying, tracking, and treating the clinical antecedents to psychosis. In this article, we review the underlying rationale for this direction, the evidence that prevention of psychosis is possible, what psychosis-risk states look like clinically, what treatment studies show to date, and the risks and benefits of early intervention. We also outline what psychiatrists can do clinically, given what we currently know.

 illustrates the typical emergence of the early stages of psychosis as it unfolds during adolescence/early adulthood. As clinicians, we usually encounter and treat patients well after the first episode, when chronic deficits in functioning are already in place and positive symptoms wax and wane with the vicissitudes of treatment adherence. However, the emphasis needs to shift to the earliest stages of this process and on how antecedent genetic vulnerability and developmental liability are initially expressed as psychopathology during the final major stage of neurodevelopment in adolescence/young adulthood.

As schematized, premorbid normality gives way to declines in school, work, and social functioning. Soon thereafter, psychological symptoms emerge that are precursors to the positive symptoms that later become the basis of a DSM diagnosis of psychosis. At this earliest stage, however, these symptoms are not as prominent or disabling as they are in full-blown psychosis, and typically they are labeled “prodromal” or “psychosis-risk” symptoms and functional deficits.

At some point, these symptoms and deficits become prominent enough to meet standard diagnostic criteria, but medical recognition and treatment usually do not occur until weeks, months, or even years later. This interval is known as the duration of untreated psychosis (DUP), which has become a major target of early intervention strategies.

The neurobiological processes underlying this emerging clinical picture are more hypothetical. One model is illustrated in 

 This model postulates that psychosis is the product of inadequate cortical synaptic connectivity that typically emerges or is “expressed” in the final adolescent/young adult stage of neurodevelopment, when cortical synapses are normally pruned.

Two paths to this connection deficit are schematized in 

. In the first path, synaptic density is already attenuated in childhood from genetic liabilities or perinatal insults such that the normal pruning of adolescence drives connectivity below the psychosis threshold density. The second path starts with normal childhood cortical volume, but then pathologically aggressive synaptic pruning in adolescence leads to psychosis. The details and the mechanisms of this process are not the focus of this article. However, 

 is presented to illustrate the hypothesis that psychosis is a product of aberrant neurodevelopment and that for any intervention to be truly preventive, it must somehow slow down, halt, or reverse this trajectory-a daunting task indeed!

Initial efforts toward secondary prevention have focused on the first psychotic episode and reducing the DUP-the period between onset and first treatment. Dozens of studies have demonstrated a robust correlation between delayed first treatment (longer DUP) and poorer outcomes.

 However, it was not until the Early Treatment and Intervention in First-Episode Psychosis (TIPS) series of studies over the past 12 years that any effort had been made to actually 

the DUP and measure its effect on outcome. The hypothesis is that a shorter DUP in first-episode psychosis would be associated with better outcomes.

The TIPS study is complex and ongoing, but the core findings are that the DUP can be significantly reduced through educational campaigns about psychosis aimed at practitioners, schools, and the general public.

 In the study, such an effort was engineered in a single Scandinavian health care sector. The outcomes for a 4-year sample of first-episode psychotic patients from this sector were compared with the outcomes for 4-year first-episode samples from 2 control health care sectors that made no effort to reduce the DUP.

The target sector achieved a significantly shorter DUP than the control sectors. Baseline and 1-, 2-, and 5-year outcomes have been significantly better in the experimental sector sample, 

 with regard to negative symptoms and functional deficits (the core chronic symptoms of schizophrenia).

 All of the study sites in the TIPS series used a standard treatment battery of antipsychotic medication, individual therapy, and family therapy. Therefore, sector outcome differences were most likely related to the different 

of the same treatments, ie, earlier treatment resulted in a genuinely healthier cohort of patients.

We regard this as preliminary but compelling evidence that earlier diagnosis and earlier administration of standard treatments in the course of first-episode psychosis may actually truncate the neurobiological process(es) that generates chronicity (eg, excessive pruning). The result requires replication, but we and our Scandinavian colleagues are excited that the data strongly endorse the validity and preventive potential of early detection and treatment of psychosis.

If treatment earlier in a first episode can improve prognosis, could treatment before onset in the prodromal phase of the disorder actually delay or prevent onset? That question, raised by TIPS, has attracted increasing attention in early-psychosis treatment centers for more than a decade. More recently, the prevention field has been moving further backward, or earlier, in the temporal course of disorder development to the psychosis-risk or the prodromal phase of psychosis.

The study of the preventive potential of pre-onset or psychosis-risk intervention requires a common and reliable diagnosis of a risk syndrome with which to construct samples that we can track and treat and that can be replicated by independent clinical investigators. Yung and McGorry

 created the Comprehensive Assessment of At-Risk Mental States (CAARMS), a structured interview for diagnosing the psychosis-risk syndrome. Our team at Yale developed the Structured Interview for Psychosis-Risk Syndromes (SIPS); this tool is used to rate the severity/frequency of key prodromal symptoms and can be used to determine the presence or absence of several psychosis-risk syndromes. It can also be used to estimate the severity of these symptoms and syndromes, including the boundary of transition from the prodrome to psychosis, called “conversion.”

The interrater reliability of the SIPS is satisfactory.

 Moreover, the SIPS has proved to be a valid predictor of psychosis insofar as psychosis developed over the next 2.5 years in approximately 33% of a large sample of treatment-seeking persons meeting SIPS criteria.

 In essence, approximately 1 of 3 persons who met an SIPS prodromal diagnosis became psychotic, which amounts to a risk for psychosis that is more than 400 times the risk for the average individual. Some of the remaining two-thirds of the sample who met an SIPS prodromal diagnosis and in whom psychosis did not develop remained prodromally symptomatic and eventually met criteria for schizotypal personality disorder; in others, Axis I disorders, such as depression, developed; and in many, prodromal symptoms remitted with time without sequelae (J. Addington et al, unpublished data, 2010).

Despite this heterogeneity of outcomes, some of which are benign, it is important to note that persons who come to our psychosis-risk research centers are almost always treatment-seeking adults and young adults. Most are referred to us by practitioners in the area who are familiar with our clinic and with what kinds of patients we are looking for. The patients we evaluate and serve are definitely not from the ranks of the “worried well.” By and large they are disturbed, dysfunctional, and struggling with new, strange, and puzzling symptoms, and their families are baffled and very worried.

Treatment research in psychosis risk has just begun, and initial findings show promise. Combined antipsychotic (risperidone) and individual psychotherapy, antipsychotic therapy alone (olanzapine), and psychotherapy (cognitive-behavioral therapy) alone all show that onset of psychosis in prodromal samples can be delayed, but often with substantial adverse effects (eg, weight gain with olanzapine).

 Most recently, a randomized trial of v-3 fatty acids delayed onset of psychosis with virtually no adverse effects.

 In this study, the risk to benefit ratio is remarkably good, and if the results can be replicated, they should essentially eliminate concerns about untoward adverse effects in false-positive cases. Overall, however, many more treatment studies are needed before integrated guidelines can be formulated.

In the absence of more data, treatment recommendations must be conservative. The American Psychiatric Association’s 1994 Psychiatric Disorders Practice Guidelines covered the psychosis-risk syndrome in 1 sentence: “Furthermore, in persons who meet criteria for being prodromally symptomatic and at risk for psychosis in the near future, careful assessment and frequent monitoring are recommended until symptoms remit spontaneously, evolve into schizophrenia, or evolve into another diagnosable and treatable mental disorder.”

This, we believe, remains the core of treatment. As formulated by the leaders of the team at our psychosis-risk syndrome clinic at the Connecticut Mental Health Center-which includes Scott Woods, MD, and Barbara Walsh, PhD, and included the late Tandy Miller, PhD-the strategies summarized in the 

 constitute the backbone of our approach. The key elements are regular meetings with patients and their families, monitoring symptoms over time, and knowing when to use psychotropics.

Antipsychotic pharmacotherapy: yes or no?

Our guidelines concerning antipsychotic medications during the prodromal phase are conservative-we wait to use them until conversion has happened or appears to be inevitable. However, this strategy is dictated in part by our research protocol, which aims to track the risk syndrome to 1 or more of its possible outcomes. We are confident that our clinical oversight is sufficiently robust and comprehensive that monitoring to conversion does not place the patient in any danger.

We realize, however, that this strategy is not what most psychiatrists can follow, or count on, especially those in solo practices. Such practitioners face a real dilemma that is confounded by a lack of clinical research data to guide the way. Using antipsychotic medication without a diagnosis of psychosis is understandable but risky, both clinically and medicolegally. Many deal with it by broadening the psychosis not otherwise specified (NOS) definition and writing a prescription, which may be a reasonable ad hoc or stopgap measure, but it begs 2 questions that we as professionals must deal with: Is the risk syndrome as a psychiatric disorder a legitimate diagnosis? What is known about the risk to benefit ratio of treating this clinical entity?

Should the psychosis-risk syndrome be a new diagnosis in DSM-5 as part of Psychotic Disorders? This question has generated intense controversy over the past year in psychiatric circles and meetings. Much as we are tempted to jump into the fray of hyperbole and invective, let me say simply that it has been obvious to me for a long time that we need the Risk Syndrome in DSM-5. It is a legitimate, and important, clinical entity and needs to be recognized as such. Official recognition is required to obtain grants to support longitudinal research into its natural history and clinical trials of the treatment of persons with the syndrome. However, it is primarily needed so that these symptomatic and endangered persons can be treated as bona fide patients and physicians can be compensated for what is often a long and labor-intensive process. What risk-positive patients need most is time and contact. The lack of an official status for their condition is, in itself, responsible for much of the inadequate care and attention they are given.

The risk to benefit ratio of psychosis risk

Much resistance to disorder status for the psychosis-risk syndrome stems from the fact that only a minority of those given the diagnosis really have the disorder. In the majority of persons, the diagnosis is a false positive; nevertheless, they get labeled as sick or “crazy.” They are also subject to unnecessary treatments, which can have long-lasting adverse effects. All of this cannot be denied, although even false positives may obtain short-term benefits for their current symptoms, but what about true-positive patients? What happens to them if they are not acknowledged, followed up and, if necessary, medicated? If the long-term results of the TIPS study has validity, withholding attention and treatment will rob this group of truly preventive options.

For me, the answer to this dilemma lies in what we see as the long-term risks for each group. For the false-positive person, time usually reveals that the threat of psychosis is unlikely. Any ongoing treatment specific for psychosis will stop and any associated stigma is likely to disappear. For the true-positive patient, however, ignoring risk and preventive treatment leaves him or her vulnerable to a first psychiatric break that is, in the short term, unexpected, ineffable, terrifying, and possibly lethal. In the long term, this approach can potentially lead to dementia, even if the patient is eventually treated. For the patient with a true-positive diagnosis who is in the prodromal phase, a major life-long risk is actual loss of brain hardware. These are the patients who have the most to lose in the long run, and their risk to benefit ratio should give them top priority in mental health care delivery systems. The bottom line for me is that the psychosis-risk syndrome should be taken seriously and be treated as a bona fide psychiatric disorder for 3 reasons: it is there, it is real, and it can be very dangerous if ignored.

 McGlashan TH, Johannessen JO. Early detection and intervention with schizophrenia: rationale. 

 McGlashan TH, Hoffman RE. Schizophrenia as a disorder of developmentally reduced synaptic connectivity. 

 Marshall M, Lewis S, Lockwood A, et al. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. 

 McGlashan TH. Duration of untreated psychosis and first-episode schizophrenia: marker or determinant of course? [published correction appears in 

 Johannessen JO, McGlashan TH, Larsen TK, et al. Early detection strategies for untreated first-episode psychosis. 

 Melle I, Larsen TK, Haahr U, et al. Reducing the duration of untreated first-episode psychosis: effects on clinical presentation. 

 Larsen TK, Melle I, Auestad B, et al. Early detection of first-episode psychosis: the effect on 1-year outcome. 

 Melle I, Larsen TK, Haahr U, et al. Prevention of negative symptom psychopathologies in first-episode schizophrenia: two-year effects of reducing the duration of untreated psychosis. 

 Larsen TK, Melle I, Auestad B, et al. Early detection of psychosis: positive effects on 5-year outcome. 

. 2010 Oct 14:1-9; [Epub ahead of print].


 Yung AR, McGorry PD. The prodromal phase of first-episode psychosis: past and current conceptualizations. 

. The Psychosis-Risk Syndrome: Handbook for Diagnosis and Follow-Up

. New York: Oxford University Press; 2010.


 Miller TJ, McGlashan TH, Rosen JL, et al. Prodromal assessment with the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms: predictive validity, interrater reliability, and training to reliability [published correction appears in 

 Cannon TD, Cadenhead K, Cornblatt B, et al. Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. 

 McGorry PD, Yung AR, Phillips LJ, et al. Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. 

 McGlashan TH, Zipursky RB, Perkins D, et al. The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis. I. Study rationale and design. 

 Morrison AP, French P, Walford L, et al. Cognitive therapy for the prevention of psychosis in people at ultra-high risk: randomised controlled trial. 

 Amminger GP, SchÃ¤fer MR, Papageorgiou K, et al. Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. 

 Lehman AF, Lieberman JA, Dixon LB, et al; American Psychiatric Association; Steering Committee on Practice Guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. 

Much resistance to disorder status for the psychosis-risk syndrome stems from the fact that only a minority of those given the diagnosis really have the disorder.

Early Antecedents and Detection of Schizophrenia

Among all the problematic suggestions for DSM5, the proposal for a "Psychosis Risk Syndrome" stands out as the most ill--conceived and potentially harmful. It aims to solve a pressing problem in psychiatry-- the need for early identification and preventive treatment. Psychotic episodes create tremendous short-term impairment and may impact negatively on long-term prognosis and treatment efficacy. It would save great suffering if we could get there early and do something useful to reduce the lifetime burden of illness before too much damage is done.


But good intentions are not enough. The whole concept of early intervention rests on 3 fundamental pillars-- being able to diagnose the right people and then providing them with a treatment that is effective and safe. "Psychosis Risk Syndrome" fails badly on all 3 counts:
1. It would misidentify many teenagers who are not really at risk for psychosis.
2. The treatment they would most often receive (atypical antipsychotic medication) has no proven efficacy, but. . .
3. It does have definite dangerous complications.


First, let's deal with the misidentification problem. Even in the most expert of hands (ie, in very highly selected research clinic settings), at least 2 of 3 people who get the diagnosis do not go on to become psychotic. Of great counterintuitive interest, the longer the research clinic operates, the lower its rate of correct identification becomes. With time and spreading reputation, the clinic attracts increasingly heterogeneous referrals-- so that it is more difficult to discriminate from among them those who are truly at risk for psychosis.


What would be the misidentification rate once the diagnosis became official and was applied in the real world? No one can say for sure, but two-thirds is certainly a lower limit of misidentification. There are several reasons to believe that the ratio of wrong diagnoses would actually be much higher:
o The raters in general practice would be much less expert than specialists in research clinics
o The "patients" would be closer to normal and harder to discriminate
o Drug company marketing would influence parents and clinicians to be especially alert to any strangeness in teenagers.

It has been estimated that the false-positive rate would jump from about 70% in specialty clinics to about 90% in general practice. This means that as many as an astounding 9 in 10 individuals identified as "risk syndrome" would not really be at risk for developing psychosis.


Those supporting the diagnosis for DSM5 have attempted to fix this overwhelming problem by inserting a definitional criterion that the person must be seeking treatment. They hope this requirement would both reduce the rate of false-positives and ensure that those who are misidentified will need some form of treatment. Their preferred treatment for "risk syndrome" is cognitive/behavior therapy which might be helpful (and is unlikely to be harmful)-- even for those who have been misidentified.


This fix fails badly on both counts-- ie, in reducing false-positives and in guaranteeing safe treatment. Under the best of circumstances, the overwhelming majority of "treatment seekers" will still be false-positive. Once the diagnosis is official and marketed, the problem will get much worse as a new army of "treatment seekers" is brought in by family members. Their perceived "strangeness" may come from many causes other than psychotic risk, including drug use; adolescent developmental issues and rebelliousness; culturally dystonic creativity; stable schizotypal personality; or normal eccentricity. A far more efficient signal to noise filter would have been to require that the individual must also have a close family member who has experienced psychotic episodes.


Then we get to the worrying treatment issues. It is the height of unrealistic wishful thinking to assume that most of the misidentified patients will get cognitve therapy. Cognitive therapy is in short supply and largely unavailable--especially for this population. On the other hand, antipsychotic medications are fairly ubiquitous and already frequently given for off-label indications-- particularly to kids on Medicaid. It has not yet been established that antipsychotic medications are effective in preventing psychotic episodes or in improving the life course in those who would meet the criteria for "risk syndrome." This is an area that to date has received little study and the few existing findings are equivocal.


In contrast, the harmful effects of atypical antipsychotics are extremely well established and frightening. Teenagers starting at an average weight of 110 pounds gained an average of 12 pounds in 12 weeks-- and one of the antipsychotics caused an 18-pound weight gain in this period. This raises the risk for diabetes, metabolic syndrome, and a shorter life span.

To sum up:
1. The "risk syndrome" would misidentify many (somewhere between 3 and 9) kids for every one correctly identified
2. The treatment most likely to be offered has no proven efficacy, but can have extremely dangerous complications.

This is a clearly the prescription for an iatrogenic public health disaster.

The goal of early identification and proactive treatment in psychiatry is laudable-- but elusive and not currently attainable. Prevention requires having a happy combination of accurate identification and effective and safe treament. Instead, we now have the opposite dangerous combination-- wildly inaccurate identification with a likely ineffective but definitely risky treatment.


The people who developed the "risk syndrome" suggestion for DSM5 are smart and have no conflict of interest motivation. How can they be promoting such a bad idea? The answer is that, like most experts, they have a blind spot when it comes to understanding the huge gulf between the real world and their rarified research experience. Perhaps in their hands, the false-positive rate can be kept to 2 out of 3 and the cognitve treatments given will be safe and generally helpful. It has been difficult for them to appreciate just how differently and destructively their pet suggestion would play were it to become prematurely official.


"Psychosis Risk Syndrome" belongs in the DSM appendix reserved for new diagnoses that deserve further study-- but that are not ready for prime time.

[Editor's note: This commentary also appears on the website of 

The proposal for a "Psychosis Risk Syndrome" aims to solve a pressing problem in psychiatry-- the need for early identification and preventive treatment.

DSM5 and "Psychosis Risk Syndrome:" Not Ready For Prime Time

Tourette syndrome is a neuropsychiatric disorder of childhood onset. It is characterized by the presence of multiple motor tics and one or more vocal tics, not necessarily concurrently, that last longer than 1 year. Formal diagnostic criteria from the World Health Organization and the American Psychiatric Association differ only slightly (

 criteria had required the patient to experience functional impairment or distress; however, this requirement, which was often criticized for its vagueness and inconsistent application, was removed in 

A tic is a sudden movement or vocalization that is rapid, recurrent, nonrhythmic, and stereotypical. Tics decrease in severity with distraction and relaxation, and increase with stress and anxiety. They can be suppressed through the patient’s own voluntary control, but they reappear when the patient’s effort is relaxed. Tics may be preceded by premonitory feelings, and patients often report that the tics are intentional responses that are executed to relieve these uncomfortable sensations.

Simple motor tics typically involve isolated muscles, producing movements such as blinking or sniffing. Complex motor tics involve contractions in different muscle groups and coordinated movements that resemble normal motor gestures. More complex motor phenomena include echopraxia (repetition of the movements of others) and copropraxia (making obscene gestures), both of which are reported in up to one-fifth of patients in specialists’ clinics.

Vocal tics are typically nonverbal (phonic tics) and involve sounds such as throat-clearing or barking. However, approximately 35% of vocal tics are verbal.

 Coprolalia (involuntary uttering of obscenities) is reported in fewer than one-third of clinical cases of Tourette syndrome; mean age at onset is 14 years. Other vocal phenomena include palilalia (repetition of one’s own sounds and words), and echolalia (imitation of sounds or words of others).

Prevalence estimates have been largely consistent and range between 0.6% and 1% in mainstream schoolchildren. Most of those affected have mild, subclinical symptoms that are unlikely to disrupt their lives. Studies conducted in special education environments have found a higher prevalence of Tourette syndrome in populations with learning difficulties and autistic spectrum disorders.

There is a significant genetic component to Tourette syndrome, although the mode of inheritance is complex and not fully understood. Tourette syndrome may be an expression of genetic vulnerability interacting with environmental factors.

 Genome scans have highlighted areas of interest in several chromosomes. Recently, rare sequence variants of the gene 

 on chromosome 13q31.1 have been associated with Tourette syndrome in certain patients, although these findings have yet to be replicated.

Studies conducted in special education environments have found a higher prevalence of Tourette syndrome in populations with learning difficulties and autistic spectrum disorders.

Environmental factors thought to affect the phenotype of Tourette syndrome include infections, perinatal problems, and hormonal influences.

One-third of children with Tourette syndrome will become symptom-free by adulthood; and one-third will exhibit only mild symptoms that require no treatment.

The most common comorbid disorder in patients with Tourette syndrome is attention-deficit/hyperactivity disorder, followed by obsessive-compulsive disorder and affective disorders.

Environmental factors thought to affect the phenotype of Tourette syndrome include infections, perinatal problems, and hormonal influences. Pediatric autoimmune neuropsychiatric disorders associated with group A b-hemolytic streptococcal infections can be associated with the onset or exacerbation of tics and/or obsessive-compulsive symptoms; compared with controls, patients with Tourette syndrome are more likely to have had a streptococcal infection 3 months before symptom onset.

 It has been suggested that an individual may inherit a susceptibility to Tourette syndrome and also to the way he or she reacts to streptococcal infections.

 Ultimately, this link requires further research and is currently too speculative to play a part in clinical practice.

Neuroimaging studies have improved understanding of the pathophysiological processes involved in Tourette syndrome. Disturbances in the basal ganglia and frontal cortical circuits have been implicated in the development of tic symptoms.

One model suggests that decreased inhibitory output from the basal ganglia results in excessive activity in the frontal cortical areas and gives rise to involuntary movements. A second model proposes that the basal ganglia facilitate desired behaviors by filtering out and preventing competing unwanted behaviors from interfering. A dysfunction in the ba-sal ganglia based on this model could result in the clinical spectrum associated with Tourette syndrome: tics, obsessive-compulsive behavior, and attention-deficit/hyperactivity disorder (ADHD), all of which involve impaired inhibition of unwanted behaviors.

The extended Tourette spectrum: assessment and diagnosis

Tourette syndrome is diagnosed through detailed personal and family history, together with physical, neurological, and mental state examinations. There are no specific diagnostic investigations, although in late-onset tic disorders, it is important to rule out brain lesions with neuroimaging and to check serum levels of copper and ceruloplasmin to exclude Wilson disease.

Tourette syndrome is a lifelong disorder. Tics, which first appear at a mean age of 7 years, characteristically wax and wane in severity, with transient periods of remission. Stress has been shown to be a factor in the increase of tic severity; as noted, there are reports of increased symptoms in stressful situations.

 Recent follow-up studies suggest symptoms reach peak severity when the patient is 10 years old; by the time the patient is 18, the severity is largely reduced.

One-third of children with Tourette syndrome will become symptom-free by adulthood, and one-third will exhibit only mild symptoms that require no treatment.

Reassurance or psychological intervention may be sufficient for patients with mild symptoms. There is considerable evidence to support the use of habit reversal training-a specific type of behavioral approach-as an alternative or adjunct treatment for some patients who have Tourette syndrome.

For the majority of patients, however, pharmacological intervention proves most beneficial in treating tic symptoms and associated behaviors. The choice of medication should be based on the predominant symptom (

). For tic symptoms, neuroleptics (such as haloperidol and pimozide) and atypical antipsychotics (including risperidone and aripiprazole) are useful. In general, the atypical antipsychotics have a better tolerability profile. Clonidine is also a first-line agent for tic symptoms and comorbid ADHD.

Only 1 in 10 patients with Tourette syndrome has no other behavioral problems, as evidenced by studies in both epidemiological and clinical settings.

 The most common comorbid psychiatric disorder in patients with Tourette syndrome is ADHD, followed by obsessive-compulsive disorder (OCD), and affective disorders. In patients who have comorbidities, higher levels of anger control problems, sleep difficulties, coprolalia, and self-injurious behaviors have been reported.

ADHD affects as many as 60% to 80% of patients with Tourette syndrome. ADHD symptoms are seen to occur even in subclinical cases identified through epidemiological studies.

 The 2 disorders share a similar clinical picture, which suggests an overlapping but unknown neurobiological basis and, more controversially, a shared genetic background.

ADHD symptoms are frequently the first to emerge in patients with a dual diagnosis (according to 

 criteria, ADHD symptoms should appear before age 7). The diagnosis of ADHD in a young patient with Tourette syndrome requires thorough assessment: apparent ADHD symptoms may be a result of the child trying to suppress tics or the restlessness the tics cause. A further complication is sleep disturbance: sleeping problems have been seen both in children with ADHD and in children with Tourette syndrome.

The cautious use of stimulants, such as methylphenidate, for the treatment of patients with both Tourette syndrome and ADHD has recently been advocated.

 As noted, clonidine has also been used successfully in patients with Tourette syndrome and ADHD.

 In addition, clonidine may be useful as an adjunctive treatment along with stimulants; some suggest that this agent extends the effects of stimulants while controlling their adverse effects.

 As a successful treatment for sleeping difficulties in children with neurodevelopmental disorders, clonidine may be useful given at night.

OCD is thought to affect from 11% to 80% of patients with Tourette syndrome. OCD and Tourette syndrome are intimately related and share similar characteristics. Both are lifelong disorders with childhood onset that feature voluntary behaviors as responses to involuntary sensations, exacerbated by stress. The similarity of the 2 disorders supports the hypothesis that certain obsessive-compulsive behaviors are part of the spectrum of Tourette syndrome.

The obsessive-compulsive behaviors found in Tourette syndrome appear to be both clinically and statistically distinct from those found in OCD in its isolated form. Patients with primary OCD more often have obsessions concerning dirt and compulsions concerning cleaning, while patients with Tourette syndrome and comorbid OCD have significantly more violent, sexual, and symmetrical obsessions along with forced touching, counting, and self-damaging compulsions.

 Those with both conditions experience compulsions that arise spontaneously, whereas patients with primary OCD characteristically experience compulsions preceded by cognitions.

OCD responds to SSRIs, such as sertraline and fluoxetine, or the tricyclic antidepressant clomipramine. Tic symptoms, however, are usually unaffected by SSRIs. Some suggest that augmentation with a typical neuroleptic is indicated for the patient with Tourette syndrome who does not respond to an SSRI.

Affective disorders are common among patients with Tourette syndrome; the lifetime risk is 10% and prevalence ranges from 1.8% to 8.9%. The cause of depression in patients with Tourette syndrome is probably multifactorial.

 Depression may arise because of the patient’s need to cope with a chronic, stigmatizing disorder, or because of bullying in school. Patients who receive pharmacological treatment may experience depression as an adverse effect of the medications (such as haloperidol and risperidone) commonly used in Tourette syndrome. Depression is also a common complication of OCD and is a major comorbid disorder in patients with ADHD. Thus, the depressive symptoms may be secondary to comorbid OCD or ADHD.

Three studies in clinical settings have consistently found a higher prevalence of personality disorders in patients with Tourette syndrome than in controls.

 The most frequent personality disorders are borderline, depressive, obsessive-compulsive, paranoid, passive-aggressive, avoidant, and schizoid types. One study found that 15% of the 102 patients with Tourette syndrome fulfilled diagnostic criteria for schizotypal personal-ity disorder, best predicted by high obsessional and anxiety ratings.

The increased prevalence of personality disorders among those with Tourette syndrome may be a consequence of comorbid ADHD, which has been found to predict behavioral problems and antisocial personality disorder in adulthood.

 Referral bias may also play a role, however, in that an individual with both Tourette syndrome and a personality disorder is more likely to be referred to a specialist than an individual with Tourette syndrome alone.

Advances in therapeutic avenues are providing specialists with new treatment options for complex cases. Specifically, deep brain stimulation, which targets the basal ganglia and/or the thalamus, is emerging as a promising neurosurgical approach for highly select, severely affected, treatment-resistant patients. Preliminary reports provide initial support for the efficacy and safety profile of this procedure.

Tourette syndrome is rarely considered in isolation: its clinical picture is often influenced by closely related conditions, such as OCD, ADHD, impulse discontrol, and affective disorders. A major topic for future research is the precise nature of the relationships between these disorders. Those who treat patients with Tourette syndrome must be prepared to deal with associated symptoms from comorbid disorders and should aim therapy at the predominant symptom. Disease-specific instruments, such as the recently developed Gilles de la Tourette syndrome–quality of life scale

 may assist physicians in the assessment of the symptoms that need to be prioritized.

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 Ludlow CL, Polinsky RJ, Caine ED, et al. Language and speech abnormalities in Tourette syndrome. 

 Kurlan R, McDermott MP, Deeley C, et al. Prevalence of tics in schoolchildren and association with placement in special education. 

 Baron-Cohen S, Scahill VL, Izaguirre J, et al. The prevalence of Gilles de la Tourette syndrome in children and adolescents with autism: a large scale study. 

 Walkup JT, LaBuda MC, Singer HS, et al. Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance. 

 Keen-Kim D, Freimer NB. Genetics and epidemiology of Tourette syndrome. 

 Abelson JF, Kwan KY, O’Roak BJ, et al. Sequence variants in SLITRK1 are associated with Tourette’s syndrome. 

 Swedo SE, Leonard HL, Mittleman BB, et al. Identification of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections by a marker associated with rheumatic fever. 

 Mell LK, Davis RL, Owens D. Association between streptococcal infection and obsessive-compulsive disorder, Tourette’s syndrome, and tic disorder. 

 Rizzo R, Gulisano M, Pavone P, et al. Increased antistreptococcal antibody titers and anti-basal ganglia antibodies in patients with Tourette syndrome: controlled cross-sectional study. 

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New Insights Into Diagnosis, Comorbidities, and Treatment Approaches

Tourette Syndrome

From Pedophilia to Addiction, Robert T. Segraves, MD

Female Sexual Dysfunction, Leonard R. Derogatis, PhD

Psychopathology and Personality Traits of Pedophiles, Lisa J. Cohen and Igor Galynker

Sexual Addiction Update, Aviel Goodman, MD

Because of recent scandals, pedophilia is one of the few psychiatric disorders widely known to the general public. Classified in DSM-IV and DSM-IV-TR as a paraphilia, pedophilia is characterized by persistent sexual attraction to prepubescent children. Although patients with pedophilic tendencies are generally seen by specialists in sexual disorders, many other clinicians are likely to encounter such patients as well. This article provides a general overview of the current literature on the psychology and psychopathology of pedophilia so that clinicians who encounter pedophilic patients will be better prepared to make an assessment and decide on the appropriate course of treatment. Moreover, a better understanding of people who are sexually attracted to children is critically important to protect against the severely destructive effects of childhood sexual abuse.


DSM-IV and DSM-IV-TR define pedophilia as “recurrent, intense sexually arousing fantasies, sexual urges, or behaviors involving activity with a prepubescent child or children (generally 13 years or younger).” These feelings, urges, or behaviors must persist for at least 6 months. The DSM-IV criterion that such urges must cause clinically significant distress or functional impairment was amended in DSM-IV-TR, such that recurrent pedophilic fantasies or arousal need not be experienced as distressing. This correction reflects the ego-syntonic nature of many pedophiles’ sexual desires and/or behavior.

According to DSM-IV, pedophilia can be diagnosed in the absence of any pedophilic behavior. Nonetheless, because of the potential legal risks of self-reporting pedophilic inclinations, the majority of pedophile research is conducted with participants who are identified by their behavior, most often via their contact with the criminal justice system.

There are 2 problems inherent with this research pool. For one, convicted or arrested sex offenders might differ considerably from pedophilic individuals who have not acted on their urges or who have acted on them but have not been caught. Second, not everyone who sexually molests a child is actually a pedophile; that is, such a person may not have a persistent sexual attraction to prepubescent children.

 Despite these difficulties, current research does reveal sufficiently consistent patterns to provide a basic overview of common psychological features associated with pedophilia.


Most sexual offenders against children are male, although female offenders may account for 0.4% to 4% of convicted sexual offenders.

 On the basis of a range of published reports, McConaghy

 estimates a 10 to 1 ratio of male-to-female child molesters. However, most researchers assume available estimates underrepresent the true number of female pedophiles.

 Several reasons for this have been proposed, including a societal tendency to dismiss the negative impact of sexual relationships between young boys and adult women as well as women’s greater access to very young children who cannot report their abuse.9 Because of the low number of females in pedophile samples, most of the studies discussed below will be drawn from exclusively male samples.


The most important diagnostic issue for clinicians who encounter a possible pedophile is the danger the patient may pose to children, although DSM-IV does not directly address this issue. Several subgroups are listed under the DSM-IV diagnosis of pedophilia:

• Individuals who are sexually attracted to males, females, or both sexes
• Those whose behavior is limited to incest
• Persons who are attracted only to children-exclusive versus nonexclusive

Although not listed in DSM-IV, the distinction between true and opportunistic pedophiles is possibly of greater diagnostic importance.

 Related terms include fixated versus regressed pedophiles or preferential versus situational pedophiles.

True pedophiles are those who show persistent and focused sexual attraction to prepubescent children. They show specific arousal to pedophilic stimuli on physiological measures of sexual arousal and have repeated sexual encounters with or recurrent sexual urges toward children. Opportunistic pedophiles have less of a focused sexual attraction to children. Their sexual engagement with children may depend on circumstances, such as the availability of a child victim, disinhibition secondary to substance abuse, or difficulty in connecting with an adult sexual partner.

There is some controversy whether this distinction reflects distinct categories or a continuum.

Clearly, it suggests that people who molest children may have distinctly different motivations. For example, true pedophiles may be motivated more by abnormal sexual desire while opportunistic pedophiles may be better characterized by failure to inhibit their impulses.

 Consequently, the distinction between true and opportunistic pedophiles may be important when considering the often conflicting findings on various psychological features within pedophile research. Perhaps more important, research supports the notion that “true” pedophiles present a higher risk of recidivism.

 Thus, this distinction may be worth addressing in DSM-V.

It is critically important for clinicians to understand that not all pedophiles are the same; in fact they may differ widely. In essence, clinicians should evaluate whether attraction to prepubescent children reflects a long-standing, deviant sexual drive or a more short-term, circumscribed problem that developed in response to circumstances or to comorbid psychopathology. Treatment and prevention implications as well as the risk to the public vary accordingly because research suggests that “true” pedophiles pose the greatest risk of recidivism.


Different psychological features give clues to the mechanisms underlying pedophilic behavior and offer potential treatment targets. More specifically, the person who sexually molests children has both impaired motivation and impaired inhibition. Possible motivational factors include social anxiety and the “abused-abuser theory.” Possible inhibitory factors include impulsivity, cognitive distortions, and psychopathy. In addition, neurobiological abnormalities may pertain to either motivational or inhibitory dysfunction. All of these factors may come into play in any one person, but individual pedophiles may differ widely in their psychological profile.

Because of recent scandals, pedophilia is one of the few psychiatric disorders widely known to the general public. 

Schizotypal Personality Disorder

The Autism “Epidemic” Marches On: What is Driving Rates Even Higher?

Early Antecedents and Detection of Schizophrenia

DSM5 and "Psychosis Risk Syndrome:" Not Ready For Prime Time

Tourette Syndrome

Psychopathology and Personality Traits of Pedophiles

Treatment Resistance: Challenges and Solutions

Exploring OCD Subtypes and Treatment Resistance

Psychological Therapies for Schizophrenia: Family and Cognitive Interventions

Biological Markers and the Future of Early Diagnosis and Treatment in Schizophrenia

The Link Between Psychotic Disorders and Substance Use