Substance dependence disorder is a chronically relapsing condition characterised by neurobiological changes leading to loss of control in restricting a substance intake, compulsion and withdrawal syndrome. In the past few years, (endo)cannabinoids have been raised as a possible target in the aetiology of drug addiction. On the other hand, although the exact mechanisms of the genesis of addiction remain poorly understood, it is possible that neuroinflammation might also play a role in the pathophysiology of this condition. Studies demonstrated that (endo)cannabinoids act as immunomodulators by inhibiting cytokines production and microglial cell activation. Thus, in the present review, we explore the possible role of neuroinflammation on the therapeutic effects of cannabinoids on drug addiction.

We conducted an evidence-based review of the literature in order to assess the role of cannabinoids on the neuroinflammatory hypothesis of addiction (terms: addiction, cannabinoids and inflammation). We searched PubMed and BioMedCentral databases up to April 2014 with no date restrictions.

In all, 165 eligible articles were included in the present review. Existing evidence suggests that disruption in cannabinoid signalling during the drug addiction process leads to microglial activation and neuroinflammation.

The literature showed that inflammation and changes in endocannabinod signalling occur in drug abuse; however, it remains uncertain whether these changes are causally or coincidentally associated with addiction. Additional studies, therefore, are needed to elucidate the contribution of neuroinflammation on the behavioural and neuroprotective effects of cannabinoids on drug addiction.

Major depressive disorder (MDD) is characterised by predominately negatively valenced emotional symptoms that are often accompanied by cognitive impairments. We posited that cognitive impairments in MDD are related to altered emotional processing in prefrontal cortex.

We compared 20 medication-free patients with MDD and 29 matched healthy controls. Both groups performed an emotional task during functional magnetic resonance imaging (fMRI). Furthermore, they completed the intra–extra dimensional set shift (IED) test probing for cognitive impairments. Then we correlated the results of the IED with the changes in fMRI BOLD signal in MDD patients and healthy subjects.

The subcategory of the IED applying extradimensional shift (EDS) showed a divergent performance of the MDD group committing significantly more errors than the control group. Correlating the EDS errors with fMRI signal changes, the healthy subjects showed a positive correlation with the right ventrolateral prefrontal cortex and the right orbitofrontal cortex. MDD subjects, in contrast, showed a positive correlation in right dorsolateral prefrontal cortex (DLPFC) and a negative correlation in the left dorsomedial prefrontal cortex (DMPFC).

We hypothesise that the differential correlation in healthy controls and MDD patients may reflect the use of different strategies in their performance. The impaired executive functions, as reflected by altered processing in right DLPFC and left DMPFC, may implicitly influence emotional processing in patients suffering from MDD.

We hypothesised that men and women who engage in extreme or high-risk sports would score higher on standardised measures of bipolarity and impulsivity compared to age and gender matched controls.

Four-hundred and eighty extreme or high-risk athletes (255 males and 225 females) and 235 age-matched control persons (107 males and 128 females) were enrolled into the web-based case-control study. The Mood Disorder Questionnaire (MDQ) and Barratt Impulsiveness Scale (BIS-11) were administered to screen for bipolarity and impulsive behaviours, respectively.

Results indicated that extreme or high-risk athletes had significantly higher scores of bipolarity and impulsivity, and lower scores on cognitive complexity of the BIS-11, compared to controls. Further, there were positive correlations between the MDQ and BIS-11 scores.

These results showed greater rates of bipolarity and impulsivity, in the extreme or high-risk athletes, suggesting these measures are sensitive to high-risk behaviours.

Some authors draw a connection between the dopaminergic pathways and emotional perception. The present study is based on that association and addresses the question whether methylphenidate and the resulting amelioration of the disturbed dopamine metabolism lead to an improvement of the facial affect recognition abilities in children with attention-deficit/hyperactivity disorder (ADHD).

A computer test was conducted on 21 participants, aged 7–14 years and with a diagnosis of ADHD – some with comorbid oppositional defiant disorder – conducted the FEFA (Frankfurt Test and Training of Facial Affect), a computer test to examine their facial affect recognition abilities. It consists of two subtests, one with faces and one with eye pairs. All participants were tested in a double-blind cross-over study, once under placebo and once under methylphenidate.

The collected data showed that methylphenidate leads to amelioration of facial affect recognition abilities, but not on a significant level. Reasons for missing significance may be the small sample size or the fact that there exists some overlapping in cerebral connections and metabolic pathways of the site of action of methylphenidate and the affected dopaminergic areas in ADHD. However, consistent with the endophenotype concept, certain gene locations of the dopaminergic metabolism as both an aetiological factor for ADHD and the deficient facial affect recognition abilities with these individuals were considered. Consulting current literature they were found to be not concordant. Therefore, we conclude that the lacking significance of the methylphenidate affect on facial affect recognition is based on this fact.

To provide a selected overview of the literature on psychosocial treatments for bipolar disorder

Selective literature review

Randomised controlled trials of psychosocial interventions in bipolar disorder fall largely into five categories, namely: psychoeducation, integrated treatments, family based therapy, cognitive behavioural therapy and interpersonal social rhythm therapy. Most studies have shown some benefit in terms of relapse prevention, but have tended to be effective for either the depressed or the manic pole, and not both. Broader outcome parameters such as quality of life have not been reported consistently. The mechanisms whereby treatments might exert their effects have not been clearly delineated. Many studies have excluded patients with bipolar II and other variants, and those with psychiatric and substance use comorbidities, reducing their generalisability.

Whilst psychosocial treatments show promise in the area of bipolar disorder, more work is required to delineate the effective elements of such interventions, and to ensure generalisability to individuals with bipolar II and other forms of bipolar disorder, as well as those with psychiatric and substance use comorbidities. Other forms of delivery, such as via the internet, deserve further exploration.

This study aimed to explore effects of adjunctive treatment with N-acetyl cysteine (NAC) on markers of inflammation and neurogenesis in bipolar depression.

This is a secondary analysis of a placebo-controlled randomised trial. Serum samples were collected at baseline, week 8, and week 32 of the open-label and maintenance phases of the clinical trial to determine changes in interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following adjunctive NAC treatment, and to explore mediation and moderator effects of the listed markers.

Levels of brain-derived neurotrophic factor (BDNF), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukins (IL) -6, 8, or 10 were not significantly changed during the course of the trial or specifically in the open-label and maintenance phases. There were no mediation or moderation effects of the biological factors on the clinical parameters.

The results suggest that these particular biological parameters may not be directly involved in the therapeutic mechanism of action of adjunctive NAC in bipolar depression.

Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms (labelled as “physio-affective phenome”) of LC has remained elusive.

The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC.

We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3–4 months later.

Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques, we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterised by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms.

The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions.

Post-traumatic stress disorder (PTSD) displays high co-morbidity with major depression and treatment-resistant depression (TRD). Earlier work demonstrated exaggerated depressive-like symptoms in a gene×environment model of TRD and an abrogated response to imipramine. We extended the investigation by studying the behavioural and monoaminergic response to multiple antidepressants, viz. venlafaxine and ketamine with/without imipramine.

Male Flinders sensitive line (FSL) rats, a genetic model of depression, were exposed to a time-dependent sensitisation (TDS) model of PTSD and compared with stress naive controls. 7 days after the TDS procedures, immobility and coping (swimming and climbing), behaviours in the forced swim test (FST) as well as hippocampal and cortical 5-hydroxyindoleacetic acid (5HIAA) and noradrenaline (NA) levels were analysed. Response to imipramine, venlafaxine and ketamine treatment (all 10 mg/kg×7 days) alone and in combination were subsequently studied.

TDS exacerbated depressive-like behaviour of FSL rats in the FST. Imipramine, venlafaxine and ketamine were ineffective as monotherapy in TDS-exposed FSL rats. However, combining imipramine with either venlafaxine or ketamine resulted in significant anti-immobility effects and enhanced coping behaviours. Only ketamine+imipramine (frontal-cortical 5HIAA and NA), ketamine alone (frontal-cortical and hippocampal NA) and venlafaxine+imipramine (frontal-cortical NA) altered monoamine responses versus untreated TDS-exposed FSL rats.

Exposure of FSL rats to TDS inhibits antidepressant response at behavioural and neurochemical levels. Congruent with TRD, imipramine plus venlafaxine or ketamine overcame treatment resistance in these animals. These data further support the hypothesis that exposure of FSL rats to a PTSD-like paradigm produces a valid animal model of TRD and warrants further investigation.

To review the available literature on obsessive–compulsive symptom (OCS)/obsessive–compulsive disorder (OCD) in patients with schizophrenia.

Electronic searches were carried out to locate studies reporting various aspects of OCS/OCD in patients with schizophrenia.

Available evidence suggests that prevalence of OCS/OCD in patients with schizophrenia is much higher than prevalence in general population and it is seen in all the stages of schizophrenia, starting from at risk mental state to chronic/stabilisation/deficit phases. Symptom profile of OCS/OCD in schizophrenia is similar to that seen in patients with OCD only. Presence of OCS/OCD is associated with higher severity of symptoms of schizophrenia and more negative outcome. At present there is very limited data on the efficacy/effectiveness of various pharmacological measures and psychological interventions, for management of OCS/OCD in patients with schizophrenia. There is some evidence pointing towards beneficial effect of certain antipsychotics, antidepressants and cognitive behaviour therapy. Management of OCS/OCD in patients with schizophrenia involves proper assessment. If the OCS/OCD is related to use of particular antipsychotic use, initial attempt must be made to reduce the dose of antipsychotics, however, if this is not effective, than addition of a selective serotonin reuptake inhibitor (SSRIs) must be considered. If the OCS/OCD is not related to the use of antipsychotic medication, than depending up on the severity of psychotic symptoms, addition of SSRIs must be considered.

This review suggests that OCS/OCD is highly prevalent among patients with schizophrenia and there is limited good quality evidence to make any specific recommendations for management.

Proton magnetic resonance spectroscopy (1H-MRS) was used to evaluate metabolic changes in the dorsolateral prefrontal cortex (DLPFC) in patients with obsessive–compulsive disorder (OCD).

In total, 14 OCD patients (mean age 28.9±7.2 years) and 14 healthy controls (mean age 32.6±7.1 years) with no history of neurological and psychiatric illness participated in this study. Brain metabolite concentrations were measured from a localised voxel on the right DLPFC using a 3-Tesla 1H-MRS.

The metabolic concentration of myo-inositol in patients with OCD increased significantly by 52% compared with the healthy controls, whereas glutamine/glutamate was decreased by 11%. However, there were no significant differences in N-acetylaspartate, choline, lactate and lipid between the two groups.

These findings would be helpful to understand the pathophysiology of OCD associated with the brain metabolic abnormalities in the right DLPFC.

Bipolar disorder in pregnancy may be difficult to treat. The dilemma is whether the women should continue medication throughout pregnancy, and maybe accept a minor risk to harm their unborn child, or discontinue medication and increase the risk of recurrence, which can lead to maternal morbidity, thereby endangering themselves and their foetus.

In September 2016, three electronic search databases; PubMed, Scopus and PsycInfo, were used searching for clinical trials concerning this question. Eight clinical trials concerning risk of recurrence after discontinuation of medication in pregnancy were included.

There is no consensus concerning the risk of discontinuation of medication during pregnancy among bipolar women. The evidence from the trials included underscore that there seem to be a group of pregnant women who are stable despite they are not receiving mood stabilisers during pregnancy. Besides, there is a group of more severe and more unstable bipolar disorders that seem to benefit of a more close monitoring, support and prophylactic medication during pregnancy and postpartum period to prevent recurrence.

For the more stable bipolar women we recommend a well planned and more slowly discontinuation of medication before pregnancy. For the unplanned pregnancies it is important to consider the possibility of a more slowly discontinuation. For the more severe conditions of bipolar disorder, it is important to secure a close monitoring of medication. As the risk of postpartum relapse is high, medication may be started soon after delivery.

Although bipolar disorder (BD) with comorbid obsessive-compulsive disorder (OCD) is highly prevalent, few controlled studies have assessed this comorbidity. The objective of this study was to investigate the clinical characteristics and expression of comorbid disorders in female BD patients with OCD.

We assessed clinically stable female outpatients with BD: 15 with comorbid OCD (BD+OCD group) and 15 without (BD/no-OCD group). All were submitted to the Structured Clinical Interview for DSM-IV, with additional modules for the diagnosis of kleptomania, trichotillomania, pathological gambling, onychophagia and skin picking.

The BD+OCD patients presented more chronic episodes, residual symptoms and previous depressive episodes than the BD/no-OCD patients. Of the BD+OCD patients, 86% had a history of treatment-emergent mania, compared with only 40% of the BD/no-OCD patients. The following were more prevalent in the BD+OCD patients than the BD/no-OCD patients: any anxiety disorder other than OCD; impulse control disorders; eating disorders; and tic disorders.

Female BD patients with OCD may represent a more severe form of disorder than those without OCD, having more depressive episodes and residual symptoms, and being at a higher risk for treatment-emergent mania, as well as presenting a greater anxiety and impulse control disorder burden.

Severe depression may be a risk factor for diagnostic conversion into bipolar disorder (BD), and psychotic depression (PD) has been consistently associated with BD. The aims of the present study were to investigate the stability of the diagnosis of severe depression and the differences between PD and non-psychotic severe depression (non-PD), as well as to assess the effectiveness of electroconvulsive therapy (ECT).

Patients who were hospitalised for severe depression (diagnosed according to ICD-10) both with and without psychotic symptoms (n=89; mean age=55.6 years, SD=13.9) from 2001 to 2010 were retrospectively assessed.

By the 75th month of follow-up assessments, 11(12.4%) patients had developed BD. Among these 11 converters, nine had developed BD within 1 year after admission. Only sub-threshold hypomanic symptoms were significantly related to developing BD. The number of depressive episodes and history of physical diseases were significantly increased in non-PD compared with PD patients, whereas ECT was significantly increased in PD compared with non-PD patients. There was a significant association between length of stay at the hospital and the number of days between admission and ECT.

Sub-threshold hypomanic symptoms may represent a prodrome of BD or an indicator of an already manifest phenotype, especially in older patients, which suggests cautious use of antidepressants. In severe depression, non-PD may often occur secondary to physical diseases and patients may experience increased recurrences compared with PD patients, which may be a more ‘primary’ disorder and often requires ECT treatments. ECT is effective for severe depression regardless of the presence of any psychotic feature; the earlier ECT is introduced, the better the expected treatment outcome.

Recent observations demonstrate a significant ameliorative effect of add-on transcranial direct current stimulation (tDCS) on auditory verbal hallucinations (AVHs) in schizophrenia. Of the many SNPs, NRG1 rs35753505 and catechol-o-methyl transferase (COMT) rs4680 polymorphisms have shown to have a strong association with neuroplasticity effect in schizophrenia.

Schizophrenia patients (n=32) with treatment resistant auditory hallucinations were administered with an add-on tDCS. The COMT (rs4680) and NRG1 (rs35753505) genotypes were determined. The COMT genotypes were categorised into Val group (GG; n=15) and Met group (GG/AG; n=17) and NRG1 genotypes were categorised into AA group (n=12) and AG/GG group (n=20).

The reduction in auditory hallucination sub-scale score was significantly affected by COMT-GG genotype [Time×COMT interaction: F(1,28)=10.55, p=0.003, ɳ2=0.27]. Further, COMT-GG effect was epistatically influenced by the co-occurrence of NRG1-AA genotype [Time×COMT×NRG1 interaction: F(1,28)=8.09, p=0.008, ɳ2=0.22]. Irrespective of genotype, females showed better tDCS response than males [Time×Sex interaction: F(1,21)=4.67, p=0.04, ɳ2=0.18].

COMT-GG and NRG1-AA genotypes aid the tDCS-induced improvement in AVHs in schizophrenia patients. Our preliminary observations need replication and further systematic research to understand the neuroplastic gene determinants that modulate the effect of tDCS.

Long haulers have been recently reported after contracting coronavirus disease (COVID-19). In the present study, we aimed to screen for the neuropsychiatric signs detected <1 to >6 months after infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to determine whether vaccination has an effect on them.

An online survey was conducted among participants who had been diagnosed with laboratory-confirmed SARS-CoV-2 infection. The clinical signs and durations of neuropsychiatric complaints and their correlations to sex, age, severity of COVID-19 signs, and vaccination status were screened.

A total of 2218 individuals, including 1358 females and 860 males, with an age range of 12–70 years, submitted their responses. The respondents experienced cognitive dysfunction, mood alteration, depression, tinnitus, sleep disorders, and loss of taste and smell, with prevalence rates ranging from 18.9% (tinnitus) to 63.9% (loss of taste and smell). Of the respondents, 2.2–7.7% confirmed the persistence of symptoms for >6 months. Tinnitus was the least common complaint, and only 2.2% of the study participants had tinnitus for >6 months. Meanwhile, mood alteration persisted for >6 months in 7.6% of the study participants. More respondents who received two doses of BNT162b2 vaccine showed persistent symptoms than those in the other groups. Disease severity and female sex were identified as potential determinants of the development and persistency of such symptoms.

Post-COVID neuropsychiatric symptoms were present in considerable percentages of the study participants with SARS-CoV-2 infection, persisting for >6 months in up to 7.6% of the participants.