Disorganized schizophrenia is characterized by incomprehensive speech as well as behavior and thought disorders. Until recently, it was considered as a subtype of schizophrenia (known as hebephrenia). These symptoms carry a poorer prognosis, primarily because these patients are much more frequently resistant to antipsychotics, but more importantly, the quality of life is severely impaired. The diagnosis is made by clinical criteria, whereas antipsychotics and psychotherapy are main therapeutic modalities.
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 . 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 . The hallmark of disorganized forms, however, is the onset of strange behavior and thinking, together with incomprehensible speech . Reduced verbal IQ and severe cognitive decline that can manifest through dysfunctional perceptional grouping are also considered as frequent findings in this form  .
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  :
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%) , drugs such as clozapine , which was shown to be effective for approximately 80% of refractory cases and amisulpride are considered as first-line agents  . 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 . 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  , 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 .
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 , as do premorbid functioning, a young age at onset and development of many negative symptoms . 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 . It is important to emphasize that the risk of suicide is several-fold greater in schizophrenic patients , and up to 10% of patients actually commit suicide . 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 . 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 . 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 .
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) . 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 . The vast majority of patients are adolescents and the diagnosis is most commonly made at 25 and 18 years for females and males, respectively . Various risk factors have been proposed :
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 . 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 . It is assumed that these cytokines are directly involved in structural changes of the developing brain , 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 . On the other hand, the cerebellum and the right striatum were structures in which increased concentrations of gray matter have been observed . 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" . Until recently, disorganized schizophrenia was considered as a specific subtype distinguished by thought and behavior changes , 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) . 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 . 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 . 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 . Risk factors include familial presence, birth defects and obstetric complications (infections, low birth weight, Rh incompatibility, fetal hypoxia), as well as socioeconomic status . Overall data suggest that the prevalence rate of schizophrenia is about 1% , with many studies identifying a slight predilection toward male gender . 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 . 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 , are constitutive symptoms of schizophrenia . 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 . Treatment initially comprises administration of antipsychotic drugs (clozapine and amisulprive have shown to be particularly effective)  , 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  .
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.