To evaluate the effects of levomilnacipran extended-release (ER) on suicidal ideation and behavior in adults with major depressive disorder (MDD).

Post hoc analyses were conducted in patients from 4 randomized, double-blind, placebo-controlled trials and a long-term, open-label extension study of levomilnacipran ER (40-120 mg/d) in adults with MDD. Analyses included incidence of suicide-related treatment-emergent adverse events (TEAEs); incidence of Columbia–Suicide Severity Rating Scale (C-SSRS) suicidal ideation (score=1–5) and behavior (score=6-10); percent of patients who shifted from no C-SSRS suicidal ideation/behavior at baseline to suicidal ideation during treatment (worsened from score=0 to score=1–5), or vice-versa (improved from score=1-5 to score=0).

Suicide-related TEAEs occurred in<1% of patients in the levomilnacipran ER studies. The incidence of C-SSRS suicidal ideation was 22.2%, 23.9%, and 21.7% for placebo, short-term levomilnacipran ER, and long-term levomilnacipran ER, respectively; C-SSRS suicidal behavior was<1% in all of these groups. In the short-term studies, the percentage of patients with C-SSRS shifts were as follows: worsening from score=0 to score=1–5 (placebo, 8.6%; levomilnacipran ER, 11.0%); improvement from score=1–5 to score=0 (placebo, 24.0%; levomilnacipran ER, 27.7%).

In adult MDD patients, the incidence of suicidal ideation and behavior was similar between placebo and short-term levomilnacipran ER as indicated by TEAE reports and C-SSRS scores. Worsening in C-SSRS scores was also similar between placebo and levomilnacipran ER. There was no indication of increased suicidality during longer courses of continued therapy. Together, these findings suggest that this medication is not associated with increased risks of suicidal ideation or behavior.

These post hoc analyses evaluate the efficacy, safety, and tolerability of vortioxetine versus placebo in patients aged ≥55 years with major depressive disorder (MDD).

Study-level efficacy data from 12 short-term, fixed-dose, randomized, placebo-controlled trials of vortioxetine 5–20 mg/day were assessed using a random-effects meta-analysis. Adverse events (AEs), vital signs, ECG values, liver enzymes, and body weight were pooled from the same studies. Patients had baseline Montgomery–Åsberg Depression Rating Scale (MADRS) total scores ranging from 22–30.

1508 patients (mean age=62.4 years; range, 55–88 years) were included. Mean differences from placebo in change from baseline to study end (6/8 weeks) in MADRS were –2.56 (5 mg, n=324, P=0.035), –2.87 (10 mg, n=222, P=0.007), –1.32 (15 mg, n=90, P=NS), and –4.65 (20 mg, n=165, P=0.012). Odds ratios for response versus placebo were 1.6 (5 mg, P=NS), 1.8 (10 mg, P=0.002), 1.2 (15 mg, P=NS), and 2.5 (20 mg, P<0.001), and for remission versus placebo were 1.5 (5 mg, P=NS), 1.5 (10 mg, P=NS), 1.4 (15 mg, P=NS), and 2.7 (20 mg, P=0.001). The proportion of patients with AEs for placebo and vortioxetine 5–20 mg was 61.5% and 62.3%, respectively, with no increase at increased doses. Vortioxetine demonstrated a placebo-level incidence of serious AEs (1.2%). AEs occurring in ≥5% of any treatment group were nausea, headache, diarrhea, dizziness, dry mouth, constipation, fatigue, vomiting, and anxiety. No clinically significant mean changes in vital signs, ECG values, liver enzymes, or body weight emerged during treatment.

Vortioxetine 5–20 mg/day is efficacious and well tolerated in MDD patients aged ≥55 years, a group that is often comorbid with other conditions and treated with other medications.

The role of dopamine (DA) in romantic love is suggested by different evidence and is supported by the findings of some brain imaging studies. The DA transporter (DAT) is a key structure in regulating the concentration of the neurotransmitter in the synaptic cleft. Given the presence of DAT in blood cells, the present study aimed to explore it in resting lymphocytes of 30 healthy subjects of both sexes in the early stage of romantic love (no longer than 6 months), as compared with 30 subjects involved in a long-lasting relationship.

All subjects had no physical or psychiatric illness. The DAT was measured by means of the [3H]-WIN 35,428 binding and the [3H]-DA reuptake to resting lymphocytes membranes. Romantic love was assessed by a specific questionnaire developed by us.

The results showed that the subjects in the early phase of romantic love had a global alteration of the lymphocyte DAT involving both a decreased number of proteins (Bmax) and a reduced functionality (Vmax).

Taken together, these findings would indicate the presence of increased levels of DA in romantic love that, if paralleled by similar concentrations in the brain, would explain some peculiar features of this human feeling.

This study examined the chronic effects of aripiprazole and cariprazine on serotonin (5-HT1A and 5-HT2A) and glutamate (NMDA and AMPA) receptor subtypes. In addition, the effects of aripiprazole on D2 and D3 receptors were tested and compared with previously reported cariprazine data.

Rats received vehicle, aripiprazole (2, 5, or 15 mg/kg), or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Receptor levels were quantified using autoradiographic assays on brain sections from the medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), nucleus accumbens (NAc), caudate-putamen medial (CPu–M), caudate-putamen lateral (CPu–L), hippocampal CA1 (HIPP–CA1) and CA3 (HIPP–CA3) regions, and the entorhinal cortex (EC).

Similar to previous findings with cariprazine, aripiprazole upregulated D2 receptor levels in various regions; D3 receptor changes were less than those reported with cariprazine. All aripiprazole doses and higher cariprazine doses increased 5-HT1A receptors in the MPC and DFC. Higher aripiprazole and all cariprazine doses increased 5-HT1A receptors in HIPP–CA1 and HIPP–CA3. Aripiprazole decreased 5-HT2A receptors in the MPC, DFC, HIPP–CA1, and HIPP–CA3 regions. Both compounds decreased NMDA receptors and increased AMPA receptors in select brain regions.

Long-term administration of aripiprazole and cariprazine had similar effects on 5-HT1A, NMDA, and AMPA receptors. However, cariprazine more profoundly increased D3 receptors while aripiprazole selectively reduced 5-HT2A receptors. These results suggest that the unique actions of cariprazine on dopamine D3 receptors, combined with its effects on serotonin and glutamate receptor subtypes, may confer the clinical benefits, safety, and tolerability of this novel compound in schizophrenia and bipolar mania.

Harm avoidance (HA) and “not just right experience” (NJRE) have been proposed to be 2 core motivational processes underlying obsessive-compulsive disorder (OCD). The objective of this study was to explore whether NJRE demarcates a neurodevelopmental OCD subgroup distinct from HA related to autistic traits and/or to a broader phenotype of cognitive rigidity and sensory processing difficulties associated with an earlier age of OCD onset.

A correlational design investigated whether NJRE and HA are distinct entities in OCD and explored their relationship to autism spectrum disorder (ASD) traits measured by the Autism Quotient (AQ), sensory processing, set-shifting, and age of OCD onset in an OCD sample (N=25).

NJRE was only moderately (r=.34) correlated to HA and not significant in this study. Consistent with predictions, NJRE was associated with sensory processing difficulties and an earlier age of OCD onset. No significant relationships were found between NJRE and ASD traits as measured by the AQ or set-shifting difficulties.

These preliminary findings suggest a lack of evidence demonstrating NJRE as a manifestation of core autistic traits as measured by the AQ. However, NJRE was associated with sensory abnormalities and an earlier age of OCD onset. The role of NJRE as a developmental, and possibly neurodevelopmental, risk factor for OCD possibly warrants further investigation.

Many studies have reported hippocampal volume reductions associated with posttraumatic stress disorder (PTSD), while others have not. Here we provide an updated meta-analysis of such reductions associated with PTSD and evaluate the association between symptom severity and hippocampal volume.

A total of 37 studies met the criteria for inclusion in the meta-analysis. Mean effect sizes (Hedges’ g) and 95% confidence intervals (CI95%) were computed for each study and then averaged to obtain an overall mean effect size across studies. Meta-regression was employed to examine the relationship between PTSD symptom severity and hippocampal volume.

Results showed that PTSD is associated with significant bilateral reduction of the hippocampus (left hippocampus effect size=–0.400, p<0.001, 5.24% reduction; right hippocampus effect size=–0.462, p<0.001, 5.23% reduction). Symptom severity, as measured by the Clinician-Administered PTSD Scale (CAPS), was significantly associated with decreased left, but not right, hippocampal volume.

PTSD was associated with significant bilateral volume reduction of the hippocampus. Increased symptom severity was significantly associated with reduced left hippocampal volume. This finding is consistent with the hypothesis that PTSD is more neurotoxic to the left hippocampus than to the right. However, whether the association between PTSD and lower hippocampal volume reflects a consequence of or a predisposition to PTSD remains unclear. More prospective studies are needed in this area.

To determine the rates and associated illness characteristics of obsessive-compulsive disorder (OCD) patients who describe their symptoms as either rewarding or habitual.

Seventy-three treatment-seeking OCD patients had their dominant compulsive behavior assessed with a structured interview (the Temporal Impulsive-Compulsive Scale–Revised) to track the progression of rewarding (ie, gain in positive affect), aversive (ie, decrease in negative affect), and neutral (or non-affective) states and a self-report scale (the Self-Report Habit Index) to evaluate their habitual features. Additional measures included structured diagnostic interviews for axis I and II disorders, measures of OCD symptoms severity, and a battery of instruments to comprehensively assess relevant aspects of sensitivity to reward and fear.

Almost half (49%) of our OCD patients (particularly washers) endorsed that they anticipated obtaining a reward (ie, positive affect) from the enactment of their dominant compulsive behavior. Washers stood out in that their positive affects during and after compulsive behaviors were highly (and positively) correlated with duration of illness. In contrast, habit strength did not differ between washers, checkers, and arrangers, although it also correlated with duration of illness among checkers. Furthermore, the severity of OCD and comorbidity with impulse control disorders predicted up to 35% of the variance in the habit strength of OCD behaviors.

Compulsive washing may be more clearly characterized by problems in reward processing. In contrast, duration of checking, severity of OCD, and comorbidity with impulse control disorders shape compulsive behaviors by imparting them with habitual tendencies.

Gambling is a commonplace phenomenon, existing along a continuum from occasional gambling to functionally impairing gambling disorder. The internet may act as a conduit for some gambling behaviors. The impact of problematic internet use on clinical and cognitive features relevant to gambling has received little research attention.

A total of 206 adults aged 18–30 years who gamble at least five times per year were recruited from the general community and undertook detailed clinical and cognitive assessments. Problematic internet use was defined using a total score of 5 or more on Young’s Diagnostic Questionnaire (YDQ). Linear regression was employed to evaluate the relative contribution of addictive-related, impulsive-related, and compulsive-related measures in predicting YDQ total scores in gamblers.

Gamblers with problematic internet use (18% of the sample) reported lower quality of life, lower self-esteem, elevated rates of intermittent explosive disorder, gambling disorder symptoms, attention deficit hyperactivity disorder (ADHD) symptoms, antisocial personality disorder, and posttraumatic stress disorder (PTSD), as well as relative deficits in decision making and spatial working memory. In linear regression, the extent of problematic internet use was most significantly associated with increased gambling disorder symptoms and increased ADHD symptoms.

Problematic internet use in gamblers is associated with worse quality of life, more problem/pathological gambling symptoms, more psychiatric morbidities, and select cognitive impairment. Refinement of the definition of problematic internet use and exploration of its clinical and cognitive associations are likely to be highly relevant to the treatment of problematic gambling.

Body dysmorphic disorder (BDD) is a debilitating disorder, characterized by obsessions and compulsions relating specifically to perceived appearance, and which has been newly classified within the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Obsessive-Compulsive and Related Disorders grouping. Until now, little research has been conducted into the cognitive profile of this disorder.

Participants with BDD (n=12) and participants without BDD (n=16) were tested using a computerized neurocognitive battery investigating attentional set-shifting (Intra/Extra Dimensional Set Shift Task), decision-making (Cambridge Gamble Task), motor response-inhibition (Stop-Signal Reaction Time Task), and affective processing (Affective Go-No Go Task). The groups were matched for age, IQ, and education.

In comparison to controls, patients with BDD showed significantly impaired attentional set-shifting, abnormal decision-making, impaired response inhibition, and greater omission and commission errors on the emotional processing task.

Despite the modest sample size, our results showed that individuals with BDD performed poorly compared to healthy controls on tests of cognitive flexibility, reward and motor impulsivity, and affective processing. Results from separate studies in OCD patients suggest similar cognitive dysfunction. Therefore, these findings are consistent with the reclassification of BDD alongside OCD. These data also hint at additional areas of decision-making abnormalities that might contribute specifically to the psychopathology of BDD.