The curious effect of an increase of the placebo effect across year of publication has been shown for depression, schizophrenia, obsessive-compulsive disorder, as well as for some medical conditions like hypertension and pain.

We aimed to observe how randomised clinical trials with a placebo control behave at this respect in panic disorder trials.

We searched the PubMed database using the strategy: (panic disorder OR panic attack disorder) AND placebo, which on 3 November 2020 produced 779 records. Inclusion criteria were the above stated, excluded were all studies focusing on the same patients as others and those not providing intelligible data. In our selection we used the PRISMA statement and reached agreement with Delphi rounds.

We identified through other sources further 3 studies. The finally eligible studies were 82, excluded were 700 studies, mainly consisting of reviews (176), challenge studies (173), not dealing with panic disorder (67), studies with unsuitable designs to detect placebo effect (53), studies using same populations as others (36), those with misfocused outcomes (57), those lumping diagnoses and not allowing to separate data for panic disorder (22), and those not using placebo at all (21). Mean response to placebo in included panic disorder studies was 36.01±19.812, ranging from 0 to 76.19%; the correlation with year of publication was positive and significant (Pearson’s r= 0.246; p=0.026).

The effect of placebo in randomised control trials has increased across the years, but this field of research appears to be idle in recent years.

No significant relationships.

Empathy is evolutionary preserved in social organisms and emotional face processing is one of its measures. Systems possibly active during empathic processing include perspective-taking, basic emotional contagion “mirroring” and “theory of mind” systems.

fMRI studies help clarifying neural correlates of empathic face processing; ALE meta-analysing fMRI studies allows identification of brain area activation/deactivation during empathy.

To identify brain areas most consistently involved in empathy.

We carried ALE meta-analysis of original studies focusing on cerebral activations during empathic face processing tasks and reporting data on Talairach or MNI space coordinates, converting the former in the latter. An 11-April-2016 PubMed search, using as keywords terms like empathy combined with functional magnetic resonance imaging (fMRI), produced 124 records of which 23 were finally included (568 participants, 247 males and 321 females; mean age 32.2 years). We followed the PRISMA statement. Whole-brain data were meta-analysed; significance was set at P = 0.0001, uncorrected.

ALE meta-analysis of data from 21 experiments (totalling 527 foci) on empathic face processing during experimental task conditions showed that emotional vs. neutral/control conditions significantly correlated with activations of left anterior cingulate cortex (BA 32), right precentral gyrus (BA 6), left amygdala, right superior frontal gyrus (BA 9), left middle occipital gyrus (BA 37), right insula (BA 13), left putamen, and left posterior cingulate cortex (BA 31).

Empathy is a complex process correlating with activation of different brain areas, which have been involved in emotional cue processing, self-other/same-different discrimination, perspective-taking, mirror neuron activation, emotional arousal and decision-making.

The authors have not supplied their declaration of competing interest.

Impulsivity is a key feature of both bipolar disorder (BD) type I (BDI) and type II (BDII).

Structural neuroimaging studies help clarifying brain mechanisms underpinning the regulation of impulsivity in BDI and BDII.

To address the question whether grey matter (GM) alterations relate differently with impulsivity in BDI and BDII.

We assessed 54 euthymic outpatients, diagnosed with BDI (n = 28) or BDII (n = 26) according to DSM-IV-TR criteria. They underwent a 3 T magnetic resonance imaging (MRI) investigation. GM brain volumes were analyzed on a voxel-by-voxel basis using Statistical Parametric Mapping 8. The Barratt Impulsiveness Scale (BIS), version 11A, was used to assess trait impulsivity.

BDI and BDII patients present an inverse relationship between impulsivity and GM volume in two cerebral areas: the right cerebellum (right crus I) and the interface between the left angular gyrus and the left inferior parietal cortex (Brodmann Area 39, 7, 40). More specifically, a negative relationship for BPI and a positive relationship for BPII were found in both areas.

Results suggest that the different diagnosis between BDI and BDII could have a significant effect on GM changes according to impulsivity severity and point up the importance of considering the BP subtype distinction in neuroimaging studies on this topic.

The authors have not supplied their declaration of competing interest.