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Sunday, April 5, 2015

VSEPR theory


From Wikipedia, the free encyclopedia

Valence shell electron pair repulsion (VSEPR) theory is a model used, in chemistry, to predict the geometry of individual molecules from the number of electron pairs surrounding their central atoms.[1] It is also named GillespieNyholm theory after its two main developers. The acronym "VSEPR" is pronounced "vesper" by some chemists.[2]

The premise of VSEPR is that the valence electron pairs surrounding an atom tend to repel each other, and will therefore adopt an arrangement that minimizes this repulsion, thus determining the molecule's geometry. The sum of the number of atoms bonded to a central atom and the number of lone pairs formed by its nonbonding valence electrons is known as the central atom's steric number.

VSEPR theory is usually compared with valence bond theory, which addresses molecular shape through orbitals that are energetically accessible for bonding. Valence bond theory concerns itself with the formation of sigma and pi bonds. Molecular orbital theory is another model for understanding how atoms and electrons are assembled into molecules and polyatomic ions.

VSEPR theory has long been criticized for not being quantitative, and therefore limited to the generation of "crude" (though structurally accurate) molecular geometries of covalently-bonded molecules. However, molecular mechanics force fields based on VSEPR have also been developed.[3]

History

The idea of a correlation between molecular geometry and number of valence electrons (both shared and unshared) was originally proposed in 1939 by Ryutaro Tsuchida in Japan,[citation needed] and was independently presented in a Bakerian Lecture in 1940 by Nevil Sidgwick and Herbert Powell of the University of Oxford.[4] In 1957, Ronald Gillespie and Ronald Sydney Nyholm of University College London refined this concept into a more detailed theory, capable of choosing between various alternative geometries.[5][6]

Description

VSEPR theory, occasionally pronounced "vesper" or "vuh-seh-per",[7] is used to predict the arrangement of electron pairs around non-hydrogen atoms in molecules, especially simple and symmetric molecules, where these key, central atoms participate in bonding to 2 or more other atoms; the geometry of these key atoms and their non-bonding electron pairs in turn determine the geometry of the larger whole.

The number of electron pairs in the valence shell of a central atom is determined after drawing the Lewis structure of the molecule, and expanding it to show all bonding groups and lone pairs of electrons.[8] In VSEPR theory, a double bond or triple bond are treated as a single bonding group.[8]

The electron pairs (or groups if multiple bonds are present) are assumed to lie on the surface of a sphere centered on the central atom and tend to occupy positions that minimizes their mutual repulsions by maximizing the distance between them.[8][9] Gillespie has emphasized that the electron-electron repulsion due to the Pauli exclusion principle is more important in determining molecular geometry than the electrostatic repulsion.[10] The number of electron pairs (or groups), therefore, determine the overall geometry that they will adopt. For example, when there are two electron pairs surrounding the central atom, their mutual repulsion is minimal when they lie at opposite poles of the sphere. Therefore, the central atom is predicted to adopt a linear geometry. If there are 3 electron pairs surrounding the central atom, their repulsion is minimized by placing them at the vertices of an equilateral triangle centered on the atom. Therefore, the predicted geometry is trigonal. Likewise, for 4 electron pairs, the optimal arrangement is tetrahedral.[8]

This overall geometry is further refined by distinguishing between bonding and nonbonding electron pairs. The bonding electron pair shared in a sigma bond with an adjacent atom lies further from the central atom than a nonbonding (lone) pair of that atom, which is held close to its positively-charged nucleus. VSEPR theory therefore views repulsion by the lone pair to be greater than the repulsion by a bonding pair. As such, when a molecule has 2 interactions with different degrees of repulsion, VSEPR theory predicts the structure where lone pairs occupy positions that allow them to experience less repulsion. Lone pair-lone pair (lp-lp) repulsions are considered stronger than lone pair-bonding pair (lp-bp) repulsions, which in turn are considered stronger than bonding pair-bonding pair (bp-bp) repulsions, distinctions that then guide decisions about overall geometry when 2 or more non-equivalent positions are possible.[8] For instance, when 5 ligands or lone pairs surround a central atom, a trigonal bipyramidal molecular geometry is specified. In this geometry, the 2 collinear "axial" positions lie 180° apart from one another, and 90° from each of 3 adjacent "equatorial" positions; these 3 equatorial positions lie 120° apart from each other and experience only two closer proximity 90° neighbors (the axial positions). The axial positions therefore experience more repulsion than the equatorial positions; hence, when there are lone pairs, they tend to occupy equatorial positions.[9]

The difference between lone pairs and bonding pairs may also be used to rationalize deviations from idealized geometries. For example, the H2O molecule has four electron pairs in its valence shell: two lone pairs and two bond pairs. The four electron pairs are spread so as to point roughly towards the apices of a tetrahedron. However, the bond angle between the two O-H bonds is only 104.5°, rather than the 109.5° of a regular tetrahedron, because the two lone pairs (whose density or probability envelopes lie closer to the oxygen nucleus) exert a greater mutual repulsion than the two bond pairs.[8][9]

AXE method

The "AXE method" of electron counting is commonly used when applying the VSEPR theory. The A represents the central atom and always has an implied subscript one. The X represents the number of ligands (atoms bonded to A). The E represents the number of lone electron pairs surrounding the central atom.[8] The sum of X and E is known as the steric number.

Based on the steric number and distribution of X's and E's, VSEPR theory makes the predictions in the following tables. Note that the geometries are named according to the atomic positions only and not the electron arrangement. For example the description of AX2E1 as a bent molecule means that the three atoms AX2 are not in one straight line, although the lone pair helps to determine the geometry.
Steric
No.
Molecular geometry[11]
0 lone pair
Molecular geometry[11]
1 lone pair
Molecular geometry[11]
2 lone pairs
Molecular geometry[11]
3 lone pairs
2 AX2E0-2D.png
Linear (CO2)
3 AX3E0-side-2D.png
Trigonal planar (BCl3)
AX2E1-2D.png
Bent (SO2)
4 AX4E0-2D.png
Tetrahedral (CH4)
AX3E1-2D.png
Trigonal pyramidal (NH3)
AX2E2-2D.png
Bent (H2O)
5 AX5E0-2D.png
Trigonal bipyramidal (PCl5)
AX4E1-2D.png
Seesaw (SF4)
AX3E2-2D.png
T-shaped (ClF3)
AX2E3-2D.png
Linear (I
3
)
6 AX6E0-2D.png
Octahedral (SF6)
AX5E1-2D.png
Square pyramidal (BrF5)
AX4E2-2D.png
Square planar (XeF4)
7 AX7E0-2D.png
Pentagonal bipyramidal (IF7)[9]
AX6E1-2D.png
Pentagonal pyramidal (XeOF
5
)[12]
AX5E2-2D.png
Pentagonal planar (XeF
5
)[13]
8
Square antiprismatic
(TaF3−
8
)[9]

9 Tricapped trigonal prismatic (ReH2−
9
)[14]
OR
Capped square antiprismatic[citation needed]
10 Bicapped square antiprismatic OR
Bicapped dodecadeltahedral[15]
11 Octadecahedral[15]
12 Icosahedral[15]
13
14 Bicapped hexagonal antiprismatic[15]

Molecule Type Shape[11] Electron arrangement[11] Geometry[11] Examples
AX2E0 Linear AX2E0-3D-balls.png Linear-3D-balls.png BeCl2,[1] HgCl2,[1] CO2[9]
AX2E1 Bent AX2E1-3D-balls.png Bent-3D-balls.png NO
2
,[1] SO2,[11] O3,[1] CCl2
AX2E2 Bent AX2E2-3D-balls.png Bent-3D-balls.png H2O,[11] OF2[16]
AX2E3 Linear AX2E3-3D-balls.png Linear-3D-balls.png XeF2,[11] I
3
,[17] XeCl2
AX3E0 Trigonal planar AX3E0-3D-balls.png Trigonal-3D-balls.png BF3,[11] CO2−
3
,[18] NO
3
,[1] SO3[9]
AX3E1 Trigonal pyramidal AX3E1-3D-balls.png Pyramidal-3D-balls.png NH3,[11] PCl3[19]
AX3E2 T-shaped AX3E2-3D-balls.png T-shaped-3D-balls.png ClF3,[11] BrF3[20]
AX4E0 Tetrahedral AX4E0-3D-balls.png Tetrahedral-3D-balls.png CH4,[11] PO3−
4
, SO2−
4
,[9] ClO
4
,[1] TiCl4,[21] XeO4[22]
AX4E1 Seesaw (also called disphenoidal) AX4E1-3D-balls.png Seesaw-3D-balls.png SF4[11][23]
AX4E2 Square planar AX4E2-3D-balls.png Square-planar-3D-balls.png XeF4[11]
AX5E0 Trigonal bipyramidal Trigonal-bipyramidal-3D-balls.png Trigonal-bipyramidal-3D-balls.png PCl5[11]
AX5E1 Square pyramidal AX5E1-3D-balls.png Square-pyramidal-3D-balls.png ClF5,[20] BrF5,[11] XeOF4[9]
AX5E2 Pentagonal planar AX5E2-3D-balls.png Pentagonal-planar-3D-balls.png XeF
5
[13]
AX6E0 Octahedral AX6E0-3D-balls.png Octahedral-3D-balls.png SF6,[11] WCl6[24]
AX6E1 Pentagonal pyramidal AX6E1-3D-balls.png Pentagonal-pyramidal-3D-balls.png XeOF
5
,[12] IOF2−
5
[12]
AX7E0 Pentagonal bipyramidal[9] AX7E0-3D-balls.png Pentagonal-bipyramidal-3D-balls.png IF7[9]
AX8E0 Square antiprismatic[9] AX8E0-3D-balls.png Square-antiprismatic-3D-balls.png IF
8
, ZrF4−
8
, ReF
8
AX9E0 Tricapped trigonal prismatic (as drawn)
OR capped square antiprismatic
AX9E0-3D-balls.png AX9E0-3D-balls.png ReH2−
9
[14]
† Electron arrangement including lone pairs, shown in pale yellow
‡ Observed geometry (excluding lone pairs)

When the substituent (X) atoms are not all the same, the geometry is still approximately valid, but the bond angles may be slightly different from the ones where all the outside atoms are the same. For example, the double-bond carbons in alkenes like C2H4 are AX3E0, but the bond angles are not all exactly 120°. Likewise, SOCl2 is AX3E1, but because the X substituents are not identical, the XAX angles are not all equal.

As a tool in predicting the geometry adopted with a given number of electron pairs, an often used physical demonstration of the principle of minimal electron pair repulsion utilizes inflated balloons. Through handling, balloons acquire a slight surface electrostatic charge that results in the adoption of roughly the same geometries when they are tied together at their stems as the corresponding number of electron pairs. For example, five balloons tied together adopt the trigonal bipyramidal geometry, just as do the five bonding pairs of a PCl5 molecule (AX5) or the two bonding and three non-bonding pairs of a XeF2 molecule (AX2E3). The molecular geometry of the former is also trigonal bipyramidal, whereas that of the latter is linear.

Examples

The methane molecule (CH4) is tetrahedral because there are four pairs of electrons. The four hydrogen atoms are positioned at the vertices of a tetrahedron, and the bond angle is cos−1(−13) ≈ 109°28'.[25][26] This is referred to as an AX4 type of molecule. As mentioned above, A represents the central atom and X represents an outer atom.[8]
The ammonia molecule (NH3) has three pairs of electrons involved in bonding, but there is a lone pair of electrons on the nitrogen atom.[27] It is not bonded with another atom; however, it influences the overall shape through repulsions. As in methane above, there are four regions of electron density. Therefore, the overall orientation of the regions of electron density is tetrahedral. On the other hand, there are only three outer atoms. This is referred to as an AX3E type molecule because the lone pair is represented by an E.[8] By definition, the molecular shape or geometry describes the geometric arrangement of the atomic nuclei only, which is trigonal-pyramidal for NH3.[8]
Steric numbers of 7 or greater are possible, but are less common. The steric number of 7 occurs in iodine heptafluoride (IF7); the base geometry for a steric number of 7 is pentagonal bipyramidal.[9] The most common geometry for a steric number of 8 is a square antiprismatic geometry.[28] Examples of this include the octacyanomolybdate (Mo(CN)4−
8
) and octafluorozirconate (ZrF4−
8
) anions.[28]

The nonahydridorhenate ion (ReH2−
9
) in potassium nonahydridorhenate is a rare example of a compound with a steric number of 9, which has a tricapped trigonal prismatic geometry.[14][29] Another example is the octafluoroxenate ion (XeF2−
8
) in nitrosonium octafluoroxenate(VI),[13][30][31] although in this case one of the electron pairs is a lone pair, and therefore the molecule actually has a distorted square antiprismatic geometry.

Possible geometries for steric numbers of 10, 11, 12, or 14 are bicapped square antiprismatic (or bicapped dodecadeltahedral), octadecahedral, icosahedral, and bicapped hexagonal antiprismatic, respectively. No compounds with steric numbers this high involving monodentate ligands exist, and those involving multidentate ligands can often be analysed more simply as complexes with lower steric numbers when some multidentate ligands are treated as a unit.[15]

Exceptions

There are groups of compounds where VSEPR fails to predict the correct geometry.

Transition metal compounds


Hexamethyltungsten, a transition metal compound whose geometry is different from that predicted by VSEPR.

Many transition metal compounds do not have the geometries predicted by VSEPR, which can be ascribed to there being no lone pairs in the valence shell and the interaction of core d electrons with the ligands.[32] The structure of some of these compounds, including metal hydrides and alkyl complexes such as hexamethyltungsten, can be predicted correctly using the VALBOND theory, which is based on sd hybrid orbitals and the three-center four-electron bonding model.[33][34] Crystal field theory is another theory that can often predict the geometry of coordination complexes.

Some AX2E0 molecules

The gas phase structures of the triatomic halides of the heavier members of group 2, (i.e., calcium, strontium and barium halides, MX2), are not linear as predicted but are bent, (approximate X-M-X angles: CaF2, 145°; SrF2, 120°; BaF2, 108°; SrCl2, 130°; BaCl2, 115°; BaBr2, 115°; BaI2, 105°).[35] It has been proposed by Gillespie that this is caused by interaction of the ligands with the electron core of the metal atom, polarising it so that the inner shell is not spherically symmetric, thus influencing the molecular geometry.[32][36] Ab initio calculations have been cited to propose that contributions from d orbitals in the shell below the valence shell are responsible.[37] Disilynes are also bent, despite having no lone pairs.[38]

Some AX2E2 molecules

One example of the AX2E2 geometry is molecular lithium oxide, Li2O, a linear rather than bent structure, which is ascribed to its bonds being essentially ionic and the strong lithium-lithium repulsion that results.[39] Another example is O(SiH3)2 with an Si-O-Si angle of 144.1°, which compares to the angles in Cl2O (110.9°), (CH3)2O (111.7°), and N(CH3)3 (110.9°).[32] Gillespie and Robinson rationalize the Si-O-Si bond angle based on the observed ability of a ligand's lone pair to most greatly repel other electron pairs when the ligand electronegativity is greater than or equal to that of the central atom.[32] In O(SiH3)2, the central atom is more electronegative, and the lone pairs are less localized and more weakly repulsive. The larger Si-O-Si bond angle results from this and strong ligand-ligand repulsion by the relatively large -SiH3 ligand.[32]

Some AX6E1 and AX8E1 molecules


Xenon hexafluoride, which has a distorted octahedral geometry.

Some AX6E1 molecules, e.g. xenon hexafluoride (XeF6) and the Te(IV) and Bi(III) anions, TeCl2−
6
, TeBr2−
6
, BiCl3−
6
, BiBr3−
6
and BiI3−
6
, are octahedra, rather than pentagonal pyramids, and the lone pair does not affect the geometry to the degree predicted by VSEPR.[40] One rationalization is that steric crowding of the ligands allows little or no room for the non-bonding lone pair;[32] another rationalization is the inert pair effect.[41] Similarly, the octafluoroxenate anion (XeF2−
8
) is a square antiprism and not a distorted square antiprism (as predicted by VSEPR theory for an AX8E1 molecule), despite having a lone pair.

Odd-electron molecules

The VSEPR theory can be extended to molecules with an odd number of electrons by treating the unpaired electron as a "half electron pair" — for example, Gillespie and Nyholm[42] suggested that the decrease in the bond angle in the series NO+
2
(180°), NO2 (134°), NO
2
(115°) indicates that a given set of bonding electron pairs exert a weaker repulsion on a single non-bonding electron than on a pair of non-bonding electrons. In effect, they considered nitrogen dioxide as an AX2E0.5 molecule with a geometry intermediate between NO+
2
and NO
2
. Similarly chlorine dioxide (ClO2) is AX2E1.5 with a geometry intermediate between ClO+
2
and ClO
2
.[citation needed]

Finally the methyl radical (CH3) is predicted to be trigonal pyramidal like the methyl anion (CH
3
), but with a larger bond angle as in the trigonal planar methyl cation (CH+
3
). However in this case the VSEPR prediction is not quite true, as CH3 is actually planar, although its distortion to a pyramidal geometry requires very little energy.[43]

VSEPR and orbital models

The VSEPR theory places each pair of valence electrons in a bond or a lone pair found in a local region of the molecule based on the Pauli exclusion principle. While this is frequently taught in chemistry textbooks in conjunction with orbital models such as orbital hybridisation and molecular orbital theory, the approach is completely different as the latter two are based on the Schrödinger equation.

Why scientific truth may hurt

The underlying realities of the world – from Earth’s rotation around the sun to Darwin’s theory of evolution – are rarely obvious or expected
The horizon
The horizon tells us the Earth is flat but our perception is often wrong.
Photograph: Alamy
All is not what it seems. Much of the universe – from the unimaginably small to the cosmological – is not how it appears to us, and our view is lamentably limited. The Earth’s rotation around the sun has been accepted for less time than it was not, and we still don’t yet know what makes up most of the cosmos. The knowledge that all life is built of cells is less than two centuries old, that all life is encoded in DNA has been known for just 50 years. When Darwin came up with evolution by natural selection, his loyal ally TH Huxley exclaimed “How extremely stupid, not to have thought of that!”

But evolution is not obvious at all, and it took thought and experiment and hard tenacious graft to reveal that truth. The real structure of the universe – the atomic, subatomic and quantum – was concealed from our eyes for all but the tiniest fragment of our tenure on Earth. We humans are awful at perceiving objective reality. We come with inbuilt preconceptions and prejudices. We’re dreadful at logic, and see patterns in things that are not there, and skip over trends that are. We attribute cause and agency to chance and coincidence, and blame the innocent as the root of all manner of evil. We use the phrase “common sense” as an admirable quality for scrutinising the world in front of us.

If this all sounds misanthropic, it’s not. Blind, directionless evolution gave us the gumption and the tools to frown at what we see, and ask if it really is how things are. Science is quite the opposite of common sense.
Common sense deceives us all the time: the horizon tells me the Earth is flat; people seem to get better after taking homeopathic pills; spiders are dangerous; a cold snap ridicules global warming. Of course, it is tricky to challenge someone’s opinion successfully if it is based on their learned experience. But that is exactly what science is for. It is to extract human flaws from reality; it is to set aside the bias that we lug around. Our senses and psychology perceive the world in very particular ways that are comically easy to fool. But the great strength of science is that it recognises the human fallibility that cripples our view of the universe. The scientific method attempts to remove these weaknesses.
 
 

That is why this should be instilled in us from as early as possible. At school, the facts must be taught, and the histories of those discoveries too. But we must bequeath the next generations the tools to question our limited perception – science as a way of knowing. It is frequently said – often by people like me – that children are born scientists, that their curiosity is inbuilt, and that this is eroded by age. It’s a pleasant sentiment, and certainly children are unsullied by the baggage of a life.

But children are not scientists. As ever, anything of value comes with effort, not by grace. Science is a particular way of thinking, not beset but enabled by doubt, and it comes from teaching. Somewhere in the country there is an eight-year-old girl who will change the world and win a Nobel prize for it. She will make people healthier, or see new stars, or merely reveal wonder. But it will be because her parents and teachers have taught her not to be satisfied with how things appear, and given her the tools to think critically and force the universe to reveal its true nature.
I was prompted to write this after I wrote on the biological non-existence of “race” a few weeks ago, and this prompted ire (and plenty of charmless racial abuse). Much of the commentariat was expressing the view that “obviously race exists because people look different, and these differences broadly cluster into traditional descriptions of race – blacks, whites, Asians”.

Modern genetics has unearthed a treasure trove of information about humans that was previously veiled or indecipherable, one of which is that some sets of genetic signatures broadly correlate with large land masses, especially ones bound by oceans. But these are neither exclusive nor essential associations with the way we use the term “race”. Last month, in the journal Nature, genetics was used to question, support and in some examples refute the history of the British people. The study catalogued the major immigrations from mainland Europe up until the 10th century, as revealed by subtle shadows of these interlopers hidden deep in our DNA. Guardian columnist Simon Jenkins opined that some of the results were “simply implausible” because the study was “strong on algorithms but weak on archaeology”. Well, evidence of all sorts is used to piece together the past, and one is not better than the other. But the algorithms used by geneticists are not there for fun, or to befuddle, but to reveal patterns that are otherwise invisible. Indeed, the scientific techniques are routinely used on actual physical artefacts to expose what is hidden. What I can say with utter confidence is that as we continue to explore and characterise the human condition, we’ll find more things that may feel untrue or implausible or uncomfortable. Maybe now is the time to get on board with uncertainty, discomfort and novelty.

Depression Isn’t What You Think It Is

Millions of people are diagnosed with major depression, while a growing number of scientists are saying it isn’t a distinct condition. It’s part of a big shake-up in psychiatry as researchers attempt to define mental disorders by what’s going wrong in the brain rather than using checklists of symptoms.

Original link:  http://www.buzzfeed.com/peteraldhous/depression-isnt-what-you-think-it-is#.taRr7joQ1m


In the wake of the Germanwings tragedy, mental health advocates are deeply concerned about misleading generalizations that may increase the stigma surrounding depression and make people less likely to seek the help that they need. But there’s been little discussion of perhaps the most misleading generalization of all: the label “depression” itself.

What we call depression seems to be a grab bag of conditions involving different parts of the brain’s circuitry. And while it’s still early days, a fresh understanding of depression’s diversity should lead to better treatments.

About 7% of U.S. adults experience at least one episode of major depression each year, according to the National Institute of Mental Health (NIMH). In terms of how many healthy years it takes from people’s lives, depression is the most damaging of all the mental and behavioral disorders. Yet according to the latest research, major depression isn’t a distinct disorder after all — despite being listed as such in the psychiatrists’ bible, the Diagnostic and Statistical Manual of Mental Disorders.

“When we throw around the label ‘depression,’ we can often be referring to very different things,” Daniel Foti, a clinical psychologist at Purdue University in Indiana, told BuzzFeed News.

Some of the confusion arises from the fact that depression is in many cases a secondary symptom of another mental disorder — about three quarters of people who meet the DSM’s criteria for major depression have at least one other psychiatric condition. But even “pure” cases of major depression can manifest themselves very differently: Some people lose interest in activities they once found pleasurable, while others become unusually sensitive to negative experiences. Still others become irritable and angry.

Little wonder, then, that doctors struggle to diagnose the condition. Before the last rewrite of the DSM in 2013, the American Psychiatric Association ran trials in which different clinicians were asked to diagnose the same patients turning up at academic psychiatric hospitals. Major depressive disorder was among the hardest diagnoses on which to get agreement, getting a rating of “questionable” reliability.

For scientists trying to understand depression and develop new treatments, that was a wake-up call. “The problem is it’s not one thing,” NIMH Director Thomas Insel told BuzzFeed News. “That’s why you have these low levels of reliability.”
Gordon Kindlmann and Andrew Alexander /
Via en.wikipedia.org

But psychiatric research is going through a shake-up.

In April 2013, Insel announced that the NIMH would shift its $1.4 billion annual research budget away from projects focusing on DSM diagnoses to instead concentrate on underlying disturbances of brain circuitry. That means using brain imaging to look at the activity of these circuits, as well as studies of brain chemistry, genetics, and thinking patterns. It will also mean studying people with conditions that cut across the disorders defined by the DSM’s checklists of symptoms.

In a blog post, Insel highlighted depression in explaining how things would change: “Clinical trials might study all patients in a mood clinic rather than those meeting strict major depressive disorder criteria.”

The new approach is starting to bear fruit, as scientists make distinctions between different forms of depression. One type, for example, involves the brain’s reward circuits. Another seems to be linked to impaired communication between the front of the brain and the amygdala, an area deep in the brain that processes emotions. The first type seems to be responsible for a phenomenon called “anhedonia” — an inability to feel pleasure — while the latter may help explain why some people are likely to be pushed into depressive episodes by negative life experiences.

Anhedonia may be particularly important, as people who don’t feel pleasure also tend to respond poorly to psychotherapy and antidepressant drugs, and are more likely to have thoughts of suicide. “Even after you control for other depressive symptoms, it’s a contributor to poor outcomes,” Diego Pizzagalli, who heads the Center for Depression, Anxiety and Stress Research at McLean Hospital in Belmont, Massachusetts, told BuzzFeed News.

Up to half of people with depression fail to respond to treatment with an antidepressant. One big hope is an anesthetic called ketamine: It seems to alleviate anhedonia, and brain imaging indicates that this improvement is linked to increased activity in parts of the brain known to be associated with anticipating rewards. The drug also reduces suicidal thoughts, and is fast-acting — on the order of hours and days, rather than weeks.

Ketamine will probably not itself be the next blockbuster antidepressant. Also known as “Special K,” it has hallucinogenic effects and is often used as a recreational drug. But after a period in which companies backed away from developing new antidepressants, big pharma is now developing drugs that mimic ketamine’s influence on depression without causing hallucinations. AstraZeneca, for instance, is working on a ketamine mimic called lanicemine.

Some psychiatrists say it’s too early to subdivide depression into different disorders.

Despite the difficulty defining exactly what it is, the label depression provides “a useful shorthand” for doctors to talk to their patients, Simon Wessely of King’s College London and president of the Royal College of Psychiatrists, told BuzzFeed News.

Wessely said he is worried that patients may be put into new pigeonholes that are no more valid than the old DSM labels — which is unlikely to lead to better treatments. “We might end up making the wrong splits,” he said.

Insel has also gotten some pushback from mental health professionals who fear that the new focus on brain circuitry will lead to an over-reliance on using drugs at the expense of other approaches to therapy.

But Insel disagrees that this will happen. “It’s been a misunderstanding for many people,” Insel said. “If we can begin to define these as brain circuit disorders, then treatments will become ways of tuning those circuits.”

That tuning might involve drugs, but could also come from psychotherapy, or computer games aimed at changing specific behaviors or emotions.
 
Peter Aldhous is a Science Reporter for BuzzFeed News and is based in San Francisco. His secure PGP fingerprint is 225F B2AF 4B8E 6E3D B1EA 7F9A B96E BF7D 9CB2 9B16
 
Contact Peter Aldhous at peter.aldhous@buzzfeed.com

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