The Ash Twins Blog

People are curious about the validity of psychiatric diagnoses. For the psychiatric disorders, there are no objective tests (like a blood concentration or imaging finding) to reliably confirm a diagnosis. Instead, psychiatrists look for characteristic patterns of symptoms to make their diagnoses. The most popular source for diagnostic criteria on psychiatric disorders is the Diagnostic and Statistical Manual, edition IV, DSM-IV for short. The DSM-IV operationalizes the diagnosis of psychiatric disorder based on symptoms which tend to cluster together. For example, someone with major depressive disorder must have 5/9 depressive symptoms (depressed mood, changes in sleep patterns, decreased interest in or pleasure from activities of life, guilt feelings, decreased energy, inability to concentrate, changes in weight or appetite, increase or decrease in spontaneous movements [called psychomotor agitation/retardation], and suicidal ideation) for over 2 weeks. These criteria are created for research purposes (to be able to directly compare different studies) and are based in clinical studies of common symptoms. For many psychiatric disorders, there is not a lot of good research to objectively define or assess the validity of diagnostic criteria.

For schizophrenia, the DSM-IV criteria are two or more of the following symptoms:

1. delusions – beliefs that have no basis in reality which are held despite evidence to the contrary
2. hallucinations – seeing, hearing, or feeling things that aren’t there
3. disorganized speech – saying random things; no logical thought process
4. disorganized or catatonic behavior – e.g. staring at the wall without responding to external stimuli
5. Negative symptoms – no spontaneous speech, flat affect (schizophrenics’ faces often look like a mask), avolition

Only one symptom is required if the delusions are bizarre (i.e. “The CIA has implanted a microchip in my brain so that aliens can control my thoughts”) or the hallucinations consist of a running commentary of voices or voices conversing with each other. The symptoms must cause significant occupational impairment. It’s called schizophrenia if symptoms last over 6 months, schizophreniform disorder if symptoms last between 1 and 6 months, and brief psychotic episode if under 1 month.  There are five subtypes of schizophrenia, with paranoid – which predicts prominent hallucinations and delusions – being the most common. Add mood symptoms (like depression or mania [which have their own DSM criteria]) and you call it schizoaffective disorder.

It is estimated that a bit less than 1% of the population suffers from schizophrenia. It has a strong genetic component, as 10% of siblings of schizophrenics also have schizophrenia, and 46% of individuals with two parents with schizophrenia or an identical twin with schizophrenia also develop schizophrenia. 14% of individuals with a nonidentical twin with schizophrenia also develops schizophrenia, suggesting a role for in utero predisposing insults. The prevalence is the same world-wide, and no significant environmental predisposing factors have been identified. Symptoms first begin to develop in the early- to mid-twenties, with males presenting a few years earlier than females. These facts confirm that schizophrenia is a definite biological disease.

The diagnosis of schizophrenia, unfortunately, is still as much an art as a science. The DSM-IV criteria have been severely criticized: To cite on example, if a patient’s delusions are bizarre, that one symptom is enough to diagnose schizophrenia, but the definition of bizarre is vague, and there is poor inter-rater reliability in categorizing delusions as bizarre or nonbizarre. It is difficult to assess the reliability of DSM IV diagnosis, because there is no “gold-standard” test to verify that someone has schizophrenia. In assessing a diagnostic test for Alzheimer disease, in contrast, one could verify the test postmortem by looking at brain tissue under a microscope – Alzheimer neurons are blighted with amyloid plaques and neurofibrillary tangles. For schizophrenia, the best we can do is check in with diagnosed patients several years later and see if they have gotten worse, as schizophrenia tends to be a chronic progressive disease. Using this criteria, the DSM has a 93% specificity and 51% sensitivity for diagnosis of schizophrenia in first-episode psychotics. In other words, only 7% of patients were incorrectly diagnosed with schizophrenia (false-positives), but 49% with schizophrenia were not diagnosed as such (false-negatives). This experiment is but one of many: there have been dozens of studies testing the reliability of schizophrenia diagnosis, each one using different experimental parameters. Jansson and Parnas review them here.

The differential diagnosis of schizophrenia is complex. Duration of symptoms differentiates schizophrenia from schizophreniform disorder (as above). If only delusions are present, and these are nonbizarre (“I know my spouse is cheating on me”) the diagnosis is delusional disorder. Substance toxicity (especially cocaine and PCP) can cause psychosis: these are differentiated with drug tests and by detox. Neurological disorders (defined by visible brain pathology) like dementia, tumors, epilepsy, or encephalitis can also present with psychosis.

The patient I mentioned in the previous post, for example, presented with prominent running-commentary hallucinations and bizarre delusions, little or no negative symptoms, and a history of alcoholism. To make the diagnosis given the clinical information, we would do a CT and a drug test to rule out organic brain pathology and substance toxicity. Alcohol toxicity is an unlikely cause, because it usually presents with slurring of speech, confusion, and loss of consciousness – hallucinations and delusions are not prominent. Alcohol withdrawal , on the other hand, can cause visual and audial hallucinations, but these rarely if ever include running commentaries, and other withdrawal symptoms (like autonomic dysfunction and delirium tremens) would also be prominent. The characteristic presentation of alcohol-induced dementia, sometimes associated with Wernicke-Korsakoff syndrome, includes symptoms of memory loss, aphasia, and disorganized cognition – again, psychotic symptoms are rare.

After ruling out other causes of psychosis, the standard of care is to attempt treatment. If antipsychotic medicines work, and the patient reports a significant drop in symptoms, the diagnosis is likely correct. Psychiatrists can never be sure, though, so a healthy dose of skepticism about previously-diagnosed psychiatric disorders is always warranted. If a patient presents with psychosis but does not fit any of the defined categories, he or she can be labeled ‘psychotic disorder not otherwise specified.’

And patient reliability is also an issue. The DSM-IV classification of Malingering is “the intentional production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives, such as avoiding military conscription or duty, avoiding work, obtaining financial compensation, evading criminal prosecution, obtaining drugs, or securing better living conditions” (Andreasen & Black 2006). The patient mentioned in the previous post, for example, could be faking his symptoms so that VA social workers would help him find a new place to live. Malingering is suspected when the patient stands to benefit from a specific diagnosis (i.e. patient is referred by an attorney), the symptoms reported are vague or contradictory, there is a marked discrepancy between patient’s subject symptoms and objective signs, or the patient has antisocial personality disorder. In this patient’s case, given his extended history of psychotic symptoms which dovetail exactly with the diagnostic criteria for schizophrenia, I find it unlikely that he is malingering, but if he has studied the DSM, he could theoretically have fabricated his entire presentation. There’s no way to know.

A new article in the Journal of Neuroscience links the placebo effect to a specific gene.

In the study, summarized here, researchers measured amygdala activity by PET scan in individuals with Social Anxiety Disorder while they recited speeches in front of an audience. Subjects gave the speech both before and after an eight week trial of SSRI or sugar pill.  A subset of the subject population demonstrated reduced anxiety and attenuated amygdala activity after the eight-week treatment period, even if they received the placebo. Notably, eight of the ten subjects who responded to the placebo had a unique allele at the tryptophan hydroxylase-2 promoter (TPH2), a gene involved in serotonin metabolism that has been ” linked to heightened amygdala activity in healthy people.”

The authors note that TPH2 is “the first genetic marker tied to any placebo response.”

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Anthropologist Nicholas Humphrey has written a book chapter about the evolution of the placebo effect in Psychology at the Turn of the Millennium, Vol. 2: Social, Developmental, and Clinical Perspectives, and it’s available online.

Humphrey reviews the power of the placebo effect here:

Indeed experimental studies have shown that placebos, as well as being particularly effective for the relief of pain and inflammation, can for example speed wound healing, boost immune responses to infection, cure angina, prevent asthma, lift depression, and even help fight cancer. Robert Buckman, a clinical oncologist and professor of medicine, concludes that “Placebos are extraordinary drugs. They seem to have some effect on almost every symptom known to mankind, and work in at least a third of patients and sometimes in up to 60%. They have no serious side-effects and cannot be given in overdose. In short they hold the prize for the most adaptable, protean, effective, safe and cheap drugs in the world’s pharmacopoeia.” Likewise, another medical authority, quoted in a recent review in the British Medical Journal, dubs placebos “the most effective medication known to science, subjected to more clinical trials than any other medicament yet nearly always doing better than anticipated. The range of susceptible conditions appears to be limitless.”

He continues:

And there’s the puzzle: the puzzle that I’ll try to address in this paper from the perspective of  evolutionary biology. If placebos can make such a contribution to human health, then what are e waiting for? Why should it be that we so often need what amounts to outside permission before taking charge of healing our own bodies? I can illustrate the paradox with one of Weil’s case histories. He describes the case of a woman with a metastatic cancer in her abdomen who refused chemotherapy and relied instead on dieting, exercise and a regime of “positive thinking” including “regular meditation incorporating visualization of tumour shrinkage” – following which, to the physicians’ astonishment, the tumour completely disappeared.

Weil asks: “What happened in this woman’s abdomen that eliminated widely disseminated cancer and restored her internal organs to good health? Her healing system, probably making use of immune mechanisms, was surely responsible; but why did it not act before?” Precisely. Why? Why should her bodily immune system be prepared, apparently, to let her die unless and until her mind decided otherwise? Weil asks the question as a doctor, and his “why?” is the why of physiological mechanism: “what happened?”. But I myself, as I said, want to take the perspective of an evolutionist, and my “why?” is the why of biological function: “why are we designed this way?”
There are two reasons for thinking that evolutionary theory may in fact have something important to say here. One reason is that the human capacity to respond to placebos must in the past have had a major impact on people’s chances of survival and reproduction (as indeed it does today), which means that it must have been subject to strong pressure from natural selection. The other reason is that this capacity apparently involves dedicated pathways linking the brain and the healing systems, which certainly look is if they have been designed to play this very role. I’d say therefore it is altogether likely that we are dealing with a trait that in one way or another has been shaped up as a Darwinian adaptation – an evolved solution to a problem that faced our ancestors. In which case, the questions are: what was the problem? and what is the solution?

After reviewing the significant evidence for evolutionary pressures that could select for the placebo effect, Humphrey concludes:

To start with, given that there are certain universals in how people fare in different situations, there are presumably general rules to be found linking global features of the physical and psychological environment to changes in the costs and benefits of health-care – features such as where you live, what the weather is like, the season of the year, what you can see out the window, how much you feel at home here, and, especially important, what social support you’ve got.

Generally speaking any such features that make you feel happy and secure – success, good company, sunshine, regular meals, comforting rituals – are going to be associated with lower benefits to having the symptoms of illness (e.g. feeling pain) and lower costs to self-cure (e.g. mounting a full scale immune response). By the same token any of them that make you feel worried and alone – failure, winter darkness, losing a job, moving house – are going to be associated with higher benefits to continuing to show the symptoms and higher costs to  elfcure.

Now, appreciating these cost/benefit changes, and switching health-care strategy accordingly, would bring clear advantages in the competition for biological survival. So it’s a fair bet that natural selection will have discovered these general rules and that humans will now be genetically designed to make good use of them – with the appropriate environmentally-activated switches being wired into the brain. And indeed there is lots of evidence that this is actually the case. People’s health does respond quite predictably to global environmental factors of the sort just listed. Much of the science of “health psychology” is now concerned with charting just how important these global effects are.