Friday, November 30, 2018

Depression treatments: The effects are probably overestimated, relapse rates for patients who respond are very high (about 50% over 2 years), there is little evidence for long-term effectiveness, & there are the problems of publication bias, sponsorship bias, & others

The Challenges of Improving Treatments for Depression. Pim Cuijpers. JAMA. Published online November 30, 2018. doi:10.1001/jama.2018.17824

In the past few decades substantial progress has been made in the research and development of treatments for major depression. Many different types of medications and psychotherapy are currently available and rigorous studies have shown that antidepressants are more effective than placebo,1 and several types of psychotherapies are more effective than waiting list or other controls.2 These findings suggest that many patients with depression can be successfully treated. Based on these significant and positive effects, many of these treatments are included in treatment guidelines and are widely used in clinical practice. However, not all patients with depression recover with available treatments and several important challenges need to be resolved to improve existing treatments and to increase the number of patients who benefit from them.
Spontaneous Recovery and Placebo Effects

An important challenge is the high rates of spontaneous response and placebo effects. More than half of patients who receive antidepressants or psychotherapy respond to treatment. However, response rates are also high when patients receive placebo or no treatment. In a meta-analysis that included 44 240 patients from 177 studies, 54% of patients responded to antidepressants, whereas 38% responded to placebo.3 Comparable numbers have been reported for psychotherapies with response rates of 54% compared with response rates of 41% across control conditions.4 Patients with depression who do not seek care show comparable response rates. These findings differ when other outcomes, such as remission or significant clinical change, are used. That does not, however, change the basic challenge that a substantial proportion of patients who improve with medication or psychotherapy would have recovered without treatment or with placebo. This poses substantial challenges for investigators and clinicians.

Individuals who respond to medication will probably continue to use them for at least several months, even with the risk of adverse effects. Patients who respond to psychotherapy invest many hours and make considerable efforts during their treatment. For a majority of patients who respond to treatment, the potential adverse effects of medications and the time investment in psychotherapy might not be necessary to get better. However, it is not possible yet to predict which patients will recover spontaneously or will respond to placebo, although innovative machine learning techniques and other biological markers may be helpful in the future.

Spontaneous recovery also complicates the validity of clinical knowledge as well as research about treatments. Because many patients recover while receiving treatment, clinicians and patients are inclined to think that the treatment is what made them better. However, because many patients also would have recovered without treatment, clinical judgements are not necessarily related to treatment effect.


In contrast to response to drug or placebo, a considerable group of patients are difficult to treat or do not respond to treatment. Although patients may respond to another drug after failure to respond to an initially prescribed drug, the chance of successful response is almost halved with every new treatment tried.5 Even after trying several different treatments, a substantial proportion of patients do not respond. One estimate suggests that approximately 30% of patients with depressive disorders have a chronic course with limited response to treatment.6

Another challenge is that the effects of treatment are probably overestimated. The relapse rates for patients who respond are very high (estimated at about 50% over 2 years),7 there is limited evidence for long-term effectiveness, and there are the problems of publication bias, sponsorship bias, and other sources of bias. Clinicians may have an optimistic view that these problems have little influence on outcomes or have a pessimistic view that no relevant treatment effect remains. In reality, the extent to which these factors affect outcomes is unknown.

How to Improve Treatments?

Worldwide, an estimated 330 million people have depression, which is linked with considerably diminished role functioning and quality of life, medical comorbidity, excess mortality, and high economic costs.8 Thus, addressing current therapeutic challenges and improving available treatments are critically important, regardless of the true effects of these treatments. How can this be done?

Additional research on the causes and etiological processes leading to depression is needed. The focus should be on which patients will respond to treatment, which could lead to the development of better and more targeted treatments for specific groups of patients. This may result in new approaches for preventing depression. However, this will take time and long-term investments.

A straightforward approach in the short-term is to develop treatments that are more effective than the current ones in acute phase depression. However, many drugs and psychotherapies have been developed over the past decades, and there is little evidence that one drug or psychotherapy is substantially more effective than the others. It is therefore unlikely that newly developed drugs and therapies will be substantially better than the ones that are currently available.

A potentially viable approach with respect to spontaneous recovery is to minimize treatments and reduce unnecessary resource use because many patients with depression will recover spontaneously, regardless of treatment. Clinicians already use a “watchful waiting” approach, by encouraging patients to wait before starting a treatment. Another option is to offer internet-based or other self-help interventions that involve no or minimal support from professionals, preferably in stepped-care models allowing patients who do not respond to these interventions to step up to more intensive treatment. Considerable evidence indicates that these internet-based interventions are effective and require less resources.9 Another option may be to clearly explain to patients what the chance for recovery is from treatment, from placebo, or from no treatment. This may stimulate patients with milder disorders to wait before starting treatment, whereas patients with severe disorders will probably prefer to initiate treatment.

There are also several priorities for patients with depression who have high relapse rates or those who do not respond to treatments. One important priority is to further examine relapse prevention. In routine practice, this often consists of maintenance treatment with drugs. However, convincing evidence indicates that psychological interventions can reduce relapse rates considerably, although these interventions are seldom implemented in routine care.

Another priority is to increase research on the treatment of chronic and resistant depression. Fortunately, these conditions are increasingly the focus of drug trials, and some promising new medications are being tested, such as ketamine.10 However, few psychological treatments are available that are specifically designed for chronic depression. The development of such therapies should have more priority than developing new therapies for acute depression that almost certainly will show comparable effects as already existing treatments.

Answering the Challenge

Evidence-based treatments can make a substantial difference in the lives of many patients. Nevertheless, for patients with depression many do not benefit from treatment, and some only partially benefit or only experience short-term improvement. Furthermore, a considerable group of treated patients would have also recovered without treatment. The group of patients in between these extremes are the ones who currently benefit from available treatments, but they are still a minority of all patients. Because of the public health effects of depression and the enormous related adverse effects on the quality of life of patients, it should be a priority to search for methods to increase the number of patients who benefit from treatment and in this way reduce the burden of depression.

Corresponding Author: Pim Cuijpers, PhD, Department of Clinical, Neuro and Developmental Psychology, Amsterdam Public Health Research Institute, Vrije Universiteit Amsterdam, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands

Conflict of Interest Disclosures: No disclosures were reported.

Cipriani  A, Furukawa  TA, Salanti  G,  et al.  Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.  Lancet. 2018;391(10128):1357-1366. doi:10.1016/S0140-6736(17)32802-7
Barth  J, Munder  T, Gerger  H,  et al.  Comparative efficacy of seven psychotherapeutic interventions for patients with depression: a network meta-analysis.  PLoS Med. 2013;10(5):e1001454. doi:10.1371/journal.pmed.1001454
Levkovitz  Y, Tedeschini  E, Papakostas  GI.  Efficacy of antidepressants for dysthymia: a meta-analysis of placebo-controlled randomized trials.  J Clin Psychiatry. 2011;72(4):509-514. doi:10.4088/JCP.09m05949blu4.
Cuijpers  P, Karyotaki  E, Weitz  E, Andersson  G, Hollon  SD, van Straten  A.  The effects of psychotherapies for major depression in adults on remission, recovery and improvement: a meta-analysis.  J Affect Disord. 2014;159:118-126. doi:10.1016/j.jad.2014.02.026
Rush  AJ, Trivedi  MH, Wisniewski  SR,  et al.  Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.  Am J Psychiatry. 2006;163(11):1905-1917. doi:10.1176/ajp.2006.163.11.1905
Murphy  JA, Byrne  GJ.  Prevalence and correlates of the proposed DSM-5 diagnosis of chronic depressive disorder.  J Affect Disord. 2012;139(2):172-180. doi:10.1016/j.jad.2012.01.033
Vittengl  JR, Clark  LA, Dunn  TW, Jarrett  RB.  Reducing relapse and recurrence in unipolar depression: a comparative meta-analysis of cognitive-behavioral therapy’s effects.  J Consult Clin Psychol. 2007;75(3):475-488. doi:10.1037/0022-006X.75.3.475
Bloom  DE, Cafiero  E, Jané-Llopis  E,  et al. The global economic burden of noncommunicable diseases. Geneva, Switzerland: World Economic Forum. Published September 2011. Accessed November 18, 2018.
Andrews  G, Basu  A, Cuijpers  P,  et al.  Computer therapy for the anxiety and depression disorders is effective, acceptable and practical health care: an updated meta-analysis.  J Anxiety Disord. 2018;55:70-78. doi:10.1016/j.janxdis.2018.01.00110.
Wilkinson  ST, Sanacora  G.  Considerations on the off-label use of ketamine as a treatment for mood disorders.  JAMA. 2017;318(9):793-794. doi:10.1001/jama.2017.10697

The article thus challenges the general notion that ‘terrorism always ends’; only certain types of jihadists will end, while others—such as al-Qaida & Islamic State—may survive indefinitely

Jihadism after the ‘Caliphate’: towards a new typology. Anne Stenersen. British Journal of Middle Eastern Studies,

ABSTRACT: The rise of the Islamic State in Iraq and Syria, and its subsequent split with al-Qaida in 2014, revealed there is still much we do not know about jihadism. Existing typologies of Islamism describe jihadism as a unitary phenomenon, characterized by a preference for violence over other methods for political change. This article presents a more fine-grained typology of jihadism that captures the core divisionary issues within the jihadist current. It argues that jihadist groups can be classified along two scales: the ‘takfirism’ scale defines how the group relates to society, and it runs from integration at one end, to separation on the other. The ‘pan-Islamism’ scale defines what the group fights for, and it runs from ethnic homeland on one end to umma on the other. The main argument is that jihadist groups ensure their survival by shifting their position along the scales—either by becoming less takfiri or more pan-Islamist. The article thus challenges the general notion that ‘terrorism always ends’. Only certain types of jihadists will end, while others—such as al-Qaida and Islamic State—may survive indefinitely.

Is creativity, hands-on modeling and cognitive learning gender-dependent?

Is creativity, hands-on modeling and cognitive learning gender-dependent? Julia Mierdel, Franz X. Bogner. Thinking Skills and Creativity, Volume 31, March 2019, Pages 91-102.

•    Combining hands-on modeling with experimentation is successful.
•    The model quality is not influenced by students’ individual creativity levels.
•    Girls produced significantly better structured DNA-models.
•    ‘Flow’ experiences and model quality are related with girls’ cognitive achievement.

Abstract: Modeling plays a key role in science research and education is considered to increase comprehensibility of abstract concepts and processes. Especially hands-on experiences in authentic learning environments offer students the opportunity to feel like real researchers and support the development of problem-based thinking skills. In our study, we applied an inquiry-based, out-of-school laboratory module that uses classic experimental challenges as well as innovative model-supported teaching to promote cognitive achievement. Our hands-on module was designed for 9th graders and combined experimentation and creative model work to visualize molecular and otherwise invisible contents of DNA-structure. After mental modeling, participants (N = 114; 40.87% female) produced a physical DNA-model using handcrafting materials. Our major aims were to evaluate the model qualities and to monitor potential relationships between successful model elaboration, individual creativity and knowledge levels. Therefore, we correlated students’ creativity levels with model quality scores as well as with cognitive achievement. While no relations were found for creativity and model elaboration further results were gender-dependent. Girls produced significantly higher model quality scores and significant positive correlations were revealed between short-term and mid-term knowledge levels. Correlations also were observed between girls’ cognitive achievement and the creativity subscale ‘flow’. In contrast, neither creativity nor model quality were decisive for boys cognitive achievement. Their average simpler modeling results did not correlate with the short-term and mid-term knowledge levels, although they achieved similar scores on both. Model elaboration seemingly provides more support for girls and offers a suitable approach for emphasizing creativity in science education. In attempting to attract girls to scientific ideas, creative modeling may further support hands-on experimentation.

Animated Disney female characters that exhibit low WHRs should be perceived as good; lower waist-to-hip ratio is more commonly associated with Disney princesses than Disney female villains

Aung, T., & Williams, L. (2018). Mirror, mirror on the wall: Whose figure is the fairest of them all? Evolutionary Behavioral Sciences,

Abstract: Although the “what is beautiful is good” phenomenon has been examined in animated Disney movies, studies have not investigated what makes a particular Disney princess more beautiful than the others. In our study, we further investigated what makes a particular Disney female character (n = 20) beautiful by measuring and analyzing their waist-to-hip ratios (WHRs). From evolutionary perspectives, lower WHRs in women signal high reproductive potential, and are attractive to men and ideal for women. Thus, we expected that animated Disney female characters that exhibit low WHRs should be perceived as good. Our analyses suggest that lower WHR is more commonly associated with Disney princesses than Disney female villains. In addition, we found that WHRs of Disney princesses (Mdn = 0.50, range = 0.31–0.69) were less varied than those of the villains (Mdn = 0.66, range = 0.47–1.29), suggesting that the “what is beautiful is good” stereotype is strongly reflected in the smaller WHRs of Disney princesses.

Some articles on psychology of animals

The mating preferences of female fruitflies are strongly influenced by the existing preferences they observe in other females, generating traditions that are repeatedly passed on to others and spread in the population
The intense selection of chickens for production traits (egg laying) is thought to cause undesirable side effects & changes in behavior due to trade-offs from energy expenditure; contrary to expectations, productive hens show increased cognitive skills

Males reversed their initial preference for larger females in the presence of a conspecific audience male because they recognized the audience male as a competitor and tried to deceive that male about their real mating preference
A female fish that today doesn't need males to clone itself copulates with other species' males to stimulate embryonic development. Those males do that probably because the interactions of a sexual male and the female are observed by conspecific females and make that male more attractive
Sumatran orangutan mothers suppressed alarm calls up to 20 min until the model was out of sight in function of perceived danger for themselves & for an infant, suggesting high-order cognition
Chimpanzees appear to perceive similarity in primate faces in a similar way to humans. Information about perceptual similarity is likely prioritized over the potential influence of previous experience
Is birth attendance a uniquely human feature? New evidence suggests that Bonobo females protect and support the parturient
Prolonged transport and cannibalism of mummified infant remains by a Tonkean macaque mother

From 2017: Exceptionalism is not exceptional in relation to sexual and reproduction mechanisms — Contrasts of human and animal sexuality

Exceptionalism is not exceptional in relation to sexual and reproduction mechanisms: Contrasts of human and animal sexuality. Roy J. Levin. Clin. Anat. 30:940–945, 2017.

Abstract: Speculation that the release of oxytocin by orgasm in the human female during coitus facilitates fertility by enhancing uterine sperm transport has been criticized as having no unequivocal empirical human evidence. However, a counter claim that this supports human “exceptionalism” as some form of uterine sperm transport occurs in other species. This is a misconception as it ignores that human uterine peristalsis, powered by contractions of the smooth muscle of the archimyometrium, facilitates sperm transport even without any systemic oxytocin involvement. Moreover, examination of various unique reproductive mechanisms in numerous animals also indicates that the claim is misjudged and rests on a biased interpretation of what “exceptionalism” means in this biological context. Ten chosen aspects of our sexuality are presented as being exceptional to humans.

From 2013: Sexual Wiring of Women's Breasts — Neuroscientists establish breasts as sexual organs

Sexual Wiring of Women's Breasts. Nigel Barber. Psychology Today, May 07, 2013.

Neuroscientists establish breasts as sexual organs

Excerpts (full text with links in the link above):

If men have sex on the brain, they are not alone. Recent research found that women’s sensory cortex has three distinct areas corresponding to stimulation of the clitoris, vagina, and cervix (1). To their surprise, researchers found that self stimulation of the nipples lights up the same areas. This sheds further light on the sexual importance of breasts.

In an earlier post, I discussed some evolutionary reasons that men are fascinated by women’s breasts and pointed out that stimulation of the breast plays a key role in women’s sexual arousal and satisfaction.

The Background

The permanently enlarged human breast is a peculiarity of our species (2). It may have some signal value in communicating fertility and plays a role in physical attractiveness.

Breasts are less eroticized in subsistence societies where women go topless than in our own where they are exploited in advertising, and in pornography. Even in subsistence societies, breasts are not entirely lacking in sexual significance and are generally stimulated in foreplay according to ethnographic accounts (3).

Moreover, the breasts play a key role in female sexual arousal and we are beginning to understand why in terms of hormones and neuroscience. In their classic report on the female sexual response, Masters and Johnson (4) pointed out that breast volume increases during sexual arousal in addition to changes in the areola and erection of the nipples.

The breast and bonding

The function of the breast in sexual behavior is sometimes attributed to face-to-face copulation that is unusual amongst mammals. If the breast is already used for mother- infant bonding, the argument goes, then it is a small step for it to be used in facilitating bonding between lovers. After all, it is in easy reach!

Stimulation of the nipple during breast feeding increases the amount of the hormone oxytocin that circulates. Oxytocin is often referred to as the “cuddling hormone” because it is released by male and female mammals during close social encounters of various kinds (5).

In addition to its general social effects, whereby a mother feels closeness for the baby she is feeding (and vice versa), there are other more specialized functions of oxytocin. One is that milk flows, a reflex known as the “milk let-down response” familiar to mothers and dairy farmers alike.

Another is sexual arousal, and orgasm. Some women experiencing intense pleasure - even orgasm - from breast feeding. This phenomenon was long written off as a mere oddity but neuroscientists are beginning to understand why it happens.

Sexual wiring of women’s brains

The great complexity of the female sexual response may be attributable to the fact that there is not one, but three sensory maps in the parietal cortex that light up in functional MRI images when the genitals are (self) stimulated. One represents the clitoris, another the vagina and the third represents the cervix.

All three of these maps also receive input when the nipple is stimulated. From a functional perspective, this means that the breast doubles as a truly sexual organ. It is not just an exciting visual stimulus for (most) men but also a key source of sexual pleasure for most women.

As to the wiring of men’s nipples the jury is out. Some men’s nipples are also responsive to sexual stimulation but the brain response has yet to be mapped.


1. Komisaruk, B. R., et al. (2011). Women’s clitoris, vagina, and cervix mapped on the sensory cortex: fMRI evidence. The Journal of Sexual Medicine, 8, 2822-2830.

2. Barber, N. (1995). The evolutionary psychology of physical attractiveness: Sexual selection and human morphology. Ethology and Sociobiology, 16, 395-424.

3. Ford, C. S., & Beach, F. A. (1951). Patterns of sexual behavior. New York: Harper.

4. Masters, W. H., & Johnson, V. E. (1966). Human sexual response. Boston: Little Brown.

5. Uvnas-Moberg, K. (1998). Oxytocin may mediate the benefits of positive social interaction and emotions. Psychoneuroendocrinology 23: 819-835.

Nigel Barber, Ph.D., is an evolutionary psychologist as well as the author of Why Parents Matter and The Science of Romance, among other books.

The mating preferences of female fruitflies are strongly influenced by the existing preferences they observe in other females, generating traditions that are repeatedly passed on to others and spread in the population

Culture and conformity shape fruitfly mating. Andrew Whiten et al. Science Vol. 362, Issue 6418, pp. 998-999. DOI: 10.1126/science.aav5674

Summary: Culture pervades every aspect of human lives, its achievements providing a compelling explanation for our species' domination of the planet (1). Defined as the matrix of traditions built by previous generations and inherited by social learning, culture was long thought to be uniquely human. In recent decades, however, mounting evidence for culture defined in this way has accumulated for numerous vertebrate species and an expanding diversity of behaviors (2). Examples include migratory knowledge in bighorn sheep (3); foraging techniques in humpback whales (4), great tits (5), and bumble bees (6); and tool use in apes (2). These discoveries suggest that although human culture has developed unprecedented complexities, it evolved from more elementary forms shared with other species. On page 1025 of this issue, Danchin et al. (7) offer evidence that a species that may surprise many should be added to this growing animal “culture club”: the humble fruitfly. They show that the mating preferences of female fruitflies are strongly influenced by the existing preferences they observe in other females, generating traditions that are repeatedly passed on to others and spread in the population. Animal culture may be a much more widespread phenomenon than hitherto acknowledged.