Thursday, June 30, 2011

Neuro Celebrity Rehab

The Neurocritic will be gone for a two week stint in a rapid detox program at an undisclosed European location. Semi-regular posting will commence shortly thereafter.

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Tuesday, June 28, 2011

JAMA on 60s Psychedelic Drug Culture

An amusing semi-anthropological study was published in JAMA by Ludwig and Levine in 1965. It was based on extensive interviews with 27 "postnarcotic drug addict inpatients" who were treated at a hospital in Lexington, Kentucky. The specific drugs of interest included peyote (from the peyotl cactus plant), mescaline, LSD, and psilocybin. The current availability of each drug, most popular methods of intake, slang terms, psychoactive properties, and subcultural norms were discussed. Hallucinogens were sometimes combined with narcotics, barbituates, amphetamines, or marijuana, depending on the specific demographic group. Basically, there were the junkies, the potheads, and the psychonauts:
There appear to be three main patterns of hallucinogenic drug use. First, there are the people who are primarily and preferentially narcotic drug addicts who have used the hallucinogenic agents on one or several occasions mainly for "kicks" or "curiosity." They seldom seek these drugs and tend to use them infrequently, as for example when these agents come their way through a friend or at a party. Rarely do they take the hallucinogenic agent alone but tend to take it after a "fix" with heroin, hydromorphone hydrochloride, morphine, or some other narcotic drug to which they are addicted at the time.
The next group sounds like your everyday 1960s hippie stereotype:
Second, there are the group of people, aptly described by one of the informants as the "professional potheads," who have had extensive experience with various drugs. The most commonly used drug by this group of people is marijuana (hence the name "potheads"), but amphetamines and barbiturates are also popular. Many have had some experience with the narcotic drugs, but on the whole they tend to avoid the opiates. "Creative" and "arty" people, such as struggling actors, musicians, artists, writers, as well as the Greenwich Village type of "beatnik," tend to fall in this category. The "frustrated," "curious," "free thinkers," "nonconformists," and "young rebels," who are seeking a temporary escape also comprise this class of hallucinogenic users, according to our informants. Although the "professional potheads" enjoy the euphoric effects produced by smoking marijuana, they also tend to relish and seek out the feelings of greater insight, inspiration, and sensory stimulation and distortions which the hallucinogens may produce. They are in constant search of agents to rouse them from their apathy, to make life more meaningful, to overcome social inhibitions, and to facilitate meaningful conversations and interpersonal relationships.

Especially enjoyable was the description of the drug parties frequented by these types:
Hallucinogenic agents are used by these people mainly on weekends (often "four-day weekends") or on special occasions, such as parties. It is rare for users to take drugs alone. They are mainly taken with friends or at intimate gatherings of people. The parties are of all varieties. Frequently, little conversation takes place while people are under the influence of these drugs, but they claim to experience a greater closeness and rapport with the other members of the group. One patient described having attended "basket weaving" and "lampshade making" parties where all members, under the influence of these drugs, squatted on the floor and silently attended to their tasks. At another type of party, overt sexual activities were carried out. Folk singing was also common. To quote another patient, "Mostly the people sit around trying to dig each other . . . everybody is sitting around and waiting, like on New Year's Eve, for something to happen."

Finally were a small number of hard core exclusive users of hallucinogens in search of an expanded consciousness, whether it be religious, spiritual, or cosmic:
Third, there are a small number of people who take the hallucinogenic agents repeatedly over a sustained period of time to the exclusion of all other drugs. The frequency of drug use during these periods of time is variable. One patient took peyote four times a day over a two-year period, while another patient took it two out of every three days over a three-month period. One patient took mescaline every day for two separate 15-day periods, while another took mescaline every two to three days over a six-month period...

Generally, these patients seemed different from those in the second group, who primarily smoke marijuana. They did not take these drugs in a group for social purposes but used them mainly as a means of attaining some personal, esoteric goal. One patient talked of having achieved an increased sensitivity to nature and a greater insight into himself after prolonged peyote usage. While living by himself on Big Sur in California, he claimed to have achieved a "Christ-like state of mind" and a greater feeling of altruism. Another patient stated that as he kept taking mescaline, he was able to control his experience and attained a state of mind in which "every little thing is projected large," where he was able to see the negative and positive aspects of everything, and where "everything is real." A third patient, of Mexican extraction, kept taking peyote to "find God."

In the last several months, there have been a spate of articles on the return of psychedelics for psychotherapeutic purposes. Maia Szalavitz has covered some of the most recent developments: 'Magic Mushrooms' Can Improve Psychological Health Long Term and A Mystery Partly Solved: How the 'Club Drug' Ketamine Lifts Depression So Quickly.

Last year, a Neurocritic post (Ketamine for Depression: Yay or Neigh?) was part of a Nature Blog Focus on hallucinogenic drugs in medicine and mental health, inspired by the Nature Reviews Neuroscience paper, The neurobiology of psychedelic drugs: implications for the treatment of mood disorders, by Franz Vollenweider & Michael Kometer. For more information on this Blog Focus, see the Table of Contents.

The secret history of psychedelic psychiatry was discussed over at Neurophilosophy. Neuroskeptic covered Serotonin, Psychedelics and Depression while Mind Hacks provided a personal look at yagé in Visions of a psychedelic future.


LUDWIG AM, & LEVINE J (1965). PATTERNS OF HALLUCINOGENIC DRUG ABUSE. JAMA : the journal of the American Medical Association, 191, 92-6 PMID: 14233246

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Saturday, June 18, 2011

Could Anthony Weiner Ace the Stroop Test?

Former U.S. Representative Anthony Weiner served New York's 9th congressional district for 12 years until his online sexual indiscretions forced him to resign on June 16, 2011. We've all been overexposed [so to speak] to the "Weinergate" scandal, so no need to recount all the lurid details. Boxer briefly, he sent lewd photos of himself to young women and underaged girls following him on Twitter. This occurred despite the fact that Huma Abedin, Deputy Chief of Staff for Hillary Rodham Clinton and his wife of 2 years less than a year, was newly pregnant. Why would a high profile politician engage in such outrageous behavior?

What a silly question! Because he could! Because of his political power and a giant ego that needed massaging from pretty girls less than half his age. And because he thought he could get away with it. Ask Bill, Arnold, John, and Eliot. For more on this phenomenon, I recommend On the biology of sexting, a monograph at the blog Neurological Correlates.

Like many other public male figures who have fallen from grace due to their sexual activities, Weiner claimed to have checked into a treatment center to seek professional help for his ill-defined problems:
"Congressman Weiner departed this morning to seek professional treatment to focus on becoming a better husband and healthier person," Weiner's spokeswoman, Risa Heller, tells Us Weekly in a statement. "In light of that, he will request a short leave of absence from the House of Representatives so that he can get evaluated and map out a course of treatment to make himself well.
This was, of course, before his resignation. The New York Times went on to state:
Ms. Heller would not identify the facility or the precise kind of counseling Mr. Weiner, who has admitted having explicit communications with six women he met online, would receive...

. . .

Ms. Pelosi had hoped that the congressman would reach the decision on his own to go. In addition to her concerns about the political distraction Mr. Weiner had become, Ms. Pelosi concluded that his behavior required medical intervention.

“When you are this self-destructive, there is obviously something deeper going on with you,” said a Pelosi adviser who spoke on condition of anonymity for fear of being seen as betraying her confidence.
This brings us to the issue of "sexual addiction", or compulsive sexuality, or hypersexuality. Establishing an agreed-upon definition and proper diagnostic critieria for this condition is a minefield (compare Kafka 2010a, 2010b and Levine, 2010). For the present blog post, I will present the view of Reid et al. (2011) from their paper on A Surprising Finding Related to Executive Control in a Patient Sample of Hypersexual Men:
The proposed diagnostic criteria for the DSM-V characterize hypersexual disorder (HD) as a repetitive and intense preoccupation with sexual fantasies, urges, and behaviors, leading to adverse consequences and clinically significant distress or impairment in social, occupational, or other important areas of functioning. One defining feature of this proposed disorder includes multiple unsuccessful attempts to control or diminish the amount of time the individual engages in sexual fantasies, urges, and behavior in response to dysphoric mood states or stressful life events. Despite a constellation of studies investigating characteristics of HD (usually defined in the literature as sexual addiction, sexual compulsivity, or hypersexual behavior), little is known about the neuropsychological correlates of this phenomenon, including possible associations with executive functioning.
Executive functions are a series of high-level cognitive processes that allow for the flexible control of thought and adaptive behavior. They include processes such as planning, decision making, multitasking, task switching, and impulse control. One might expect that executive functions (or at least some of them) would be impaired in those who show problematic hypersexual behavior. For example, although Weiner may be witty and reasonably intelligent, his apparent narcissism, poor impulse control, and terrible decision making abilities in the sexting realm proved to be his downfall.

Anthony Weiner's comedy routine at the Congressional Correspondent's Dinner, March 30, 2011.

  • Ambitions to run for mayor of NY
  • Weiner jokes
  • Praises his lovely wife - "opposites attract"
  • Outlines his use of social media, including Twitter
  • Follow me @RepWeiner! (18,000 followers at that time, now over 83,000)
  • Named to Time's 140 Best Twitter Feeds

To jump to the conclusion, the study of Reid et al. (2011) was surprising because the executive function scores of 30 men diagnosed with HD were the same as a group of 30 male volunteers without HD. All participants were administered a series of standardized neuropsychological tests that included the Stroop Color-Word Interference Test (shown above in Weiner's thought bubble), the Wisconsin Card Sorting Test (WCST), the Trail Making Test, and the Verbal Fluency Test. All of these tasks involve planning or overcoming automatic responses.

In the Stroop task, the participant is instructed to say the font color and ignore the word. It's much more automatic to read the word than to say the font color, so people are slower to respond when the two dimensions are in conflict:

Trail Making version B is an attention switching task where the participant connects the dots on the sheet below by alternating between letters and numbers: 1-A-2-B-3-C, etc.

Before we examine the authors' interpretation of this interesting null effect, let's take a closer look at some of the defining characteristics of the HD group. The majority of the patients were men seeking treatment for hypersexual behavior at clinics in Los Angeles (a few were from Utah). All participants were carefully screened to exclude those with history of a head injury, stroke, alcohol or drug abuse, and any other neurological or psychiatric condition (including ADHD).
In the clinical interview, participants were asked about the degree to which they use sex to cope with stress or uncomfortable emotions, consequences they have experienced as a result of their sexual choices, and ways in which they may have felt unable to control their sexual behavior. For patients referred for the hypersexual group, classification as such was verified based on elevated scores on the hypersexuality measures and (i) a reported pattern of hypersexual behavior that persisted for at least 6 months; (ii) reported preoccupation with sexual thoughts, urges, and the pursuit of sexual activities that interfered with at least two aspects of their daily life (e.g., academic or scholastic goals, work, parenting); and (iii) reported experiencing at least one significant consequence (e.g., contraction of a sexually transmitted disease [STD], loss of employment, debt, arrest, relational discord) as a result of their sexual behavior.

The controls were fairly well-matched to the patient group on all variables except their sexual behavior. Why were there no differences in neuropsychological test performance between the two groups? One of the most plausible reasons was context. The patients did not have to demonstrate restraint in tests involving pornographic images, internet use, or access to sex partners.
There are a number of potential explanations as to why executive deficits did not emerge among the patient sample in this study despite a pattern of impulsive and risky sexual behavior. First, difficulties in executive functioning of a magnitude that would show up on performance-based measures may be present in only a subset of hypersexual patients... Second, it is possible that the neuropsychological tests of executive functions were not sensitive to detect subtle deficits that may have existed in the patient sample. Third, it may be that hypersexual men may exhibit impaired judgment, difficulty with impulse control, and cognitive rigidity but only in situations where they encounter opportunities for sex. ... In other words, hypersexual men may indeed exhibit impaired judgment, difficulty with impulse control, cognitive rigidity, and so forth only in situations where they encounter opportunities for sex or are exposed to specific cues that have been paired with sex.
In other words, the hypersexual participants might have had more difficulty on the Sex Stroop task:



Perhaps I can go into the business of designing customized neuropsychological tests of executive functions for use on VH1 reality shows like Sex Rehab with Dr. Drew...


Kafka MP. (2010a). Hypersexual disorder: a proposed diagnosis for DSM-V. Arch Sex Behav. 39:377-400.

Kafka MP. (2010b). "What is sexual addiction?" A response to Stephen Levine. J Sex Marital Ther. 36:276-81.

Levine SB. (2010). What is sexual addiction? J Sex Marital Ther. 36:261-75.

Reid, R., Garos, S., Carpenter, B., & Coleman, E. (2011). A Surprising Finding Related to Executive Control in a Patient Sample of Hypersexual Men. The Journal of Sexual Medicine DOI: 10.1111/j.1743-6109.2011.02314.x

Anthony Weiner's resignation speech.

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Sunday, June 12, 2011

Akiskal and the Bipolar Spectrum

In the last post, we learned that the Editor-in-Chief of the Journal of Affective Disorders has published 165 papers in the journal, 155 of these since becoming editor in 1996. Excluding commentaries and editorials, that makes for a grand total of 142 articles thus far during his tenure as editor.

The two major themes of Dr. Hagop Akiskal's papers are (1) the bipolar spectrum, and (2) temperament as the basis of mood, behavior and personality (e.g., Lara et al., 2006). Clearly, I cannot begin to summarize the content of these papers, but I will give some background material on the bipolar spectrum and "soft" bipolar (Akiskal & Pinto, 1999 - not published in JAD).

Bipolar disorder, one of the most serious mental illnesses, is marked by periodic bouts of depression and mania (Bipolar I) or by depression and hypomania (Bipolar II). Given that depression often presents as the initial polarity, bipolar is frequently misdiagnosed as major depressive disorder (MDD), with disastrous consequences.1 The rigid categories of DSM-IV, however, may not capture everyone who displays clinically significant symptoms of bipolar disorder. Ghaemi et al. (2002) have noted that:
...limitations of the DSM-IV nosology may impede the diagnosis of BD, because the DSM-IV has rather broad criteria for MDD and narrow criteria for BD.
According to Akiskal and Pinto, the evolving bipolar spectrum (circa 1999) includes:



BIPOLAR II½: CYCLOTHYMIC DEPRESSIONS [often labeled as borderline personality disorder]



BIPOLAR IV: HYPERTHYMIC DEPRESSION - "patients with clinical depression that occurs later in life and superimposed on a lifelong hyperthymic temperament."
Each of the diagnostic categories was illustrated by a clinical case report. Cyclothymia is included in DSM-IV: "A history of hypomanic episodes with periods of depression that do not meet criteria for major depressive episodes. There is a low-grade cycling of mood which appears to the observer as a personality trait, and interferes with functioning." Hyperthymia, however, is not a diagnosis but an affective temperament "characterized by exuberant, upbeat, overenergetic, and overconfident lifelong traits." More specifically (Akiskal & Pinto, 1999):
The attributes of a hyperthymic temperament are not episode-bound and constitute part of the habitual long-term functioning of the individual. Patients are typically men in their 50s whose lifelong drive, ambition, high energy, confidence, and extroverted interpersonal skills helped them to advance in life, to achieve successes in a variety of business domains or political life.
Arnold Schwarzenegger comes to mind [if he had started having depressive episodes several years ago]. In fact, the case study of bipolar IV was presented as a highly successful, 53 year old married lawyer with three other families in different countries.

Do powerful, philandering, middle-aged men who become depressed in their 50s really need their own special diagnosis??

There are critics, of course... In his critique of the spectrum, Paris (2009) called it "bipolar imperialism" and said: "Until further research clarifies the boundaries of bipolarity, we should be conservative about extending its scope." It seems that no one is safe any more. Recurrent depression? Bipolar. Anxious and depressed? Most certainly bipolar.

But the worst frontier of all has to be Bipolar Type VI: Dementia (Ng et al., 2008). This paper presents "selected" case histories of 10 elderly patients from the California/Mexico border and Brazil. These patients presented with "late-onset mood and related behavioral symptomatology and cognitive decline without past history of clear-cut bipolar disorder." In other words: dementia (caused by neurodegenerative disease), with classic symptoms such as:
  • Having hallucinations, arguments, striking out, and violent behavior

  • Having delusions, depression, agitation

Are we surprised that mood stabilizers and atypical antipsychotics were said to be beneficial??

click on image for a larger view

Adapted from Table 1 (Ng et al., 2008). Clinical features and response to treatment in elderly patients with bipolar disorder type VI. [NOTE from The Neurocritic: atypical antipsychotics are in red, mood stabilizers are in blue.]

Cases 1-5 are poor elderly Latino patients attending an adult day treatment center, and cases 6-10 are from private practice in a more affluent area of Brazil. Galantamine, donepezil, and rivastigmine are acetylcholinesterase inhibitors typically used to treat Alzheimer's disease [with limited effectiveness], while memantine blocks NMDA glutamate receptors. So why would the authors claim that the mood and behavioral problems had anything to do with bipolar disorder?

Omitted from Table 1 (for space reasons and ease of presentation) are columns for premorbid temperament (as judged by family members) and family history. The temperaments were mostly cyclothymic or hyperthymic. Family histories included none (n=3), mood & anxiety (n=2), alcohol (n=2), and bipolar disorder (n=3). OK then, only 3 of the 10 patients had a family history of bipolar disorder. Again, what's the rationale for creating the new category of "bipolar type VI"?
We present our perspective as an alternative to the more commonly held clinical–neurological view that agitation, impulsivity and related mood instability in Alzheimer's and other dementia patients merely represents frontal lobe dysfunction (Senanarong et al., 2004). A more sophisticated view in the literature argues that behavioral–cognitive syndrome in Alzheimer's disease is a prodromal stage, whereas in fronto-temperal dementia the behavioral disorder appears when the cognitive deficit is relatively mild (Jenner et al., 2006). Our perspective, while ostensibly recognizing the dementia setting postulates the possible contribution of pre-existing familial and/or temperamental diathesis for bipolarity in patients presenting with dementia-like clinical pictures with marked mood and behavioral disturbances.
Are they grasping at straws to justify prescribing mood stabilizers and atypical antipsychotics to these patients, perhaps? Let's look at the declared Conflicts of Interest of the senior author on this paper:
Dr. Akiskal is on the US GSK Advisory Board, Abbott's Latin American Bipolar Advisory Board, and International Advisor to Sanofi-Aventis. He has received honoraria for lectures from these companies, as well as from Lilly.
Branded formulations of generic valproic acid, one of the most common mood stabilizers, include:
  • Depakene (Abbott Laboratories in U.S. & Canada)
  • Depakine (Sanofi Aventis French)
  • Depakine (Sanofi Synthelabo Romania)
  • Deprakine (Sanofi Aventis Finland)
  • Epival (Abbott Laboratories U.S. & Canada)
  • Epilim (Sanofi Synthelabo Australia)
  • Valcote (Abbott Laboratories Argentina)
GSK products include two other mood stabilizers, Lamictal (lamotrigine, given to six of the patients) and Keppra (levetiracetam). Besides the antidepressants Prozac and Cymbalta, which are thought to be bad for bipolar spectrum patients, Lilly manufactures Zyprexa (olanazpine), the atypical prescribed to three of the patients.

However, it appears that all Conflicts of Interest might not have been declared in the JAD paper. Three additional pharmaceutical companies were mentioned in a 2010 American Journal of Psychiatry article:
Dr. Akiskal has served on speakers or advisory boards for Abbott, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, and Janssen.
AstraZeneca makes Seroquel (quetiapine), an atypical prescribed to five patients, Bristol-Myers Squibb makes Abilify (aripiprazole), an atypical that was not given to any of the patients, and Janssen's products include Risperdal (risperidone), an atypical prescribed to one patient.

For a summary of the well-publicized scandal that atypical antipsychotics are overprescribed to elderly patients as a means of behavioral control, see Drugging the Vulnerable: Atypical Antipsychotics in Children and the Elderly:
In nursing homes, 14% of residents have been given at least one prescription for a second-generation antipsychotic, according to a government investigation. A full 88% of these prescriptions are given to people with dementia, despite the fact that these drugs may double the risk of death in these patients (there is a black box warning on the drug to this effect). The investigation estimated that $116 million Medicare dollars have been spent filling antipsychotic prescriptions that never should have been written.
If these elderly patients were diagnosed with the official label of Bipolar Disorder Type VI, then the prescriptions could potentially be justified, and an old discredited market becomes new once again.


1 Antidepressants can trigger mania or hypomania.


Akiskal, H.; Pinto, O. (1999). THE EVOLVING BIPOLAR SPECTRUM Prototypes I, II, III, and IV. Psychiatric Clinics of North America, 22 (3), 517-534 DOI: 10.1016/S0193-953X(05)70093-9

Ghaemi SN, Ko JY, Goodwin FK. (2002). "Cade's disease" and beyond: misdiagnosis, antidepressant use, and a proposed definition for bipolar spectrum disorder. Can J Psychiatry 47:125-34.

Lara DR, Pinto O, Akiskal K, Akiskal HS. (2006). Toward an integrative model of the spectrum of mood, behavioral and personality disorders based on fear and anger traits: I. Clinical implications. J Affect Disord. 94(1-3):67-87.

Ng, B., Camacho, A., Lara, D., Brunstein, M., Pinto, O., & Akiskal, H. (2008). A case series on the hypothesized connection between dementia and bipolar spectrum disorders: Bipolar type VI? Journal of Affective Disorders, 107 (1-3), 307-315 DOI: 10.1016/j.jad.2007.08.018

Paris J. (2009). The bipolar spectrum: a critical perspective. Harv Rev Psychiatry 17:206-13.

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