Schizophrenia is clinically heterogeneous: patient-cases
Marta is a 65-year-old woman with schizophrenia. She suffered her first psychotic break at age 25 and has had multiple hospitalizations over the years. Her primary delusion is centered on the belief that she is a psychiatrist. She believes that medications she had taken in the past allowed the Central Intelligence Agency (CIA) to gain control of her mind and that the CIA sends people “mindreaders” to follow her. She refutes the diagnosis of schizophrenia and declines treatment. She’s been arrested multiple times for vandalism, terrorist threats, and assault. Although she’s been intermittently homeless, most recently, she was living at a motel, hit another guest whom she believed was sent by the CIA, and was arrested. In jail, correctional officers notice that she wears her clothes inside out, talks to herself, and when she talks to them, what she says doesn’t make sense.
DeShawn is a 23-year-old man with schizophrenia. He played sports in school, earned average grades, and had a large circle of friends. In high school, he began smoking cannabis and slowly withdrew from all activities. He suffered his first psychotic break at age 19 and was hospitalized for three months. While hospitalized, he felt so hopeless about the diagnosis of schizophrenia that he tried to hang himself in the bathroom. He attempted suicide again shortly after he was discharged. After spending several years recovering, he returned to community college. While his parents are thrilled with his progress, they worry that he spends so much time in his room, seldom talks with them, and has few friends. They miss the energetic, outgoing young man that he used to be and wonder if there’s a medication or something they can do to bring him back.
Marta and DeShawn illustrate the substantial variation in how individuals experience schizophrenia. The clinical complexity of the disorder manifests in different symptom domains, associated symptoms, comorbidities, disease trajectories, and in treatment response. The variation in the presentation and course of the illness was recognized when schizophrenia was first described over 150 years ago.
The two patient cases illustrate the core schizophrenia symptom clusters (Table 1). The diagnosis of schizophrenia is based on a combination of distinctive symptoms of sufficient duration and severity in the absence of other possible causes, e.g., substance use, medical or neurological illnesses, or other psychiatric illnesses. The diagnostic criteria for schizophrenia are outlined in the two diagnostic classification systems currently used in clinical practice—the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) and the International Classification of Diseases, 11th Revision (ICD-11) (Table 2). A key difference between the two systems is the DSM-5-TR’s inclusion of functional deficits as a criterion. This inclusion acknowledges the importance of neurocognitive and social cognitive impairments, symptoms that are largely responsible for the magnitude of disability in schizophrenia.Reference Bowie and Harvey1-Reference Harvey, Strassnig and Silberstein5
Table 1. Schizophrenia Symptoms and Comorbidities
Table 2. Comparison of DSM-5-TR and ICD-11 Diagnostic Criteria for Schizophrenia
Natural history of schizophrenia
For many individuals, schizophrenia follows a typical course that can be divided into four phases: premorbid, prodromal, psychotic, and chronic/residual (Figure 1).
Figure 1. The natural history of schizophrenia.
Premorbid stage
Children who go on to develop schizophrenia later in life are not prospectively distinguishable from their peers. If any abnormalities are present, they are subtle and nonspecific. Given schizophrenia’s neurodevelopmental origin, abnormalities in brain development manifest as early intellectual Reference Kahn and Keefe 6 -Reference Woodberry, Giuliano and Seidman 8 and neuromotor abnormalities.Reference Filatova, Koivumaa-Honkanen and Hirvonen 9 Academic underachievement is often observed in elementary school and onwards in children who later develop schizophrenia compared with peers who do not go on to develop schizophrenia.Reference Tempelaar, Termorshuizen, MacCabe, Boks and Kahn 10
Prodromal stage
About 75-80% of people who develop schizophrenia experience a prodromal phase.Reference Häfner, Löffler, Maurer, Hambrecht and an der Heiden 11 For most patients, this stage lasts years and typically occurs in adolescence or early adulthood. Depressive symptoms are typically the first to emerge and appear on average 52 months prior to the first hospitalization.Reference Häfner, Löffler, Maurer, Hambrecht and an der Heiden 11 Other changes in thinking and feeling include anxiety, sleep disruption, and difficulties concentrating. Social withdrawal, role failure resulting in academic/occupational problems, and a decline in self-care are common. As the prodrome progresses, attenuated psychotic symptoms may develop. These include perceptual changes (colors may seem brighter or distorted, increased sensitivity to sounds), paranoia, uneasiness, preoccupation with certain ideas, and ideas of reference.
Psychotic stage
This stage begins with the onset of frank psychosis, which may emerge abruptly over a period of days to weeks or insidiously over months or longer. The onset for men is in the early to mid-20s and for women in the late-20s or after age 40. Psychosis is characterized by the loss of touch with reality, altered perceptions, and can be profoundly distressing to the individual. Symptoms include hallucinations, delusions, and disorganized speech and behavior. The first psychotic episode is a crucial timepoint for intervention as patients tend to be more responsive to antipsychotics and psychosocial treatment. Delays in treatment result in a longer duration of psychosis which is associated with poorer outcomes in a variety of domains including increased severity of symptoms and decreased likelihood of remission.Reference Marshall, Lewis, Lockwood, Drake, Jones and Croudace 12 -Reference Perkins, Gu, Boteva and Lieberman 14
Chronic/residual stage
There is considerable variation in the trajectory of the disease after the first psychotic episode, and many factors influence the course of the illness including genetics, gender, premorbid functioning, substance use, adherence to treatment, and physical health. After the first psychotic episode, about 20% of patients will recover as defined by clinical and social/functional recovery for at least one year.Reference Hansen, Speyer and Starzer 15 Others experience recurring psychotic relapses. Frequent and/or severe relapses can result in clinical deterioration or disease progression, which leads to decreased responsiveness to treatment, inability to achieve full recovery, and greater degrees of disability.Reference Emsley, Chiliza and Asmal 16 , Reference Lin, Joshi and Keenan 17 Only one in seven patients experiences recovery when recovery is defined as a very good outcome in two domains—clinical and social/functional for at least two years.Reference Jääskeläinen, Juola and Hirvonen 18
Primary symptoms of schizophrenia
Positive symptoms
Positive symptoms—hallucinations and delusions—refer to ideas, beliefs, and perceptions that add to or distort an individual’s normal functioning.
A delusion is a false belief, judgment, or knowledge that is held despite evidence to the contrary. The decision to call a belief a delusion is made by an observer, not by the believer, since the believer holds the delusional belief with the same conviction as nondelusional beliefs. A delusion transforms an individual’s basic experience of the world. For example, Marta’s experience of the world is one of malevolence and persecution. Twelve delusional themes have been identified with persecutory delusions being the most common with a pooled point prevalence of 64.5% (60.6-68.3), followed by referential delusions 39.7% (34.5-45.3), grandiose delusions 28.2% (24.8-31.0), delusions of control 21.6% (17.8-26.0), and religious delusions 18.3% (15.4-21.6).Reference Collin, Rowse, Martinez and Bentall 19 It is not uncommon for patients to have multiple delusions.Reference Brakoulias and Starcevic 20
Hallucinations are false perceptions that occur spontaneously in any sensory modality (sight, hearing, smell, taste, touch). Auditory hallucinations are the most common type of hallucinations with a lifetime prevalence of up to 80%.Reference McCarthy-Jones, Smailes and Corvin 21 Auditory hallucinations can take the form of sounds (bells, screeches, screams) or voices (auditory verbal hallucinations, AVH). AVH can range from single words to conversations involving multiple different voices to voices giving commands. Visual hallucinations have been observed in up to 26% of patients, followed by tactile hallucinations, olfactory hallucinations, and gustatory hallucinations, which occur less frequently.Reference Chouinard, Shinn and Valeri 22 -Reference Mueser, Bellack and Brady 24 Visual hallucinations have been associated with more severe illness, suicide attempts, and with certain types of delusions.Reference Chouinard, Shinn and Valeri 22 , Reference Kreis, Wold and Åsbø 25
Hallucinations and delusions may emerge concomitantly, one may emerge before the other, or only one or the other may be present.Reference Compton, Potts, Wan and Ionescu 26 The formation and content are influenced by the social and cultural background of the patient.Reference Ghanem, Evangeli-Dawson and Georgiades 27 , Reference Lucas, Sainsbury and Collins 28 Positive symptoms typically follow a remitting and relapsing course.Reference Addington, Heinssen and Robinson 29 -Reference Rosen, Harrow, Humpston, Tong, Jobe and Harrow 31 Persistent delusions and hallucinations can interfere with employment,Reference Harvey, Heaton, Carpenter, Green, Gold and Schoenbaum 32 relationships, daily function, and increase the risk of violence.Reference Swanson, Swartz and Van Dorn 33 Activity (as opposed to inactivity) and frequent social contacts are protective. Positive symptoms are the symptom cluster that responds best to currently available antipsychotic medications; however, the rate of response drops from 90% to 65% across the first two relapses.Reference Lieberman, Alvir and Koreen 34
Negative symptoms
Symptoms that are consistent with a deficit or loss of function are called negative symptoms and are apparent in two domains: expression (blunted affect, alogia) and motivation (amotivation, asociality, anhedonia). Negative symptoms commonly emerge during the prodromal phase and are a risk factor for progression to psychosis.Reference Piskulic, Addington and Cadenhead 35 In chronic schizophrenia, almost 60% of patients demonstrate at least one negative symptom with social withdrawal being the most common (45.8%), followed by emotional withdrawal (39.1%), poor rapport (35.8%), and blunted affect (33.1%).Reference Bobes, Arango, Garcia-Garcia and Rejas 36 Negative symptoms worsen with age and are poorly responsive to most currently available pharmacologic treatments,Reference Correll and Schooler 30 , Reference Crow 37 although potential treatments may be on the horizon.Reference Marder and Umbricht 38 Primary negative symptoms are directly related to the pathophysiology of the illness, while secondary negative symptoms are caused by antipsychotic side effects, comorbid depression, substance use, social deprivation, or as sequelae of positive symptoms.Reference Kirschner, Aleman and Kaiser 39 Since secondary negative symptoms can be treated, disentangling them from primary negative symptoms is important.
As shown in Table 3, negative symptoms significantly impact an individual’s ability to live independently, build relationships, and maintain employment. They are a key contributor to schizophrenia-related disability.Reference Foussias, Agid, Fervaha and Remington 40 -Reference Okada, Hirano and Taniguchi 44
Table 3. Negative Symptoms, Association with Other Impairments, and Functional Outcome
Disorganization
Disorganization emerged as a symptom cluster when it separated from positive and negative symptoms in studies using factor analysis.Reference Andreasen and Grove 45 -Reference Blanchard and Cohen 47 Since an individual’s thought process cannot be known, it is inferred through communication or speech. Disorganized speech infers disorganization of the form of thoughts and reflects a cluster of related cognitive and linguistic disturbances.Reference Roche, Creed, MacMahon, Brennan and Clarke 48 This became known over time as a formal thought disorder to distinguish it from pathology involving the content of thought, i.e., delusions and ideas of reference. Ozbek and Alptekin (2022) define a formal thought disorder as “…any deficiency of organizing words, concepts, phrases, or ideas in a logical order to express a certain purpose.”Reference Uzman Özbek and Alptekin 49 Disorganization is commonly identified in speech that seems to slip off track or derails, is tangential, or is circumstantial.Reference Andreasen and Grove 45 More pathological forms of disorganization are incoherent speech, neologisms, clang association, thought blocking, and echolalia.
As an individual becomes increasingly psychotic, the degree of disorganization increases exponentially.Reference Roche, Creed, MacMahon, Brennan and Clarke 48 Disorganization is a prominent feature in first-episode patients, and it diminishes with treatment.Reference Pelizza, Leuci and Maestri 50 It affects approximately half of patients with schizophrenia.Reference Breier and Berg 51 As expected, there is a strong relationship between disorganization and all domains of neurocognitive functioningReference Ventura, Hellemann, Thames, Koellner and Nuechterlein 41 and a significant, inverse relationship with social functioning.Reference Marggraf, Lysaker, Salyers and Minor 52
Cognition in schizophrenia
Cognition encompasses neurocognition and social cognition. Neurocognition refers mental abilities such as attention, memory and learning, reasoning and problem-solving. Social cognition includes processes involved with perceiving, processing, and regulating information about other people and ourselves. Deficits in neurocognition and social cognition result in difficulties in social, educational, and occupational spheres of life.Reference Bowie and Harvey 1 , Reference Harvey, Bosia and Cavallaro 2 , Reference Green 4 , Reference Harvey, Strassnig and Silberstein 5 , Reference Harvey, Heaton, Carpenter, Green, Gold and Schoenbaum 32 , Reference Green, Horan and Lee 53 -Reference Fett, Viechtbauer, Dominguez, Penn, van Os and Krabbendam 55
Neurocognition in schizophrenia
There is considerable cognitive heterogeneity among individuals with schizophrenia. Three cognitive subgroups have been identified: a group that is relatively cognitive intact with mild impairments (25% of sample), an intermediate group, and a group with severe and widespread deficits (44% of the sample).Reference Carruthers, Van Rheenen, Gurvich, Sumner and Rossell 56 The magnitude of the neurocognitive deficits can be significant with scores of 1-2 standard deviations below healthy controls across multiple domains.Reference Heinrichs and Zakzanis 57 -Reference McCutcheon, Keefe and McGuire 59
Evidence of neurocognitive impairments can be seen as early as childhood. Woodberry and colleagues (2008) found that years before the onset of psychotic symptoms, as a group, individuals with schizophrenia demonstrated mean IQ scores that were one-half standard deviation below those of healthy controls.Reference Woodberry, Giuliano and Seidman 8 Deficits in attention, memory, executive functions, and processing speed have been observed in the premorbid stage.Reference Sheffield, Karcher and Barch 60 Although data from shorter-term cohort studies suggests that cognition remains fairly stable after illness onset, Jonas and colleagues (2022) performed the largest long-term cohort study of cognition which showed that the trajectory of general cognitive ability is stable until 14 years prior to psychosis onset. Then, general cognitive ability declines from adolescence through the first psychotic episode and during the first two decades of the illness. At age 49, a second decline in cognitive abilities commences, well before that seen in healthy controls.Reference Fett, Velthorst and Reichenberg 61 , Reference Jonas, Lian and Callahan 62 This earlier decline may be due in part to accelerated aging.Reference Seeman 63
Neurocognitive impairment is correlated with functional disability (Table 4) and is responsible for the indirect costs of the disease. Typical goals of adulthood—educational achievement, competitive employment, self-sufficiency, self-care—may not be attained by individuals with schizophrenia due to cognitive impairments and social deficits. For example, at any given time, as few as 10% of individuals with schizophrenia are employed.Reference Marwaha, Johnson and Bebbington 64 Approximately 25-40% of people with schizophrenia live independently, and over 75% of this group is supported by disability compensation.Reference Harvey, Heaton, Carpenter, Green, Gold and Schoenbaum 32 Only 31% of people with schizophrenia own a car.Reference Steinert, Veit, Schmid, Jacob Snellgrove and Borbé 65 Cognitive impairments interfere with patients’ ability to manage chronic medical conditions and medications. Medical problems go untreated, and poor medication adherence increases the risk of a psychotic relapse.Reference Harvey, Heaton, Carpenter, Green, Gold and Schoenbaum 32
Table 4. Profile of Neurocognitive Dysfunction in Schizophrenia and Real-World Example Using a Patient-Case
Social cognitive impairment
Approximately 75% of people with schizophrenia demonstrate at least mild impairments in social cognition.Reference Hajdúk, Harvey, Penn and Pinkham 66 Similar to neurocognitive deficits, there is considerable heterogeneity with most people experiencing mild-moderate deficits and one-third of patients suffering from severe impairments (Table 5). Severe impairments are associated with older age, fewer years of education, symptom burden, more neurocognitive impairment, and poorer function.Reference Hajdúk, Harvey, Penn and Pinkham 66 , Reference Vaskinn, Sundet and Haatveit 67 Social cognitive impairments are present well before the onset of the first psychotic break and remain stable over the course of the illness.Reference Bowie and Harvey 1 , Reference Green, Horan and Lee 53 , Reference Green, Horan, Lee, McCleery, Reddy and Wynn 68
Table 5. Social Cognitive Processes and Real-World Example of Impairment Using Patient Case
Social cognition demonstrates an even stronger link to community functioning than does neurocognitive impairment and accounts for about 16% of the variance in functioning compared to 6% for neurocognitive functioning.Reference Fett, Viechtbauer, Dominguez, Penn, van Os and Krabbendam 55 Deficits in mental state attribution, or the ability to infer the mental state of another, account for most of the variance. Social disability encompasses three areas: independent living, education and employment, and interpersonal relationships. In terms of interpersonal relationships, friendship networks tend to be small (mean number of friends is 1.57) but when present, friendships are highly valued.Reference Harley, Boardman and Craig 69 Although approximately one-third of patients never marry, those who do find marriage to be a source of support.Reference Lyngdoh, Antony, Basavarajappa, Kalyanasundaram and Ammapattian 70 People with schizophrenia may experience social disconnection, which appears to be due to impairments in both social cognition as well as social motivation.Reference Green, Horan, Lee, McCleery, Reddy and Wynn 68 Social disconnection is associated with an increased risk of adverse health outcomes and all-cause mortality.
Accessory symptoms of schizophrenia
Mood disturbances
Depression is common in all phases of schizophrenia with factor analysis identifying it as a major symptom dimension. Over 40% of help-seeking individuals at high risk for developing psychosis fulfill criteria for a depressive disorder.Reference Fusar-Poli, Borgwardt and Bechdolf 71 During the prodromal phase of the illness, over 60% of patients fulfilled criteria for a lifetime depressive disorder.Reference Rosen, Miller, D’Andrea, McGlashan and Woods 72 Nearly 50% of first-episode patients have clinically relevant levels of depressive symptoms, with 25% experiencing a full-depressive episode.Reference Herniman, Allott and Phillips 73 In chronic schizophrenia, higher rates of depression—up to 60% of patients—are seen during acute episodesReference Upthegrove, Marwaha and Birchwood 74 compared to a rate of 30% during periods of stability.Reference Etchecopar-Etchart, Korchia and Loundou 75 , Reference Fond, Boyer and Berna 76
Depression is linked to negative outcomes in schizophrenia. It is a major risk factor for suicide and is present in over 50% of patients who die by suicide.Reference Popovic, Benabarre and Crespo 77 Following a cohort of depressed patients with schizophrenia over three years, Connelly and colleagues (2007) found that depressed patients were more likely to suffer a relapse of psychosis, use substances, be a safety concern (violent, arrested, victimized, suicidal), report poorer relationships and greater functional impairment, suffer from poorer health (mental, physical), and be less adherent with treatment.Reference Conley, Ascher-Svanum, Zhu, Faries and Kinon 78 Despite the high prevalence and association with negative outcomes, major depressive disorder in schizophrenia is underdiagnosed. Moreover, when diagnosed and treated with antidepressants, 44% of patients remain symptomatic.Reference Fond, Boyer and Berna 76
The diagnosis of depression in schizophrenia is not straightforward. First, there is a significant overlap between depressive symptoms and other symptom clusters. For example, anhedonia, apathy, and social withdrawal are negative symptoms and are seen in depression. Cognitive dysfunction is common to both depression and schizophrenia. Antipsychotic treatments and their effects on dopaminergic neurotransmission can produce drug-induced parkinsonism, which may be associated with anergia and emotional withdrawal or akathisia, which is associated with dysphoria. Patients who use illicit substances may experience dysphoria during substance withdrawal.
Anxiety
In parallel with what is observed for depression, anxiety symptoms and syndromes are common in all phases of schizophrenia with rates several-fold that seen in the general population. They contribute to negative outcomesReference Temmingh and Stein 79 , Reference Buonocore, Bosia and Baraldi 80 and are underrecognized.Reference Wilk, West and Narrow 81 In terms of prevalence, 38.5% of schizophrenia patients have at least one comorbid anxiety disorder with 14.9% fulfilling criteria for social anxiety disorder, 12.4% for post-traumatic stress disorder (PTSD), 12.2% for obsessive-compulsive disorder (OCD), and 10.9% for generalized anxiety disorder, followed by panic disorder and specific phobia.Reference Achim, Maziade, Raymond, Olivier, Mérette and Roy 82 Although the DSM-5-TR has reconceptualized PTSD as a trauma and stressor-related disorder as opposed to an anxiety disorder, it shares neurobiological features with anxiety disorders.Reference Williamson, Jaffee and Jorge 83
Violence
Although most patients with schizophrenia do not engage in violent behavior, schizophrenia increases the risk for violence.Reference Fazel, Gulati, Linsell, Geddes and Grann 84 -Reference Whiting, Gulati, Geddes and Fazel 87 Short et al (2013) used a case linkage design to compare patterns of violence between 4168 schizophrenia patients and community controls. Of the schizophrenia sample, one in four patients had been charged with a criminal offense, and one in ten had been convicted, a rate higher than that seen in the community sample (10% of people charged, 2.4% convicted).Reference Short, Thomas, Mullen and Ogloff 85 Substance use disorders (SUDs) increase risk; however, violence cannot be entirely attributed to substance use.Reference Short, Thomas, Mullen and Ogloff 85 , Reference Witt, van Dorn and Fazel 88 Women with schizophrenia are at greater risk of committing a violent act than men with schizophrenia.Reference Fazel, Gulati, Linsell, Geddes and Grann 84 , Reference Short, Thomas, Mullen and Ogloff 85 Victims of violence are acquaintances (49.7%), followed by relatives (28.9%), and strangers (21.4%).Reference He, Gu, Yu, Li, Li and Hu 89 Among relatives, mothers of individuals with schizophrenia are the most common target of violent acts and threats.Reference Estroff, Swanson, Lachicotte, Swartz and Bolduc 90 Many factors have the potential to increase the risk of violence in schizophrenia. These include the catechol-O-methyltransferase genotype, developmental factors (childhood trauma, conduct disorders), antisocial personality disorder, substance use, neurocognitive impairment, treatment nonadherence, and certain positive symptoms such as persecutory delusions.Reference Jones, Zammit and Norton 91 , Reference Volavka and Citrome 92
Comorbidities in schizophrenia
Substance use
Substance use often predates the first psychotic episode with half of first-episode patients fulfilling criteria for a co-occurring SUD.Reference Brunette, Mueser and Babbin 93 Cannabis exerts a dose-dependent effect on the risk of developing a psychotic illness and accelerates illness onset by almost three years in regular users compared to non-users.Reference Myles, Myles and Large 94 , Reference Myles, Newall, Nielssen and Large 95 Methamphetamine appears to increase the risk of developing schizophrenia on par with cannabis.Reference Callaghan, Cunningham and Allebeck 96 In patients with an established illness, 50% have a lifetime history of a SUD, a rate five-times greater than that in the general population.Reference Regier, Farmer and Rae 97 , Reference Sara, Burgess, Malhi, Whiteford and Hall 98 Alcohol is the most used substance, followed by cannabis, and then followed by other drugs.Reference Martins and Gorelick 99 , Reference Volkow 100 At any timepoint in the illness, SUDs are associated with greater positive symptom severity, less treatment adherence, more aggression and violence, and poorer social functioning.Reference Ward, Nemeroff and Carpenter 101 Several different hypotheses attempt to explain the high prevalence of SUDs in people with schizophrenia. These include the primary addiction hypothesis, which proposes that substance use and schizophrenia share abnormalities in striatal dopaminergic neurotransmission and the two-hit model in which substance use is an environmental stressor that precipitates the development of psychosis in vulnerable individuals.Reference Volkow 100 -Reference Chambers, Krystal and Self 103
Suicide
Psychotic disorders have one of the highest rates of mortality among mental disorders.Reference Walker, McGee and Druss 104 Suicide is the greatest relative risk factor for mortality in people with schizophrenia.Reference Correll, Solmi and Croatto 105 Using linked national databases to follow approximately 76,000 people with schizophrenia for up to 20 years, Zahar and colleagues (2020) found that 1 in 58 individuals died by suicide, with suicide typically occurring within 4 years of the initial diagnosis.Reference Zaheer, Olfson and Mallia 106 Further, 25-50% of patients attempt suicideReference Meltzer 107 for an overall increase of 50-100-fold compared to that of the general population.Reference Cassidy, Yang, Kapczinski and Passos 108
Popovic and colleagues (2015) performed a systematic review of 77 studies to identify risk factors for suicide with the most conclusive evidence base. Factors that were strongly associated with suicide in hospitalized patients and outpatients were depressed mood, history of suicide attempt(s), and the number of psychiatric hospitalizations. Other factors included hopelessness, younger age, close proximity to illness onset, and hospital admission (during admission or within one week of discharge). While male gender and substance use have been associated with suicide in the general population, the data in schizophrenia are mixed.Reference Popovic, Benabarre and Crespo 77 Command auditory hallucinations often command self-harm or suicide; however, the data have not shown them to be a consistent risk factor for suicide.Reference Pompili, Amador and Girardi 109 Nevertheless, this type of auditory verbal hallucination should prompt careful suicide risk assessment and safety planning. The primary protective factor against suicide is adherence to comprehensive treatment including pharmacotherapy and psychosocial treatments.Reference Correll, Solmi and Croatto 105 , Reference Pompili, Amador and Girardi 109 , Reference Sher and Kahn 110
Conclusion
The symptoms and signs of schizophrenia and schizophrenia-spectrum disorders are well established. The patient cases—Marta and DeShawn—illustrate the heterogeneity in the clinical presentation of schizophrenia, the disease trajectory, and in functional outcomes. While Marta’s hallucinations, delusions, and disorganization or DeShawn’s asociality and alogia are obvious, both patients suffer from neurocognitive and social cognitive impairments that impact their ability to engage in meaningful activities, manage independent living, and navigate productive interactions with others. Figure 2 illustrates the relationship between schizophrenia symptom clusters and functional impairments.
Figure 2. The relationship between core schizophrenia symptoms and functional impairment. Core symptoms affect each other to varying degrees. For example, there is a strong relationship between disorganization and all domains of neurocognitive functioning and an inverse relationship with social functioning. Negative symptoms are associated with deficits in empathy and the ability to infer emotions, impacting social cognition. Neurocognitive and social cognitive deficits along with negative symptoms have the greatest impact on functional outcome.
These patients’ experience confirms that treatment of positive symptoms is the first step in improving function.Reference Harvey, Strassnig and Silberstein 5 , Reference Harvey, Heaton, Carpenter, Green, Gold and Schoenbaum 32 , Reference Swanson, Swartz and Van Dorn 33 , Reference Sher and Kahn 110 , Reference Helldin, Kane, Karilampi, Norlander and Archer 111 There’s a clear relationship between Marta’s persecutory delusions and violence. When her illness is optimally treated with antipsychotic medication, the conviction with which she holds delusional beliefs diminishes, her perception of others as malevolent dissipates, and violence risk decreases, outcomes described in the literature.Reference Sariaslan, Leucht, Zetterqvist, Lichtenstein and Fazel 112 -Reference Faden and Citrome 114 For Deshawn, pharmacologic treatment of positive symptoms after the first psychotic break resolved suicidality and prevented rehospitalization. Treatment at the time of the first psychotic episode is critical to improving symptomatic and functional recovery.Reference Perkins, Gu, Boteva and Lieberman 14 , Reference Lieberman, Alvir and Koreen 34 , Reference Correll, Solmi and Croatto 105 , Reference Kane and Correll 115 -Reference Tiihonen, Tanskanen and Taipale 118 Psychiatric stability allowed Deshawn to resume his education. The next step in treatment is implementing psychosocial treatment for negative symptoms, neurocognitive symptoms, and social cognitive symptoms, with the goal of improving interpersonal relationships and facilitating academic and occupational success.
Author contribution
Conceptualization: J.S.; Supervision: J.S.; Writing – original draft: J.S.; Writing – review & editing: J.S.
Disclosure
Dr. Striebel reports no disclosures
Funding
None
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