Tuesday, September 16, 2014

New Reseach on Schizophrenia - 5 Recent Studies


Presented below are five new studies on schizophrenia from the last week or two. The first three come from Science Daily, which posts press releases from researchers and journals about new studies. All three of these studiers are behind paywalls, and they cannot be accessed to assess their validity.

The last two articles are from Frontiers in Psychiatry: Schizophrenia and are open access articles.

I have added some comments to a few of these.

Schizophrenia not a single disease but multiple genetically distinct disorders

Date: September 15, 2014
Source: Washington University in St. Louis
Schizophrenia isn’t a single disease but a group of eight genetically distinct disorders, each with its own set of symptoms, research shows. The finding could be a first step toward improved diagnosis and treatment for the debilitating psychiatric illness.


Cloninger, the Wallace Renard Professor of Psychiatry and Genetics, and his colleagues matched precise DNA variations in people with and without schizophrenia to symptoms in individual patients. In all, the researchers analyzed nearly 700,000 sites within the genome where a single unit of DNA is changed, often referred to as a single nucleotide polymorphism (SNP). They looked at SNPs in 4,200 people with schizophrenia and 3,800 healthy controls, learning how individual genetic variations interacted with each other to produce the illness.

In some patients with hallucinations or delusions, for example, the researchers matched distinct genetic features to patients' symptoms, demonstrating that specific genetic variations interacted to create a 95 percent certainty of schizophrenia. In another group, they found that disorganized speech and behavior were specifically associated with a set of DNA variations that carried a 100 percent risk of schizophrenia.

"What we've done here, after a decade of frustration in the field of psychiatric genetics, is identify the way genes interact with each other, how the 'orchestra' is either harmonious and leads to health, or disorganized in ways that lead to distinct classes of schizophrenia," Cloninger said.
Although individual genes have only weak and inconsistent associations with schizophrenia, groups of interacting gene clusters create an extremely high and consistent risk of illness, on the order of 70 to 100 percent. That makes it almost impossible for people with those genetic variations to avoid the condition. In all, the researchers identified 42 clusters of genetic variations that dramatically increased the risk of schizophrenia.
Full Citation:
Javier Arnedo, Dragan M. Svrakic, Coral del Val, Rocío Romero-Zaliz, Helena Hernández-Cuervo, Ayman H. Fanous, Michele T. Pato, Carlos N. Pato, Gabriel A. de Erausquin, C. Robert Cloninger, Igor Zwir. Uncovering the Hidden Risk Architecture of the Schizophrenias: Confirmation in Three Independent Genome-Wide Association Studies. American Journal of Psychiatry, 2014; DOI: 10.1176/appi.ajp.2014.14040435

Of course, the article is behind a paywall.

I remain skeptical of these results. As has long been the case in studies of schizophrenia and its genetic origins, the researchers do not account for HOW those single nucleotide polymorphisms (SNPs) get triggered in the first place. There is a LOT of research demonstrating powerful correlations between childhood abuse and neglect and epigenetic changes in the brain which can lea to schizophrenia and other psychoses.

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Is the pattern of brain folding a 'fingerprint' for schizophrenia?

Date: September 11, 2014
Source: Elsevier

Anyone who has seen pictures or models of the human brain is aware that the outside layer, or cortex, of the brain is folded in an intricate pattern of “hills”, called gyri, and “valleys”, called sulci. It turns out that the patterns of cortical folding are largely consistent across healthy humans, broadly speaking. However, disturbances in cortical folding patterns suggest deeper disturbances in brain structure and function.

Anyone who has seen pictures or models of the human brain is aware that the outside layer, or cortex, of the brain is folded in an intricate pattern of "hills," called gyri, and "valleys," called sulci.

It turns out that the patterns of cortical folding are largely consistent across healthy humans, broadly speaking. However, disturbances in cortical folding patterns suggest deeper disturbances in brain structure and function..

A new study published in the current issue of Biological Psychiatry suggests that schizophrenia is associated with reductions in the complexity of the cortical folding pattern that may reflect deficits in the structural connections between brain regions.

"The cortical folding pattern itself may not be so important, but the disturbances in connections between brain regions implicated by the changes in cortical folding could provide critical clues to deficits in the integrity of brain circuits that contribute to symptoms and functional impairment in schizophrenia," commented Dr. John Krystal, Editor of Biological Psychiatry.
Full Citation:
Pranav Nanda, Neeraj Tandon, Ian T. Mathew, Christoforos I. Giakoumatos, Hulegar A. Abhishekh, Brett A. Clementz, Godfrey D. Pearlson, John Sweeney, Carol A. Tamminga, Matcheri S. Keshavan. Local Gyrification Index in Probands with Psychotic Disorders and Their First-Degree Relatives. Biological Psychiatry, 2014; 76 (6): 447 DOI: 10.1016/j.biopsych.2013.11.018

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Brain development in schizophrenia strays from normal path

Date: September 15, 2014
Source: Elsevier

Schizophrenia is generally considered to be a disorder of brain development and it shares many risk factors, both genetic and environmental, with other neurodevelopmental disorders such as autism and intellectual disability. The normal path for brain development is determined by the combined effects of a complex network of genes and a wide range of environmental factors. However, longitudinal brain imaging studies in both healthy and patient populations are required in order to map the disturbances in brain structures as they emerge, researchers say.


A new study by an international, collaborative group of researchers has measured neurodevelopment in schizophrenia, by studying brain development during childhood and adolescence in people with and without this disorder. With access to new statistical approaches and long-term follow-up with participants, in some cases over more than a decade, the researchers were able to describe brain development patterns associated with schizophrenia.

"Specifically, this paper shows that parts of the brain's cortex develop differently in people with schizophrenia," said first author Dr. Aaron F. Alexander-Bloch, from the National Institute of Mental Health.

"The mapping of the path that the brain follows in deviating from normal development provides important clues to the underlying causes of the disorder," said Dr. John Krystal, Editor of Biological Psychiatry.

The findings were derived by investigating the trajectory of cortical thickness growth curves in 106 patients with childhood-onset schizophrenia and a comparison group of 102 healthy volunteers.

Each participant, ranging from 7-32 years of age, had repeated imaging scans over the course of several years. Then, using over 80,000 vertices across the cortex, the researchers modeled the effect of schizophrenia on the growth curve of cortical thickness.

This revealed differences that occur within a specific group of highly-connected brain regions that mature in synchrony during typical development, but follow altered trajectories of growth in schizophrenia.
Full Citation:
Aaron F. Alexander-Bloch, Philip T. Reiss, Judith Rapoport, Harry McAdams, Jay N. Giedd, Ed T. Bullmore, Nitin Gogtay. Abnormal Cortical Growth in Schizophrenia Targets Normative Modules of Synchronized Development. Biological Psychiatry, 2014; 76 (6): 438 DOI: 10.1016/j.biopsych.2014.02.010

It wold be interesting (i.e., essential) to know what types of environmental factors played into this atypical developmental patterns. Decreased cortical thickness has long been associated with adverse childhood experiences (neglect, abuse, molestation, etc.).

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Deficits in agency in schizophrenia, and additional deficits in body image, body schema, and internal timing, in passivity symptoms

Kyran T. Graham [1,2], Mathew T. Martin-Iverson [1,2], Nicholas P. Holmes [3], Assen Jablensky [4] and Flavie Waters [2,4]
1. Pharmacology, Pharmacy and Anaesthesiology Unit, School of Medicine and Pharmacology, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, Perth, WA, Australia
2. Statewide Department of Neurophysiology and Clinical Research Centre, Graylands Hospital, North Metropolitan Health Services – Mental Health, Perth, WA, Australia
3. Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
4. Centre for Clinical Research in Neuropsychiatry, School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia

Individuals with schizophrenia, particularly those with passivity symptoms, may not feel in control of their actions, believing them to be controlled by external agents. Cognitive operations that contribute to these symptoms may include abnormal processing in agency as well as body representations that deal with body schema and body image. However, these operations in schizophrenia are not fully understood, and the questions of general versus specific deficits in individuals with different symptom profiles remain unanswered. Using the projected-hand illusion (a digital video version of the rubber-hand illusion) with synchronous and asynchronous stroking (500 ms delay), and a hand laterality judgment task, we assessed sense of agency, body image, and body schema in 53 people with clinically stable schizophrenia (with a current, past, and no history of passivity symptoms) and 48 healthy controls. The results revealed a stable trait in schizophrenia with no difference between clinical subgroups (sense of agency) and some quantitative (specific) differences depending on the passivity symptom profile (body image and body schema). Specifically, a reduced sense of self-agency was a common feature of all clinical subgroups. However, subgroup comparisons showed that individuals with passivity symptoms (both current and past) had significantly greater deficits on tasks assessing body image and body schema, relative to the other groups. In addition, patients with current passivity symptoms failed to demonstrate the normal reduction in body illusion typically seen with a 500 ms delay in visual feedback (asynchronous condition), suggesting internal timing problems. Altogether, the results underscore self-abnormalities in schizophrenia, provide evidence for both trait abnormalities and state changes specific to passivity symptoms, and point to a role for internal timing deficits as a mechanistic explanation for external cues becoming a possible source of self-body input.

Full Citation: 
Graham KT, Martin-Iverson MT, Holmes NP, Jablensky A and Waters F. (2014, Sep 10). Deficits in agency in schizophrenia, and additional deficits in body image, body schema, and internal timing, in passivity symptoms. Front. Psychiatry 5:126. doi: 10.3389/fpsyt.2014.00126

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Social cognition in schizophrenic patients: the effect of semantic content and emotional prosody in the comprehension of emotional discourse

Perrine Brazo [1,2], Virginie Beaucousin [3], Laurent Lecardeur [1,2], Annick Razafimandimby [2] and Sonia Dollfus [1,2]
1. Service de Psychiatrie, Centre Hospitalier Universitaire de Caen, Caen, France
2. UMR6301 Imagerie et Stratégies Thérapeutiques des Pathologies Cérébrales et Tumorales (ISTCT), ISTS Team, Université de Caen Basse-Normandie, Caen, France
3. Laboratoire de Psychopathologie et Neuropsychologie, Université de Paris 8, Saint Denis, France

Background: The recognition of the emotion expressed during conversation relies on the integration of both semantic processing and decoding of emotional prosody. The integration of both types of elements is necessary for social interaction. No study has investigated how these processes are impaired in patients with schizophrenia during the comprehension of an emotional speech. Since patients with schizophrenia have difficulty in daily interactions, it would be of great interest to investigate how these processes are impaired. We tested the hypothesis that patients present lesser performances regarding both semantic and emotional prosodic processes during emotional speech comprehension compared with healthy participants.
Methods: The paradigm is based on sentences built with emotional (anger, happiness, or sadness) semantic content uttered with or without congruent emotional prosody. The study participants had to decide with which of the emotional categories each sentence corresponded.
Results: Patients performed significantly worse than their matched controls, even in the presence of emotional prosody, showing that their ability to understand emotional semantic content was impaired. Although prosody improved performances in both groups, it benefited the patients more than the controls.
Conclusion: Patients exhibited both impaired semantic and emotional prosodic comprehensions. However, they took greater advantage of emotional prosody adjunction than healthy participants. Consequently, focusing on emotional prosody during carrying may improve social communication.

Full Citation: 
Brazo P, Beaucousin V, Lecardeur L, Razafimandimby A and Dollfus S. (2014, Sep 10). Social cognition in schizophrenic patients: the effect of semantic content and emotional prosody in the comprehension of emotional discourse. Front. Psychiatry 5:120. doi: 10.3389/fpsyt.2014.00120

This is an interesting finding - it confirms one of the beliefs I am developing in working with clients who exhibit schizophrenic symptoms. My belief is that this inability to recognize and/or experience emotions is part of the genesis of the symptoms. For the clients I have seen, their emotions and the emotions of others are unbearable,  overwhelming, or simply incomprehensible.

The disconnect from the emotional (and therefore the sotmatic) self results, in my opinion, in the majority of symptoms, including the thought disorders and delusional beliefs. In this sense, schizophrenia is the defense mechanism of last resort, and the most extreme of all of the defense mechanisms. If we approach it that way in treatment, and slowly move the client into their emotions, I suspect there is a much better chance of a positive outcome.
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