We have to thank this one male juror in the Clancy triple infanticide case who would not acquit the defendant

Update of 9/11/2026: "The revelation Friday morning that the one holdout Lindsay Clancy juror was a black man on an otherwise all-white jury has made news ... That one juror reportedly wanted to convict Clancy of first-degree murder ... it was nine women [???], three men ..." (Source) Why the heck were there so many women jurors in this case?

I blogged here about some the grave issues surrounding this case.

Presumably, the the three prosecutors in this case were not sharpest knives in the kitchen!

Assistant District Attorneys Jennifer Sprague. She looks tame to me! (Source)

District Attorney Timothy J. Cruz. He was overseeing the case. (Source, official photo)

Lindsay Clancy Trial: Jurors ask to examine knife, pill bottles she used to slit her throat and wrists

What? So the killer of her three children did not only jump out a window after the killing? So she also cut her throat and wrists as well? How did she survive, but not her children?

Why did she have three children with postpartum psychosis? When did the alleged postpartum psychosis begin, only after the third child? Postpartum psychosis appears to be very rare, only 1-2 women in 1000 after delivery are affected by it.

It strikes me again that if a woman commits a horrific crime then she must be crazy fallacy applies here again. Women are angels and men are brutes. In the age of gender equality such bias should be dismissed.

What did the husband know and do about it? I am not aware of news reporting on about the husband in this case. Strange!

This case is weird in several respects!

Caveat I am not familiar with the details of the case.

Lindsay Clancy Trial: Jurors ask to examine knife, pill bottles (behind paywall)

Lindsay Clancy Jury Asks to See Bloody Knife, Prescription Pill Bottles as 2 Days Pass Without Verdict

Forensic Psychiatrists on both sides agree the mother heard voices the day she killed her three children. Really!

How is that even possible? Seems to be junk headline! The forensic psychiatrists did not agree, they just heard the same story from the killer.

What did the husband know and what did he do about it?

"Forensic psychiatrists for both the defense and prosecution agree that Duxbury mother Lindsay Clancy was hearing voices on the day she strangled her three children but disagree on whether that makes her culpable for their murders.

Her uttering “Go to God” as she killed her children, one expert argued, suggests the mom knew what she was doing was wrong. ..."

"... [forensic psychiatrist Dr. Avram Mack] said Clancy recounted the killings to him, saying she heard a loud male voice telling her to kill the children so she could kill herself. She recalled strangling the children and saying "go to God" as she did so, he told jurors. ..."

Psychiatrists agree Lindsay Clancy heard voices the day she killed her children: 'Go to God' "The defense rests its case that she is not criminally responsible"

Hundreds of women rally outside courthouse to show support for woman accused of murdering her 3 children. Really!

Did the killer have postpartum psychosis only after her third child? Why did she have three children?

What did the husband know or do about it?

Caveat: I am not familiar with the case.

"Hundreds of Lindsay Clancy supporters, many wearing pink clothing emblazoned with phrases such as "Believe," "She Needed Help" and "Peace For Lindsay," gathered Thursday outside the courthouse where she is on trial in the killings of her three children. ..."

Hundreds of women rally outside courthouse to show support for woman accused of murdering her 3 children | Blaze Media

Women rally in support of Lindsay Clancy at her trial

My abusive mother was not a victim — and neither is the three children murderer Lindsay Clancy (a former labor and delivery nurse)

Update: A female Chaplain says Lindsay Clancy reported hearing 'voice' after killings. The killer heard voices after the killing? I did not know until now that the killer jumped out of the window after the crime and became paralyzed and wheel-chair bound.

Food for thought!

Was the children murderer Lindsay Clancy abusive to her children before she killed them? For how long and how abusive? What did her husband know about it and/or what did he do about it?

"Postpartum psychosis is a [very] rare, severe psychiatric emergency affecting about 1 to 2 in 1,000 women after childbirth." (Google Search) And how many women suffering from it become abusive or murderers of their own children?

P.S. My late mother was not abusive, on the contrary!

"... Then I witnessed the extraordinary outpouring of female sympathy for Lindsay Clancy, the Massachusetts mother who killed her three children in 2023.

Some Clancy girls now claim Lindsay’s poor husband, Patrick, actually killed the kids and framed her. How do they know this? Astrology of course.

Clancy, a former labor and delivery nurse, is now on trial for murder. Her children were Cora, 5, Dawson, 3, and Callan, eight months old.

There is no dispute about who killed them. Clancy's defense admits she strangled all three children with exercise bands in the basement of the family's home while her husband, Patrick, was out picking up medicine and takeout. The question for the jury is whether she was criminally responsible when she did it.

Her lawyers say she wasn't. They argue that Clancy suffered from postpartum psychosis and bipolar disorder and that psychiatric medications worsened her condition. Prosecutors say she deliberately arranged to get her husband out of the house and knew exactly what she was doing. ..."

My abusive mother was not a victim — and neither is Lindsay Clancy | Blaze Media (partially behind paywall) "We have a dire, immediate, society-wide problem of women identifying with evil, sympathizing with evil, and financially supporting evil."

Source

Why brain imaging struggles to identify psychiatric disorder signatures

This is very odd indeed!

"... Researchers ... analyzed thousands of brain scans collected in earlier studies to better understand the reasons for these observed inconsistencies. Their findings ... suggest that many widely used experimental designs and tools might fail to reliably capture the subtle differences in brain structure linked with distinct psychiatric disorders. ...

"... To quantify the severity of this inconsistency, the study involved a world-first analysis of more than 6,000 brain scans, evaluating the consistency of grey matter volume and cortical thickness. Researchers pooled existing MRI data from 25 studies across 59 sites globally, covering five major psychiatric disorders: schizophrenia, schizoaffective disorder, autism spectrum disorder, major depressive disorder, and bipolar disorder. ..."

but decades of research using brain-scanning technologies such as magnetic resonance imaging (MRI) have failed to reach a consensus about which brain changes are most characteristic of different psychiatric disorders. ...

the findings suggest categories like "depression" may not describe people with the same underlying brain condition; instead, they may represent an umbrella term that groups together people with symptoms caused by distinct sets of brain changes. ..."

From the abstract:

"Decades of structural magnetic resonance imaging (MRI) studies have documented alterations of gray matter morphometry in psychiatric disorders, but the field has failed to identify any consensus disease phenotypes.

Here we examine whether current approaches will ever converge on such phenotypes by evaluating the consistency of brain-wide maps of gray matter volume and cortical thickness differences obtained for each of 59 study sites of five psychiatric disorders (schizophrenia, schizoaffective disorder, autism spectrum disorder, major depressive disorder and bipolar disorder), totaling 2,437 patients and 2,065 controls.

We find that cross-site consistency is low (median r ≤ 0.16); markedly reduced compared to Alzheimer’s disease (r = 0.54); unexplained by demographic, clinical or scanner differences; and robust to analytic choices.

Using bootstrapping, we observe that consistency may improve for sample sizes ≥200 per group for schizophrenia but that other disorders may require much larger samples.

Our findings indicate that current widespread practices in structural MRI are unlikely to identify robust morphometric phenotypes for psychiatric disorders."

Why brain imaging struggles to identify psychiatric disorder signatures

Monash study reveals decades of psychiatric brain imaging research has failed to replicate (original news release)

The cross-site reproducibility of MRI morphometric phenotypes in psychiatric disorders (open access)

Fig. 1: Analysis pipeline.

A step towards psychedelics with none of the undesirable side effects/symptoms

Good news! Amazing stuff!

"Psychedelic drugs hold great promise for treating mental health conditions like depression and anxiety. But beyond their otherworldly hallucinogenic manifestations, many of these drugs also come with all-too-familiar side effects like nausea, vomiting, and gastrointestinal discomfort.

This occurs because the psychedelic compounds activate several off-target pathways as well as the intended serotonin receptors in the brain.

Reducing these unwanted interactions and the unpleasant symptoms that come with them is an important step for demonstrating the safety of psychedelics.

In a new study ... researchers pushed closer to this reality by re-engineering the synthetic psychedelic drug quipazine to activate only the desired receptors .

The pharmacologists began by examining quipazine atom-by-atom to identify how the drug could bind to both the target 5-HT2AR receptor and the 5-HT3R receptor that causes nausea and other gastrointestinal symptoms.

After singling out the nitrogen atom responsible, they replaced it and rearranged the whole molecule. The resultant drug could still bind to the desired 5-HT2AR receptor, but it bounced off 5-HT3R receptors.

To test the new psychedelic’s effectiveness, the researchers gave the drug to mice with symptoms of depression and anxiety. Once the hallucinogenic effects subsided, the mice exhibited fewer symptoms and showed no apparent discomfort. When they examined the animals’ brains, the researchers found an increased density of neuron structures called dendritic spines, a telltale sign that the psychedelic had restored some of the brain activity lost to depression. ..."

From the editor's summary and abstract:

"Editor’s summary

The clinical use of serotonergic psychedelics is limited by their side effects. Younkin et al. generated a derivative (called VCU-1012) of the psychedelic quipazine with greater activity at the serotonin receptor subtype that mediates the clinically desirable effects (5-HT2AR) than at the serotonin receptor subtype responsible for the undesirable ones.

Similar to quipazine, VCU-1012 exerted antidepressant and antianxiolytic effects in mice but without the gastrointestinal side effects of quipazine. Moreover, like other psychedelics, VCU-1012 increased dendritic spine density in the frontal cortex in a 5-HT2AR–dependent manner.

Thus, VCU-1012 shows promise as a 5-HT2AR agonist with a more favorable side effect profile than those of typical psychedelics. ...

Abstract

Psychedelics that target serotonin 2A receptors (5-HT2ARs) hold therapeutic promise for neuropsychiatric disorders but are often hindered by off-target actions. The 5-HT2AR agonist quipazine also activates 5-HT3R, which contributes to undesirable side effects.

Here, we developed VCU-1012, a quipazine-based, structurally distinct 5-HT2AR agonist devoid of 5-HT3R activity.

VCU-1012 was developed by applying a strategic chemical design that combined deconstruction to pinpoint the nitrogen atom critical for 5-HT2AR activation with structure-activity relationship studies to minimize 5-HT3R agonism.

We showed that VCU-1012 modulated dendritic spine structural plasticity in the frontal cortex and produced antidepressant-like effects in mice through 5-HT2AR without activating 5-HT3R, thereby avoiding the gastrointestinal side effects of quipazine.

In addition, our molecular modeling and mutant analysis suggested that VCU-1012 interacted in the canonical orthosteric binding pocket of 5-HT2AR.

Together, these findings establish VCU-1012 as a potential therapeutic agent with reduced gastrointestinal impact, emphasize how differences in ligand-receptor interactions influence ligand positioning in the receptor binding pocket, and provide guidance for designing psychedelics with targeted therapeutic benefits."

ScienceAdviser

Design of a new psychedelic quipazine analog with therapeutic efficacy and potentially fewer side effects (no public access)

Design and Synthesis of Quipazine Analogs for Programmable Control of Psychedelic Effects (A PhD thesis covering a similar topic. The author was not part of the team authoring the above research article.)

VCU-1012 (Wikipedia page indicating this psychedelic drug was already developed in 2024)

VCU-1012 2D chemical structure

Severe depression tied to immune system imbalance, not just brain chemistry

Good news! What about lack of sunshine?

"... They found that this immune abnormality affects brain function, and the "Immune Neural Axis" imbalance is the core mechanism of depression, opening up the possibility for the discovery of new biomarkers and the development of new drugs for depression treatment. ...

performed a multi-omics analysis combining blood analysis, single-cell analysis, and patient-derived brain organoids (mini-brains). ..."

From the abstract:

"Major depressive disorder (MDD) with atypical features accompanied by psychotic symptoms represents a severe and under-researched subtype of depression and severe mental illness, characterized by significant personal and social impact.

This study aims to explore novel biomarkers through a precision medicine approach by combining clinical data, white blood cell (WBC) single-cell RNA sequencing (scRNA-seq), plasma proteomics, and brain organoid models to uncover immunological and neurological alterations in patients with this condition. Patients exhibited elevated stress, anxiety, depression, and increased WBC counts, although the difference in WBC count is not significant after adjusting for age.

Plasma proteomic profiling identified an upregulation of proteins implicated in synaptic formation, including Doublecortin-Like Kinase 3 (DCLK3) and Calcyon (CALY), as well as immune-related proteins such as Complement Component 5 (C5).

WBC scRNA-seq revealed significant neutrophil and monocyte transcriptomic alterations, suggesting increased inflammation and immune dysregulation. Patient-derived brain organoids display reduced growth and distinct gene expression patterns compared to controls, particularly under dexamethasone-induced stress conditions.

Combining WBC scRNA-seq, plasma proteomics, and brain organoid models offers a novel framework for understanding the pathophysiology of psychiatric disorders, which is one of the most complex disorders."

Depression tied to immune system imbalance, not just brain chemistry

Depression is Not Only a Disease of the Mind. KAIST Discovers the Immune-Brain Connection​ (original news release)

Exploration of Novel Biomarkers Through a Precision Medicine Approach Using Multi-Omics and Brain Organoids in Patients With Atypical Depression and Psychotic Symptoms (open access)

Figure 2

Differential WBC Single-cell Transcriptomic Profiles in the Patient Group Elevated Inflammatory Gene Expression in Neutrophils and Monocytes

Inflammation during pregnancy may prime offspring for anxiety

Good news! It has been suspected for decades that events during a woman's pregnancy may cause serious disorders etc. affecting her child possibly for the rest of the child's life. 

"Increased risk for anxiety may begin before birth, shaped by infection or stressful events during pregnancy, according to a new preclinical study ...

While scientists have long known that maternal difficulty during pregnancy may raise a child’s risk for psychiatric illness, the biological pathways between these prenatal experiences and later mental health have been unclear. ..."

From the highlights and abstract:

"Highlights

• Adverse gestational environment is a risk factor for psychiatric disorders

• Gestational adversity has variable neuronal transcriptomic effects

• The most affected hippocampal neurons are activated in a stressful environment

• Higher neuronal activity during transition from safe to threatening environment

Summary

An adverse gestational environment is a risk factor for the development of psychiatric disorders. Although studies have implicated modifications in neuronal DNA and chromatin, how these changes come about and lead to abnormal behaviors is not known.

We sought to identify persistent DNA/chromatin and transcriptomic signatures induced by a proinflammatory gestational environment in the ventral dentate gyrus (vDG), a hippocampal region linked to anxiety. 

A proinflammatory environment shifted DNA methylation of enhancers and promoters and altered synapse-related gene expression, resulting in transcriptional heterogeneity in the vDG.

In animals with prior adversity, exposure to a threatening environment recruited vDG neurons with the greatest transcriptional changes, notably in synapse-relevant genes that also tended to be differentially methylated.

Finally, vDG activity was increased during transition from a safe to a threatening environment in animals with prior adversity but not in controls, suggesting their enhanced perception of a potential threat.

Our data outline a proinflammatory gestational environment-induced neurobiological sequence that leads to anxiety."

Inflammation during pregnancy may prime offspring for anxiety | Cornell Chronicle

Adverse gestational environment configures a subpopulation of ventral dentate granule cells for recruitment to drive innate anxiety (open access)

Graphical abstract

Figure 2 An adverse gestational environment preferentially alters methylation at intermediately methylated CGs in vDGCs

Study identifies 55 independent genetic loci that link brain structure and various psychiatric disorders

Good news!

"... Their paper ... pinpoints several genetic loci (i.e., locations on a chromosome where a gene or genetic variant is found) that are linked both to the risk that an individual will develop a psychiatric condition and to specific patterns in the structure of the cortex. ..."

From the abstract:

"Both psychiatric vulnerability and cortical structure are shaped by the cumulative effect of common genetic variants across the genome. However, the shared genetic underpinnings between psychiatric disorders and brain structural phenotypes, such as thickness and surface area of the cerebral cortex, remain elusive.

Here we use pleiotropy-informed conjunctional false discovery rate analysis to investigate shared loci across genome-wide association scans of regional cortical thickness, surface area and eight psychiatric disorders in individuals of European ancestry.

Aggregating regional measures, we identified 55 independent genetic loci shared between psychiatric disorders and surface area, as well as 29 independent genetic loci shared with cortical thickness.

Risk alleles exhibited bidirectional effects on both cortical thickness and surface area, such that some risk alleles for each disorder were associated with increased regional brain size while other risk alleles were associated with decreased regional brain size.

Due to bidirectional effects, in many cases we observed extensive pleiotropy between an imaging phenotype and a psychiatric disorder even in the absence of a significant genetic correlation between them.

The impact of genetic risk for psychiatric disorders on regional brain structure did exhibit a consistent pattern across highly comorbid psychiatric disorders, with 80% of the independent genetic loci shared across multiple disorders displaying consistent directions of effect.

Cortical patterning of genetic overlap revealed a hierarchical genetic architecture, with the association cortex and sensorimotor cortex representing two extremes of shared genetic influence on psychiatric disorders and brain structural variation. Integrating multiscale functional annotations and transcriptomic profiles, we observed that shared genetic loci were enriched in active genomic regions, converged on neurobiological and metabolic pathways and showed differential expression in postmortem brain tissue from individuals with psychiatric disorders. Cumulatively, these findings provide a significant advance in our understanding of the overlapping polygenic architecture between psychopathology and cortical brain structure."

Study identifies genetic loci that link brain structure and various psychiatric disorders

The overlapping genetic architecture of psychiatric disorders and cortical brain structure (no public access)

The overlapping genetic architecture of psychiatric disorders and cortical brain structure (prepint, open access, but it is dated (10/5/2023), not sure whether it was updated to match the journal article)

Figure 1 Shared genetic loci between psychiatric disorders and cortical thickness and surface area measures

New drug evenamide shows promise for schizophrenia

Good news!

"A novel drug, evenamide, quieted overactive brain circuits in an animal model of schizophrenia, improving memory, social interaction, and dopamine balance, offering hope for tackling symptoms that current antipsychotics can’t touch. ...

Schizophrenia causes a mix of positive (delusions, hallucinations), negative (social withdrawal, loss of pleasure) and cognitive (memory, decision-making) symptoms. For some people with schizophrenia, though, existing antipsychotic medications only treat positive symptoms. Still others develop treatment resistance.

A new drug, evenamide, has performed promisingly well in pre-clinical trials using animal models, improving positive, negative, and cognitive symptoms of schizophrenia. ..."

From the abstract:

"Schizophrenia is characterized by positive, negative, and cognitive symptoms. However, current D2-based antipsychotic drugs only address primarily positive symptoms.

Limbic hippocampus hyperexcitability is a key pathological state of schizophrenia, representing an ideal therapeutic target.

Evenamide is a selective voltage-gated sodium channel blocker that reduces neuronal hyperexcitability.

We examined the effect of acute evenamide treatment on the hyperdopaminergic state, hippocampal hyperexcitability, social deficits, and recognition memory in the methylazoxymethanol acetate (MAM) neurodevelopmental model. Male and female Sprague-Dawley offspring from dams treated with saline or MAM on gestational day 17 were tested as adults (postnatal day >65). Electrophysiological recordings were made in the ventral tegmental area (VTA) and ventral hippocampus (vHipp) and social approach and novel object recognition were tested.

Evenamide (3 mg/kg i.p.) normalized the number of spontaneously active DA neurons in the VTA of female and male MAM rats and reduced pyramidal neuron hyperactivity in the vHipp. The hyperdopaminergic state in the VTA of female and male MAM rats was also rescued by local evenamide injection in the vHipp (1 µM).

Systemic evenamide also reversed the recognition memory impairment of female and male MAM rats.

For social deficits, only male MAM rats exhibit a reduced social sniffing time that was normalized by evenamide.

These findings suggest that evenamide’s efficacy in downregulating the hyperdopaminergic state, social deficits, and recognition memory impairment may result from its ability to attenuate vHipp hyperexcitability. Therefore, evenamide could offer a novel therapeutic strategy that is capable of addressing positive, cognitive, and negative symptoms of schizophrenia."

New drug evenamide shows promise for schizophrenia

Evenamide reverses schizophrenia-related dysfunction in a neurodevelopmental animal model (no public access)

Study finds an overlap between genes linked to subjective well-being and psychiatric disorders

Amazing stuff! About the fine line between sanity and madness! Which genes make you happy! 😊

Unfortunately, I was not able to find e.g. an original news release for this study, which is unusual. I suspect, research produced in South Korea is still not very well accessible.

"In psychology, the term subjective well-being (SWB) is used to describe the extent to which different people feel happy and satisfied with their lives. While some studies have found that there is a link between SWB and the diagnosis of some psychiatric disorders, such as depression and anxiety disorders, their possible genetic commonalities have not yet been clearly delineated.

Researchers ... recently carried out a study aimed at better understanding the genes that could contribute to people's feelings of happiness and life satisfaction, as well as their possible connection to psychiatric disorders.

Their findings ... pin-point some brain tissues and genes linked to SWB, suggesting that they might also play a part in the development of psychiatric disorders. ...

For instance, the team found that approximately 93% of the genetic variants linked to depression were also tied to how happy people feel in their everyday lives. ..."

From the abstract:

"Subjective well-being (SWB) is important for understanding human behaviour and health. Although the connection between SWB and psychiatric disorders has been studied, common genetic mechanisms remain unclear. This study aimed to explore the genetic relationship between SWB and psychiatric disorders. Bivariate causal mixture modelling (MiXeR), polygenic risk score (PRS) and Mendelian randomization (MR) analyses showed substantial polygenic overlap and associations between SWB and the psychiatric disorders.

Subsequent replication studies in East Asian populations confirmed the polygenic overlap between schizophrenia and SWB.

The conditional and conjunctional false discovery rate analyses identified additional or shared genetic loci associated with SWB or psychiatric disorders. Functional annotation revealed enrichment of specific brain tissues and genes associated with SWB.

The identified genetic loci showed cross-ancestry transferability between the European and Korean populations. Our findings provide valuable insights into the common genetic mechanisms underlying SWB and psychiatric disorders."

Study finds an overlap between genes linked to subjective well-being and psychiatric disorders

Polygenic overlap between subjective well-being and psychiatric disorders and cross-ancestry validation (no public access)

Scientists uncover 95 regions of the genome linked to PTSD

Good news, but that is a lot of regions!

"... Now, a new genetic study of more than 1.2 million people has pinpointed 95 loci, or locations in the genome, that are associated with risk of developing PTSD, including 80 that had not been previously identified. The study ... is the largest and most diverse of its kind, and also identified 43 genes that appear to have a role in causing PTSD. ..."

From the abstract:

"Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation."

Scientists uncover 95 regions of the genome linked to PTSD | Broad Institute Findings from the largest genetic study of PTSD to date could help explain why only some people develop the condition after experiencing trauma.

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder (no public access)

A catatonic woman awakened after 20 years. Her story may change psychiatry

Amazing stuff! However, a very long article!

Another intriguing example that often physical factors are behind severe psychiatric disorders.

You may wonder why it took almost 20 years to discover that this catatonic patient had also lupus.

"... [patient] was diagnosed [in 2000?] with a severe form of schizophrenia, an often devastating mental illness that affects approximately 1 percent of the global population and can drastically impair how patients behave and perceive reality. ...

It would be nearly two decades before their paths crossed again. But in 2018, another chance encounter led to several medical discoveries reminiscent ...

[doctors] discovered that although [patient]’s illness was clinically indistinguishable from schizophrenia, she also had lupus, an underlying and treatable autoimmune condition that was attacking her brain.
After months of targeted treatments — and more than two decades trapped in her mind — [patient] woke up. ..."

How autoimmune disease can attack the brain, cause psychiatric symptoms - The Washington Post New research suggests that a subset of patients with psychiatric conditions such as schizophrenia may actually have autoimmune disease that attacks the brain

Credits: Human Progress Weekly Links

Survey of brain cell synaptic junctions shows striking similarities between schizophrenia and bipolar disorder

Good news! Are finally getting closer to better treatments!

"Although bipolar disorder and schizophrenia are diagnosed as distinct psychiatric conditions, both are considerably heritable with molecular roots that are poorly understood. Some people diagnosed with one disorder have symptoms and clinical features in common with the other, supporting the notion that the conditions lie on a spectrum. And human genetics studies have suggested that the junctions between brain cells, known as synapses, play a key role in both conditions. ...
Their analysis revealed changes in synapse proteins that were remarkably similar in the two conditions. In mice with a mutated gene that’s been linked to both conditions, the scientists found that related biochemical pathways were similarly altered. ...

Synaptic surprises

Isolating and purifying synapses from brain tissue samples is no easy task, but that is what the team had to do to analyze the structure’s proteins — its working parts — at a large scale. ...

In the current study, the researchers purified synapses from postmortem tissue from an area of the brain known as the dorsolateral prefrontal cortex, from 35 individuals who had been diagnosed with schizophrenia, 35 people with bipolar disorder, and 35 unaffected individuals. Collaborators in the Proteomics Platform analyzed the purified synapses by mass spectrometry, measuring the abundance of thousands of proteins and protein fragments in an unbiased way. ...

In samples from people with each disorder, the team observed changes in the levels of hundreds of proteins compared to control individuals. Strikingly, more than 200 of these proteins were either enriched or depleted similarly in both conditions. The scientists were surprised by how comparable the patterns of protein changes were between the disorders. ..."

From the highlights and abstract:

"Highlights

• Considerable and similar synapse proteome changes in SCZ and BP

• Core synaptic, mitochondrial, and ribosomal protein networks are reduced in SCZ/BP

• Increase in vesicle tethering-, trafficking- and autophagy-related protein networks

• Similar pathway changes in synapses from patients with SCZ/BP and Akap11-deficient mice

Summary

Synaptic dysfunction is implicated in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BP). We use quantitative mass spectrometry to carry out deep, unbiased proteomic profiling of synapses purified from the dorsolateral prefrontal cortex of 35 cases of SCZ, 35 cases of BP, and 35 controls. Compared with controls, SCZ and BP synapses show substantial and similar proteomic alterations. Network analyses reveal upregulation of proteins associated with autophagy and certain vesicle transport pathways and downregulation of proteins related to synaptic, mitochondrial, and ribosomal function in the synapses of individuals with SCZ or BP. Some of the same pathways are similarly dysregulated in the synaptic proteome of mutant mice deficient in Akap11, a recently discovered shared risk gene for SCZ and BP. Our work provides biological insights into molecular dysfunction at the synapse in SCZ and BP and serves as a resource for understanding the pathophysiology of these disorders."

Survey of brain cell junctions shows striking similarities between schizophrenia and bipolar disorder | Broad Institute An unbiased protein analysis comparing synapses from people with the disorders uncovers shared patterns.

Deep proteomics identifies shared molecular pathway alterations in synapses of patients with schizophrenia and bipolar disorder and mouse model (open access)

Graphical abstract

Scientists find key brain abnormality that may explain why some people are psychopaths

Are we finally coming closer to objective indicators or marker for psychopathic behavior? How much is inherited or developed during childhood?

Let's keep in mind that most individuals with psychiatric disorders are not dangerous.

"... By looking at the brain scans of the individuals who scored higher on the psychopathy test, the researchers noticed that an area of the forebrain, known as the striatum, was about 10% larger in psychopathic people compared to individuals with low or no psychopathic traits. ...
It’s also the first time that psychopathy was linked to enlarged striatum in both males and females. ..."

From the abstract:

"Prior studies have inconsistently reported increased volumes of the striatum in adults with psychopathy. A meta-analysis presented here indicates an overall effect size of d = 0.44. Nevertheless, variability in findings exist, and questions remain on confounding clinical conditions and generalizability to females. This study tests the hypothesis that striatal volumes are increased in adults with psychopathic traits, and that this relationship is mediated by stimulation-seeking and impulsivity. Striatal volume was assessed using magnetic resonance imaging in 108 adult community-dwelling males alongside psychopathy using the Psychopathy Checklist – Revised. ... Correlational analyses showed that increased striatal volumes were associated with more psychopathic traits (p = .001). Effects were observed for all striatal regions, controlling for age, substance dependence and abuse, antisocial personality disorder, attention deficit hyperactivity disorder, social adversity, and total brain volume. An analysis of 18 psychopathic individuals showed that striatal volumes were increased 9.4% compared with 18 matched controls (p = .01). Psychopathy in females was also significantly associated with increased striatal volume (p = .02). Stimulation-seeking and impulsivity partly mediated the striatal-psychopathy relationship, accounting for 49.4% of this association. Findings from these two samples replicate and build on initial studies indicating striatal enlargement in adults with psychopathy, yielding an updated effect size of d = 0.48. Results are consistent with the notion that striatal abnormalities in individuals with psychopathy partly reflect increased sensation-seeking and impulsivity, and support the hypothesis of abnormal reward processing in psychopathy."

Scientists find key brain abnormality that may explain why some people are psychopaths

Larger striatal volume is associated with increased adult psychopathy (no public access)

Largest study of its kind reveals that many psychiatric disorders arise from common genes

Good news!

"To identify these multi-purpose [pleiotropic] gene variants, the researchers used a technique called genome-wide association to analyze genetic data from 494,162 healthy control subjects and 232,964 people diagnosed with at least one of eight common psychiatric disorders. The analysis identified 109 gene variants that affect the risk for more than one psychiatric disorder.

Certain disorders shared many variants, allowing the researchers to divide the conditions into three groups of genetically-related conditions: disorders characterized by compulsive behaviors (anorexia nervosa, obsessive-compulsive disorder and, to a lesser extent, Tourette syndrome); mood and psychotic disorders (bipolar disorder, major depression and schizophrenia); and early-onset neurodevelopmental disorders (autism spectrum disorder, ADHD and Tourette syndrome). The researchers also found evidence that genes associated with multiple disorders show increased expression beginning in the second trimester of pregnancy and appear to play an important role in brain development"

Largest study of its kind reveals that many psychiatric disorders arise from common genes