EFAs and ADHD

Behavioural disorders, impulsivity and violent behaviour Attention deficit hyperactivity disorder (ADHD) is characterised by inattentive, impulsive and hyperactive behaviour occurring in children but some aspects of the condition may persist into adulthood (Richardson and Puri 2000, Richardson and Ross 2000, Arnold 2001). ADHD is a significant and increasing problem. It is estimated that it affects about 2% of school-aged children in the UK and 4% of school-aged children in the USA (Richardson and Puri 2000) and the use of medication to treat ADHD has increased dramatically in the last 10 years. Results of one study suggest that fish consumption may be associated with violent and impulsive behaviour (Hibbeln 2001). This cross-national survey of seafood consumption in 26 countries found that those with higher rates of seafood consumption tended to have lower rates of mortality due to homicide. The authors point out, however, there were many potentially confounding factors in this study and the hypothesis that fish consumption may help to reduce impulsive and violent behaviour should be tested in double-blind, placebo-controlled trials. Boys aged 6-12 years with ADHD were found to have significantly lower plasma levels of AA, EPA and DHA compared to normal controls (Stevens, Zentall, Deck et al 1995). In a further study of boys of the same age, significantly greater scores indicating behaviour problems, temper tantrums and sleep problems were reported in subjects with lower plasma total n-3 fatty acid concentrations (Stevens, Zentall, Abate et al 1995). However, a double-blind placebo controlled trial of DHA supplementation (345 mg/day for 4 months) in children with ADHD found that DHA treatment did not decrease ADHD symptoms compared with placebo (Voigt, Llorente, Jensen et al 2001). The authors pointed out however, that lack of response to DHA supplementation did not necessarily mean that a low brain content of DHA is not involved in the aetiology of ADHD. It is possible that in the population studied, a benefit of DHA was not produced because other essential nutrients were also lacking. It was suggested in recent reviews that ADHD may be linked to some other behavioural and neurological disorders, namely dyslexia, dyspraxia and autism, by an involvement of fatty acid metabolism (Richardson and Ross 2000; Bell, Sargent, Tocher et al 2000) and some studies of violent, impulsive and antisocial behaviour have also made this connection. Such behaviour has been linked to tissue deficiencies of n-3 fatty acids (Corrigan, Gray, Strathdee et al 1994; Stevens, Zentall , Deck et al 1995; Stevens, Zentall, Abate et al 1995; Hibbeln, Umhau, Linnoila et al 1998; Burgess, Stevens, Zhang et al 2000) and other nutrients including vitamins and minerals (Schoenthaler, Amos, Doraz et al 1997, Walsh, Isaacson, Rehman et al 1997). Virkkunen, Horrobin, Jenkins et al (1986) found that in a group of violent and impulsive offenders, plasma DHA was significantly lower than controls while n6 fatty acids were significantly elevated. In a double-blind, placebo-controlled trial on young adult male prisoners, dietary supplementation with vitamins and minerals, as well as fish oil (80 mg per day EPA and 44 mg per day DHA) and evening primrose oil, resulted in 26% fewer disciplinary offences in the supplemented group compared to placebo and 35% fewer disciplinary offences in the supplemented group compared to the baseline frequency (Gesch, Hammond, Hampson et al 2002). A recent double-blind placebo-controlled trial investigated the effects of dietary supplementation for 12 weeks with tuna oil (186 mg per day EPA, 480 mg per day DHA) and evening primrose oil in children with specific learning difficulties such as dyslexia (Richardson and Puri 2002). It was found that supplementation produced significant benefits. It has also been suggested that DHA in particular might be useful in treatment of dyslexia and dyspraxia as well as ADHD (Stordy 1995, 1997, 2000). Dyspraxia is a condition involving reduced motor skills manifesting as excessive clumsiness and there is a close link between dyspraxia and dyslexia (Stordy 1997). Stordy (1995) reported that, in a preliminary study, supplementation for one month with 480 mg per day DHA significantly improved an aspect of vision called dark adaptation in five dyslexic children. In a later open study of 15 children with dyspraxia, supplementation with the same dose of tuna oil and evening primrose oil as used in the study by Richardson and Puri (2002), produced significant improvements in scores for manual dexterity, ball skills and static and dynamic balance. The studies described above, of impulsive and violent behaviour amongst prisoners and its possible association with PUFA status (Virkkunen, Horrobin, Jenkins et al 1986, Gesch, Hammond, Hampson et al 2002) may be compared to a series of studies of aggression in Japanese students. Hamazaki, Sawazaki, Itomura et al (1996) conducted a double-blind, placebo-controlled trial of fish oil supplementation (1.5-1.8 g DHA per day) and after three months of treatment, aggression scores were significantly lower in the DHA group compared to placebo. However, the reason for the difference was that aggression scores in the placebo group had increased while those in the DHA group did not change significantly. The difference was accounted for by the fact that the final assessment in the trial occurred just before academic examinations, which it was suggested had caused psychological stress. A similar trial was conducted on different students who did not face such stress and no significant change in hostility was recorded in the DHA or placebo group (Hamazaki, Sawazaki, Nagao et al 1998). The authors concluded that DHA administration could help to control aggression only at times of psychological stress (Hamazaki, Sawazaki, Itomura et al 2001). Hibbeln, Umhau, George et al (1997) pointed out that an apparent prevention of increased aggression is surprising because baseline intake of n-3 PUFA in the study population was relatively high. In a third double-blind, placebo- controlled trial on students. Plasma catecholamines were measured during a two-month period of continuous psychological stress due to university examinations (Sawazaki, Hamazaki, Yazawa et al 1999). In the DHA group, who took 1.5g DHA per day during the examination period, noradrenaline levels were significantly reduced. The authors interpreted this change as indicating that subjects in the DHA group adapted to stress more favourably than controls and that DHA may help to reduce the risk of stress-related diseases in individuals under long-lasting psychological stress (Hamazaki, Sawazaki, Nagasawa et al 1999, Hamazaki, Itomura, Sawazaki et al 2000). In another study by the same group, Thai subjects aged 50-60 years, from a university and surrounding villages, were studied in a double-blind placebo-controlled trial in which the treatment was the same DHA supplement as used in the previous trials (Hamazaki, Thienprasert, Kheovichai et al 2002). DHA administration reduced aggression scores amongst university employees but not amongst village-dwellers. The authors speculated that the difference was caused by a larger placebo effect amongst villagers or a lower sensitivity amongst villagers to the psychological stressor (a video of stressful events) used in the study. Conclusion The epidemiological evidence that DHA-deficiency is a cause of violent and impulsive behaviour is supportive but not conclusive. Also, the few available studies of plasma fatty acids demonstrate lower DHA levels in individuals with ADHD. Data from supplementation studies are inconsistent but there are sufficient positive results to strengthen the view that DHA deficiency may be associated with adverse behavioural consequences.

Impulse Control and Serotonin

Impulse Control Disorders Introduction Impulsivity is a fundamental aspect of the human personality in addition to being a prominent feature of many psychiatric disorders. Defined broadly, impulsivity can refer to: 1. acting on the spur of the moment without previous planning 2. rapid decision making without consideration of alternative action 3. carefreeness, taking each day as it comes. Other authors place impulsivity in a class of action oriented personality predispositions that includes extroversion, sensation seeking, and a lack of inhibitory controls. Difficulties with impulse control are present in a number of Axis I disorders, including intermittent explosive disorder (IED), kleptomania, pyromania, pathological gambling and trichotillomania. With the exception of IED, these impulse control disorders have the diagnostic feature of a tension release cycle and/or gratification after engaging in the behavior. Compulsive shopping falls within the DSM-IV category of Impulse-Control Disorders Not Otherwise Specified. Preoccupation with, and inability to resist purchasing unneeded items characterize compulsive shopping. There are many other disorders where impulsive behavior is secondary to a more primary problem. For example patients with dementia, psychosis, mania, and organic brain syndromesoften exhibit impulsive behavior but both pathological conceptualization as well as treatment focus on the primary disorder. In addition Cluster B personality disorders (borderline, antisocial, histrionic and narcissistic) also have prominent impulsive traits. For the purpose of this lecture we will concentrate on those conditions where impulse control is a core feature. Neurobiology The emerging view is that the serotonin system is important in the expression of impulsivity. Research over the past twenty years has been fairly consistent in finding lowered indices of serotonin function associated with behaviors characterized by impulsivity. One conceptualization of the function of serotonin is that it serves in a capacity of behavioral restraint checking for signals of nonreward, punishment and uncertainty. Pharmacologic manipulations support this model. For example, animals with impaired serotonin levels (due to blockade of serotonin synthesis or lesion of raphe nuclei) exhibit behavior described as hyperirritable and hyperexciteable. Approaches for studying serotonin function in this population have included measuring the serotonin metabolite 5-HIAA in CSF, neuroendocrine challenge studies, and studies of serotonin receptors and transporters on platelets. More recent methods have focused on second messenger signaling, genetic polymorphisms associated with important serotonin related proteins (eg. tryptophan hydroxylase) and application of brain imaging techniques. These studies have been generally consistent in finding low serotonin function in populations with impulsive behavior. It is not surprising that biologic factors may be important in this dimension of behavior as at least two studies support a heritable component of impulsiveness and aggressive behavior. Intermittent Explosive Disorder (IED) Diagnostic Criteria 1. Several discrete episodes of failure to resist aggressive impulses that result in serious assaultive acts or destruction of property. 2. The degree of aggressiveness expressed during the episodes is grossly out of proportion to any precipitating psychosocial stressors. 3. The aggressive episodes are not better accounted for by another mental disorder. Clinical Features IED is characterized by aggressive outbursts that typically have a rapid onset, are short lived (less than 30 minutes) and can involve verbal assault , assault against property or physical assault. The episode can be associated with a provocation but the response is out of proportion. This pattern of behavior leads to significant distress and impairment in the interpersonal and occupational spheres. In addition, legal or financial problems may result. Epidemiology Although IED can occur in childhood, the mean age of onset is 15. It is more common in males (3:1). The lifetime prevalence has been estimated to be about 2.4%. Differential Diagnosis 1. Substance Intoxication or Withdrawal: Aggressive outbursts can be associated with alcohol, cocaine, PCP, barbiturate and inhalant use. 2. Personality Change Due to a General Medical Condition: This diagnosis is made when behavior is associated with a diagnosable medical condition (eg. traumatic brain injury). 3. Oppositional Defiant Disorder, Conduct Disorder, Cluster B personality disorders: IED should be distinguished from the aggressive behavior associated with these disorders. 4. Purposeful behavior: In this case the aggressive behavior has a clear primary gain. 5. Malingering: Individuals may try to feign IED to avoid responsibility for their aggressive behavior. Treatment Serotonin reuptake inhibitors are a logical first choice in treating IED. Clinical trials indicate their efficacy in decreasing verbal and non-assaultive physical aggression in personality disordered subjects as well as in IED. Trials have generally used doses higher than what are typically used for treatment of depression. Among the anticonvulsants, valproate has been studied the most extensively. There is evidence, that like SSRIs, that valproate can reduce impulsive aggression in a variety of diagnostic categories. A number of studies have demonstrated efficacy of lithium in reducing impulsive aggressive acts in prison populations. Side-effects, however, have limited its use. There is some evidence that treatment response is maximized when pharmacological treatment is combined with psychological interventions. Psychological interventions center primarily on cognitive-behavioral group therapy. Specific treatments include relaxation training, problem-solving, negative thought reduction, cognitive therapy alone or in various combinations. While combination approaches appear to be more effective, there has been little ability to discriminate which specific treatment is superior to others. Kleptomania Diagnostic Criteria 1. Recurrent failure to resist impulses to steal objects that are not needed for personal use or for their monetary value. 2. Increasing sense of tension immediately before committing the theft. 3. Pleasure, gratification, or relief at the time of committing the theft. 4. The stealing is not committed to express anger or vengeance and is not in response to a delusion or a hallucination. 5. The stealing is not better accounted for by Conduct Disorder, Mania, or Antisocial Personality Disorder. Clinical Features & Epidemiology The diagnosis of kleptomania is reserved for a relatively rare group of individuals who engage in shoplifting of items they neither want nor need. Fewer than 5% of shoplifters are thought to represent this disorder. The diagnosis is made most frequently in women and the average age at presentation is about 35 years, although the age of onset is much younger (~20 years old). Patients with this disorder appear to have high rates of depression and social isolation. Bulimia also is associated with this disorder. Differential Diagnosis Ordinary theft, which is deliberate and motivated by primary gain (usefulness or monetary value of the object), should be distinguished from Kleptomania. Treatment Cognitive behavioral therapy has been used often in conjunction with medications such as lithium and antidepressants including SSRIs. Systematic long-term treatment studies are lacking. This disorder can have a chronic course despite repeated convictions for shoplifting. Pyromania Diagnostic Criteria 1. Deliberate and purposeful fire setting on more than one occasion. 2. Tension or affective arousal before the act 3. Fascination with, interest in, curiosity about, or attraction to fire and its situational contexts. 4. The fire setting is not done for monetary gain, as an expression of sociopolitical ideology, to conceal criminal activity, to express anger of vengeance, to improve one's living circumstances, in response to a delusion or hallucination, or as a result of impaired judgment. 5. The fire setting is not better accounted for by Conduct Disorder, Mania or Antisocial Personality Disorder. Little is known about this relatively rare disorder. While arson is a major source of property damage, studies indicate that patients with pyromania represent a small fraction of perpetrators, as little as 1%. Similarly, while childhood fire setting is quite common, rarely is the diagnosis of pyromania made. This suggests that efforts should be directed towards evaluating fire setters first for other diagnoses such as conduct disorder, antisocial personality disorder, substance abuse, or other conditions where judgement can be impaired (mental retardation, psychosis, etc). Because of its low prevalence, there is insufficient data in regard to treatment and outcome. Trichotillomania Diagnostic Criteria 1. Recurring pulling out of one's hair resulting in noticeable hair loss.\ 2. An increasing sense of tension immediately before pulling out the hair or when attempting to resist the behavior. 3. Pleasure, gratification, or relief when pulling out the hair. 4. The disturbance is not better accounted for by another mental disorder and is not due to a general medical condition. 5. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning. Clinical Features While hair pulling can occur at any site on the body, and frequently at multiple sites, the most common sites are the scalp, eyelashes, eye brows and pubic hair. This behavior can be prompted by stressful circumstances, depressed mood or contemplative states (such as may occur during reading, driving, or lying in bed). Of particular note is the impact trichotillomania has on social functioning. Feelings of shame and embarrassment lead to avoidance behavior and the use of wigs, hats and scarves to disguise hair loss. Case reports describe patients that eat hair (trichophagia) resulting in the development of bezoars (hairballs) that can lead to abdominal pain, bowel obstruction, and vomiting. Patients with trichotillomania are more likely to suffer from mood, anxiety and substance abuse disorders. Eating disorders and body dysmorphic disorder have also been reported to occur at a higher frequency in this population. Epidemiology Available literature suggests the prevalence in the United States to be less than 1%. The prevalence, however, of chronic hair pulling that does not meet criteria for the disorder may be as high as 10%. Surveys suggest that it is more common in women than men. The mean age of onset is estimated to be 13 years. Hair pulling in children is typically considered a benign "habit" and is self-limited. Etiology In contrast to the current DSM-IV classification of trichotillomania as an impulse control disorder, there is an alternate view that it more closely resembles OCD in its phenomenology, pathophysiology, and reported response to serotonergic agents. Others focus on the reinforcing, anxiety-reducing aspects of the behavior and suggest that trichotillomania might be related to anxiety disorders. A third interesting view is that trichotillomania is best viewed as part of a spectrum of biologically determined "pathological 'grooming' behaviors" such as compulsive feather-picking in birds and acral lick dermatitis in dogs. Treatment Antidepressants with prominent serotonergic effects (such as clomipramine and SSRIs) are most often prescribed. There is not, however, a consistent literature supporting efficacy. Combination approaches with atypical antipsychotics have been used with some success. Evidence suggests that even in those patients who show a good response initially to medication treatment, the potential for relapse is quite high. A variety of behavioral techniques have been applied to treating this population. Habit reversal training is designed to increase awareness of the behavior and teach alternative coping skills. Cognitive behavioral therapy is also used. There is a lack of systematic studies to determine efficacy of these interventions. The course of trichotillomania is highly variable without a consistent pattern. Pathological Gambling 1. Persistent and recurrent maladaptive gambling behavior as indicated by five (or more) of the following: 1. preoccupation with gambling 2. needs to gamble with increasing amounts of money 3. has repeated unsuccessful efforts to control, cut back, or stop gambling 4. is restless or irritable when attempting to cut down or stop gambling 5. gambles as a way of escaping from problems or of relieving a dysphoric mood 6. after losing money gambling, often returns another day to get even 7. lies to others to conceal extent of involvement with gambling 8. has committed illegal acts to finance gambling (forgery, fraud, theft, etc) 9. has jeopardized or lost a significant relationship, job, or educational or career opportunity because of gambling 10. relies on others to provide money to relieve a desperate financial situation caused by gambling 2. The gambling behavior is not better accounted for by a Manic Episode Clinical Features The gambling related costs in the United States of gambling are estimated to exceed $5 billion annually. While 86% of the general adult population was estimated (in 1998) to have gambled at some point in their lives, less than 10% of adult gamblers develop a gambling problem (as defined by impairment in occupational, interpersonal or financial functioning). Individuals with this disorder tend to be competitive, energetic, restless and easily bored. Pathological gambling is complicated by high rates of mood, psychotic, anxiety, attention-deficit, personality (antisocial), and substance use disorders (alchohol, nicotine, and stimulants). Rates of attempted suicide are higher than the general population (17% to 24%) Epidemiology The lifetime prevalence of pathological gambling in adults is estimated to be between 1.1-1.6%. Not surprisingly, these rates are much higher in patrons of gambling venues. Similarly states with increased access to legalized gambling have an even greater prevalence. The rates of pathological gambling also appear to be higher in populations receiving mental health or substance abuse treatment. Males outnumber females 2:1 with females being less likely to receive treatment (perhaps reflecting greater stigma in females). Of interest is that individuals with a family history of gambling are more at risk (a number of twin studies support this conclusion). Neurobiology In addition to a link with the serotonin system (as is generally seen with impulsive behavior) other studies of gambling behavior have focused on limbic brain regions, such as the anterior cingulate cortex, that are also thought to be involved in the underlying drug craving in cocaine dependence. Dopamine, involved in mediating the rewarding and reinforcing aspects of drugs of abuse, has been implicated in biochemical studies of pathological gambling, with cerebrospinal fluid levels of dopamine and its metabolites that are suggestive of increased dopamine neurotransmission. This overlap with substance abuse is supported by studies of decision making, neuroimaging, and neuropsychological testing. Treatment Behavioral treatments that have been effective in substance abuse have also been applied in treating pathological gambling. These include Gamblers Anonymous, motivational interviewing techniques, and cognitive behavioral therapy. There have not been many studies to convincingly establish their efficacy. Studies suggest that drop out rates as high as 90% occur with self-help groups. A number of well-controlled studies, however, have been completed showing benefit from SSRI treatment. While not definitive, these results are encouraging. SSRI doses higher than typically used for treating mood disorders were required. Other pharmacological approaches have been with the opiod antagonist naltrexone. Course Without intervention, there is generally a progression of in the frequency of gambling, the amount wagered, and the preoccupations with gambling. References American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC, American Psychiatric Association, 1994. Diefenbach, GJ; Reitman, D; Williamson, DA. Trichotillomania: a challenge to research and practice. Clinical Psychology Review. 20(3):289-309, 2000 Sarasalo, E; Bergman, B; Toth, J. Theft behaviour and its consequences among kleptomaniacs and shoplifters--a comparative study. Forensic Science International. 86(3):193-205, 1997 Potenza MN, Kosten TR, Rounsaville BJ. Pathological gambling. JAMA 11;286(2):141-144, 2001 Reist C. Serotonin and Impulsivity. Directions in Psychiatry. 17:297-301, 1997. Coccaro EF, Kavoussi RK. Fluoxetine and impulsive aggressive behavior in personality disordered subjects. Arch Gen Psychiatry 54: 1081-1088, 1997.

Serotonin and behavior -- from vanGoozen article

5-HT and Aggression In an influential thesis, Spoont (1992) argued that 5-HT stabilizes information processing in neural systems, resulting in controlled behavioral, affective, and cognitive output, whereas disturbances in 5-HT activity result in altered information processing tendencies. High levels of 5-HT were proposed to lead to excessive restraint, cognitive inflexibility and anxiety, whereas low levels were thought to lead to behavioral disinhibition and distractibility. Coccaro and Kavoussi (1996) proposed a model for impulsive aggression in which the threshold for aggressive action, given the proper environmental circumstances, is modulated by overall 5-HT system function. Diminished serotonergic function is thought to disinhibit aggression directed against the self and others, perhaps by sharpening sensitivity to stimuli that elicit irritation and aggression and blunting sensitivity to cues that signal punishment(Spoont, 1992). =============== To date, only three studies have measured 5-HIAA in CSF in children (Castellano´s et al., 1994; Kruesi et al., 1990, 1992; see Table 3). Kruesi et al. (1990) found that children with DBD and/or ADHD had lower 5-HIAA levels compared with children suffering from obsessive-compulsive disorder. CSF 5-HIAA concentrations were also inversely correlated with ratings of aggressive behavior in the disruptive group. At the 2-year follow-up, CSF 5-HIAA levels were found to be a predictor of the severity of physical aggressive behavior and poor outcome (Kruesi et al., 1992). In contrast, Castellano´s et al. (1994) found in their study of 29 boys with ADHD that CSF 5-HIAA levels were positively correlated with measures of aggression and impulsivity.

How the Opioid Theory Explains Many Maladaptive Behaviors

Worth Reading: One of the main objectives of conferences is that people with differing background and understanding can come together and not only promote their own studies and points of view but also learn from the experience of others. This is particularly important in the study of autism where so many disciplines are involved. Courchesne & Courchesne (1997) discussed this issue with regard to the differing needs of clinicians and practitioners, and scientific researchers and have pointed out the commonalities and dichotomies inherent in their approaches. There is an additional difficulty within the field of autism in that a number of apparently totally different and, at first sight, incompatible sets of understanding and experience are required. Although the syllabi for modern degrees in psychology require a basic appreciation of neurology, graduates cannot be expected to be comfortable with more complex biological and neurological processes. Even worse, those with a physiological or pharmacological training are often dismissive of concepts, which involve measuring elements, which cannot be seen, weighed or quantified by physical methods. One of the most intractable divides, within the field of autism at least, is that which separates brain biochemistry and the psychological theories, which underlie the symptoms by which autism is still defined. This paper represents an attempt to explore some aspect of that gap. Given that no one really understands the neurochemical workings involved in the central nervous system especially when they may well be abnormal, as in the case of autism, the task is a difficult one. The speculations contained in the following pages, are offered and can be accepted as no more than that. Basic Principles a) Biological We subscribe to the opioid excess theory for the causation of autism. The theory has been expounded on a number of occasions (Shattock et al, 1990; Shattock & Lowdon, 1991). In brief, we suspect that peptides and other related compounds, some with opioid (morphine-like) activity, resulting from the incomplete digestion of certain foods in particular gluten from wheat and certain other cereals and from casein from milk and dairy produce, find their way into the bloodstream from the lumen of the intestine. Once in the bloodstream a proportion will cross into the brain. They will either act directly as neuroregulators by mimicking the bodies own natural opioids (such as the enkephalins or endorphins) or act as ligands to the enzymes which would break down these naturally occurring compounds. In either case, the consequence is an increase in opioid and other activities. In the brain the opioids act in a variety of ways at a variety of specific receptors but their effects are basically neuromodulatory. They do not, usually, act as direct neurotransmitters (such as 5-HT (serotonin) or dopamine) but they regulate their activity usually in a diminutive manner. Details will be discussed in the course of the specific examples described later in this paper. b) Psychological There are a number of psychological models, which have been presented as capable of explaining the symptoms of autism. Each theory has its proponents and detractors. Each theory has strengths and weaknesses but it is beyond the scope of this presentation to discuss each of these in detail. In particular, in the UK at least, much attention is given to the “Theory of Mind” deficit ideas (as proposed by Baron-Cohen, Leslie & Frith, 1985) and of “Weak Central Coherence” as advocated by, for example, Hobson (1991; 1995). This study will concentrate upon the ideas of deficits in “Executive Function” as described by Ozonoff (1991) and elaborated by Hughes (1993; 1994; 1996). It is readily conceded that this has been done because the concepts of the theory fit happily with the theories we espouse rather than for any quarrels with the other proposals. Executive Function Deficits There seems, to us, to be one problem inherent with theories based around these concepts: how “autism specific” these deficits would be [see reference]. A case could be made for abnormalities in this process being relevant in many forms of learning difficulty as well as autism spectrum disorders. However, we remain of the opinion that possible links are worthy of exploration. Hughes has listed these deficits as including the following: - planning; - impulse control; - inhibition of pre-potent but incorrect responses; - set maintenance; - organised search; - flexibility of thought and action; - ability to disengage from control by the external context; - ability to guide behaviour by mental models or internal representations. It would seem to us, that these could be summarised in terms of deficits in the process by which the “clever” elements of “the brain” tell the “thick bits” what to do. It is characteristic of scientists, including psychologists (such as Ozonoff and Hughes), to concentrate on some of the more interesting and complex of the deficits which are possible and to ignore some of the very basic systems to which the same principles are known to apply but which would not attract and hold the attention of the trained specialist. We would start by exploring a couple of these simpler systems. 1. Extra-Pyramidal Movements and Dyskinesias One of the features of autism which is well known but which has not been the subject of intensive investigation is the constant movement, which some (but not all) subjects show. Many children appear completely unable to keep still; to sit at a table or to take a meal without standing up and walking around. However much parents and teachers attempt to stop this movement the child will find difficulty. There appears to be a severe, but variable inner drive directed towards this constant movement. To an observer it seems this drive and many of the associated movements are very similar to the constant activity seen in people, diagnosed with schizophrenia but who are taking neuroleptic (anti-dopaminergic) medications. People taking medications such as thioridazine (Melleril), chlorpromazine (Largactil) or haloperidol (Serenace; Haldol) are nearly always given other medications (e.g. orphenadrine (Disipal)) to eradicate or minimise these side effects. It is likely that the movements induced by these medications are in fact the same as those seen in people with autism because they are the result of the same causal mechanism. These neuroleptic drugs act by inhibiting transmission in dopaminergic systems; we are proposing that in autism the dopaminergic system is inhibited not by medications but by the opioid peptides. The consequence is, however, the same. Impulses from the system make use of acetylcholine as their transmitter and such impulses will cause “movement” in many parts of the body. Under normal circumstances, these movements are inhibited by a system (the nigrostriatal system) utilising dopamine as its transmitter. If, therefore, these inhibitory systems are themselves inhibited, the constant movements described above will become evident. The usual medical response is then to give further medications, which are anticholinergic. The phenomenon does bring into question the practice of using neuroleptic drugs, which are basically anti-dopaminergic in their action) in cases where dopaminergic systems are already inhibited. This example is, perhaps, stretching the original description of “executive function” into an area not considered by those who originally proposed the ideas but the principle is entirely analogous. (Medical note: Some neuroleptic drugs, such as haloperidol and sulpiride when used at low doses and risperidone at low or moderate doses, have a selective activity in blocking the pre-synaptic receptors. The net result would be an increase in transmission and amelioration of these particular symptoms) 2) Control of Aggression Being aggressive is “normal” for humans under certain circumstances. Theories of aggression being a basic drive receive support from studies (e.g. Smuts, 1986) showing a biological basis of aggression in other mammalian animals. Whether in response to a stressor (i.e. an aggressive response to a conflict situation), or as a result of frustration (i.e. inability to reach a goal), animal studies have shown that aggression is a primary motivator of behaviour. In humans, the exhibition of aggression is described in many terms, some acceptable and justifiable (e.g. during periods of human conflict as seen in the world wars of the twentieth century) and others deemed socially unacceptable (e.g. committing murder). Often the justification for aggression is defined in terms of factors such as cultural and communicative processes and according to individual perspectives (e.g. attributing the aggressive behaviour of others as being “aggressive” or “assertive” and the aggressive behaviour of ourselves as being “defensive”). Humans need to be prepared to act in this way and the mechanisms to do so are already in place (i.e. fight-or-flight response). However under normal circumstances, they are “inhibited” by other systems and in particular by systems under serotonergic (using serotonin (5-HT) as their transmitter) control. If these systems are themselves inhibited the tendency towards aggressive activity will become evident and more difficult to control. Opioid peptides will inhibit these systems. Diagram of synaptic cleft (Medical note: Drugs such as fluoxetine (Prozac), which increase the availability of serotonin are frequently given to minimise aggression. Eltoprazine is, unfortunately, no longer available but its “serenic” activity is said to be due to its ability to stimulate the postsynaptic receptors. Risperidone will inhibit the presynaptic receptors and so result in a net increase in serotonin availability and decrease in aggression. Note that risperidone will, at appropriate doses, increase dopaminergic transmission in the nigro-striatal system whilst, as the same time, increase serotonergic transmission in these systems. Both of these effects would be predicted as being beneficial.) Taken together these two functions of being primed for immediate movement (dopaminergic system) and being mentally appeared to fight (serotonergic system) are important for the preservation of the individual and normal physiological and behavioural responses to environmental stress. It is well known that under conditions of stress, opioids such as beta-endorphin are released in the brain. These consequences are characteristic of the fear – “fight-or-flight” response and are part of the overall requirement for self-preservation. The same responses would be anticipated as resulting from the presence of opioids from exogenous sources such as food. 3) Sensory Filtration Moving up the scale of complexity from these comparatively simple examples consideration should be given to the effects on sensory systems. The human sensory system comprises of a complex set of devices and channels, which deliver to us the ability to explore the outside world. The properties of this system are made up through a complex association between biological and psychological processes, drawing on information from our five senses and the subsequent coding, organisation and retention of this information. Because of the vast amount of information made available to us from our sensory organs and our finite ability to process this information, we undertake a process of filtration to separate the information, which is meaningful to us from the background information. Cognitive psychological investigation has suggested various theories as to the nature of this filtration process (e.g. Deutsch & Deutsch, 1963; Johnston & Heinz, 1979). Evidence of unusual sensory responses throughout the range of sensory mediums in autism has been catalogued both through psychological research (Courchesne, Akshoomoff & Townsend, 1990) and through various self-report measures by people with autism (Williams, 1996). Studies carried out at the Autism Research Unit have also provided supportive evidence (Taylor, 1998). The presence of opioid peptides will affect transmission in all of the sensory or perceptual systems of the CNS. At the same time as affecting the transmission of signals from the sense organs (sight; sound; gustation; touch; pain; proprioception) these same chemicals will affect the filtration of these signals. As described earlier, under normal circumstances, a perceiver will be able to automatically filter out those sensations which are deemed to be of no interest but which are fairly constant. Thus, the background noise in a classroom or of the traffic; the feel of ones clothing; the constant bombardment by visual stimuli can be ignored and we can concentrate on the task or point of particular interest. In biological terms, this “filtration” is achieved by the intelligent (cortical) areas of the brain sending messages to the more automatic areas to cut down on those impulses. If these inhibitory signals are themselves inhibited then the filtration processes will be inhibited and all of these phenomena will have equal significance. It is not possible to focus on particular areas without unusual effort and concentration. The Attention Deficit Disorder (ADD) problems are explicable in these terms. Similarly, if combined with the problems described above, we would see the additional problems of hyperactivity as shown in Attention-Deficit Hyperactivity Disorder (ADHD) and which so frequently accompany symptoms of dyslexia the symptoms of which are also explicable in terms of perceptual and cognitive abnormalities of this type. 4) Attention Switching Many people with autism have described the difficulties that they experience in switching from one sensory mode to another. For example (Williams 1996), whilst concentrating on processing visual stimuli which may be arriving in overwhelming quantities, they find it difficult, if not impossible, to make sense of auditory inputs. Many people with autism have described themselves as “visual learners” Courchesne (1994), by means of electrophysiological measurements, has provided very convincing evidence that people with autism do have great difficulty in switching their attention from one perceptual mode to another. Once in “visual mode” the time lag before switching to “auditory mode” is very much greater. The control of this switching system could, once again, be described as an “Executive Function” and, once again, could be the consequence of opioid activity within the CNS. 5) Higher Executive Functions The theorists (such as Ozonoff and Hughes) mentioned previously, have concentrated upon activities, which are more complex than the simple examples described here but by extending the explanation to more complex systems one can see how the same principles could apply and how these biochemical abnormalities could result in irregularities in functioning. For example, children with autism find it especially difficult to make choices. When presented with an array of sweets such as is seen in sweet shops and told to choose something the child will appear to “choose” in an arbitrary fashion. Alternatively, (s)he may choose the same thing every time (whether or not (s)he actually likes the chosen entity) or, sometimes, always choose the product nearest to the hand. Making choices is about filtering through options and if, as described above this filtration is affected such processes are far from easy for the subject. Psychologists have drawn attention to the problems people with autism have in planning future activities. Once again, planning involves a consideration of a variety of possible activities. In this case it is even harder than simply choosing sweets as the possibilities are imaginary rather than real. Thus filtering through a range of possibilities; visualising; considering and rejecting possibilities and making choices is asking too much from people where the basic processes are impaired by the presence of these comparatively simple chemicals. Conclusions and General Observations It is not necessary to explain how the other deficits in Executive Functioning, referred to earlier, are explicable in terms of this process but it can be done. In the same way, it may be possible to extend the process further to explain the perceived difficulties in “Theory of Mind” or Central Coherence” tasks. We do not see these psychological abnormalities as being “the cause” of autism although they are sometimes described in these terms. Rather, they are symptoms of underlying psychological abnormalities, which may themselves result, in particular difficulties, which will modify the semi-automatic behaviours described above, or behaviours which are not otherwise directly related to these basic biochemically inspired phenomena. Finally, we totally accept that each person with autism is different. The symptoms described above are superimposed upon the characters of individual human beings who have their own personalities and characteristics, foibles, preferences and inconsistencies. In no way are we attempting to define real people in terms of chemically driven automata. We must also consider how each and every one of us is affected to a greater or lesser extent by such forces, which are difficult to explain. References. Baron-Cohen, S., Leslie, A.M., Frith, U. (1985) Does the Autistic Child have a “Theory of Mind”? Cognition 21: 37-46 Courchesne, E., Akshoomoff, N.A., Townsend, J. (1990) Recent advances in autism. Current Opinion in Pediatrics 2: 685-693 Courchesne, E., Towsend J., Akshoomoff N.A., Saitoh O., Yeung-Courchesne R., Lincoln A.J., James H.E., Haas R.H., Schreibman L., Lau L. (1994) Impairment in shifting attention in autistic and cerebellar patients. Behavioural Neuroscience 108: 848-865 [View Abstract] Courchesne, R.Y., Courchesne, E. (1997) From Impasse to Insight in Autism Research: From behavioural symptoms to biological explanations. Developmental and Psychopathology 9: 389-419 [View Abstract] Deutsch, J.A., Deutsch, D. (1963) Attention: Some theoretical considerations. Psychological Review 70: 80-90 Eysenck, M.W., Keane, M.T. (1993) Cognitive Psychology: A student’s handbook. London (UK), Hillsdale (USA): Lawrence Erlbaum Associates, Publishers Hobson, R.P. (1991) Against the Theory of Mind. British Journal of Developmental Psychology 9: 33-51 Hobson, R.P. (1995) Apprehending attitudes and actions: Separable abilities in early development? Development and Psychopathology 7: 171-182 Hughes, C., Russell, J. (1993) Autistic Children’s Difficulties with Mental Disengagement from an Object: It’s implications for theories of autism. Developmental Psychology 29: 498-510 Hughes, C., Russell, J., Robbins, T.W. (1994) Evidence for Executive Dysfunction in Autism. Neuropsychology 32: 477-492 [View Abstract] Hughes, C. (1996) Brief Report: Planning problems in autism at the level of motor control. Journal of Autism and Developmental Disorders 26: 99-107 Johnston, W.A., Heinz, S.P. (1979) Depth of Non-target Processing in an Attention Task. Journal of Experimental Psychology 5: 168-175 Ozonoff, S., Pennington, B.F., Rogers, S.J. (1991) Executive Function Deficits in High-Functioning Autistic Individuals: Relationship to Theory of Mind. Journal of Child Psychology and Psychiatry 32: 1081-1105 [View Abstract] Shattock, P., Kennedy, A., Rowell, F., Berney, T.P. (1990) Role of Neuropeptides in Autism and their Relationship with Classical Neurotransmitters. Brain Dysfunction 3: 328-45 Shattock, P., Lowdon, G. (1991) Proteins, Peptides and Autism. Part 2: Implications for the education and care of people with autism. Brain Dysfunction 4: 323-334 Shattock, P., Savery, D. (1996) Urinary Profiles of People with Autism: Possible implications and relevance to other research. Conference proceedings from ‘Therapeutic Intervention in Autism’, University of Durham 309-25 Smuts, B.B. (1986) in Atkinson, R.L., Atkinson, R.C., Smith, E.E., Bem, D.J. (eds) Introduction to Psychology (11th edition), p.439. Fort Worth: Harcourt Brace Jovanovich College Publishers Taylor, S.A. (1998) A study of gustational sensitivity using solutions of varying concentrations within a sample of ASD and non-ASD individuals. Conference proceedings from ‘Psychobiology of Autism’, University of Durham. Williams, D. (1996) Autism: An Inside-Out Approach. London, England. Jessica Kingsley Publishers

Can vitamins, omega fats improve behavior?

Study links diet to mental health San Francisco Chronicle Carol Ness Wednesday, January 15, 2003 Nutritional Epidemic?: Studies on animal and human brains... When your parents told you to take your vitamins, they wanted you to grow up big and strong. They weren't thinking it might keep you out of trouble. But listen to this: In a recent study from England, inmates given daily vitamins, minerals and omega fatty acids drastically reduced their bad behavior. Compared to inmates who didn't get the nutritional supplements, they didn't fight as often, break as many rules, mouth off or act out as much. The study, done at an Aylesbury juvenile jail by Oxford University physiology researcher Bernard Gesch, is far from conclusive. But it suggests that the connection between what we eat and how we behave goes much deeper than "too much sugar makes my kids crazy." The logical extension of its findings could reach far beyond prison walls. If good nutrition can keep an inmate in line, think what it could do for road rage and violent crime. "This data is very interesting, although it raises as many questions as it answers," says James Gilligan, an expert on violence at New York University and consultant to the San Francisco jail's anti-violence education program. He adds that the Gesch study, along with a couple of other recent studies of omega 3 fatty acids' effects on mental illness, "at least suggest the possibility that ordinary foodstuffs like fatty fish may decrease impulsive behavior -- which includes a variety of antisocial behaviors." The study isn't the first to connect nutrition and behavior. Small studies have shown that vitamin supplements may raise kids' grades and improve their behavior at school. But Gilligan says the protocol for the new studies is far more rigorous. Most nutrition research looks at the body. We all know how saturated fats strangle our hearts, and studiously track the ways substances like lycopene in tomatoes might prevent cancer. But when it comes to behavior and mental health, the role of nutrition in general and fatty acids in particular is just emerging. Gesch, a former probation officer, runs a nonprofit called Natural Justice, which researches the causes of criminal behavior. His study involved 231 juvenile offenders. Half got a daily multivitamin and four pills containing essential fatty acids. The other half got five pills containing only vegetable oil. Their diets and behavior were monitored both before and during the study, which ranged from weeks up to 9 months. Results appeared in the British Journal of Psychiatry last year. Antisocial incidents -- everything from assault and hostage taking to insolence and rule- breaking -- dropped at least one-third among prisoners who got the supplements, but insignificantly among the ones taking the placebo. Gesch says he's not saying nutrition is the only cause of antisocial behavior, but that the results "could not be explained by ethnic or social factors." He cautions that the results need to be replicated -- and then more studies done to explain them. But they show the potential for reducing violence in prisons, and in the community, he says. His study stirred up enough interest that Gesch will present his work at the American Psychiatric Association's annual conference in San Francisco in May. The study drew the interest of Dr. Joseph Hibbeln, a researcher on nutrition and behavior at the U.S. National Institute on Alcohol Abuse and Alcoholism. For Hibbeln, who has labored in relative obscurity for 15 years on the effects of omega fatty acids on humans, Gesch's study is like gold. The human brain is made up largely of fat, Hibbeln says. And his theory is that American brains have changed over the last century as Americans have eaten less seafood and vastly more soybean oil, the ubiquitous "vegetable oil" that's in most processed foods. The shift means Americans now consume far more omega 6 fatty acids (present in the oil) than omega 3s (present in seafood) -- and the two affect the brain very differently, Hibbeln says. Omega 6 fats compete with omega 3s, and omega 3s are losing the battle in the American diet, Hibbeln said. And studies on animal and human brains have shown that without enough omega 3s, serotonin levels plummet. Low serotonin can lead to depression and impulsive behavior, and Hibbeln is convinced that our dietary changes are one reason American levels of depression and violence have risen. Gesch's study and new ones underway build on ongoing work by California State University at Turlock researcher Stephen Schoenthaler, who also has run tests on both offenders and schoolchildren that suggest improving nutrition affects behavior. In some of the new studies just coming out, omega 3 supplements helped reverse depression and bipolar disorder. Gesch says his study doesn't prove anything about why the inmates who got supplements acted better -- and much more research is needed. Gilligan cautions against thinking that finding one biological key to bad behavior is the answer to violence, which has deeply complicated social, psychological and cultural causes. And, he says, making sweeping policy changes would be wrong until more is known. But at the same time, adding a nutritional component to RSVP, the San Francisco jail's successful anti-violence program, might make sense. "It's hard to see where it would do any harm," he says. In California, however, the new research is unlikely to affect what prisoners are fed, let alone get them daily vitamins. State law says prisoners' meals must meet government nutrition guidelines, but in fact the regulations only address protein and a couple of the major vitamins like C and A. In San Francisco jails, inmates get 2,900 calories a day, at 99 cents per meal -- which means a lot of starch. Jan Wyatt-Lucha, food director in the Marin County Jail and consultant to the state Board of Corrections, says inmates' minimum diets are updated every few years. But vitamin supplements? "They are not going to do it because it costs too much," she says. Money aside, improving the diet of a captive population is one thing. People in jail already eat better than a lot of people on the street, Wyatt- Lucha says. "Getting the nutrients into people is matter for social policy," says Gesch. And parents. Carol Ness is a Chronicle staff writer. E-mail her at cness@sfchronicle.com. http://sfgate.com/cgi-bin/article.cgi?f=/c/a/2003/01/15/FD182842.DTL This article appeared on page FD - 1 of the San Francisco Chronicle

Low Cholesterol May Be Related to Impulsivity

Original Article The cholesterol conundrum - low cholesterol levels may lead to impulsive behavior Why do people on low-cholesterol diets die somewhat less often what less often of heart disease, yet a lot more often of suicide, accidents, and homicide than the rest of the population? Although the finding has cropped up in numerous studies over the past decade, it has met with much disbelief in medical circles. Nevertheless, an expert in heart disease research decided to test whether there might be any behavioral basis for the results. His studies link cholesterol in the diet with the neurotransmitter serotonin and its manifestation in impulsive behavior. Jay Kaplan, Ph.D., looked at monkeys who were eating diets high in fat, but either low or high in cholesterol. After eight months, he found that the low-cholesterol monkeys, who had cholesterol readings of about 220, had no heart disease but were more hostile than the monkeys on a cheeseburger-like diet, whose levels hit 600. "These monkeys went at it hammer and tong," says Kaplan, a professor of comparative medicine. "They engaged in more contact aggression - highly charged impulsive fighting - than the other monkeys." Impulsivity, an increasingly scrutinized category of behavior, plays out in violence, suicide, and risk taking. And, impulsive people are likely to have a deficit of serotonin. "People in cholesterol-lowering trials might have been experiencing impulsivity, which led to the higher rates of suicide and accidents," suggests Kaplan. He then measured serotonin levels in the monkeys' cerebrospinal fluid. Sure enough, the low-cholesterol aggressive monkeys had less serotonin than the high-cholesterol monkeys. Cholesterol is a major component of brain-cell membranes. Alterations in dietary cholesterol affect the fluidity and viscosity of the membranes, which house receptors for serotonin. So altering the condition of neuronal membranes may well alter the function of these serotonin receptors, explains Kaplan. The findings, reported in Psychosomatic Medicine (Vol. 56), raise questions about the National Cholesterol Education Program recommendations that Americans over the age of two significantly lower their intake of fat and cholesterol. "Can this diet do harm?" asks Kaplan. "For people who already have low serotonergic activity, a low-cholesterol diet might shove them across some threshold that makes them more likely to do things they might not otherwise do." Or into depression. A recent study of men being treated for heart disease showed that those receiving cholesterol-lowering drugs experienced more symptoms of depression and anxiety than those who were not on the drugs. Kaplan is swimming against a strong current. "The NIH," he laments, "has billions of dollars tied up in the [cholesterol] hypothesis." COPYRIGHT 1995 Sussex Publishers, Inc. COPYRIGHT 2004 Gale Group

Mood and Neurotransmitters

The Mood Hormones Although brain chemical imbalances that cause depression are complex, researchers believe that a few main hormones are responsible for promoting feelings of wellbeing. These hormones are norepinephrine, dopamine and serotonin. Another name for these hormones is monoamine transporters; that is they carry important messages along the neural pathway in the brain. Where an imbalance of these hormones occurs, a mood, energy or cognitive problem results. This is why these hormones are closely associated with depression. Norepinephrine is produced by the adrenal glands and nerve cells to help us maintain energy and activity. Norepinephrine is also called noradrenalin and behaves similar to adrenalin, in that it is released in reaction to anger or emergency. As with serotonin related antidepressants, norepinephrine related medications do not increase levels of norepinephrine, but attempt to help the sympathetic nervous system to process it more efficiently. Dopamine is associated with euphoria and our desire or motivation. Dopamine is also connected with the information pathway in the brain. A dopamine disorder or imbalance can cause memory and cognitive loss as well as difficulty with problem solving. Serotonin may help us feel energetic, calm and assured. Most mood problems are associated with serotonin imbalances. Because the vast majority of depression sufferers may have low levels of serotonin, and because most medications seek to increase serotonin levels, serotonin is discussed here in more detail. Low levels of serotonin not only affect mood, but the ability to cope with strong emotions. Low serotonin may also inhibit sensitivity to possible consequences, which may explain why aggression, impulsive behavior and suicide are prolific in people with low serotonin levels. How Low Serotonin Causes Depression Serotonin may affect depression in two ways. First, someone may suffer from a genetic disorder that causes serotonin to be processed inefficiently in the brain. Researchers have found that the 5HTT serotonin receptors can be too short, causing serotonin to be absorbed too quickly. This depletes the available supply of serotonin, causing mood and energy problems. Most antidepressant medications are designed to slow down this process and so are called ‘selective serotonin reuptake inhibitors’ (SSRI’s). The second way that serotonin may be depleted is through the brain’s defensive reaction to strong emotional stimuli, such as stress or trauma. Limiting the amount of serotonin causes one to be insensitive to impending danger or consequences. Repeated thoughts about or exposure to these conditions reinforces the brain’s reduced serotonin production. While this may help insulate one from a harmful consequence, it also causes mood problems, aggression and impulsive or risky behavior because the sufferer is no longer sensitive to possible consequences. Suicide is the most extreme, self-directed form of this type of aggression. Raising Serotonin Several drugs have been successful at increasing serotonin levels. Tricyclic antidepressants were first discovered almost 50 years ago and are effective at blocking serotonin from being absorbed. However, tricyclics caused many side effects and in some cases increased the risk of suicides. Tricyclics are so named for their distinctive three-ring molecular composition. Doctors now generally favor SSRI’s over tricyclics because of fewer side effects. SSRI’s are the most common antidepressant medications, and some variations work on both serotonin as well as norepinephrine. Monoamine oxidase inhibitors ( MAOIs ) prolong the effect of monoamines such as serotonin, by retarding the breakdown of these hormones. However, MAOI’s increase the risk of several side effects and react negatively with other medications and some foods. MAOI’s are generally prescribed only for specific conditions such as agraphobia or when SSRI’s are ineffective. Medications Alone Aren’t the Answer Although newer forms of anti depressants promise fewer side effects, one single approach is rarely effective, leaving doctors and patients searching for additional methods or a combination to safely restore serotonergic balance. Additionally, antidepressants can cause serious withdrawal symptoms such as rebound depression and insomnia that are worse than the original malady. Are Antidepressants Ineffective? FDA Advisory Letter on Depression In March of 2004, after an exhaustive review of depression studies, the FDA released a position letter on the effectiveness of current antidepressants. Some of the previously private studies revealed a higher placebo vs medication response, and critical editorials of this information claimed that antidepressants aren’t nearly as effective as once believed. As a result, the FDA lists the need for closer physician monitoring, especially in the case of children and those professing suicide ideology. For more information on the FDA’s advisory, click here. Breakthrough in Depression Research One of the most promising discoveries in depression research is the discovery of specialized bright light’s role as an active antidepressant. In 1984, researchers at the National Institute of Health (NIH) successfully used light to treat Seasonal Affective Disorder (SAD). Since then, specialized light has been used to treat sleep disorders and other mood disorders including depression. Specialized bright light causes an antidepressant response in three ways: 1. Bright light activates the production of brain serotonin. In 2002, the Lancet reported that exposure to bright light immediately increased brain serontonin, while dark and cloudy days depleted serotonin levels. 2. Bright light regulates the Suprachaismatic Nucleus, or body clock. With the discovery of specialized light in 1984, researchers discovered that the body clock, located in the hypothalamus, was responsible for sleep/wake and energy/mood cycles. In addition to becoming imbalanced from the lack of light (As with Seasonal Affective Disorder, researchers have also learned that the body clock can easily become inbalanced from stress, trauma, surgery, age, etc. Many people who suffer from depression also have a body clock problem, as they suffer from sleep problems and feel worse at a particular time of day. 3. Bright light suppresses the hormone melatonin. Melatonin is released in the evening time as a signal for the body to withdraw and prepare for sleep. Melatonin is converted from serotonin, and so lowers available serotonin. It also causes feelings of irritablity, withdrawl and sadness. Melatonin is important as a nighttime hormone but daytime or too much melatonin can cause mood problems. Several studies have documented the advantage of specialized light for depression. Patients responed to light within a week verses several weeks for medication, and light posed no long-term negative side effects. A review of light therapy in Archves of General Psychiatry concluded the following: “The evidence is in that light is an active neurobiological agent. But light therapy has little chance to be widely and properly used for a variety of ills, as long as it appears to the policymakers and grantgivers to lie uncomfortably between pharmaceutical company neglect (for obvious reasons) and the molecular reductionism of academe. These attitudes strikingly contrast with patients' acceptance of light therapy. Light therapy is easy to administer in outpatient settings, lacks major side effects, and, importantly, is cost-effective. Whatever its mode of action, it demands inclusion in the antidepressant armamentarium, now.” —Archives of General Psychiatry, October 1998 More Effective Than Medication Although light has been found to be effective by itself, studies show that a combination of light and medication is more effective than either method alone. Patients responded much quicker with a higher quality of response. Sleep problems improved as well. In addition to standard light therapy, a novel new treatment, called wake therapy offers relief within 24 hours. Wake therapy involves partial sleep deprivation and morning light therapy to sustain the anti depressant effects of wake therapy. As with standard light therapy treatment, a combination of wake therapy, bright light and medication is most effective. Offical Recommendation Specialized bright light is recommended by the American Psychiatric Association (APA) as well as the American Acadamy of Sleep Medicine. In January 2004, the Cochrane Medical Library issued the Cochrane Review of all depression related light therapy studies, and recommends light therapy for depression treatment. (Cochrane is considered by the medical industry to be the gold standard in medical review.)

Serotonin and Judgement

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Depression can hit at any age. More than the blues, the overall feeling of doom can trigger some people to kill themselves. Researchers now are looking at this behavior from a new angle. Studies show that low levels of the brain chemical serotonin can in part lead to an overall insensitivity to future consequences, setting off impulsive and aggressive behaviors and perhaps culminating in suicide. By selectively restoring the chemicals' activity researchers hope to prevent destructive behavior as well as head off suicide -- the eighth leading cause of death in the U.S.

Grades are posted. Alex . . . 98 percent. Pam ... 85 percent. Nick...91 percent. Your grade? 20 percent. You're upset so you talk to your teacher to find out where you went wrong. But what if your feelings went out of control? You rip up the posted mid-term grades and glare at your teacher as you exit the classroom. In the days that follow you experience overwhelming feelings of sadness and thoughts of ending your life. Why would a person behave one way rather than another? For years, scientists have agreed that some behavior flaws can arise from environmental influences including how your parents raised you or from a traumatic life crisis such as the death of a loved one. Now a growing body of evidence suggests that a chemical dubbed serotonin (ser-oh-TOE-nin) also may play a part. Some scientists believe that low activity of the chemical in the brain can lead to an underlying inability to handle powerful feelings, which can result in impulsive acts, aggressive behaviors and suicidal tendencies.

This new line of research may lead to:

• The use of brain imaging techniques for identifying those who may be impulsively aggressive or suicidal.
• A method to monitor the serotonin medications given to suicidal depressed patients.
• New insights on the mechanisms of serotonin.

Serotonin is one of a group of chemical messengers known as neurotransmitters that carry out communication in the brain and body. The message molecules flow from a nerve cell or neuron onto other neurons that act as receivers. There, they attach to a distinctly shaped area on the neuron called a receptor site. This union, which is like a key fitting into a lock, triggers signals that either allow the message to be passed on to other cells or prevent the message from being forwarded. Since the discovery of serotonin in the 1950s, researchers are finding evidence that one of its roles is to mediate emotions and judgment. For example, in animal studies, scientists discovered that low serotonin levels may be associated with impulsive or risky behavior. Researchers observed monkeys and found that the ones who took more dangerous leaps traveling from tree to tree had lower serotonin levels and more injuries from falling. Other scientists examined rats and found the ones with low serotonin levels chose a small immediate reward instead of waiting for a bigger prize. Scientists also have compiled studies that show serotonin is implicated in aggressive acts. One example involves mice who lack one type of receptor that responds to serotonin. These defective mice attack intruders faster and more intensely. Other researchers examined the spinal fluid of murderers in Finland. Their results indicate that these individuals have abnormally low levels of serotonin. Some researchers now believe that suicide may be the ultimate act of inwardly directed impulsive aggression. In one new area of research, scientists are examining humans with brain imaging techniques and believe defects in serotonin processing are partially responsible for suicidal behavior. Preliminary results show that depressed people who have attempted suicide exhibit lower serotonin activity (see brain images) in response to a drug that boosts the amount of the chemical in the brain. In addition, the depressed had a history of comitting impulsive acts including overeating and aggressive behaviors such as lighting fires or fighting. Scientists plan to uncover the brain areas where serotonin's inactivity causes the most havoc and identify all the components that play a role in the defective processing. Researchers view the brain in action with a special imaging technique called positron emission tomography (pet). These pet scans compare the brain activity of a severely depressed patient (left) to a healthy volunteer (right). Both people received a drug called fenfluramine that is known to increase the availability of serotonin in the brain. The scans demonstrate that only the healthy patient has an increase in serotonin activity, which is represented by the orange and yellow shading. This suggests that the severely depressed have a very blunted response to the neurotransmitter or very low serotonin levels. Researchers plan to use the technology to devise imaging guidelines that would identify patients with this deficiency.

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J. John Mann, Columbia Presbyterian Medical Center