Self Portrait 1967

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Fellow wordpress blogger erikleo posted a portrait of himself today at age 20, which he painted in 1966. It inspired me to dig out this self-portrait at age 17, in 1967. A sheet of plastic was the etching medium. I scratched the drawing into the surface, inked it and made prints. I was a big fan of Albrecht Durer at the time.

A Decisive Moment for an Asperger Child

imagesLUQ8KKG2My cousin Bette hated her hair because it was so curly that she shrieked and whimpered whenever my aunt yanked a comb through it. My mother loved Bette’s red hair, but regretted my fence-straight bob. The tone of voice she used when referring to my straight hair was an accusation – I made it grow that way.

The hair situation had nothing to do with an important event that happened during a visit to my mother’s sister in Pennsylvania, which happened to coincide with Vacation Bible School. I don’t recall the denomination my relatives supported (there are so many), but the audience didn’t stand, kneel, or sing much. Instead of real wine, grape juice was passed around in paper cups with a tray of white bread croutons.

This scandalized my mother. How could materials available at any grocery store be expected to turn into the blood and flesh of Jesus Christ? Before marrying, my mother had sung professionally in churches: based on those experiences, she had chosen to align our family with the Episcopalians, because not only the priests and acolytes got dressed up, so did the audience, and she still got to sing beautiful songs.

My mother (and the other Episcopalian women) took advantage of God’s demand that women wear hats to church to amass vast collections of seasonal head gear. Judging by the extravagant and expensive hats bobbing about in church, I suspected that it was mortal women who had actually made up the rule, not God.

“Wear the Donald Duck hat,” I would tell my mother whenever we were late for church and she couldn’t decide which hat to wear. The Donald Duck hat was woven from white straw with a blue bill that jutted out above her forehead.

Vacation Bible School had nothing to do with hats, and my attendance could not be prevented by a plea for exemption. Even humor failed. My mother had noticed a reluctant streak in her daughter whenever it came time to cooperate with formal institutions and she insisted that I join my cousin in one more attempt at forced religious indoctrination.

My red-haired cousin and I were dropped off outside the church, where we were seated at a picnic table with kids our age. Adults handed each of us a board covered with blue felt, plus pictures of Jesus and a few loose sheep. Paper cut-out Jesus had typical Sunday school eyes, the kind that look nowhere and everywhere, but which have the power to pry into the shallow secrets of the boring human brain. The sheep were suitably adorable and adoring.

The adults directed us to stick the paper figures to the felt board. No reason was given as to why we should do this. I looked to my cousin and the others, expecting one of them to ask the adults why we were doing this, but the rest were busy deciding whether Jesus should float above the flock near heaven, or to have the sheep crowd around his temporarily earth-bound feet.

I tilted my board for a better look and a breeze caught the pictures. Jesus floated onto the grass. Cousin Bette screamed: “Look what you did! You let Jesus touch the ground!”

Another girl shrieked, “Pick him up. Quick!” as if the three second rule applied to religious pictures as well as to gum.

“Stop shouting,” I told my cousin. “It’s just a piece of paper.”

“No-it-is-not! It’s Jesus, and you let him touch the ground: You are in big trouble!”

“God is gonna punish you,” the other girl gasped.

A feeling passed through me, as if I been removed to a foreign universe, where simple pieces of paper are possessed by invisible beings and small girls are punished by tyrants for trifles.

Of course, at that age, I didn’t think this out, but I surely sensed what had just happened, and it had nothing to do with standing and kneeling; with the squabble over wafers and Wonder Bread, real wine or Welch’s grape juice, or with a rule that said women’s hair had to be covered with shame. Bette and the other children had been taught to fear imaginary entities and to believe that pieces of paper have supernatural power. Did adults lie to children, or did they really believe such things? The unease that had pestered me when adults spoke about ‘God things’ was sharpened into Ah-ha! focus.

My father hedged when I asked him for an explanation. His avoidance told me that his mind was not united in his approach to the world; the engineer wanted to confirm my suspicions of sheer puffery, but deep inside a superstitious and primal fear haunts all people. Collusion in these matters is required by society regardless of personal belief.

A custom developed between us. “Well you know and I know, but keep it quiet around your mother.”

Cousin Bette was correct about being in big trouble, but not in the way she had imagined. Never again would I feel comfortable with people who let crazy ideas rule their minds. Although my questioning nature was sometimes rewarded in school, skepticism in matters of religion would need to be stifled in public, a Herculean task for an Asperger child. A tiny raft of reason and cunning that lay hidden in my brain would ever after have to support me on a journey that led away from my own kind.

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We don’t really know children as individual expressions of the human experiment, because we do our best as a society to never let that person emerge.

 

Why Healthcare in the U.S. Stinks

No, I’m not going to get into an argument over Obamacare or insurance. I want to relate a specific experience with prescription medications that typifies how dangerous corporate power has become.

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As I have stated in other posts, I am Bipolar and Asperger. I’ve also stated that taking lithium has created a remarkable diminution in bipolar symptoms for close to 30 years. For the last few years I have utilized a specific brand from an American pharmaceutical company, but suddenly that product is ‘unavailable’ – the company continues to manufacture and distribute the product, so that is not a problem, but all the pharmacies in my area have switched to a product made overseas by a company using an American-sounding name, but which is foreign. The local pharmacists all insist that “no drug enters the U.S. without being inspected.” SEE FDA POLICY DOCUMENT BELOW

This simply is not true: the problem is, suddenly you’re ingesting chemicals that you, as an individual, have no way of knowing are safe or include the specific medication in the correct amounts and what “fillers” have been added. And should you have a reaction or bad outcome, whom do you contact? We can be sure that doctors, pharmacies, distributors – all those concerned up the chain of profit, have exempted themselves from legal responsibility and will pass along the blame to a factory in a country far, far away.

This chain of manufacture and distribution is disconcerting, but the cause of my inability to get the brand I have relied on for years is simply infuriating and challenges the very basis of American healthcare. The cost to me of the ‘overseas brand’ is the same as for that for the U.S. brand, but costs the pharmacy less, so their profit per pill has increased. (Multiply that by billions of pills sold) The individual pharmacy does not, and cannot, control which medications they order: corporate money crunchers make deals with the manufacturers and distributors, deals that have nothing to do patient health or safety or product quality.

The fact on the ground is that my choice of medication (and my doctor’s ability to prescribe) has been nullified by the profit motive of Walmart, Kmart, Walgreens, grocery chains and any mega retailer that has put local pharmacies out of business. These companies now dictate a huge segment of healthcare for millions of Americans, and serve the out-of-control prescription industry.

I’m old – I remember having an actual relationship with a local pharmacist, not just here in Wyoming, but everywhere else I have lived. A knowledgeable and experienced professional who had a stake in the well-being of customers. Often the information that the prescriber was too busy to impart, would be filled in at no charge by the pharmacist, along with pertinent instructions or updates from pharmaceutical companies.

The truly sad and scary situation is that the option of having good personal healthcare is going, going gone and with it the likelihood that the corporate takeover of healthcare will only increase.

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U.S. Food and Drug Administration

Foreign Pharmaceutical Manufacturers (5/96)

GUIDE TO INSPECTIONS

http://www.fda.gov  

PROCEDURES AND CONCEPTS

Inspections at foreign drug facilities are expected to be approached in the same manner as domestic inspections. One main difference that poses a significant challenge to the inspection team abroad is the logistics borne by the program itself. The majority of foreign inspections are pre-set (the manufacturer is alerted to the inspection) and relatively tight time-framed. Unless the inspection is prepared in advance and sharply focused, it is difficult to meet the objectives of the program satisfactorily.

Another factor to keep in mind is that the authority to inspect foreign drug facilities does not come from Section 704 of the Food, Drug and Cosmetic Act (the Act,) but from the agency’s ability to exercise Section 801 of the Act and commitments made by the sponsors (who is this?) of applications, if applicable. For that reason, the agency is not required to provide stringent documentary evidence to establish violations of the Act. However, the inspection team is expected to collect sufficient records to substantiate its findings and to aid in the further review process by the agency.

As a general rule, sample collection is not required during inspections at foreign facilities. However, some compliance programs, such as the drug pre-approval and post-approval programs, may require sample collection as part of the inspection process. Be guided by the respective compliance program. The inspection team leader is responsible for contacting the assigned Center application reviewers and discussing the need for sample collections. When significantly violative conditions are observed during an inspection, the team leader should alert ITOB with its findings either by phone or FAX for timely evaluation of the situation. At the end of each inspection, the inspection team leader is expected to communicate the result of the inspection to ITOB, if possible, by FAX, (301) 443-6919, transmission of the form FDA 483, a brief summary of findings, and a proposed recommendation.

INSPECTION SCHEDULING

ITOB headquarters staff is responsible for scheduling all foreign inspectional activities. When requests for inspection from various components of the agency are received by ITOB, it schedules and assigns inspections to foreign inspection cadre members according to their specialties and availability. Geographical factor also influences the assignment of the inspections; i.e., ITOB tries to assign inspections to the lead investigator of the home district where the sponsor firm is located. This proximity to the sponsor firm will provide the inspection team some advantage in dealing with the US representative at all stages of the inspection.

At the initial stage of inspection planning, ITOB (International and Technical Operations Branch) headquarters staff contact the domestic sponsor (who is this?) of an application to obtain any pertinent information necessary for preparation of the inspection scheduling. If any documents or data regarding the facility to be inspected need to be obtained, ITOB will arrange with the sponsor to have them forwarded directly to the inspection team leader in sufficient time prior to the trip departure date.

ITOB will coordinate the collection and the routing of documents and information from various headquarters offices to the team leaders. When deemed appropriate, a briefing may be held at the headquarters office prior to the trip. For those who are travelling abroad on an inspection trip for the first time, they are required to be briefed at the headquarters office.

REVIEWING DOCUMENTS PRIOR TO TRIP AND WHILE AT THE FIRM

Responsibility of the inspection team is to evaluate the foreign facility’s compliance with cGMPs and its adherence to application commitments and DMF information, if applicable. The inspection team is expected to review background documents and records whenever possible and prepare for the inspection prior to travelling abroad. This is necessary due to the tight time-frame usually assigned to each inspection; without advance preparation, an adequate inspectional coverage cannot realistically be attained in most cases. At this stage of planning, the inspection team will have to determine tentatively those issues needing attention during the on-site inspection.

Cut for length: for full document go to FDA website

_____________________________________ More from the FDA:

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Counterfeit Medicine

Counterfeit medicine is fake medicine. It may be contaminated or contain the wrong or no active ingredient. They could have the right active ingredient but at the wrong dose. Counterfeit drugs are illegal and may be harmful to your health.

FDA takes all reports of suspect counterfeits seriously and, in order to combat counterfeit medicines, is working with other agencies and the private sector to help protect the nation’s drug supply from the threat of counterfeits.

Love of Animals / Another Defect in Asperger Types

Psychologists claim that caring about an animal  companion, or animals in general, is abnormal, but only if you are Asperger. 

Remember: You're therapist probably thinks this is perfectly okay behavior toward animals.
Remember: The people who diagnose Asperger types as defective probably tortured lab animals in college. 

Asperger individuals supposedly love animals to an extent that is abnormal. This assertion, like much of what is said about Asperger individuals, is hearsay, and either anecdotal, or like other claims about Aspergers, is repeated so often that no one questions whether or not such an absurdity is accurate.

Aspergers are also accused of being devoid of the empathy and caring behavior that love of animals or humans requires. The inhumane treatment of animals by neurotypicals is simply never mentioned, because neurotypicals by definition are perfect humans. The real question is: What the Hell is wrong with loving animals? 

Asperger people have been labeled as “Psychopaths Lite” by certain psychologists. Torturing animals, not caring for them, is a symptom of being a psychopath.

Torturing animals in labs: how psycho is that?

Torturing animals in labs: how psycho is that?

An Aspie being social

So much fuss is made by social typical humans concerning proper social behavior that an Asperger feels pressured into following silly prescriptions for person-person interaction that are alien to our way of being. In fact, our instincts are much freer and more spontaneous than lists of demeaning rules that codify social class hierarchy and rely on lies and deception to discriminate against select human groups. Asperger  social interactions are open to a wide variety of human beings regardless of social status, wealth, class, gender, race or ideology.

My father was undiagnosed Asperger, but in hindsight he was a classic demonstration of an “alternative” way of being, especially in his social habits. In short, my father would interact with whomever he pleased, whenever he felt like it, and refused to change. This made my mother furious; she wanted him to socialize with “the right kind of people. ” In other words, to present phony interest in and admiration for the “correct class” of people from whom my mother wanted approval.

That’s it in a nutshell: Asperger individuals want to be around another person just because he or she is a “regular person” with whom we have something in common. A person who doesn’t regard people as objects to be exploited, who doesn’t prejudge and can respond to the content of the conversation. Someone who is present in mind and body and is not preoccupied with doing something ‘more important.’

I was reminded of this wonderful Asperger advantage yesterday when I went to a local bookstore to replenish a few books that have literally fallen to pieces over the years. The store employees showed no interest in helping me find what I wanted, but a customer stepped in; a large young man in rough clothing who took me straight to the correct section of shelves, saying that he knew the store better than the clerks. That was it – a conversation took off as easily as a tumble weed in the wind (LOL) and lasted nearly forty-five minutes. I found out that at present he’s an oil field worker, an extremely dangerous job, and a native of Wyoming, who grew up on a ranch about 100 miles north of here. If any social person had viewed the two of us yacking on and on – an old lady and a roughneck- no doubt their reaction would register somewhere in the peculiar mismatch range.

An interesting detail emerged: he had been diagnosed ADHD by the counselor at his elementary school, but his father had told her (in colorful language) that of course a 6-year old boy is fidgety. He wants to be outdoors, playing and learning and being a kid. That was the end of that. He’d clearly grown up to be healthy and intelligent and an avid reader and thinker.

The tell-tale sign that this type of impromptu social exchange suits me as an Asperger, is that despite a long period of conversation, I didn’t feel exhausted. I was simply happy at meeting an interesting person, whose appearance would have been rejected by a socially obsessed neurotypical, but I don’t have those prejudices. I interact with whomever I please, whenever I feel like it, and like my father, refuse to change.

 

 

 

Contemplating Dream Experiences

Where did the world go?

Where did the world go?

After I woke up from a particularly confusing jumble of dream images one morning, it occurred to me that the brain during sleep may be reacting to being cut off from the environment, as if it’s locked in a dark closet. The brain depends on a stream of information arriving from the senses; it uses this information to make sense of the environment and to model “reality.” Maybe it ‘freaks out’ when the visual information stream shuts down.

During REM sleep the brain tries to combine peripheral sensations with memory (like sounds from the street, or temperature changes in the room) but without the necessary full connection to the “outer world” via the senses, a coherent story can’t be composed. That is, the brain’s function, which is to make sense of the environment, is  to write an ongoing story that integrates all the available information that the brain needs to direct and control the body.

Deprived during sleep of sense information, especially visual orientation, the brain simply can’t thread images, sounds and motion into a coherent story. Whatever we may “dream” it is mostly forgotten, and if we do remember, the brain then strives to make a reasonable story from fragments that we can recall.

Behavioral Neuroscience Article / Circadian Rhythms and Psychiatric Illness

(Full article starts below.)

A note on my personal experience with circadian rhythm-related problems and bipolar disorder.

I was fortunate to be diagnosed in 1986 by a competent psychiatrist who had a “nuts & bolts” attitude toward medication. She prescribed lithium carbonate only; nothing else. She described its effects and side effects clearly, and explained that for the first three months or so my body would experience one or more adjustments as the dosage was increased to achieve therapeutic blood levels. This straightforward approach was excellent for an Asperger. I had the facts and a timeline; yes there were side effects like tremors, rubbery legs, a bit of stomach irritation, but these dissipated within a few months and were nothing in comparison with the total disruption and disaster in my life caused by bipolar disorder.

Within a few months lithium effectively transformed my ability to function, to travel, sleep normally, and endure reasonable stress. What was left to deal with was the toll taken by adapting over a lifetime to the chaotic and uncertain experiences of living with bipolar.

My point in relating this is that lithium carbonate has become “unpopular” in the arsenal of pharmacology. New concoctions of psychoactive drugs have made lithium “old-fashioned” and less profitable. A bipolar friend takes a $600.00 / month prescription, which he claims is of little help, but it’s paid for by insurance. In response, his psychiatrist just keeps adding more types of drugs. My lithium costs about $25.00 / month.

Lithium is one of a very few substances that can affect the circadian cycle in humans. (More about that later.) One reads often that a “replacement” for lithium is needed due to its terrible side effects, as if the new drugs being prescribed don’t have awful side affects. I think this is a red herring! I suspect that alongside the profit motive is plain old laziness on the part of prescribers who don’t want to take the time to work with patients to adjust lithium dosages. Over nearly thirty years of taking lithium, I have had to fight with prescribers who rely on Big Pharm propaganda and simply would not accept that a “mental=stupid” patient could possibly know anything about how a medication works in her body. Several (I’ve moved around a lot) wanted to stop prescribing lithium in favor of “something new” even though lithium has worked successfully for so many years. I found these attempts to be  irresponsible and unethical – especially with the clutter of trinkets from Big Pharm cluttering their offices. It was as if the prescriber was trading my health and safety for a pizza and pen holder.

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Website: FRONTIERS in Behavioral Neuroscience Front. Behav. Neurosci., 06 May 2014 | doi: 10.3389/fnbeh.2014.00162

Links between circadian rhythms and psychiatric disease

Ilia N. Karatsoreos*

  • Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, WA, USA

Determining the cause of psychiatric disorders is a goal of modern neuroscience, and will hopefully lead to the discovery of treatments to either prevent or alleviate the suffering caused by these diseases. One roadblock to attaining this goal is the realization that neuropsychiatric diseases are rarely due to a single gene polymorphism, environmental exposure, or developmental insult. Rather, it is a complex interaction between these various influences that likely leads to the development of clinically relevant syndromes. Our lab is exploring the links between environmental exposures and neurobehavioral function by investigating how disruption of the circadian (daily) clock alters the structure and function of neural circuits, with the hypothesis that disrupting this crucial homeostatic system can directly contribute to altered vulnerability of the organism to other factors that interact to produce psychiatric illness. This review explores some historical and more recent findings that link disrupted circadian clocks to neuropsychiatric disorders, particularly depression, mania, and schizophrenia. We take a comparative approach by exploring the effects observed in human populations, as well as some experimental models used in the laboratory to unravel mechanistic and causal relationships between disruption of the circadian clock and behavioral abnormalities. This is a rich area of research that we predict will contribute greatly to our understanding of how genes, environment, and development interact to modulate an individual’s vulnerability to psychiatric disorders.

Introduction

A significant problem that modern neuroscience aims to solve is the distress caused by neuropsychiatric disorders. The fundamental challenge is that these disorders are far from the unitary constructs we sometimes imagine, and almost certainly not caused by a single event, gene mutation, or neurotransmitter abnormality. Instead, these disorders are multifaceted neurobehavioral dysfunctions that in many cases also include symptoms outside the central nervous system. As such, neuroscience needs to address these challenges in an integrated fashion, leveraging the advances made using genetic, molecular, and physiological approaches. Several research groups are tackling the puzzle of neuropsychiatric disorders by exploring the hypothesis that homeostatic perturbations are at the root of such disease states. Understanding the mechanisms that maintain homeostasis and respond to environmental challenges that threaten homeostasis is of crucial importance. One such system is the circadian (daily) timing system, and studying how circadian rhythms are perturbed in psychiatric disorders may provide insight into their contribution to neurobehavioral changes in some mental disease.

This review will describe the function of the circadian timing system, discuss how various neuropsychiatric disorders such as depression, anxiety, and schizophrenia display disruptions in circadian timing, and present the hypothesis that in some cases these disorders may be triggered or exacerbated by a dysfunction in this crucial homeostatic system.

Circadian Rhythms: A Brief Review

One of the most salient environmental signals available to organisms is the rotation of the Earth about its axis. The reliable and predicable circadian (daily) changes in light and temperature (to mention only a few variables) have provided organisms – from single-celled organisms to humans – a framework on which to temporally organize physiology. This framework allows organisms to accomplish two major tasks. The first task is predicting regularly repeating changes in the environment. Anticipating such changes in the environment can aid even the simplest single-celled photosynthetic organism in the prediction of daylight hours to optimize energy collection by allowing different biochemical pathways to become active at appropriate times. This then allows potentially incompatible biochemical processes to exist in their own temporal compartments, ensuring they do not interfere with each other. Equally as important is the adaptation to unanticipated or less periodic changes in the environment. The circadian system allows for stimuli in the environment to “phase shift” the endogenous clock, pushing it forward or backward, in order to adapt to changes in the outside world. Unfortunately, modern industrialized society can regularly produce light at the wrong times of day (e.g., light at night from electronics) that then can activate phase shifting processes inappropriately. This problem is exacerbated when individuals are chronically living “out of time” with their circadian clocks, such as shift workers, airline pilots, and medical workers to name a few. Growing evidence suggests that chronic circadian disruption can result in significant mental and physical health problems. However, the mechanisms by which disrupted circadian clocks lead to these health problems remain unknown. To determine potential pathways by which disrupted clocks can contribute to neuropsychiatric disease, we need to explore the processes that underlie circadian timing at the molecular and cellular levels.

Almost all biological processes in organisms with lifespans longer than 24 h display circadian rhythms. In more complex animals, the most obvious of these is the regulation of the rest–activity cycle. In mammals, the master circadian clock regulating nearly all circadian rhythms in the organism is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This neural structure contains a self-sustaining oscillator that synchronizes local clocks throughout the brain and body (Moore-Ede et al., 1984; Butler et al., 2009). These “peripheral” clocks are thought to set local time in many body tissues, and are hypothesized to allow optimal functioning by temporally organizing biochemical and cellular processes throughout the organism. Animal studies have shown that shifting the SCN clock by light causes an almost instant resetting of oscillators there, but oscillators in the rest of the body take numerous cycles to fully resynchronize to the SCN and the external environment (Yamazaki et al., 2000), the root cause of the general malaise associated with jet lag. The mechanisms by which this resynchronization occurs remain unclear, although numerous candidates have been suggested (Cheng et al., 2002, 2006; Buhr et al., 2010).

How Does Circadian Disruption Affect Neurobehavioral Function?

Anecdotally, most of us are aware that disruptions in circadian timing through shift work, jet lag, or other processes can lead to neurobehavioral deficits. Such changes can manifest as alterations in mood, affect, or cognitive function. It should be noted that several of the most notorious industrial accidents in the past few decades, including the Bhopal disaster in India, the Chernobyl nuclear accident in Ukraine, and the Exxon Valdez oil spill in Alaska occurred during the night, with the individuals involved being shift workers of one sort or another. It is thought that several factors, including fatigue, interacted in each of these cases to cause or exacerbate the chain of events that lead to catastrophe (Colten and Altevogt, 2006). Thus, particularly in occupations with high cognitive loads, disrupted circadian clocks and sleep cycles could lead to significant degradation in cognitive function. An intriguing study in flight crews demonstrated that short recovery crews (those that are traveling mostly on transmeridian flights requiring repeated resynchronizations) showed decreased reaction times, increased error rates, and marked temporal lobe atrophy (Cho, 2001).

Animal models have also been applied to probe the connection between disrupted circadian clocks and neural and behavioral deficits. Gibson et al. (2010) used a repeated jet lag model in Syrian hamsters to explore the effects of chronic experimental “jet lag” on behavioral outcomes and neurogenesis in the hippocampus, since hippocampal neurogenesis is related to both cognitive and affective regulation, and may underlie depression (Samuels and Hen, 2011). They demonstrated that chronic jet lag by repeated phase shifting of the light–dark cycle results in learning and memory deficits accompanied by reductions in hippocampal neurogenesis. An important contribution of this study was the finding that deficits in hippocampal-dependent learning and memory persisted after cessation of the experimental jet lag (Gibson et al., 2010), suggesting that there may be long-lasting negative consequences of circadian disruption on brain function, even after the disrupting stimulus has been removed. In mice, Karatsoreos et al. (2011) demonstrated profound effects of circadian misalignment on the structure and function of prefrontal cortical neurons (Karatsoreos et al., 2011). Chronic (12 weeks) exposure to a shortened 20-h day (10 h light, 10 h dark) resulted in morphological changes in neurons in the medial prefrontal cortex (mPFC). Specifically, following circadian disruption neurons in layer II/III of the prelimbic mPFC had significant shrinkage of the apical dendrite, without observed changes in the basal dendrites. These gross changes were accompanied by simplification of the apical dendritic tree (Karatsoreos et al., 2011). Although the neural effects of the circadian disruption were stark, the behavioral effects were equally clear. Using a modified Morris Water Maze task that is sensitive to damage in the mPFC, circadian disrupted mice showed marked decreases in cognitive flexibility. In addition to the cognitive impairments, circadian disrupted mice demonstrated an “impulsive”-like phenotype, evidenced by entering a novel environment more quickly than controls. These findings were some of the first to experimentally link chronic circadian disruption to a reduction in the complexity of neurons that are important for attention, cognitive flexibility, and executive function. Although the mechanisms are still unknown, accumulating evidence supports a role for circadian disruption as a causative contributor to neurocognitive deficits.

Links between Circadian Disruption and Psychiatric Disorders: Unfortunate Side Effect or Contributing Factor?

One of the most common, and highly disruptive co-morbid problems in many psychiatric conditions, including depression, obsessive–compulsive disorder, and schizophrenia, is disruption in the sleep–wake cycle. However, there is ample debate if these effects are merely symptoms of these disorders, or in fact, if they may be contributing causes.

Depressive disorders are characterized by multiple physiological and psychological symptoms, and present with circadian disruption in both behavior and in physiology. The disruption of the circadian clock can manifest as changes in sleep–wake cycles (Van Cauter and Turek, 1986; Turek, 2007), but growing evidence also shows circadian disruption at the level of the molecular circadian clock (Mendlewicz, 2009). Recent findings show that intensity of major depressive symptoms in humans is correlated with the misalignment of circadian rhythms (Emens et al., 2009), in that more severe depressive states are associated with the circadian pacemaker being more delayed relative to the timing of sleep onset. Whether this is a causal change is still unclear, but shift workers often suffer from mood disturbances and an increased risk for depression (Scott et al., 1997; Asaoka et al., 2013). It is important to consider that links between circadian function and depression might occur at many levels (Wirz-Justice, 2009). An interesting example of this multi-level interaction is evident in the development and use of agomelatine, a melatonin agonist that also has serotonergic activity. This drug is actively being used for its antidepressant actions, with significant results (de Bodinat et al., 2010). It is thought that agomelatine can also act as a circadian “resynchronizer” in models of depression (Morley-Fletcher et al., 2011; Koresh et al., 2012; Mairesse et al., 2013). In human studies, it has been demonstrated that agomelatine can increase the relative amplitude of circadian rhythms in the rest–activity cycle, including effects on sleep, which was accompanied by parallel improvement in depressive symptoms (Kasper et al., 2010). When taken as a whole, these findings suggest that circadian disruption may contribute to depression, though unraveling the etiology from symptomology can be difficult. Given that changes in hippocampal neurogenesis are observed following chronic circadian disruption, and that cell birth and proliferation in the hippocampus is related to mood and antidepressant efficacy (Gibson et al., 2010), it is evident that circadian disruption may contribute to the development or exacerbation of depressive disorders. As yet, how these various pathways interact and synergize is unknown, though changes in multiple interacting physiological systems induced by chronic circadian dysfunction are likely to be a precipitating factor. Although it is clear that there is a strong relationship between circadian disruption and depression, these effects are likely bidirectional.

In addition to cognitive deficits and depression, circadian rhythm abnormalities have also been explored in mania. It is well established that during manic episodes, sleep patterns are significantly altered (Wehr et al., 1983; Plante and Winkelman, 2008; Robillard et al., 2013), and circadian patterns of several physiological functions are attenuated (Goetze and Tolle, 1987; Souetre et al., 1988; McClung, 2007). To probe potential causative links between disrupted circadian clocks and mania, animal models must be leveraged. Several lines of evidence demonstrate that treating hamsters with lithium chloride (a potent pharmacological agent used to treat manic depressive disorders) significantly lengthens the period of their circadian clock (Terao, 1992; LeSauter and Silver, 1993; Klemfuss and Kripke, 1995; Iwahana et al., 2007). Detailed molecular work has shown that lithium treatment can alter several intracellular signaling cascades, including glycogen synthase kinase-3beta, a link to the circadian molecular clockworks (Iwahana et al., 2004; Padiath et al., 2004; Iitaka et al., 2005; Ko et al., 2010; Lamont et al., 2010; Osland et al., 2011). These studies suggest that this pharmacological treatment can reduce the symptoms of mania while also having direct effects on the circadian clock at both the cell/molecular level and the behavioral level. More recent work has begun to explore how defects in several key clock genes affect behaviors in mouse (McClung, 2011, 2013). Mutations in the core clock gene Clock can lead to mania-like behaviors (Roybal et al., 2007), and site-specific knockdown of Clock in the VTA can induce similar manic-like behaviors (Mukherjee et al., 2010). Together, the human and non-human animal models provide strong evidence that circadian dysfunction is not only a component of some forms of mania, but that altering the function of the molecular circadian clock can mimic many of these effects.

While pathways linking disrupted circadian clocks to cognitive function, depression, and perhaps even mania are being more clearly elucidated, links between circadian abnormalities and schizophrenia are less clear, both at the epidemiological and mechanistic levels. One reason for this lack of clarity is that the cause of schizophrenia remains elusive, and is likely a result of a combination of genetic and experiential factors. However, there are lines of evidence that point to strong links between disrupted circadian clocks and schizophrenia (reviewed in Jamadar et al., 2013; Monti et al., 2013). Epidemiological studies show that fragmented circadian rhythms, as measured by changes in rest–activity cycles or in sleep regulation, are observed in schizophrenic patients (Wirz-Justice et al., 1997, 2001; Wulff et al., 2006, 2012; Pritchett et al., 2012). This includes both sleep onset and sleep maintenance insomnia. Correlations have also been observed between the phasing of the melatonin rhythm and sleep in schizophrenia, and are commonly observed in many schizophrenic patients (Mills et al., 1977; Rao et al., 1994; Wirz-Justice et al., 1997). It is interesting to note that in most cases, the sleep/circadian effects observed in schizophrenia are independent of either the course of the disease or the pharmacological status of the patient (Monti et al., 2013). Several animal models are now being applied to attempt to gain a mechanistic handle on the interaction between circadian timing and schizophrenia. The “blind-drunk” (Bdr) mouse line, which presents schizophrenic-like symptoms (Jeans et al., 2007), has been shown to have phase-advanced (i.e., earlier starting) rest–activity cycles while also showing a fragmentation of their circadian cycles (Oliver et al., 2012). The Bdr mouse carries a mutation in the gene for synaptosomal-associated protein (Snap)-25 that leads to disruption of exocytosis. This points to an association between altered synaptic activity and neurobehavioral function observed in schizophrenia-like models and circadian rhythms. However, this work should be interpreted cautiously, as the effects of this mutation on circadian rhythms may have little to do with the effects of the mutation on schizophrenia-like behavior. It is more likely that rather than directly causing schizophrenia, disruption of the circadian clock may somehow alter susceptibility in individuals at risk of developing schizophrenia. Work by Vacic et al. (2011) shows that in humans, a copy number variant in the gene encoding for the receptor for vasoactive intestinal polypeptide that is found in the SCN (i.e., Vipr2) can result in an increase risk of developing schizophrenia (Vacic et al., 2011). As such, there is compelling and somewhat provocative evidence that disruption of the circadian clock may not only be a symptom of schizophrenia, but perhaps a contributing cause.

Conclusion and Future Directions

The circadian timing system controls all physiological and behavioral rhythms, synchronizes them to the external environment, and ensures temporal isolation of incompatible physiological or behavioral processes (Kalsbeek et al., 2007; Karatsoreos and Silver, 2007; Butler et al., 2009). Thus, the circadian system sits at the center of a “web,” and can modulate the function of myriad physiological systems, both peripherally and centrally (Reppert and Weaver, 2002; Hastings et al., 2003). Since circadian rhythms are phylogenetically ancient, with many molecular components conserved between diverse species, from Drosophila to mouse to human (Bell-Pedersen et al., 2005), understanding how optimal functioning of this system contributes to fitness or vulnerability could have significant impact. That disrupted rhythms are observed in psychiatric conditions as diverse as depression, bipolar disorder, and schizophrenia (Mansour et al., 2005; Roybal et al., 2007; Mendlewicz, 2009; Cortesi et al., 2010; Sacco et al., 2010; Karatsoreos, 2012), makes it intriguing to hypothesize that they may play a role in their etiology. However, as this and many other reviews indicate, whether circadian disruption represents a symptom or an etiology is unclear, and the specific contributions of disrupted circadian rhythms to mental disease are poorly understood.

This review has presented several findings from both the human and non-human animal literature that support a role for disrupted circadian clocks in the etiology of mental disease. Since the causes of many of these neuropsychiatric disorders are multifaceted, it is unlikely that a single circadian mutation, or single instance of circadian disruption, would directly cause the development of a mental disorder. It is also important to note that while there is ample and growing evidence of a circadian contribution to many of the disorders discussed in this review, some of the evidence is indirect, and none of the evidence specifically obviates other causes for these neuropsychiatric diseases. It is our hope that this review provides an additional context to the already rich work on the genetic, developmental, and environmental etiologies of mental disorders. We hypothesize that disrupted circadian clocks may instead make individuals more susceptible to the development of neuropsychiatric disorders (Karatsoreos and McEwen, 2011, 2013). This effect may be in a manner similar to the stress-diathesis model, whereby environmental challenges have more severe outcomes due to underlying genetic or experiential differences (Morley, 1983). Thus, chronic circadian disruption through genetic abnormalities or environmental perturbation could make neural systems less able to cope with insults. This failure in resilience could lead to the onset of neuropsychiatric conditions in those individuals who are made more vulnerable because of other factors such as genetics, developmental experiences, or environmental exposures. While still conjecture, we feel that this is an exciting area for future research that will hopefully lead to great strides being made in understanding the complex causes of mental disorders.

Conflict of Interest Statement

The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

A note on my personal experience with circadian rhythm-related problems and bipolar disorder.

I was fortunate to be diagnosed in 1986 by a competent psychiatrist who had a “nuts & bolts” attitude toward medication. She prescribed lithium carbonate only; nothing else. She described its effects and side effects clearly, and explained that for the first three months or so my body would experience one or more adjustments as the dosage was increased to achieve therapeutic blood levels. This straightforward approach was excellent for an Asperger (although I wasn’t diagnosed at that time.) I had the facts and a timeline; yes there were side effects like tremors, rubbery legs, a bit of stomach irritation, but this did dissipate within a few months and were nothing in comparison with the total disruption and disaster in my life caused by bipolar disorder.

Within a few months lithium effectively transformed my ability to function, to travel, sleep normally, and endure reasonable stress. What was left to deal with was the toll taken by adapting over a lifetime to the chaotic and uncertain experiences of living with bipolar.

My point in relating this is that lithium carbonate has become “unpopular” in the arsenal of pharmacology. New concoctions of psychoactive drugs have made lithium “old-fashioned” and less profitable. A bipolar friend takes a $600.00 / month prescription, which he claims is of little help, but it’s paid for by insurance. In response, his psychiatrist just keeps adding more types of drugs. My lithium costs about $25.00 / month.

Lithium is one of a very few substances that can affect the circadian cycle in humans. (More about that later.) One reads often that a “replacement” for lithium is needed due to its terrible side effects, as if the new drugs being prescribed don’t have awful side affects. I think this is a red herring! I suspect that alongside the profit motive is plain old laziness on the part of prescribers who don’t want to take the time to work with patients to adjust lithium dosages. Over the nearly thirty years of taking lithium, I have had to fight with prescribers who rely on Big Pharm propaganda and simply would not accept that a “mental=stupid” patient could possibly know anything about how a medication works in her body. Several (I’ve moved around a lot) wanted to stop prescribing lithium in favor of “something new” even though lithium has worked successfully for so many years. I found these attempts to be  irresponsible and unethical – especially with the clutter of trinkets from Big Pharm cluttering their offices. It was as if the prescriber was trading my health and safety for a pizza and pen holder.

The poverty of the male imagination is astounding

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Men have ruled the world for millennia, but have they done a good job? Hardly: the results have been disastrous for the majority of human beings, and the future of Homo sapiens and millions of other species is bleak. The invention of increasingly destructive weapons, and the stubborn reliance on inefficient and toxic technologies, combined with the escalation of violence to a state of permanent and migrating global warfare, is not progress. Would women have done any better? How can we know? A crucial turn in the path toward the present ecological destruction of our planet is the male (delusion) of the overthrow of nature and the inextricably-linked diminution of women. Women’s contributions to the intellectual health of the species have been blocked by brutal means. Reduced to her biological functions, and labeled as categorically evil by the pathologic mind of archaic agricultural god-kings,  the female half of the species was reduced to perpetual slavery (juvenalization), no better in fact or treatment than a domesticated animal.

The rejection of female intelligence is possibly the most colossal act of stupidity in all human history.

Please refrain from commenting on my lack of femininity, my stupidity and my supposed hatred of men: obscenities are not new, intelligent or effective.

War is a social activity.

Conceptual Contamination / Paleoanthropology

I keep hammering away at “conceptual contamination” for a reason. Archaic Biblical notions are embedded in JudeoChristian cultures, never really go away, and wind up in the minds and works of scientists.

Most blatantly as:  Every ‘researcher’ gets to create one species in his/her own image. The goal of 4 billion years of evolution was to produce Homo sapiens sapiens, specifically EuroAmerican white males, as the perfect representation of God on Earth. And I’m not alone in being peevish.

It doesn’t have to be that way: Gregor Mendel, Geneticist and Augustinian Monk

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Anat Rec. 2002 Feb 15;269(1):50-66.

Morphology-based systematics (MBS) and problems with fossil hominoid and hominid systematics.

Author information

  • 1Division of Vertebrate Zoology, American Museum of Natural History, New York, NY 10024, USA. est@amnh.org

Abstract

The generalized/primitive nature of the hominoid dentition and often fragmentary nature of fossils, coupled with enthusiastic optimism for making revolutionary finds, has wreaked havoc with recognition of early human ancestors and reconstruction of fossil hominoid phylogeny. As such, the history of paleoanthropology is one of repeated misidentification of fossil ancestors and of occasional fraud. Although this history has led many workers to lose confidence in morphology based systematics (MBS), past and present misidentifications are actually due to a disregard of systematic methodology. Systematics depends on the continuity of life and gains its objectivity largely from the order alpha taxonomy imposes on morphologic discontinuities in closely related taxa (i.e., species and genera). Transformation of characters fixed in species into character complexes, as manifested in taxa nested at different levels of relationship, form the foundation for higher-level taxonomy and for phylogeny. Because in most cases, hominoid fossils are unable to provide the data needed to resolve alpha taxonomy, classification and phylogeny of fossil taxa must be guided by analogies to living taxa. Hominid and hominoid fossil taxonomy and phylogeny, however, has been based largely on pre-evolutionary notions and on misinterpretations of the polarity of assumed diagnostic characters. More often than not, fossils lack resolution for the taxonomic level or rank they are assigned to and taxa are erected without appropriate analogies to living forms. As such, phylogenies based on these classifications are unlikely to be correct. More in-depth anatomical studies that are in accordance with systematic methodology are likely to hold the key to correctly classifying fossils and unraveling hominoid and hominid phylogeny.

PMID: 11891624 [PubMed – indexed for MEDLINE] Full article available online

Warning: Psychological Gobbledygook

Empathy

Have you ever met someone who could actually do this? Hint: it’s describing telepathy or “mind reading.” Of course not – that person would have to have supernatural power. Note that there is no requirement for the person “performing empathy” to be in the presence of the subject – it should “work” across galaxies and even the Universe! What it does say is that using your intellect to understand people is “cheating.” Asperger individuals use our intellects, which according to psychological dogma is cheating; therefore, we are defective (we have an unfair advantage called a bull-shit detector) and are not quite human.

This is fiction, not non-fiction. Science is non-fiction, not fiction.

Yes, Deanna Troi was a Betazoid Empath, but she’s a fictional character. Perhaps today’s psychologists watched too many episodes of Star Trek Enterprise as kids!

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