October 2021 - Colorado Recovery

Antipsychotics and Cognition in the Treatment of Schizophrenia

“People with schizophrenia can be treated in a variety of settings,” wrote the late Colorado Recovery founder Richard Warner, MD, in The Environment of Schizophrenia (2000). “Medications are an important part of treatment but they are only part of the answer. They can reduce or eliminate positive symptoms but they have a negligible effect on negative symptoms.”

Antipsychotics, also known as neuroleptics have had a dramatic impact on the treatment of schizophrenia since they were first introduced in the 1950s. “Time after time, in many thousands of treatment settings, clinical experience has shown that the antipsychotic drugs can bring dramatic relief from psychotic symptoms in most schizophrenic patients,” Dr. Warner wrote in Recovery from Schizophrenia.

In a recent presentation for Psych Congress Network, Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, NY, examined neurobiological targets, the current research regarding antipsychotics, and other schizophrenia treatment options. “As we are working towards improvement in the pharmacological approaches to schizophrenia, greater attention has been paid to cognition.”

“The neurobiology of cognitive impairment in schizophrenia is complex and does involve the interplay of a number of neurotransmitter systems. They include our favorite players here, dopamine, but also glutamate and acetylcholine,” said Dr. Citrome.

“The role of dopamine has long been of interest to schizophrenia researchers because drugs such as amphetamines that increase dopamine’s effects can cause psychoses that resemble schizophrenia, and drugs that block or decrease dopamine’s effect are useful for the treatment of psychoses,” wrote Dr. Warner in The Environment of Schizophrenia.

The current focus is on “the dorsolateral prefrontal cortex or DLPFC, and its interactions with other brain regions,” explained Citrome. “Now, in the DLPFC, dopaminergic transmission is mainly mediated through dopamine D1 receptors, not D2.”

“Chronic low levels of dopamine in the DLPFC in people with schizophrenia have been demonstrated,” Citrome said. “This is very different from our understanding of the positive symptoms of schizophrenia, which are thought to be due to excess amounts of dopamine in the ventral striatum, and where the dopamine D2 receptor is the target of antipsychotic medications.”

So, it seems to be D1 versus D2—a case of “not enough dopamine” versus “too much dopamine.”

“Actually, what we have in the brain is too much dopamine in one place and too little in the other,” said Citrome. How can this be remedied? “Second-generation antipsychotics also possess strong antagonism at presynaptic serotonin 5-HT2A receptors on the dopaminergic neuron. This facilitates the release of dopamine and theoretically boosts the dopamine levels in the DLPFC. However, attempts to measure this effect have resulted in disappointment,” Dr. Citrome said.

Many studies have been done with second-generation antipsychotics comparing them generally with the classic first generation antipsychotic Haloperidol. As it turned out, “there were only small improvements compared to Haloperidol and very little difference amongst the second-generation antipsychotics themselves.”

Citrome suggested that we have to look at other neurobiological targets. “Of increasing interest is the glutamate system, with its connections with dopamine circuitry. Glutamate is widely distributed in the brain, and it’s the primary excitatory neurotransmitter” in the human central nervous system.

“Experimentally, glutamate has shown to be involved in neuroplasticity and higher cognitive functioning, such as memory,” Citrome said. “In the DLPFC, NMDA glutamate receptors are involved in high-level processes, such as executive functioning.”

The final common pathway, though, is dopamine. “Glutamate neurons regulate the dopamine neurons, either directly, boosting dopamine, or indirectly, acting as a brake, decreasing dopamine. Depending on where we look, we see either effect,” explained Dr. Citrome.

The NMDA receptor has been a target of significant interest in terms of improving its functioning. One theory of schizophrenia is the hypo-functioning NMDA receptor hypothesis. “We can’t give glutamate, but if we give medicines or other interventions that boost signaling in the NMDA receptor” we can boost its functioning.

One option is to increase glycine at the NMDA receptor. Glycine is required for the NMDA receptor to function and theoretically, hypo-functioning NMDA receptors can be boosted by providing more glycine.

“We can do that with a glycine transporter inhibitor, GlyT1 inhibition,” said Dr. Citrome. “You’re going to hear about this. There is a medicine currently being evaluated for this purpose.”

Concluding his presentation, Citrome said that “cognition is an important determinant of function, and cognitive impairment is very common in people with schizophrenia. The effect of medications on cognition is actually independent of how well they work on the positive symptoms. We know we can treat the positive symptoms quite well, but our second-generation antipsychotics don’t quite do the job with cognition. One strategy is to improve on that.”

“In the meantime, we have vocational rehabilitation. We have cognitive remediation, and we should use those to the hilt while waiting for a more definitive intervention,” Dr. Citrome said.

Vocational rehabilitation is an important element in the treatment approach at Colorado Recovery. Our program approaches mental healthcare with a focus on self-reliance through developed practiced skills. Our non-institutionalized philosophy offers comprehensive levels of care supported by an expert medical and clinical team, engaging patients in increasing community participation.

Our treatment facility provides the services needed to address schizophrenia, bipolar disorder, and other serious mental illnesses. Call us at 720-218-4068 to discuss treatment options for you or the person you would like to help.

Sounds and Syllables in Schizophrenia

Speech and language disturbances have been recognized as core components of schizophrenia since the early days of modern psychiatry. In his description of “dementia praecox,” which is often credited as the first modern characterization of schizophrenia, German psychiatrist Emil Kraepelin described both positive (e.g. incoherence, derailment, stereotypy, neologisms) and negative symptoms (e.g. mutism) associated with speech.

Another psychiatry pioneer, Eugen Bleuler, noted that the primary symptoms of schizophrenia “find their expression in language,” but “here the abnormality lies not in language itself, but in what it has to say.”

“The words, phrases, sentences, and dialogues from our patients say so much,” wrote Sunny Tang, assistant professor of psychiatry at the Feinstein Institutes for Medical Research and the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell in a recent article on Psychiatric Times. “So does their breaths in between, and their voice and its dynamics, and the cadence and tonality used. These are the building blocks and foundations of our work as psychiatrists, whether we are an analyst in an armchair, dissecting and reconstructing a patient’s narrative, or a biological psychiatrist with pen in hand, translating the patient’s report into scales and delving for correlates in the brain.”

Even the most innovative methods of biological psychiatry—from neuroimaging to magnetoencephalography—cannot replace patient reports. “Syllable and sound are still the primary means for taking the measure of thoughts and emotions,” according to Tang.

Since the 1980s, researchers have been able to quantify speech disturbance in patients. They found that many features were shared with speech from patients in manic episodes, although mania was associated with greater positive thought disorder and schizophrenia with greater negative thought disorder.

“Through advancements of machine learning and artificial intelligence, we have new tools for taking the measure of speech and thought disturbance,” explained Dr. Tang. “Methods for extracting information from speech can be roughly divided into two areas. First, acoustics analysis extracts and quantifies information on pitch, amplitude, and vocal qualities on a millisecond-by-millisecond scale. Second, lexical analysis focuses on the content of speech, including word choice, grammar, the ideas being represented, and the relationship between words and ideas.”

Recently, Tang and her colleagues compared traditional clinical rating scales with “natural language processing” (NLP) methods for differentiating speech in individuals with schizophrenia spectrum disorders from that of comparison participants without schizophrenia. “When classifying participants into either the schizophrenia or health comparison group, we found machine learning algorithms performed significantly better using NLP-derived features (87 percent accuracy) than clinical ratings (68 percent accuracy), suggesting that important information is being captured by NLP.”

Perhaps, with additional research, it will soon be possible to link specific speech markers to changes in specific brain circuits. However, speech disturbance in schizophrenia is likely multifaceted and should not be treated as a single uniform entity.

“It is important to remember that our mission is the healing and well-being of individuals and families,” wrote Dr. Tang. “This is not technology for the sake of novelty, no matter how nifty the gadget. Finally, the availability of brain measures should not mandate reliance on pharmacology over psychosocial interventions—quite the opposite. Automated language processing can be harnessed to measure changes in thought and brain structure on a personalized level. This layer of technology should not occlude the individual but rather allow clinicians to delve deeper into each unique case.”

Psychosocial interventions are central to the Warner treatment model at Colorado Recovery which emphasizes the experience of empowerment, the strengthening of social relationships, and overall support for people with schizophrenia to improve all aspects of their lives. Our treatment facility provides the services needed to address schizophrenia, bipolar disorder, and other serious mental illnesses which are specific to each individual. Call us at 720-218-4068 to discuss treatment options for you or the person you would like to help.

The Prodromal Stage of Schizophrenia

Schizophrenia is a mental health disorder characterized by continuous or relapsing episodes of psychosis. “When schizophrenia is active, symptoms can include delusions, hallucinations, disorganized speech, trouble with thinking, and lack of motivation,” according to the American Psychiatric Association. “With treatment, most symptoms of schizophrenia will greatly improve and the likelihood of a recurrence can be diminished.”

As the late Colorado Recovery founder Richard Warner made clear in The Environment of Schizophrenia, the popular view that “schizophrenia has a progressive and downhill course with universally poor outcome is a myth. Over the course of months or years, about 20 to 25 percent of people with schizophrenia recover completely from the illness—all their psychotic symptoms disappear and they return to their previous level of functioning.”

As Dr. Warner explained, there is wide variation in the course of schizophrenia. In some cases the onset is gradual, “extending over the course of months or years; in others it can begin suddenly, within hours or days. Some people have episodes of illness lasting weeks or months with full remission of symptoms between each episode; others have a fluctuating course in which symptoms are continuous; others again have very little variation in their symptoms of illness over the course of years.”

Schizophrenia symptoms often only emerge well into adulthood, typically from the late teens to early 40s. The actual onset of psychosis is frequently preceded by a prodromal stage, wrote Michelle Pugle in a recent article on Verywellhealth.com, “where people (often still in adolescence) begin experiencing pre-psychotic mild or moderate disturbances in everyday functioning, including speech and movement difficulties. These changes can be attributed to heredity, genetic, environmental, and other causes.”

“Psychosis is preceded by a 3–4-year prodromal phase characterized by non-specific symptoms and deficits in approximately 75 percent of patients with a first episode of psychosis (FEP),” according to Michael First, Professor of Clinical Psychiatry at Columbia University in New York.

Since the prodromal phase is the earliest phase and schizophrenia symptoms are absent, it’s commonly diagnosed only after a person has entered the active phase of the disorder.

“Prodromal symptoms are generally seen as unspecific symptoms of schizophrenia (those involving an absence of normal interactions and functioning) that evolve over time,” wrote Pugle. “They can fluctuate in intensity, severity, and length of time. Such symptoms can begin in adolescence and the teenage years, although they aren’t likely to be seen as such unless a future diagnosis of schizophrenia is made later in life (a retrospective diagnosis).”

Early indicators are easy to miss. Small changes to personality and behavior or normal routine could be some of the first signs of prodromal phase schizophrenia. As we reported on this blog, researchers recently found new clues in young adults that could help predict the severity of symptoms later in life. According to their study published in the Journal of Abnormal Psychology, “Early detection of subtle, nonpsychotic forms of perceptual disturbance may aid in identifying individuals at increased risk for nonaffective psychosis outcomes in adulthood. Perceptual aberrations may constitute a useful endophenotype for genetic, neurobiological, and cognitive neuroscience investigations of schizophrenia liability.”

Early signs and symptoms of schizophrenia may include:

Nervousness and/or restlessness
Depression
Anxiety
Thinking or concentration difficulties
Worrying
Lack of self-confidence
Lack of energy and/or slowness
A significant drop in grades or job performance
Social isolation or uneasiness around other people
Lack of attention to or care for personal hygiene

“Some of the prodromal signs, such as a significant change in personal hygiene and a worrisome drop in grades or job performance, can also be early warning signs of other issues, including psychosis or detachment from reality,” explained Pugle in the article.

If your child or teen starts showing the above signs and symptoms, talk to a pediatrician or mental health professional as soon as possible. Our treatment facility provides the services needed to address schizophrenia, bipolar disorder, and other serious mental illnesses which are specific to each individual. About half of our clients are under 35 years of age and we expect good outcomes regardless of the duration of the disorder. Clients of any age will feel comfortable in our program. Call us at 720-218-4068 to discuss treatment options for you or the person you would like to help.

How Vocational Rehabilitation Can Reduce the Symptoms of Schizophrenia

People with schizophrenia can be treated effectively in a variety of settings with hospitalization mostly reserved for acute cases. Outside of a hospital environment, treatment should include social rehabilitation. People with schizophrenia typically need help to improve their functioning in the community. This can include training in basic living skills, assistance with a host of day-to-day tasks, job training, job placement, and work support.

Sadly this aspect of treatment is frequently missing. “Lacking a useful social role, many people with mental illness face lives of profound purposelessness,” wrote the late Colorado Recovery founder Richard Warner, MD, in The Environment of Schizophrenia (2000).

This situation leads to severe functional deficits in schizophrenia, In a recent presentation for Psych Congress Network, Leslie Citrome, MD, MPH, clinical professor of psychiatry and behavioral sciences at New York Medical College, Valhalla, NY, in a recent presentation for Psych Congress Network about he importance of psychological rehabilitation, such as cognitive remediation and vocational rehabilitation in the treatment of schizophrenia.

The numbers are quite shocking. “Only 10 percent of all patients with schizophrenia work full-time. Only one-third ever worked part-time,” said Citrome. “Fewer than 10 percent of male patients with schizophrenia have a child, and the self-care deficit is reflected in high rates of medical comorbidity.”

These deficits are a big problem but there are things that can be done to change the situation. “Cognitive behavioral therapy or CBT, although it’s labor-intensive, can be helpful, even in patients considered treatment-refractory, and has been evaluated in controlled clinical trials in patients with treatment-resistant schizophrenia,” explained Dr. Citrome.

“Cognitive remediation is a very specific type of treatment. It’s a set of drills or interventions designed to enhance cognitive functioning. It’s a therapy that engages the patient in learning activities that enhance neurocognitive skills relevant to their chosen recovery goals. It’s very personalized.”

Ultimately, psychosocial rehabilitation includes improving functional and subjective outcomes. It consists of is a range of techniques, including CBT and cognition remediation, as well as addressing patient employment.

Meaningful employment is an important aspect of the treatment model originated by Dr. Warner. Clinical research shows that “patients discharged from psychiatric hospital who have a job are much less likely to be readmitted to hospital than those who are unemployed, regardless of the patient’s level of pathology,” as Dr. Warner wrote The Environment of Schizophrenia.

Dr. Citrome agreed. “One of the key goals in psychosocial rehabilitation is helping patients live independently and be employed. Employment is identified as a goal for most of our patients. They’ll tell us on many occasions, ‘Yes, I’d like to have a job.’”

There are multiple barriers to employment that need to be addressed starting with the psychiatric symptoms. In addition, there may be substance misuse, non-psychiatric medical conditions, stigma from employers, internalized stigma, and low self-confidence—even the fear of losing disability benefits.

“Vocational rehabilitation addresses these barriers by providing skill training, sheltered workshops, transitional employment, and supported employment, as well as the maintenance of benefits,” said Citrome.

Finding appropriate employment for patients is an important part of the treatment plan at Colorado Recovery. Employment support includes helping clients find a job, go back to school, or find volunteer work in the community.

“Patients who received both cognitive remediation and vocational rehabilitation demonstrated significantly greater improvements on a cognitive battery over three months than those who received vocational rehab alone and had better work outcomes over the two-year follow-up period,” explained Citrome. “A comprehensive approach is better, and for those community settings that can offer this, their patients are better off. With employment, one may expect increased self-esteem, reduction in symptoms and hospitalizations, enhanced social functioning, and improvement in overall quality of life.”

Empowerment and vocational rehabilitation are crucial elements of the Warner model. “Work helps people recover from schizophrenia. Productive activity is basic to a person’s sense of identity and worth,” Dr. Warner wrote. “Given training and support, most people with schizophrenia can work.”

The Colorado Recovery program approaches mental healthcare with a focus on self-reliance through developed practiced skills. Our non-institutionalized philosophy offers comprehensive levels of care supported by an expert medical and clinical team, engaging patients in increasing community participation. Those in our care go to school, volunteer, or are employed in the beautiful surrounding Boulder area where they regularly take advantage of all it has to offer recreationally.