Web-Based Intervention for Depression

Effect of a Web-Based Guided Self-help Intervention for Prevention of Major Depression in Adults With Subthreshold Depression
A Randomized Clinical Trial
Claudia Buntrock, MSc, et al.
JAMA. 2016;315(17):1854-1863.

Conclusions and Relevance  Among patients with subthreshold depression, the use of a web-based guided self-help intervention compared with enhanced usual care reduced the incidence of MDD over 12 months. Further research is needed to understand whether the effects are generalizable to both first onset of depression and depression recurrence as well as efficacy without the use of an online trainer.
depressive disorders ;  follow-up ;  internet ;  major depressive disorder ;  guided self-help ;  prevention ;  symptom onset

journalistic version:

Computerised cognitive behaviour therapy (cCBT) as treatment for depression in primary care (REEACT trial): large scale pragmatic randomised controlled trial
BMJ 2015; 351


Subclinical delusional thinking

Subclinical delusional thinking predicts lateral temporal cortex responses during social reflection
Soc Cogn Affect Neurosci (2014)   9  (3):  273-282.
Benjamin K. Brent

Neuroimaging studies have demonstrated associations between delusions in psychotic disorders and abnormalities of brain areas involved in social cognition, including medial prefrontal cortex (MPFC), posterior cingulate cortex, and lateral temporal cortex (LTC).
General population studies have linked subclinical delusional thinking to impaired social cognition, raising the question of whether a specific pattern of brain activity during social perception is associated with delusional beliefs.

Here, we tested the hypothesis that subclinical delusional thinking is associated with changes in neural function, while subjects made judgments about themselves or others [‘social reflection’ (SR)]. Neural responses during SR and non-social tasks, as well as resting-state activity, were measured using functional magnetic resonance imaging in 22 healthy subjects. Delusional thinking was measured using the Peters et al. Delusions Inventory.

Delusional thinking was negatively correlated with responses of the left LTC during SR (r = −0.61, P = 0.02, Bonferroni corrected), and connectivity between the left LTC and left ventral MPFC, and was positively correlated with connectivity between the left LTC and the right middle frontal and inferior temporal cortices. Thus, delusional thinking in the general population may be associated with reduced activity and aberrant functional connectivity of cortical areas involved in SR.

Key words:
lateral temporal cortex
default mode network

Halting Schizophrenia Before It Starts

Halting Schizophrenia Before It Starts
October 20, 2014

… That first psychotic break can lead to a series of disasters: social isolation, hospitalization, medications with sometimes disabling side effects, and future psychotic episodes.

So, what if you could intervene earlier, before any of that? Could you stop the process from snowballing?

At 19, Meghan hadn’t had a psychotic break. She still had insight. That made her eligible for a new type of program taking shape in California that aims to prevent schizophrenia before it officially begins.

The program draws on research suggesting that schizophrenia unfolds much more slowly than might be obvious, even to families.

“You start to see a decline in their functioning,” says Dr. Daniel Mathalon, who studies brain development in the early stages of psychosis at the University of California, San Francisco.

“They were doing better in school, now they’re doing worse,” he says. “Maybe they had friends but they’re starting to be more isolated.”

BDNF-based synaptic repair

Neurodegenerative disease progression (specifically, the functional deficits associated with disease progression)

BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases
Bai Lu,    et al.
Nature Reviews Neuroscience  14, 401–416 (May? 2013)

Increasing evidence suggests that synaptic dysfunction is a key pathophysiological hallmark in neurodegenerative disorders, including Alzheimer’s disease.
Understanding the role of brain-derived neurotrophic factor (BDNF) in synaptic plasticity and synaptogenesis, the impact of the BDNF Val66Met polymorphism in Alzheimer’s disease-relevant endophenotypes — including episodic memory and hippocampal volume — and the technological progress in measuring synaptic changes in humans all pave the way for a ‘synaptic repair’ therapy for neurodegenerative diseases that targets pathophysiology rather than pathogenesis.

This article reviews the key issues in translating BDNF biology into synaptic repair therapies.

Schizotypy & COMT high activity allele

Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele
Molecular Psychiatry, 2002, Volume 7, Number 7, Pages 706-711
D Avramopoulos, et al.

Schizotypal personality often precedes the development of schizophrenia and it is considered by some to be a low end of the schizophrenia spectrum.
It has also been found to be present in high frequency in schizophrenics’ relatives (reviewed by Webb et al), suggesting a common genetic background with the disease.
Although many studies have shown aggregation of schizotypal personality in schizophrenics’ families, when positive or negative symptoms are examined there is lack of consistency in the findings.
Nevertheless there have been reports of significant heritability for schizotypal personality and it has been suggested that positive and negative symptoms in schizophrenia correlate with the corresponding symptoms in schizotypal relatives.
It therefore seems likely, that schizotypal personality represents a condition attributable to some (but possibly not all) of the genes that predispose to schizophrenia, as it is a common but not a consistent premorbid finding.


Subthreshold depression. Subsyndromal depression.

A tune in “a minor” can “b major”: a review of epidemiology, illness course, and public health implications of subthreshold depression in older adults.
J Affect Disord. 2011 Mar;129(1-3):126-42.
Meeks TW, et al.

With emphasis on dimensional aspects of psychopathology in development of the upcoming DSM-V, we systematically review data on epidemiology, illness course, risk factors for, and consequences of late-life depressive syndromes not meeting DSM-IV-TR criteria for major depression or dysthymia.
We termed these syndromes subthreshold depression, including minor depression and subsyndromal depression.

We searched PubMed (1980-Jan 2010) using the terms: subsyndromal depression, subthreshold depression, and minor depression in combination with elderly, geriatric, older adult, and late-life.
Data were extracted from 181 studies of late-life subthreshold depression.

In older adults subthreshold depression was generally at least 2-3 times more prevalent (median community point prevalence 9.8%) than major depression. Prevalence of subthreshold depression was lower in community settings versus primary care and highest in long-term care settings. Approximately 8-10% of older persons with subthreshold depression developed major depression per year. The course of late-life subthreshold depression was more favorable than that of late-life major depression, but far from benign, with a median remission rate to non-depressed status of only 27% after ≥1 year. Prominent risk factors included female gender, medical burden, disability, and low social support; consequences included increased disability, greater healthcare utilization, and increased suicidal ideation.

Heterogeneity of the data, especially related to definitions of subthreshold depression limit our ability to conduct meta-analysis.

The high prevalence and associated adverse health outcomes of late-life subthreshold depression indicate the major public health significance of this condition and suggest a need for further research on its neurobiology and treatment. Such efforts could potentially lead to prevention of considerable morbidity for the growing number of older adults.

Subclinical manifestations of a disease. Preclinical symptoms.

The trajectory of disease.

Personalized Lifestyle Medicine: Relevance for Nutrition and Lifestyle Recommendations
ScientificWorldJournal. 2013; 2013: 129841.
Deanna M. Minich and Jeffrey S. Bland

For several years before disease onset, a patient may have subclinical manifestations of a disease, indicated by low and/or high normal laboratory values, and the presence of ill-defined symptoms which do not classically qualify for a determined diagnosis. Personalized lifestyle medicine can be integral throughout a patient’s life, from prevention to preclinical symptoms to disease manifestation and progression.

Pre-symptomatic diagnosis in FFI

Pre-symptomatic diagnosis in fatal familial insomnia: serial neurophysiological and 18FDG-PET studies
Brain (2006), 129, 668–675

A puzzling feature that FFI shares with other familial neurodegenerative diseases is that the clinical onset generally occurs at a mature or advanced age although the mutation is congenital, leaving an ample interval free of clinical signs during which the pathogenic effect of the mutation is unknown.

The presence of insomnia was confirmed in all subjects by a 24 h polygraphic recording, which typically showed a disappearance of slow wave sleep, brief episodes of REM sleep without atonia and the lack of circadian rhythms of blood pressure, heart rate and body core temperature.
Patients lost weight and died from sudden cardiorespiratory arrest.

Two major unanswered questions concerning familial neurodegenerative diseases are when and where the degenerative process starts. This issue is raised by the common observation that familial neurodegenerative diseases usually become symptomatic at mature or advanced age although the mutated protein thought to trigger the disease is present from the early stages of brain development. However, prion diseases may differ from other neurodegenerative diseases in that the mutated protein probably maintains a normal conformation until some time in adulthood, when it changes conformation converting adjacent PrPs and ultimately leading to neuronal injury and loss.

function of neuronal populations during the pre-symptomatic and symptomatic stages of the disease in subjects carrying the FFI genetic mutation.

FFI has a rapid course and high penetrance, therefore, it is easier to follow the disease progression, and virtually all mutation carriers become symptomatic. The disease presents with impairment of sleep and autonomic functions that can be tested fairly accurately.

Keywords: fatal familial insomnia; 18FDG-PET; pre-symptomatic diagnosis; thalamus