Neil is this not what is called a circular question? For example... She is depressed. Why is she depressed? Because she is sad. Why is she sad? Because she is depressed.... I think most of us would be depressed if we were given a sz diagnosis.

Here again we have this assumption that depression is a 'cause' and not a symptom. If it is a cause of itself please could you show me where I can find evidence of this. Apart from the DSM series which has every human emotion now a causal factor of disorder. Personally I feel many real physical causes are being missed or ignored with this pseudo medical model.

It seems that the questions from Neil and Heather are like two ships passing in the night. Neil: "Sadness" is a symptom associated with both major clincla depressive disorder and with schizophrenia (just as abdominal pain is a symptom of both appendicitis and cholecystitis). To distinguish between the symptom of "sadness" (or even "depression") associated with major depression and schizophrenia would seem to require understanding the specific characteristics of such symptoms as they are unique to each clinical disorder. I don't know if there is literature on this. Heather: Not sure if Neil's question is circular. Whether a specific symptom is a "cause" or "effect" is not so much the question (for Neil's question) as the fact that the symptom is "associated with" that disorder (whether major depression or schizophrenia). So "sadness" does not so much "cause" major depression as it is the key element (when present in profound extent and associated with specified behavioral effects) to meet the diagnostic criteria for major clinical depression. It seems that is a problem in medicine when a commonly recognized "symptom" or "sign" is also given a diagnosis. For example, "bleeding" (or, when extensive, "hemorrhage") is a clinical sign but also a diagnosis. (Similarly for "high blood pressure" and "hypertension"). Maybe if we knew the underlying root cause of major clinical depression then it would be better to label it by the neurotransmitter defect/imbalance and not use the term for the symptom ("depression").

Excellent response Mr. Bowman.

James,

I sincerely hope we may someday be able to isolate causal elements (at least primary causes, as with infectious agents, like malaria) in psychiatric disorders. Unfortunately, many conditions are overdetermined, as Freud would say, and environmental factors certainly play a huge role in when or if a psychiatric symptom is expressed..

Heather,

I think that many clinicians who work with schizophrenia patients would say that the negative symptoms listed in DSM-IV are qualitatively different from depressive symptoms. My question seeks to understand how these two classes of symptoms are related.

BTW, I don't think my question is circular. There are many individuals that experience avolition, poverty of speech, etc in non-psychiatric settings. So these individuals cannot possibly be sad because they have been told they have schizophrenia - they have not been diagnosed at all, and there are likely tens of thousands of such untreated, undiagnosed individuals in the USA.

Interesting discussion. Not circular, but highly overlapping. As previously noted, this area of inquiry is hindered by the (mostly implicit) assumption that symptoms and their etiology are systematically divided across diagnostic categories. It sounds like perhaps one relevant dimension is the difference between alexithymia, anhedonia, amotivation, and other alliterative negative symptoms as opposed to highly-emotive (or hysteric) symptoms of sadness, despair, hopelessness, etc, but of course these constructs are also highly overlapping. The Google Scholar results from searching, "negative symptoms depression schizophrenia" seem useful. This area of research has branched significantly since researchers began re-conceptualizing cognitive and psychodynamic constructs in behavioral terms, and the literatures around attributional style / locus of control; amotivation; dysfunctional attitudes; emotion regulation; and other constructs seem relevant. Social learning is (as always) extremely important as well, especially effects of chronic institutionalization.

I am not (yet...) an expert in this area, but I would recommend perusing some research following Beck's ongoing re-conceptualizations (e.g., http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414437/ ).

Finally, it is especially important to consider the impact of psychotropic medication. In some cases, the difference between the nature of a person's negative symptoms or depression at a given time may be entirely a result of medication and/or withdrawal.

I look forward to hearing other responses!

I do not think of this as a circular question either. It has to do with various decision trees, co-morbid (or not) conditions and other such elements as I would see it. Certainly clinical judgment at times plays a role, but for general guidance the DSM decision trees would be a first stop in many cases if one is not familiar with the process personally.

Back to Neil's original question: Isn't this is the common problem in all of mediicine where a symptom is not necessarily unique to a single clinical condition but can be observed in multiple different disorders (diagnoses)? "Pain" is the most obvious symptom that comes to mind - and there are many features (history and characteristics) that clearly distinguish "abdominal pain" due to renal colic from pain due to acute pancreatitis. Neil's specific question is more problematic because one of the clinical disorders he refers to ("major depression") is itself a diagnosis that shares a commone symtpom ("depression") with numerous other psychiatric and non-psychiatric clinical conditions. There are obvious varying degrees or intensity of depression (from mild sadness to full blown clinical major depressive disorder) but from personal experience I'm not sure how you can chareacterize different "types" or varieties of "depression" or "sadness" symptoms. Hopefully some of you have some professional experience with that question.

symptoms of clinical depression? Sure, most of us feel sad, lonely, or depressed at times. And feeling depressed is a normal reaction to loss, life's struggles, or an injured self-esteem. But when these feelings become overwhelming and last for long periods of time.

Difficulty concentrating, remembering details, and making decisions

Fatigue and decreased energy

Feelings of guilt, worthlessness, and/or helplessness

Feelings of hopelessness and/or pessimism

Insomnia, early-morning wakefulness, or excessive sleeping

Irritability, restlessness

Social symptoms include:

•not doing well at work

•taking part in fewer social activities and avoiding contact with friends

•neglecting your hobbies and interests

•having difficulties in your home and family life

This is another major "can of worms" issue about which I don't care to take a stand. However, when thinking about differential symptom constructs in negative symptoms of schizophrenia spectrum disorders, the corresponding literature about "depression" vs. "anxiety" is instructive. For example, "According to Clark and Watson (1991) ... the variance in anxiety and depression can be decomposed into: (a) negative affect, which is common to anxiety and depression, (b) physiological hyperarousal, which is specific to anxiety and (c) anhedonia which, is specific to depression" (cited in: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2869473/ ). Such conceptualizations help organize thoughts about one grey area that takes on another grey dimension when psychotic and bipolar symptoms are added to the mix.

I also agree with other commenters: The DSM decision trees are helpful and clearly illustrate conventional wisdom about this dichotomy, and RDoC constructs more reliably and precisely characterize individual differences and symptom patterns.

Could that DSM tree be leading people further away from the tree roots? Away from cause and focusing on disorder within the person rather that epigentetic factors?

Here is some research from the mid 1990's which seems to contain so many exciting research possibilities... certainly many reasons why people might experience non social/trauma induced depression.

The Toxic Metal connection to ADD, Aggressiveness, Impulsive ... http://www.flcv.com/violence.html

Heather, it seems that other prenatal environmental factors besides heavy metals can result in epigenetic disturbances/defects that can result in neurologic and psychological conditions. The recent article last year by Olena Babenko et al is pretty compelling. Brain Res. 2012 Mar 20;1444:96-111. Dr Babenko is on RG here.

"Epigenetic programming of neurodegenerative diseases by an adverse environment" Babenko O, Kovalchuk I, Metz GA.Dept of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, Canada. Brain Res. 2012 Mar 20;1444:96-111

Abstract

Experience and environment can critically influence the risk and progression of neurodegenerative disorders. Epigenetic mechanisms, such as miRNA expression, DNA methylation, and histone modifications, readily respond to experience and environmental factors. Here we propose that epigenetic regulation of gene expression and environmental modulation thereof may play a key role in the onset and course of common neurological conditions, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. For example, epigenetic mechanisms may mediate long-term responses to adverse experience, such as stress, to affect disease susceptibility and the course of neurodegenerative events. This review introduces the epigenetic components and their possible role in mediating neuropathological processes in response to stress. We argue that epigenetic modifications will affect neurodegenerative events through altered gene function. The study of epigenetic states in neurodegenerative diseases presents an opportunity to gain new insights into risk factors and pathogenic mechanisms. Moreover, research into epigenetic regulation of disease may revolutionize health care by opening new avenues of personalized, preventive and curative medicine.

This review by Ho et al from Cincinnati is even more comprehensive. It discusses the pathogenesis whereby epigentetic effects of heavy metals and many other environmental factors can result in various disorders and disease.

ILAR JournalVolume 53, Issue 3-4 (2012) r.53.3-4.289

"Environmental Epigenetics and Its Implication on Disease Risk and Health Outcomes" Shuk-Mei Ho et al Email [email protected]

Division of Environmental Genetics and Molecular Toxicology, Department of Environmental Health, College of Medicine, University of Cincinnati, Ohio.

Abstract

This review focuses on how environmental factors through epigenetics modify disease risk and health outcomes. Major epigenetic events, such as histone modifications, DNA methylation, and microRNA expression, are described. The function of dose, duration, composition, and window of exposure in remodeling the individual's epigenetic terrain and disease susceptibility are addressed. The ideas of lifelong editing of early-life epigenetic memories, transgenerational effects through germline transmission, and the potential role of hydroxylmethylation of cytosine in developmental reprogramming are discussed. Finally, the epigenetic effects of several major classes of environmental factors are reviewed in the context of pathogenesis of disease. These include endocrine disruptors, tobacco smoke, polycyclic aromatic hydrocarbons, infectious pathogens, particulate matter, diesel exhaust particles, dust mites, fungi, heavy metals, and other indoor and outdoor pollutants. We conclude that the summation of epigenetic modifications induced by multiple environmental exposures, accumulated over time, represented as broad or narrow, acute or chronic, developmental or lifelong, may provide a more precise assessment of risk and consequences. Future investigations may focus on their use as readouts or biomarkers of the totality of past exposure for the prediction of future disease risk and the prescription of effective countermeasures.