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Thesis

OVERVIEW:  I AM EDISON.

Sitting in his chair in the study, Edison stares at his new invention.  He’s convinced the world will come running to his feet, begging for this new way to illuminate their homes, their streets, the buildings that will no longer need to use gas lamps or candles or fires to make them glow.  But the world does not come to his feet, nor do they even knock on his door, at least initially.  The wise people of his era find all kinds of excuses not to value this new invention.  You need to string electric wires all over they say, or it could burst and cause a fire.  It’s hot to the touch and children will burn their fingers.  So he sits there, bulb in hand, scratching his head, muttering, “Now what?”  

I AM Edison.  Psychiatry is woefully lacking in answers about schizophrenia.  Besides the fact that it is an illness that starts in late adolescence and that reduces your overall functional expectations, the rest is controversy.  Despite decades of research we’ve never found a schizophrenia gene.  Despite theories about connectivity and abnormal brain networks we have yet to reveal a process in schizophrenia.  We know that with each relapse their brains may deteriorate a bit more.  Yet most workers in the field concede that it is not a dementia.  Psychiatrists sit in offices day after day treating an illness they know little about, giving medications they don’t fully understand to patients who don’t believe they’re sick.  

One reason for this is that there are many red herrings in schizophrenia.  The obvious answers don’t enlighten us.  It’s not a brain injury, a toxic ingestion or a virus.  A major symptom is psychosis, or ‘craziness’ but we see that with methamphetamine use, Alzheimer’s, Parkinson’s, alcohol withdrawal and many other conditions.  

My theory explains it all.  

Let’s begin.  Darwinian evolution works on a simple principle, protoplasm+mutation x time=man.  The crucible of evolution rules on the capabilities of mutations like Siskel and Ebert.  Thumbs up to anything that promotes survival and thumbs down to anything that impedes it.  Survival of the fittest lorded over mankind’s possibilities like a spell and with the largesse of time protoplasm simmered in a crucible that eventually yielded ever improving life forms.  Evolution indemnified time so to speak, DNA being a powerful time enhancement project.  Even with a detour like dinosaurs and massive body weight, evolution pushed ahead and course corrected to a new mantra… cunning.  The brain began to enlarge with natural selection’s blessing, making its silent contribution to hominin survival.  Still, the genus Homo and Homo sapiens in particular were far from the top of the food chain.  

Then something happened.  A sixth sense in the form of language arose, some say gradually others say like a tsunami.  The Captain Kirk of the mind, the ego, garnered a huge promotion, being the word processor supreme.  It organized words into sentences under the rules of syntax.  Borrowing from Freud’s metapsychology, one can say that language was a boon to the ego, and as such, the post-verbal mind coalesced around this new flag.  Words became the organizing principle of the mind, rendering post-verbal man a new reality and a shining beacon of mental complexity following the dictums of Werner’s development psychology.  Symbol formation, the basis of all language, enlarged the left hemisphere to encompass all that language was.  For the first time, humans were able to participate in their thought processes with the help of the ego and its language production.  It was able to deliver, like a sixth sense, conceptual contents to the fore brain, resulting in a fertilizing effect and a euphoria unknown to primitives.  We were gradually able to leave our primitivity behind and in so doing conquered the Neanderthals and Denisovans.  

We went from the jungle to the disco.  By neutralizing most of the predators that plagued us for millions of years we developed an expectation of survival.  We conquered the other species of Homo and started civilizations, religion, education, science.  The golden rule ruled and with it the superego, allowing us to feel joy when we did something good for others.  Humankind created a whole new geodome of reality in which to live.  The neurotransmitter dopamine, once the engine of mental vitality, had to undergo a suppression which allowed thought to emerge clearly in the mind without interference.  By the end of adolescence it is in a state of controlled modulation, while still promoting our thinking and orchestrating coordinated movement.  

All of these changes took place within the last fifty thousand years or so.  Humans have been around for about six million years.  The changes that accrued in such short period of time, language, thinking, complexity of brain structure, enactment of the Freudian metapsychology of id ego and superego, civilization, communal living, etc, all happened in lightening speed.  Evolution had to make a course correction.  No longer was survival of the fittest the mantra, but now survival of the most reproductive took precedence.  The barge of evolution started shifting, loosening the reign of survivalism.  Massive changes were set in motion, all by language and what it wrought.  But it would not be surprising that some of us, in the midst of all this metamorphosis would be unable to leave the old ways.  Just as they are about to leave adolescence, suppress dopamine and abandon our primitive past, primitivity reasserts itself.  It rushes back to grab hold and with a vicious intensity reminiscent of the brutality and fear of our ancestors, recaptures the mind.  This primitive organization causes a regression to childlike thinking and a resurgence of dopamine.   The dreams of Neanderthals and our dreams are quite similar, except that layers of civilization induce us to disguise them.  One could justify the view that schizophrenia is a waking dream.  

Dopamine, as it turns out, is involved in many diseases, including Parkinson’s disease, Huntington’s chorea, attention deficit disorder, Tourette’s, stuttering, etc.  Something about dopamine is crucial in our evolution.  Every medication that psychiatrists use to treat schizophrenia blocks the receptors of dopamine.  These drugs were discovered serendipitously, and they work too inconsistently and with massive side effects.  They also lose traction over time and seem to do less and less for patients.  Yet by blocking the dopaminergic rush that impedes the schizophrenic’s ability to think, they help calm the mind and restore somewhat the utilization of forebrain structures that is specifically usurped by the primitive organization.  These forebrain structures begin to behave as if the individual was asleep and, in a state of relative sensory deprivation, create their own dream-like stimulation in the form of hallucinations.  But the primitive organization that has taken control utilizes them to attack the ego, the outpost of civilization as it were.  

Schizophrenia may begin gradually or abruptly.  The primitive organization finds a way relentlessly to gain control of the individual’s mind.  As sinister as a virus that thwarts the immune system, the primitive organization convinces the individual that there is not only nothing wrong with their new lifestyle, but everything right about it.  The patient’s relatives see that the person is not the same, but cannot define how.  Whether they’re running around a roof top claiming to have killed people with their minds or living on a church stoop expecting a helicopter to come down and rescue them, the thought that they might be schizophrenic does not occur to the newly attacked patient.  Each schizophrenic responds to the takeover their own way.  Most simply ignore it as preposterous.  After all no one ever warned them that a primitive organization from our prehistoric past might suddenly overwhelm their psyche.    

Each individual handles it in their own way.  In a famous example, Judge Daniel Paul Schreber took the primitive organization as a masculine invasion and was able to sexualize the experience.  Their thinking is altered and reflects the primitive organization’s roots in pre-verbal logic.  Schizophrenics think by different rules comparable to children and hallucinogen users.  They use autistic, idiosyncratic terminology that is rooted in their own mental experience not external reality.  This reflects the lower state of excitation in the primitive organization which is one magnetic force that drags sufferers back to the old ways.  All the gains of civilization are lost.  Although schizophrenics are able to speak, their ego strengths are diminished.  

Primitive organization theory explains the anthropo-parity principle since schizophrenia is now defined as an evolutionary glitch, not a genetic infraction.  This also explains the lack of extinction, in an illness that is part of evolution’s course correction, not Darwinian evolution. The age of onset of schizophrenia is also accounted for as the primitive organization needs to develop before it overtakes the civilized brain and times its invasion to the moment just before dopamine is fully suppressed.  Atrophy of forebrain structures is clearly due to their functional replacement by the primitive organization.  Relative sensory deprivation causes the fore-brain to exude hallucinatory material to self stimulate.  The use of dopamine blocking agents is due to the resurgence of dopamine by the primitive organization which counters the gradual dopamine suppression that leads us out of adolescence and facilitates clarity of thinking.  Psychosis can be explained as a product of cognitive regression, coupled with the hallucinations generated by a a sensorily deprived fore-brain, and the brutal attack on the ego that ensues.  Primitive organization theory explains what we call Schneiderian symptoms.  Feeling that thoughts are broadcast out to others or are generated from someone else’s mind can be explained as a function of the replacement pre-verbal ego reacting to the adult word processing ego as a foreign entity.  As humankind pulls away from its lengthy past primitivity, it will be less and less likely that individuals will be called back to it in this entropic way.  

Mood disorders also reflect a return to primitivity.  Depression can be characterized as a return to a primal hibernation state of dread.  Mania can be compared to a state of revery when a predator was vanquished.  Both may result in excessive dopaminergic activity which impinges on concentration and expression.  They respond to dopamine blocking agents.  Other illnesses like Parkinson’s disease, Huntington’s chorea, attention deficit disorder, Tourette’s disorder, stuttering, substance use and others revolve around dopaminergic alterations and reflect the transformation of dopaminergic functioning in modern humans.  But evolution has left us with an imperfect dopamine system prone to errors.  

Mental illness follows a number of principles. Foremost among the is a return of the primitive. All major mental illnesses, especially schizophrenia demonstrate this. The primitivity that draws us back has the advantage of entropy. Just as we regress in sleep to a lower state of excitation, aided by the paralysis accompanying that state, mental illness is swept magnetically to an entropic trough that threatens to entrap us all.

There are many other theories of schizophrenia and evolution. None of them have the encompassing nature of my primitive organization theory. T.J. Crow acknowledges evolution’s role in schizophrenia but ultimately falls back on a genetic explanation. My ideas inhabit the category of ‘byproduct’ theory in attributing schizophrenia to a byproduct of some other process, in this case a course correction of evolution itself. Some theories attempt to assert an advantage to schizophrenia which would make it less likely to become extinct. No advantage to being schizophrenic has ever been proven or genuinely endorsed. Burns blames schizophrenia on abnormal connectivity and a failure to achieve a social brain. This ill defined theory lacks the specificity or clarity of my own, nor does it account for the anthropo-parity principle, the central paradox of schizophrenia namely lack of extinction, atrophy of higher brain structure and so on. Some theories explain schizophrenic’s survival by labeling them ‘shamans’ who were leaders of past societies and spoke to God therefore making them holy men. This cannot explain their ongoing survival today.

Resources

 The references listed here are but a fraction of the written material on evolution, anthropology, Freudian psychology and schizophrenia research available. I have annotated some of it, but there is so much more, that one would have to dig for oneself in the huge cornucopia of related topics that are available for study. That is why schizophrenia continues to elude. It is a complex condition encompassing a broad range of disciplines. It is my hope the Neanderthal’s Dream: Evolutions and Insanity, will reduce confusion, add a framework with which to proceed, and advance the science of mental illness further than previously known.

References

BOOKS

Zimmer, C.  Smithsonian Intimate Guide to Human Origins. Toronto, Ontario, Canada: Madison Press Books, 2005.

Leakey, R. The Origin of Humankind.  New York, New York: Basic Books, 1994.

Niederland, WG.  The Schreber Case:Psychoanalytic Profile of a Paranoid Personality.  New York, New York: Quadrangle/The New York Times Book Company, 1974.

Schreber, DP.  Memoirs of My Nervous Illness.  Cambridge, MA: Harvard University Press, 1988. (A detailed account of schizophrenia from an obsessively detailed individual. Freud then analyzed these memoirs and developed his classic theory of paranoia.)

Chabot, CB.  Freud on Schreber:Psychoanalytic Theory and the Critical Act.  Amherst, MA: The University of Massachusetts Press, 1982.

Harari, YN.  Sapiens:A Brief History of Humankind.  New York, New York: HarperCollins Publishers, 2015.

Lee, SH, Yoon, SY.  Close Encounters with Humankind: A Paleoanthropologist Investigates Our Evolving Species. New York, New York:W.W. Norton and Company, 2018.

Werner, H. Comparative Psychology of Mental Development.  New York, New York: International Universities Press, 1948. (An overview of developmental psychology applicable to every element of an evolving system.)

Werner, H and Kaplan, B.  Symbol Formation: An Organismic-Developmental Approach to the Psychology of Language. (Very complicated but worth the effort.) 

Psychology of Language.  Hillsdale, New Jersey: Lawrence Erlbaum Associates, Inc., 1963.

Freud, S. Beyond the Pleasure Principle.  New York: W.W.Norton and Co., 1961. (Describes the tendency of human psyche to seek the lowest level of excitation.)

Freud, S. The Ego and the Id.  New York:W.W.Norton and Co., 1960

Freud, S. A General Selection from the Works of Sigmund Freud.  Garden City, New York: Doubleday and Company, Inc., 1957.

Freud, S, Three Case Histories. New York:Macmillan Publishing Co., 1963. (Includes the Schreber case.)

Howells, JF, ed.  The Concept of Schizophrenia: Historical Perspectives.  Washington, DC: American Psychiatric Press, 1991.

Wang, EW.  The Collected Schizophrenias.  Minneapolis, MN: Graywolf Press, 2019. (An account of one person’s journey through various diagnoses.)

Saks, ER.  The Center Cannot Hold: My Journey Through Madness.  New York, New York: Hachette Books, 2007. (A most readable and intensely moving chronology of schizophrenia in a gifted person.)

Yeiser, B.  Mind Estranged:My Journey from Schizophrenia and Homelessness to Recovery.  United States of America, Create Space, 2014. (Another account by a gifted woman of her torturous decline into madness and ultimate recovery.)

JOURNAL ARTICLES

Burns, JK. “An Evolutionary theory of schizophrenia: Cortical connectivity, metarepresentation, and the social brain.”  Behavioral and Brain Sciences 27 (2004): 831-885.

Hofman, MA. “Evolution of the human brain:when bigger is better.” Frontiers Neuroanatomy Mar. (2014): PMID 24723857.

Bolu, A, et al.  “The ratios of 2nd to 4th digit may be a predictor of schizophrenia in male patients.”  Clinical Anatomy 28 (2015): 551-556.

Lesk, S. “A different view of patients with schizophrenia.” Current Psychiatry 17 (2018): e1-e3.

Lesk, S. “Taking Acid.” Letter to the editor, New York Times Book Review, June 24, (2018).

Goff, DC.  “Longer duration of untreated psychosis linked to loss of brain volume.”  JAMA Psychiatry Feb (2018) 

Hacksell, U, et al.  “On the discovery and development of pimavanserin: a novel drug candidate for Parkinson’s psychosis.”  Neurochem Res 10 (2014):2008-2017.

Sullivan, PF, et al.  “Schizophrenia as a complex trait: Evidence from a Meta-analysis of Twin Studies.”  Archive Gen Psychiatry 60 (2003):1187-1192.

Joseph, J. “Don Jackson’s “A critique of the literature on the genetics of schizophrenia”: a reappraisal after 40 years.”  Genet Soc Gen Psychol Monogr 127 (2001):27-57.

Cardno, AG, Gottesman, ll.  Twin Studies of Schizophrenia:from bow and arrow concordances to star wars Mx and functional genomics.”  Am J Med Genet 97 (2000):12-7.

Ocklenburg, S, et al.  “Laterality and mental disorders in the postgenomic age- A closer look at schizophrenia and language lateralization.”  Neuroscience and Biovehavioral Reviews 59 (2015):100-110.

Lothane, Z.  “The Teachings of Honorary Professor of Psychiatry Daniel Paul Schreber, J.D., to Psychiatrists and Psychoanalysts, or Dramatology’s Challenge to Psychiatry and Psychoanalysis.”  Psychoanalytic Review 98 (2011):775-815.

Schatzman, M.  “Paranoia of Persecution: The Case of Schreber.”  Int J of Psychiatry 10 (1972):     53-78.

Callier, S., et al.  “Evolution and cell biology of dopamine receptors in vertebrates.”  Biology of the Cell 95 (2003):489-502.

Vernier, P, et al.  “Bioamine Receptors: Evolutionary and functional variations of a structural leitmotiv.”  In, “Comparative Molecular Biology,” Pichon, Y. ed.  Birkhauser Verlag: Basel, Switzerland, 297-337, 1993.

Vernier P, et al.  “The Degeneration of Dopamine Neurons in Parkinson’s Disease: Insights from the Embryology and Evolution of the Mesostriatocortical System.”  Ann. N.Y. Acad. Sci. 1035 (2004): 231-249 

Sacheli, MA, et al.  “Habitual exercisers versus sedentary subjects with Parkinson’s Disease: Multimodal PET and fMRI study.” Movement Disorders 0 (2018).

Ferre, S. “Mechanisms of the psycho-stimulant effects of caffeine: Implications for substance use disorders.” Psychopharmacology 233 (2016):1963-1979.

Ferre, S, et al.  “New Developments on the Adenosine Mechanisms of the Central Effects of Caffeine and Their Implications for Neuropsychiatric Disorders.” J of Caffeine and Adenosine Research 8 (2018):121-131.

Qi H, Li S.  “Dose-response meta-analysis on coffee, tea and caffeine consumption with risk of Parkinson’s disease.”  Geriatr Gerontol Int 14 (2014):430-439.

Dani, JA.  “Neuronal Nicotinic Acetylcholine Receptor Structure and Function and Response to Nicotine.”  Int rev Neurobiol 124 (2015):3-19.

Tausk, V. “On the Origin of the “Influencing Machine” in Schizophrenia.”  J of Psychotherapy Practice and Research 1 (1992):185-206.

Kalmady, SV, et al.  “Relationship between Brain-Derived Neurotrophic Factor and Schneiderian First Rank Symptoms in Antipsychotic-Naive Schizophrenia.” Front Psychiatry 4 (2013):PMID:23847552.

Wearne, TA, Cornish JL.  “A Comparison of Methamphetamine-Induced Psychosis and Schizophrenia: A Review of Positive, Negative, and Cognitive Symptomatology.” Front Psychiatry 9 (2018):491.

Llado-Pelfort L, et al.  “Effects of Hallucinogens on Neuronal Activity.” Curt Top Behav Neurosci 36 (2018):75-105.

Seeman, P. “Cannibidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose.” Transl Psychiatry 6 (2016):1-4.

Riga, MS, et al.  “The serotonin hallucinogen 5-MeO-DMT alters portico-thalamic activity in freely moving mice:Regionally-selective involvement of 5-Ht1a and 5-HT2a receptors.” Neuropharmacology 142 (2018):219-230.

De Gregoria, D., et al.  “D-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.  Int. J. Mol. Sci. 17 (2016):1953-1973.

Brebion, G, et al.  “Verbal Fluency in Male and Female Schizophrenia Patients:Different Patterns of Association With Processing Speed, Working Memory Span, and Clinical Symptoms.” Neuropsychology 32 (2018):65-76.

Tikka, S.K., et al.  “Schneiderian first rank symptoms in schizophrenia: A developmental neuroscience evaluation.”  Int. J. Devel. Neuroscience 50 (2016):39-46.

Heal D.J., et al.  “Amphetamine, past and present-a pharmacological and clinical perspective.” J of Psychopharmacology 27 (2013): 479-496.

Huber, R., et al.  “Human Cortical Excitability Increases with Time Awake.” Cerebral Cortex 23 (2013):332-338.

Commons, K.G., Linnros, S.E.  “Delayed Antidepressant Efficacy and the Desensitization Hypothesis.”  ACS. Chem Neurosci (2019):A-E.

Zant, J.C, et al.  “Increases in extracellular serotonin and dopamine metabolite levels in the basal forebrain during sleep deprivation.”  Brain Research 1399 (2011):40-48.

Martiny, K.  “Novel Augmentation Strategies in Major Depression.”  Dan Med J 64 (2017)

Boland, E.M., et al.  “Meta-Analysis of the Antidepressant Effects of Acute Sleep Deprivation.” J Clin Psychiatry 78 (2017)

Trautmann, N., et al.  “Response to therapeutic sleep deprivation: a naturalistic study of clinical and genetic factors and post-treatment depressive symptom trajectory.” Neuropsychopharmacology 43 (2018):2572-2577.

Wolf, E., et al.  “Synaptic plasticity model of therapeutic sleep deprivation in major depression.”  Sleep Medicine Reviews 30 (2016):53-62.

Satoh, H., et al.  “Downregulation of Dopamine D1-like Receptor Pathways of GABAergic Interneurons in the Anterior Cingulate Cortex of Spontaneously Hypertensive Rats.”  Neuroscience 394 (2018):267-285.

Klein, M.O., et al.  “Dopamine:Functions, Signaling, and Associations with Neurological Diseases.” Cellular and Molecular Neurobiology 39 (2019):31-59.

Pearlson, G.D., Folley B.S.  “Schizophrenia, psychiatric genetics and Darwinian psychiatry: an evolutionary framework.”  Schizophrenia Bulletin 34 (2008):722-733.

Srinivasan, S., et al.  “Genetic Markers of Human Evolution Are Enriched in Schizophrenia.”  Biological Psychiatry 80 (2016):284-292.

Uher, R.  “Gene-Environment Interactions in Severe Mental Illness.”  Front Psychiatry 5 (2014): 48.

Power, R.A., et al.  “Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs. their unaffected siblings.”  JAMA Psychiatry 70 (2013):22-30.  

Polimeni, J., et al.  “Evolutionary Perspectives on Schizophrenia.”  Can J Psychiatry 48 (2003): 34-39.

Uher, R.  “The role of genetic variation in the causation of mental illness: an evolution-informed framework.”  Molecular Psychiatry 14 (2009):1072-1082.

Crow, T.J.  “Schizophrenia as the price that Homo sapiens pays for language: a resolution of the central paradox in the origin of the species.”  Brain Research Reviews 31 (2000): 118-129.

Crow, T.J.  “The missing gene: what happened to the heritability of psychiatric disorders?”  Molecular Psychiatry 16 (2011):362-364.

Crow TJ.  “March 27, 1827 and what happened later-the impact of psychiatry on evolutionary theory.”  Progress in Neuro-Psychopharmacology & Biol. Psychiat. 30 (2006): 785-796. 

Lowery, R.K., et al.  “Neanderthal and Denison genetic affinities with contemporary humans: introgression versus common ancestral polymorphisms.”  Gene 530 (2013):83-94.

Berlim, M.T. “The etiology of schizophrenia and the origin of language: overview of a theory.”

Compr Psychiatry 44 (2003):7-14.

Brune, M. “Schizophrenia-an evolutionary enigma?”  Neurosci Biobehav Rev. 28 (2004):41-53.

Hofman MA.  “Evolution of the Human Brain: When Bigger is Better.”  Frontiers in Neuroanat 8 (2014); 1-12. 

Ostler T.  “Heinz Werner: His Life, Ideas, and Contributions to Developmental Psychology in the First Half of the 20th Century.”  J Genet Psychol. (2016): 177, 231-243. 

Venkatasubramanian, G, et al.  “Digit Ratio (2D:4D) asymmetry and Schneiderian first rank symptoms: Implications for cerebral lateralization theories of schizophrenia.”  Laterality 16 (2011): 499-512.

Rudan I.  “New Technologies Provide Insights into the Genetic Basis of Psychiatric Disorders and Explain their Co-morbidity.”  Psychiatry Danub, 22 (2010).

Stabenau JR, Pollin W.  “Heredity and Environment in Schizophrenia, Revisited: The Contribution of Twin and High-Risk Studies.” J. Nerv and Mental Dis. 181 (1993): 290-297.

Moser DA, et al.  “Multivariate analyses reveal link between brain variance, psychosis.”  JAMA Psychiatry (2017).

Cahn W, et al.  “Brain Volume Changes in First Episode Schizophrenia; a 1-year Follow-up Study.”  Arch. Gen Psychiat. 59 (2002):, 1002-1010.

Lerario a, et al.  “Charles Bonnet syndrome: two case reports and review of the literature.”  J Neurol 260 (2013): 1180-1186.

Green JR, et al.  “Orbitofrontal Lobotomy with reference to effects on 55 psychotic patients.”  Presented at the joint meetings of the San Francisco Neurological, Southern California Neurosurgical and western Electroencephalographic Societies, Del Monte Lodge, Pebble Beach California, 1952, 2/29.

Swerdlow NR, et al.  “Startle Gating Deficits in a Large Cohort of Patients With Schizophrenia.”  Arch Gen Psychiat 63 (2006): 1325-1335.

Takahashi H, et al.  “Prepulse Inhibition of Startle Response: Recent Advances in Human Studies of Psychiatric Disease.”  Clin Psychopharmacol Neurosci 201 (2011): 102-111.

Mansbach RS, et al.  “Blockade of drug-induced deficits in prepulse inhibition of acoustic startle by ziprasidone.”  Pharmacy Biochem Behave.  69 (2001): 535-542.

Gebhardt J, et al.  “Maturation of prepulse inhibition (PPI) in childhood.”  Psychophysiology, 49 (2012): 484-488.

There are many more that have either been tossed or lost.  Oh, the cost!  (I sound like Dr. Seuss.)