Aspergers: Aggression, Anxiety, Depression, Hyperactivity, Inflexibility and Repetitive Behaviors

In this article, we will discuss the major symptoms associated with Aspergers and High Functioning Autism…


Aggression is seldom an isolated problem and is particularly complex in kids with Aspergers (high functioning autism) [23]. It is important to understand that aggressive behavior is not always associated with just one condition and can have highly varied sources. An array of theoretic models has been proposed to understand aggressive behavior in children with Aspergers [24]. There are promising biologic models that suggest the behavior arises from alterations in dopaminergic reward mechanisms [25], and cognitive models, suggesting that such acts are an outcome of conditioned learning [26], [27]. Tantrums and physical aggression are often responses to a variety of circumstances and occur in the context of diverse emotions [23]. It has become fashionable to consider aggression as prima facie evidence of bipolar disorder, particularly when Aspergers kids are distractible, restless, and have chronically decreased need for sleep. It is increasingly important to consider, however, whether features of bipolar illness appear together and depart from chronic baseline functioning. It is also relevant if they are associated with pharmacologic (eg, serotonin reuptake inhibitor) side effects. It is useful to know the circumstances preceding and following aggressive outbursts before selecting a pharmacologic agent. For example, when aggression is a response to anxiety or frustration, the most helpful interventions target those symptoms and the circumstances that produce them rather than exclusively focusing on aggressive behavior.

Unfortunately, the request for treatment typically follows a crisis and the press for a rapid, effective end to the behaviors may not permit the gathering of much data or discussion. Nevertheless, it is not appropriate to “always” begin with one agent or another. Moving to a more “surefire” agent too quickly may mean that the patient takes on cardiovascular, endocrinologic, and cognitive risks that might be otherwise avoided. There are reports in support of using serotonin reuptake inhibitors (SRIs) [28], [29], [30], [31], [32], [33], [34], alpha-adrenergic agonists [35], beta-blocking agents [36], [37] ( 3), “mood stabilizers,” (or anticonvulsants) [38] ( 3), and neuroleptics [39], [40], [41], [42], [43], [44], [45] ( 4) for aggressive behavior. When a clinician has the luxury of time, the support of family, and collaboration with staff where the individual is working or attending school (or living), then an agent that is safer, but perhaps takes a longer time to work or is a little less likely to help, can be tried. It does seem that those agents with a greater likelihood of success pose greater risks [22], [46]. The most evidence supports use of dopamine blocking agents (neuroleptics) for aggression [22] ( 4), but the side effects and long-term risks from these agents are greater than others listed earlier.


Kids with Aspergers are particularly vulnerable to anxiety [47], [48]. This vulnerability may be an intrinsic feature of Aspergers [49] through specific neurotransmitter system defects [50], a breakdown in circuitry related to extinguishing fear responses [51], or a secondary consequence of their inability to make social judgments [15], [16], [17] throughout development. The social limitations of Aspergers make it difficult for kids with the disorder to develop coping strategies for soothing themselves and containing difficult emotions. Limitations in their ability to grasp social cues and their highly rigid style act in concert to create repeated social errors. They are frequently victimized and teased by their peers and cannot mount effective socially adaptive responses. Limitations in generalizing from one situation to another also may contribute to repeating the same social gaffs. Furthermore, the lack of empathy severely limits skills for autonomous social problem solving. For higher functioning kids, there is sufficient grasp of situations to recognize that others “get it” when they do not. For others there is only the discomfort that comes from somatic responses that are disconnected from events and experience.

Several agents have been tried for treatment of anxiety. There is no reason to suspect that kids with Aspergers are less likely to respond to the medications used for anxiety in children without Aspergers. Thus, SRIs [28], [29], [30], [31], [32], [33], [34], [52] ( 1), buspirone [53] ( 3), and alpha-adrenergic agonist medications such as clonidine or guanfacine all have been tried [35] ( 2). The best evidence to date supports use of selective serotonin reuptake inhibitors ( 1). It is also true that kids with Aspergers may be more vulnerable to side effects and to exhibit unusual side effects. Disinhibition is particularly prominent and can be seen with any of the serotonin reuptake inhibitors; in some circles this is regarded as evidence of bipolar “switching,” although there are no studies to suggest that among children with Aspergers this reaction is a portent of later nonmedication-related mania. Similarly, excessive doses may produce an amotivational syndrome [54].


Depression seems to be common among Aspergers kids in adolescence and adulthood [55]. Many of the same deficits that produce anxiety may conspire to generate depression. The relationship between serotonin functioning and depression has been explored in detail [56], [57], [58], [59]. There is also good evidence that serotonin functions may be impaired in children with Aspergers [60] and which suggest that depression and Aspergers would be more likely. Another possibility is that the basic circuitry related to frontal lobe functions in depression may be affected in children with Aspergers [61]. In addition, deficits in social relationships and responses that permit one to compensate for disappointment and frustration may fuel a vulnerability to depression [15], [16], [17], [55]. There is some genetic evidence suggesting that depression and social anxiety are more common among first-degree relatives of autistic kids [62], even when accounting for the subsequent effects of stress.

The medications that are useful for depression in typical kids and adolescents should be considered for kids with Aspergers who display symptoms of depression. It exceeds the scope of this discussion to detail the diverse forms depression may take in children with Aspergers or the complexities of how one might make the diagnosis of depression in children with comorbid Aspergers. It should be pointed out, however, that because some features of depression and Aspergers overlap, it is important to track that the changes in mood are a departure from baseline functioning. Thus, the presence of social withdrawal in a person with Aspergers should not be considered a symptom of depression unless there is an acute decline from that person's baseline level of functioning.

A second important point is that the core symptoms of depression should arise together. Thus, the simultaneous appearance of symptoms such as sleep and appetite changes, irritability, sadness, loss of pleasure in activities, decreased energy, further withdrawal from interactions, and self-deprecating statements would point to depression. An additional important point is that patients who display affective and vocal monotony are at higher risk for having their remarks minimized. Higher functioning kids can make suicidal statements in a manner that suggests an off-hand remark, without emotional impact. When comments are made this way, clinicians and others may underestimate them. In children with Aspergers, the content of such comments may be more crucial than the emotional emphasis with which they are delivered.

Agents that are useful for treatment of depression in children with Aspergers are serotonin reuptake inhibitors ( 1). There also may be indications for considering tricyclic agents with appropriate monitoring of ECG, pulse, and blood pressure ( 5). There are no agents that have been shown to be particularly more beneficial for depressive symptoms in children with Aspergers. Thus, the decision as to which agents to use is determined by side effect profiles, previous experience, and, perhaps, responses to these medications in other family members.

Hyperactivity and Inattention—

Hyperactivity and inattention are common in Aspergers kids, particularly in early childhood [5], [63], [64]. Differential diagnostic considerations are paramount, particularly in the context of Aspergers [63]. Hyperactivity and inattention is seen in a variety of other disorders, such as developmental receptive language disorders, anxiety, and depression. Thus, the appearance of inattention or hyperactivity does not point exclusively to attention deficit hyperactivity disorder (ADHD). The compatibility of the patient and his or her school curriculum is particularly important when evaluating symptoms of hyperactivity and inattention. There is a risk that a school program that is poorly matched to the individual's needs, by overestimating or underestimating a youngster's abilities, may be frustrating, boring, or unrewarding. If the verbal or social demands exceed what he or she can manage, they may produce anxiety or other problems that mimic inattention or induce hyperactivity.

Virtually every variety of medication has been tried to reduce hyperactive behavior and increase attention. The best evidence at this point supports dopamine blocking agents [39], [40], [41], [42], [43], [44], [45], [46] ( 4), stimulants [65] ( 6), alpha-adrenergic agonists [35] ( 2), and naltrexone [66], [67], [68] ( 3).

Inflexibility and Behavioral Rigidity—

Symptoms of inflexibility or behavioral rigidity are often difficult to quantify and yet often introduce some of the most disruptive chronic behaviors exhibited by patients with Aspergers. These can be manifest by difficulties tolerating changes in routine, minor differences in the environment (such as changes in location for certain activities), or changes to plans that have been previously laid out. For some kids this inflexibility can lead to aggression, or to extremes of frustration and anxiety that thwart activities. Families and school staff may find themselves “walking on eggshells” in an effort to circumvent any extreme reaction from brittle patients. In addition, the patients themselves may articulate their anxiety over fears that things will not go according to plan or that they will be forced to make changes that they cannot handle.

Sometimes these behaviors are identified as “obsessive-compulsive” because of the patient's need for ritualized order or nonfunctional routine. This is a phenomenologic error, as OCD has features that can be differentiated from PDD spectrum disorders [69]. Nevertheless, the idea that OCD and these “needs for sameness” might share some biologic features is attractive. It is not known now whether these symptoms are produced by disturbances in the same cortico-striatal-thalamo-cortical circuitry that is believed to produce OCD [70]. The model of obsessive-compulsive disorder, however, has suggested that use of SRI agents might be useful in ameliorating this problem [28], [33]. Whether the effect of SRI agents on this symptom cluster is mediated by a general reduction in anxiety [48] or is specific for “needs for sameness” is not known. An alternative hypothesis suggests that the impairment might be located in circuitry subserving reward systems that rely on norepinephrine and dopamine [24], [71]. If so, this would point to study of other agents and systems in future investigations.

To add further support to this hypothesis, reports from studies of alpha-adrenergic agents like clonidine [35] and guanfacine also suggest a decrease in these rigid behaviors. These short-term trials do not establish whether the benefits were sustained over a longer time, however. Agents that have been most useful are SRIs ( 1), but there may be a role for dopamine blocking agents for refractory symptoms [43], [44], [45] ( 4).

Stereotypies and Perseveration—

Stereotyped movements and repetitive behaviors are a common feature of Aspergers [64]. As with behavioral rigidity and inflexibility, similar models for stereotypy and obsessive-compulsive disorder have been proposed [72]. Stereotypy also may be closely related to tic disorders and Parkinson disease, however, in which repetitive behaviors emerge from impairment in dopaminergic [73] and glutamaturgic systems [74]. There are also interesting analogs to L-dopa toxicity in Parkinson disease [75].

The treatments for stereotyped movements and perseveration closely parallel those for behavioral inflexibility and the two clusters are often grouped together in studies of treatment efficacy. Thus, serotonin reuptake inhibitors ( 1) and alpha-adrenergic agonists may be helpful ( 2). In addition, the hypothesis that dopamine might play a role suggests that dopaminergic blocking agents should be added to the possibilities ( 4). Reports from studies of olanzapine [41], risperidone [42], [43], [44], and ziprasidone [45] suggest this is warranted.

Complementary and Alternative Medicine—

The pharmacologic treatment of Aspergers kids is in a very early stage. As a result of more organized and systematic investigation, the field is making advances in the discovery of more effective treatments [76]. A large gap remains, however, between the need for effective treatments and the effectiveness of the known agents. When there is such a disparity, opportunities for scientifically unfounded, anecdotal experience or highly biased efforts to capture the attention of parents, physicians, and educators are great. In the case of Aspergers, one can cite many examples; the recent experience with secretin [77], [78], [79], [80] is one. This does not mean that everything about secretin in autism is now understood, only that is unreasonable to recommend secretin for Aspergers [81]. A similar point might be made for the variety of dietary and nutritional therapies—in the absence of carefully designed, scientifically valid, controlled studies, it is hard to justify recommending specific treatments.

Nevertheless, clinicians still have to answer families who ask about trying novel treatments. Among investigators and concerned practitioners, broad guidelines have been suggested (Klin, personal communication). The first is that treatments should be safe. A variety of diets and mineral supplements are apparently safe, but some can be toxic; the frequency of toxic reactions should be spelled out and signs of toxicity should be thoroughly comprehended. More extraordinary interventions such as neurosurgery obviously are not reversible. The second guideline is that treatments should be affordable. At the height of the secretin rush, some practitioners were charging many hundreds of dollars for medication and supplies that totaled less than fifty dollars. For most families, these treatments are not covered by insurance and money that goes to novel treatment is not available for other services. The third guideline is that novel treatments should not interfere with a youngster's participation in daily programs or treatments that are known to be helpful. Focusing on communication and social enhancement through education should be the first priority of every multimodal treatment plan. Attending school, having a detailed evaluation, and receiving behavioral supports that promote socialization and communication should not be curtailed by the pursuit of novel somatic, dietary, and complementary medical treatments.


The treatment of complex, polymorphous disorders like Aspergers always brings a particular challenge to pharmacotherapy. Additionally, the specific characteristics presented by Aspergers introduce unique complications to patient care and place unusual demands on a clinician's skill and experience. To provide safe and effective treatment, the clinician must understand the core features of the disorder and the manifestations of the condition in his or her patient. Furthermore, a thorough understanding of the family, school, and community resources and limitations is necessary.

Once an assessment has been made, focusing on target symptoms provides a crucial framework for care. Knowing manifestations of symptoms and characterizing their distribution and behavior in that patient is most important. For patients with Aspergers it is particularly essential to coordinate behavioral and pharmacologic objectives. The target symptoms should be tracked carefully and placed into a priority system that is based on the risks and disability they create for the patient. The skill of pharmacotherapy also means setting out realistic expectations, keeping track of the larger systems of care at school and home, and collaboration with parents and care providers.

There is an expanding range and pace of biologic and intervention research into Aspergers. The genetic work has produced exciting leads that are likely to be helpful to future generations [82], [83], [84], but the task of clinicians is to tend to today's patients. As we discover more about the complex neural circuitry subserving repetitive behaviors, reward systems, and social cognition, there are good reasons to believe our treatments will become more sophisticated and specific. Psychopharmacology is also moving to design medications that target more specific populations of receptor and brain functions. This is likely to produce medicines that have fewer side effects, are more effective, and are more symptom-specific.

Pharmacotherapy is not the ultimate treatment for Aspergers but it has a definite place. Medication can be a critical element in a comprehensive treatment plan. There is a wider range of medications with more specific biologic effects than ever before. For patients with Aspergers these newer agents are safer and less disruptive. When paired with clinicians who are becoming more skilled at recognizing and managing symptoms, patients have a greater opportunity to reach their potential and lead pleasurable lives.


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Anonymous said...

Kelly is actually on Lexapro and is seeing a psychiatrist. I have been on anti-depressants for years and have periods of depression although I have had little problems lately. Since depression can be hereditary, I do watch for signs in my daughter. Where we are right now is I have talked to several people about Kelly possibly having aspergers. The psychiatrist, therapist, school guidance counselor and school psychologist all seem to think she has mild aspergers. The psychiatrist we just had an appointment with a couple of hours ago is very nice and encouraging. He has treated Kelly for several years, but only sees her every few months. I had sent him an e-mail telling him there was concern that she may have aspergers and asked what he thought. Kelly and I both talked with him for about an hour and a half. He never mentioned the word aspergers, but told me afterwards that she probably does have a mild case. He told her he admired her dedication to her school work (all AP classes, 4.0 and 32 on her ACT) and that she was on the right path. He brought up several times how people's brains function differently. But he told her it was important to do things with other people and to have a friend that you can share your feelings with. He suggested a therapist, but as always, she said she wouldn't go to one. She said she doesn't want to tell anyone what she is thinking. Kelly does not have a single friend although she is in clubs and likes to go horseback riding where there are other girls who ride. Kelly has been bugging us about getting another dog since our golden retriever died. (We still have one dog, a cat, and two sugar gliders) She told the psychiatrist that everything would be better if we got another dog. Kelly is a huge animal lover which I've been told is common among people with aspergers. The psychiatrist asked her why it would be better... because that's who she would spend time with and confide in? She laughed and said, "yes." He suggested she could make a deal with me like if she went out and did something with other kids, say, 12 times, then we could get a dog. He suggested meeting them at Barnes and Noble to study (which kids at her high school do) or going to a movie or getting something to eat. She had tears in her eyes and said that was too hard. He told her if she didn't feel like she could do it, to call him and he would set her up with a therapist who could help her. He told her to look at it like a class where she can learn things from her. That about ended our session and Kelly left and went to the car very upset. Later, Kelly said how about if she did something socially two times and then we could get a dog. I told her that was not enough, because it would take a while for her to get comfortable asking people to do things. We never reached an agreement.
Also, I met with the school psychologist again today to give her a questionnaire she had me complete regarding Kelly. She is also having one of Kelly's teachers complete a form. Kelly's teachers love her and one even has her babysit for him. She loves school, but I think it is primarily because she likes her classes and teachers. The guidance counselor says when she has looked in on Kelly in class, she seems to be comfortable with the kids in her classes and talks to them. The school psychologist asked me if I want her to talk with Kelly after she gets the questionnaire back from her teacher. Dr. Littleton, the psychiatrist, said it might be a good idea, so Kelly doesn't think he and I are ganging up on her. I guess it is coming to the point of how to tell her she may have aspergers. I tried to bring it up recently and she said she does not have it and to not tell anyone that I think she does. She has a cousin that does have it but is much more severe and I'm sure she doesn't want to be thought of in the same way.

Mark said...

Don't just assume she has Aspergers. It would be best to have her evaluated by a child and adolescent psychiatrist who specializes in ASDs... then go from there.

If it turns out that she does have Aspergers -- it's good that she knows. My bias is that it is better to know than not to know. If you have Aspergers and don’t know, it affects you anyway; if you do know, you may be able to minimize the negative impact and leverage the positive. Without the knowledge that one has Aspergers, one often fills that void with other, more damaging explanations such as failure, weird, disappointment, not living up to one’s potential, etc.

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