The clinical presentation can either have a gradual or abrupt onset and it is established that patients experience symptoms for up to 2 years before being recognized by physicians [2]. Initial findings may include mild social, cognitive or perceptual changes, but gradual worsening and the appearance of positive (delusions and various forms of hallucinations, including visual, auditory, tactile, olfactory or gustatory) and/or negative symptoms (anhedonia, poor speech, asociality) are typical features [2]. The hallmark of disorganized forms, however, is the onset of strange behavior and thinking, together with incomprehensible speech [2]. Reduced verbal IQ and severe cognitive decline that can manifest through dysfunctional perceptional grouping are also considered as frequent findings in this form [13] [14].

• Antipsychotic Agent

  We report the case of a patient suffering from disorganized schizophrenia who had life-threatening hematological side effects to treatment with antipsychotic agents. [ncbi.nlm.nih.gov]

  […] loxapine Rx N N X 4 reviews 6.0 Generic name: loxapine systemic Brand names: Loxitane, Adasuve Drug class: miscellaneous antipsychotic agents For consumers: dosage, interactions, For professionals: A-Z Drug Facts, AHFS DI Monograph, Prescribing Information [drugs.com]

  Moreover, the newer antipsychotic drugs block both dopamine D2 and serotonin (5-hydroxytryptamine [5-HT]) receptors. Clozapine, perhaps the most effective antipsychotic agent, is a particularly weak dopamine D2 antagonist. [emedicine.medscape.com]

• Camping

  A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: comparison of antipsychotics for metabolic problems (CAMP). Am J Psychiatry. 2011 Sep. 168(9):947-56. [emedicine.medscape.com]

• Disorganized Behavior

  Clinical Information A subtype of schizophrenia characterized by disorganized speech, disorganized behavior, and a flat or inappropriate affect; associated features include grimacing, mannerisms, and other oddities of behavior. [icd9data.com]

  Disorganized Behavior The symptoms include: disorganized thinking grossly disorganized behavior absent or inappropriate emotional expression. 6 The onset for disorganized schizophrenia is usually in the late teens. 19. [sites.google.com]

  When their cognitive disorganization is severe, their speech will usually be impossible to understand. When this occurs it is often referred to as “word salad”. Disorganized Behavior Disorganized behavior may be exhibited in a variety of ways. [psyweb.com]

  People with disorganized schizophrenia display disorganized thinking, grossly disorganized behavior, and absent or inappropriate emotional expression. [knowyourdisease.com]

• Auditory Hallucination

  While hallucinations can occur among any of the senses, for people with schizophrenia, auditory hallucinations are the most common. [riverwoodsbehavioral.com]

  Auditory hallucinations may accompany a delusion and are, therefore, usually related to its theme. [healthcommunities.com]

  Paranoid Schizophrenia Paranoid schizophrenia causes delusions and auditory hallucinations that result in paranoia and anxiety. Paranoid schizophrenia is considered one of the most treatable types of schizophrenia. [psychiatric-disorders.com]

  The patient is preoccupied with at least one delusion (usually persecutory in nature) or is experiencing frequent auditory hallucinations. [psycom.net]

• Anhedonia

  Sometimes, there is a complete lack of emotion, including anhedonia (lack of pleasure), and avolition (lack of motivation). [en.wikipedia.org]

  Examples of negative symptoms can include things like: Flattened affect Anhedonia Reduced speech Lack of initiative Flattened Affect People with flattened affect appear emotionless or have a very limited range of emotions. [schizophrenia.about.com]

  These are due to anhedonia and avolition, the disinterest in pleasure and a lack of motivation in seeking enjoyment. [schizlife.com]

  Sometimes, there is a complete lack of emotion, including anhedonia (the lack of pleasure ), and avolition (a lack of motivation). [ipfs.io]

  Sometimes there is a complete lack of emotion, including anhedonia (the lack of pleasure ), and avolition (a lack of motivation). [research.omicsgroup.org]

• Anger

  The website includes resources specifically focused to; general Mental Health, Depression, Stress, Anxiety, Insecurities, Self-harm Schizophrenia, Bipolar, Anger Management, Eating Disorders, Coping, general Addiction, Alcohol, Smoking, Gambling, Drugs [haveigotaproblem.com]

  Symptoms common to other subtypes, like disorganized speech and flattened affect, are not usually prominent in episodes of paranoia, but anger, irritability, and extreme anxiety are. [healthcommunities.com]

  This can lead to physical and emotional detachment, social withdrawal, anger, and anxiety. Many people with symptoms of paranoia will be fearful and seek to avoid others. [medicalnewstoday.com]

  People with a condition called paranoid schizophrenia develop problems that commonly include anxiety, unpredictable anger, and a delusional belief in the hostile intentions of others. [elementsbehavioralhealth.com]

  They can also exhibit the following: anxiety anger aloof or argumentative behavior Those with persecutory delusions may also be violent or suicidal, but have the greatest ability to become functionally stable over time. [healthline.com]

• Withdrawn

  A person may seem depressed and withdrawn. Cognitive symptoms affect the thought process. These include trouble using information, making decisions, and paying attention. No one is sure what causes schizophrenia. [icdlist.com]

  They are also often socially withdrawn. Treatment Disorganized schizophrenia usually requires lifelong treatment. [psyweb.com]

  Withdrawn and lifeless: Showing no feelings or motivation, or lacking interest in normal daily activities. People with schizophrenia have at least two of these symptoms for at least 6 months. [webmd.com]

  Belief that thoughts are being inserted or withdrawn from one’s consciousness or are being broadcasted to others. A person may show all or none of these symptoms. [trialx.com]

• Agitation

  You can recognize a disorganized schizophrenia sufferer by the disinhibited, agitated and purposeless behavior. This is considered to be one of the most debilitating mental illnesses. [getholistichealth.com]

  Disorganized schizophrenia is a type of schizophrenia characterized by disinhibited, agitated, and purposeless behavior. [depression-guide.com]

  Also, frustration and agitation may cause them to lash out. [schizophrenia53.weebly.com]

  Alternative names Hebephrenic schizophrenia ; Schizophrenia - disorganized type Definition Disorganized schizophrenia is a type of schizophrenia characterized by disinhibited, agitated, and purposeless behavior. [health.am]

  Individuals with this type of schizophrenia may become agitated for no apparent reason. They may engage in very inappropriate sexual behavior, such as touching themselves while in a public place. [psyweb.com]

• Confusion

  […] behavior; usually becomes evident during puberty; the most common diagnostic category in mental institutions disorganized lacking order or methodical arrangement or function disorganised lacking order or methodical arrangement or function disorientation confusion [vocabulary.com]

  I should like, however, to draw your attention to the fact that all this is taking place in a framework in which there is confusion and a schizophrenic attitude about criminal law. [fi.bab.la]

  Occasional confusion and disorganization is normal for most people. In schizophrenia, however, the degree of confusion and disorganization significantly reduces or destroys a person's ability to communicate. [healthcommunities.com]

  This can lead to fear, confusion, and suicidal thoughts and behavior. [medicalnewstoday.com]

  The confusion of emotions and facial affect also arises at inappropriate times, causing others to view the person as deranged, sadistic, depressed, etc. [schizlife.com]

• Stupor

  […] disorganisation a condition in which an orderly system has been disrupted disorganization a condition in which an orderly system has been disrupted catatonic type schizophrenia a form of schizophrenia characterized by a tendency to remain in a fixed stuporous [vocabulary.com]

  Catatonic schizophrenia was marked by striking motor behaviour, such as remaining motionless in a rigid posture for hours or even days, and by stupor, mutism,… Read More [britannica.com]

  […] loss of contact with reality;appearance in young adulthood consisting of hallucinations and delusions, psychotic Catatoic Stupor-immobile, expressionless, coma like state Paranoid-delusions of gradeur, persecution or jealousy Disorganized-incoherent thoughts [quizlet.com]

  Disorganized schizophrenia Hebephrenia F20.2 Catatonic schizophrenia Catatonic schizophrenia is dominated by prominent psychomotor disturbances that may alternate between extremes such as hyperkinesis and stupor, or automatic obedience and negativism. [apps.who.int]

• Irritability

  […] to unsuitable reading, the naive occupation of the mind with the "highest problems," the crude "readiness" of judgment, the pleasure in catch words and sounding phrases, also sudden changes of mood, depression and unrestrained merriment, occasional irritability [ipfs.io]

  You could feel very down, or swing between super high-energy or highly irritable and very low, too. Psychotic symptoms have to sometimes happen even when your mood is OK for you to have schizoaffective disorder. [webmd.com]

  Fecal transplant is used to treat gut infections and is now being studied as a treatment for obesity, urinary tract infections, irritable bowel syndrome and more. [nytimes.com]

• Excitement

  […] a condition in which an orderly system has been disrupted catatonic type schizophrenia a form of schizophrenia characterized by a tendency to remain in a fixed stuporous state for long periods; the catatonia may give way to short periods of extreme excitement [vocabulary.com]

  Catatonic schizophrenia deals more with psychomotor poverty and excitement. Disorganized schizophrenia, however, is concerned with behavioral, emotional, and psychological disorganization. [schizlife.com]

  […] boastful, half-embarrassed, shy behaviour, the foolish laughing, the unsuitable jokes, the affected speech, the sought-out coarseness and the violent witticisms are phenomena which in healthy individuals, as in the patients, indicate that slight inward excitement [ipfs.io]

  […] factors create a vulnerability or susceptibility, inclusion of brain trauma, family environment a form of schizophrenia characterized by a tendency to remain in a fixed, stuporous state for long periods or expereince a state of hyperactivity or catatonic excitement [quizlet.com]

• Sexual Dysfunction

  […] with other psychoactive substance-induced disorders F19.980 Other psychoactive substance use, unspecified with psychoactive substance-induced anxiety disorder F19.981 Other psychoactive substance use, unspecified with psychoactive substance-induced sexual [icd10data.com]

A detailed heterogeneous patient history (including relatives and friends of the patient) is the single most important step when it comes to making the diagnosis of disorganized schizophrenia. Diagnostic criteria for the newly classified "general" type of schizophrenia that have been proposed are on the basis of clinical findings only and include [3] [9]:

• Presence of two or more symptoms such as disorganized speech, delusions, hallucinations, catatonic behavior and negative symptoms, including diminished emotional expression or avolition.
• These symptoms should persist for a significant amount of time during a 1 month period over the course of 6 months.
• Significant impairment of socio-occupational activities, such as work, self-care or interpersonal relationships.
• Exclusion of other similar conditions, such as mood disorders, depression, bipolar disorder and drug abuse, in which case a full drug panel should be conducted.
• For children in whom autism is suspected, the presence of significant delusions and hallucinations are considered as a necessary criterion.

Although there are no laboratory tests to further evaluate schizophrenia, several inquiries and questionnaires can be used to asses the mental status of the patients. Basic blood studies, however, consisting of a complete blood count (CBC), serum electrolyte levels and liver transaminases, should be conducted.

Treatment principles initially rely on antipsychotics because of their beneficial effect in many patients. Although drug resistance was reported to be significant among patient with disorganized symptoms (up to 30%) [1], drugs such as clozapine [15], which was shown to be effective for approximately 80% of refractory cases and amisulpride are considered as first-line agents [1] [10]. An additional issue encountered when using pharmacological agents is drug adherence, and for this reason, newer drugs are administered less frequently in higher doses and various formulations exist [2]. Because drug resistance is often encountered, however, various forms of psychotherapy are introduced as an important therapeutic method for many patients. As a modality of last resort, electroconvulsive therapy (ECT) may be successful in patients who do not respond to medications. Despite the fact that several case reports have advocated the use of ECT [11] [16], clear guidelines on its use still need to be defined. Regardless of the treatment method, is it essential to ensure a pleasant and supporting environment that can enable the patient to continue his/her daily activities with variable levels of support [2].

Numerous factors determine the both short-term and long term-outcomes of schizophrenia. Usually, one third of patients can recover and significantly improve, one third suffers from intermittent relapses, whereas one third of patients are profoundly affected by this disorder. The presence of disorganized symptoms usually indicates a poor prognosis [12], as do premorbid functioning, a young age at onset and development of many negative symptoms [2]. One of the reasons for such prognosis is the issue of drug resistance, which was shown to occur in up to 30% of patients suffering from disorganized symptoms [1]. It is important to emphasize that the risk of suicide is several-fold greater in schizophrenic patients [7], and up to 10% of patients actually commit suicide [2]. For these reasons, it is imperative to make an early diagnosis and initiate appropriate treatment as soon as possible.

The exact cause of schizophrenia remains to be fully disclosed. Current theories most likely include an immune-mediated pathogenesis that involves aberrant concentrations of cytokines such as IL-1, IL-6 and EGF and several other in both the central nervous system and peripheral blood [4]. Moreover, genetic mutations involving colony-stimulating factor receptor 2 alpha (CSF2RA) and interleukin 3 receptor alpha (IL3RA) genes, as well ass major histocompatibility complex (MHC) mutations that have been discovered further support this theory [4]. Various obstetric complications, such as maternal influenza infection and fetal hypoxia that lead to neurodevelopmental abnormalities, have also been strongly implicated as one of the main culprits [2].

Although the exact prevalence rates of disorganized schizophrenia are unknown, its recent deletion as a separate category mandates observation of overall epidemiological data regarding schizophrenia. A prevalence rate of 1% on a global scale was determined for this psychiatric disorder, with minimal differences across genders, although a slightly higher number of cases was encountered among males in recent studies (1.4:1 male-to-female ratio) [7]. Incidence rates are established around 15.2 per 100,000 persons, ranging from 7.7-43.0 per 100,000 individuals, whereas a lifetime risk was estimated a 7.2 per 1,000 individuals [7]. The vast majority of patients are adolescents and the diagnosis is most commonly made at 25 and 18 years for females and males, respectively [2]. Various risk factors have been proposed [6]:

• Maternal infections such as influenza (during second trimester), rubella and toxoplasmosis.
• Obstetric factors - Complications encountered during pregnancy (bleeding, Rh incompatibility, diabetes), impaired fetal growth (low birth weight, usually < 2500 g, congenital diseases), and complications during delivery (asphyxia and uterine atony) have shown to be significantly associated with higher incidence rates of schizophrenia open link [2] [6].
• Positive family history - the risk of developing schizophrenia is almost 10 times higher for individuals with a 1st degree relative who suffers from this disorder [2].
• Socioeconomic factors - poverty, famine, migrant status and extensive emotional trauma are all considered to be important [2] [6].
• Drug use - A 2-25 fold increased risk of schizophrenia is seen in individuals who have previously consumed cannabis and it was further established that cannabis can, in fact, trigger the onset of symptoms [6].

Despite the fact that the exact pathophysiological mechanism of schizophrenia remains to be elucidated, numerous advances toward this goal have been made. Some theories suggest abnormalities of the dopaminergic and glutamate neurotransmitter system, which is supported by the efficacy of antipsychotic drugs that primarily reduce the activity of dopamine and its receptors throughout the central nervous system [2]. Recent studies, however, have highlighted the role of inflammatory changes in the brain. Namely, animal models in whom concentrations of IL-1, IL-6, EGF and neuregulin-1 during embryonal development or as neonates are abnormal, have shown to develop schizophrenia-like symptoms after puberty [4]. It is assumed that these cytokines are directly involved in structural changes of the developing brain [4], as studies have determined a decreased size of the anterior hippocampus, enlargement of the ventricular system and changes in gray matter concentrations, particularly in the left insular, mediofrontal, anterior cingulate and dorsolateral prefrontal regions [5]. On the other hand, the cerebellum and the right striatum were structures in which increased concentrations of gray matter have been observed [5]. The combined effects of impaired neurotransmitter signaling, cytokine expression and consequent brain changes could provide a more detailed perspective on the etiology and development of schizophrenia and further studies should aim to resolve this multifactorial condition.

Having in mind the fact that the exact mechanism of disease remains unknown, not much can be done in terms of prevention. In order to ensure the best possible chances for patients in whom a clinical diagnosis is made, it is essential to obtain an early diagnosis, as numerous studies have indicated its benefit.

Disorganized schizophrenia was initially described at the end of the 19th century in adolescents who developed severe cognitive and functional impairment preceded by mood changes and disorganized symptoms, leading to the term "hebephrenia" [1]. Until recently, disorganized schizophrenia was considered as a specific subtype distinguished by thought and behavior changes [2], but because poor reliability and stability in terms of treatment and discrimination between various forms, it was removed as a specific diagnosis from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) [3]. Numerous theories that include genetic, environmental, infectious, obstetric and autoimmune factors have been proposed in the pathogenesis of schizophrenia. A strong association between abnormal concentrations of various inflammatory cytokines such as interleukin-1 (IL-1), IL-6 and epidermal growth factor (EGF) and the development of this psychiatric disorder has been well-established [4]. Additionally, polymorphisms of genes that are responsible for white blood cell (WBC) maturation and formation of several components of the immune system have been identified [4]. Although the exact pathophysiological mechanism remains unclear, various macroscopic changes in cerebral structures were solidified. Concentrations of gray matter in the cerebellum and right striatum were shown to be substantially increased in schizophrenic patients, emphasizing the important role of paralimbic structures in the development of schizophrenia [5]. Risk factors include familial presence, birth defects and obstetric complications (infections, low birth weight, Rh incompatibility, fetal hypoxia), as well as socioeconomic status [6]. Overall data suggest that the prevalence rate of schizophrenia is about 1% [2], with many studies identifying a slight predilection toward male gender [7]. The diagnostic criteria for disorganized schizophrenia include the appearance of symptoms such as disorganized thinking and speech that may be incomprehensible, in addition to the standard clinical course of schizophrenia that involves several phases and appearance of various symptoms [2]. Delusions and hallucinations (positive symptoms), anhedonia and reduction in normal functioning (negative symptoms) and cognitive decline, which was in particularly shown to be present in these patients [8], are constitutive symptoms of schizophrenia [2]. The diagnosis rests on clinical criteria - the presence of such symptoms for a significant portion of time during a period of 1 month within at least 6 months and exclusion of other conditions that may have a similar clinical presentation, such as mood disorders or drug abuse [9]. Treatment initially comprises administration of antipsychotic drugs (clozapine and amisulprive have shown to be particularly effective) [1] [10], but the presence of disorganized symptoms is a strong indicator of poor prognosis, mainly because of drug resistance. For these reasons, psychotherapy is becoming more important in long-term management of patients, while electroconvulsive therapy, as a last resort, has shown good results in isolated case reports [2] [11].

Disorganized schizophrenia (sometimes referred to as "hebephrenia") was, until recently, a distinct form of schizophrenia, a psychiatric disorder characterized by delusions, hallucinations and disorganized speech and thinking. The introduction of new clinical criteria, however, led to abolition of all subtypes and the specific symptoms are now a constitutive part of schizophrenia in general. Since its initial description at the end of the 19th century, much has been discovered regarding its occurrence, but the exact cause remains unknown. Studies have determined that genetic mutations, activation of substances that cause inflammation (cytokines), activity of dopamine and glutamate as main neurotransmitters of the central nervous system and various maternal factors all contribute to the development of schizophrenia. Estimations regarding its presence in the world suggest that approximately 1% of the population is suffering from schizophrenia and numerous risk factors have been identified. Young age, cannabis abuse, maternal and obstetric events (infections by influenza, rubella and toxoplasmosis, together with both pregnancy and delivery complications) and presence of a close family member suffering from schizophrenia are considered as most important. The diagnosis can be made only by clinical criteria, which is why the importance of a detailed patient interview must be highlighted. Equally important are conversations between the physician and the family or friends of the patient that may provide key data that can aid in the diagnostic workup. Most prominent symptoms include delusions, hallucinations (such as visual or auditory), disorganized thinking and incomprehensible speech. Lower verbal IQ and severe cognitive impairment are also frequent manifestations of disorganized schizophrenia. Symptoms must be widely present for at least 1 month over the course of 6 months, while exclusion of other conditions that have similar symptoms such as mood and bipolar disorders, depression, but also drug abuse must be carried out. Treatment principles rely on the use of antipsychotic drugs, which unfortunately show markedly poorer results in patients with disorganized symptoms. Clozapine, and to a lesser extent, amisulpride, however, have shown to be effective in patients with refractory schizophrenia and their use is highly recommended. Psychotherapy is becoming the mainstay of therapy due to increasing drug resistance, while electroconvulsive therapy (ECT) is interpreted as the last resort because of its unclear indications, although good results were achieved in isolated cases. The overall prognosis of schizophrenia is variable, but individuals who present with disorganized symptoms carry a substantially poorer prognosis. In general, one third of patients suffer from life-long inability to continue their daily activities as independent individuals, which is why a supportive environment is equally important in therapy. Because up to 10% of schizophrenic patients commit suicide and because significant disability may be caused by this condition, an early diagnosis through meticulous patient interviews may substantially reduce the burden of this condition in the population.

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