Limited research has examined the early neuropsychological and neurobiological changes associated with comorbid affective disorders and alcohol dependence.

To investigate the cognitive and volumetric changes in individuals diagnosed with affective disorders with or without comorbid alcohol dependence.

Young adults (n = 21) who were undergoing medically-managed inpatient alcohol detoxification with comorbid affective disorders were neuropsychologically assessed 4-weeks following hospital discharge, and additionally underwent MRI brain scans during admission and 4-weeks following discharge. An affective disorders-only group (n = 21) with an equal distribution of anxiety and mood disorders was recruited through a youth mental health clinic.

Compared to affective disorders only (M = 31.8 ± 4.4 years old), individuals with affective disorders and alcohol dependence (M = 33.9 ± 6.3 years old; M = 21.1 ± 9.2 standard drinks/day) exhibited worse sustained attention and visual memory functioning. There was a highly significant association between drinking levels since detoxification and total brain volume change, such that resumption of heavy drinking attenuated brain volume gains associated with short-term abstinence (r = -0.87, p < 0.001).

In young adults with affective disorders, comorbid alcohol dependence is associated with more pronounced cognitive dysfunction, suggesting that these deficits are most relevant for cognitive remediation interventions. Crucially, abstinence or reduced drinking was associated with brain volume gains, whereas resumption of heavy drinking was associated with brain volume reductions, suggesting that medically-managed alcohol detoxification may, at least, partially reverse the neurobiological changes associated with prolonged alcohol dependence in young adults.

Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.

Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.

CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.

Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Learning and memory impairments in older adults with depression are linked to hippocampal atrophy. However, other subcortical regions may also be contributing to these deficits. We aimed to examine whether anterior caudate nucleus volume is significantly reduced in older adults with depression compared to controls; whether anterior caudate volume is associated with performance on tasks of episodic learning and memory, and if so, whether this association is independent of the effects of the hippocampus.

Eighty-four health-seeking participants meeting criteria for lifetime major depressive disorder (mean age = 64.2, s.d. = 9.1 years) and 27 never-depressed control participants (mean age = 63.9, s.d. = 8.0 years) underwent neuropsychological assessment including verbal episodic memory tests [Rey Auditory Verbal Learning Test and Logical Memory (WMS-III)]. Magnetic resonance imaging was conducted, from which subregions of the caudate nucleus were manually demarcated bilaterally and hippocampal volume was calculated using semi-automated methods.

Depressed subjects had smaller right anterior caudate (RAC) (t = 2.3, p = 0.026) and poorer memory compared to controls (t = 2.5, p < 0.001). For depressed subjects only, smaller RAC was associated with poorer verbal memory (r = 0.3, p = 0.003) and older age (r = −0.46, p < 0.001). Multivariable regression showed that the RAC and hippocampus volume uniquely accounted for 5% and 3% of the variance in memory, respectively (β = 0.25, t = 2.16, p = 0.033; β = 0.19, t = 1.71, p = 0.091).

In older people with depression, the anterior caudate nucleus and the hippocampus play independent roles in mediating memory. While future studies examining this structure should include larger sample sizes and adjust for multiple comparisons, these findings support the critical role of the striatum in depression.

Between 30 and 60% of adults with unipolar or bipolar disorders exhibit impairments across multiple domains. However, little is known about impaired functioning in youth with mood disorders.

To examine the prevalence of objective, subjective and observer-rated disability in a large, representative sample of young people with a primary mood disorder.

Individuals aged 16–25 years presenting to youth mental health services for the first time with a primary mood disorder participated in a systematic diagnostic and clinical assessment. Impairment was assessed using objective (unemployment or disability payments), observer- (Social and Occupational Functioning Assessment Scale; SOFAS) and self-rated measures (role functioning according to the Brief Disability Questionnaire).

Of 1241 participants (83% unipolar; 56% female), at least 30% were functionally impaired on the objective, self-rated and/or observer-rated measures, with 16% impaired according to all three criteria. Even when current distress levels were taken into account, daily use of cannabis and/or nicotine were significantly associated with impairment, with odds ratios (OR) ranging from about 1.5 to 3.0. Comorbid anxiety disorders were related to lower SOFAS scores (OR = 2–5).

Levels of disability were significant, even in those presenting for mental healthcare for the first time. Functional impairment did not differ between unipolar and bipolar cases, but some evidence suggested that females with bipolar disorder were particularly disabled. The prevalence of comorbid disorders (50%) and polysubstance use (28%) and their association with disability indicate that more meaningful indicators of mood episode outcomes should focus on functional rather than symptom-specific measures. The association between functioning and nicotine use requires further exploration.